Sample records for early domain shuffling

  1. Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an early domain shuffling event.

    PubMed

    Kyndt, Tina; Haegeman, Annelies; Gheysen, Godelieve

    2008-11-03

    the whole gene cassette, i.e. the GHF5 catalytic domain and the CBM2, rather than that it evolved by domain shuffling. Our evolutionary model for the gene structure in PPN GHF5 endoglucanases implies the occurrence of an early duplication event, and more recent gene duplications at genus or species level.

  2. Shuffle Optimizer: A Program to Optimize DNA Shuffling for Protein Engineering.

    PubMed

    Milligan, John N; Garry, Daniel J

    2017-01-01

    DNA shuffling is a powerful tool to develop libraries of variants for protein engineering. Here, we present a protocol to use our freely available and easy-to-use computer program, Shuffle Optimizer. Shuffle Optimizer is written in the Python computer language and increases the nucleotide homology between two pieces of DNA desired to be shuffled together without changing the amino acid sequence. In addition we also include sections on optimal primer design for DNA shuffling and library construction, a small-volume ultrasonicator method to create sheared DNA, and finally a method to reassemble the sheared fragments and recover and clone the library. The Shuffle Optimizer program and these protocols will be useful to anyone desiring to perform any of the nucleotide homology-dependent shuffling methods.

  3. Population shuffling between ground and high energy excited states

    PubMed Central

    Sabo, T Michael; Trent, John O; Lee, Donghan

    2015-01-01

    Stochastic processes powered by thermal energy lead to protein motions traversing time-scales from picoseconds to seconds. Fundamental to protein functionality is the utilization of these dynamics for tasks such as catalysis, folding, and allostery. A hierarchy of motion is hypothesized to connect and synergize fast and slow dynamics toward performing these essential activities. Population shuffling predicts a “top-down” temporal hierarchy, where slow time-scale conformational interconversion leads to a shuffling of the free energy landscape for fast time-scale events. Until now, population shuffling was only applied to interconverting ground states. Here, we extend the framework of population shuffling to be applicable for a system interconverting between low energy ground and high energy excited states, such as the SH3 domain mutants G48M and A39V/N53P/V55L from the Fyn tyrosine kinase, providing another tool for accessing the structural dynamics of high energy excited states. Our results indicate that the higher energy gauche− rotameric state for the leucine χ2 dihedral angle contributes significantly to the distribution of rotameric states in both the major and minor forms of the SH3 domain. These findings are corroborated with unrestrained molecular dynamics (MD) simulations on both the major and minor states of the SH3 domain demonstrating high correlations between experimental and back-calculated leucine χ2 rotameric populations. Taken together, we demonstrate how fast time-scale rotameric side-chain population distributions can be extracted from slow time-scale conformational exchange data further extending the scope and the applicability of the population shuffling model. PMID:26316263

  4. Population shuffling between ground and high energy excited states.

    PubMed

    Sabo, T Michael; Trent, John O; Lee, Donghan

    2015-11-01

    Stochastic processes powered by thermal energy lead to protein motions traversing time-scales from picoseconds to seconds. Fundamental to protein functionality is the utilization of these dynamics for tasks such as catalysis, folding, and allostery. A hierarchy of motion is hypothesized to connect and synergize fast and slow dynamics toward performing these essential activities. Population shuffling predicts a "top-down" temporal hierarchy, where slow time-scale conformational interconversion leads to a shuffling of the free energy landscape for fast time-scale events. Until now, population shuffling was only applied to interconverting ground states. Here, we extend the framework of population shuffling to be applicable for a system interconverting between low energy ground and high energy excited states, such as the SH3 domain mutants G48M and A39V/N53P/V55L from the Fyn tyrosine kinase, providing another tool for accessing the structural dynamics of high energy excited states. Our results indicate that the higher energy gauche - rotameric state for the leucine χ2 dihedral angle contributes significantly to the distribution of rotameric states in both the major and minor forms of the SH3 domain. These findings are corroborated with unrestrained molecular dynamics (MD) simulations on both the major and minor states of the SH3 domain demonstrating high correlations between experimental and back-calculated leucine χ2 rotameric populations. Taken together, we demonstrate how fast time-scale rotameric side-chain population distributions can be extracted from slow time-scale conformational exchange data further extending the scope and the applicability of the population shuffling model. © 2015 The Protein Society.

  5. Domain Shuffling in a Sensor Protein Contributed to the Evolution of Insect Pathogenicity in Plant-Beneficial Pseudomonas protegens

    PubMed Central

    Kupferschmied, Peter; Péchy-Tarr, Maria; Imperiali, Nicola; Maurhofer, Monika; Keel, Christoph

    2014-01-01

    Pseudomonas protegens is a biocontrol rhizobacterium with a plant-beneficial and an insect pathogenic lifestyle, but it is not understood how the organism switches between the two states. Here, we focus on understanding the function and possible evolution of a molecular sensor that enables P. protegens to detect the insect environment and produce a potent insecticidal toxin specifically during insect infection but not on roots. By using quantitative single cell microscopy and mutant analysis, we provide evidence that the sensor histidine kinase FitF is a key regulator of insecticidal toxin production. Our experimental data and bioinformatic analyses indicate that FitF shares a sensing domain with DctB, a histidine kinase regulating carbon uptake in Proteobacteria. This suggested that FitF has acquired its specificity through domain shuffling from a common ancestor. We constructed a chimeric DctB-FitF protein and showed that it is indeed functional in regulating toxin expression in P. protegens. The shuffling event and subsequent adaptive modifications of the recruited sensor domain were critical for the microorganism to express its potent insect toxin in the observed host-specific manner. Inhibition of the FitF sensor during root colonization could explain the mechanism by which P. protegens differentiates between the plant and insect host. Our study establishes FitF of P. protegens as a prime model for molecular evolution of sensor proteins and bacterial pathogenicity. PMID:24586167

  6. Characterization of an alternative low energy fold for bovine α-lactalbumin formed by disulfide bond shuffling.

    PubMed

    Lewney, Sarah; Smith, Lorna J

    2012-03-01

    Bovine α-lactalbumin (αLA) forms a misfolded disulfide bond shuffled isomer, X-αLA. This X-αLA isomer contains two native disulfide bridges (Cys 6-Cys 120 and Cys 28-Cys 111) and two non-native disulfide bridges (Cys 61-Cys 73 and Cys 77-Cys 91). MD simulations have been used to characterize the X-αLA isomer and its formation via disulfide bond shuffling and to compare it with the native fold of αLA. In the simulations of the X-αLA isomer the structure of the α-domain of native αLA is largely retained in agreement with experimental data. However, there are significant rearrangements in the β-domain, including the loss of the native β-sheet and calcium binding site. Interestingly, the energies of X-αLA and native αLA in simulations in the absence of calcium are closely similar. Thus, the X-αLA isomer represents a different low energy fold for the protein. Calcium binding to native αLA is shown to help preserve the structure of the β-domain of the protein limiting possibilities for disulfide bond shuffling. Hence, binding calcium plays an important role in both maintaining the native structure of αLA and providing a mechanism for distinguishing between folded and misfolded species. Copyright © 2011 Wiley Periodicals, Inc.

  7. Analysis of Network Address Shuffling as a Moving Target Defense

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

    Carroll, Thomas E.; Crouse, Michael B.; Fulp, Errin W.

    2014-06-10

    Address shuffling is a type of moving target defense that prevents an attacker from reliably contacting a system by periodically remapping network addresses. Although limited testing has demonstrated it to be effective, little research has been conducted to examine the theoretical limits of address shuffling. As a result, it is difficult to understand how effective shuffling is and under what circumstances it is a viable moving target defense. This paper introduces probabilistic models that can provide insight into the performance of address shuffling. These models quantify the probability of attacker success in terms of network size, quantity of addresses scanned,more » quantity of vulnerable systems, and the frequency of shuffling. Theoretical analysis will show that shuffling is an acceptable defense if there is a small population of vulnerable systems within a large network address space, however shuffling has a cost for legitimate users. These results will also be shown empirically using simulation and actual traffic traces.« less

  8. Computational and experimental analysis of DNA shuffling

    PubMed Central

    Maheshri, Narendra; Schaffer, David V.

    2003-01-01

    We describe a computational model of DNA shuffling based on the thermodynamics and kinetics of this process. The model independently tracks a representative ensemble of DNA molecules and records their states at every stage of a shuffling reaction. These data can subsequently be analyzed to yield information on any relevant metric, including reassembly efficiency, crossover number, type and distribution, and DNA sequence length distributions. The predictive ability of the model was validated by comparison to three independent sets of experimental data, and analysis of the simulation results led to several unique insights into the DNA shuffling process. We examine a tradeoff between crossover frequency and reassembly efficiency and illustrate the effects of experimental parameters on this relationship. Furthermore, we discuss conditions that promote the formation of useless “junk” DNA sequences or multimeric sequences containing multiple copies of the reassembled product. This model will therefore aid in the design of optimal shuffling reaction conditions. PMID:12626764

  9. Genome shuffling of Lactobacillus plantarum C88 improves adhesion.

    PubMed

    Zhao, Yujuan; Duan, Cuicui; Gao, Lei; Yu, Xue; Niu, Chunhua; Li, Shengyu

    2017-01-01

    Genome shuffling is an important method for rapid improvement in microbial strains for desired phenotypes. In this study, ultraviolet irradiation and nitrosoguanidine were used as mutagens to enhance the adhesion of the wild-type Lactobacillus plantarum C88. Four strains with better property were screened after mutagenesis to develop a library of parent strains for three rounds of genome shuffling. Fusants F3-1, F3-2, F3-3, and F3-4 were screened as the improved strains. The in vivo and in vitro tests results indicated that the population after three rounds of genome shuffling exhibited improved adhesive property. Random Amplified Polymorphic DNA results showed significant differences between the parent strain and recombinant strains at DNA level. These results suggest that the adhesive property of L. plantarum C88 can be significantly improved by genome shuffling. Improvement in the adhesive property of bacterial cells by genome shuffling enhances the colonization of probiotic strains which further benefits to exist probiotic function.

  10. Exploring metazoan evolution through dynamic and holistic changes in protein families and domains

    PubMed Central

    2012-01-01

    Background Proteins convey the majority of biochemical and cellular activities in organisms. Over the course of evolution, proteins undergo normal sequence mutations as well as large scale mutations involving domain duplication and/or domain shuffling. These events result in the generation of new proteins and protein families. Processes that affect proteome evolution drive species diversity and adaptation. Herein, change over the course of metazoan evolution, as defined by birth/death and duplication/deletion events within protein families and domains, was examined using the proteomes of 9 metazoan and two outgroup species. Results In studying members of the three major metazoan groups, the vertebrates, arthropods, and nematodes, we found that the number of protein families increased at the majority of lineages over the course of metazoan evolution where the magnitude of these increases was greatest at the lineages leading to mammals. In contrast, the number of protein domains decreased at most lineages and at all terminal lineages. This resulted in a weak correlation between protein family birth and domain birth; however, the correlation between domain birth and domain member duplication was quite strong. These data suggest that domain birth and protein family birth occur via different mechanisms, and that domain shuffling plays a role in the formation of protein families. The ratio of protein family birth to protein domain birth (domain shuffling index) suggests that shuffling had a more demonstrable effect on protein families in nematodes and arthropods than in vertebrates. Through the contrast of high and low domain shuffling indices at the lineages of Trichinella spiralis and Gallus gallus, we propose a link between protein redundancy and evolutionary changes controlled by domain shuffling; however, the speed of adaptation among the different lineages was relatively invariant. Evaluating the functions of protein families that appeared or disappeared at the

  11. The Skeletal Proteome of the Coral Acropora millepora: The Evolution of Calcification by Co-Option and Domain Shuffling

    PubMed Central

    Ramos-Silva, Paula; Kaandorp, Jaap; Huisman, Lotte; Marie, Benjamin; Zanella-Cléon, Isabelle; Guichard, Nathalie; Miller, David J.; Marin, Frédéric

    2013-01-01

    In corals, biocalcification is a major function that may be drastically affected by ocean acidification (OA). Scleractinian corals grow by building up aragonitic exoskeletons that provide support and protection for soft tissues. Although this process has been extensively studied, the molecular basis of biocalcification is poorly understood. Notably lacking is a comprehensive catalog of the skeleton-occluded proteins—the skeletal organic matrix proteins (SOMPs) that are thought to regulate the mineral deposition. Using a combination of proteomics and transcriptomics, we report the first survey of such proteins in the staghorn coral Acropora millepora. The organic matrix (OM) extracted from the coral skeleton was analyzed by mass spectrometry and bioinformatics, enabling the identification of 36 SOMPs. These results provide novel insights into the molecular basis of coral calcification and the macroevolution of metazoan calcifying systems, whereas establishing a platform for studying the impact of OA at molecular level. Besides secreted proteins, extracellular regions of transmembrane proteins are also present, suggesting a close control of aragonite deposition by the calicoblastic epithelium. In addition to the expected SOMPs (Asp/Glu-rich, galaxins), the skeletal repertoire included several proteins containing known extracellular matrix domains. From an evolutionary perspective, the number of coral-specific proteins is low, many SOMPs having counterparts in the noncalcifying cnidarians. Extending the comparison with the skeletal OM proteomes of other metazoans allowed the identification of a pool of functional domains shared between phyla. These data suggest that co-option and domain shuffling may be general mechanisms by which the trait of calcification has evolved. PMID:23765379

  12. Evolution of EF-hand calcium-modulated proteins. IV. Exon shuffling did not determine the domain compositions of EF-hand proteins

    NASA Technical Reports Server (NTRS)

    Kretsinger, R. H.; Nakayama, S.

    1993-01-01

    In the previous three reports in this series we demonstrated that the EF-hand family of proteins evolved by a complex pattern of gene duplication, transposition, and splicing. The dendrograms based on exon sequences are nearly identical to those based on protein sequences for troponin C, the essential light chain myosin, the regulatory light chain, and calpain. This validates both the computational methods and the dendrograms for these subfamilies. The proposal of congruence for calmodulin, troponin C, essential light chain, and regulatory light chain was confirmed. There are, however, significant differences in the calmodulin dendrograms computed from DNA and from protein sequences. In this study we find that introns are distributed throughout the EF-hand domain and the interdomain regions. Further, dendrograms based on intron type and distribution bear little resemblance to those based on protein or on DNA sequences. We conclude that introns are inserted, and probably deleted, with relatively high frequency. Further, in the EF-hand family exons do not correspond to structural domains and exon shuffling played little if any role in the evolution of this widely distributed homolog family. Calmodulin has had a turbulent evolution. Its dendrograms based on protein sequence, exon sequence, 3'-tail sequence, intron sequences, and intron positions all show significant differences.

  13. Random domain name and address mutation (RDAM) for thwarting reconnaissance attacks

    PubMed Central

    Chen, Xi; Zhu, Yuefei

    2017-01-01

    Network address shuffling is a novel moving target defense (MTD) that invalidates the address information collected by the attacker by dynamically changing or remapping the host’s network addresses. However, most network address shuffling methods are limited by the limited address space and rely on the host’s static domain name to map to its dynamic address; therefore these methods cannot effectively defend against random scanning attacks, and cannot defend against an attacker who knows the target’s domain name. In this paper, we propose a network defense method based on random domain name and address mutation (RDAM), which increases the scanning space of the attacker through a dynamic domain name method and reduces the probability that a host will be hit by an attacker scanning IP addresses using the domain name system (DNS) query list and the time window methods. Theoretical analysis and experimental results show that RDAM can defend against scanning attacks and worm propagation more effectively than general network address shuffling methods, while introducing an acceptable operational overhead. PMID:28489910

  14. Doing the Meiosis Shuffle.

    ERIC Educational Resources Information Center

    Krauskopf, Sara

    1999-01-01

    Presents a game called the Meiosis Shuffle that helps students simulate the process of meiosis in which homologous cards representing chromosomes pair up, line up, and split apart. Students respond well to the simulation and are better able to conceptualize what chromosomes do and how independent assortment causes genetic variation. (CCM)

  15. An assessment of 'shuffle algorithm' collision mechanics for particle simulations

    NASA Technical Reports Server (NTRS)

    Feiereisen, William J.; Boyd, Iain D.

    1991-01-01

    Among the algorithms for collision mechanics used at present, the 'shuffle algorithm' of Baganoff (McDonald and Baganoff, 1988; Baganoff and McDonald, 1990) not only allows efficient vectorization, but also discretizes the possible outcomes of a collision. To assess the applicability of the shuffle algorithm, a simulation was performed of flows in monoatomic gases and the calculated characteristics of shock waves was compared with those obtained using a commonly employed isotropic scattering law. It is shown that, in general, the shuffle algorithm adequately represents the collision mechanics in cases when the goal of calculations are mean profiles of density and temperature.

  16. Development of novel vaccines using DNA shuffling and screening strategies.

    PubMed

    Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha

    2004-02-01

    DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.

  17. Algorithms for optimizing cross-overs in DNA shuffling.

    PubMed

    He, Lu; Friedman, Alan M; Bailey-Kellogg, Chris

    2012-03-21

    DNA shuffling generates combinatorial libraries of chimeric genes by stochastically recombining parent genes. The resulting libraries are subjected to large-scale genetic selection or screening to identify those chimeras with favorable properties (e.g., enhanced stability or enzymatic activity). While DNA shuffling has been applied quite successfully, it is limited by its homology-dependent, stochastic nature. Consequently, it is used only with parents of sufficient overall sequence identity, and provides no control over the resulting chimeric library. This paper presents efficient methods to extend the scope of DNA shuffling to handle significantly more diverse parents and to generate more predictable, optimized libraries. Our CODNS (cross-over optimization for DNA shuffling) approach employs polynomial-time dynamic programming algorithms to select codons for the parental amino acids, allowing for zero or a fixed number of conservative substitutions. We first present efficient algorithms to optimize the local sequence identity or the nearest-neighbor approximation of the change in free energy upon annealing, objectives that were previously optimized by computationally-expensive integer programming methods. We then present efficient algorithms for more powerful objectives that seek to localize and enhance the frequency of recombination by producing "runs" of common nucleotides either overall or according to the sequence diversity of the resulting chimeras. We demonstrate the effectiveness of CODNS in choosing codons and allocating substitutions to promote recombination between parents targeted in earlier studies: two GAR transformylases (41% amino acid sequence identity), two very distantly related DNA polymerases, Pol X and β (15%), and beta-lactamases of varying identity (26-47%). Our methods provide the protein engineer with a new approach to DNA shuffling that supports substantially more diverse parents, is more deterministic, and generates more predictable

  18. T2 shuffling: Sharp, multicontrast, volumetric fast spin-echo imaging.

    PubMed

    Tamir, Jonathan I; Uecker, Martin; Chen, Weitian; Lai, Peng; Alley, Marcus T; Vasanawala, Shreyas S; Lustig, Michael

    2017-01-01

    A new acquisition and reconstruction method called T 2 Shuffling is presented for volumetric fast spin-echo (three-dimensional [3D] FSE) imaging. T 2 Shuffling reduces blurring and recovers many images at multiple T 2 contrasts from a single acquisition at clinically feasible scan times (6-7 min). The parallel imaging forward model is modified to account for temporal signal relaxation during the echo train. Scan efficiency is improved by acquiring data during the transient signal decay and by increasing echo train lengths without loss in signal-to-noise ratio (SNR). By (1) randomly shuffling the phase encode view ordering, (2) constraining the temporal signal evolution to a low-dimensional subspace, and (3) promoting spatio-temporal correlations through locally low rank regularization, a time series of virtual echo time images is recovered from a single scan. A convex formulation is presented that is robust to partial voluming and radiofrequency field inhomogeneity. Retrospective undersampling and in vivo scans confirm the increase in sharpness afforded by T 2 Shuffling. Multiple image contrasts are recovered and used to highlight pathology in pediatric patients. A proof-of-principle method is integrated into a clinical musculoskeletal imaging workflow. The proposed T 2 Shuffling method improves the diagnostic utility of 3D FSE by reducing blurring and producing multiple image contrasts from a single scan. Magn Reson Med 77:180-195, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Efficient preparation of shuffled DNA libraries through recombination (Gateway) cloning.

    PubMed

    Lehtonen, Soili I; Taskinen, Barbara; Ojala, Elina; Kukkurainen, Sampo; Rahikainen, Rolle; Riihimäki, Tiina A; Laitinen, Olli H; Kulomaa, Markku S; Hytönen, Vesa P

    2015-01-01

    Efficient and robust subcloning is essential for the construction of high-diversity DNA libraries in the field of directed evolution. We have developed a more efficient method for the subcloning of DNA-shuffled libraries by employing recombination cloning (Gateway). The Gateway cloning procedure was performed directly after the gene reassembly reaction, without additional purification and amplification steps, thus simplifying the conventional DNA shuffling protocols. Recombination-based cloning, directly from the heterologous reassembly reaction, conserved the high quality of the library and reduced the time required for the library construction. The described method is generally compatible for the construction of DNA-shuffled gene libraries. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Nucleotide exchange and excision technology DNA shuffling and directed evolution.

    PubMed

    Speck, Janina; Stebel, Sabine C; Arndt, Katja M; Müller, Kristian M

    2011-01-01

    Remarkable success in optimizing complex properties within DNA and proteins has been achieved by directed evolution. In contrast to various random mutagenesis methods and high-throughput selection methods, the number of available DNA shuffling procedures is limited, and protocols are often difficult to adjust. The strength of the nucleotide exchange and excision technology (NExT) DNA shuffling described here is the robust, efficient, and easily controllable DNA fragmentation step based on random incorporation of the so-called 'exchange nucleotides' by PCR. The exchange nucleotides are removed enzymatically, followed by chemical cleavage of the DNA backbone. The oligonucleotide pool is reassembled into full-length genes by internal primer extension, and the recombined gene library is amplified by standard PCR. The technique has been demonstrated by shuffling a defined gene library of chloramphenicol acetyltransferase variants using uridine as fragmentation defining exchange nucleotide. Substituting 33% of the dTTP with dUTP in the incorporation PCR resulted in shuffled clones with an average parental fragment size of 86 bases and revealed a mutation rate of only 0.1%. Additionally, a computer program (NExTProg) has been developed that predicts the fragment size distribution depending on the relative amount of the exchange nucleotide.

  1. Wavelet-based image compression using shuffling and bit plane correlation

    NASA Astrophysics Data System (ADS)

    Kim, Seungjong; Jeong, Jechang

    2000-12-01

    In this paper, we propose a wavelet-based image compression method using shuffling and bit plane correlation. The proposed method improves coding performance in two steps: (1) removing the sign bit plane by shuffling process on quantized coefficients, (2) choosing the arithmetic coding context according to maximum correlation direction. The experimental results are comparable or superior for some images with low correlation, to existing coders.

  2. Drug resistance marker-aided genome shuffling to improve acetic acid tolerance in Saccharomyces cerevisiae.

    PubMed

    Zheng, Dao-Qiong; Wu, Xue-Chang; Wang, Pin-Mei; Chi, Xiao-Qin; Tao, Xiang-Lin; Li, Ping; Jiang, Xin-Hang; Zhao, Yu-Hua

    2011-03-01

    Acetic acid existing in a culture medium is one of the most limiting constraints in yeast growth and viability during ethanol fermentation. To improve acetic acid tolerance in Saccharomyces cerevisiae strains, a drug resistance marker-aided genome shuffling approach with higher screen efficiency of shuffled mutants was developed in this work. Through two rounds of genome shuffling of ultraviolet mutants derived from the original strain 308, we obtained a shuffled strain YZ2, which shows significantly faster growth and higher cell viability under acetic acid stress. Ethanol production of YZ2 (within 60 h) was 21.6% higher than that of 308 when 0.5% (v/v) acetic acid was added to fermentation medium. Membrane integrity, higher in vivo activity of the H+-ATPase, and lower oxidative damage after acetic acid treatment are the possible reasons for the acetic acid-tolerance phenotype of YZ2. These results indicated that this novel genome shuffling approach is powerful to rapidly improve the complex traits of industrial yeast strains.

  3. The analysis of genomic structures in the L1 family of cell adhesion molecules provides no evidence for exon shuffling events after the separation of arthropod and chordate lineages.

    PubMed

    Zhao, G; Hortsch, M

    1998-07-17

    Members of the L1 family of neural cell adhesion molecules consist of multiple extracellular immunoglobulin and fibronectin type III domains that mediate the adhesive properties of this group of transmembrane proteins. In vertebrate genomes, these protein domains are separated by introns, and it has been suggested that L1-type genes might have been subject to exon-shuffling events during evolution. However, comparison of the human L1-CAM and the chicken neurofascin gene with the genomic structure of their Drosophila homologue, neuroglian, indicates that no major rearrangement of protein domains has taken place subsequent to the split of the arthropod and chordate phyla. The Drosophila neuroglian gene appears to have lost most of the introns that have been conserved in the human L1-CAM and the chicken neurofascin gene. Nevertheless, exon shuffling or the generation of new exons by mutational changes might have been responsible for the generation of additional, alternatively spliced exons in L1-type genes.

  4. Enhanced production of fructosyltransferase in Aspergillus oryzae by genome shuffling.

    PubMed

    Wang, Shenghai; Duan, Mengjie; Liu, Yalan; Fan, Sen; Lin, Xiaoshan; Zhang, Yi

    2017-03-01

    To breed Aspergillus oryzae strains with high fructosyltransferase (FTase) activity using intraspecific protoplast fusion via genome-shuffling. A candidate library was developed using UV/LiCl of the conidia of A. oryzae SBB201. By screening for enzyme activity and cell biomass, two mutants (UV-11 and UV-76) were chosen for protoplast fusion and subsequent genome shuffling. After three rounds of genome recombination, a fusion mutant RIII-7 was obtained. Its FTase activity was 180 U g -1 , approximately double that of the original strain, and RIII-7 was genetically stable. In fermentation culture, FTase activity of the genome-shuffled strain reached a maximum of 353 U g -1 using substrate-feeding method, and this value was approximately 3.4-times higher than that of the original strain A. oryzae SBB201. Intraspecific protoplast fusion of A. oryzae significantly enhanced FTase activity and generated a potentially useful strain for industrial production.

  5. A Benes-like theorem for the shuffle-exchange graph

    NASA Technical Reports Server (NTRS)

    Schwabe, Eric J.

    1992-01-01

    One of the first theorems on permutation routing, proved by V. E. Beness (1965), shows that given a set of source-destination pairs in an N-node butterfly network with at most a constant number of sources or destinations in each column of the butterfly, there exists a set of paths of lengths O(log N) connecting each pair such that the total congestion is constant. An analogous theorem yielding constant-congestion paths for off-line routing in the shuffle-exchange graph is proved here. The necklaces of the shuffle-exchange graph play the same structural role as the columns of the butterfly in Beness' theorem.

  6. Development of Fuel Shuffling Module for PHISICS

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

    Allan Mabe; Andrea Alfonsi; Cristian Rabiti

    2013-06-01

    PHISICS (Parallel and Highly Innovative Simulation for the INL Code System) [4] code toolkit has been in development at the Idaho National Laboratory. This package is intended to provide a modern analysis tool for reactor physics investigation. It is designed with the mindset to maximize accuracy for a given availability of computational resources and to give state of the art tools to the modern nuclear engineer. This is obtained by implementing several different algorithms and meshing approaches among which the user will be able to choose, in order to optimize his computational resources and accuracy needs. The software is completelymore » modular in order to simplify the independent development of modules by different teams and future maintenance. The package is coupled with the thermo-hydraulic code RELAP5-3D [3]. In the following the structure of the different PHISICS modules is briefly recalled, focusing on the new shuffling module (SHUFFLE), object of this paper.« less

  7. Xylose-fermenting Pichia stipitis by genome shuffling for improved ethanol production.

    PubMed

    Shi, Jun; Zhang, Min; Zhang, Libin; Wang, Pin; Jiang, Li; Deng, Huiping

    2014-03-01

    Xylose fermentation is necessary for the bioconversion of lignocellulose to ethanol as fuel, but wild-type Saccharomyces cerevisiae strains cannot fully metabolize xylose. Several efforts have been made to obtain microbial strains with enhanced xylose fermentation. However, xylose fermentation remains a serious challenge because of the complexity of lignocellulosic biomass hydrolysates. Genome shuffling has been widely used for the rapid improvement of industrially important microbial strains. After two rounds of genome shuffling, a genetically stable, high-ethanol-producing strain was obtained. Designated as TJ2-3, this strain could ferment xylose and produce 1.5 times more ethanol than wild-type Pichia stipitis after fermentation for 96 h. The acridine orange and propidium iodide uptake assays showed that the maintenance of yeast cell membrane integrity is important for ethanol fermentation. This study highlights the importance of genome shuffling in P. stipitis as an effective method for enhancing the productivity of industrial strains. © 2013 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  8. Combined immunotherapy of breast cancer with EGF and VEGF vaccines from DNA shuffling in a mouse model.

    PubMed

    Jin, Dong; Yu, Xin; Chen, Bing; Li, Zhitao; Ding, Jia; Zhao, Xiuyun; Qi, Gaofu

    2017-06-01

    Development of EGF and VEGF vaccines with high antigenicity for combined immunotherapy of EGF-EGFR signaling-dependent epithelial tumors such as breast cancer. EGF genes from mouse, human and chicken were randomly assembled to chimeric genes by DNA shuffling, then a chimeric EGF was selected out by PCR, SDS-PAGE and immunization for combined immunotherapy of breast cancer with a previously constructed chimeric VEGF vaccine from shuffling. Combined vaccination with chimeric EGF and VEGF from shuffling could induce high titer of antibodies against EGF and VEGF to inhibit tumor growth and angiogenesis, and improve the survival rate of mice with breast cancer. Combined vaccination with EGF and VEGF from shuffling showed better immunotherapy on EGF-EGFR signaling-dependent epithelial tumors such as breast cancer than the single-agent EGF vaccination.

  9. Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer's Disease.

    PubMed

    Cheng, Bo; Liu, Mingxia; Shen, Dinggang; Li, Zuoyong; Zhang, Daoqiang

    2017-04-01

    Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer's Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multi-domain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods.

  10. Symbiont shuffling linked to differential photochemical dynamics of Symbiodinium in three Caribbean reef corals

    NASA Astrophysics Data System (ADS)

    Cunning, Ross; Silverstein, Rachel N.; Baker, Andrew C.

    2018-03-01

    Dynamic symbioses with functionally diverse dinoflagellate algae in the genus Symbiodinium may allow some reef corals to alter their phenotypes through `symbiont shuffling', or changes in symbiont community composition. In particular, corals may become more bleaching resistant by increasing the relative abundance of thermally tolerant Symbiodinium in clade D after bleaching. Despite the immediate relevance of this phenomenon to corals living in warming oceans—and to interventions aimed at boosting coral resilience—the mechanisms governing how, why, and when symbiont shuffling occurs are still poorly understood. Here, we performed controlled thermal bleaching and recovery experiments on three species of Caribbean corals hosting mixtures of D1a ( S. trenchii) and other symbionts in clades B or C. We show that the degree of symbiont shuffling is related to (1) the duration of stress exposure and (2) the difference in photochemical efficiency ( F v /F m) of co-occurring symbionts under stress (i.e., the `photochemical advantage' of one symbiont over the other). The advantage of D1a under stress was greatest in Montastraea cavernosa, intermediate in Siderastrea siderea, and lowest in Orbicella faveolata and correlated positively with the magnitude of shuffling toward D1a. In holobionts where D1a had less of an advantage over co-occurring symbionts (i.e., only slightly higher F v /F m under stress), a longer stress duration was required to elicit commensurate increases in D1a abundance. In fact, across these three coral species, 92.9% of variation in the degree of symbiont shuffling could be explained by the time-integrated photochemical advantage of D1a under heat stress. Although F v /F m is governed by numerous factors that this study is unable to resolve mechanistically, its strong empirical relationship with symbiont shuffling helps elucidate general features that govern this process in reef corals, which will help refine predictions of coral responses to

  11. Prospecting Metagenomic Enzyme Subfamily Genes for DNA Family Shuffling by a Novel PCR-based Approach*

    PubMed Central

    Wang, Qiuyan; Wu, Huili; Wang, Anming; Du, Pengfei; Pei, Xiaolin; Li, Haifeng; Yin, Xiaopu; Huang, Lifeng; Xiong, Xiaolong

    2010-01-01

    DNA family shuffling is a powerful method for enzyme engineering, which utilizes recombination of naturally occurring functional diversity to accelerate laboratory-directed evolution. However, the use of this technique has been hindered by the scarcity of family genes with the required level of sequence identity in the genome database. We describe here a strategy for collecting metagenomic homologous genes for DNA shuffling from environmental samples by truncated metagenomic gene-specific PCR (TMGS-PCR). Using identified metagenomic gene-specific primers, twenty-three 921-bp truncated lipase gene fragments, which shared 64–99% identity with each other and formed a distinct subfamily of lipases, were retrieved from 60 metagenomic samples. These lipase genes were shuffled, and selected active clones were characterized. The chimeric clones show extensive functional and genetic diversity, as demonstrated by functional characterization and sequence analysis. Our results indicate that homologous sequences of genes captured by TMGS-PCR can be used as suitable genetic material for DNA family shuffling with broad applications in enzyme engineering. PMID:20962349

  12. Statistical mechanics of two-dimensional shuffled foams: prediction of the correlation between geometry and topology.

    PubMed

    Durand, Marc; Käfer, Jos; Quilliet, Catherine; Cox, Simon; Talebi, Shirin Ataei; Graner, François

    2011-10-14

    We propose an analytical model for the statistical mechanics of shuffled two-dimensional foams with moderate bubble size polydispersity. It predicts without any adjustable parameters the correlations between the number of sides n of the bubbles (topology) and their areas A (geometry) observed in experiments and numerical simulations of shuffled foams. Detailed statistics show that in shuffled cellular patterns n correlates better with √A (as claimed by Desch and Feltham) than with A (as claimed by Lewis and widely assumed in the literature). At the level of the whole foam, standard deviations Δn and ΔA are in proportion. Possible applications include correlations of the detailed distributions of n and A, three-dimensional foams, and biological tissues.

  13. Enhancement and Analysis of Human Antiaflatoxin B1 (AFB1) scFv Antibody-Ligand Interaction Using Chain Shuffling.

    PubMed

    Rangnoi, Kuntalee; Choowongkomon, Kiattawee; O'Kennedy, Richard; Rüker, Florian; Yamabhai, Montarop

    2018-06-06

    A human antiaflatoxin B1 (AFB1) scFv antibody (yAFB1-c3), selected from a naı̈ve human phage-displayed scFv library, was used as a template for improving and analysis of antibody-ligand interactions using the chain-shuffling technique. The variable-heavy and variable-light (VH/VL)-shuffled library was constructed from the VH of 25 preselected clones recombined with the VL of yAFB1-c3 and vice versa. Affinity selection from these libraries demonstrated that the VH domain played an important role in the binding of scFv to free AFB1. Therefore, in the next step, VH-shuffled scFv library was constructed from variable-heavy (VH) chain repertoires, amplified from the naı̈ve library, recombined with the variable-light (VL) chain of the clone yAFB1-c3. This library was then used to select a specific scFv antibody against soluble AFB1 by a standard biopanning method. Three clones that showed improved binding properties were isolated. Amino acid sequence analysis indicated that the improved clones have amino acid mutations in framework 1 (FR1) and the complementarity determining region (CDR1) of the VH chain. One clone, designated sAFH-3e3, showed 7.5-fold improvement in sensitivity over the original scFv clone and was selected for molecular binding studies with AFB1. Homology modeling and molecular docking were used to compare the binding of this and the original clones. The results confirmed that VH is more important than VL for AFB1 binding.

  14. Functional analysis of the plant disease resistance gene Pto using DNA shuffling.

    PubMed

    Bernal, Adriana J; Pan, Qilin; Pollack, Jeff; Rose, Laura; Kozik, Alexander; Willits, Neil; Luo, Yao; Guittet, Muriel; Kochetkova, Elena; Michelmore, Richard W

    2005-06-17

    Pto is a serine/threonine kinase that mediates resistance in tomato to strains of Pseudomonas syringae pv. tomato expressing the (a)virulence proteins AvrPto or AvrPtoB. DNA shuffling was used as a combinatorial in vitro genetic approach to dissect the functional regions of Pto. The Pto gene was shuffled with four of its paralogs from a resistant haplotype to create a library of recombinant products that was screened for interaction with AvrPto in yeast. All interacting clones and a representative sample of noninteracting clones were sequenced, and their ability to signal downstream was tested by the elicitation of a hypersensitive response in an AvrPto-dependent or -independent manner in planta. Eight candidate regions important for binding to AvrPto or for downstream signaling were identified by statistical correlations between individual amino acid positions and phenotype. A subset of the regions had previously been identified as important for recognition, confirming the validity of the shuffling approach. Three novel regions important for Pto function were validated by site-directed mutagenesis. Several chimeras and point mutants exhibited a differential interaction with (a)virulence proteins in the AvrPto and VirPphA family, demonstrating distinct binding requirements for different ligands. Additionally, the identification of chimeras that are both constitutively active as well as capable of binding AvrPto indicates that elicitation of downstream signaling does not involve a conformational change that precludes binding of AvrPto, as previously hypothesized. The correlations between phenotypes and variation generated by DNA shuffling paralleled natural variation observed between orthologs of Pto from Lycopersicon spp.

  15. Exon Shuffling and Origin of Scorpion Venom Biodiversity

    PubMed Central

    Wang, Xueli; Gao, Bin; Zhu, Shunyi

    2016-01-01

    Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences. PMID:28035955

  16. Exon Shuffling and Origin of Scorpion Venom Biodiversity.

    PubMed

    Wang, Xueli; Gao, Bin; Zhu, Shunyi

    2016-12-26

    Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences.

  17. Adaptive Grouping Cloud Model Shuffled Frog Leaping Algorithm for Solving Continuous Optimization Problems

    PubMed Central

    Liu, Haorui; Yi, Fengyan; Yang, Heli

    2016-01-01

    The shuffled frog leaping algorithm (SFLA) easily falls into local optimum when it solves multioptimum function optimization problem, which impacts the accuracy and convergence speed. Therefore this paper presents grouped SFLA for solving continuous optimization problems combined with the excellent characteristics of cloud model transformation between qualitative and quantitative research. The algorithm divides the definition domain into several groups and gives each group a set of frogs. Frogs of each region search in their memeplex, and in the search process the algorithm uses the “elite strategy” to update the location information of existing elite frogs through cloud model algorithm. This method narrows the searching space and it can effectively improve the situation of a local optimum; thus convergence speed and accuracy can be significantly improved. The results of computer simulation confirm this conclusion. PMID:26819584

  18. Improving isopropanol tolerance and production of Clostridium beijerinckii DSM 6423 by random mutagenesis and genome shuffling.

    PubMed

    Gérando, H Máté de; Fayolle-Guichard, F; Rudant, L; Millah, S K; Monot, F; Ferreira, Nicolas Lopes; López-Contreras, A M

    2016-06-01

    Random mutagenesis and genome shuffling was applied to improve solvent tolerance and isopropanol/butanol/ethanol (IBE) production in the strictly anaerobic bacteria Clostridium beijerinckii DSM 6423. Following chemical mutagenesis with N-methyl-N-nitro-N-nitrosoguanidine (NTG), screening of putatively improved strains was done by submitting the mutants to toxic levels of inhibitory chemicals or by screening for their tolerance to isopropanol (>35 g/L). Suicide substrates, such as ethyl or methyl bromobutyrate or alcohol dehydrogenase inhibitors like allyl alcohol, were tested and, finally, 36 mutants were isolated. The fermentation profiles of these NTG mutant strains were characterized, and the best performing mutants were used for consecutive rounds of genome shuffling. Screening of strains with further enhancement in isopropanol tolerance at each recursive shuffling step was then used to spot additionally improved strains. Three highly tolerant strains were finally isolated and able to withstand up to 50 g/L isopropanol on plates. Even if increased tolerance to the desired end product was not always accompanied by higher production capabilities, some shuffled strains showed increased solvent titers compared to the parental strains and the original C. beijerinckii DSM 6423. This study confirms the efficiency of genome shuffling to generate improved strains toward a desired phenotype such as alcohol tolerance. This tool also offers the possibility of obtaining improved strains of Clostridium species for which targeted genetic engineering approaches have not been described yet.

  19. Improvement of industrially important microbial strains by genome shuffling: Current status and future prospects.

    PubMed

    Magocha, Tinashe Archbold; Zabed, H; Yang, Miaomiao; Yun, Junhua; Zhang, Huanhuan; Qi, Xianghui

    2018-06-01

    The growing demand for biotechnological products against limited metabolic capacity of industrially used microorganisms has led to an increased interest on strain-improvement over the last several decades, which aimed to enhance metabolite yield, substrate uptake and tolerance of the strains. Among a few techniques of strain-improvement, genome shuffling is the most recent and promising approach used for rapid strain-improvement that can yield a new strain by combining whole genomes of multi-parental microorganisms using the principles of protoplast fusion. Genome shuffling has brought a major breakthrough in the strain-improvement concept as it is found to be effective and reliable for expressing complex phenotypes. This review will discuss the technical aspects and applications of genome shuffling for various industrial strains to present its current status and recent progress. In the concluding remarks, a summary will be presented focusing on the major challenges and future outlooks of this technology. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer’s Disease

    PubMed Central

    Cheng, Bo; Liu, Mingxia; Li, Zuoyong

    2017-01-01

    Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer’s Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multidomain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods. PMID:27928657

  1. Enhanced succinic acid production by Actinobacillus succinogenes after genome shuffling.

    PubMed

    Zheng, Pu; Zhang, Kunkun; Yan, Qiang; Xu, Yan; Sun, Zhihao

    2013-08-01

    Succinic acid is an important platform chemical for synthesis of C4 compounds. We applied genome shuffling to improve fermentative production of succinic acid by A. succinogenes. Using a screening strategy composed of selection in fermentation broth, cultured in 96-deep-well plates, and condensed HPLC screening, a starting population of 11 mutants producing a higher succinic acid concentration was selected and subjected to recursive protoplasts fusion. After three rounds of genome shuffling, strain F3-II-3-F was obtained, producing succinic acid at 1.99 g/l/h with a yield of 95.6 g/l. The genome shuffled strain had about a 73 % improvement in succinic acid production compared to the parent strain after 48 h in fed-batch fermentation. The genomic variability of F3-II-3-F was confirmed by amplified fragment-length polymorphism. The activity levels of key enzymes involved in end-product formation from glucose and metabolic flux distribution during succinic acid production were compared between A. succinogenes CGMCC 1593 and F3-II-3-F. Increased activity of glucokinase, fructose-1,6-bisphosphate aldolase, PEP carboxykinase and fumarase, as well as decreased activity of pyruvate kinase, pyruvate formate-lyase, and acetate kinase explained the enhanced succinic acid production and decreased acetic acid formation. Metabolic flux analysis suggested that increased flux to NADH was the main reason for increased activity of the C4 pathway resulting in increased yields of succinic acid. The present work will be propitious to the development of a bio-succinic acid fermentation industry.

  2. Genome shuffling improves production of the low-temperature alkalophilic lipase by Acinetobacter johnsonii.

    PubMed

    Wang, HaiKuan; Zhang, Jie; Wang, XiaoJie; Qi, Wei; Dai, YuJie

    2012-01-01

    The production of a low-temperature alkalophilic lipase from Acinetobacter johnsonii was improved using genome shuffling. The starting populations, obtained by UV irradiation and diethyl sulfate mutagenesis, were subjected to recursive protoplast fusion. The optimal conditions for protoplast formation and regeneration were 0.15 mg lysozyme/ml for 45 min at 37°C. The protoplasts were inactivated under UV for 20 min or heated at 60°C for 60 min and a fusant probability of ~98% was observed. The positive colonies were created by fusing the inactivated protoplasts. After two rounds of genome shuffling, one strain, F22, with a lipase activity of 7 U/ml was obtained.

  3. Modified Shuffled Frog Leaping Optimization Algorithm Based Distributed Generation Rescheduling for Loss Minimization

    NASA Astrophysics Data System (ADS)

    Arya, L. D.; Koshti, Atul

    2018-05-01

    This paper investigates the Distributed Generation (DG) capacity optimization at location based on the incremental voltage sensitivity criteria for sub-transmission network. The Modified Shuffled Frog Leaping optimization Algorithm (MSFLA) has been used to optimize the DG capacity. Induction generator model of DG (wind based generating units) has been considered for study. Standard test system IEEE-30 bus has been considered for the above study. The obtained results are also validated by shuffled frog leaping algorithm and modified version of bare bones particle swarm optimization (BBExp). The performance of MSFLA has been found more efficient than the other two algorithms for real power loss minimization problem.

  4. Foot pressure and center of pressure in athletes with ankle instability during lateral shuffling and running gait.

    PubMed

    Huang, P-Y; Lin, C-F; Kuo, L-C; Liao, J-C

    2011-12-01

    This study evaluates foot pressure and center of pressure (COP) patterns in individuals with ankle instability during running and lateral shuffling. Eleven participants with ankle instability (AI) and 11 normal subjects (Normal) performed running and lateral shuffling tasks. The outcome measures were foot progression angle, peak pressure, and displacement of COP during stance phase. During running, the foot progression angle, that is, the angle of foot abduction, was lower in the AI group (Normal: 13.46° ± 4.45°; AI: 8.78° ± 3.91°), and the 1st metatarsal contact pressure (Normal: 0.76 ± 0.47 N/cm(2)·kg; AI: 1.05 ± 0.70 N/cm(2)·kg) and the 3rd metatarsal peak pressure were higher in the AI (Normal: 0.96 ± 0.60 N/cm(2)·kg; AI: 1.54 ± 0.68 N/cm(2)·kg). The medial-lateral (M-L) COP in the late-stance phase of running for the AI group transferred faster from lateral to medial foot than the Normal group. For lateral shuffling, the AI group had greater peak pressure at the 1st (Normal: 0.76 ± 0.67 N/cm(2)·kg; AI: 1.49 ± 1.04 N/cm(2)·kg), 2nd (Normal: 0.57 ± 0.39 N/cm(2)·kg; AI: 0.87 ± 0.68 N/cm(2)·kg), 3rd (Normal: 0.70 ± 0.54 N/cm(2)·kg; AI: 1.42 ± 0.87 N/cm(2)·kg), and 4th (Normal: 0.52 ± 0.38 N/cm(2)·kg; AI: 1.12 ± 0.78 N/cm(2)·kg) metatarsal areas than the Normal group. The M-L COP located more laterally from the early to mid-stance phase in the AI compared with the Normal group. The findings suggest that COP displacement during lateral shuffle may be a factor in ankle instability while the foot progression angle during running may be a compensatory strategy. © 2011 John Wiley & Sons A/S.

  5. A new approach for breeding low-temperature-resistant Volvariella volvacea strains: Genome shuffling in edible fungi.

    PubMed

    Zhu, Ziping; Wu, Xiao; Lv, Beibei; Wu, Guogan; Wang, Jinbin; Jiang, Wei; Li, Peng; He, Jianhua; Chen, Jianzhong; Chen, Mingjie; Bao, Dapeng; Zhang, Jinsong; Tan, Qi; Tang, Xueming

    2016-09-01

    Volvariella volvacea is difficult to store fresh because of the lack of low-temperature resistance. Many traditional mutagenic strategies have been applied in order to select out strains resistant to low temperature, but few commercially efficient strains have been produced. In order to break through the bottleneck of traditional breeding and significantly improve low-temperature resistance of the edible fungus V. volvacea, strains resistant to low temperature were constructed by genome shuffling. The optimum conditions of V. volvacea strain mutation, protoplast regeneration, and fusion were determined. After protoplasts were treated with 1% (v/v) ethylmethylsulfonate (EMS), 40 Sec of ultraviolet (UV) irradiation, 600 Gy electron beam implantation, and 750 Gy 60 Co-γ irradiation, separately, the lethality was within 70%-80%, which favored generating protoplasts being used in following forward mutation. Under these conditions, 16 strains of V. volvacea mutated by EMS, electron beam, UV irradiation, and 60 Co-γ irradiation were obtained. The 16 mutated protoplasts were selected to serve as the shuffling pool based on their excellent low-temperature resistance. After four rounds of genome shuffling and low-temperature resistance testing, three strains (VF 1 , VF 2 , and VF 3 ) with high genetic stability were screened. VF 1 , VF 2 , and VF 3 significantly enhanced fruit body shelf life to 20, 28, and 28 H at 10 °C, respectively, which exceeded 25%, 75%, and 75%, respectively, compared with the storage time of V23, the most low-temperature-resistant strain. Genome shuffling greatly improved the low-temperature resistance of V. volvacea, and shortened the course of screening required to generate desirable strains. To our knowledge, this is the first paper to apply genome shuffling to breeding new varieties of mushroom, and offers a new approach for breeding edible fungi with optimized phenotype. © 2015 International Union of Biochemistry and Molecular Biology

  6. Shuffling cross-validation-bee algorithm as a new descriptor selection method for retention studies of pesticides in biopartitioning micellar chromatography.

    PubMed

    Zarei, Kobra; Atabati, Morteza; Ahmadi, Monire

    2017-05-04

    Bee algorithm (BA) is an optimization algorithm inspired by the natural foraging behaviour of honey bees to find the optimal solution which can be proposed to feature selection. In this paper, shuffling cross-validation-BA (CV-BA) was applied to select the best descriptors that could describe the retention factor (log k) in the biopartitioning micellar chromatography (BMC) of 79 heterogeneous pesticides. Six descriptors were obtained using BA and then the selected descriptors were applied for model development using multiple linear regression (MLR). The descriptor selection was also performed using stepwise, genetic algorithm and simulated annealing methods and MLR was applied to model development and then the results were compared with those obtained from shuffling CV-BA. The results showed that shuffling CV-BA can be applied as a powerful descriptor selection method. Support vector machine (SVM) was also applied for model development using six selected descriptors by BA. The obtained statistical results using SVM were better than those obtained using MLR, as the root mean square error (RMSE) and correlation coefficient (R) for whole data set (training and test), using shuffling CV-BA-MLR, were obtained as 0.1863 and 0.9426, respectively, while these amounts for the shuffling CV-BA-SVM method were obtained as 0.0704 and 0.9922, respectively.

  7. Self-similar grid patterns in free-space shuffle-exchange networks

    NASA Astrophysics Data System (ADS)

    Haney, Michael W.

    1993-12-01

    Self-similar grid patterns are proposed as an alternative to rectangular grid, array optoelectronic sources, and detectors of smart pixels. For shuffle based multistage interconnection networks, it is suggested that smart pixel should not be arrayed on a rectangular grid and that smart pixel unit cell should be the kernel of a self-similar grid pattern.

  8. Genome Shuffling and Gentamicin-Resistance to Improve ε-Poly-L-Lysine Productivity of Streptomyces albulus W-156.

    PubMed

    Wang, Liang; Chen, Xusheng; Wu, Guangyao; Zeng, Xin; Ren, Xidong; Li, Shu; Tang, Lei; Mao, Zhonggui

    2016-12-01

    Genome shuffling has been a recently effective method for screening the desirable phenotypes of industrial strains. Here, we combined genome shuffling and gentamicin resistance to improve the production of ε-poly-L-lysine in Streptomyces albulus W-156. Five starting mutants with higher ε-poly-L-lysine (ε-PL) productivities were firstly obtained by atmospheric and room temperature plasma (ARTP) mutagenesis. After three rounds of genome shuffling with increasing concentration of gentamicin for selection, S. albulus AG3-28, was finally got with a production of 3.43 g/L in shaking flask. In a 5-L fermenter, AG3-28 exhibited a higher ε-PL productivity (56.5 g/L) than the initial strain W-156 (37.5 g/L). Key enzyme activities in primary and secondary metabolic pathways were analyzed, and the transcription levels of hrdD and pls were determined by quantitative real time-polymerase chain reaction (qRT-PCR). Increase of key enzyme activities and the upregulation of the gene transcriptional levels demonstrated that ε-PL synthetic pathway in AG3-28 was obviously strengthened, which might be responsible for the high productivity. Moreover, hyper-yield strain AG3-28 was found to produce a slightly lower ε-PL polymerization degree than the parent strain. Amplified fragment length polymorphism (AFLP) analysis reflects the genetic diversity among the derivates after genome shuffling.

  9. Underwater sonar image detection: A combination of non-local spatial information and quantum-inspired shuffled frog leaping algorithm.

    PubMed

    Wang, Xingmei; Liu, Shu; Liu, Zhipeng

    2017-01-01

    This paper proposes a combination of non-local spatial information and quantum-inspired shuffled frog leaping algorithm to detect underwater objects in sonar images. Specifically, for the first time, the problem of inappropriate filtering degree parameter which commonly occurs in non-local spatial information and seriously affects the denoising performance in sonar images, was solved with the method utilizing a novel filtering degree parameter. Then, a quantum-inspired shuffled frog leaping algorithm based on new search mechanism (QSFLA-NSM) is proposed to precisely and quickly detect sonar images. Each frog individual is directly encoded by real numbers, which can greatly simplify the evolution process of the quantum-inspired shuffled frog leaping algorithm (QSFLA). Meanwhile, a fitness function combining intra-class difference with inter-class difference is adopted to evaluate frog positions more accurately. On this basis, recurring to an analysis of the quantum-behaved particle swarm optimization (QPSO) and the shuffled frog leaping algorithm (SFLA), a new search mechanism is developed to improve the searching ability and detection accuracy. At the same time, the time complexity is further reduced. Finally, the results of comparative experiments using the original sonar images, the UCI data sets and the benchmark functions demonstrate the effectiveness and adaptability of the proposed method.

  10. Underwater sonar image detection: A combination of non-local spatial information and quantum-inspired shuffled frog leaping algorithm

    PubMed Central

    Liu, Zhipeng

    2017-01-01

    This paper proposes a combination of non-local spatial information and quantum-inspired shuffled frog leaping algorithm to detect underwater objects in sonar images. Specifically, for the first time, the problem of inappropriate filtering degree parameter which commonly occurs in non-local spatial information and seriously affects the denoising performance in sonar images, was solved with the method utilizing a novel filtering degree parameter. Then, a quantum-inspired shuffled frog leaping algorithm based on new search mechanism (QSFLA-NSM) is proposed to precisely and quickly detect sonar images. Each frog individual is directly encoded by real numbers, which can greatly simplify the evolution process of the quantum-inspired shuffled frog leaping algorithm (QSFLA). Meanwhile, a fitness function combining intra-class difference with inter-class difference is adopted to evaluate frog positions more accurately. On this basis, recurring to an analysis of the quantum-behaved particle swarm optimization (QPSO) and the shuffled frog leaping algorithm (SFLA), a new search mechanism is developed to improve the searching ability and detection accuracy. At the same time, the time complexity is further reduced. Finally, the results of comparative experiments using the original sonar images, the UCI data sets and the benchmark functions demonstrate the effectiveness and adaptability of the proposed method. PMID:28542266

  11. Improved wrist pannus volume measurement from contrast-enhanced MRI in rheumatoid arthritis using shuffle transform.

    PubMed

    Xanthopoulos, Emily; Hutchinson, Charles E; Adams, Judith E; Bruce, Ian N; Nash, Anthony F P; Holmes, Andrew P; Taylor, Christopher J; Waterton, John C

    2007-01-01

    Contrast-enhanced MRI is of value in assessing rheumatoid pannus in the hand, but the images are not always easy to quantitate. To develop and evaluate an improved measurement of volume of enhancing pannus (VEP) in the hand in human rheumatoid arthritis (RA). MR images of the hand and wrist were obtained for 14 patients with RA at 0, 1 and 13 weeks. Volume of enhancing pannus was measured on images created by subtracting precontrast T1-weighted images from contrast-enhanced T1-weighted images using a shuffle transformation technique. Maximum intensity projection (MIP) and 3D volume rendering of the images were used as a guide to identify the pannus and any contrast-enhanced veins. Visualisation of pannus was much improved following the shuffle transform. Between 0 weeks and 1 week, the mean value of the within-subject coefficient of variation (CoV) was 0.13 and the estimated total CoV was 0.15. There was no evidence of significant increased variability within the 13-week interval for the complete sample of patients. Volume of enhancing pannus can be measured reproducibly in the rheumatoid hand using 3D contrast-enhanced MRI and shuffle transform.

  12. Supra-domains: evolutionary units larger than single protein domains.

    PubMed

    Vogel, Christine; Berzuini, Carlo; Bashton, Matthew; Gough, Julian; Teichmann, Sarah A

    2004-02-20

    Domains are the evolutionary units that comprise proteins, and most proteins are built from more than one domain. Domains can be shuffled by recombination to create proteins with new arrangements of domains. Using structural domain assignments, we examined the combinations of domains in the proteins of 131 completely sequenced organisms. We found two-domain and three-domain combinations that recur in different protein contexts with different partner domains. The domains within these combinations have a particular functional and spatial relationship. These units are larger than individual domains and we term them "supra-domains". Amongst the supra-domains, we identified some 1400 (1203 two-domain and 166 three-domain) combinations that are statistically significantly over-represented relative to the occurrence and versatility of the individual component domains. Over one-third of all structurally assigned multi-domain proteins contain these over-represented supra-domains. This means that investigation of the structural and functional relationships of the domains forming these popular combinations would be particularly useful for an understanding of multi-domain protein function and evolution as well as for genome annotation. These and other supra-domains were analysed for their versatility, duplication, their distribution across the three kingdoms of life and their functional classes. By examining the three-dimensional structures of several examples of supra-domains in different biological processes, we identify two basic types of spatial relationships between the component domains: the combined function of the two domains is such that either the geometry of the two domains is crucial and there is a tight constraint on the interface, or the precise orientation of the domains is less important and they are spatially separate. Frequently, the role of the supra-domain becomes clear only once the three-dimensional structure is known. Since this is the case for only a

  13. Enhancement of ε-poly-lysine production in ε-poly-lysine-tolerant Streptomyces sp. by genome shuffling.

    PubMed

    Zhou, Yong-Peng; Ren, Xi-Dong; Wang, Liang; Chen, Xu-Sheng; Mao, Zhong-Gui; Tang, Lei

    2015-09-01

    ε-Poly-L-lysine (ε-PL) has been widely used as food additive. However, the self-inhibition of ε-PL on cell growth limits the accumulation of ε-PL in the wild-type strain. Here, we screened ε-PL-tolerant strain of Streptomyces sp. with higher ε-PL productivity by genome shuffling and studied the mechanism for the improvement. The initial mutant library was constructed by diethyl sulfate mutagenesis. After four rounds of protoplast fusion, a shuffled strain F4-22 with 3.11 g/L ε-PL productivity in shake flask, 1.81-fold in comparison with that of parent strain, was obtained. The higher aspartokinase activity was induced in F4-22 whereas no obvious changes have been found in ε-PL synthetic and degrading enzymes which indicated that the upstream reregulation of the precursor lysine synthesis rather than lysine polymerization or ε-PL degradation in shuffled strain accounted for the higher productivity. The activities of key enzymes in the central metabolic pathway were also enhanced in F4-22 which resulted in increased vigor of the strain and in delayed strain lysis during fermentation. These improved properties of shuffled strain led to the success of combining general two-stage fermentation into one-stage one in 5-L bioreactor with 32.7 % more ε-PL production than that of parent strain. The strategy used in this study provided a novel strain breeding approach of producers which suffered from ε-PL-like self-inhibition of the metabolites.

  14. Genome shuffling improves thermotolerance and glutamic acid production of Corynebacteria glutamicum.

    PubMed

    Zheng, Pu; Liu, Miao; Liu, Xiao-de; Du, Qiao-Yan; Ni, Ye; Sun, Zhi-Hao

    2012-03-01

    Genome shuffling was used to improve the thermotolerance of L: -glutamic acid-producing strain Corynebacteria glutamicum. Five strains with subtle improvements in high temperature tolerance and productivity were selected by ultraviolet irradiation and diethyl sulfate mutagenesis. An improved strain (F343) was obtained by three rounds of genome shuffling of the five strains as mentioned above. The cell density of F343 was four times higher than that of ancestor strains after 24 h of cultivation at 44°C, and importantly, the yield of L: -glutamic acid was increased by 1.8-times comparing with that of the ancestor strain at 38°C in a 5-L fermentor. With glucose supplement and two-stage pH control, the L: -glutamate acid concentration of F343 reached 119 g/L after fermentation for 30 h. The genetic diversity between F343 and its ancestors was also evaluated by amplified fragment length polymorphism analysis. Results suggest that the phenotypes for both thermotolerance and L: -glutamic acid production in F343 were evolved.

  15. Genome shuffling of Saccharomyces cerevisiae for enhanced glutathione yield and relative gene expression analysis using fluorescent quantitation reverse transcription polymerase chain reaction.

    PubMed

    Yin, Hua; Ma, Yanlin; Deng, Yang; Xu, Zhenbo; Liu, Junyan; Zhao, Junfeng; Dong, Jianjun; Yu, Junhong; Chang, Zongming

    2016-08-01

    Genome shuffling is an efficient and promising approach for the rapid improvement of microbial phenotypes. In this study, genome shuffling was applied to enhance the yield of glutathione produced by Saccharomyces cerevisiae YS86. Six isolates with subtle improvements in glutathione yield were obtained from populations generated by ultraviolet (UV) irradiation and nitrosoguanidine (NTG) mutagenesis. These yeast strains were then subjected to recursive pool-wise protoplast fusion. A strain library that was likely to yield positive colonies was created by fusing the lethal protoplasts obtained from both UV irradiation and heat treatments. After two rounds of genome shuffling, a high-yield recombinant YSF2-19 strain that exhibited 3.2- and 3.3-fold increases in glutathione production in shake flask and fermenter respectively was obtained. Comparative analysis of synthetase gene expression was conducted between the initial and shuffled strains using FQ (fluorescent quantitation) RT-PCR (reverse transcription polymerase chain reaction). Delta CT (threshold cycle) relative quantitation analysis revealed that glutathione synthetase gene (GSH-I) expression at the transcriptional level in the YSF2-19 strain was 9.9-fold greater than in the initial YS86. The shuffled yeast strain has a potential application in brewing, other food, and pharmaceutical industries. Simultaneously, the analysis of improved phenotypes will provide more valuable data for inverse metabolic engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Evolutionary Novelty in a Butterfly Wing Pattern through Enhancer Shuffling

    PubMed Central

    Pardo-Diaz, Carolina; Hanly, Joseph J.; Martin, Simon H.; Mallet, James; Dasmahapatra, Kanchon K.; Salazar, Camilo; Joron, Mathieu; Nadeau, Nicola; McMillan, W. Owen; Jiggins, Chris D.

    2016-01-01

    An important goal in evolutionary biology is to understand the genetic changes underlying novel morphological structures. We investigated the origins of a complex wing pattern found among Amazonian Heliconius butterflies. Genome sequence data from 142 individuals across 17 species identified narrow regions associated with two distinct red colour pattern elements, dennis and ray. We hypothesise that these modules in non-coding sequence represent distinct cis-regulatory loci that control expression of the transcription factor optix, which in turn controls red pattern variation across Heliconius. Phylogenetic analysis of the two elements demonstrated that they have distinct evolutionary histories and that novel adaptive morphological variation was created by shuffling these cis-regulatory modules through recombination between divergent lineages. In addition, recombination of modules into different combinations within species further contributes to diversity. Analysis of the timing of diversification in these two regions supports the hypothesis of introgression moving regulatory modules between species, rather than shared ancestral variation. The dennis phenotype introgressed into Heliconius melpomene at about the same time that ray originated in this group, while ray introgressed back into H. elevatus much more recently. We show that shuffling of existing enhancer elements both within and between species provides a mechanism for rapid diversification and generation of novel morphological combinations during adaptive radiation. PMID:26771987

  17. Evolutionary Novelty in a Butterfly Wing Pattern through Enhancer Shuffling.

    PubMed

    Wallbank, Richard W R; Baxter, Simon W; Pardo-Diaz, Carolina; Hanly, Joseph J; Martin, Simon H; Mallet, James; Dasmahapatra, Kanchon K; Salazar, Camilo; Joron, Mathieu; Nadeau, Nicola; McMillan, W Owen; Jiggins, Chris D

    2016-01-01

    An important goal in evolutionary biology is to understand the genetic changes underlying novel morphological structures. We investigated the origins of a complex wing pattern found among Amazonian Heliconius butterflies. Genome sequence data from 142 individuals across 17 species identified narrow regions associated with two distinct red colour pattern elements, dennis and ray. We hypothesise that these modules in non-coding sequence represent distinct cis-regulatory loci that control expression of the transcription factor optix, which in turn controls red pattern variation across Heliconius. Phylogenetic analysis of the two elements demonstrated that they have distinct evolutionary histories and that novel adaptive morphological variation was created by shuffling these cis-regulatory modules through recombination between divergent lineages. In addition, recombination of modules into different combinations within species further contributes to diversity. Analysis of the timing of diversification in these two regions supports the hypothesis of introgression moving regulatory modules between species, rather than shared ancestral variation. The dennis phenotype introgressed into Heliconius melpomene at about the same time that ray originated in this group, while ray introgressed back into H. elevatus much more recently. We show that shuffling of existing enhancer elements both within and between species provides a mechanism for rapid diversification and generation of novel morphological combinations during adaptive radiation.

  18. Significant expansion of exon-bordering protein domains during animal proteome evolution

    PubMed Central

    Liu, Mingyi; Walch, Heiko; Wu, Shaoping; Grigoriev, Andrei

    2005-01-01

    We present evidence of remarkable genome-wide mobility and evolutionary expansion for a class of protein domains whose borders locate close to the borders of their encoding exons. These exon-bordering domains are more numerous and widely distributed in the human genome than other domains. They also co-occur with more diverse domains to form a larger variety of domain architectures in human proteins. A systematic comparison of nine animal genomes from nematodes to mammals revealed that exon-bordering domains expanded faster than other protein domains in both abundance and distribution, as well as the diversity of co-occurring domains and the domain architectures of harboring proteins. Furthermore, exon-bordering domains exhibited a particularly strong preference for class 1-1 intron phase. Our findings suggest that exon-bordering domains were amplified and interchanged within a genome more often and/or more successfully than other domains during evolution, probably the result of extensive exon shuffling and gene duplication events. The diverse biological functions of these domains underscore the important role they play in the expansion and diversification of animal proteomes. PMID:15640447

  19. Antimicrobial activity predictors benchmarking analysis using shuffled and designed synthetic peptides.

    PubMed

    Porto, William F; Pires, Állan S; Franco, Octavio L

    2017-08-07

    The antimicrobial activity prediction tools aim to help the novel antimicrobial peptides (AMP) sequences discovery, utilizing machine learning methods. Such approaches have gained increasing importance in the generation of novel synthetic peptides by means of rational design techniques. This study focused on predictive ability of such approaches to determine the antimicrobial sequence activities, which were previously characterized at the protein level by in vitro studies. Using four web servers and one standalone software, we evaluated 78 sequences generated by the so-called linguistic model, being 40 designed and 38 shuffled sequences, with ∼60 and ∼25% of identity to AMPs, respectively. The ab initio molecular modelling of such sequences indicated that the structure does not affect the predictions, as both sets present similar structures. Overall, the systems failed on predicting shuffled versions of designed peptides, as they are identical in AMPs composition, which implies in accuracies below 30%. The prediction accuracy is negatively affected by the low specificity of all systems here evaluated, as they, on the other hand, reached 100% of sensitivity. Our results suggest that complementary approaches with high specificity, not necessarily high accuracy, should be developed to be used together with the current systems, overcoming their limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Domain Specificity in Relationship History, Social-Information Processing, and Violent Behavior in Early Adulthood

    PubMed Central

    Pettit, Gregory S.; Lansford, Jennifer E.; Malone, Patrick S.; Dodge, Kenneth A.; Bates, John E.

    2013-01-01

    Using prospective longitudinal data, we tested 5 hypotheses: (a) that the relation between earlier developmental experiences (peer social rejection and victimization in a romantic relationship) and adult violent behavior toward peers and romantic partners is specific to relationship domain; (b) that the relation between social-information processing (SIP) biases and subsequent violence is also specific to relational domain (romantic partner vs. peer); (c) that the relation between developmental experiences and SIP biases is domain specific; (d) that domain-specific SIP mediates the impact of earlier developmental experiences on later violent behavior; and (e) that harsh parenting early in life is a domain-general predictor of SIP and later violent behavior. Harsh parenting was assessed through interviews with parents when their children were age 5 years. Classroom sociometric assessments indexing peer rejection were completed in elementary school, and self-report of victimization by romantic partners was provided at age 18 years. SIP was assessed via interview at age 22 years, and violent behavior was measured via self-and partner report at ages 23 years and 24 years. Structural equation analyses revealed specificity in the relation between developmental experiences and violence and in the prediction to and from SIP in the peer domain, but not in the romantic-relationship domain. The impact of early harsh treatment on violence toward peers was mediated by SIP biases in the peer domain. These findings provide support for domain specificity in the peer domain but for cross-domain generality in the romantic relationship domain in the development of violent behavior in early adulthood. PMID:20085394

  1. Increased xylose affinity of Hxt2 through gene shuffling of hexose transporters in Saccharomyces cerevisiae.

    PubMed

    Nijland, J G; Shin, H Y; de Waal, P P; Klaassen, P; Driessen, A J M

    2018-02-01

    Optimizing D-xylose transport in Saccharomyces cerevisiae is essential for efficient bioethanol production from cellulosic materials. We have used a gene shuffling approach of hexose (Hxt) transporters in order to increase the affinity for D-xylose. Various libraries were transformed to a hexose transporter deletion strain, and shuffled genes were selected via growth on low concentrations of D-xylose. This screening yielded two homologous fusion proteins (fusions 9,4 and 9,6), both consisting of the major central part of Hxt2 and various smaller parts of other Hxt proteins. Both chimeric proteins showed the same increase in D-xylose affinity (8·1 ± 3·0 mmol l -1 ) compared with Hxt2 (23·7 ± 2·1 mmol l -1 ). The increased D-xylose affinity could be related to the C terminus, more specifically to a cysteine to proline mutation at position 505 in Hxt2. The Hxt2 C505P mutation increased the affinity for D-xylose for Hxt2, thus providing a way to increase D-xylose transport flux at low D-xylose concentration. The gene shuffling protocol using the highly homologues hexose transporters family provides a powerful tool to enhance the D-xylose affinity of Hxt transporters in S. cerevisiae, thus providing a means to increase the D-xylose uptake flux at low D-xylose concentrations. © 2017 The Society for Applied Microbiology.

  2. The combination of glycerol metabolic engineering and drug resistance marker-aided genome shuffling to improve very-high-gravity fermentation performances of industrial Saccharomyces cerevisiae.

    PubMed

    Wang, Pin-Mei; Zheng, Dao-Qiong; Liu, Tian-Zhe; Tao, Xiang-Lin; Feng, Ming-Guang; Min, Hang; Jiang, Xin-Hang; Wu, Xue-Chang

    2012-03-01

    A challenge associated with the ethanol productivity under very-high-gravity (VHG) conditions, optimizing multi-traits (i.e. byproduct formation and stress tolerance) of industrial yeast strains, is overcome by a combination of metabolic engineering and genome shuffling. First, industrial strain Y12 was deleted with a glycerol exporter Fps1p and hetero-expressed with glyceraldehydes-3-phosphate dehydrogenase, resulting in the modified strain YFG12 with lower glycerol yield. Second, YFG12 was subjected to three rounds of drug resistance marker-aided genome shuffling to increase its ethanol tolerance, and the best shuffled strain TS5 was obtained. Compared with wild strain Y12, shuffled strain TS5 not only decreased glycerol formation by 14.8%, but also increased fermentation rate and ethanol yield by 3.7% and 7.6%, respectively. Moreover, the system of genetic modification and Cre/loxP in aid of three different drug-resistance markers presented in the study significantly improved breeding efficiency and will facilitate the application of breeding technologies in prototrophic industrial microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Biogeography and body size shuffling of aquatic salamander communities on a shifting refuge

    PubMed Central

    Bonett, Ronald M.; Trujano-Alvarez, Ana Lilia; Williams, Michael J.; Timpe, Elizabeth K.

    2013-01-01

    Freshwater habitats of coastal plains are refugia for many divergent vertebrate lineages, yet these environments are highly vulnerable to sea-level fluctuations, which suggest that resident communities have endured dynamic histories. Using the fossil record and a multi-locus nuclear phylogeny, we examine divergence times, biogeography, body size evolution and patterns of community assembly of aquatic salamanders from North American coastal plains since the Late Cretaceous. At least five salamander families occurred on the extensive Western Interior Coastal Plain (WICP), which existed from the Late Cretaceous through the Eocene. Four of these families subsequently colonized the emergent Southeastern Coastal Plain (SECP) by the Early Oligocene to Late Miocene. Three families ultimately survived and underwent extensive body size evolution in situ on the SECP. This included at least two major size reversals in recent taxa that are convergent with confamilial WICP ancestors. Dynamics of the coastal plain, major lineage extinctions and frequent extreme changes in body size have resulted in significant shuffling of the size structure of aquatic salamander communities on this shifting refuge since the Cretaceous. PMID:23466988

  4. Cumulants, free cumulants and half-shuffles

    PubMed Central

    Ebrahimi-Fard, Kurusch; Patras, Frédéric

    2015-01-01

    Free cumulants were introduced as the proper analogue of classical cumulants in the theory of free probability. There is a mix of similarities and differences, when one considers the two families of cumulants. Whereas the combinatorics of classical cumulants is well expressed in terms of set partitions, that of free cumulants is described and often introduced in terms of non-crossing set partitions. The formal series approach to classical and free cumulants also largely differs. The purpose of this study is to put forward a different approach to these phenomena. Namely, we show that cumulants, whether classical or free, can be understood in terms of the algebra and combinatorics underlying commutative as well as non-commutative (half-)shuffles and (half-) unshuffles. As a corollary, cumulants and free cumulants can be characterized through linear fixed point equations. We study the exponential solutions of these linear fixed point equations, which display well the commutative, respectively non-commutative, character of classical and free cumulants. PMID:27547078

  5. Enhanced degradation of perfluorooctanoic acid by a genome shuffling-modified Pseudomonas parafulva YAB-1.

    PubMed

    Yi, Langbo; Peng, Qingzhong; Liu, Deming; Zhou, Lulu; Tang, Chongjian; Zhou, Yaoyu; Chai, Liyuan

    2018-05-02

    Perfluorooctanoic acid (PFOA) as an emerging persistent organic pollutant is hard to be degraded by conventional methods because of its stable physical and chemical properties. Microbial transformation is an attractive remediation approach to prevent and clean up PFOA contamination. To date, several strains of wild microbes have been reported to have limited capacity to degrade PFOA, selection of superior strains degrading PFOA become urgently necessary. Here, we report the application of genome shuffling to improve the PFOA-degrading bacterium Pseudomonas Parafulva YAB-1. The initial mutant populations of strain YAB1 were generated by nitrosoguanidine and ultraviolet irradiation mutagenesis respectively, resulting in mutants YM-9 and YM-19 with slightly improved PFOA-degrading ability. YM-9 and YM-19 were used as the starting strains for three rounds of recursive protoplast fusion. The positive mutants were screened on inorganic salt medium plates containing different concentrations of PFOA and selected based on their PFOA degradability in shake-flask fermentation test. The best performing recombinant F3-52 was isolated after three rounds of genome shuffling. In batch fermentation, the PFOA degradation rate of mutant F3-52 was up to 58.6%, which was 1.8-fold higher than that of the parent strain YAB1, and 1.6-fold higher than the initial mutants YM-9 and YM-19. Pass-generation test indicated that the heredity character of F3-52 was stable. The results demonstrated that genome shuffling was an efficient method for improving PFOA degradation of Pseudomonas Parafulva YAB1. The bred mutant F3-52 with 58.6% PFOA-degrading rate could be used for the environmental control of PFOA pollutant.

  6. Magnetic shuffling of coronal downdrafts

    NASA Astrophysics Data System (ADS)

    Petralia, A.; Reale, F.; Orlando, S.

    2017-02-01

    Context. Channelled fragmented downflows are ubiquitous in magnetized atmospheres, and have recently been addressed based on an observation after a solar eruption. Aims: We study the possible back-effect of the magnetic field on the propagation of confined flows. Methods: We compared two 3D magnetohydrodynamic simulations of dense supersonic plasma blobs that fall down along a coronal magnetic flux tube. In one, the blobs move strictly along the field lines; in the other, the initial velocity of the blobs is not perfectly aligned with the magnetic field and the field is weaker. Results: The aligned blobs remain compact while flowing along the tube, with the generated shocks. The misaligned blobs are disrupted and merge through the chaotic shuffling of the field lines. They are structured into thinner filaments. Alfvén wave fronts are generated together with shocks ahead of the dense moving front. Conclusions: Downflowing plasma fragments can be chaotically and efficiently mixed if their motion is misaligned with field lines, with broad implications for disk accretion in protostars, coronal eruptions, and rain, for example. Movies associated to Figs. 2 and 3 are available at http://www.aanda.org

  7. Constraining antimatter domains in the early universe with big bang nucleosynthesis.

    PubMed

    Kurki-Suonio, H; Sihvola, E

    2000-04-24

    We consider the effect of a small-scale matter-antimatter domain structure on big bang nucleosynthesis and place upper limits on the amount of antimatter in the early universe. For small domains, which annihilate before nucleosynthesis, this limit comes from underproduction of 4He. For larger domains, the limit comes from 3He overproduction. Since most of the 3He from &pmacr; 4He annihilation are themselves annihilated, the main source of primordial 3He is the photodisintegration of 4He by the electromagnetic cascades initiated by the annihilation.

  8. Domain architecture conservation in orthologs

    PubMed Central

    2011-01-01

    Background As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. Results The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. Conclusions On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the

  9. Anthropogenic climate change drives shift and shuffle in North Atlantic phytoplankton communities.

    PubMed

    Barton, Andrew D; Irwin, Andrew J; Finkel, Zoe V; Stock, Charles A

    2016-03-15

    Anthropogenic climate change has shifted the biogeography and phenology of many terrestrial and marine species. Marine phytoplankton communities appear sensitive to climate change, yet understanding of how individual species may respond to anthropogenic climate change remains limited. Here, using historical environmental and phytoplankton observations, we characterize the realized ecological niches for 87 North Atlantic diatom and dinoflagellate taxa and project changes in species biogeography between mean historical (1951-2000) and future (2051-2100) ocean conditions. We find that the central positions of the core range of 74% of taxa shift poleward at a median rate of 12.9 km per decade (km⋅dec(-1)), and 90% of taxa shift eastward at a median rate of 42.7 km⋅dec(-1) The poleward shift is faster than previously reported for marine taxa, and the predominance of longitudinal shifts is driven by dynamic changes in multiple environmental drivers, rather than a strictly poleward, temperature-driven redistribution of ocean habitats. A century of climate change significantly shuffles community composition by a basin-wide median value of 16%, compared with seasonal variations of 46%. The North Atlantic phytoplankton community appears poised for marked shift and shuffle, which may have broad effects on food webs and biogeochemical cycles.

  10. A protein domain-based interactome network for C. elegans early embryogenesis

    PubMed Central

    Boxem, Mike; Maliga, Zoltan; Klitgord, Niels; Li, Na; Lemmens, Irma; Mana, Miyeko; de Lichtervelde, Lorenzo; Mul, Joram D.; van de Peut, Diederik; Devos, Maxime; Simonis, Nicolas; Yildirim, Muhammed A.; Cokol, Murat; Kao, Huey-Ling; de Smet, Anne-Sophie; Wang, Haidong; Schlaitz, Anne-Lore; Hao, Tong; Milstein, Stuart; Fan, Changyu; Tipsword, Mike; Drew, Kevin; Galli, Matilde; Rhrissorrakrai, Kahn; Drechsel, David; Koller, Daphne; Roth, Frederick P.; Iakoucheva, Lilia M.; Dunker, A. Keith; Bonneau, Richard; Gunsalus, Kristin C.; Hill, David E.; Piano, Fabio; Tavernier, Jan; van den Heuvel, Sander; Hyman, Anthony A.; Vidal, Marc

    2008-01-01

    Summary Many protein-protein interactions are mediated through independently folding modular domains. Proteome-wide efforts to model protein-protein interaction or “interactome” networks have largely ignored this modular organization of proteins. We developed an experimental strategy to efficiently identify interaction domains and generated a domain-based interactome network for proteins involved in C. elegans early embryonic cell divisions. Minimal interacting regions were identified for over 200 proteins, providing important information on their domain organization. Furthermore, our approach increased the sensitivity of the two-hybrid system, resulting in a more complete interactome network. This interactome modeling strategy revealed new insights into C. elegans centrosome function and is applicable to other biological processes in this and other organisms. PMID:18692475

  11. bcc-to-hcp transformation pathways for iron versus hydrostatic pressure: Coupled shuffle and shear modes

    NASA Astrophysics Data System (ADS)

    Liu, J. B.; Johnson, D. D.

    2009-04-01

    Using density-functional theory, we calculate the potential-energy surface (PES), minimum-energy pathway (MEP), and transition state (TS) versus hydrostatic pressure σhyd for the reconstructive transformation in Fe from body-centered cubic (bcc) to hexagonal closed-packed (hcp). At fixed σhyd , the PES is described by coupled shear (γ) and shuffle (η) modes and is determined from structurally minimized hcp-bcc energy differences at a set of (η,γ) . We fit the PES using symmetry-adapted polynomials, permitting the MEP to be found analytically. The MEP is continuous and fully explains the transformation and its associated magnetization and volume discontinuity at TS. We show that σhyd (while not able to induce shear) dramatically alters the MEP to drive reconstruction by a shuffle-only mode at ≤30GPa , as observed. Finally, we relate our polynomial-based results to Landau and nudge-elastic-band approaches and show they yield incorrect MEP in general.

  12. An improved shuffled frog leaping algorithm based evolutionary framework for currency exchange rate prediction

    NASA Astrophysics Data System (ADS)

    Dash, Rajashree

    2017-11-01

    Forecasting purchasing power of one currency with respect to another currency is always an interesting topic in the field of financial time series prediction. Despite the existence of several traditional and computational models for currency exchange rate forecasting, there is always a need for developing simpler and more efficient model, which will produce better prediction capability. In this paper, an evolutionary framework is proposed by using an improved shuffled frog leaping (ISFL) algorithm with a computationally efficient functional link artificial neural network (CEFLANN) for prediction of currency exchange rate. The model is validated by observing the monthly prediction measures obtained for three currency exchange data sets such as USD/CAD, USD/CHF, and USD/JPY accumulated within same period of time. The model performance is also compared with two other evolutionary learning techniques such as Shuffled frog leaping algorithm and Particle Swarm optimization algorithm. Practical analysis of results suggest that, the proposed model developed using the ISFL algorithm with CEFLANN network is a promising predictor model for currency exchange rate prediction compared to other models included in the study.

  13. Allergy multivaccines created by DNA shuffling of tree pollen allergens.

    PubMed

    Wallner, Michael; Stöcklinger, Angelika; Thalhamer, Theresa; Bohle, Barbara; Vogel, Lothar; Briza, Peter; Breiteneder, Heimo; Vieths, Stefan; Hartl, Arnulf; Mari, Adriano; Ebner, Christof; Lackner, Peter; Hammerl, Peter; Thalhamer, Josef; Ferreira, Fatima

    2007-08-01

    The major allergens of trees belonging to the Fagales order are collectively known as the Bet v 1 family. Members of the Fagales order have distinct geographic distribution, and it is expected that depending on the exposure pattern of the individual, inclusion of other Bet v 1 family members might increase the efficacy of the treatment. We aimed to generate molecules that are suitable for specific immunotherapy not only against birch pollen allergy but also against allergies caused by other cross-reactive tree pollens. Fourteen genes of the Bet v 1 family were randomly recombined in vitro by means of DNA shuffling. This library of chimeric proteins was screened for molecules displaying low capacity to induce release of inflammatory mediators but with T-cell immunogenicity higher than that of the parental allergens. Two chimeric proteins were selected from the library of shuffled clones displaying low allergenicity and high immunogenicity, as determined in in vitro assays using human and animal cells and antibodies, as well as in vivo in animal models of allergy. Our results show that it is possible to randomly recombine in vitro T- and B-cell epitopes of a family of related allergens and to select chimeric proteins that perfectly match the criteria presently thought to be relevant for improving allergen-specific immunotherapy. The hypoallergenic chimeras described here recombine epitopes of the major Fagales pollen allergens and thus can efficiently substitute a mixture of extracts used for treating patients with tree pollen-induced spring pollinosis worldwide.

  14. Nod-shuffle 3D spectroscopy with PMAS

    NASA Astrophysics Data System (ADS)

    Roth, Martin M.; Fechner, Thomas; Becker, Thomas; Kelz, Andreas

    2004-09-01

    PMAS is a versatile integral field spectrograph based on the principle of a fiber-coupled lens array type of IFU. The instrument was commissioned at the Calar Alto 3.5m Telescope in May 2001. PMAS is offered as a common user instrument at Calar Alto since 2002. However, it has remained flexible enough to be used as a testbed for new observing techniques. Since the instrument is sensitive in the wavelength range from 0.35 to 1 μm, it is being used to experiment with faint object 3D spectroscopy for a variety of objects in stellar and extragalactic astronomy. Among these experiments, we have implemented a nod-shuffle mode of operation, which is a beam switching technique to achieve a high degree of sky subtraction accuracy. We describe the technical details of the special solution found for PMAS and first results obtained in test observations of faint haloes of planetary nebulae.

  15. When the Earth's Inner Core Shuffles

    NASA Astrophysics Data System (ADS)

    Tkalcic, H.; Young, M. K.; Bodin, T.; Ngo, S.; Sambridge, M.

    2011-12-01

    Shuffling is a tribal dance recently adapted by teenagers as a street dance. In one of the most popular moves, the so-called "Running Man", a stomp forward on one foot, shifted without being lifted from the ground, is followed by a change of position backwards on the same foot. Here, we present strong observational evidence from a newly observed collection of earthquake doublets that the Earth's inner core "shuffles" exhibiting both prograde and retrograde rotation in the reference frame of the mantle. This discovery is significant on several levels. First, the observed pattern consists of intermittent intervals of quasi-locked and differentially rotating inner core with respect to the Earth's mantle. This means that the angular alignment of the inner core and mantle oscillates in time over the past five decades. Jolting temporal changes are revealed, indicating that during the excursions from the quasi-locked state, the Earth's inner core can rotate both faster and slower than the rest of the planet, thus exhibiting both eastward and westward rotation. According to our results, a short time interval (on the order of one to two years) is needed for the inner core to accelerate to a differential rotation rate of several degrees per year, and typically a slightly longer time is needed to decelerate down to a negligibly small differential rotation rate. These time scales are in agreement with experimental spin-up times obtained when the magnetic torque alone is used to accelerate the inner core. Second, when we integrate the rotation rate over different time intervals, it is possible to explain discrepancies between the body wave and normal modes results for the rate of the inner core differential rotation found by previous authors. We show that the integrated shift in angular alignment and average rotation rates (previously determined to be constant) in normal mode studies are much smaller that those for the body waves. The repeating earthquakes from the South

  16. A copyright protection scheme for digital images based on shuffled singular value decomposition and visual cryptography.

    PubMed

    Devi, B Pushpa; Singh, Kh Manglem; Roy, Sudipta

    2016-01-01

    This paper proposes a new watermarking algorithm based on the shuffled singular value decomposition and the visual cryptography for copyright protection of digital images. It generates the ownership and identification shares of the image based on visual cryptography. It decomposes the image into low and high frequency sub-bands. The low frequency sub-band is further divided into blocks of same size after shuffling it and then the singular value decomposition is applied to each randomly selected block. Shares are generated by comparing one of the elements in the first column of the left orthogonal matrix with its corresponding element in the right orthogonal matrix of the singular value decomposition of the block of the low frequency sub-band. The experimental results show that the proposed scheme clearly verifies the copyright of the digital images, and is robust to withstand several image processing attacks. Comparison with the other related visual cryptography-based algorithms reveals that the proposed method gives better performance. The proposed method is especially resilient against the rotation attack.

  17. Do the shuffle: Changes in Symbiodinium consortia throughout juvenile coral development

    PubMed Central

    Reich, Hannah G.; Robertson, Deborah L.; Goodbody-Gringley, Gretchen

    2017-01-01

    Previous studies of symbiotic associations between scleractinians corals and Symbiodinium have demonstrated that the consortium of symbionts can change in response to environmental conditions. However, less is known about symbiont shuffling during early coral development, particularly in brooding species. This study examined whether Symbiodinium consortia (1) varied in Porites astreoides on shallow (10m) and upper mesophotic (30m) reefs, (2) changed during coral development, and (3) influenced growth of juveniles in different environments. Symbiodinium ITS2 sequences were amplified using universal primers and analyzed using phylotype-specific primers designed for phylotypes A, B, and C. Adults from both depths were found to host only phylotype A, phylotypes A and B, or phylotypes A, B, and C and the frequency of the phylotype composition did not vary with depth. However, phylotype A was the dominant symbiont that was vertically transmitted to the planulae. The presence of phylotypes B and C was detected in the majority of juveniles when transplanted onto the shallow and upper mesophotic reefs whereas only phylotype A was detected in the majority of juveniles reared in outdoor aquaria. In addition, growth of juvenile P. astreoides harboring different combinations of Symbiodinium phylotypes did not vary when transplanted to different reef zones. However, juveniles reared in in situ reef environments grew faster than those reared in ex situ outdoor aquaria. These results show that Symbiodinium consortia change during development of P. astreoides and are influenced by environmental conditions. PMID:28182684

  18. Residual Shuffling Convolutional Neural Networks for Deep Semantic Image Segmentation Using Multi-Modal Data

    NASA Astrophysics Data System (ADS)

    Chen, K.; Weinmann, M.; Gao, X.; Yan, M.; Hinz, S.; Jutzi, B.; Weinmann, M.

    2018-05-01

    In this paper, we address the deep semantic segmentation of aerial imagery based on multi-modal data. Given multi-modal data composed of true orthophotos and the corresponding Digital Surface Models (DSMs), we extract a variety of hand-crafted radiometric and geometric features which are provided separately and in different combinations as input to a modern deep learning framework. The latter is represented by a Residual Shuffling Convolutional Neural Network (RSCNN) combining the characteristics of a Residual Network with the advantages of atrous convolution and a shuffling operator to achieve a dense semantic labeling. Via performance evaluation on a benchmark dataset, we analyze the value of different feature sets for the semantic segmentation task. The derived results reveal that the use of radiometric features yields better classification results than the use of geometric features for the considered dataset. Furthermore, the consideration of data on both modalities leads to an improvement of the classification results. However, the derived results also indicate that the use of all defined features is less favorable than the use of selected features. Consequently, data representations derived via feature extraction and feature selection techniques still provide a gain if used as the basis for deep semantic segmentation.

  19. PrecisePrimer: an easy-to-use web server for designing PCR primers for DNA library cloning and DNA shuffling.

    PubMed

    Pauthenier, Cyrille; Faulon, Jean-Loup

    2014-07-01

    PrecisePrimer is a web-based primer design software made to assist experimentalists in any repetitive primer design task such as preparing, cloning and shuffling DNA libraries. Unlike other popular primer design tools, it is conceived to generate primer libraries with popular PCR polymerase buffers proposed as pre-set options. PrecisePrimer is also meant to design primers in batches, such as for DNA libraries creation of DNA shuffling experiments and to have the simplest interface possible. It integrates the most up-to-date melting temperature algorithms validated with experimental data, and cross validated with other computational tools. We generated a library of primers for the extraction and cloning of 61 genes from yeast DNA genomic extract using default parameters. All primer pairs efficiently amplified their target without any optimization of the PCR conditions. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. The role of internal duplication in the evolution of multi-domain proteins.

    PubMed

    Nacher, J C; Hayashida, M; Akutsu, T

    2010-08-01

    Many proteins consist of several structural domains. These multi-domain proteins have likely been generated by selective genome growth dynamics during evolution to perform new functions as well as to create structures that fold on a biologically feasible time scale. Domain units frequently evolved through a variety of genetic shuffling mechanisms. Here we examine the protein domain statistics of more than 1000 organisms including eukaryotic, archaeal and bacterial species. The analysis extends earlier findings on asymmetric statistical laws for proteome to a wider variety of species. While proteins are composed of a wide range of domains, displaying a power-law decay, the computation of domain families for each protein reveals an exponential distribution, characterizing a protein universe composed of a thin number of unique families. Structural studies in proteomics have shown that domain repeats, or internal duplicated domains, represent a small but significant fraction of genome. In spite of its importance, this observation has been largely overlooked until recently. We model the evolutionary dynamics of proteome and demonstrate that these distinct distributions are in fact rooted in an internal duplication mechanism. This process generates the contemporary protein structural domain universe, determines its reduced thickness, and tames its growth. These findings have important implications, ranging from protein interaction network modeling to evolutionary studies based on fundamental mechanisms governing genome expansion.

  1. Predicting first-grade mathematics achievement: the contributions of domain-general cognitive abilities, nonverbal number sense, and early number competence.

    PubMed

    Hornung, Caroline; Schiltz, Christine; Brunner, Martin; Martin, Romain

    2014-01-01

    Early number competence, grounded in number-specific and domain-general cognitive abilities, is theorized to lay the foundation for later math achievement. Few longitudinal studies have tested a comprehensive model for early math development. Using structural equation modeling and mediation analyses, the present work examined the influence of kindergarteners' nonverbal number sense and domain-general abilities (i.e., working memory, fluid intelligence, and receptive vocabulary) and their early number competence (i.e., symbolic number skills) on first grade math achievement (i.e., arithmetic, shape and space skills, and number line estimation) assessed 1 year later. Latent regression models revealed that nonverbal number sense and working memory are central building blocks for developing early number competence in kindergarten and that early number competence is key for first grade math achievement. After controlling for early number competence, fluid intelligence significantly predicted arithmetic and number line estimation while receptive vocabulary significantly predicted shape and space skills. In sum we suggest that early math achievement draws on different constellations of number-specific and domain-general mechanisms.

  2. Predicting first-grade mathematics achievement: the contributions of domain-general cognitive abilities, nonverbal number sense, and early number competence

    PubMed Central

    Hornung, Caroline; Schiltz, Christine; Brunner, Martin; Martin, Romain

    2014-01-01

    Early number competence, grounded in number-specific and domain-general cognitive abilities, is theorized to lay the foundation for later math achievement. Few longitudinal studies have tested a comprehensive model for early math development. Using structural equation modeling and mediation analyses, the present work examined the influence of kindergarteners' nonverbal number sense and domain-general abilities (i.e., working memory, fluid intelligence, and receptive vocabulary) and their early number competence (i.e., symbolic number skills) on first grade math achievement (i.e., arithmetic, shape and space skills, and number line estimation) assessed 1 year later. Latent regression models revealed that nonverbal number sense and working memory are central building blocks for developing early number competence in kindergarten and that early number competence is key for first grade math achievement. After controlling for early number competence, fluid intelligence significantly predicted arithmetic and number line estimation while receptive vocabulary significantly predicted shape and space skills. In sum we suggest that early math achievement draws on different constellations of number-specific and domain-general mechanisms. PMID:24772098

  3. Evolution of synthetic signaling scaffolds by recombination of modular protein domains.

    PubMed

    Lai, Andicus; Sato, Paloma M; Peisajovich, Sergio G

    2015-06-19

    Signaling scaffolds are proteins that interact via modular domains with multiple partners, regulating signaling networks in space and time and providing an ideal platform from which to alter signaling functions. However, to better exploit scaffolds for signaling engineering, it is necessary to understand the full extent of their modularity. We used a directed evolution approach to identify, from a large library of randomly shuffled protein interaction domains, variants capable of rescuing the signaling defect of a yeast strain in which Ste5, the scaffold in the mating pathway, had been deleted. After a single round of selection, we identified multiple synthetic scaffold variants with diverse domain architectures, able to mediate mating pathway activation in a pheromone-dependent manner. The facility with which this signaling network accommodates changes in scaffold architecture suggests that the mating signaling complex does not possess a single, precisely defined geometry into which the scaffold has to fit. These relaxed geometric constraints may facilitate the evolution of signaling networks, as well as their engineering for applications in synthetic biology.

  4. Soluble expression of an amebic cysteine protease in the cytoplasm of Escherichia coli SHuffle Express cells and purification of active enzyme.

    PubMed

    Jalomo-Khayrova, Ekaterina; Mares, Rosa E; Muñoz, Patricia L A; Meléndez-López, Samuel G; Rivero, Ignacio A; Ramos, Marco A

    2018-04-03

    Recombinant production of amebic cysteine proteases using Escherichia coli cells as the bacterial system has become a challenging effort, with protein insolubility being the most common issue. Since many of these enzymes need a native conformation stabilized by disulfide bonds, an elaborate process of oxidative folding is usually demanded to get a functional protein. The cytoplasm of E. coli SHuffle Express cells owns an enhanced ability to properly fold proteins with disulfide bonds. Because of this cellular feature, it was possible to assume that this strain represents a reliable expression system and worthwhile been considered as an efficient bacterial host for the recombinant production of amebic cysteine proteases. Using E. coli SHuffle Express cells as the bacterial system, we efficiently produce soluble recombinant EhCP1protein. Enzymatic and inhibition analyses revealed that it exhibits proper catalytic abilities, proceeds effectively over the substrate (following an apparent Michaelis-Menten kinetics), and displays a typical inhibition profile. We report the first feasibility study of the recombinant production of amebic cysteine proteases using E. coli SHuffle Express as the bacterial host. We present a simple protocol for the recombinant expression and purification of fully soluble and active EhCP1 enzyme. We confirm the suitability of recombinant EhCP1 as a therapeutic target. We propose an approachable bacterial system for the recombinant production of amebic proteins, particularly for those with a need for proper oxidative folding.

  5. Why do proteases mess up with antigen presentation by re-shuffling antigen sequences?

    PubMed

    Liepe, Juliane; Ovaa, Huib; Mishto, Michele

    2018-04-30

    The sequence of a large number of MHC-presented epitopes is not present as such in the original antigen because it has been re-shuffled by the proteasome or other proteases. Why do proteases throw a spanner in the works of our model of antigen tagging and immune recognition? We describe in this review what we know about the immunological relevance of post-translationally spliced epitopes and why proteases seem to have a second (dark) personality, which is keen to create new peptide bonds. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Identification of amino acids important for substrate specificity in sucrose transporters using gene shuffling.

    PubMed

    Reinders, Anke; Sun, Ye; Karvonen, Kayla L; Ward, John M

    2012-08-31

    Plant sucrose transporters (SUTs) are H(+)-coupled uptake transporters. Type I and II (SUTs) are phylogenetically related but have different substrate specificities. Type I SUTs transport sucrose, maltose, and a wide range of natural and synthetic α- and β-glucosides. Type II SUTs are more selective for sucrose and maltose. Here, we investigated the structural basis for this difference in substrate specificity. We used a novel gene shuffling method called synthetic template shuffling to introduce 62 differentially conserved amino acid residues from type I SUTs into OsSUT1, a type II SUT from rice. The OsSUT1 variants were tested for their ability to transport the fluorescent coumarin β-glucoside esculin when expressed in yeast. Fluorescent yeast cells were selected using fluorescence-activated cell sorting (FACS). Substitution of five amino acids present in type I SUTs in OsSUT1 was found to be sufficient to confer esculin uptake activity. The changes clustered in two areas of the OsSUT1 protein: in the first loop and the top of TMS2 (T80L and A86K) and in TMS5 (S220A, S221A, and T224Y). The substrate specificity of this OsSUT1 variant was almost identical to that of type I SUTs. Corresponding changes in the sugarcane type II transporter ShSUT1 also changed substrate specificity, indicating that these residues contribute to substrate specificity in type II SUTs in general.

  7. Identification of Amino Acids Important for Substrate Specificity in Sucrose Transporters Using Gene Shuffling*

    PubMed Central

    Reinders, Anke; Sun, Ye; Karvonen, Kayla L.; Ward, John M.

    2012-01-01

    Plant sucrose transporters (SUTs) are H+-coupled uptake transporters. Type I and II (SUTs) are phylogenetically related but have different substrate specificities. Type I SUTs transport sucrose, maltose, and a wide range of natural and synthetic α- and β-glucosides. Type II SUTs are more selective for sucrose and maltose. Here, we investigated the structural basis for this difference in substrate specificity. We used a novel gene shuffling method called synthetic template shuffling to introduce 62 differentially conserved amino acid residues from type I SUTs into OsSUT1, a type II SUT from rice. The OsSUT1 variants were tested for their ability to transport the fluorescent coumarin β-glucoside esculin when expressed in yeast. Fluorescent yeast cells were selected using fluorescence-activated cell sorting (FACS). Substitution of five amino acids present in type I SUTs in OsSUT1 was found to be sufficient to confer esculin uptake activity. The changes clustered in two areas of the OsSUT1 protein: in the first loop and the top of TMS2 (T80L and A86K) and in TMS5 (S220A, S221A, and T224Y). The substrate specificity of this OsSUT1 variant was almost identical to that of type I SUTs. Corresponding changes in the sugarcane type II transporter ShSUT1 also changed substrate specificity, indicating that these residues contribute to substrate specificity in type II SUTs in general. PMID:22807445

  8. Spike Pattern Structure Influences Synaptic Efficacy Variability under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks

    PubMed Central

    Bi, Zedong; Zhou, Changsong

    2016-01-01

    Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations) influence the efficacy variability under pair-wise additive spike-timing dependent plasticity (STDP) and synaptic homeostasis (the mean strength of plastic synapses into a neuron is bounded), by implementing spike shuffling methods onto spike patterns self-organized by a network of excitatory and inhibitory leaky integrate-and-fire (LIF) neurons. With the increase of the decay time scale of the inhibitory synaptic currents, the LIF network undergoes a transition from asynchronous state to weak synchronous state and then to synchronous bursting state. We first shuffle these spike patterns using a variety of methods, each designed to evidently change a specific pattern statistics; and then investigate the change of efficacy variability of the synapses under STDP and synaptic homeostasis, when the neurons in the network fire according to the spike patterns before and after being treated by a shuffling method. In this way, we can understand how the change of pattern statistics may cause the change of efficacy variability. Our results are consistent with those of our previous study which implements spike-generating models on converging motifs. We also find that burstiness/regularity is important to determine the efficacy variability under asynchronous states, while heterogeneity of cross-correlations is the main factor to cause efficacy variability when the network moves into synchronous bursting states (the states observed in epilepsy). PMID:27555816

  9. Features Extraction of Flotation Froth Images and BP Neural Network Soft-Sensor Model of Concentrate Grade Optimized by Shuffled Cuckoo Searching Algorithm

    PubMed Central

    Wang, Jie-sheng; Han, Shuang; Shen, Na-na; Li, Shu-xia

    2014-01-01

    For meeting the forecasting target of key technology indicators in the flotation process, a BP neural network soft-sensor model based on features extraction of flotation froth images and optimized by shuffled cuckoo search algorithm is proposed. Based on the digital image processing technique, the color features in HSI color space, the visual features based on the gray level cooccurrence matrix, and the shape characteristics based on the geometric theory of flotation froth images are extracted, respectively, as the input variables of the proposed soft-sensor model. Then the isometric mapping method is used to reduce the input dimension, the network size, and learning time of BP neural network. Finally, a shuffled cuckoo search algorithm is adopted to optimize the BP neural network soft-sensor model. Simulation results show that the model has better generalization results and prediction accuracy. PMID:25133210

  10. Protein domain organisation: adding order.

    PubMed

    Kummerfeld, Sarah K; Teichmann, Sarah A

    2009-01-29

    Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and

  11. Image encryption using random sequence generated from generalized information domain

    NASA Astrophysics Data System (ADS)

    Xia-Yan, Zhang; Guo-Ji, Zhang; Xuan, Li; Ya-Zhou, Ren; Jie-Hua, Wu

    2016-05-01

    A novel image encryption method based on the random sequence generated from the generalized information domain and permutation-diffusion architecture is proposed. The random sequence is generated by reconstruction from the generalized information file and discrete trajectory extraction from the data stream. The trajectory address sequence is used to generate a P-box to shuffle the plain image while random sequences are treated as keystreams. A new factor called drift factor is employed to accelerate and enhance the performance of the random sequence generator. An initial value is introduced to make the encryption method an approximately one-time pad. Experimental results show that the random sequences pass the NIST statistical test with a high ratio and extensive analysis demonstrates that the new encryption scheme has superior security.

  12. Mutation by DNA shuffling of 5-enolpyruvylshikimate-3-phosphate synthase from Malus domestica for improved glyphosate resistance.

    PubMed

    Tian, Yong-Sheng; Xu, Jing; Peng, Ri-He; Xiong, Ai-Sheng; Xu, Hu; Zhao, Wei; Fu, Xiao-Yan; Han, Hong-Juan; Yao, Quan-Hong

    2013-09-01

    A new 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene from Malus domestica (MdEPSPS) was cloned and characterized by rapid amplification of cDNA ends to identify an EPSPS gene appropriate for the development of transgenic glyphosate-tolerant plants. However, wild-type MdEPSPS is not suitable for the development of transgenic glyphosate-tolerant plants because of its poor glyphosate resistance. Thus, we performed DNA shuffling on MdEPSPS, and one highly glyphosate-resistant mutant with mutations in eight amino acids (N63D, N86S, T101A, A187T, D230G, H317R, Y399R and C413A.) was identified after five rounds of DNA shuffling and screening. Among the eight amino acid substitutions on this mutant, only two residue changes (T101A and A187T) were identified by site-directed mutagenesis as essential and additive in altering glyphosate resistance, which was further confirmed by kinetic analyses. The single-site A187T mutation has also never been previously reported as an important residue for glyphosate resistance. Furthermore, transgenic rice was used to confirm the potential of MdEPSPS mutant in developing glyphosate-resistant crops. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  13. Estimation of beech pyrolysis kinetic parameters by Shuffled Complex Evolution.

    PubMed

    Ding, Yanming; Wang, Changjian; Chaos, Marcos; Chen, Ruiyu; Lu, Shouxiang

    2016-01-01

    The pyrolysis kinetics of a typical biomass energy feedstock, beech, was investigated based on thermogravimetric analysis over a wide heating rate range from 5K/min to 80K/min. A three-component (corresponding to hemicellulose, cellulose and lignin) parallel decomposition reaction scheme was applied to describe the experimental data. The resulting kinetic reaction model was coupled to an evolutionary optimization algorithm (Shuffled Complex Evolution, SCE) to obtain model parameters. To the authors' knowledge, this is the first study in which SCE has been used in the context of thermogravimetry. The kinetic parameters were simultaneously optimized against data for 10, 20 and 60K/min heating rates, providing excellent fits to experimental data. Furthermore, it was shown that the optimized parameters were applicable to heating rates (5 and 80K/min) beyond those used to generate them. Finally, the predicted results based on optimized parameters were contrasted with those based on the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Prediction of Scar Size in Rats Six Months after Burns Based on Early Post-injury Polarization-Sensitive Optical Frequency Domain Imaging

    PubMed Central

    Kravez, Eli; Villiger, Martin; Bouma, Brett; Yarmush, Martin; Yakhini, Zohar; Golberg, Alexander

    2017-01-01

    Hypertrophic scars remain a major clinical problem in the rehabilitation of burn survivors and lead to physical, aesthetic, functional, psychological, and social stresses. Prediction of healing outcome and scar formation is critical for deciding on the best treatment plan. Both subjective and objective scales have been devised to assess scar severity. Whereas scales of the first type preclude cross-comparison between observers, those of the second type are based on imaging modalities that either lack the ability to image individual layers of the scar or only provide very limited fields of view. To overcome these deficiencies, this work aimed at developing a predictive model of scar formation based on polarization sensitive optical frequency domain imaging (PS-OFDI), which offers comprehensive subsurface imaging. We report on a linear regression model that predicts the size of a scar 6 months after third-degree burn injuries in rats based on early post-injury PS-OFDI and measurements of scar area. When predicting the scar area at month 6 based on the homogeneity and the degree of polarization (DOP), which are signatures derived from the PS-OFDI signal, together with the scar area measured at months 2 and 3, we achieved predictions with a Pearson coefficient of 0.57 (p < 10−4) and a Spearman coefficient of 0.66 (p < 10−5), which were significant in comparison to prediction models trained on randomly shuffled data. As the model in this study was developed on the rat burn model, the methodology can be used in larger studies that are more relevant to humans; however, the actual model inferred herein is not translatable. Nevertheless, our analysis and modeling methodology can be extended to perform larger wound healing studies in different contexts. This study opens new possibilities for quantitative and objective assessment of scar severity that could help to determine the optimal course of therapy. PMID:29249978

  15. Differential associations of early callous-unemotional, oppositional, and ADHD behaviors: multiple domains within early-starting conduct problems?

    PubMed

    Waller, Rebecca; Hyde, Luke W; Grabell, Adam S; Alves, Martha L; Olson, Sheryl L

    2015-06-01

    Early-starting child conduct problems (CP) are linked to the development of persistent antisocial behavior. Researchers have theorized multiple pathways to CP and that CP comprise separable domains, marked by callous-unemotional (CU) behavior, oppositional behavior, or ADHD symptoms. However, a lack of empirical evidence exists from studies that have examined whether there are unique correlates of these domains. We examined differential correlates of CU, oppositional, and ADHD behaviors during the preschool years to test their potentially distinct nomological networks. Multimethod data, including parent and teacher reports and observations of child behavior, were drawn from a prospective, longitudinal study of children assessed at age 3 and age 6 (N = 240; 48% female). Dimensions of CU, oppositional, and ADHD behaviors were separable within Confirmatory Factor Analyses across mother and father reports. There were differential associations between CU, oppositional, and ADHD behaviors and socioemotional, cognitive, and behavioral outcomes: CU behavior was uniquely related to lower moral regulation, guilt, and empathy. ADHD was uniquely related to lower attentional focusing and observed effortful control. Finally, CU behavior uniquely predicted increases in teacher-reported externalizing from ages 3-6 over and above covariates, and ADHD and oppositional behavior. Consistent with theory, dimensions of CU, ADHD, and oppositional behavior demonstrated separable nomological networks representing separable facets within early-starting CP. © 2014 Association for Child and Adolescent Mental Health.

  16. Strain improvement of Sporolactobacillus inulinus ATCC 15538 for acid tolerance and production of D-lactic acid by genome shuffling.

    PubMed

    Zheng, Huijie; Gong, Jixian; Chen, Tao; Chen, Xun; Zhao, Xueming

    2010-02-01

    Improvement of acid tolerance and production of D-lactic acid by Sporolactobacillus inulinus ATCC 15538 was performed by using recursive protoplast fusion in a genome shuffling format. The starting population was generated by ultraviolet irradiation, diethyl sulfate mutagenesis, and pH-gradient filter and then, subjected for the recursive protoplast fusion. The concentration of lysozyme, time, and temperature for enzyme treatment were optimized by response surface methodology based on the central composite design. Based on contour plots and variance analysis, the model predicted a maximum Y (multiply protoplasts formation ratio by protoplasts regeneration ratio), 60.4%, and the corresponding above used values were 7.75 mg/ml lysozyme, 1.59 h, and 38 degrees C. A pH-5-resistant recombinant, F3-4, was obtained after three rounds of genome shuffling and its production of D-lactic acid reached 93.4 g/l in a 5 L bioreactor, which was increased by 39.8% and 119% in comparison with that of UV generated strain and the original strain S. inulinus ATCC 15538, respectively. The subculture experiments indicated that F3-4 was genetically stable.

  17. Footprinting reveals that nogalamycin and actinomycin shuffle between DNA binding sites.

    PubMed Central

    Fox, K R; Waring, M J

    1986-01-01

    The hypothesis that sequence-selective DNA-binding antibiotics locate their preferred binding sites by a process involving migration from nonspecific sites has been tested by footprinting with DNAase I. Footprinting patterns on the tyrT DNA fragment produced by nogalamycin and actinomycin change with time after mixing the antibiotic with the DNA. Sites of protection as well as enhanced cleavage are seen to develop in a fashion which is both temperature and concentration-dependent. At certain sites cutting is transiently enhanced, then blocked. Limited evidence for slow reaction with echinomycin and mithramycin is presented, but the kinetics of footprinting with daunomycin and distamycin appear instantaneous. The feasibility of adducing direct evidence for shuffling by footprinting seems to be governed by slow dissociation of the antibiotic-DNA complex. It may also be dependent upon the mode of binding, be it intercalative or non-intercalative in character. Images PMID:2421246

  18. Measurement Invariance of Early Development Instrument (EDI) Domain Scores across Gender and ESL Status

    ERIC Educational Resources Information Center

    Mousavi, Amin; Krishnan, Vijaya

    2016-01-01

    The Early Development Instrument (EDI) is a widely used teacher rating tool to assess kindergartners' developmental outcomes in Canada and a number of other countries. This paper examines the measurement invariance of EDI domains across ESL status and gender by means of multi-group confirmatory factor analysis. The results suggest evidence of…

  19. High efficiency family shuffling based on multi-step PCR and in vivo DNA recombination in yeast: statistical and functional analysis of a combinatorial library between human cytochrome P450 1A1 and 1A2.

    PubMed

    Abécassis, V; Pompon, D; Truan, G

    2000-10-15

    The design of a family shuffling strategy (CLERY: Combinatorial Libraries Enhanced by Recombination in Yeast) associating PCR-based and in vivo recombination and expression in yeast is described. This strategy was tested using human cytochrome P450 CYP1A1 and CYP1A2 as templates, which share 74% nucleotide sequence identity. Construction of highly shuffled libraries of mosaic structures and reduction of parental gene contamination were two major goals. Library characterization involved multiprobe hybridization on DNA macro-arrays. The statistical analysis of randomly selected clones revealed a high proportion of chimeric genes (86%) and a homogeneous representation of the parental contribution among the sequences (55.8 +/- 2.5% for parental sequence 1A2). A microtiter plate screening system was designed to achieve colorimetric detection of polycyclic hydrocarbon hydroxylation by transformed yeast cells. Full sequences of five randomly picked and five functionally selected clones were analyzed. Results confirmed the shuffling efficiency and allowed calculation of the average length of sequence exchange and mutation rates. The efficient and statistically representative generation of mosaic structures by this type of family shuffling in a yeast expression system constitutes a novel and promising tool for structure-function studies and tuning enzymatic activities of multicomponent eucaryote complexes involving non-soluble enzymes.

  20. Inversions and Gene Order Shuffling in Anopheles gambiae and A. funestus

    NASA Astrophysics Data System (ADS)

    Sharakhov, Igor V.; Serazin, Andrew C.; Grushko, Olga G.; Dana, Ali; Lobo, Neil; Hillenmeyer, Maureen E.; Westerman, Richard; Romero-Severson, Jeanne; Costantini, Carlo; Sagnon, N'Fale; Collins, Frank H.; Besansky, Nora J.

    2002-10-01

    In tropical Africa, Anopheles funestus is one of the three most important malaria vectors. We physically mapped 157 A. funestus complementary DNAs (cDNAs) to the polytene chromosomes of this species. Sequences of the cDNAs were mapped in silico to the A. gambiae genome as part of a comparative genomic study of synteny, gene order, and sequence conservation between A. funestus and A. gambiae. These species are in the same subgenus and diverged about as recently as humans and chimpanzees. Despite nearly perfect preservation of synteny, we found substantial shuffling of gene order along corresponding chromosome arms. Since the divergence of these species, at least 70 chromosomal inversions have been fixed, the highest rate of rearrangement of any eukaryote studied to date. The high incidence of paracentric inversions and limited colinearity suggests that locating genes in one anopheline species based on gene order in another may be limited to closely related taxa.

  1. Investigating the causes and consequences of symbiont shuffling in a multi-partner reef coral symbiosis under environmental change.

    PubMed

    Cunning, R; Silverstein, R N; Baker, A C

    2015-06-22

    Dynamic symbioses may critically mediate impacts of climate change on diverse organisms, with repercussions for ecosystem persistence in some cases. On coral reefs, increases in heat-tolerant symbionts after thermal bleaching can reduce coral susceptibility to future stress. However, the relevance of this adaptive response is equivocal owing to conflicting reports of symbiont stability and change. We help reconcile this conflict by showing that change in symbiont community composition (symbiont shuffling) in Orbicella faveolata depends on the disturbance severity and recovery environment. The proportion of heat-tolerant symbionts dramatically increased following severe experimental bleaching, especially in a warmer recovery environment, but tended to decrease if bleaching was less severe. These patterns can be explained by variation in symbiont performance in the changing microenvironments created by differentially bleached host tissues. Furthermore, higher proportions of heat-tolerant symbionts linearly increased bleaching resistance but reduced photochemical efficiency, suggesting that any change in community structure oppositely impacts performance and stress tolerance. Therefore, even minor symbiont shuffling can adaptively benefit corals, although fitness effects of resulting trade-offs are difficult to predict. This work helps elucidate causes and consequences of dynamism in symbiosis, which is critical to predicting responses of multi-partner symbioses such as O. faveolata to environmental change. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  2. Comparative study on fermentation performance in the genome shuffled Candida versatilis and wild-type salt tolerant yeast strain.

    PubMed

    Qi, Wei; Guo, Hong-Lian; Wang, Chun-Ling; Hou, Li-Hua; Cao, Xiao-Hong; Liu, Jin-Fu; Lu, Fu-Ping

    2017-01-01

    The fermentation performance of a genome-shuffled strain of Candida versatilis S3-5, isolated for improved tolerance to salt, and wild-type (WT) strain were analysed. The fermentation parameters, such as growth, reducing sugar, ethanol, organic acids and volatile compounds, were detected during soy sauce fermentation process. The results showed that ethanol produced by the genome shuffled strain S3-5 was increasing at a faster rate and to a greater extent than WT. At the end of the fermentation, malic acid, citric acid and succinic acid formed in tricarboxylic acid cycle after S3-5 treatment elevated by 39.20%, 6.85% and 17.09% compared to WT, respectively. Moreover, flavour compounds such as phenethyl acetate, ethyl vanillate, ethyl acetate, isoamyl acetate, ethyl myristate, ethyl pentadecanoate, ethyl palmitate and phenylacetaldehyde produced by S3-5 were 2.26, 2.12, 2.87, 34.41, 6.32, 13.64, 2.23 and 78.85 times as compared to WT. S3-5 exhibited enhanced metabolic ability as compared to the wild-type strain, improved conversion of sugars to ethanol, metabolism of organic acid and formation of volatile compounds, especially esters, Moreover, S3-5 might be an ester-flavour type salt-tolerant yeast. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  3. Vertical transportation systems embedded on shuffled frog leaping algorithm for manufacturing optimisation problems in industries.

    PubMed

    Aungkulanon, Pasura; Luangpaiboon, Pongchanun

    2016-01-01

    Response surface methods via the first or second order models are important in manufacturing processes. This study, however, proposes different structured mechanisms of the vertical transportation systems or VTS embedded on a shuffled frog leaping-based approach. There are three VTS scenarios, a motion reaching a normal operating velocity, and both reaching and not reaching transitional motion. These variants were performed to simultaneously inspect multiple responses affected by machining parameters in multi-pass turning processes. The numerical results of two machining optimisation problems demonstrated the high performance measures of the proposed methods, when compared to other optimisation algorithms for an actual deep cut design.

  4. Evolution of domain walls in the early universe. Ph.D. Thesis - Chicago Univ.

    NASA Technical Reports Server (NTRS)

    Kawano, Lawrence

    1989-01-01

    The evolution of domain walls in the early universe is studied via 2-D computer simulation. The walls are initially configured on a triangular lattice and then released from the lattice, their evolution driven by wall curvature and by the universal expansion. The walls attain an average velocity of about 0.3c and their surface area per volume (as measured in comoving coordinates) goes down with a slope of -1 with respect to conformal time, regardless of whether the universe is matter or radiation dominated. The additional influence of vacuum pressure causes the energy density to fall away from this slope and steepen, thus allowing a situation in which domain walls can constitute a significant portion of the energy density of the universe without provoking an unacceptably large perturbation upon the microwave background.

  5. Activity Augmentation of Amphioxus Peptidoglycan Recognition Protein BbtPGRP3 via Fusion with a Chitin Binding Domain

    PubMed Central

    Wang, Wen-Jie; Cheng, Wang; Luo, Ming; Yan, Qingyu; Yu, Hong-Mei; Li, Qiong; Cao, Dong-Dong; Huang, Shengfeng; Xu, Anlong; Mariuzza, Roy A.; Chen, Yuxing; Zhou, Cong-Zhao

    2015-01-01

    Peptidoglycan recognition proteins (PGRPs), which have been identified in most animals, are pattern recognition molecules that involve antimicrobial defense. Resulting from extraordinary expansion of innate immune genes, the amphioxus encodes many PGRPs of diverse functions. For instance, three isoforms of PGRP encoded by Branchiostoma belcheri tsingtauense, termed BbtPGRP1~3, are fused with a chitin binding domain (CBD) at the N-terminus. Here we report the 2.7 Å crystal structure of BbtPGRP3, revealing an overall structure of an N-terminal hevein-like CBD followed by a catalytic PGRP domain. Activity assays combined with site-directed mutagenesis indicated that the individual PGRP domain exhibits amidase activity towards both DAP-type and Lys-type peptidoglycans (PGNs), the former of which is favored. The N-terminal CBD not only has the chitin-binding activity, but also enables BbtPGRP3 to gain a five-fold increase of amidase activity towards the Lys-type PGNs, leading to a significantly broadened substrate spectrum. Together, we propose that modular evolution via domain shuffling combined with gene horizontal transfer makes BbtPGRP1~3 novel PGRPs of augmented catalytic activity and broad recognition spectrum. PMID:26479246

  6. Furfural-tolerant Zymomonas mobilis derived from error-prone PCR-based whole genome shuffling and their tolerant mechanism.

    PubMed

    Huang, Suzhen; Xue, Tingli; Wang, Zhiquan; Ma, Yuanyuan; He, Xueting; Hong, Jiefang; Zou, Shaolan; Song, Hao; Zhang, Minhua

    2018-04-01

    Furfural-tolerant strain is essential for the fermentative production of biofuels or chemicals from lignocellulosic biomass. In this study, Zymomonas mobilis CP4 was for the first time subjected to error-prone PCR-based whole genome shuffling, and the resulting mutants F211 and F27 that could tolerate 3 g/L furfural were obtained. The mutant F211 under various furfural stress conditions could rapidly grow when the furfural concentration reduced to 1 g/L. Meanwhile, the two mutants also showed higher tolerance to high concentration of glucose than the control strain CP4. Genome resequencing revealed that the F211 and F27 had 12 and 13 single-nucleotide polymorphisms. The activity assay demonstrated that the activity of NADH-dependent furfural reductase in mutant F211 and CP4 was all increased under furfural stress, and the activity peaked earlier in mutant than in control. Also, furfural level in the culture of F211 was also more rapidly decreased. These indicate that the increase in furfural tolerance of the mutants may be resulted from the enhanced NADH-dependent furfural reductase activity during early log phase, which could lead to an accelerated furfural detoxification process in mutants. In all, we obtained Z. mobilis mutants with enhanced furfural and high concentration of glucose tolerance, and provided valuable clues for the mechanism of furfural tolerance and strain development.

  7. Roots of angiosperm formins: The evolutionary history of plant FH2 domain-containing proteins

    PubMed Central

    2008-01-01

    Background Shuffling of modular protein domains is an important source of evolutionary innovation. Formins are a family of actin-organizing proteins that share a conserved FH2 domain but their overall domain architecture differs dramatically between opisthokonts (metazoans and fungi) and plants. We performed a phylogenomic analysis of formins in most eukaryotic kingdoms, aiming to reconstruct an evolutionary scenario that may have produced the current diversity of domain combinations with focus on the origin of the angiosperm formin architectures. Results The Rho GTPase-binding domain (GBD/FH3) reported from opisthokont and Dictyostelium formins was found in all lineages except plants, suggesting its ancestral character. Instead, mosses and vascular plants possess the two formin classes known from angiosperms: membrane-anchored Class I formins and Class II formins carrying a PTEN-like domain. PTEN-related domains were found also in stramenopile formins, where they have been probably acquired independently rather than by horizontal transfer, following a burst of domain rearrangements in the chromalveolate lineage. A novel RhoGAP-related domain was identified in some algal, moss and lycophyte (but not angiosperm) formins that define a specific branch (Class III) of the formin family. Conclusion We propose a scenario where formins underwent multiple domain rearrangements in several eukaryotic lineages, especially plants and chromalveolates. In plants this replaced GBD/FH3 by a probably inactive RhoGAP-like domain, preserving a formin-mediated association between (membrane-anchored) Rho GTPases and the actin cytoskeleton. Subsequent amplification of formin genes, possibly coincident with the expansion of plants to dry land, was followed by acquisition of alternative membrane attachment mechanisms present in extant Class I and Class II formins, allowing later loss of the RhoGAP-like domain-containing formins in angiosperms. PMID:18430232

  8. The role of intra-domain disulfide bonds in heat-induced irreversible denaturation of camelid single domain VHH antibodies

    PubMed Central

    Akazawa-Ogawa, Yoko; Uegaki, Koichi; Hagihara, Yoshihisa

    2016-01-01

    Camelid-derived single domain VHH antibodies are highly heat resistant, and the mechanism of heat-induced VHH denaturation predominantly relies on the chemical modification of amino acids. Although chemical modification of disulfide bonds has been recognized as a cause for heat-induced denaturation of many proteins, there have been no mutagenesis studies, in which the number of disulfide bonds was controlled. In this article, we examined a series of mutants of two different VHHs with single, double or no disulfide bonds, and scrutinized the effects of these disulfide bond modifications on VHH denaturation. With the exception of one mutant, the heat resistance of VHHs decreased when the number of disulfide bonds increased. The effect of disulfide bonds on heat denaturation was more striking if the VHH had a second disulfide bond, suggesting that the contribution of disulfide shuffling is significant in proteins with multiple disulfide bonds. Furthermore, our results directly indicate that removal of a disulfide bond can indeed increase the heat resistance of a protein, irrespective of the negative impact on equilibrium thermodynamic stability. PMID:26289739

  9. Predicting Children's Reading and Mathematics Achievement from Early Quantitative Knowledge and Domain-General Cognitive Abilities

    PubMed Central

    Chu, Felicia W.; vanMarle, Kristy; Geary, David C.

    2016-01-01

    reading and mathematics achievement at the end of kindergarten. Preliteracy skills were more strongly related to word reading, whereas sensitivity to relative quantity was more strongly related to mathematics achievement. The overall results indicate that a combination of domain-general and domain-specific abilities contribute to development of children's early mathematics and reading achievement. PMID:27252675

  10. Predicting Children's Reading and Mathematics Achievement from Early Quantitative Knowledge and Domain-General Cognitive Abilities.

    PubMed

    Chu, Felicia W; vanMarle, Kristy; Geary, David C

    2016-01-01

    reading and mathematics achievement at the end of kindergarten. Preliteracy skills were more strongly related to word reading, whereas sensitivity to relative quantity was more strongly related to mathematics achievement. The overall results indicate that a combination of domain-general and domain-specific abilities contribute to development of children's early mathematics and reading achievement.

  11. MOCASSIN-prot: A multi-objective clustering approach for protein similarity networks

    USDA-ARS?s Scientific Manuscript database

    Motivation: Proteins often include multiple conserved domains. Various evolutionary events including duplication and loss of domains, domain shuffling, as well as sequence divergence contribute to generating complexities in protein structures, and consequently, in their functions. The evolutionary h...

  12. Baseline shifts in coral skeletal oxygen isotopic composition: a signature of symbiont shuffling?

    NASA Astrophysics Data System (ADS)

    Carilli, J. E.; Charles, C. D.; Garren, M.; McField, M.; Norris, R. D.

    2013-06-01

    Decades-long records of the stable isotopic composition of coral skeletal cores were analyzed from four sites on the Mesoamerican Reef. Two of the sites exhibited baseline shifts in oxygen isotopic composition after known coral bleaching events. Changes in pH at the calcification site caused by a change in the associated symbiont community are invoked to explain the observed shift in the isotopic composition. To test the hypothesis that changes in symbiont clade could affect skeletal chemistry, additional coral samples were collected from Belize for paired Symbiodinium identification and skeletal stable isotopic analysis. We found some evidence that skeletal stable isotopic composition may be affected by symbiont clade and suggest this is an important topic for future investigation. If different Symbiodinium clades leave consistent signatures in skeletal geochemical composition, the signature will provide a method to quantify past symbiont shuffling events, important for understanding how corals are likely to respond to climate change.

  13. The role of intra-domain disulfide bonds in heat-induced irreversible denaturation of camelid single domain VHH antibodies.

    PubMed

    Akazawa-Ogawa, Yoko; Uegaki, Koichi; Hagihara, Yoshihisa

    2016-01-01

    Camelid-derived single domain VHH antibodies are highly heat resistant, and the mechanism of heat-induced VHH denaturation predominantly relies on the chemical modification of amino acids. Although chemical modification of disulfide bonds has been recognized as a cause for heat-induced denaturation of many proteins, there have been no mutagenesis studies, in which the number of disulfide bonds was controlled. In this article, we examined a series of mutants of two different VHHs with single, double or no disulfide bonds, and scrutinized the effects of these disulfide bond modifications on VHH denaturation. With the exception of one mutant, the heat resistance of VHHs decreased when the number of disulfide bonds increased. The effect of disulfide bonds on heat denaturation was more striking if the VHH had a second disulfide bond, suggesting that the contribution of disulfide shuffling is significant in proteins with multiple disulfide bonds. Furthermore, our results directly indicate that removal of a disulfide bond can indeed increase the heat resistance of a protein, irrespective of the negative impact on equilibrium thermodynamic stability. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  14. Separated matter and antimatter domains with vanishing domain walls

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

    Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S.

    2015-10-01

    We present a model of spontaneous (or dynamical) C and CP violation where it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP) violation existed only in the early universe and later it disappeared with the only trace of generated baryonic and/or antibaryonic domains. So the problem of domain walls in this model does not exist. These features are achieved through a postulated form of interaction between inflaton and a new scalar field, realizing short time C(CP) violation.

  15. A parallel approximate string matching under Levenshtein distance on graphics processing units using warp-shuffle operations

    PubMed Central

    Ho, ThienLuan; Oh, Seung-Rohk

    2017-01-01

    Approximate string matching with k-differences has a number of practical applications, ranging from pattern recognition to computational biology. This paper proposes an efficient memory-access algorithm for parallel approximate string matching with k-differences on Graphics Processing Units (GPUs). In the proposed algorithm, all threads in the same GPUs warp share data using warp-shuffle operation instead of accessing the shared memory. Moreover, we implement the proposed algorithm by exploiting the memory structure of GPUs to optimize its performance. Experiment results for real DNA packages revealed that the performance of the proposed algorithm and its implementation archived up to 122.64 and 1.53 times compared to that of sequential algorithm on CPU and previous parallel approximate string matching algorithm on GPUs, respectively. PMID:29016700

  16. Predicting Negative Life Outcomes from Early Aggressive-Disruptive Behavior Trajectories: Gender Differences in Maladaptation across Life Domains

    ERIC Educational Resources Information Center

    Bradshaw, Catherine P.; Schaeffer, Cindy M.; Petras, Hanno; Ialongo, Nicholas

    2010-01-01

    Transactional theories of development suggest that displaying high levels of antisocial behavior early in life and persistently over time causes disruption in multiple life domains, which in turn places individuals at risk for negative life outcomes. We used longitudinal data from 1,137 primarily African American urban youth (49.1% female) to…

  17. The zoom lens of attention: Simulating shuffled versus normal text reading using the SWIFT model

    PubMed Central

    Schad, Daniel J.; Engbert, Ralf

    2012-01-01

    Assumptions on the allocation of attention during reading are crucial for theoretical models of eye guidance. The zoom lens model of attention postulates that attentional deployment can vary from a sharp focus to a broad window. The model is closely related to the foveal load hypothesis, i.e., the assumption that the perceptual span is modulated by the difficulty of the fixated word. However, these important theoretical concepts for cognitive research have not been tested quantitatively in eye movement models. Here we show that the zoom lens model, implemented in the SWIFT model of saccade generation, captures many important patterns of eye movements. We compared the model's performance to experimental data from normal and shuffled text reading. Our results demonstrate that the zoom lens of attention might be an important concept for eye movement control in reading. PMID:22754295

  18. Nonlinear Rayleigh wave inversion based on the shuffled frog-leaping algorithm

    NASA Astrophysics Data System (ADS)

    Sun, Cheng-Yu; Wang, Yan-Yan; Wu, Dun-Shi; Qin, Xiao-Jun

    2017-12-01

    At present, near-surface shear wave velocities are mainly calculated through Rayleigh wave dispersion-curve inversions in engineering surface investigations, but the required calculations pose a highly nonlinear global optimization problem. In order to alleviate the risk of falling into a local optimal solution, this paper introduces a new global optimization method, the shuffle frog-leaping algorithm (SFLA), into the Rayleigh wave dispersion-curve inversion process. SFLA is a swarm-intelligence-based algorithm that simulates a group of frogs searching for food. It uses a few parameters, achieves rapid convergence, and is capability of effective global searching. In order to test the reliability and calculation performance of SFLA, noise-free and noisy synthetic datasets were inverted. We conducted a comparative analysis with other established algorithms using the noise-free dataset, and then tested the ability of SFLA to cope with data noise. Finally, we inverted a real-world example to examine the applicability of SFLA. Results from both synthetic and field data demonstrated the effectiveness of SFLA in the interpretation of Rayleigh wave dispersion curves. We found that SFLA is superior to the established methods in terms of both reliability and computational efficiency, so it offers great potential to improve our ability to solve geophysical inversion problems.

  19. Unsupervised domain adaptation for early detection of drought stress in hyperspectral images

    NASA Astrophysics Data System (ADS)

    Schmitter, P.; Steinrücken, J.; Römer, C.; Ballvora, A.; Léon, J.; Rascher, U.; Plümer, L.

    2017-09-01

    Hyperspectral images can be used to uncover physiological processes in plants if interpreted properly. Machine Learning methods such as Support Vector Machines (SVM) and Random Forests have been applied to estimate development of biomass and detect and predict plant diseases and drought stress. One basic requirement of machine learning implies, that training and testing is done in the same domain and the same distribution. Different genotypes, environmental conditions, illumination and sensors violate this requirement in most practical circumstances. Here, we present an approach, which enables the detection of physiological processes by transferring the prior knowledge within an existing model into a related target domain, where no label information is available. We propose a two-step transformation of the target features, which enables a direct application of an existing model. The transformation is evaluated by an objective function including additional prior knowledge about classification and physiological processes in plants. We have applied the approach to three sets of hyperspectral images, which were acquired with different plant species in different environments observed with different sensors. It is shown, that a classification model, derived on one of the sets, delivers satisfying classification results on the transformed features of the other data sets. Furthermore, in all cases early non-invasive detection of drought stress was possible.

  20. SHuffle, a novel Escherichia coli protein expression strain capable of correctly folding disulfide bonded proteins in its cytoplasm

    PubMed Central

    2012-01-01

    Background Production of correctly disulfide bonded proteins to high yields remains a challenge. Recombinant protein expression in Escherichia coli is the popular choice, especially within the research community. While there is an ever growing demand for new expression strains, few strains are dedicated to post-translational modifications, such as disulfide bond formation. Thus, new protein expression strains must be engineered and the parameters involved in producing disulfide bonded proteins must be understood. Results We have engineered a new E. coli protein expression strain named SHuffle, dedicated to producing correctly disulfide bonded active proteins to high yields within its cytoplasm. This strain is based on the trxB gor suppressor strain SMG96 where its cytoplasmic reductive pathways have been diminished, allowing for the formation of disulfide bonds in the cytoplasm. We have further engineered a major improvement by integrating into its chromosome a signal sequenceless disulfide bond isomerase, DsbC. We probed the redox state of DsbC in the oxidizing cytoplasm and evaluated its role in assisting the formation of correctly folded multi-disulfide bonded proteins. We optimized protein expression conditions, varying temperature, induction conditions, strain background and the co-expression of various helper proteins. We found that temperature has the biggest impact on improving yields and that the E. coli B strain background of this strain was superior to the K12 version. We also discovered that auto-expression of substrate target proteins using this strain resulted in higher yields of active pure protein. Finally, we found that co-expression of mutant thioredoxins and PDI homologs improved yields of various substrate proteins. Conclusions This work is the first extensive characterization of the trxB gor suppressor strain. The results presented should help researchers design the appropriate protein expression conditions using SHuffle strains. PMID:22569138

  1. Fast hydrological model calibration based on the heterogeneous parallel computing accelerated shuffled complex evolution method

    NASA Astrophysics Data System (ADS)

    Kan, Guangyuan; He, Xiaoyan; Ding, Liuqian; Li, Jiren; Hong, Yang; Zuo, Depeng; Ren, Minglei; Lei, Tianjie; Liang, Ke

    2018-01-01

    Hydrological model calibration has been a hot issue for decades. The shuffled complex evolution method developed at the University of Arizona (SCE-UA) has been proved to be an effective and robust optimization approach. However, its computational efficiency deteriorates significantly when the amount of hydrometeorological data increases. In recent years, the rise of heterogeneous parallel computing has brought hope for the acceleration of hydrological model calibration. This study proposed a parallel SCE-UA method and applied it to the calibration of a watershed rainfall-runoff model, the Xinanjiang model. The parallel method was implemented on heterogeneous computing systems using OpenMP and CUDA. Performance testing and sensitivity analysis were carried out to verify its correctness and efficiency. Comparison results indicated that heterogeneous parallel computing-accelerated SCE-UA converged much more quickly than the original serial version and possessed satisfactory accuracy and stability for the task of fast hydrological model calibration.

  2. Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

    PubMed

    Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn

    2017-11-09

    Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

  3. Solving Energy-Aware Real-Time Tasks Scheduling Problem with Shuffled Frog Leaping Algorithm on Heterogeneous Platforms

    PubMed Central

    Zhang, Weizhe; Bai, Enci; He, Hui; Cheng, Albert M.K.

    2015-01-01

    Reducing energy consumption is becoming very important in order to keep battery life and lower overall operational costs for heterogeneous real-time multiprocessor systems. In this paper, we first formulate this as a combinatorial optimization problem. Then, a successful meta-heuristic, called Shuffled Frog Leaping Algorithm (SFLA) is proposed to reduce the energy consumption. Precocity remission and local optimal avoidance techniques are proposed to avoid the precocity and improve the solution quality. Convergence acceleration significantly reduces the search time. Experimental results show that the SFLA-based energy-aware meta-heuristic uses 30% less energy than the Ant Colony Optimization (ACO) algorithm, and 60% less energy than the Genetic Algorithm (GA) algorithm. Remarkably, the running time of the SFLA-based meta-heuristic is 20 and 200 times less than ACO and GA, respectively, for finding the optimal solution. PMID:26110406

  4. A Helitron transposon reconstructed from bats reveals a novel mechanism of genome shuffling in eukaryotes.

    PubMed

    Grabundzija, Ivana; Messing, Simon A; Thomas, Jainy; Cosby, Rachel L; Bilic, Ilija; Miskey, Csaba; Gogol-Döring, Andreas; Kapitonov, Vladimir; Diem, Tanja; Dalda, Anna; Jurka, Jerzy; Pritham, Ellen J; Dyda, Fred; Izsvák, Zsuzsanna; Ivics, Zoltán

    2016-03-02

    Helitron transposons capture and mobilize gene fragments in eukaryotes, but experimental evidence for their transposition is lacking in the absence of an isolated active element. Here we reconstruct Helraiser, an ancient element from the bat genome, and use this transposon as an experimental tool to unravel the mechanism of Helitron transposition. A hairpin close to the 3'-end of the transposon functions as a transposition terminator. However, the 3'-end can be bypassed by the transposase, resulting in transduction of flanking sequences to new genomic locations. Helraiser transposition generates covalently closed circular intermediates, suggestive of a replicative transposition mechanism, which provides a powerful means to disseminate captured transcriptional regulatory signals across the genome. Indeed, we document the generation of novel transcripts by Helitron promoter capture both experimentally and by transcriptome analysis in bats. Our results provide mechanistic insight into Helitron transposition, and its impact on diversification of gene function by genome shuffling.

  5. PTESFinder: a computational method to identify post-transcriptional exon shuffling (PTES) events.

    PubMed

    Izuogu, Osagie G; Alhasan, Abd A; Alafghani, Hani M; Santibanez-Koref, Mauro; Elliott, David J; Elliot, David J; Jackson, Michael S

    2016-01-13

    Transcripts, which have been subject to Post-transcriptional exon shuffling (PTES), have an exon order inconsistent with the underlying genomic sequence. These have been identified in a wide variety of tissues and cell types from many eukaryotes, and are now known to be mostly circular, cytoplasmic, and non-coding. Although there is no uniformly ascribed function, several have been shown to be involved in gene regulation. Accurate identification of these transcripts can, however, be difficult due to artefacts from a wide variety of sources. Here, we present a computational method, PTESFinder, to identify these transcripts from high throughput RNAseq data. Uniquely, it systematically excludes potential artefacts emanating from pseudogenes, segmental duplications, and template switching, and outputs both PTES and canonical exon junction counts to facilitate comparative analyses. In comparison with four existing methods, PTESFinder achieves highest specificity and comparable sensitivity at a variety of read depths. PTESFinder also identifies between 13 % and 41.6 % more structures, compared to publicly available methods recently used to identify human circular RNAs. With high sensitivity and specificity, user-adjustable filters that target known sources of false positives, and tailored output to facilitate comparison of transcript levels, PTESFinder will facilitate the discovery and analysis of these poorly understood transcripts.

  6. Early Paleozoic tectonic reactivation of the Shaoxing-Jiangshan fault zone: Structural and geochronological constraints from the Chencai domain, South China

    NASA Astrophysics Data System (ADS)

    Sun, Hanshen; Li, Jianhua; Zhang, Yueqiao; Dong, Shuwen; Xin, Yujia; Yu, Yingqi

    2018-05-01

    The Shaoxing-Jiangshan fault zone (SJFZ), as a fundamental Neoproterozoic block boundary that separates the Yangtze Block from the Cathaysia Block, is the key to understanding the evolution of South China from Neoproterozoic block amalgamation to early Paleozoic crustal reworking. New structural observations coupled with geochronological ages from the Chencai domain indicate that intense ductile deformation and metamorphism along the SJFZ occurred at ∼460-420 Ma, in response to the early Paleozoic orogeny in South China. To the east of the SJFZ, the deformation involves widespread generations of NE-striking foliation, intrafolial folds, and local development of sinistral-oblique shear zones. The shearing deformation occurred under amphibolite facies conditions at temperatures of >550 °C (locally even >650 °C). To the west of the SJFZ, the deformation corresponds to sinistral-oblique shearing along NE-striking, steep-dipping zones under greenschist facies conditions at temperatures of 400-500 °C. These deformation styles, as typical mid-crustal expressions of continental reworking, reflect tectonic reactivation of the pre-existing, deeply rooted Neoproterozoic block boundary in the early Paleozoic. We infer that the tectonic reactivation, possibly induced by oblique underthrusting of north Cathaysia, facilitated ductile shearing and burial metamorphic reactions, giving rise to the high-strain zones and high-grade metamorphic rocks. With respect to pre-existing mechanical weakness, our work highlights the role of tectonic reactivation of early structures in localizing later deformation before it propagates into yet undeformed domains.

  7. Achieving Integrated Care for Older People: Shuffling the Deckchairs or Making the System Watertight For the Future?

    PubMed Central

    Harvey, Gill; Dollard, Joanne; Marshall, Amy; Mittinty, Manasi Murthy

    2018-01-01

    Integrated care has been recognised as a key initiative to resolve the issues surrounding care for older people living with multi-morbidity. Multiple strategies and policies have been implemented to increase coordination of care globally however, evidence of effectiveness remains mixed. The reasons for this are complex and multifactorial, yet many strategies deal with parts of the problem rather than taking a whole systems view with the older person clearly at the centre. This approach of fixing parts of the system may be akin to shuffling the deckchairs on the Titanic, rather than dealing with the fundamental reasons why the ship is sinking. Attempts to make the ship more watertight need to be firmly centred on the older person, pay close attention to implementation and embrace approaches that promote collaborative working between all the stakeholders involved. PMID:29626395

  8. Methods and apparatuses for self-generating fault-tolerant keys in spread-spectrum systems

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

    Moradi, Hussein; Farhang, Behrouz; Subramanian, Vijayarangam

    Self-generating fault-tolerant keys for use in spread-spectrum systems are disclosed. At a communication device, beacon signals are received from another communication device and impulse responses are determined from the beacon signals. The impulse responses are circularly shifted to place a largest sample at a predefined position. The impulse responses are converted to a set of frequency responses in a frequency domain. The frequency responses are shuffled with a predetermined shuffle scheme to develop a set of shuffled frequency responses. A set of phase differences is determined as a difference between an angle of the frequency response and an angle ofmore » the shuffled frequency response at each element of the corresponding sets. Each phase difference is quantized to develop a set of secret-key quantized phases and a set of spreading codes is developed wherein each spreading code includes a corresponding phase of the set of secret-key quantized phases.« less

  9. Sensitivity of visual evoked potentials and spectral domain optical coherence tomography in early relapsing remitting multiple sclerosis.

    PubMed

    Behbehani, Raed; Ahmed, Samar; Al-Hashel, Jasem; Rousseff, Rossen T; Alroughani, Raed

    2017-02-01

    Visual evoked potentials and spectral-domain optical coherence tomography are common ancillary studies that assess the visual pathways from a functional and structural aspect, respectively. To compare prevalence of abnormalities of Visual evoked potentials (VEP) and spectral-domain optical coherence tomography (SDOCT) in patients with relapsing remitting multiple sclerosis (RRMS). A cross-sectional study of 100 eyes with disease duration of less than 5 years since the diagnosis. Correlation between retinal nerve fiber layer and ganglion-cell/inner plexiform layer with pattern-reversal visual evoked potentials amplitude and latency and contrast sensitivity was performed. The prevalence of abnormalities in pattern-reversal visual VEP was 56% while that of SOCT was 48% in all eyes. There was significant negative correlations between the average RNFL (r=-0.34, p=0.001) and GCIPL (r=-0.39, p<0.001) with VEP latency. In eyes with prior optic neuritis, a significant negative correlation was seen between average RNFL (r=-0.33, p=0.037) and GCIPL (r=-0.40, p=0.010) with VEP latency. We have found higher prevalence of VEP abnormalities than SCOCT in early relapsing-remitting multiple sclerosis. This suggests that VEP has a higher sensitivity for detecting lesions of the visual pathway in patients with early RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Seeing faces is necessary for face-domain formation.

    PubMed

    Arcaro, Michael J; Schade, Peter F; Vincent, Justin L; Ponce, Carlos R; Livingstone, Margaret S

    2017-10-01

    Here we report that monkeys raised without exposure to faces did not develop face domains, but did develop domains for other categories and did show normal retinotopic organization, indicating that early face deprivation leads to a highly selective cortical processing deficit. Therefore, experience must be necessary for the formation (or maintenance) of face domains. Gaze tracking revealed that control monkeys looked preferentially at faces, even at ages prior to the emergence of face domains, but face-deprived monkeys did not, indicating that face looking is not innate. A retinotopic organization is present throughout the visual system at birth, so selective early viewing behavior could bias category-specific visual responses toward particular retinotopic representations, thereby leading to domain formation in stereotyped locations in inferotemporal cortex, without requiring category-specific templates or biases. Thus, we propose that environmental importance influences viewing behavior, viewing behavior drives neuronal activity, and neuronal activity sculpts domain formation.

  11. Barriers and Enablers to Implementation of Dietary Guidelines in Early Childhood Education Centers in Australia: Application of the Theoretical Domains Framework.

    PubMed

    Grady, Alice; Seward, Kirsty; Finch, Meghan; Fielding, Alison; Stacey, Fiona; Jones, Jannah; Wolfenden, Luke; Yoong, Sze Lin

    2018-03-01

    To identify perceived barriers and enablers to implementation of dietary guidelines reported by early childhood education center cooks, and barriers and enablers associated with greater implementation based on assessment of center menu compliance. Cross-sectional telephone interview. Early childhood education centers, New South Wales, Australia. A total of 202 cooks responsible for menu planning; 70 centers provided a menu for review of compliance with dietary guidelines. Barriers and enablers to dietary guideline implementation were determined using a tool assessing constructs of the Theoretical Domains Framework (TDF). Higher scores (≥6) for each construct indicated enablers to guideline implementation; lower scores (<6) suggested barriers. Multivariable linear regression identified TDF constructs associated with greater guideline implementation. Scores were lowest for reinforcement (mean, 5.85) and goals (mean, 5.89) domains, and highest for beliefs about consequences (mean, 6.51) and social/professional role and identity (mean, 6.50). The skills domain was positively associated with greater implementation of guidelines based on menu review (P = .01). Cooks perceived social/professional role and identity, and beliefs about consequences to be enablers to dietary guideline implementation; however, only the skills domain was associated with greater implementation. There are opportunities to target the incongruence in perceptions vs reality of the barriers and enablers to implementation. Future research could examine the utility of the TDF to identify barriers and enablers to implementation to inform intervention development and for evaluating interventions to examine intervention mechanisms. Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  12. New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome

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

    Jouet, M.; Kenwick, S.; Moncla, A.

    1995-06-01

    The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the firstmore » examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function. 39 refs., 5 figs., 3 tabs.« less

  13. Matter antimatter domains: A possible solution to the CP domain wall problem in the early universe

    NASA Technical Reports Server (NTRS)

    Mohanty, A. K.; Stecker, F. W.

    1984-01-01

    An SU(5) grand unified theory model is used to show how the degeneracy between vacua with different spontaneously broken charge parity can be dynamically lifted by a condensate of heavy fermion pairs. This drives a phase transition to a unique vacuum state with definite charge parity. The transition eliminates the domain walls in a matter antimatter symmetric domain cosmology.

  14. Design and characterizations of two novel cellulases through single-gene shuffling of Cel12A (EG3) gene from Trichoderma reseei.

    PubMed

    Yenenler, Asli; Sezerman, Osman Ugur

    2016-06-01

    Cellulases have great potential to be widely used for industrial applications. In general, naturally occurring cellulases are not optimized and limited to meet the industrial needs. These limitations lead to demand for novel cellulases with enhanced enzymatic properties. Here, we describe the enzymatic and structural properties of two novel enzymes, EG3_S1 and EG3_S2, obtained through the single-gene shuffling approach of Cel12A(EG3) gene from Trichoderma reseei EG3_S1 and EG3_S2 shuffled enzymes display 59 and 75% identity in protein sequence with respect to native, respectively. Toward 4-MUC, the minimum activity of EG3_S1 was reported as 5.9-fold decrease in native at 35°C, whereas the maximum activity of EG3_S2 was reported as 15.4-fold increase in native activity at 40°C. Also, the diminished enzyme activity of EG3_S1 was reported within range of 0.6- to 0.8-fold of native and within range of 0.5- to 0.7-fold of native toward CMC and Na-CMC, respectively. For EG3_S2 enzyme, the improved enzymatic activities within range of 1.1- to 1.4-fold of native and within range of 1.1- to 1.6-fold of native were reported toward CMC and Na-CMC, respectively. Moreover, we have reported 6.5-fold increase in the kcat/Km ratio of EG3_S2 with respect to native and suggested EG3_S2 enzyme as more efficient catalysis for hydrolysis reactions than its native counterpart. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. A novel high-throughput (HTP) cloning strategy for site-directed designed chimeragenesis and mutation using the Gateway cloning system

    PubMed Central

    Suzuki, Yasuhiro; Kagawa, Naoko; Fujino, Toru; Sumiya, Tsuyoshi; Andoh, Taichi; Ishikawa, Kumiko; Kimura, Rie; Kemmochi, Kiyokazu; Ohta, Tsutomu; Tanaka, Shigeo

    2005-01-01

    There is an increasing demand for easy, high-throughput (HTP) methods for protein engineering to support advances in the development of structural biology, bioinformatics and drug design. Here, we describe an N- and C-terminal cloning method utilizing Gateway cloning technology that we have adopted for chimeric and mutant genes production as well as domain shuffling. This method involves only three steps: PCR, in vitro recombination and transformation. All three processes consist of simple handling, mixing and incubation steps. We have characterized this novel HTP method on 96 targets with >90% success. Here, we also discuss an N- and C-terminal cloning method for domain shuffling and a combination of mutation and chimeragenesis with two types of plasmid vectors. PMID:16009811

  16. Structural determinants at the interface of the ARC2 and leucine-rich repeat domains control the activation of the plant immune receptors Rx1 and Gpa2.

    PubMed

    Slootweg, Erik J; Spiridon, Laurentiu N; Roosien, Jan; Butterbach, Patrick; Pomp, Rikus; Westerhof, Lotte; Wilbers, Ruud; Bakker, Erin; Bakker, Jaap; Petrescu, Andrei-José; Smant, Geert; Goverse, Aska

    2013-07-01

    Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins.

  17. Chemical Shift Assignments of the C-terminal Eps15 Homology Domain-3 EH Domain*

    PubMed Central

    Caplan, Steve; Sorgen, Paul L.

    2013-01-01

    The C-terminal Eps15 homology (EH) domain 3 (EHD3) belongs to a eukaryotic family of endocytic regulatory proteins and is involved in the recycling of various receptors from the early endosome to the endocytic recycling compartment or in retrograde transport from the endosomes to the Golgi. EH domains are highly conserved in the EHD family and function as protein-protein interaction units that bind to Asn-Pro-Phe (NPF) motif-containing proteins. The EH domain of EHD1 was the first C-terminal EH domain from the EHD family to be solved by NMR. The differences observed between this domain and proteins with N-terminal EH domains helped describe a mechanism for the differential binding of NPF-containing proteins. Here, structural studies were expanded to include the EHD3 EH domain. While the EHD1 and EHD3 EH domains are highly homologous, they have different protein partners. A comparison of these structures will help determine the selectivity in protein binding between the EHD family members and lead to a better understanding of their unique roles in endocytic regulation. PMID:23754701

  18. An Effective Hybrid Cuckoo Search Algorithm with Improved Shuffled Frog Leaping Algorithm for 0-1 Knapsack Problems

    PubMed Central

    Wang, Gai-Ge; Feng, Qingjiang; Zhao, Xiang-Jun

    2014-01-01

    An effective hybrid cuckoo search algorithm (CS) with improved shuffled frog-leaping algorithm (ISFLA) is put forward for solving 0-1 knapsack problem. First of all, with the framework of SFLA, an improved frog-leap operator is designed with the effect of the global optimal information on the frog leaping and information exchange between frog individuals combined with genetic mutation with a small probability. Subsequently, in order to improve the convergence speed and enhance the exploitation ability, a novel CS model is proposed with considering the specific advantages of Lévy flights and frog-leap operator. Furthermore, the greedy transform method is used to repair the infeasible solution and optimize the feasible solution. Finally, numerical simulations are carried out on six different types of 0-1 knapsack instances, and the comparative results have shown the effectiveness of the proposed algorithm and its ability to achieve good quality solutions, which outperforms the binary cuckoo search, the binary differential evolution, and the genetic algorithm. PMID:25404940

  19. ARTP mutation and genome shuffling of ABE fermentation symbiotic system for improvement of butanol production.

    PubMed

    Gu, Chunkai; Wang, Genyu; Mai, Shuai; Wu, Pengfei; Wu, Jianrong; Wang, Gehua; Liu, Hongjuan; Zhang, Jianan

    2017-03-01

    Butanol is an ideal renewable biofuel which possesses superior fuel properties. Previously, butanol-producing symbiotic system TSH06 was isolated in our lab, with microoxygen tolerance ability. To boost butanol yield for large-scale industrial production, TSH06 was used as parental strain and subjected to atmospheric and room temperature plasma (ARTP) and four rounds of genome shuffling (GS). ARTP mutant and GS strain were co-cultured with facultative anaerobic Bacillus cereus TSH2 to form a symbiotic system with microoxygen tolerance, which was then subjected to fermentation. Relative messenger RNA (mRNA) level of key enzyme gene was measured by real-time PCR. The highest butanol titer of TS4-30 reached 15.63 g/L, which was 34% higher than TSH06 (12.19 g/L). Compared with parental strain, mRNA of acid-forming gene in TS4-30 decreased in acidogenesis phase, while solvent-forming gene increased in solventogenesis phase. This gene expression pattern was consistent with high butanol yield and low acid level in TS4-30. In summary, symbiotic system TS4-30 was obtained with butanol titer improvement and microoxygen tolerance.

  20. Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa21[C][W][OA

    PubMed Central

    Slootweg, Erik J.; Spiridon, Laurentiu N.; Roosien, Jan; Butterbach, Patrick; Pomp, Rikus; Westerhof, Lotte; Wilbers, Ruud; Bakker, Erin; Bakker, Jaap; Petrescu, Andrei-José; Smant, Geert; Goverse, Aska

    2013-01-01

    Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins. PMID:23660837

  1. A new maximum power tracking in PV system during partially shaded conditions based on shuffled frog leap algorithm

    NASA Astrophysics Data System (ADS)

    Sridhar, R.; Jeevananthan, S.; Dash, S. S.; Vishnuram, Pradeep

    2017-05-01

    Maximum Power Point Trackers (MPPTs) are power electronic conditioners used in photovoltaic (PV) system to ensure that PV structures feed maximum power for the given ambient temperature and sun's irradiation. When the PV panels are shaded by a fraction due to any environment hindrances then, conventional MPPT trackers may fail in tracking the appropriate peak power as there will be multi power peaks. In this work, a shuffled frog leap algorithm (SFLA) is proposed and it successfully identifies the global maximum power point among other local maxima. The SFLA MPPT is compared with a well-entrenched conventional perturb and observe (P&O) MPPT algorithm and a global search particle swarm optimisation (PSO) MPPT. The simulation results reveal that the proposed algorithm is highly advantageous than P&O, as it tracks nearly 30% more power for a given shading pattern. The credible nature of the proposed SFLA is ensured when it outplays PSO MPPT in convergence. The whole system is realised in MATLAB/Simulink environment.

  2. Structural Determination of Functional Domains in Early B-cell Factor (EBF) Family of Transcription Factors Reveals Similarities to Rel DNA-binding Proteins and a Novel Dimerization Motif*

    PubMed Central

    Siponen, Marina I.; Wisniewska, Magdalena; Lehtiö, Lari; Johansson, Ida; Svensson, Linda; Raszewski, Grzegorz; Nilsson, Lennart; Sigvardsson, Mikael; Berglund, Helena

    2010-01-01

    The early B-cell factor (EBF) transcription factors are central regulators of development in several organs and tissues. This protein family shows low sequence similarity to other protein families, which is why structural information for the functional domains of these proteins is crucial to understand their biochemical features. We have used a modular approach to determine the crystal structures of the structured domains in the EBF family. The DNA binding domain reveals a striking resemblance to the DNA binding domains of the Rel homology superfamily of transcription factors but contains a unique zinc binding structure, termed zinc knuckle. Further the EBF proteins contain an IPT/TIG domain and an atypical helix-loop-helix domain with a novel type of dimerization motif. The data presented here provide insights into unique structural features of the EBF proteins and open possibilities for detailed molecular investigations of this important transcription factor family. PMID:20592035

  3. Longitudinal Prediction of Disruptive Behavior Disorders in Adolescent Males from Multiple Risk Domains

    PubMed Central

    Trentacosta, Christopher J.; Hyde, Luke W.; Goodlett, Benjamin D.; Shaw, Daniel S.

    2012-01-01

    The disruptive behavior disorders are among the most prevalent youth psychiatric disorders, and they predict numerous problematic outcomes in adulthood. This study examined multiple domains of risk during early childhood and early adolescence as longitudinal predictors of disruptive behavior disorder diagnoses among adolescent males. Early adolescent risks in the domains of sociodemographic factors, the caregiving context, and youth attributes were examined as mediators of associations between early childhood risks and disruptive behavior disorder diagnoses. Participants were 309 males from a longitudinal study of low-income mothers and their sons. Caregiving and youth risk during early adolescence each predicted the likelihood of receiving a disruptive behavior disorder diagnosis. Furthermore, sociodemographic and caregiving risk during early childhood were indirectly associated with disruptive behavior disorder diagnoses via their association with early adolescent risk. The findings suggest that preventive interventions targeting risk across domains may reduce the prevalence of disruptive behavior disorders. PMID:23239427

  4. The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

    PubMed

    Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

    2017-07-15

    Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

  5. The Conserved Foot Domain of RNA Pol II Associates with Proteins Involved in Transcriptional Initiation and/or Early Elongation

    PubMed Central

    García-López, M. Carmen; Pelechano, Vicent; Mirón-García, M. Carmen; Garrido-Godino, Ana I.; García, Alicia; Calvo, Olga; Werner, Michel; Pérez-Ortín, José E.; Navarro, Francisco

    2011-01-01

    RNA polymerase (pol) II establishes many protein–protein interactions with transcriptional regulators to coordinate different steps of transcription. Although some of these interactions have been well described, little is known about the existence of RNA pol II regions involved in contact with transcriptional regulators. We hypothesize that conserved regions on the surface of RNA pol II contact transcriptional regulators. We identified such an RNA pol II conserved region that includes the majority of the “foot” domain and identified interactions of this region with Mvp1, a protein required for sorting proteins to the vacuole, and Spo14, a phospholipase D. Deletion of MVP1 and SPO14 affects the transcription of their target genes and increases phosphorylation of Ser5 in the carboxy-terminal domain (CTD). Genetic, phenotypic, and functional analyses point to a role for these proteins in transcriptional initiation and/or early elongation, consistent with their genetic interactions with CEG1, a guanylyltransferase subunit of the Saccharomyces cerevisiae capping enzyme. PMID:21954159

  6. Evolution of vacuolar proton pyrophosphatase domains and volutin granules: clues into the early evolutionary origin of the acidocalcisome

    PubMed Central

    2011-01-01

    domains support the early origin of the acidocalcisome organelle. In particular, the universality of volutin granules and presence of a functional V-H+PPase domain in the three superkingdoms of life reveals that the acidocalcisomes may have appeared earlier than the divergence of the superkingdoms. This result is remarkable and highlights the possibility that a high degree of cellular compartmentalization could already have been present in the LUCA. Reviewers This article was reviewed by Anthony Poole, Lakshminarayan Iyer and Daniel Kahn PMID:21974828

  7. Comparative genomics of phylogenetically diverse unicellular eukaryotes provide new insights into the genetic basis for the evolution of the programmed cell death machinery.

    PubMed

    Nedelcu, Aurora M

    2009-03-01

    Programmed cell death (PCD) represents a significant component of normal growth and development in multicellular organisms. Recently, PCD-like processes have been reported in single-celled eukaryotes, implying that some components of the PCD machinery existed early in eukaryotic evolution. This study provides a comparative analysis of PCD-related sequences across more than 50 unicellular genera from four eukaryotic supergroups: Unikonts, Excavata, Chromalveolata, and Plantae. A complex set of PCD-related sequences that correspond to domains or proteins associated with all main functional classes--from ligands and receptors to executors of PCD--was found in many unicellular lineages. Several PCD domains and proteins previously thought to be restricted to animals or land plants are also present in unicellular species. Noteworthy, the yeast, Saccharomyces cerevisiae--used as an experimental model system for PCD research, has a rather reduced set of PCD-related sequences relative to other unicellular species. The phylogenetic distribution of the PCD-related sequences identified in unicellular lineages suggests that the genetic basis for the evolution of the complex PCD machinery present in extant multicellular lineages has been established early in the evolution of eukaryotes. The shaping of the PCD machinery in multicellular lineages involved the duplication, co-option, recruitment, and shuffling of domains already present in their unicellular ancestors.

  8. Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan.

    PubMed

    Chiou, Chien-Shun; Wang, You-Wun; Chen, Pei-Ling; Wang, Wan-Ling; Wu, Ping-Fuai; Wei, Hsiao-Lun

    2009-06-01

    The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of Streptococcus pyogenes were collected from scarlet fever patients in central Taiwan and were characterized by emm sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends. A total of 23 emm types were identified in 1,218 S. pyogenes isolates. The five most prevalent emm types were emm12 (50.4%), emm4 (23.2%), emm1 (16.4%), emm6 (3.8%) and emm22 (3.0%). PFGE analysis with SmaI suggested that, with a few exceptions, strains with a common emm type belonged to the same clone. There were two large emm12 clones, one with DNA resistant to cleavage by SmaI. Each prevalent emm clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2-3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent emm clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan. The occurrences of scarlet fever in central Taiwan in 2000-2006 were primarily caused by five emm types, which accounted for 96.8% of the isolates collected. Most of the S. pyogenes strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent emm clones and to the SARS outbreak in 2003.

  9. Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan

    PubMed Central

    2009-01-01

    Background The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of Streptococcus pyogenes were collected from scarlet fever patients in central Taiwan and were characterized by emm sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends. Results A total of 23 emm types were identified in 1,218 S. pyogenes isolates. The five most prevalent emm types were emm12 (50.4%), emm4 (23.2%), emm1 (16.4%), emm6 (3.8%) and emm22 (3.0%). PFGE analysis with SmaI suggested that, with a few exceptions, strains with a common emm type belonged to the same clone. There were two large emm12 clones, one with DNA resistant to cleavage by SmaI. Each prevalent emm clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2–3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent emm clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan. Conclusion The occurrences of scarlet fever in central Taiwan in 2000–2006 were primarily caused by five emm types, which accounted for 96.8% of the isolates collected. Most of the S. pyogenes strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent emm clones and to the SARS outbreak in 2003. PMID:19486515

  10. Single Domain Antibodies as New Biomarker Detectors

    PubMed Central

    Fischer, Katja; Leow, Chiuan Yee; Chuah, Candy; McCarthy, James

    2017-01-01

    Biomarkers are defined as indicators of biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers have been widely used for early detection, prediction of response after treatment, and for monitoring the progression of diseases. Antibodies represent promising tools for recognition of biomarkers, and are widely deployed as analytical tools in clinical settings. For immunodiagnostics, antibodies are now exploited as binders for antigens of interest across a range of platforms. More recently, the discovery of antibody surface display and combinatorial chemistry techniques has allowed the exploration of new binders from a range of animals, for instance variable domains of new antigen receptors (VNAR) from shark and variable heavy chain domains (VHH) or nanobodies from camelids. These single domain antibodies (sdAbs) have some advantages over conventional murine immunoglobulin owing to the lack of a light chain, making them the smallest natural biomarker binders thus far identified. In this review, we will discuss several biomarkers used as a means to validate diseases progress. The potential functionality of modern singe domain antigen binders derived from phylogenetically early animals as new biomarker detectors for current diagnostic and research platforms development will be described. PMID:29039819

  11. Frequency doubling technique perimetry and spectral domain optical coherence tomography in patients with early glaucoma.

    PubMed

    Horn, F K; Mardin, C Y; Bendschneider, D; Jünemann, A G; Adler, W; Tornow, R P

    2011-01-01

    To assess the combined diagnostic power of frequency-doubling technique (FDT)-perimetry and retinal nerve fibre layer (RNFL) thickness measurements with spectral domain optical coherence tomography (SDOCT). The study included 330 experienced participants in five age-related groups: 77 'preperimetric' open-angle glaucoma (OAG) patients, 52 'early' OAG, 50 'moderate' OAG, 54 ocular hypertensive patients, and 97 healthy subjects. For glaucoma assessment in all subjects conventional perimetry, evaluation of fundus photographs, FDT-perimetry and RNFL thickness measurement with SDOCT was done. Glaucomatous visual field defects were classified using the Glaucoma Staging System. FDT evaluation used a published method with casewise calculation of an 'FDT-score', including all missed localized probability levels. SDOCT evaluation used mean RNFL thickness and a new individual SDOCT-score considering normal confidence limits in 32 sectors of a peripapillary circular scan. To examine the joined value of both methods a combined score was introduced. Significance of the difference between Receiver-operating-characteristic (ROC) curves was calculated for a specificity of 96%. Sensitivity in the preperimetric glaucoma group was 44% for SDOCT-score, 25% for FDT-score, and 44% for combined score, in the early glaucoma group 83, 81, and 89%, respectively, and in the moderate glaucoma group 94, 94, and 98%, respectively, all at a specificity of 96%. ROC performance of the newly developed combined score is significantly above single ROC curves of FDT-score in preperimetric and early OAG and above RNFL thickness in moderate OAG. Combination of function and morphology by using the FDT-score and the SDOCT-score performs equal or even better than each single method alone.

  12. Frequency doubling technique perimetry and spectral domain optical coherence tomography in patients with early glaucoma

    PubMed Central

    Horn, F K; Mardin, C Y; Bendschneider, D; Jünemann, A G; Adler, W; Tornow, R P

    2011-01-01

    Purpose To assess the combined diagnostic power of frequency-doubling technique (FDT)-perimetry and retinal nerve fibre layer (RNFL) thickness measurements with spectral domain optical coherence tomography (SDOCT). Methods The study included 330 experienced participants in five age-related groups: 77 ‘preperimetric' open-angle glaucoma (OAG) patients, 52 ‘early' OAG, 50 ‘moderate' OAG, 54 ocular hypertensivepatients, and 97 healthy subjects. For glaucoma assessment in all subjects conventional perimetry, evaluation of fundus photographs, FDT-perimetry and RNFL thickness measurement with SDOCT was done. Glaucomatous visual field defects were classified using the Glaucoma Staging System. FDT evaluation used a published method with casewise calculation of an ‘FDT-score', including all missed localized probability levels. SDOCT evaluation used mean RNFL thickness and a new individual SDOCT-score considering normal confidence limits in 32 sectors of a peripapillary circular scan. To examine the joined value of both methods a combined score was introduced. Significance of the difference between Receiver-operating-characteristic (ROC) curves was calculated for a specificity of 96%. Results Sensitivity in the preperimetric glaucoma group was 44% for SDOCT-score, 25% for FDT-score, and 44% for combined score, in the early glaucoma group 83, 81, and 89%, respectively, and in the moderate glaucoma group 94, 94, and 98%, respectively, all at a specificity of 96%. ROC performance of the newly developed combined score is significantly above single ROC curves of FDT-score in preperimetric and early OAG and above RNFL thickness in moderate OAG. Conclusion Combination of function and morphology by using the FDT-score and the SDOCT-score performs equal or even better than each single method alone. PMID:21102494

  13. Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes.

    PubMed

    Huang, Shengfeng; Chen, Zelin; Yan, Xinyu; Yu, Ting; Huang, Guangrui; Yan, Qingyu; Pontarotti, Pierre Antoine; Zhao, Hongchen; Li, Jie; Yang, Ping; Wang, Ruihua; Li, Rui; Tao, Xin; Deng, Ting; Wang, Yiquan; Li, Guang; Zhang, Qiujin; Zhou, Sisi; You, Leiming; Yuan, Shaochun; Fu, Yonggui; Wu, Fenfang; Dong, Meiling; Chen, Shangwu; Xu, Anlong

    2014-12-19

    Vertebrates diverged from other chordates ~500 Myr ago and experienced successful innovations and adaptations, but the genomic basis underlying vertebrate origins are not fully understood. Here we suggest, through comparison with multiple lancelet (amphioxus) genomes, that ancient vertebrates experienced high rates of protein evolution, genome rearrangement and domain shuffling and that these rates greatly slowed down after the divergence of jawed and jawless vertebrates. Compared with lancelets, modern vertebrates retain, at least relatively, less protein diversity, fewer nucleotide polymorphisms, domain combinations and conserved non-coding elements (CNE). Modern vertebrates also lost substantial transposable element (TE) diversity, whereas lancelets preserve high TE diversity that includes even the long-sought RAG transposon. Lancelets also exhibit rapid gene turnover, pervasive transcription, fastest exon shuffling in metazoans and substantial TE methylation not observed in other invertebrates. These new lancelet genome sequences provide new insights into the chordate ancestral state and the vertebrate evolution.

  14. Early Life Stress, Mood, and Anxiety Disorders.

    PubMed

    Syed, Shariful A; Nemeroff, Charles B

    2017-02-01

    Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health's proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.

  15. Developmental Change in the Influence of Domain-General Abilities and Domain-Specific Knowledge on Mathematics Achievement: An Eight-Year Longitudinal Study

    PubMed Central

    Geary, David C.; Nicholas, Alan; Li, Yaoran; Sun, Jianguo

    2016-01-01

    The contributions of domain-general abilities and domain-specific knowledge to subsequent mathematics achievement were longitudinally assessed (n = 167) through 8th grade. First grade intelligence and working memory and prior grade reading achievement indexed domain-general effects and domain-specific effects were indexed by prior grade mathematics achievement and mathematical cognition measures of prior grade number knowledge, addition skills, and fraction knowledge. Use of functional data analysis enabled grade-by-grade estimation of overall domain-general and domain-specific effects on subsequent mathematics achievement, the relative importance of individual domain-general and domain-specific variables on this achievement, and linear and non-linear across-grade estimates of these effects. The overall importance of domain-general abilities for subsequent achievement was stable across grades, with working memory emerging as the most important domain-general ability in later grades. The importance of prior mathematical competencies on subsequent mathematics achievement increased across grades, with number knowledge and arithmetic skills critical in all grades and fraction knowledge in later grades. Overall, domain-general abilities were more important than domain-specific knowledge for mathematics learning in early grades but general abilities and domain-specific knowledge were equally important in later grades. PMID:28781382

  16. Bacterial expression and purification of a heterodimeric adrenomedullin receptor extracellular domain complex using DsbC-assisted disulfide shuffling.

    PubMed

    Hill, Heather E; Pioszak, Augen A

    2013-03-01

    Adrenomedullin (AM) is a peptide hormone that is a potent vasodilator and is essential for vascular development. The AM receptor is a heterodimeric cell surface receptor composed of the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor, in association with either of two receptor activity modifying protein (RAMP) coreceptors, RAMP2 or -3. The extracellular domains (ECDs) of CLR and the RAMPs form the primary AM binding site. Here, we present novel methodology for expression and purification of a heterodimeric AM receptor ECD complex as an MBP-CLR ECD fusion protein in association with the RAMP2 ECD. Co-expression of the RAMP2 ECD with the disulfide bond isomerase DsbC in the oxidizing cytoplasm of E. coli trxB gor enabled proper disulfide formation in vivo. The isolated RAMP2 ECD was purified to homogeneity. Co-expression of a soluble MBP-CLR ECD fusion protein with DsbC in E. coli trxB gor yielded a heterogeneous mixture of species with misfolded ECD. Incubation of affinity-purified MBP-CLR ECD in vitro with purified RAMP2 ECD, DsbC, and glutathione redox buffer promoted proper folding of the CLR ECD and formation of a stable MBP-CLR ECD:RAMP2 ECD complex that was purified by size-exclusion chromatography and which exhibited specific AM binding. Approximately 40mg of highly purified complex was obtained starting with 6L bacterial cultures for each protein. The methodology reported here will facilitate structure/function studies of the AM receptor. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Herpesvirus tegument and immediate early proteins are pioneers in the battle between viral infection and nuclear domain 10-related host defense.

    PubMed

    Zhang, Kuan; van Drunen Littel-van den Hurk, Sylvia

    2017-06-15

    The sophisticated anti-viral functions of nuclear domain 10 (ND10) are revealed by identifying the role of each component and the countermeasures applied by viruses. Several ND10 proteins suppress herpesviruses at initial and early phases of infection. Herpesviruses need to antagonize these anti-viral proteins to start a productive infection. In this review the recently identified similarities and differences among the strategies adopted by the three subfamilies of herpesviruses are discussed, highlighting that one of the significant purposes of incorporating tegument proteins into the viral particles might be to counteract ND10 proteins immediately after the viral genome enters the host nucleus. Once the infection progresses, a sufficient amount of immediate early proteins is expressed to disperse and hydrolyze ND10 proteins, accelerating the development of infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes

    PubMed Central

    Huang, Shengfeng; Chen, Zelin; Yan, Xinyu; Yu, Ting; Huang, Guangrui; Yan, Qingyu; Pontarotti, Pierre Antoine; Zhao, Hongchen; Li, Jie; Yang, Ping; Wang, Ruihua; Li, Rui; Tao, Xin; Deng, Ting; Wang, Yiquan; Li, Guang; Zhang, Qiujin; Zhou, Sisi; You, Leiming; Yuan, Shaochun; Fu, Yonggui; Wu, Fenfang; Dong, Meiling; Chen, Shangwu; Xu, Anlong

    2014-01-01

    Vertebrates diverged from other chordates ~500 Myr ago and experienced successful innovations and adaptations, but the genomic basis underlying vertebrate origins are not fully understood. Here we suggest, through comparison with multiple lancelet (amphioxus) genomes, that ancient vertebrates experienced high rates of protein evolution, genome rearrangement and domain shuffling and that these rates greatly slowed down after the divergence of jawed and jawless vertebrates. Compared with lancelets, modern vertebrates retain, at least relatively, less protein diversity, fewer nucleotide polymorphisms, domain combinations and conserved non-coding elements (CNE). Modern vertebrates also lost substantial transposable element (TE) diversity, whereas lancelets preserve high TE diversity that includes even the long-sought RAG transposon. Lancelets also exhibit rapid gene turnover, pervasive transcription, fastest exon shuffling in metazoans and substantial TE methylation not observed in other invertebrates. These new lancelet genome sequences provide new insights into the chordate ancestral state and the vertebrate evolution. PMID:25523484

  19. Statistics of “Cold” Early Impulsive Solar Flares in X-Ray and Microwave Domains

    NASA Astrophysics Data System (ADS)

    Lysenko, Alexandra L.; Altyntsev, Alexander T.; Meshalkina, Natalia S.; Zhdanov, Dmitriy; Fleishman, Gregory D.

    2018-04-01

    Solar flares often happen after a preflare/preheating phase, which is almost or entirely thermal. In contrast, there are the so-called early impulsive flares that do not show a (significant) preflare heating, but instead often show the Neupert effect—a relationship where the impulsive phase is followed by a gradual, cumulative-like, thermal response. This has been interpreted as a dominance of nonthermal energy release at the impulsive phase, even though a similar phenomenology is expected if the thermal and nonthermal energies are released in comparable amounts at the impulsive phase. Nevertheless, some flares do show a good quantitative correspondence between the nonthermal electron energy input and plasma heating; in such cases, the thermal response was weak, which results in them being called “cold” flares. We undertook a systematic search for such events among early impulsive flares registered by the Konus-Wind instrument in the triggered mode from 11/1994 to 4/2017, and selected 27 cold flares based on relationships between hard X-ray (HXR) (Konus-Wind) and soft X-ray (Geostationary Operational Environmental Satellite) emission. For these events, we put together all available microwave data from different instruments. We obtained temporal and spectral parameters of HXR and microwave emissions of the events and examined correlations between them. We found that, compared to a “mean” flare, the cold flares: (i) are weaker, shorter, and harder in the X-ray domain; (ii) are harder and shorter, but not weaker in the microwaves; (iii) have a significantly higher spectral peak frequencies in the microwaves. We discuss the possible physical reasons for these distinctions and implication of the finding.

  20. FB elements can promote exon shuffling: a promoter-less white allele can be reactivated by FB mediated transposition in Drosophila melanogaster.

    PubMed

    Moschetti, R; Marsano, R M; Barsanti, P; Caggese, C; Caizzi, R

    2004-05-01

    Foldback ( FB) elements are transposable elements found in many eukaryotic genomes; they are thought to contribute significantly to genome plasticity. In Drosophila melanogaster, FBs have been shown to be involved in the transposition of large chromosomal regions and in the genetic instability of some alleles of the white gene. In this report we show that FB mediated transposition of w(67C23), a mutation that deletes the promoter of the white gene and its first exon, containing the start codon, can restore expression of the white gene. We have characterized three independent events in which a 14-kb fragment from the w(67C23) locus was transposed into an intron region in three different genes. In each case a local promoter drives the expression of white, producing a chimeric mRNA. These findings suggest that, on an evolutionary timescale, FB elements may contribute to the creation of new genes via exon shuffling.

  1. Early selection of resistance-associated mutations in HIV-1 RT C-terminal domains across different subtypes: role of the genetic barrier to resistance.

    PubMed

    Muniz, Cláudia P; Soares, Marcelo A; Santos, André F

    2014-10-01

    Interpretation of drug resistance mutation (DRM) has been based solely on HIV-1 subtype B. Reverse transcriptase (RT) C-terminal domains have been disregarded in resistance interpretation, as their clinical relevance is still controversial. We determined the emergence of DRM in RT C-terminal domains of different HIV-1 subtypes, the genetic barrier for the acquisition of these DRM and their temporal appearance with 'classical' RT inhibitor (RTI) mutations. HIV-1 RT sequences were obtained from information from 6087 treatment-naive and 3795 RTI-treated patients deposited in the Stanford HIV Resistance Database, including all major subtypes. DRM emergence was evaluated for subtype B, and was correlated with the number of DRM in the polymerase domain. Genetic barrier was calculated for each DRM studied and in each subtype. N348I, T369I and A360V were found at low prevalence in treatment-naive isolates of all subtypes. A371V was common to treatment-naive isolates. N348I was observed in all subtypes, while T369I was only selected in subtype C. A360V and T369V were selected by RTI treatment in several subtypes. A371V was selected in subtypes B and C, but is a signature in subtype A. RT C-terminal mutations were correlated with early drug resistance in subtype B. All subtypes have a low calculated genetic barrier towards C-terminal DRM acquisition, despite a few disparities having been observed. C-terminal mutations were selected in all HIV-1 subtypes, while some represent subtype-specific signatures. The selection of C-terminal DRMs occurs early in RTI resistance failure in subtype B. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain.

    PubMed

    Tabarani, Georges; Thépaut, Michel; Stroebel, David; Ebel, Christine; Vivès, Corinne; Vachette, Patrice; Durand, Dominique; Fieschi, Franck

    2009-08-07

    DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.

  3. Improved antimicrobial activity of Pediococcus acidilactici against Salmonella Gallinarum by UV mutagenesis and genome shuffling.

    PubMed

    Han, Geon Goo; Song, Ahn Ah; Kim, Eun Bae; Yoon, Seong-Hyun; Bok, Jin-Duck; Cho, Chong-Su; Kil, Dong Yong; Kang, Sang-Kee; Choi, Yun-Jaie

    2017-07-01

    Pediococcus acidilactici is a widely used probiotic, and Salmonella enterica serovar Gallinarum (SG) is a significant pathogen in the poultry industry. In this study, we improved the antimicrobial activity of P. acidilactici against SG using UV mutation and genome shuffling (GS). To improve antimicrobial activity against SG, UV mutagenesis was performed against wild-type P. acidilactici (WT), and five mutants showed improved antimicrobial activity. To further improve antimicrobial activity, GS was performed on five UV mutants. Following GS, four mutants showed improved antimicrobial activity compared with the UV mutants and WT. The antimicrobial activity of GS1 was highest among the mutants; however, the activity was reduced when the culture supernatant was treated with proteinase K, suggesting that the improved antimicrobial activity is due to a proteinous substance such as bacteriocin. To validate the activity of GS1 in vivo, we designed multi-species probiotics and performed broiler feeding experiments. Groups consisted of no treatment (NC), avilamycin-treated (PC), probiotic group 1 containing WT (T1), and probiotic group 2 containing GS1 (T2). In broiler feeding experiments, coliform bacteria were significantly reduced in T2 compared with NC, PC, and T1. The cecal microbiota was modulated and pathogenic bacteria were reduced by GS1 oral administration. In this study, GS1 showed improved antimicrobial activity against SG in vitro and reduced pathogenic bacteria in a broiler feeding experiment. These results suggest that GS1 can serve as an efficient probiotic, as an alternative to antibiotics in the poultry industry.

  4. Statistical mechanics of two-dimensional shuffled foams: Geometry-topology correlation in small or large disorder limits

    NASA Astrophysics Data System (ADS)

    Durand, Marc; Kraynik, Andrew M.; van Swol, Frank; Käfer, Jos; Quilliet, Catherine; Cox, Simon; Ataei Talebi, Shirin; Graner, François

    2014-06-01

    Bubble monolayers are model systems for experiments and simulations of two-dimensional packing problems of deformable objects. We explore the relation between the distributions of the number of bubble sides (topology) and the bubble areas (geometry) in the low liquid fraction limit. We use a statistical model [M. Durand, Europhys. Lett. 90, 60002 (2010), 10.1209/0295-5075/90/60002] which takes into account Plateau laws. We predict the correlation between geometrical disorder (bubble size dispersity) and topological disorder (width of bubble side number distribution) over an extended range of bubble size dispersities. Extensive data sets arising from shuffled foam experiments, surface evolver simulations, and cellular Potts model simulations all collapse surprisingly well and coincide with the model predictions, even at extremely high size dispersity. At moderate size dispersity, we recover our earlier approximate predictions [M. Durand, J. Kafer, C. Quilliet, S. Cox, S. A. Talebi, and F. Graner, Phys. Rev. Lett. 107, 168304 (2011), 10.1103/PhysRevLett.107.168304]. At extremely low dispersity, when approaching the perfectly regular honeycomb pattern, we study how both geometrical and topological disorders vanish. We identify a crystallization mechanism and explore it quantitatively in the case of bidisperse foams. Due to the deformability of the bubbles, foams can crystallize over a larger range of size dispersities than hard disks. The model predicts that the crystallization transition occurs when the ratio of largest to smallest bubble radii is 1.4.

  5. Terrorism in the Maritime Domain

    DTIC Science & Technology

    2013-03-01

    Indonesia-based terrorist group formed in the early 1990s to establish an Islamic state encompassing southern Thailand, Malaysia , Singapore, Indonesia...overseas. There are instances where the warships need to replenish their fuel and food supplies in a foreign country’s harbor. The terrorist group...initiated to improve the maritime domain awareness in the tri-border area (TBA) between the Philippines, Malaysia , and Indonesia, where terrorist

  6. Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo

    PubMed Central

    Stadler, Michael R; Haines, Jenna E

    2017-01-01

    High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their establishment remain poorly understood. Here we present high resolution Hi-C data from early Drosophila embryos. We demonstrate that boundaries between topological domains of various sizes map to DNA elements that resemble classical insulator elements: short genomic regions sensitive to DNase digestion that are strongly bound by known insulator proteins and are frequently located between divergent promoters. Further, we show a striking correspondence between these elements and the locations of mapped polytene interband regions. We believe it is likely this relationship between insulators, topological boundaries, and polytene interbands extends across the genome, and we therefore propose a model in which decompaction of boundary-insulator-interband regions drives the organization of interphase chromosomes by creating stable physical separation between adjacent domains. PMID:29148971

  7. Topologically associating domains are stable units of replication-timing regulation.

    PubMed

    Pope, Benjamin D; Ryba, Tyrone; Dileep, Vishnu; Yue, Feng; Wu, Weisheng; Denas, Olgert; Vera, Daniel L; Wang, Yanli; Hansen, R Scott; Canfield, Theresa K; Thurman, Robert E; Cheng, Yong; Gülsoy, Günhan; Dennis, Jonathan H; Snyder, Michael P; Stamatoyannopoulos, John A; Taylor, James; Hardison, Ross C; Kahveci, Tamer; Ren, Bing; Gilbert, David M

    2014-11-20

    Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program. In mammals, replication timing is cell-type-specific with at least half the genome switching replication timing during development, primarily in units of 400-800 kilobases ('replication domains'), whose positions are preserved in different cell types, conserved between species, and appear to confine long-range effects of chromosome rearrangements. Early and late replication correlate, respectively, with open and closed three-dimensional chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, late replication correlates with lamina-associated domains (LADs). Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains. However, TADs can be further sub-stratified into smaller domains, challenging the significance of structures at any particular scale. Moreover, attempts to reconcile TADs and LADs to replication-timing data have not revealed a common, underlying domain structure. Here we localize boundaries of replication domains to the early-replicating border of replication-timing transitions and map their positions in 18 human and 13 mouse cell types. We demonstrate that, collectively, replication domain boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure replication domain boundaries, largely accounting for the previously reported lack of alignment. Moreover, cell-type-specific replication timing of TADs partitions the genome into two large-scale sub-nuclear compartments revealing that replication-timing transitions are indistinguishable from late-replicating regions in chromatin composition and lamina association and accounting for the

  8. Language, Play and Early Literacy for Deaf Children: The Role of Parent Input

    ERIC Educational Resources Information Center

    Brown, P. Margaret; Watson, Linda M.

    2017-01-01

    This paper reviews and synthesizes research into the ways in which parents support their child across three major developmental domains in early childhood: early language, play and early literacy. We show how these domains are linked to each other and suggest that there is some evidence that interventions in all of them will promote mutual…

  9. Using Topdown Conceptual Analysis To Accelerate The Learning Of New Domains For Knowledge Engineers & Domain Experts

    NASA Astrophysics Data System (ADS)

    Xuan, Albert L.; Shinghal, Rajjan

    1989-03-01

    As the need for knowledge-based systems increases, an increasing number of domain experts are becoming interested in taking more active part in the building of knowledge-based systems. However, such a domain expert often must deal with a large number of unfamiliar terms concepts, facts, procedures and principles based on different approaches and schools of thought. He (for brevity, we shall use masculine pronouns for both genders) may need the help of a knowledge engineer (KE) in building the knowledge-based system but may encounter a number of problems. For instance, much of the early interaction between him and the knowl edge engineer may be spent in educating each other about their seperate kinds of expertise. Since the knowledge engineer will usually be ignorant of the knowledge domain while the domain expert (DE) will have little knowledge about knowledge-based systems, a great deal of time will be wasted on these issues ad the DE and the KE train each other to the point where a fruitful interaction can occur. In some situations, it may not even be possible for the DE to find a suitable KE to work with because he has no time to train the latter in his domain. This will engender the need for the DE to be more knowledgeable about knowledge-based systems and for the KE to find methods and techniques which will allow them to learn new domains as fast as they can. In any event, it is likely that the process of building knowledge-based systems will be smooth, er and more efficient if the domain expert is knowledgeable about the methods and techniques of knowledge-based systems building.

  10. Technical Report: Kindergarten Early Learning Scale

    ERIC Educational Resources Information Center

    Riley-Ayers, Shannon; Jung, Kwanghee; Quinn, Jorie

    2014-01-01

    The Kindergarten Early Learning Scale (KELS) was developed as a concise observational assessment for young children. It examines three domains including (1) Math/Science, (2) Social Emotional/Social Studies, and (3) Language and Literacy, with a total of 10 items across the domains. Scores reported for each of the 10 items are based upon…

  11. Early literacy and early numeracy: the value of including early literacy skills in the prediction of numeracy development.

    PubMed

    Purpura, David J; Hume, Laura E; Sims, Darcey M; Lonigan, Christopher J

    2011-12-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a year later on the PENS test and on the Applied Problems and Calculation subtests of the Woodcock-Johnson III Tests of Achievement. Three mixed effect regressions were conducted using Time 2 PENS, Applied Problems, and Calculation as the dependent variables. Print Knowledge and Vocabulary accounted for unique variance in the prediction of Time 2 numeracy scores. Phonological Awareness did not uniquely predict any of the mathematics domains. The findings of this study identify an important link between early literacy and early numeracy development. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. A role for chromatin topology in imprinted domain regulation.

    PubMed

    MacDonald, William A; Sachani, Saqib S; White, Carlee R; Mann, Mellissa R W

    2016-02-01

    Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

  13. Phylogenetic Tracings of Proteome Size Support the Gradual Accretion of Protein Structural Domains and the Early Origin of Viruses from Primordial Cells

    PubMed Central

    Nasir, Arshan; Kim, Kyung Mo; Caetano-Anollés, Gustavo

    2017-01-01

    Untangling the origin and evolution of viruses remains a challenging proposition. We recently studied the global distribution of protein domain structures in thousands of completely sequenced viral and cellular proteomes with comparative genomics, phylogenomics, and multidimensional scaling methods. A tree of life describing the evolution of proteomes revealed viruses emerging from the base of the tree as a fourth supergroup of life. A tree of domains indicated an early origin of modern viral lineages from ancient cells that co-existed with the cellular ancestors. However, it was recently argued that the rooting of our trees and the basal placement of viruses was artifactually induced by small genome (proteome) size. Here we show that these claims arise from misunderstanding and misinterpretations of cladistic methodology. Trees are reconstructed unrooted, and thus, their topologies cannot be distorted a posteriori by the rooting methodology. Tracing proteome size in trees and multidimensional views of evolutionary relationships as well as tests of leaf stability and exclusion/inclusion of taxa demonstrated that the smallest proteomes were neither attracted toward the root nor caused any topological distortions of the trees. Simulations confirmed that taxa clustering patterns were independent of proteome size and were determined by the presence of known evolutionary relatives in data matrices, highlighting the need for broader taxon sampling in phylogeny reconstruction. Instead, phylogenetic tracings of proteome size revealed a slowdown in innovation of the structural domain vocabulary and four regimes of allometric scaling that reflected a Heaps law. These regimes explained increasing economies of scale in the evolutionary growth and accretion of kernel proteome repertoires of viruses and cellular organisms that resemble growth of human languages with limited vocabulary sizes. Results reconcile dynamic and static views of domain frequency distributions that are

  14. Piaget's Developmental Theories Used in an Early Childhood Program for Mentally Retarded Students.

    ERIC Educational Resources Information Center

    Francis Christi, Sister

    The author describes a Piaget based curriculum involving three main themes (classification, number measurement/space, and seriation) for young mentally retarded children. Students solve problems by doing something physically and mentally to the data, shuffling the facts about in their minds, so that they will come to a logical solution. Language…

  15. Relationship between the neighbourhood built environment and early child development.

    PubMed

    Christian, Hayley; Ball, Stephen J; Zubrick, Stephen R; Brinkman, Sally; Turrell, Gavin; Boruff, Bryan; Foster, Sarah

    2017-11-01

    The relationship between features of the neighbourhood built environment and early child development was investigated using area-level data from the Australian Early Development Census. Overall 9.0% of children were developmentally vulnerable on the Physical Health and Well-being domain, 8.1% on the Social Competence domain and 8.1% on the Emotional Maturity domain. After adjustment for socio-demographic factors, Local Communities with the highest quintile of home yard space had significantly lower odds of developmental vulnerability on the Emotional Maturity domain. Residing in a Local Community with fewer main roads was associated with a decrease in the proportion of children developmentally vulnerable on the Social Competence domain. Overall, sociodemographic factors were more important than aspects of the neighbourhood physical environment for explaining variation between Local Communities in the developmental vulnerability of children. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Products resulting from cleavage of the interglobular domain of aggrecan in samples of synovial fluid collected from dogs with early- and late-stage osteoarthritis.

    PubMed

    Innes, John F; Little, Chris B; Hughes, Clare E; Caterson, Bruce

    2005-10-01

    To investigate interglobular domain (IGD) cleavage of aggrecan in dogs with naturally developing osteoarthritis (OA). Samples of synovial fluid (SF) obtained from 3 cubital (elbow) joints and 3 stifle joints of 4 clinically normal dogs, 24 elbow joints of 12 dogs with early-stage OA, 8 stifle joints of 5 dogs with early-stage OA, and 10 stifle joints of 9 dogs with late-stage OA. Fractions of SF were assayed for total glycosaminoglycan (GAG) content and also subjected to Western blot analysis by use of monoclonal antibodies against neoepitopes generated by cleavage of the IGD of the aggrecan protein core by matrix metalloproteinase (MMP; BC-14) and aggrecanase (BC-3). Total GAG content of SF from joints of clinically normal dogs did not differ from that of dogs with early-stage OA. The GAG content of SF from joints of dogs with late-stage OA was significantly lower, compared with GAG content for other SF samples. Aggrecanase-generated fragments were detected in SF from all groups but not in all samples. Matrix metalloproteinase-generated fragments were not detected in any SF samples. In early-stage OA, high-molecular-weight aggrecanase-generated aggrecan catabolites were evident. GAG content of SF obtained from dogs with late-stage OA is significantly decreased, suggesting proteoglycan depletion of cartilage. Aggrecanases, but not MMPs, are the major proteolytic enzymes responsible for IGD cleavage of aggrecan in canine joints. Analyses of SF samples to detect aggrecanase-generated catabolites may provide an early biomarker for discriminating early- and late-stage OA in dogs.

  17. Early Maladaptive Schemas and Aggression in Men Seeking Residential Substance Use Treatment

    PubMed Central

    Shorey, Ryan C.; Elmquist, Joanna; Anderson, Scott; Stuart, Gregory L.

    2015-01-01

    Social-cognitive theories of aggression postulate that individuals who perpetrate aggression are likely to have high levels of maladaptive cognitive schemas that increase risk for aggression. Indeed, recent research has begun to examine whether early maladaptive schemas may increase the risk for aggression. However, no known research has examined this among individuals in substance use treatment, despite aggression and early maladaptive schemas being more prevalent among individuals with a substance use disorder than the general population. Toward this end, we examined the relationship between early maladaptive schemas and aggression in men in a residential substance use treatment facility (N = 106). Utilizing pre-existing patient records, results demonstrated unique associations between early maladaptive schema domains and aggression depending on the type of aggression and schema domain examined, even after controlling for substance use, antisocial personality, age, and education. The Impaired Limits domain was positively associated with verbal aggression, aggressive attitude, and overall aggression, whereas the Disconnection and Rejection domain was positively associated with physical aggression. These findings are consistent with social-cognitive models of aggression and advance our understanding of how early maladaptive schemas may influence aggression. The implications of these findings for future research are discussed. PMID:25897180

  18. Numerical capacities as domain-specific predictors beyond early mathematics learning: a longitudinal study.

    PubMed

    Reigosa-Crespo, Vivian; González-Alemañy, Eduardo; León, Teresa; Torres, Rosario; Mosquera, Raysil; Valdés-Sosa, Mitchell

    2013-01-01

    The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3(rd) and 4(th) grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively "start-up" tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school.

  19. The CW domain, a structural module shared amongst vertebrates, vertebrate-infecting parasites and higher plants.

    PubMed

    Perry, Jason; Zhao, Yunde

    2003-11-01

    A previously undetected domain, named CW for its conserved cysteine and tryptophan residues, appears to be a four-cysteine zinc-finger motif found exclusively in vertebrates, vertebrate-infecting parasites and higher plants. Of the twelve distinct nuclear protein families that comprise the CW domain-containing superfamily, only the microrchida (MORC) family has begun to be characterized. However, several families contain other domains suggesting a relationship between the CW domain and either chromatin methylation status or early embryonic development.

  20. Astigmatism and early academic readiness in preschool children.

    PubMed

    Orlansky, Gale; Wilmer, Jeremy; Taub, Marc B; Rutner, Daniella; Ciner, Elise; Gryczynski, Jan

    2015-03-01

    This study investigated the relationship between uncorrected astigmatism and early academic readiness in at-risk preschool-aged children. A vision screening and academic records review were performed on 122 three- to five-year-old children enrolled in the Philadelphia Head Start program. Vision screening results were related to two measures of early academic readiness, the teacher-reported Work Sampling System (WSS) and the parent-reported Ages and Stages Questionnaire (ASQ). Both measures assess multiple developmental and skill domains thought to be related to academic readiness. Children with astigmatism (defined as >|-0.25| in either eye) were compared with children who had no astigmatism. Associations between astigmatism and specific subscales of the WSS and ASQ were examined using parametric and nonparametric bivariate statistics and regression analyses controlling for age and spherical refractive error. Presence of astigmatism was negatively associated with multiple domains of academic readiness. Children with astigmatism had significantly lower mean scores on Personal and Social Development, Language and Literacy, and Physical Development domains of the WSS, and on Personal/Social, Communication, and Fine Motor domains of the ASQ. These differences between children with astigmatism and children with no astigmatism persisted after statistically adjusting for age and magnitude of spherical refractive error. Nonparametric tests corroborated these findings for the Language and Literacy and Physical Health and Development domains of the WSS and the Communication domain of the ASQ. The presence of astigmatism detected in a screening setting was associated with a pattern of reduced academic readiness in multiple developmental and educational domains among at-risk preschool-aged children. This study may help to establish the role of early vision screenings, comprehensive vision examinations, and the need for refractive correction to improve academic success in

  1. Numerical Capacities as Domain-Specific Predictors beyond Early Mathematics Learning: A Longitudinal Study

    PubMed Central

    Reigosa-Crespo, Vivian; González-Alemañy, Eduardo; León, Teresa; Torres, Rosario; Mosquera, Raysil; Valdés-Sosa, Mitchell

    2013-01-01

    The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3rd and 4th grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively “start-up” tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school. PMID:24255710

  2. Screening retinal transplants with Fourier-domain OCT

    NASA Astrophysics Data System (ADS)

    Rao, Bin

    2009-02-01

    Transplant technologies have been studied for the recovery of vision loss from retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In several rodent retinal degeneration models and in patients, retinal progenitor cells transplanted as layers to the subretinal space have been shown to restore or preserve vision. The methods for evaluation of transplants are expensive considering the large amount of animals. Alternatively, time-domain Stratus OCT was previously shown to be able to image the morphological structure of transplants to some extent, but could not clearly identify laminated transplants. The efficacy of screening retinal transplants with Fourier-domain OCT was studied on 37 S334ter line 3 rats with retinal degeneration 6-67 days after transplant surgery. The transplants were morphologically categorized as no transplant, detachment, rosettes, small laminated area and larger laminated area with both Fourier-domain OCT and histology. The efficacy of Fourier-domain OCT in screening retinal transplants was evaluated by comparing the categorization results with OCT and histology. Additionally, 4 rats were randomly selected for multiple OCT examinations (1, 5, 9, 14 and 21days post surgery) in order to determine the earliest image time of OCT examination since the transplanted tissue may need some time to show its tendency of growing. Finally, we demonstrated the efficacy of Fourier-domain OCT in screening retinal transplants in early stages and determined the earliest imaging time for OCT. Fourier-domain OCT makes itself valuable in saving resource spent on animals with unsuccessful transplants.

  3. Birdsong dialect patterns explained using magnetic domains

    NASA Astrophysics Data System (ADS)

    Burridge, James; Kenney, Steven

    2016-06-01

    The songs and calls of many bird species, like human speech, form distinct regional dialects. We suggest that the process of dialect formation is analogous to the physical process of magnetic domain formation. We take the coastal breeding grounds of the Puget Sound white crowned sparrow as an example. Previous field studies suggest that birds of this species learn multiple songs early in life, and when establishing a territory for the first time, retain one of these dialects in order to match the majority of their neighbors. We introduce a simple lattice model of the process, showing that this matching behavior can produce single dialect domains provided the death rate of adult birds is sufficiently low. We relate death rate to thermodynamic temperature in magnetic materials, and calculate the critical death rate by analogy with the Ising model. Using parameters consistent with the known behavior of these birds we show that coastal dialect domain shapes may be explained by viewing them as low-temperature "stripe states."

  4. Evolutionarily conserved structural and functional roles of the FYVE domain.

    PubMed

    Hayakawa, Akira; Hayes, Susan; Leonard, Deborah; Lambright, David; Corvera, Silvia

    2007-01-01

    The FYVE domain is an approx. 80 amino acid motif that binds to the phosphoinositide PtdIns3P with high specificity and affinity. It is present in 38 predicted gene products within the human genome, but only in 12-13 in Caenorhabditis elegans and Drosophila melanogaster. Eight of these are highly conserved in all three organisms, and they include proteins that have not been characterized in any species. One of these, WDFY2, appears to play an important role in early endocytosis and was revealed in a RNAi (RNA interference) screen in C. elegans. Interestingly, some proteins contain FYVE-like domains in C. elegans and D. melanogaster, but have lost this domain during evolution. One of these is the homologue of Rabatin-5, a protein that, in mammalian cells, binds both Rab5 and Rabex-5, a guanine-nucleotide exchange factor for Rab5. Thus the Rabatin-5 homologue suggests that mechanisms to link PtdIns3P and Rab5 activation developed in evolution. In mammalian cells, these mechanisms are apparent in the existence of proteins that bind PtdIns3P and Rab GTPases, such as EEA1, Rabenosyn-5 and Rabip4'. Despite the comparable ability to bind to PtdIns3P in vitro, FYVE domains display widely variable abilities to interact with endosomes in intact cells. This variation is due to three distinct properties of FYVE domains conferred by residues that are not involved in PtdIns3P head group recognition: These properties are: (i) the propensity to oligomerize, (ii) the ability to insert into the membrane bilayer, and (iii) differing electrostatic interactions with the bilayer surface. The different binding properties are likely to regulate the extent and duration of the interaction of specific FYVE domain-containing proteins with early endosomes, and thereby their biological function.

  5. PREFACE: Domain wall dynamics in nanostructures Domain wall dynamics in nanostructures

    NASA Astrophysics Data System (ADS)

    Marrows, C. H.; Meier, G.

    2012-01-01

    forms of ordered phases such as antiferromagnetism and ferroelectricity. We would like to thank the scientists from all over the world who happily agreed to contribute their latest results to this special issue, and the Journal of Physics: Condensed Matter staff for their help, patience and professionalism. In such a fast-moving field it is not possible to give a definitive account, and this special issue can be no more than a snapshot of the current state of knowledge regarding this topic. Nevertheless, we hope that this collection of papers is a useful resource for experienced workers in the field, forms a useful introduction to researchers early in their careers and inspires others in related areas of nanotechnology to enter into the study of domain dynamics in nanostructures. Domain wall dynamics in nanostructures contents Temperature estimation in a ferromagnetic Fe-Ni nanowire involving a current-driven domain wall motionA Yamaguchi, A Hirohata, T Ono and H Miyajima Magnetization reversal in magnetic nanostripes via Bloch wall formation M Zeisberger and R Mattheis Magnetic soft x-ray microscopy of the domain wall depinning process in permalloy magnetic nanowiresMi-Young Im, Lars Bocklage, Guido Meier and Peter Fischer Domain wall propagation in meso- and nanoscale ferroelectrics R G P McQuaid, M McMillen, L-W Chang, A Gruverman and J M Gregg Transverse and vortex domain wall structure in magnetic nanowires with uniaxial in-plane anisotropyM T Bryan, S Bance, J Dean, T Schrefl and D A Allwood The stochastic nature of the domain wall motion along high perpendicular anisotropy strips with surface roughness Eduardo Martinez Temperature-dependent dynamics of stochastic domain-wall depinning in nanowiresClemens Wuth, Peter Lendecke and Guido Meier Controlled pinning and depinning of domain walls in nanowires with perpendicular magnetic anisotropyTheo Gerhardt, André Drews and Guido Meier The interaction of transverse domain wallsBenjamin Krüger The increase of the

  6. Prioritisation of associations between protein domains and complex diseases using domain-domain interaction networks.

    PubMed

    Wang, W; Zhang, W; Jiang, R; Luan, Y

    2010-05-01

    It is of vital importance to find genetic variants that underlie human complex diseases and locate genes that are responsible for these diseases. Since proteins are typically composed of several structural domains, it is reasonable to assume that harmful genetic variants may alter structures of protein domains, affect functions of proteins and eventually cause disorders. With this understanding, the authors explore the possibility of recovering associations between protein domains and complex diseases. The authors define associations between protein domains and disease families on the basis of associations between non-synonymous single nucleotide polymorphisms (nsSNPs) and complex diseases, similarities between diseases, and relations between proteins and domains. Based on a domain-domain interaction network, the authors propose a 'guilt-by-proximity' principle to rank candidate domains according to their average distance to a set of seed domains in the domain-domain interaction network. The authors validate the method through large-scale cross-validation experiments on simulated linkage intervals, random controls and the whole genome. Results show that areas under receiver operating characteristic curves (AUC scores) can be as high as 77.90%, and the mean rank ratios can be as low as 21.82%. The authors further offer a freely accessible web interface for a genome-wide landscape of associations between domains and disease families.

  7. The Development of STAR Early Literacy. Report.

    ERIC Educational Resources Information Center

    School Renaissance Inst., Inc., Madison, WI.

    This report describes the development and testing of a computerized early literacy diagnostic assessment for students in prekindergarten to grade 3 that can measure skills across a variety of preliteracy and reading domains. The STAR Early Literacy assessment was developed by a team of more than 50 people, including literacy experts,…

  8. Domain walls in the extensions of the Standard Model

    NASA Astrophysics Data System (ADS)

    Krajewski, Tomasz; Lalak, Zygmunt; Lewicki, Marek; Olszewski, Paweł

    2018-05-01

    Our main interest is the evolution of domain walls of the Higgs field in the early Universe. The aim of this paper is to understand how dynamics of Higgs domain walls could be influenced by yet unknown interactions from beyond the Standard Model. We assume that the Standard Model is valid up to certain, high, energy scale Λ and use the framework of the effective field theory to describe physics below that scale. Performing numerical simulations with different values of the scale Λ we are able to extend our previous analysis [1]. Our recent numerical simulations show that evolution of Higgs domain walls is rather insensitive to interactions beyond the Standard Model as long as masses of new particles are grater than 1012 GeV. For lower values of Λ the RG improved effective potential is strongly modified at field strengths crucial to the evolution of domain walls. However, we find that even for low values of Λ, Higgs domain walls decayed shortly after their formation for generic initial conditions. On the other hand, in simulations with specifically chosen initial conditions Higgs domain walls can live longer and enter the scaling regime. We also determine the energy spectrum of gravitational waves produced by decaying domain walls of the Higgs field. For generic initial field configurations the amplitude of the signal is too small to be observed in planned detectors.

  9. Quality of the Home Learning Environment during Preschool Age--Domains and Contextual Conditions

    ERIC Educational Resources Information Center

    Kluczniok, Katharina; Lehrl, Simone; Kuger, Susanne; Rossbach, Hans-Guenther

    2013-01-01

    The quality of the home learning environment has been proven to be of major importance for child development, but little is known about the role of domain specificity in promoting early childhood learning at home and its dependence on family background. This article presents a framework of the home learning environment in early childhood that…

  10. Eminence, IQ, physical and mental health, and achievement domain : Cox's 282 Geniuses revisited.

    PubMed

    Simonton, Dean Keith; Song, Anna V

    2009-04-01

    Catharine Cox published two studies of highly eminent creators and leaders, the first in 1926 as the second volume of Terman's landmark Genetic Studies of Genius and the second in 1936 as a coauthored article. The former publication concentrated on the relation between IQ and achieved eminence, and the latter focused on early physical and mental health. Taking advantage of unpublished data from the second study, we examined, for the first time, the relationships among achieved eminence, IQ, early physical and mental health, and achievement domain. The correlation and regression analyses showed, for these 282 individuals, that eminence is a positive function of IQ and that IQ is a positive function of mental health and a negative function of physical health, implying an indirect effect of physical and mental health on eminence. Furthermore, levels of early physical and mental health vary across 10 specific domains of achievement.

  11. A chimeric virus created by DNA shuffling of the capsid genes of different subtypes of porcine circovirus type 2 (PCV2) in the backbone of the non-pathogenic PCV1 induces protective immunity against the predominant PCV2b and the emerging PCV2d in pigs.

    PubMed

    Matzinger, Shannon R; Opriessnig, Tanja; Xiao, Chao-Ting; Catanzaro, Nicholas; Beach, Nathan M; Slade, David E; Nitzel, Gregory P; Meng, Xiang-Jin

    2016-11-01

    Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated disease (PCVAD). Available commercial vaccines all target PCV2a subtype, although the circulating predominant subtype worldwide is PCV2b, and the emerging PCV2d subtype is also increasingly associated with PCVAD. Here we molecularly bred genetically-divergent strains representing PCV2a, PCV2b, PCV2c, PCV2d, and "divergent PCV2a" subtypes by DNA-shuffling of the capsid genes to produce a chimeric virus representing PCV2 global genetic diversity. When placed in the PCV2a backbone, one chimeric virus (PCV2-3cl14) induced higher neutralizing antibody titers against different PCV2 subtypes. Subsequently, a candidate vaccine (PCV1-3cl14) was produced by cloning the shuffled 3cl14 capsid into the backbone of the non-pathogenic PCV1. A vaccine efficacy study revealed that chimeric virus PCV1-3cl14 induces protective immunity against challenge with PCV2b or PCV2d in pigs. The chimeric PCV1-3cl14 virus is a strong candidate for a novel vaccine in pigs infected with variable PCV2 strains. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Palaeogeographic evolution of the central segment of the South Atlantic during Early Cretaceous times: palaeotopographic and geodynamic implications

    NASA Astrophysics Data System (ADS)

    Chaboureau, A. C.; Guillocheau, F.; Robin, C.; Rohais, S.; Moulin, M.; Aslanian, D.

    2012-04-01

    The tectonic and sedimentary evolution of the Early Cretaceous rift of the central segment of the South Atlantic Ocean is debated. Our objective is to better constraint the timing of its evolution by drawing palaeogeographic and deformation maps. Eight palaeogeographic and deformations maps were drawn from the Berriasian to the Middle-Late Aptian, based on a biostratigraphic (ostracodes and pollens) chart recalibrated on absolute ages (chemostratigraphy, interstratified volcanics, Re-Os dating of the organic matter). The central segment of the South Atlantic is composed of two domains that have a different history in terms of deformation and palaeogeography. The southern domain includes Namibe, Santos and Campos Basins. The northern domain extends from Espirito Santo and North Kwanza Basins, in the South, to Sergipe-Alagoas and North Gabon Basins to the North. Extension started in the northern domain during Late Berriasian (Congo-Camamu Basin to Sergipe-Alagoas-North Gabon Basins) and migrated southward. At that time, the southern domain was not a subsiding domain. This is time of emplacement of the Parana-Etendeka Trapp (Late Hauterivian-Early Barremian). Extension started in this southern domain during Early Barremian. The brittle extensional period is shorter in the South (5-6 Ma, Barremian to base Aptian) than in the North (19 to 20 Myr, Upper Berriasian to Base Aptian). From Late Berriasian to base Aptian, the northern domain evolves from a deep lake with lateral highs to a shallower one, organic-rich with no more highs. The lake migrates southward in two steps, until Valanginian at the border between the northern and southern domains, until Early Barremian, North of Walvis Ridge. The Sag phase is of Middle to Late Aptian age. In the southern domain, the transition between the brittle rift and the sag phase is continuous. In the northern domain, this transition corresponds to a hiatus of Early to Middle Aptian age, possible period of mantle exhumation. Marine

  13. Is it about "pink" or about "girls"? The inherence heuristic across social and nonsocial domains.

    PubMed

    Kinzler, Katherine D; Sullivan, Kathleen R

    2014-10-01

    The inherence heuristic provides an intriguing and novel explanation for early thought in a variety of domains. Exploring similarities and differences in inherent reasoning across social and nonsocial domains can help us understand the role that inherent thinking plays in the development of human reasoning and the process by which more elaborate essentialist reasoning develops.

  14. Functional hierarchy of two L domains in porcine endogenous retrovirus (PERV) that influence release and infectivity

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

    Marcucci, Katherine T.; Kellogg School of Science and Technology, Scripps Research Institute, La Jolla, CA, 92037; Martina, Yuri

    2008-06-05

    The porcine endogenous retrovirus (PERV) Gag protein contains two late (L) domain motifs, PPPY and P(F/S)AP. Using viral release assays we demonstrate that PPPY is the dominant L domain involved in PERV release. PFAP represents a novel retroviral L domain variant and is defined by abnormal viral assembly phenotypes visualized by electron microscopy and attenuation of early PERV release as measured by viral genomes. PSAP is functionally dominant over PFAP in early PERV release. PSAP virions are 3.5-fold more infectious in vitro by TCID{sub 50} and in vivo results in more RNA positive tissues and higher levels of proviral DNAmore » using our human PERV-A receptor (HuPAR-2) transgenic mouse model [Martina, Y., Marcucci, K.T., Cherqui, S., Szabo, A., Drysdale, T., Srinivisan, U., Wilson, C.A., Patience, C., Salomon, D.R., 2006. Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection. J. Virol. 80 (7), 3135-3146]. The functional hierarchies displayed by PERV L domains, demonstrates that L domain selection in viral evolution exists to promote efficient viral assembly, release and infectivity in the virus-host context.« less

  15. Evidence for a role of SNX16 in regulating traffic between the early and later endosomal compartments.

    PubMed

    Hanson, Brendon J; Hong, Wanjin

    2003-09-05

    Sorting nexins (SNXs) are a growing family of proteins characterized by the presence of a PX domain. The PX domain mediates membrane association by interaction with phosphoinositides. The SNXs are generally believed to participate in membrane trafficking, but information regarding the function of individual proteins is limited. In this report, we describe the major characteristics of one member, SNX16. SNX16 is a novel 343-amino acid protein consisting of a central PX domain followed by a potential coiled-coil domain and a C-terminal region. Like other sorting nexins, SNX16 associates with the membrane via the PX domain which interacts with the phospholipid phosphatidylinositol 3-phosphate. We show via biochemical and cellular studies that SNX16 is distributed in both early and late endosome/lysosome structures. The coiled-coil domain is necessary for localization to the later endosomal structures, as mutant SNX16 lacking this domain was found only in early endosomes. Trafficking of internalized epidermal growth factor was also delayed by this SNX16 mutant, as these cells showed a delay in the segregation of epidermal growth factor in the early endosome for its delivery to later compartments. In addition, the coiled-coil domain is shown here to be important for homo-oligomerization of SNX16. Taken together, these results suggest that SNX16 is a sorting nexin that may function in the trafficking of proteins between the early and late endosomal compartments.

  16. Cortical geometry may influence placement of interface between Par protein domains in early Caenorhabditis elegans embryos.

    PubMed

    Dawes, Adriana T; Iron, David

    2013-09-21

    During polarization, proteins and other polarity determinants segregate to the opposite ends of the cell (the poles) creating biochemically and dynamically distinct regions. Embryos of the nematode worm Caenorhabditis elegans (C. elegans) polarize shortly after fertilization, creating distinct regions of Par protein family members. These regions are maintained through to first cleavage when the embryo divides along the plane specified by the interface between regions, creating daughter cells with different protein content. In wild type single cell embryos the interface between these Par protein regions is reliably positioned at approximately 60% egg length, however, it is not known what mechanisms are responsible for specifying the position of the interface. In this investigation, we use two mathematical models to investigate the movement and positioning of the interface: a biologically based reaction-diffusion model of Par protein dynamics, and the analytically tractable perturbed Allen-Cahn equation. When we numerically simulate the models on a static 2D domain with constant thickness, both models exhibit a persistently moving interface that specifies the boundary between distinct regions. When we modify the simulation domain geometry, movement halts and the interface is stably positioned where the domain thickness increases. Using asymptotic analysis with the perturbed Allen-Cahn equation, we show that interface movement depends explicitly on domain geometry. Using a combination of analytic and numeric techniques, we demonstrate that domain geometry, a historically overlooked aspect of cellular simulations, may play a significant role in spatial protein patterning during polarization. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Identification of bearing faults using time domain zero-crossings

    NASA Astrophysics Data System (ADS)

    William, P. E.; Hoffman, M. W.

    2011-11-01

    In this paper, zero-crossing characteristic features are employed for early detection and identification of single point bearing defects in rotating machinery. As a result of bearing defects, characteristic defect frequencies appear in the machine vibration signal, normally requiring spectral analysis or envelope analysis to identify the defect type. Zero-crossing features are extracted directly from the time domain vibration signal using only the duration between successive zero-crossing intervals and do not require estimation of the rotational frequency. The features are a time domain representation of the composite vibration signature in the spectral domain. Features are normalized by the length of the observation window and classification is performed using a multilayer feedforward neural network. The model was evaluated on vibration data recorded using an accelerometer mounted on an induction motor housing subjected to a number of single point defects with different severity levels.

  18. δ-COP contains a helix C-terminal to its longin domain key to COPI dynamics and function

    PubMed Central

    Arakel, Eric C.; Richter, Kora P.; Clancy, Anne; Schwappach, Blanche

    2016-01-01

    Membrane recruitment of coatomer and formation of coat protein I (COPI)-coated vesicles is crucial to homeostasis in the early secretory pathway. The conformational dynamics of COPI during cargo capture and vesicle formation is incompletely understood. By scanning the length of δ-COP via functional complementation in yeast, we dissect the domains of the δ-COP subunit. We show that the μ-homology domain is dispensable for COPI function in the early secretory pathway, whereas the N-terminal longin domain is essential. We map a previously uncharacterized helix, C-terminal to the longin domain, that is specifically required for the retrieval of HDEL-bearing endoplasmic reticulum-luminal residents. It is positionally analogous to an unstructured linker that becomes helical and membrane-facing in the open form of the AP2 clathrin adaptor complex. Based on the amphipathic nature of the critical helix it may probe the membrane for lipid packing defects or mediate interaction with cargo and thus contribute to stabilizing membrane-associated coatomer. PMID:27298352

  19. Getting Men Involved: Strategies for Early Childhood Programs.

    ERIC Educational Resources Information Center

    Levine, James A.; And Others

    Designed as a guide for early childhood professionals, this book outlines specific success strategies for getting men--fathers or any significant male in a child's life--involved in early childhood education and child care, moving away from the traditional view of these fields as women's domains. The first section of the guide focuses on…

  20. Jumonji domain-containing protein 3 regulates the early inflammatory response epigenetically in human periodontal ligament cells.

    PubMed

    Wang, Puyu; Yue, Junli; Xu, Weizhe; Chen, Xi; Yi, Xiaowei; Ye, Ling; Zhang, Lan; Huang, Dingming

    2018-05-30

    To investigate the role of the histone 3 lysine 27 trimethylation (H3K27me3) demethylase Jumonji domain-containing protein 3 (Jmjd3) in the epigenetic regulation of the inflammatory response in human periodontal ligament cells (HPDLs). HPDLs were stimulated with lipopolysaccharide from E. coli. The expression of Jmjd3 in HPDLs was examined by quantitative real-time polymerase chain reaction (Q-PCR), Western Blot and immunofluorescent staining. Potential target genes were selected by silencing Jmjd3 and were confirmed by Chromatin Immunoprecipitation (ChIP). Q-PCR, Western Blot and immunofluorescent staining revealed that the expression of Jmjd3 was increased in inflamed HPDLs. Knockdown of Jmjd3 led to the suppression of inflammation-induced up-regulation of interleukin-6 and interleukin-12. Moreover, ChIP assays demonstrated that Jmjd3 was recruited to the promoters of interleukin-6 and interleukin-12b and this recruitment was associated with decreased levels of trimethylated histone 3 lysine 27 (H3K27). It was concluded that Jmjd3 regulated the activation of interleukin-6 and interleukin-12b in the early inflammatory response of HPDLs via demethylation of H3K27me3 at promoters. This molecular event may play an important role in the regulation of the inflammatory response in HPDLs. Copyright © 2018. Published by Elsevier Ltd.

  1. Domain atrophy creates rare cases of functional partial protein domains.

    PubMed

    Prakash, Ananth; Bateman, Alex

    2015-04-30

    Protein domains display a range of structural diversity, with numerous additions and deletions of secondary structural elements between related domains. We have observed a small number of cases of surprising large-scale deletions of core elements of structural domains. We propose a new concept called domain atrophy, where protein domains lose a significant number of core structural elements. Here, we implement a new pipeline to systematically identify new cases of domain atrophy across all known protein sequences. The output of this pipeline was carefully checked by hand, which filtered out partial domain instances that were unlikely to represent true domain atrophy due to misannotations or un-annotated sequence fragments. We identify 75 cases of domain atrophy, of which eight cases are found in a three-dimensional protein structure and 67 cases have been inferred based on mapping to a known homologous structure. Domains with structural variations include ancient folds such as the TIM-barrel and Rossmann folds. Most of these domains are observed to show structural loss that does not affect their functional sites. Our analysis has significantly increased the known cases of domain atrophy. We discuss specific instances of domain atrophy and see that there has often been a compensatory mechanism that helps to maintain the stability of the partial domain. Our study indicates that although domain atrophy is an extremely rare phenomenon, protein domains under certain circumstances can tolerate extreme mutations giving rise to partial, but functional, domains.

  2. Cosmological baryon number domain structure from symmetry-breaking in grand unified field theories

    NASA Technical Reports Server (NTRS)

    Brown, R. W.; Stecker, F. W.

    1979-01-01

    It is suggested that grand unified field theories with spontaneous symmetry breaking in the very early big-bang can lead more naturally to a baryon symmetric cosmology with a domain structure than to a totally baryon asymmetric cosmology. The symmetry is broken in a randomized manner in causally independent domains, favoring neither a baryon nor an antibaryon excess on a universal scale. Arguments in favor of this cosmology and observational tests are discussed.

  3. Cosmological baryon-number domain structure from symmetry breaking in grand unified field theories

    NASA Technical Reports Server (NTRS)

    Brown, R. W.; Stecker, F. W.

    1979-01-01

    It is suggested that grand unified field theories with spontaneous symmetry breaking in the very early big bang can lead more naturally to a baryon-symmetric cosmology with a domain structure than to a totally baryon-asymmetric cosmology. The symmetry is broken in a randomized manner in causally independent domains, favoring neither a baryon nor an antibaryon excess on a universal scale. Arguments in favor of this cosmology and observational tests are discussed.

  4. Time- and frequency-domain parameters of heart rate variability and sympathetic skin response in Parkinson's disease.

    PubMed

    Maetzler, Walter; Karam, Marie; Berger, Monika Fruhmann; Heger, Tanja; Maetzler, Corina; Ruediger, Heinz; Bronzova, Juliana; Lobo, Patricia Pita; Ferreira, Joaquim J; Ziemssen, Tjalf; Berg, Daniela

    2015-03-01

    The autonomic nervous system (ANS) is regularly affected in Parkinson's disease (PD). Information on autonomic dysfunction can be derived from e.g. altered heart rate variability (HRV) and sympathetic skin response (SSR). Such parameters can be quantified easily and measured repeatedly which might be helpful for evaluating disease progression and therapeutic outcome. In this 2-center study, HRV and SSR of 45 PD patients and 26 controls were recorded. HRV was measured during supine metronomic breathing and analyzed in time- and frequency-domains. SSR was evoked by repetitive auditory stimulation. Various ANS parameters were compared (1) between patients and healthy controls, (2) to clinical scales (Unified Parkinson's disease rating scale, Mini-Mental State Examination, Becks Depression Inventory), and (3) to disease duration. Root mean square of successive differences (RMSSD) and low frequency/high frequency (LF/HF) ratio differed significantly between PD and controls. Both, HRV and SSR parameters showed low or no association with clinical scores. Time-domain parameters tended to be affected already at early PD stages but did not consistently change with longer disease duration. In contrast, frequency-domain parameters were not altered in early PD phases but tended to be lower (LF, LF/HF ratio), respectively higher (HF) with increasing disease duration. This report confirms previous results of altered ANS parameters in PD. In addition, it suggests that (1) these ANS parameters are not relevantly associated with motor, behavioral, and cognitive changes in PD, (2) time-domain parameters are useful for the assessment of early PD, and (3) frequency-domain parameters are more closely associated with disease duration.

  5. Commentary and Challenges to Grusec and Davidov's Domain-Specific Approach

    ERIC Educational Resources Information Center

    Dunn, Judy

    2010-01-01

    J. E. Grusec and M. Davidov's article (this issue) about domains of parenting and their links with different aspects of childhood outcome raises both interesting questions and challenges. Four of these concerns are discussed in relation to early childhood. First is the issue of bidirectionality. Recent studies highlight the contribution of…

  6. The relationship between early giftedness and later achievement.

    PubMed

    Gardner, H

    1993-01-01

    Although some prodigies grow up to become creative masters as adults, there is no necessary link between early signs of talent and ultimate achievement. Four possible relations between early and late achievement are explored here. The analysis draws upon two lines of evidence: (1) a new theoretical approach that posits the existence of multiple intelligences and examines the important role of the domains and fields in which individuals work; (2) case studies of seven highly creative individuals who lived at the turn of the century. A strong contrast emerges between the adult creator, who must discover the domain in which he or she can excel and the child prodigy, who must invent a creative personality.

  7. Young Children Bet On Their Numerical Skills: Metacognition in the Numerical Domain

    PubMed Central

    Vo, Vy A.; Li, Rosa; Kornell, Nate; Pouget, Alexandre; Cantlon, Jessica F.

    2014-01-01

    Metacognition, the ability to assess one’s own knowledge, has been targeted as a critical learning mechanism in mathematics education. Yet, the early childhood origins of metacognition have proven difficult to study. Using a novel nonverbal task and a comprehensive set of metacognitive measures, we provide the strongest evidence to date that young children are metacognitive. We show that children as young as 5 years make metacognitive “bets” on their numerical discriminations in a wagering task. However, contrary to previous reports from adults, children’s metacognition proved to be domain-specific: children’s metacognition in the numerical domain was unrelated to their metacognition in another domain (emotion discrimination). Moreover, children’s metacognitive ability in only the numerical domain predicted their school-based mathematics knowledge. The data provide novel evidence that metacognition is a fundamental, domain-dependent cognitive ability in children. The findings have implications for theories of uncertainty and reveal new avenues for training metacognition in children. PMID:24973137

  8. Massive expansion of the calpain gene family in unicellular eukaryotes.

    PubMed

    Zhao, Sen; Liang, Zhe; Demko, Viktor; Wilson, Robert; Johansen, Wenche; Olsen, Odd-Arne; Shalchian-Tabrizi, Kamran

    2012-09-29

    Calpains are Ca2+-dependent cysteine proteases that participate in a range of crucial cellular processes. Dysfunction of these enzymes may cause, for instance, life-threatening diseases in humans, the loss of sex determination in nematodes and embryo lethality in plants. Although the calpain family is well characterized in animal and plant model organisms, there is a great lack of knowledge about these genes in unicellular eukaryote species (i.e. protists). Here, we study the distribution and evolution of calpain genes in a wide range of eukaryote genomes from major branches in the tree of life. Our investigations reveal 24 types of protein domains that are combined with the calpain-specific catalytic domain CysPc. In total we identify 41 different calpain domain architectures, 28 of these domain combinations have not been previously described. Based on our phylogenetic inferences, we propose that at least four calpain variants were established in the early evolution of eukaryotes, most likely before the radiation of all the major supergroups of eukaryotes. Many domains associated with eukaryotic calpain genes can be found among eubacteria or archaebacteria but never in combination with the CysPc domain. The analyses presented here show that ancient modules present in prokaryotes, and a few de novo eukaryote domains, have been assembled into many novel domain combinations along the evolutionary history of eukaryotes. Some of the new calpain genes show a narrow distribution in a few branches in the tree of life, likely representing lineage-specific innovations. Hence, the functionally important classical calpain genes found among humans and vertebrates make up only a tiny fraction of the calpain family. In fact, a massive expansion of the calpain family occurred by domain shuffling among unicellular eukaryotes and contributed to a wealth of functionally different genes.

  9. Massive expansion of the calpain gene family in unicellular eukaryotes

    PubMed Central

    2012-01-01

    Background Calpains are Ca2+-dependent cysteine proteases that participate in a range of crucial cellular processes. Dysfunction of these enzymes may cause, for instance, life-threatening diseases in humans, the loss of sex determination in nematodes and embryo lethality in plants. Although the calpain family is well characterized in animal and plant model organisms, there is a great lack of knowledge about these genes in unicellular eukaryote species (i.e. protists). Here, we study the distribution and evolution of calpain genes in a wide range of eukaryote genomes from major branches in the tree of life. Results Our investigations reveal 24 types of protein domains that are combined with the calpain-specific catalytic domain CysPc. In total we identify 41 different calpain domain architectures, 28 of these domain combinations have not been previously described. Based on our phylogenetic inferences, we propose that at least four calpain variants were established in the early evolution of eukaryotes, most likely before the radiation of all the major supergroups of eukaryotes. Many domains associated with eukaryotic calpain genes can be found among eubacteria or archaebacteria but never in combination with the CysPc domain. Conclusions The analyses presented here show that ancient modules present in prokaryotes, and a few de novo eukaryote domains, have been assembled into many novel domain combinations along the evolutionary history of eukaryotes. Some of the new calpain genes show a narrow distribution in a few branches in the tree of life, likely representing lineage-specific innovations. Hence, the functionally important classical calpain genes found among humans and vertebrates make up only a tiny fraction of the calpain family. In fact, a massive expansion of the calpain family occurred by domain shuffling among unicellular eukaryotes and contributed to a wealth of functionally different genes. PMID:23020305

  10. Early Domain-Specific Knowledge? Nonlinear Developmental Trajectories Further Erode a House of Sand

    ERIC Educational Resources Information Center

    Deak, Gedeon O.

    2011-01-01

    Rakison and Yermolayeva (this issue) argue that domain specificity is difficult to reconcile with U-, N-, or M-shaped developmental trends. They are justified because: (1) There is no compelling evidence that nonlinear trends require mechanisms beyond general, well-known cognitive processes; and (2) epigenetic neuroscience provides no clear…

  11. Strain induced parametric pumping of a domain wall and its depinning from a notch

    NASA Astrophysics Data System (ADS)

    Nepal, Rabindra; Gungordu, Utkan; Kovalev, Alexey

    Using Thiele's method and detailed micromagnetic simulations, we study resonant oscillation of a domain wall in a notch of a ferromagnetic nanowire due to the modulation of magnetic anisotropy by external AC strain. Such resonant oscillation results from the parametric pumping of domain wall by AC strain at frequency about double the free domain wall oscillation frequency, which is mainly determined by the perpendicular anisotropy and notch geometry. This effect leads to a substantial reduction in depinning field or current required to depin a domain wall from the notch, and offers a mechanism for efficient domain wall motion in a notched nanowire. Our theoretical model accounts for the pinning potential due to a notch by explicitly calculating ferromagnetic energy as a function of notch geometry parameters. We also find similar resonant domain wall oscillations and reduction in the domain wall depinning field or current due to surface acoustic wave in soft ferromagnetic nanowire without uniaxial anisotropy that energetically favors an in-plane domain wall. DOE Early Career Award DE-SC0014189 and DMR- 1420645.

  12. A phenological mid-domain effect in flowering diversity.

    PubMed

    Morales, Manuel A; Dodge, Gary J; Inouye, David W

    2005-01-01

    In this paper, we test the mid-domain hypothesis as an explanation for observed patterns of flowering diversity in two sub-alpine communities of insect-pollinated plants. Observed species richness patterns showed an early-season increase in richness, a mid-season peak, and a late-season decrease. We show that a "mid-domain" null model can qualitatively match this pattern of flowering species richness, with R(2) values typically greater than 60%. We find significant or marginally significant departures from expected patterns of diversity for only 3 out of 12 year-site combinations. On the other hand, we do find a consistent pattern of departure when comparing observed versus null-model predicted flowering diversity averaged across years. Our results therefore support the hypothesis that ecological factors shape patterns of flowering phenology, but that the strength or nature of these environmental forcings may differ between years or the two habitats we studied, or may depend on species-specific characteristics of these plant communities. We conclude that mid-domain null models provide an important baseline from which to test departure of expected patterns of flowering diversity across temporal domains. Geometric constraints should be included first in the list of factors that drive seasonal patterns of flowering diversity.

  13. Detection of inter-frame forgeries in digital videos.

    PubMed

    K, Sitara; Mehtre, B M

    2018-05-26

    Videos are acceptable as evidence in the court of law, provided its authenticity and integrity are scientifically validated. Videos recorded by surveillance systems are susceptible to malicious alterations of visual content by perpetrators locally or remotely. Such malicious alterations of video contents (called video forgeries) are categorized into inter-frame and intra-frame forgeries. In this paper, we propose inter-frame forgery detection techniques using tamper traces from spatio-temporal and compressed domains. Pristine videos containing frames that are recorded during sudden camera zooming event, may get wrongly classified as tampered videos leading to an increase in false positives. To address this issue, we propose a method for zooming detection and it is incorporated in video tampering detection. Frame shuffling detection, which was not explored so far is also addressed in our work. Our method is capable of differentiating various inter-frame tamper events and its localization in the temporal domain. The proposed system is tested on 23,586 videos of which 2346 are pristine and rest of them are candidates of inter-frame forged videos. Experimental results show that we have successfully detected frame shuffling with encouraging accuracy rates. We have achieved improved accuracy on forgery detection in frame insertion, frame deletion and frame duplication. Copyright © 2018. Published by Elsevier B.V.

  14. Evaluation of spectral domain optical coherence tomography parameters in ocular hypertension, preperimetric, and early glaucoma.

    PubMed

    Aydogan, Tuğba; Akçay, BetÜl İlkay Sezgin; Kardeş, Esra; Ergin, Ahmet

    2017-11-01

    The objective of this study is to evaluate the diagnostic ability of retinal nerve fiber layer (RNFL), macular, optic nerve head (ONH) parameters in healthy subjects, ocular hypertension (OHT), preperimetric glaucoma (PPG), and early glaucoma (EG) patients, to reveal factors affecting the diagnostic ability of spectral domain-optical coherence tomography (SD-OCT) parameters and risk factors for glaucoma. Three hundred and twenty-six eyes (89 healthy, 77 OHT, 94 PPG, and 66 EG eyes) were analyzed. RNFL, macular, and ONH parameters were measured with SD-OCT. The area under the receiver operating characteristic curve (AUC) and sensitivity at 95% specificity was calculated. Logistic regression analysis was used to determine the glaucoma risk factors. Receiver operating characteristic regression analysis was used to evaluate the influence of covariates on the diagnostic ability of parameters. In PPG patients, parameters that had the largest AUC value were average RNFL thickness (0.83) and rim volume (0.83). In EG patients, parameter that had the largest AUC value was average RNFL thickness (0.98). The logistic regression analysis showed average RNFL thickness was a risk factor for both PPG and EG. Diagnostic ability of average RNFL and average ganglion cell complex thickness increased as disease severity increased. Signal strength index did not affect diagnostic abilities. Diagnostic ability of average RNFL and rim area increased as disc area increased. When evaluating patients with glaucoma, patients at risk for glaucoma, and healthy controls RNFL parameters deserve more attention in clinical practice. Further studies are needed to fully understand the influence of covariates on the diagnostic ability of OCT parameters.

  15. Transcriptional activation is a conserved feature of the early embryonic factor Zelda that requires a cluster of four zinc fingers for DNA binding and a low-complexity activation domain.

    PubMed

    Hamm, Danielle C; Bondra, Eliana R; Harrison, Melissa M

    2015-02-06

    Delayed transcriptional activation of the zygotic genome is a nearly universal phenomenon in metazoans. Immediately following fertilization, development is controlled by maternally deposited products, and it is not until later stages that widespread activation of the zygotic genome occurs. Although the mechanisms driving this genome activation are currently unknown, the transcriptional activator Zelda (ZLD) has been shown to be instrumental in driving this process in Drosophila melanogaster. Here we define functional domains of ZLD required for both DNA binding and transcriptional activation. We show that the C-terminal cluster of four zinc fingers mediates binding to TAGteam DNA elements in the promoters of early expressed genes. All four zinc fingers are required for this activity, and splice isoforms lacking three of the four zinc fingers fail to activate transcription. These truncated splice isoforms dominantly suppress activation by the full-length, embryonically expressed isoform. We map the transcriptional activation domain of ZLD to a central region characterized by low complexity. Despite relatively little sequence conservation within this domain, ZLD orthologs from Drosophila virilis, Anopheles gambiae, and Nasonia vitripennis activate transcription in D. melanogaster cells. Transcriptional activation by these ZLD orthologs suggests that ZLD functions through conserved interactions with a protein cofactor(s). We have identified distinct DNA-binding and activation domains within the critical transcription factor ZLD that controls the initial activation of the zygotic genome. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like β-grasp domains

    PubMed Central

    Iyer, Lakshminarayan M; Burroughs, A Maxwell; Aravind, L

    2006-01-01

    Background Ubiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation reactions in thiamine and molybdenum/tungsten cofactor biosynthesis. However, there is no evidence for entire protein modification systems with Ub-like proteins and deconjugation by deubiquitinating enzymes in prokaryotes. Hence, the evolutionary assembly of the eukaryotic Ub-signaling apparatus remains unclear. Results We systematically analyzed prokaryotic Ub-related β-grasp fold proteins using sensitive sequence profile searches and structural analysis. Consequently, we identified novel Ub-related proteins beyond the characterized ThiS, MoaD, TGS, and YukD domains. To understand their functional associations, we sought and recovered several conserved gene neighborhoods and domain architectures. These included novel associations involving diverse sulfur metabolism proteins, siderophore biosynthesis and the gene encoding the transfer mRNA binding protein SmpB, as well as domain fusions between Ub-like domains and PIN-domain related RNAses. Most strikingly, we found conserved gene neighborhoods in phylogenetically diverse bacteria combining genes for JAB domains (the primary de-ubiquitinating isopeptidases of the proteasomal complex), along with E1-like adenylating enzymes and different Ub-related proteins. Further sequence analysis of other conserved genes in these neighborhoods revealed several Ub-conjugating enzyme/E2-ligase related proteins. Genes for an Ub-like protein and a JAB domain peptidase were also found in the tail assembly gene cluster of certain caudate bacteriophages. Conclusion These observations imply that members of the Ub family had already formed strong functional associations with E1-like proteins, UBC/E2-related proteins, and JAB peptidases in the bacteria. Several of these Ub-like proteins and the associated protein families are likely to

  17. Discovery of a novel oocyte-specific Krüppel-associated box domain-containing zinc finger protein required for early embryogenesis in cattle.

    PubMed

    Hand, Jacqelyn M; Zhang, Kun; Wang, Lei; Koganti, Prasanthi P; Mastrantoni, Kristen; Rajput, Sandeep K; Ashry, Mohamed; Smith, George W; Yao, Jianbo

    2017-04-01

    Zinc finger (ZNF) transcription factors interact with DNA through zinc finger motifs and play important roles in a variety of cellular functions including cell growth, proliferation, development, apoptosis, and intracellular signal transduction. One-third of ZNF proteins in metazoans contain a highly conserved N-terminal motif known as the Krüppel-associated box (KRAB) domain, which acts as a potent, DNA-binding dependent transcriptional repression module. Analysis of RNA-Seq data generated from a bovine oocyte cDNA library identified a novel transcript, which encodes a KRAB-containing ZNF transcription factor (named ZNFO). Characterization of ZNFO mRNA expression revealed that it is exclusively expressed in bovine oocytes and early embryos. A GFP reporter assay demonstrated that ZNFO protein localizes specifically to the nucleus, supporting its role in transcriptional regulation. To test the role of ZNFO in early embryonic development, zygotes were generated by in vitro maturation and fertilization of oocytes, and injected with small interfering RNA (siRNA) designed to knockdown ZNFO. Cleavage rates were not affected by ZNFO siRNA injection. However, embryonic development to 8- to 16-cell stage and blastocyst stage was significantly reduced relative to the uninjected and negative control siRNA-injected embryos. Further, interaction of ZNFO with the highly conserved co-factor, KRAB-associated protein-1 (KAP1), was demonstrated, and evidence supporting transcriptional repression by ZNFO was demonstrated using a GAL4-luciferase reporter system. Results of described studies demonstrate that ZNFO is a maternally-derived oocyte-specific nuclear factor required for early embryonic development in cattle, presumably functioning by repressing transcription. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. AIDA: ab initio domain assembly for automated multi-domain protein structure prediction and domain–domain interaction prediction

    PubMed Central

    Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam

    2015-01-01

    Motivation: Most proteins consist of multiple domains, independent structural and evolutionary units that are often reshuffled in genomic rearrangements to form new protein architectures. Template-based modeling methods can often detect homologous templates for individual domains, but templates that could be used to model the entire query protein are often not available. Results: We have developed a fast docking algorithm ab initio domain assembly (AIDA) for assembling multi-domain protein structures, guided by the ab initio folding potential. This approach can be extended to discontinuous domains (i.e. domains with ‘inserted’ domains). When tested on experimentally solved structures of multi-domain proteins, the relative domain positions were accurately found among top 5000 models in 86% of cases. AIDA server can use domain assignments provided by the user or predict them from the provided sequence. The latter approach is particularly useful for automated protein structure prediction servers. The blind test consisting of 95 CASP10 targets shows that domain boundaries could be successfully determined for 97% of targets. Availability and implementation: The AIDA package as well as the benchmark sets used here are available for download at http://ffas.burnham.org/AIDA/. Contact: adam@sanfordburnham.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701568

  19. Identification of functional domains of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication

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

    Kim, Seong K., E-mail: skim1@lsuhsc.edu; Kim, Seongman; Dai Gan

    2011-09-01

    The equine herpesvirus 1 (EHV-1) negative regulatory IR2 protein (IR2P), an early 1,165-amino acid (aa) truncated form of the 1487-aa immediate-early protein (IEP), lacks the trans-activation domain essential for IEP activation functions but retains domains for binding DNA, TFIIB, and TBP and the nuclear localization signal. IR2P mutants of the N-terminal region which lack either DNA-binding activity or TFIIB-binding activity were unable to down-regulate EHV-1 promoters. In EHV-1-infected cells expressing full-length IR2P, transcription and protein expression of viral regulatory IE, early EICP0, IR4, and UL5, and late ETIF genes were dramatically inhibited. Viral DNA levels were reduced to 2.1% ofmore » control infected cells, but were vey weakly affected in cells that express the N-terminal 706 residues of IR2P. These results suggest that IR2P function requires the two N-terminal domains for binding DNA and TFIIB as well as the C-terminal residues 707 to 1116 containing the TBP-binding domain. - Highlights: > We examine the functional domains of IR2P that mediates negative regulation. > IR2P inhibits at the transcriptional level. > DNA-binding mutant or TFIIB-binding mutant fails to inhibit. > C-terminal aa 707 to 1116 are required for full inhibition. > Inhibition requires the DNA-binding domain, TFIIB-binding domain, and C-terminus.« less

  20. Investigating the incremental validity of cognitive variables in early mathematics screening.

    PubMed

    Clarke, Ben; Shanley, Lina; Kosty, Derek; Baker, Scott K; Cary, Mari Strand; Fien, Hank; Smolkowski, Keith

    2018-03-26

    The purpose of this study was to investigate the incremental validity of a set of domain general cognitive measures added to a traditional screening battery of early numeracy measures. The sample consisted of 458 kindergarten students of whom 285 were designated as severely at-risk for mathematics difficulty. Hierarchical multiple regression results indicated that Wechsler Abbreviated Scales of Intelligence (WASI) Matrix Reasoning and Vocabulary subtests, and Digit Span Forward and Backward measures explained a small, but unique portion of the variance in kindergarten students' mathematics performance on the Test of Early Mathematics Ability-Third Edition (TEMA-3) when controlling for Early Numeracy Curriculum Based Measurement (EN-CBM) screening measures (R² change = .01). Furthermore, the incremental validity of the domain general cognitive measures was relatively stronger for the severely at-risk sample. We discuss results from the study in light of instructional decision-making and note the findings do not justify adding domain general cognitive assessments to mathematics screening batteries. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  1. Effects of oral versus transdermal menopausal hormone treatments on self-reported sleep domains and their association with vasomotor symptoms in recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)

    PubMed Central

    Cintron, Dahima; Lahr, Brian D.; Bailey, Kent R.; Santoro, Nanette; Lloyd, Robin; Manson, JoAnn E.; Neal-Perry, Genevieve; Pal, Lubna; Taylor, Hugh S.; Wharton, Whitney; Naftolin, Fredrick; Harman, S. Mitchell; Miller, Virginia M.

    2018-01-01

    Abstract Objective: This study determined whether two different formulations of hormone therapy (HT): oral conjugated equine estrogens (o-CEE; 0.45 mg/d, n = 209), transdermal 17β-estradiol (t-E2; 50 μg/d, n = 201) plus cyclic progesterone (Prometrium, 200 mg) or placebo (PBO, n = 243) affected sleep domains in participants of the Kronos Early Estrogen Prevention Study. Methods: Participants completed the Pittsburgh Sleep Quality Index at baseline and during the intervention at 6, 18, 36, and 48 months. Global sleep quality and individual sleep domain scores were compared between treatments using analysis of covariance, and correlated with vasomotor symptom (VMS) scores using Spearman correlation coefficients. Results: Global Pittsburgh Sleep Quality Index scores (mean 6.3; 24% with score >8) were similar across groups at baseline and were reduced (improved sleep quality) by both HT (average change −1.27 [o-CEE] and −1.32 [t-E2]) when compared with PBO (−0.60; P = 0.001 [o-CEE vs PBO] and P = 0.002 [t-E2 vs PBO]). Domain scores for sleep satisfaction and latency improved with both HT. The domain score for sleep disturbances improved more with t-E2 than o-CEE or PBO. Global sleep scores significantly correlated with VMS severity (rs = 0.170, P < 0.001 for hot flashes; rs = 0.177, P < 0.001 for night sweats). Change in scores for all domains except sleep latency and sleep efficiency correlated with change in severity of VMS. Conclusions: Poor sleep quality is common in recently menopausal women. Sleep quality improved with both HT formulations. The relationship of VMS with domains of sleep suggests that assessing severity of symptoms and domains of sleep may help direct therapy to improve sleep for postmenopausal women. PMID:28832429

  2. Effects of oral versus transdermal menopausal hormone treatments on self-reported sleep domains and their association with vasomotor symptoms in recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS).

    PubMed

    Cintron, Dahima; Lahr, Brian D; Bailey, Kent R; Santoro, Nanette; Lloyd, Robin; Manson, JoAnn E; Neal-Perry, Genevieve; Pal, Lubna; Taylor, Hugh S; Wharton, Whitney; Naftolin, Fredrick; Harman, S Mitchell; Miller, Virginia M

    2018-02-01

    This study determined whether two different formulations of hormone therapy (HT): oral conjugated equine estrogens (o-CEE; 0.45 mg/d, n = 209), transdermal 17β-estradiol (t-E2; 50 μg/d, n = 201) plus cyclic progesterone (Prometrium, 200 mg) or placebo (PBO, n = 243) affected sleep domains in participants of the Kronos Early Estrogen Prevention Study. Participants completed the Pittsburgh Sleep Quality Index at baseline and during the intervention at 6, 18, 36, and 48 months. Global sleep quality and individual sleep domain scores were compared between treatments using analysis of covariance, and correlated with vasomotor symptom (VMS) scores using Spearman correlation coefficients. Global Pittsburgh Sleep Quality Index scores (mean 6.3; 24% with score >8) were similar across groups at baseline and were reduced (improved sleep quality) by both HT (average change -1.27 [o-CEE] and -1.32 [t-E2]) when compared with PBO (-0.60; P = 0.001 [o-CEE vs PBO] and P = 0.002 [t-E2 vs PBO]). Domain scores for sleep satisfaction and latency improved with both HT. The domain score for sleep disturbances improved more with t-E2 than o-CEE or PBO. Global sleep scores significantly correlated with VMS severity (rs = 0.170, P < 0.001 for hot flashes; rs = 0.177, P < 0.001 for night sweats). Change in scores for all domains except sleep latency and sleep efficiency correlated with change in severity of VMS. Poor sleep quality is common in recently menopausal women. Sleep quality improved with both HT formulations. The relationship of VMS with domains of sleep suggests that assessing severity of symptoms and domains of sleep may help direct therapy to improve sleep for postmenopausal women.

  3. Inferring Domain-Domain Interactions from Protein-Protein Interactions with Formal Concept Analysis

    PubMed Central

    Khor, Susan

    2014-01-01

    Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains. PMID:24586450

  4. Application of Shuffled Frog Leaping Algorithm and Genetic Algorithm for the Optimization of Urban Stormwater Drainage

    NASA Astrophysics Data System (ADS)

    Kumar, S.; Kaushal, D. R.; Gosain, A. K.

    2017-12-01

    Urban hydrology will have an increasing role to play in the sustainability of human settlements. Expansion of urban areas brings significant changes in physical characteristics of landuse. Problems with administration of urban flooding have their roots in concentration of population within a relatively small area. As watersheds are urbanized, infiltration decreases, pattern of surface runoff is changed generating high peak flows, large runoff volumes from urban areas. Conceptual rainfall-runoff models have become a foremost tool for predicting surface runoff and flood forecasting. Manual calibration is often time consuming and tedious because of the involved subjectivity, which makes automatic approach more preferable. The calibration of parameters usually includes numerous criteria for evaluating the performances with respect to the observed data. Moreover, derivation of objective function assosciat6ed with the calibration of model parameters is quite challenging. Various studies dealing with optimization methods has steered the embracement of evolution based optimization algorithms. In this paper, a systematic comparison of two evolutionary approaches to multi-objective optimization namely shuffled frog leaping algorithm (SFLA) and genetic algorithms (GA) is done. SFLA is a cooperative search metaphor, stimulated by natural memetics based on the population while, GA is based on principle of survival of the fittest and natural evolution. SFLA and GA has been employed for optimizing the major parameters i.e. width, imperviousness, Manning's coefficient and depression storage for the highly urbanized catchment of Delhi, India. The study summarizes the auto-tuning of a widely used storm water management model (SWMM), by internal coupling of SWMM with SFLA and GA separately. The values of statistical parameters such as, Nash-Sutcliffe efficiency (NSE) and Percent Bias (PBIAS) were found to lie within the acceptable limit, indicating reasonably good model performance

  5. Topologically-associating domains are stable units of replication-timing regulation

    PubMed Central

    Pope, Benjamin D.; Ryba, Tyrone; Dileep, Vishnu; Yue, Feng; Wu, Weisheng; Denas, Olgert; Vera, Daniel L.; Wang, Yanli; Hansen, R. Scott; Canfield, Theresa K.; Thurman, Robert E.; Cheng, Yong; Gülsoy, Günhan; Dennis, Jonathan H.; Snyder, Michael P.; Stamatoyannopoulos, John A.; Taylor, James; Hardison, Ross C.; Kahveci, Tamer; Ren, Bing; Gilbert, David M.

    2014-01-01

    Summary Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program1. During mammalian development, at least half the genome changes replication timing, primarily in units of 400–800 kb (“replication domains”; RDs), whose positions are preserved in different cell types, conserved between species, and appear to confine long-range effects of chromosome rearrangements2–7. Early and late replication correlate strongly with open and closed chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, lamina-associated domains (LADs)4,5,8,9. Recent Hi-C mapping has unveiled a substructure of topologically-associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to RDs8,10. However, TADs can be further sub-stratified into smaller domains, challenging the significance of structures at any particular scale11,12. Moreover, attempts to reconcile TADs and LADs to replication-timing data have not revealed a common, underlying domain structure8,9,13. Here, we localize boundaries of RDs to the early-replicating border of replication-timing transitions and map their positions in 18 human and 13 mouse cell types. We demonstrate that, collectively, RD boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure RD boundaries, largely accounting for the previously reported lack of alignment. Moreover, cell-type specific replication timing of TADs partitions the genome into two large-scale sub-nuclear compartments revealing that replication-timing transitions are indistinguishable from late-replicating regions in chromatin composition and lamina association and accounting for the reduced correlation of replication timing to LADs and heterochromatin. Our results reconcile cell type specific sub-nuclear compartmentalization with developmentally

  6. Pervasive influence of maternal and paternal criminal offending on early childhood development: a population data linkage study.

    PubMed

    Laurens, K R; Tzoumakis, S; Kariuki, M; Green, M J; Hamde, M; Harris, F; Carr, V J; Dean, K

    2017-04-01

    Parental criminal offending is an established risk factor for offending among offspring, but little evidence is available indicating the impact of offending on early childhood functioning. We used data from a large Australian population cohort to determine associations between exposure to parental offending and a range of developmental outcomes at age 5 years. Multi-generation data in 66 477 children and their parents from the New South Wales Child Development Study were combined using data linkage. Logistic and multinomial regressions tested associations between any and violent offending histories of parents (fathers, mothers, or both parents) obtained from official records, and multiple measures of early childhood developmental functioning (social, emotional-behavioural, cognitive, communication and physical domains) obtained from the teacher-reported 2009 Australian Early Development Census. Parental offending conferred significantly increased risk of vulnerability on all domains, particularly the cognitive domain. Greater risk magnitudes were observed for offending by both parents and by mothers than by fathers, and for violent than for any offending. For all parental offending exposures, vulnerability on multiple domains (where medium to large effects were observed) was more likely than on a single domain (small to medium effects). Relationships remained significant and of comparable magnitude following adjustment for sociodemographic covariates. The effect of parental offending on early childhood developmental outcomes is pervasive, with the strongest effects on functioning apparent when both parents engage in violent offending. Supporting affected families in early childhood might mitigate both early developmental vulnerability and the propensity for later delinquency among these offspring.

  7. Conceptual Foundations and Components of a Contextual Intervention to Promote Student Engagement during Early Adolescence: The Supporting Early Adolescent Learning and Social Success (SEALS) Model

    ERIC Educational Resources Information Center

    Farmer, Thomas W.; Hamm, Jill V.; Lane, Kathleen L.; Lee, David; Sutherland, Kevin S.; Hall, Cristin M.; Murray, Robert A.

    2013-01-01

    Decades of research indicate that many early adolescents are at risk for developing significant school adjustment problems in the academic, behavioral, and social domains during the transition to middle school. The Supporting Early Adolescent Learning and Social Success (SEALS) model has been developed as a professional development and…

  8. Analysis of nonuniformity in intron phase distribution.

    PubMed Central

    Fedorov, A; Suboch, G; Bujakov, M; Fedorova, L

    1992-01-01

    The distribution of different intron groups with respect to phases has been analyzed. It has been established that group II introns and nuclear introns have a minimum frequency of phase 2 introns. Since the phase of introns is an extremely conservative measure the observed minimum reflects evolutionary processes. A sample of all known, group I introns was too small to provide a valid characteristic of their phase distribution. The findings observed for the unequal distribution of phases cannot be explained solely on the basis of the mobile properties of introns. One of the most likely explanations for this nonuniformity in the intron phase distribution is the process of exon shuffling. It is proposed that group II introns originated at the early stages of evolution and were involved in the process of exon shuffling. PMID:1598214

  9. Identification of functional domains of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication

    PubMed Central

    Kim, Seong K.; Kim, Seongman; Dai, Gan; Zhang, Yunfei; Ahn, Byung C.; O'Callaghan, Dennis J.

    2012-01-01

    The equine herpesvirus 1 (EHV-1) negative regulatory IR2 protein (IR2P), an early 1,165-amino acid (aa) truncated form of the 1,487-aa immediate-early protein (IEP), lacks the trans-activation domain essential for IEP activation functions but retains domains for binding DNA, TFIIB, and TBP and the nuclear localization signal. IR2P mutants of the N-terminal region which lack either DNA-binding activity or TFIIB-binding activity were unable to down-regulate EHV-1 promoters. In EHV-1-infected cells expressing full-length IR2P, transcription and protein expression of viral regulatory IE, early EICP0, IR4, and UL5, and late ETIF genes were dramatically inhibited. Viral DNA levels were reduced to 2.1% of control infected cells, but were vey weakly affected in cells that express the N-terminal 706 residues of IR2P. These results suggest that IR2P function requires the two N-terminal domains for binding DNA and TFIIB as well as the C-terminal residues 707 to 1116 containing the TBP-binding domain. PMID:21794889

  10. Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines

    PubMed Central

    2010-01-01

    Background Protein-protein interaction (PPI) plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI) is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs), based on domains represented as interaction profile hidden Markov models (ipHMM) where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB). Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD). Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure), an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on the web at http

  11. Polarization-resolved second-harmonic generation microscopy as a method to visualize protein-crystal domains

    PubMed Central

    DeWalt, Emma L.; Begue, Victoria J.; Ronau, Judith A.; Sullivan, Shane Z.; Das, Chittaranjan; Simpson, Garth J.

    2013-01-01

    Polarization-resolved second-harmonic generation (PR-SHG) microscopy is described and applied to identify the presence of multiple crystallographic domains within protein-crystal conglomerates, which was confirmed by synchrotron X-ray diffraction. Principal component analysis (PCA) of PR-SHG images resulted in principal component 2 (PC2) images with areas of contrasting negative and positive values for conglomerated crystals and PC2 images exhibiting uniformly positive or uniformly negative values for single crystals. Qualitative assessment of PC2 images allowed the identification of domains of different internal ordering within protein-crystal samples as well as differentiation between multi-domain conglomerated crystals and single crystals. PR-SHG assessments of crystalline domains were in good agreement with spatially resolved synchrotron X-ray diffraction measurements. These results have implications for improving the productive throughput of protein structure determination through early identification of multi-domain crystals. PMID:23275165

  12. Mutational analysis of varicella-zoster virus (VZV) immediate early protein (IE62) subdomains and their importance in viral replication

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

    Khalil, Mohamed I., E-mail: mkhalil2@stanford.edu; Department of Molecular Biology, National Research Centre, El-Buhouth St., Cairo; Che, Xibing

    VZV IE62 is an essential, immediate-early, tegument protein and consists of five domains. We generated recombinant viruses carrying mutations in the first three IE62 domains and tested their influence on VZV replication kinetics. The mutations in domain I did not affect replication kinetics while domain II mutations, disrupting the DNA binding and dimerization domain (DBD), were lethal for VZV replication. Mutations in domain III of the nuclear localization signal (NLS) and the two phosphorylation sites S686A/S722A resulted in slower growth in early and late infection respectively and were associated with IE62 accumulation in the cytoplasm and nucleus respectively. This studymore » mapped the functional domains of IE62 in context of viral infection, indicating that DNA binding and dimerization domain is essential for VZV replication. In addition, the correct localization of IE62, whether nuclear or cytoplasmic, at different points in the viral life cycle, is important for normal progression of VZV replication. - Highlights: • Mutation of IE62 domain I did not affect VZV replication in melanoma cells. • IE62 domain II and III are important for VZV replication in melanoma cells. • Mutations of IE62 domain II (DBD) were lethal for virus replication. • Mutations of IE62 NLS and phosphorylation sites inhibited VZV replication. • NLS and S686A/S722A mutations altered localization of IE62 during early and late infection.« less

  13. Evaluation of spectral domain optical coherence tomography parameters in ocular hypertension, preperimetric, and early glaucoma

    PubMed Central

    Aydoğan, Tuğba; Akçay, Betül İlkay Sezgin; Kardeş, Esra; Ergin, Ahmet

    2017-01-01

    Purpose: The objective of this study is to evaluate the diagnostic ability of retinal nerve fiber layer (RNFL), macular, optic nerve head (ONH) parameters in healthy subjects, ocular hypertension (OHT), preperimetric glaucoma (PPG), and early glaucoma (EG) patients, to reveal factors affecting the diagnostic ability of spectral domain-optical coherence tomography (SD-OCT) parameters and risk factors for glaucoma. Methods: Three hundred and twenty-six eyes (89 healthy, 77 OHT, 94 PPG, and 66 EG eyes) were analyzed. RNFL, macular, and ONH parameters were measured with SD-OCT. The area under the receiver operating characteristic curve (AUC) and sensitivity at 95% specificity was calculated. Logistic regression analysis was used to determine the glaucoma risk factors. Receiver operating characteristic regression analysis was used to evaluate the influence of covariates on the diagnostic ability of parameters. Results: In PPG patients, parameters that had the largest AUC value were average RNFL thickness (0.83) and rim volume (0.83). In EG patients, parameter that had the largest AUC value was average RNFL thickness (0.98). The logistic regression analysis showed average RNFL thickness was a risk factor for both PPG and EG. Diagnostic ability of average RNFL and average ganglion cell complex thickness increased as disease severity increased. Signal strength index did not affect diagnostic abilities. Diagnostic ability of average RNFL and rim area increased as disc area increased. Conclusion: When evaluating patients with glaucoma, patients at risk for glaucoma, and healthy controls RNFL parameters deserve more attention in clinical practice. Further studies are needed to fully understand the influence of covariates on the diagnostic ability of OCT parameters. PMID:29133640

  14. Contrasting tectonothermal domains and faulting in the Potomac terrane, Virginia-Maryland - Discrimination by 40Ar/39Ar and fission-track thermochronology

    USGS Publications Warehouse

    Kunk, Michael J.; Wintsch, R.P.; Naeser, C.W.; Naeser, N.D.; Southworth, C.S.; Drake, Avery A.; Becker, J.L.

    2005-01-01

    New 40Ar/39Ar data reveal ages and thermal discontinuities that identify mapped and unmapped fault boundaries in the Potomac terrane in northern Virginia, thus confirming previous interpretations that it is a composite terrane. The rocks of the Potomac terrane were examined along the Potomac River, where it has been previously subdivided into three units: the Mather Gorge, Sykesville, and Laurel Formations. In the Mather Gorge Formation, at least two metamorphic thermal domains were identified, the Blockhouse Point and Bear Island domains, separated by a fault active in the late Devonian. Early Ordovician (ca. 475 Ma) cooling ages of amphibole in the Bear Island domain reflect cooling from Taconic metamorphism, whereas the Blockhouse Point domain was first metamorphosed in the Devonian. The 40Ar/39Ar data from muscovites in a third (eastern) domain within the Mather Gorge Formation, the Stubblefield Falls domain, record thrusting of the Sykesville Formation over the Mather Gorge Formation on the Plummers Island fault in the Devonian. The existence of two distinctly different thermal domains separated by a tectonic boundary within the Mather Gorge argues against its status as a formation. Hornblende cooling ages in the Sykesville Formation are Early Devonian (ca. 400 Ma), reflecting cooling from Taconic and Acadian metamorphism. The ages of retrograde and overprinting muscovite in phyllonites from domain-bounding faults are late Devonian (Acadian) and late Pennsylvanian (Alleghanian), marking the time of assembly of these domains and subsequent movement on the Plummers Island fault. Our data indicate that net vertical motion between the Bear Island domain of the Mather Gorge complex and the Sykesville Formation across the Plummers Island fault is east-side-up. Zircon fission-track cooling ages demonstrate thermal equillbrium across the Potomac terrane in the early Permian, and apatite fission-track cooling ages record tilting of the Potomac terrane in the Cretaceous

  15. The neural signature of self-concept development in adolescence: The role of domain and valence distinctions.

    PubMed

    van der Cruijsen, R; Peters, S; van der Aar, L P E; Crone, E A

    2017-11-22

    Neuroimaging studies in adults showed that cortical midline regions including medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) are important in self-evaluations. The goals of this study were to investigate the contribution of these regions to self-evaluations in late childhood, adolescence, and early adulthood, and to examine whether these differed per domain (academic, physical and prosocial) and valence (positive versus negative). Also, we tested whether this activation changes across adolescence. For this purpose, participants between ages 11-21-years (N = 150) evaluated themselves on trait sentences in an fMRI session. Behaviorally, adolescents rated their academic traits less positively than children and young adults. The neural analyses showed that evaluating self-traits versus a control condition was associated with increased activity in mPFC (domain-general effect), and positive traits were associated with increased activity in ventral mPFC (valence effect). Self-related mPFC activation increased linearly with age, but only for evaluating physical traits. Furthermore, an adolescent-specific decrease in striatum activation for positive self traits was found. Finally, we found domain-specific neural activity for evaluating traits in physical (dorsolateral PFC, dorsal mPFC) and academic (PPC) domains. Together, these results highlight the importance of domain distinctions when studying self-concept development in late childhood, adolescence, and early adulthood. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Ring-like oligomers of Synaptotagmins and related C2 domain proteins

    PubMed Central

    Zanetti, Maria N; Bello, Oscar D; Wang, Jing; Coleman, Jeff; Cai, Yiying; Sindelar, Charles V; Rothman, James E; Krishnakumar, Shyam S

    2016-01-01

    We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca2+-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts). Evidently, circular oligomerization is a general and conserved structural aspect of many C2 domain proteins, including Synaptotagmins. Further, using electron microscopy combined with targeted mutations, we show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca2+ involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. Our data suggests that ring formation may be triggered at an early step in synaptic vesicle docking and positions Syt1 to synchronize neurotransmitter release to Ca2+ influx. DOI: http://dx.doi.org/10.7554/eLife.17262.001 PMID:27434670

  17. The Leptospiral Antigen Lp49 is a Two-Domain Protein with Putative Protein Binding Function

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

    Oliveira Giuseppe,P.; Oliveira Neves, F.; Nascimento, A.

    2008-01-01

    Pathogenic Leptospira is the etiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. Currently available vaccines have limited effectiveness and therapeutic interventions are complicated by the difficulty in making an early diagnosis of leptospirosis. The genome of Leptospira interrogans was recently sequenced and comparative genomic analysis contributed to the identification of surface antigens, potential candidates for development of new vaccines and serodiagnosis. Lp49 is a membrane-associated protein recognized by antibodies present in sera from early and convalescent phases of leptospirosis patients. Its crystal structure was determined by single-wavelength anomalous diffraction using selenomethionine-labelled crystals and refined at 2.0 Angstromsmore » resolution. Lp49 is composed of two domains and belongs to the all-beta-proteins class. The N-terminal domain folds in an immunoglobulin-like beta-sandwich structure, whereas the C-terminal domain presents a seven-bladed beta-propeller fold. Structural analysis of Lp49 indicates putative protein-protein binding sites, suggesting a role in Leptospira-host interaction. This is the first crystal structure of a leptospiral antigen described to date.« less

  18. Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains

    PubMed Central

    Vishwanath, Sneha

    2018-01-01

    The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

  19. Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

    PubMed

    Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

    2018-02-01

    The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

  20. The Early Identity Exploration Scale-a measure of initial exploration in breadth during early adolescence.

    PubMed

    Kłym, Maria; Cieciuch, Jan

    2015-01-01

    The existing models and measurement instruments concerning identity appear to primarily focus on adolescence and early adulthood, and studies extending identity research to younger stages of life are scarce. There has been a particular lack of instruments measuring the early stages of identity formation, especially the process of exploration, which has been portrayed as a central process during this particular period of life. Our aim is to help fill the gap in the literature and facilitate further studies of the exploration process by providing an appropriate instrument to measure exploration in breadth during early adolescence. As a coherent and mature sense of identity is closely associated with psychosocial well-being, an effective identity exploration scale will enable researchers to assess the predictors of young adolescents' well-being. We propose a model of identity exploration domains based on the literature and considering 12 exploration domains: physical appearance, free time, family, work, boyfriend-girlfriend relationships, own opinion formation, perception of own place in the life cycle, self-reflection, future, future family, outlook on life, and attitude toward rules. The study was conducted on a group of N = 454 adolescents (50% males, M age = 13.04, SD = 0.98). Both reliability and structural validity, as verified by confirmatory factor analysis were satisfactory. The instrument is invariant across gender groups at the scalar level of measurement invariance.

  1. The Early Identity Exploration Scale—a measure of initial exploration in breadth during early adolescence

    PubMed Central

    Kłym, Maria; Cieciuch, Jan

    2015-01-01

    The existing models and measurement instruments concerning identity appear to primarily focus on adolescence and early adulthood, and studies extending identity research to younger stages of life are scarce. There has been a particular lack of instruments measuring the early stages of identity formation, especially the process of exploration, which has been portrayed as a central process during this particular period of life. Our aim is to help fill the gap in the literature and facilitate further studies of the exploration process by providing an appropriate instrument to measure exploration in breadth during early adolescence. As a coherent and mature sense of identity is closely associated with psychosocial well-being, an effective identity exploration scale will enable researchers to assess the predictors of young adolescents' well-being. We propose a model of identity exploration domains based on the literature and considering 12 exploration domains: physical appearance, free time, family, work, boyfriend-girlfriend relationships, own opinion formation, perception of own place in the life cycle, self-reflection, future, future family, outlook on life, and attitude toward rules. The study was conducted on a group of N = 454 adolescents (50% males, Mage = 13.04, SD = 0.98). Both reliability and structural validity, as verified by confirmatory factor analysis were satisfactory. The instrument is invariant across gender groups at the scalar level of measurement invariance. PMID:25983707

  2. The PYRIN domain: A member of the death domain-fold superfamily

    PubMed Central

    Fairbrother, Wayne J.; Gordon, Nathaniel C.; Humke, Eric W.; O'Rourke, Karen M.; Starovasnik, Melissa A.; Yin, Jian-Ping; Dixit, Vishva M.

    2001-01-01

    PYRIN domains were identified recently as putative protein–protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The ∼95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. PMID:11514682

  3. Early Combinations of Words and Actions.

    ERIC Educational Resources Information Center

    Shore, Cecilia

    Previous research has shown a similar starting time for early combinations of words and play actions in children and has suggested that similar cognitive processes underlie the transition to combining activities in language, symbolic play, and manipulative play. A study was undertaken to investigate combining activities in these three domains and…

  4. Mutation of domain III and domain VI in L gene conserved domain of Nipah virus

    NASA Astrophysics Data System (ADS)

    Jalani, Siti Aishah; Ibrahim, Nazlina

    2016-11-01

    Nipah virus (NiV) is the etiologic agent responsible for the respiratory illness and causes fatal encephalitis in human. NiV L protein subunit is thought to be responsible for the majority of enzymatic activities involved in viral transcription and replication. The L protein which is the viral RNA dependent RNA polymerase has high sequence homology among negative sense RNA viruses. In negative stranded RNA viruses, based on sequence alignment six conserved domain (domain I-IV) have been determined. Each domain is separated on variable regions that suggest the structure to consist concatenated functional domain. To directly address the roles of domains III and VI, site-directed mutations were constructed by the substitution of bases at sequences 2497, 2500, 5528 and 5532. Each mutated L gene can be used in future studies to test the ability for expression on in vitro translation.

  5. LenVarDB: database of length-variant protein domains.

    PubMed

    Mutt, Eshita; Mathew, Oommen K; Sowdhamini, Ramanathan

    2014-01-01

    Protein domains are functionally and structurally independent modules, which add to the functional variety of proteins. This array of functional diversity has been enabled by evolutionary changes, such as amino acid substitutions or insertions or deletions, occurring in these protein domains. Length variations (indels) can introduce changes at structural, functional and interaction levels. LenVarDB (freely available at http://caps.ncbs.res.in/lenvardb/) traces these length variations, starting from structure-based sequence alignments in our Protein Alignments organized as Structural Superfamilies (PASS2) database, across 731 structural classification of proteins (SCOP)-based protein domain superfamilies connected to 2 730 625 sequence homologues. Alignment of sequence homologues corresponding to a structural domain is available, starting from a structure-based sequence alignment of the superfamily. Orientation of the length-variant (indel) regions in protein domains can be visualized by mapping them on the structure and on the alignment. Knowledge about location of length variations within protein domains and their visual representation will be useful in predicting changes within structurally or functionally relevant sites, which may ultimately regulate protein function. Non-technical summary: Evolutionary changes bring about natural changes to proteins that may be found in many organisms. Such changes could be reflected as amino acid substitutions or insertions-deletions (indels) in protein sequences. LenVarDB is a database that provides an early overview of observed length variations that were set among 731 protein families and after examining >2 million sequences. Indels are followed up to observe if they are close to the active site such that they can affect the activity of proteins. Inclusion of such information can aid the design of bioengineering experiments.

  6. Oracle, a novel PDZ-LIM domain protein expressed in heart and skeletal muscle.

    PubMed

    Passier, R; Richardson, J A; Olson, E N

    2000-04-01

    In order to identify novel genes enriched in adult heart, we performed a subtractive hybridization for genes expressed in mouse heart but not in skeletal muscle. We identified two alternative splicing variants of a novel PDZ-LIM domain protein, which we named Oracle. Both variants contain a PDZ domain at the amino-terminus and three LIM domains at the carboxy-terminus. Highest homology of Oracle was found with the human and rat enigma proteins in the PDZ domain (62 and 61%, respectively) and in the LIM domains (60 and 69%, respectively). By Northern hybridization analysis, we showed that expression is highest in adult mouse heart, low in skeletal muscle and undetectable in other adult mouse tissues. In situ hybridization in mouse embryos confirmed and extended these data by showing high expression of Oracle mRNA in atrial and ventricular myocardial cells from E8.5. From E9.5 low expression of Oracle mRNA was detectable in myotomes. These data suggest a role for Oracle in the early development and function of heart and skeletal muscle.

  7. Domain wall nanoelectronics

    NASA Astrophysics Data System (ADS)

    Catalan, G.; Seidel, J.; Ramesh, R.; Scott, J. F.

    2012-01-01

    Domains in ferroelectrics were considered to be well understood by the middle of the last century: They were generally rectilinear, and their walls were Ising-like. Their simplicity stood in stark contrast to the more complex Bloch walls or Néel walls in magnets. Only within the past decade and with the introduction of atomic-resolution studies via transmission electron microscopy, electron holography, and atomic force microscopy with polarization sensitivity has their real complexity been revealed. Additional phenomena appear in recent studies, especially of magnetoelectric materials, where functional properties inside domain walls are being directly measured. In this paper these studies are reviewed, focusing attention on ferroelectrics and multiferroics but making comparisons where possible with magnetic domains and domain walls. An important part of this review will concern device applications, with the spotlight on a new paradigm of ferroic devices where the domain walls, rather than the domains, are the active element. Here magnetic wall microelectronics is already in full swing, owing largely to the work of Cowburn and of Parkin and their colleagues. These devices exploit the high domain wall mobilities in magnets and their resulting high velocities, which can be supersonic, as shown by Kreines’ and co-workers 30 years ago. By comparison, nanoelectronic devices employing ferroelectric domain walls often have slower domain wall speeds, but may exploit their smaller size as well as their different functional properties. These include domain wall conductivity (metallic or even superconducting in bulk insulating or semiconducting oxides) and the fact that domain walls can be ferromagnetic while the surrounding domains are not.

  8. The Australian Early Development Index, Who Does It Measure: Piaget or Vygotsky's Child?

    ERIC Educational Resources Information Center

    Agbenyega, Joseph

    2009-01-01

    Several psychological instruments have been developed and used over the years to measure various domains of child development. The Australian Early Development Index (AEDI) is a current assessment tool being used as a community measure of young children's development. It measures the following domains: Physical health and wellbeing; Social…

  9. Behavioral and anatomical consequences of early versus late symbol training in macaques.

    PubMed

    Srihasam, Krishna; Mandeville, Joseph B; Morocz, Istvan A; Sullivan, Kevin J; Livingstone, Margaret S

    2012-02-09

    Distinct brain regions, reproducible from one person to the next, are specialized for processing different kinds of human expertise, such as face recognition and reading. Here, we explore the relationship between age of learning, learning ability, and specialized brain structures. Specifically, we ask whether the existence of reproducible cortical domains necessarily means that certain abilities are innate, or innately easily learned, or whether reproducible domains can be formed, or refined, by interactions between genetic programs and common early experience. Functional MRI showed that intensive early, but not late, experience caused the formation of category-selective regions in macaque temporal lobe for stimuli never naturally encountered by monkeys. And behaviorally, early training produced more fluent processing of these stimuli than the same training in adults. One explanation for these results is that in higher cortical areas, as in early sensory areas, experience drives functional clustering and functional clustering determines how that information is processed. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Folding of a single domain protein entering the endoplasmic reticulum precedes disulfide formation.

    PubMed

    Robinson, Philip J; Pringle, Marie Anne; Woolhead, Cheryl A; Bulleid, Neil J

    2017-04-28

    The relationship between protein synthesis, folding, and disulfide formation within the endoplasmic reticulum (ER) is poorly understood. Previous studies have suggested that pre-existing disulfide links are absolutely required to allow protein folding and, conversely, that protein folding occurs prior to disulfide formation. To address the question of what happens first within the ER, that is, protein folding or disulfide formation, we studied folding events at the early stages of polypeptide chain translocation into the mammalian ER using stalled translation intermediates. Our results demonstrate that polypeptide folding can occur without complete domain translocation. Protein disulfide isomerase (PDI) interacts with these early intermediates, but disulfide formation does not occur unless the entire sequence of the protein domain is translocated. This is the first evidence that folding of the polypeptide chain precedes disulfide formation within a cellular context and highlights key differences between protein folding in the ER and refolding of purified proteins. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Domain Engineering

    NASA Astrophysics Data System (ADS)

    Bjørner, Dines

    Before software can be designed we must know its requirements. Before requirements can be expressed we must understand the domain. So it follows, from our dogma, that we must first establish precise descriptions of domains; then, from such descriptions, “derive” at least domain and interface requirements; and from those and machine requirements design the software, or, more generally, the computing systems.

  12. Visualizing domain wall and reverse domain superconductivity.

    PubMed

    Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D

    2014-08-28

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.

  13. Visualizing domain wall and reverse domain superconductivity

    PubMed Central

    Iavarone, M.; Moore, S. A.; Fedor, J.; Ciocys, S. T.; Karapetrov, G.; Pearson, J.; Novosad, V.; Bader, S. D.

    2014-01-01

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application. PMID:25164004

  14. Interferometrically enhanced sub-terahertz picosecond imaging utilizing a miniature collapsing-field-domain source

    NASA Astrophysics Data System (ADS)

    Vainshtein, Sergey N.; Duan, Guoyong; Mikhnev, Valeri A.; Zemlyakov, Valery E.; Egorkin, Vladimir I.; Kalyuzhnyy, Nikolay A.; Maleev, Nikolai A.; Näpänkangas, Juha; Sequeiros, Roberto Blanco; Kostamovaara, Juha T.

    2018-05-01

    Progress in terahertz spectroscopy and imaging is mostly associated with femtosecond laser-driven systems, while solid-state sources, mainly sub-millimetre integrated circuits, are still in an early development phase. As simple and cost-efficient an emitter as a Gunn oscillator could cause a breakthrough in the field, provided its frequency limitations could be overcome. Proposed here is an application of the recently discovered collapsing field domains effect that permits sub-THz oscillations in sub-micron semiconductor layers thanks to nanometer-scale powerfully ionizing domains arising due to negative differential mobility in extreme fields. This shifts the frequency limit by an order of magnitude relative to the conventional Gunn effect. Our first miniature picosecond pulsed sources cover the 100-200 GHz band and promise milliwatts up to ˜500 GHz. Thanks to the method of interferometrically enhanced time-domain imaging proposed here and the low single-shot jitter of ˜1 ps, our simple imaging system provides sufficient time-domain imaging contrast for fresh-tissue terahertz histology.

  15. N-terminal Domains Elicit Formation of Functional Pmel17 Amyloid Fibrils*

    PubMed Central

    Watt, Brenda; van Niel, Guillaume; Fowler, Douglas M.; Hurbain, Ilse; Luk, Kelvin C.; Stayrook, Steven E.; Lemmon, Mark A.; Raposo, Graça; Shorter, James; Kelly, Jeffery W.; Marks, Michael S.

    2009-01-01

    Pmel17 is a transmembrane protein that mediates the early steps in the formation of melanosomes, the subcellular organelles of melanocytes in which melanin pigments are synthesized and stored. In melanosome precursor organelles, proteolytic fragments of Pmel17 form insoluble, amyloid-like fibrils upon which melanins are deposited during melanosome maturation. The mechanism(s) by which Pmel17 becomes competent to form amyloid are not fully understood. To better understand how amyloid formation is regulated, we have defined the domains within Pmel17 that promote fibril formation in vitro. Using purified recombinant fragments of Pmel17, we show that two regions, an N-terminal domain of unknown structure and a downstream domain with homology to a polycystic kidney disease-1 repeat, efficiently form amyloid in vitro. Analyses of fibrils formed in melanocytes confirm that the polycystic kidney disease-1 domain forms at least part of the physiological amyloid core. Interestingly, this same domain is also required for the intracellular trafficking of Pmel17 to multivesicular compartments within which fibrils begin to form. Although a domain of imperfect repeats (RPT) is required for fibril formation in vivo and is a component of fibrils in melanosomes, RPT is not necessary for fibril formation in vitro and in isolation is unable to adopt an amyloid fold in a physiologically relevant time frame. These data define the structural core of Pmel17 amyloid, imply that the RPT domain plays a regulatory role in timing amyloid conversion, and suggest that fibril formation might be physically linked with multivesicular body sorting. PMID:19840945

  16. Domain Specific vs Domain General: Implications for Dynamic Assessment

    ERIC Educational Resources Information Center

    Kaniel, Shlomo

    2010-01-01

    The article responds to the need for evidence-based dynamic assessment. The article is divided into two sections: In Part 1 we examine the scientific answer to the question of how far human mental activities and capabilities are domain general (DG) / domain specific (DS). A highly complex answer emerges from the literature review of domains such…

  17. Correlated Longitudinal Changes across Linguistic, Achievement, and Psychomotor Domains in Early Childhood: Evidence for a Global Dimension of Development

    ERIC Educational Resources Information Center

    Rhemtulla, Mijke; Tucker-Drob, Elliot M.

    2011-01-01

    An important question within developmental psychology concerns the extent to which the maturational gains that children make across multiple diverse domains of functioning can be attributed to global (domain-general) developmental processes. The present study investigated this question by examining the extent to which individual differences in…

  18. Structure of the Fibrillin-1 N-Terminal Domains Suggests that Heparan Sulfate Regulates the Early Stages of Microfibril Assembly

    PubMed Central

    Yadin, David A.; Robertson, Ian B.; McNaught-Davis, Joanne; Evans, Paul; Stoddart, David; Handford, Penny A.; Jensen, Sacha A.; Redfield, Christina

    2013-01-01

    Summary The human extracellular matrix glycoprotein fibrillin-1 is the primary component of the 10- to 12-nm-diameter microfibrils, which perform key structural and regulatory roles in connective tissues. Relatively little is known about the molecular mechanisms of fibrillin assembly into microfibrils. Studies using recombinant fibrillin fragments indicate that an interaction between the N- and C-terminal regions drives head-to-tail assembly. Here, we present the structure of a fibrillin N-terminal fragment comprising the fibrillin unique N-terminal (FUN) and the first three epidermal growth factor (EGF)-like domains (FUN-EGF3). Two rod-like domain pairs are separated by a short, flexible linker between the EGF1 and EGF2 domains. We also show that the binding site for the C-terminal region spans multiple domains and overlaps with a heparin interaction site. These data suggest that heparan sulfate may sequester fibrillin at the cell surface via FUN-EGF3 prior to aggregation of the C terminus, thereby regulating microfibril assembly. PMID:24035709

  19. Personality Domains, Duration of Untreated Psychosis, Functioning, and Symptom Severity in First-Episode Psychosis

    PubMed Central

    Compton, Michael T.; Bakeman, Roger; Alolayan, Yazeed; Balducci, Pierfrancesco Maria; Bernardini, Francesco; Broussard, Beth; Crisafio, Anthony; Cristofaro, Sarah; Amar, Patrick; Johnson, Stephanie; Wan, Claire Ramsay

    2015-01-01

    Objectives Early-course psychotic disorders have been extensively studied in terms of phenomenology, but little is known about the influence of personality traits on clinical features of first-episode psychosis. The aim of this study was to explore how the “big five” personality domains (neuroticism, extraversion, openness, agreeableness, and conscientiousness) are associated with treatment delay (duration of untreated psychosis, DUP), functioning, and positive and negative symptom severity. Methods Data for these analyses were obtained from 104 participants enrolled from psychiatric inpatient units in Atlanta, Georgia, between August 2008 and March 2011. The NEO Five-Factor Inventory (NEO-FFI) was used to assess personality domains, and all other variables were measured in a standardized and rigorous manner using psychometrically sound instruments. Correlational analyses and multiple linear regressions were carried out to examine the strength of associations between variables of interest. Results Findings indicated that except for openness, all the other personality variables contributed to some extent to the variance in DUP. Conscientiousness was positively correlated with functioning. Agreeableness was independently negatively associated with positive symptom severity and extraversion was independently negatively correlated with negative symptom severity. Conclusions We report the first evidence suggesting that DUP is in part driven by personality domains. Functioning and symptom severity are also associated with those domains. Personality should be taken into account in order to better understand the phenomenology of early-course psychotic disorders as well as treatment-seeking behaviors. PMID:26209478

  20. Influences of the inner retinal sublayers and analytical areas in macular scans by spectral-domain OCT on the diagnostic ability of early glaucoma.

    PubMed

    Nakatani, Yusuke; Higashide, Tomomi; Ohkubo, Shinji; Sugiyama, Kazuhisa

    2014-10-23

    We investigated the influences of the inner retinal sublayers and analytical areas in macular scans by spectral-domain optical coherence tomography (OCT) on the diagnostic ability of early glaucoma. A total of 64 early (including 24 preperimetric) glaucomatous and 40 normal eyes underwent macular and peripapillary retinal nerve fiber layer (pRNFL) scans (3D-OCT-2000). The area under the receiver operating characteristics (AUC) for glaucoma diagnosis was determined from the average thickness of the total 100 grids (6 × 6 mm), central 44 grids (3.6 × 4.8 mm), and peripheral 56 grids (outside of the 44 grids), and for each macular sublayer: macular RNFL (mRNFL), ganglion cell layer plus inner plexiform layer (GCL/IPL), and mRNFL plus GCL/IPL (ganglion cell complex [GCC]). Correlation of OCT parameters with visual field parameters was evaluated by Spearman's rank correlation coefficients (rs). The GCC-related parameters had a significantly larger AUC (0.82-0.97) than GCL/IPL (0.81-0.91), mRNFL-related parameters (0.72-0.94), or average pRNFL (0.88) in more than half of all comparisons. The central 44 grids had a significantly lower AUC than other analytical areas in GCC and mRNFL thickness. Conversely, the peripheral 56 grids had a significantly lower AUC than the 100 grids in GCL/IPL inferior thickness. Inferior thickness of GCC (rs, 0.45-0.49) and mRNFL (rs, 0.43-0.51) showed comparably high correlations with central visual field parameters to average pRNFL thickness (rs, 0.41, 0.47) even in the central 44 grids. The diagnostic ability of macular OCT parameters for early glaucoma differed by inner retinal sublayers and also by the analytical areas studied. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  1. Early, on-time, and late behavioural autonomy in adolescence: psychosocial correlates in young and middle adulthood.

    PubMed

    Pavlova, Maria K; Haase, Claudia M; Silbereisen, Rainer K

    2011-04-01

    Drawing on two nationally representative German studies (N(1) = 1744, N(2) = 759), we examined correlates of early, on-time, and late curfew autonomy, a retrospective indicator of behavioural autonomy, in young and middle adulthood (19-37 years of age). Adjustment in four domains was considered: educational attainment, externalizing problem behaviour, subjective well-being, and interpersonal relationships. The early group showed lower adjustment in multiple domains across young and middle adulthood. The late group reported a mixed pattern of adjustment at younger ages (lower externalizing problems, but lower positive affect, lower importance of peers, and lower likelihood to have a partner) and positive adjustment in all domains at older ages. Timing effects were controlled for sociodemographic characteristics and retrospective measures of early adversities, pubertal timing, disclosure to parents, and peer group affiliation in adolescence. Findings show that late behavioural autonomy in its correlates is not simply the opposite of early behavioural autonomy. Copyright © 2010 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  2. Endoscopic spectral-domain polarization-sensitive optical coherence tomography system

    NASA Astrophysics Data System (ADS)

    Wang, Yi; Chen, Xiaodong; Hu, Zhiqiang; Li, Qiao; Yu, Daoyin

    2008-02-01

    In this paper, we introduced a fiber-based endoscopic Spectral-domain Polarization-sensitive OCT (SD-PS-OCT) experimental scheme for detecting the internal organ disease, which is based on low-coherence interferometer and two spectrometers. The SD-PS-OCT has the advantages of both Spectral-domain OCT (SD-OCT) and Polarization-sensitive OCT (PS-OCT). It is able to get the real-time image of reflectivity and birefringence distribution of tissue at the same time. The usage of SD-PS-OCT in endoscopic diagnosing system provides it the possibility to detect the internal organ disease. Since SD-PS-OCT can image the pathological changes of biological tissue below surface (1-3mm) with high resolution (1-15μm), it is able to help diagnosing early diseases of internal organs, which makes it a biomedical technology with bright future.

  3. Rab7 Associates with Early Endosomes to Mediate Sorting and Transport of Semliki Forest Virus to Late Endosomes

    PubMed Central

    Vonderheit, Andreas

    2005-01-01

    Semliki forest virus (SFV) is internalized by clathrin-mediated endocytosis, and transported via early endosomes to late endosomes and lysosomes. The intracellular pathway taken by individual fluorescently labeled SFV particles was followed using immunofluorescence in untransfected cells, and by video-enhanced, triple-color fluorescence microscopy in live cells transfected with GFP- and RFP-tagged Rab5, Rab7, Rab4, and Arf1. The viruses progressed from Rab5-positive early endosomes to a population of early endosomes (about 10% of total) that contained both Rab5 and Rab7. SFV were sequestered in the Rab7 domains, and they were sorted away from the early endosomes when these domains detached as separate transport carriers devoid of Rab5, Rab4, EEA1, Arf1, and transferrin. The process was independent of Arf1 and the acidic pH in early endosomes. Nocodazole treatment showed that the release of transport carriers was assisted by microtubules. Expression of constitutively inactive Rab7T22N resulted in accumulation of SFV in early endosomes. We concluded that Rab7 is recruited to early endosomes, where it forms distinct domains that mediate cargo sorting as well as the formation of late-endosome-targeted transport vesicles. PMID:15954801

  4. Noncoding RNAs of the Ultrabithorax Domain of the Drosophila Bithorax Complex

    PubMed Central

    Pease, Benjamin; Borges, Ana C.; Bender, Welcome

    2013-01-01

    RNA transcripts without obvious coding potential are widespread in many creatures, including the fruit fly, Drosophila melanogaster. Several noncoding RNAs have been identified within the Drosophila bithorax complex. These first appear in blastoderm stage embryos, and their expression patterns indicate that they are transcribed only from active domains of the bithorax complex. It has been suggested that these noncoding RNAs have a role in establishing active domains, perhaps by setting the state of Polycomb Response Elements A comprehensive survey across the proximal half of the bithorax complex has now revealed nine distinct noncoding RNA transcripts, including four within the Ultrabithorax transcription unit. At the blastoderm stage, the noncoding transcripts collectively span ∼75% of the 135 kb surveyed. Recombination-mediated cassette exchange was used to invert the promoter of one of the noncoding RNAs, a 23-kb transcript from the bxd domain of the bithorax complex. The resulting animals fail to make the normal bxd noncoding RNA and show no transcription across the bxd Polycomb Response Element in early embryos. The mutant flies look normal; the regulation of the bxd domain appears unaffected. Thus, the bxd noncoding RNA has no apparent function. PMID:24077301

  5. Fungal-type carbohydrate binding modules from the coccolithophore Emiliania huxleyi show binding affinity to cellulose and chitin.

    PubMed

    Rooijakkers, Bart J M; Ikonen, Martina S; Linder, Markus B

    2018-01-01

    Six fungal-type cellulose binding domains were found in the genome of the coccolithophore Emiliania huxleyi and cloned and expressed in Escherichia coli. Sequence comparison indicate high similarity to fungal cellulose binding domains, raising the question of why these domains exist in coccolithophores. The proteins were tested for binding with cellulose and chitin as ligands, which resulted in the identification of two functional carbohydrate binding modules: EHUX2 and EHUX4. Compared to benchmark fungal cellulose binding domain Cel7A-CBM1 from Trichoderma reesei, these proteins showed slightly lower binding to birch and bacterial cellulose, but were more efficient chitin binders. Finally, a set of cellulose binding domains was created based on the shuffling of one well-functioning and one non-functional domain. These were characterized in order to get more information of the binding domain's sequence-function relationship, indicating characteristic differences between the molecular basis of cellulose versus chitin recognition. As previous reports have showed the presence of cellulose in coccoliths and here we find functional cellulose binding modules, a possible connection is discussed.

  6. Early Head Start and African American Families: Impacts and Mechanisms of Child Outcomes

    ERIC Educational Resources Information Center

    Harden, Brenda Jones; Sandstrom, Heather; Chazan-Cohen, Rachel

    2012-01-01

    Persistent disparities exist between African American children and their European American counterparts across developmental domains. Early childhood intervention may serve to promote more positive outcomes among African American children. The current study examined whether and how the Early Head Start (EHS) program benefited African American…

  7. Spectral-domain optical coherence tomography of roth spots.

    PubMed

    Giovinazzo, Jerome; Mrejen, Sarah; Freund, K Bailey

    2013-01-01

    To describe the retinal findings of subacute bacterial endocarditis, their evolution after treatment, and analysis with spectral-domain optical coherence tomography. Retrospective chart review. A 21-year-old man presented with the sudden onset of a central scotoma in his left eye because of a sub-internal limiting membrane hemorrhage overlying the left fovea. When examined 2 weeks later, Roth spots were noted in his right eye. The patient was immediately referred to his internist and diagnosed with subacute bacterial endocarditis with cultures positive for Streptococcus viridans. He subsequently underwent aortic valve replacement surgery after 4 weeks of intravenous antibiotic therapy. When examined 4 weeks after valve replacement surgery, there was regression of the Roth spots. The present case demonstrates the importance of a funduscopic examination in the early diagnosis and management of subacute bacterial endocarditis. The analysis of Roth spots with spectral-domain optical coherence tomography suggested that they were septic emboli.

  8. Domain-to-domain coupling in voltage-sensing phosphatase.

    PubMed

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

  9. Domain-to-domain coupling in voltage-sensing phosphatase

    PubMed Central

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain. PMID:28744425

  10. Diagnostic Capability of Spectral Domain Optical Coherence Tomography for Glaucoma

    PubMed Central

    Wu, Huijuan; de Boer, Johannes F.; Chen, Teresa C.

    2012-01-01

    Purpose To determine the diagnostic capability of spectral domain optical coherence tomography (OCT) in glaucoma patients with visual field (VF) defects. Design Prospective, cross-sectional study. Methods Setting Participants were recruited from a university hospital clinic. Study Population One eye of 85 normal subjects and 61 glaucoma patients [with average VF mean deviation (MD) of -9.61 ± 8.76 dB] were randomly selected for the study. A subgroup of the glaucoma patients with early VF defects was calculated separately. Observation Procedures Spectralis OCT circular scans were performed to obtain peripapillary retinal nerve fiber layer (RNFL) thicknesses. The RNFL diagnostic parameters based on the normative database were used alone or in combination for identifying glaucomatous RNFL thinning. Main Outcome Measures To evaluate diagnostic performance, calculations included areas under the receiver operating characteristic curve (AROC), sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. Results Overall RNFL thickness had the highest AROC value (0.952 for all patients, 0.895 for the early glaucoma subgroup). For all patients, the highest sensitivity (98.4%, CI 96.3-100%) was achieved by using two criteria: ≥1 RNFL sectors being abnormal at the < 5% level, and overall classification of borderline or outside normal limits, with specificities of 88.9% (CI 84.0-94.0%) and 87.1% (CI 81.6-92.5%) respectively for these two criteria. Conclusions Statistical parameters for evaluating the diagnostic performance of the Spectralis spectral domain OCT were good for early perimetric glaucoma and excellent for moderately-advanced perimetric glaucoma. PMID:22265147

  11. Skyrmion domain wall collision and domain wall-gated skyrmion logic

    NASA Astrophysics Data System (ADS)

    Xing, Xiangjun; Pong, Philip W. T.; Zhou, Yan

    2016-08-01

    Skyrmions and domain walls are significant spin textures of great technological relevance to magnetic memory and logic applications, where they can be used as carriers of information. The unique topology of skyrmions makes them display emergent dynamical properties as compared with domain walls. Some studies have demonstrated that the two topologically inequivalent magnetic objects could be interconverted by using cleverly designed geometric structures. Here, we numerically address the skyrmion domain wall collision in a magnetic racetrack by introducing relative motion between the two objects based on a specially designed junction. An electric current serves as the driving force that moves a skyrmion toward a trapped domain wall pair. We see different types of collision dynamics depending on the driving parameters. Most importantly, the modulation of skyrmion transport using domain walls is realized in this system, allowing a set of domain wall-gated logical NOT, NAND, and NOR gates to be constructed. This work provides a skyrmion-based spin-logic architecture that is fully compatible with racetrack memories.

  12. Professional Development for Early Childhood Educators: Efforts to Improve Math and Science Learning Opportunities in Early Childhood Classrooms

    ERIC Educational Resources Information Center

    Piasta, Shayne B.; Logan, Jessica A. R.; Pelatti, Christina Yeager; Capps, Janet L.; Petrill, Stephen A.

    2015-01-01

    Because recent initiatives highlight the need to better support preschool-aged children's math and science learning, the present study investigated the impact of professional development in these domains for early childhood educators. Sixty-five educators were randomly assigned to experience 10.5 days (64 hr) of training on math and science or on…

  13. MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

    PubMed

    Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

    2013-05-01

    The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

  14. Early and middle adolescents' disclosure to parents about activities in different domains.

    PubMed

    Smetana, Judith G; Villalobos, Myriam; Tasopoulos-Chan, Marina; Gettman, Denise C; Campione-Barr, Nicole

    2009-06-01

    Disclosure, disclosure strategies, and justifications for nondisclosure for prudential, peer, multifaceted, and personal acts were assessed using a sorting task with 118 lower-middle class early and middle adolescents (Ms=12.77 and 15.68 years). Adolescents were less involved in prudential than other behaviors, although prudential behavior was greater among middle than early adolescents; adolescents disclosed more about prudential and personal than multifaceted and peer behaviors. Nondisclosure was primarily due to concerns about parental disapproval (for prudential acts), claims that acts were personal or not harmful (for personal acts), and their mixture (for peer and multifaceted acts). When concerned about parental disapproval, older adolescents fully disclosed less (and lied somewhat more) than younger adolescents, whereas adolescents primarily avoided discussing the issue when they viewed acts as personal. Full disclosure was associated with better relationships with parents and less depressed mood; lying was associated with more parental behavioral control over personal issues and poorer relationships with fathers.

  15. H3S10ph broadly marks early-replicating domains in interphase ESCs and shows reciprocal antagonism with H3K9me2.

    PubMed

    Chen, Carol C L; Goyal, Preeti; Karimi, Mohammad M; Abildgaard, Marie H; Kimura, Hiroshi; Lorincz, Matthew C

    2018-01-01

    Phosphorylation of histone H3 at serine 10 (H3S10ph) by Aurora kinases plays an important role in mitosis; however, H3S10ph also marks regulatory regions of inducible genes in interphase mammalian cells, implicating mitosis-independent functions. Using the fluorescent ubiquitin-mediated cell cycle indicator (FUCCI), we found that 30% of the genome in interphase mouse embryonic stem cells (ESCs) is marked with H3S10ph. H3S10ph broadly demarcates gene-rich regions in G1 and is positively correlated with domains of early DNA replication timing (RT) but negatively correlated with H3K9me2 and lamin-associated domains (LADs). Consistent with mitosis-independent kinase activity, this pattern was preserved in ESCs treated with Hesperadin, a potent inhibitor of Aurora B/C kinases. Disruption of H3S10ph by expression of nonphosphorylatable H3.3S10A results in ectopic spreading of H3K9me2 into adjacent euchromatic regions, mimicking the phenotype observed in Drosophila JIL-1 kinase mutants . Conversely, interphase H3S10ph domains expand in Ehmt1 (also known as Glp ) null ESCs, revealing that H3S10ph deposition is restricted by H3K9me2. Strikingly, spreading of H3S10ph at RT transition regions (TTRs) is accompanied by aberrant transcription initiation of genes co-oriented with the replication fork in Ehmt1 -/- and Ehmt2 -/- ESCs, indicating that establishment of repressive chromatin on the leading strand following DNA synthesis may depend upon these lysine methyltransferases. H3S10ph is also anti-correlated with H3K9me2 in interphase murine embryonic fibroblasts (MEFs) and is restricted to intragenic regions of actively transcribing genes by EHMT2. Taken together, these observations reveal that H3S10ph may play a general role in restricting the spreading of repressive chromatin in interphase mammalian cells. © 2018 Chen et al.; Published by Cold Spring Harbor Laboratory Press.

  16. Predicting detection performance with model observers: Fourier domain or spatial domain?

    PubMed

    Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

    2016-02-27

    The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

  17. Predicting detection performance with model observers: Fourier domain or spatial domain?

    PubMed Central

    Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

    2016-01-01

    The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images. PMID:27239086

  18. Domain-General and Domain-Specific Strategies for the Assessment of Distress Intolerance

    PubMed Central

    McHugh, R. Kathryn; Otto, Michael W.

    2011-01-01

    Recent research has provided evidence that distress intolerance—the perceived inability to tolerate distressing states—varies based on the domain of distress (e.g., pain, anxiety). Although domain-specific assessment strategies may provide information targeted to specific disorders or maladaptive behaviors, domain-general measures have the potential to facilitate comparisons across studies, disorders, and populations. The current study evaluated the utilization of self-report measures of distress intolerance as domain-general measures by examining their association with indices of behavioral avoidance and substance craving. Two groups of participants (N = 55) were recruited including a substance-dependent group and a comparison group equated based on the presence of an affective disorder. Results provided support for the validity of domain-general measures for assessing distress intolerance across varied domains. The importance of both domain-general and domain-specific measurement of distress intolerance is discussed. PMID:21823763

  19. Early and Middle Adolescents' Disclosure to Parents about Activities in Different Domains

    ERIC Educational Resources Information Center

    Smetana, Judith G.; Villalobos, Myriam; Tasopoulos-Chan, Marina; Gettman, Denise C.; Campione-Barr, Nicole

    2009-01-01

    Disclosure, disclosure strategies, and justifications for nondisclosure for prudential, peer, multifaceted, and personal acts were assessed using a sorting task with 118 lower-middle class early and middle adolescents (Ms = 12.77 and 15.68 years). Adolescents were less involved in prudential than other behaviors, although prudential behavior was…

  20. Evidence of early ultrastructural photoreceptor abnormalities in light-induced retinal degeneration using spectral domain optical coherence tomography.

    PubMed

    Aziz, Mehak K; Ni, Aiguo; Esserman, Denise A; Chavala, Sai H

    2014-07-01

    To study spatiotemporal in vivo changes in retinal morphology and quantify thickness of retinal layers in a mouse model of light-induced retinal degeneration using spectral domain optical coherence tomography (SD-OCT). BALB/c mice were exposed to 5000 lux of constant light for 3 h. SD-OCT images were taken 3 h, 24 h, 3 days, 1 week and 1 month after light exposure and were compared with histology at the same time points. SD-OCT images were also taken at 0, 1 and 2 h after light exposure in order to analyse retinal changes at the earliest time points. The thickness of retinal layers was measured using the Bioptigen software InVivoVue Diver. SD-OCT demonstrated progressive outer retinal thinning. 3 h after light exposure, the outer nuclear layer converted from hyporeflective to hyper-reflective. At 24 h, outer retinal bands and nuclear layer demonstrated similar levels of hyper-reflectivity. Significant variations in outer retinal thickness, vitreous opacities and retinal detachments occurred within days of injury. Thinning of the retina was observed at 1 month after injury. It was also determined that outer nuclear layer changes precede photoreceptor segment structure disintegration and the greatest change in segment structure occurs between 1 and 2 h after light exposure. Longitudinal SD-OCT reveals intraretinal changes that cannot be observed by histopathology at early time points in the light injury model. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Psychometric Properties and Normative values of Early Maladaptive Schema Questionnaires Set for Children and Adolescents (SQS).

    PubMed

    Güner, Olcay

    2017-03-01

    The Early Maladaptive Schema Questionnaires Set for Children and Adolescents (SQS) was developed to assess early maladaptive schemas in children between the ages of 10 and 16 in Turkey. The SQS consists of five questionnaires that represent five schema domains in Young's schema theory. Psychometric properties (n = 983) and normative values (n = 2250) of SQS were investigated in children and adolescents between the ages of 10 and 16. Both exploratory and confirmatory factor analyses were performed. Results revealed 15 schema factors under five schema domains, with good fit indexes. A total of 14 schema factors were in line with Young's early maladaptive schemas. In addition to these factors, one new schema emerged: self-disapproval. Reliability analyses showed that SQS has high internal consistency and consistency over a 1-month interval. Correlations of SQS with the Adjective Check List (ACL), the Inventory of Parent and Peer Attachment (IPPA), the Symptom Assessment (SA-45) and the Young Schema Questionnaire (YSQ) were investigated to assess criterion validity, and the correlations revealed encouraging results. SQS significantly differentiated between children who have clinical diagnoses (n = 78) and children who have no diagnosis (n = 100). Finally, general normative values (n = 2,250) were determined for age groups, gender and age/gender groups. In conclusion, the early maladaptive schema questionnaires set for children and adolescents turned out to be a reliable and valid questionnaire with standard scores.Copyright © 2016 John Wiley & Sons, Ltd. The early maladaptive schema questionnaires set for children and adolescents (SQS) is a psychometrically reliable and valid measure of early maladaptive schemas for children between the ages of 10 and 16. SQS consists of five schema domains that represent Young's schema domains including 15 early maladaptive schemas and 97 items. Normative values for each schema were determined for age, gender and

  2. The Relationship Between Preservice Early Childhood Teachers' Cultural Values and their Perceptions of Scientists' Cultural Values

    NASA Astrophysics Data System (ADS)

    Akerson, Valarie L.; Buzzelli, Cary A.; Eastwood, Jennifer

    2010-03-01

    This paper describes research that compares preservice early childhood teachers’ cultural values and the values they believe are held by scientists. Using the Schwartz Values Inventory (SVI) (Schwartz (1992) Adv Exp Soc Psychol 25:331-351) preservice early childhood teachers cultural values were assessed, followed by an assessment of the values they believed were held by scientists. Schwartz postulated that cultural values could be aggregated into 11 domains (universalism, benevolence, tradition, self-direction, stimulation, hedonism, achievement, power, conformity, spirituality, and security). Paired T-tests indicated significant differences between preservice early childhood teachers’ cultural values from those they believed scientists held on the domains of power, achievement, stimulation, benevolence, conformity, and security. The discussion explores the meaning of these results and provides implications for early childhood science teacher education.

  3. Early Life Factors and Adult Leisure Time Physical Inactivity Stability and Change.

    PubMed

    Pinto Pereira, Snehal M; Li, Leah; Power, Chris

    2015-09-01

    Physical inactivity has a high prevalence and associated disease burden. A better understanding of influences on sustaining and changing inactive lifestyles is needed. We aimed to establish whether leisure time inactivity was stable in midadulthood and whether early life factors were associated with inactivity patterns. In the 1958 British birth cohort (n = 12,271), leisure time inactivity (frequency, less than once a week) assessed at 33 and 50 yr was categorized as "never inactive," "persistently inactive," "deteriorating," or "improving." Early life factors (birth to 16 yr) were categorized into three (physical, social, and behavioral) domains. Using multinomial logistic regression, we assessed associations with inactivity persistence and change of factors within each early life domain and the three domains combined with and without adjustment for adult factors. Inactivity prevalence was similar at 33 and 50 yr (approximately 31%), but 17% deteriorated and 18% improved with age. In models adjusted for all domains simultaneously, factors associated with inactivity persistence versus never inactive were prepubertal stature (8% lower risk/height SD), poor hand control/coordination (17% higher risk/increase on four-point scale), cognition (16% lower/SD in ability) (physical); parental divorce (25% higher), class at birth (7% higher/reduction on four-point scale), minimal parental education (16% higher), household amenities (2% higher/increase in 19-point score (high = poor)) (social); and inactivity (22% higher/reduction in activity on four-point scale), low sports aptitude (47% higher), smoking (30% higher) (behavioral). All except stature, parental education, sports aptitude, and smoking were associated also with inactivity deterioration. Poor hand control/coordination was the only factor associated with improved status (13% lower/increase on four-point scale) versus persistently inactive. Adult leisure time inactivity is moderately stable. Early life factors are

  4. Symbiosis Island Shuffling with Abundant Insertion Sequences in the Genomes of Extra-Slow-Growing Strains of Soybean Bradyrhizobia

    PubMed Central

    Iida, Takayuki; Itakura, Manabu; Anda, Mizue; Sugawara, Masayuki; Isawa, Tsuyoshi; Okubo, Takashi; Sato, Shusei; Chiba-Kakizaki, Kaori

    2015-01-01

    Extra-slow-growing bradyrhizobia from root nodules of field-grown soybeans harbor abundant insertion sequences (ISs) and are termed highly reiterated sequence-possessing (HRS) strains. We analyzed the genome organization of HRS strains with the focus on IS distribution and symbiosis island structure. Using pulsed-field gel electrophoresis, we consistently detected several plasmids (0.07 to 0.4 Mb) in the HRS strains (NK5, NK6, USDA135, 2281, USDA123, and T2), whereas no plasmids were detected in the non-HRS strain USDA110. The chromosomes of the six HRS strains (9.7 to 10.7 Mb) were larger than that of USDA110 (9.1 Mb). Using MiSeq sequences of 6 HRS and 17 non-HRS strains mapped to the USDA110 genome, we found that the copy numbers of ISRj1, ISRj2, ISFK1, IS1632, ISB27, ISBj8, and IS1631 were markedly higher in HRS strains. Whole-genome sequencing showed that the HRS strain NK6 had four small plasmids (136 to 212 kb) and a large chromosome (9,780 kb). Strong colinearity was found between 7.4-Mb core regions of the NK6 and USDA110 chromosomes. USDA110 symbiosis islands corresponded mainly to five small regions (S1 to S5) within two variable regions, V1 (0.8 Mb) and V2 (1.6 Mb), of the NK6 chromosome. The USDA110 nif gene cluster (nifDKENXSBZHQW-fixBCX) was split into two regions, S2 and S3, where ISRj1-mediated rearrangement occurred between nifS and nifB. ISs were also scattered in NK6 core regions, and ISRj1 insertion often disrupted some genes important for survival and environmental responses. These results suggest that HRS strains of soybean bradyrhizobia were subjected to IS-mediated symbiosis island shuffling and core genome degradation. PMID:25862225

  5. Toward domain-specific design environments: Some representation ideas from the telecommunications domain

    NASA Technical Reports Server (NTRS)

    Greenspan, Sol; Feblowitz, Mark

    1992-01-01

    ACME is an experimental environment for investigating new approaches to modeling and analysis of system requirements and designs. ACME is built on and extends object-oriented conceptual modeling techniques and knowledge representation and reasoning (KRR) tools. The most immediate intended use for ACME is to help represent, understand, and communicate system designs during the early stages of system planning and requirements engineering. While our research is ostensibly aimed at software systems in general, we are particularly motivated to make an impact in the telecommunications domain, especially in the area referred to as Intelligent Networks (IN's). IN systems contain the software to provide services to users of a telecommunications network (e.g., call processing services, information services, etc.) as well as the software that provides the internal infrastructure for providing the services (e.g., resource management, billing, etc.). The software includes not only systems developed by the network proprietors but also by a growing group of independent service software providers.

  6. A new principle technic for the transformation from frequency domain to time domain

    NASA Astrophysics Data System (ADS)

    Gao, Ben-Qing

    2017-03-01

    A principle technic for the transformation from frequency domain to time domain is presented. Firstly, a special type of frequency domain transcendental equation is obtained for an expected frequency domain parameter which is a rational or irrational fraction expression. Secondly, the inverse Laplace transformation is performed. When the two time-domain factors corresponding to the two frequency domain factors at two sides of frequency domain transcendental equation are known quantities, a time domain transcendental equation is reached. At last, the expected time domain parameter corresponding to the expected frequency domain parameter can be solved by the inverse convolution process. Proceeding from rational or irrational fraction expression, all solving process is provided. In the meantime, the property of time domain sequence is analyzed and the strategy for choosing the parameter values is described. Numerical examples are presented to verify the proposed theory and technic. Except for rational or irrational fraction expressions, examples of complex relative permittivity of water and plasma are used as verification method. The principle method proposed in the paper can easily solve problems which are difficult to be solved by Laplace transformation.

  7. Domain Adaptation for Alzheimer’s Disease Diagnostics

    PubMed Central

    Wachinger, Christian; Reuter, Martin

    2016-01-01

    With the increasing prevalence of Alzheimer’s disease, research focuses on the early computer-aided diagnosis of dementia with the goal to understand the disease process, determine risk and preserving factors, and explore preventive therapies. By now, large amounts of data from multi-site studies have been made available for developing, training, and evaluating automated classifiers. Yet, their translation to the clinic remains challenging, in part due to their limited generalizability across different datasets. In this work, we describe a compact classification approach that mitigates overfitting by regularizing the multinomial regression with the mixed ℓ1/ℓ2 norm. We combine volume, thickness, and anatomical shape features from MRI scans to characterize neuroanatomy for the three-class classification of Alzheimer’s disease, mild cognitive impairment and healthy controls. We demonstrate high classification accuracy via independent evaluation within the scope of the CADDementia challenge. We, furthermore, demonstrate that variations between source and target datasets can substantially influence classification accuracy. The main contribution of this work addresses this problem by proposing an approach for supervised domain adaptation based on instance weighting. Integration of this method into our classifier allows us to assess different strategies for domain adaptation. Our results demonstrate (i) that training on only the target training set yields better results than the naïve combination (union) of source and target training sets, and (ii) that domain adaptation with instance weighting yields the best classification results, especially if only a small training component of the target dataset is available. These insights imply that successful deployment of systems for computer-aided diagnostics to the clinic depends not only on accurate classifiers that avoid overfitting, but also on a dedicated domain adaptation strategy. PMID:27262241

  8. Occurrence of Cyclic di-GMP-Modulating Output Domains in Cyanobacteria: an Illuminating Perspective

    PubMed Central

    Agostoni, Marco; Koestler, Benjamin J.; Waters, Christopher M.; Williams, Barry L.; Montgomery, Beronda L.

    2013-01-01

    ABSTRACT Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical role in regulating cellular processes such as biofilm formation and cellular motility. Cyclic di-GMP signaling systems have been largely characterized in pathogenic bacteria; however, proteins that can impact the synthesis or degradation of c-di-GMP are prominent in cyanobacterial species and yet remain largely underexplored. In cyanobacteria, many putative c-di-GMP synthesis or degradation domains are found in genes that also harbor light-responsive signal input domains, suggesting that light is an important signal for altering c-di-GMP homeostasis. Indeed, c-di-GMP-associated domains are often the second most common output domain in photoreceptors—outnumbered only by a histidine kinase output domain. Cyanobacteria differ from other bacteria regarding the number and types of photoreceptor domains associated with c-di-GMP domains. Due to the widespread distribution of c-di-GMP domains in cyanobacteria, we investigated the evolutionary origin of a subset of genes. Phylogenetic analyses showed that c-di-GMP signaling systems were present early in cyanobacteria and c-di-GMP genes were both vertically and horizontally inherited during their evolution. Finally, we compared intracellular levels of c-di-GMP in two cyanobacterial species under different light qualities, confirming that light is an important factor for regulating this second messenger in vivo. PMID:23943760

  9. A Logic for Inclusion of Administrative Domains and Administrators in Multi-domain Authorization

    NASA Astrophysics Data System (ADS)

    Iranmanesh, Zeinab; Amini, Morteza; Jalili, Rasool

    Authorization policies for an administrative domain or a composition of multiple domains in multi-domain environments are determined by either one administrator or multiple administrators' cooperation. Several logic-based models for multi-domain environments' authorization have been proposed; however, they have not considered administrators and administrative domains in policies' representation. In this paper, we propose the syntax, proof theory, and semantics of a logic for multi-domain authorization policies including administrators and administrative domains. Considering administrators in policies provides the possibility of presenting composite administration having applicability in many collaborative applications. Indeed, administrators and administrative domains stated in policies can be used in authorization. The presented logic is based on modal logic and utilizes two calculi named the calculus of administrative domains and the calculus of administrators. It is also proved that the logic is sound. A case study is presented signifying the logic application in practical projects.

  10. Somatic POLE exonuclease domain mutations are early events in sporadic endometrial and colorectal carcinogenesis, determining driver mutational landscape, clonal neoantigen burden and immune response.

    PubMed

    Temko, Daniel; Van Gool, Inge C; Rayner, Emily; Glaire, Mark; Makino, Seiko; Brown, Matthew; Chegwidden, Laura; Palles, Claire; Depreeuw, Jeroen; Beggs, Andrew; Stathopoulou, Chaido; Mason, John; Baker, Ann-Marie; Williams, Marc; Cerundolo, Vincenzo; Rei, Margarida; Taylor, Jenny C; Schuh, Anna; Ahmed, Ahmed; Amant, Frédéric; Lambrechts, Diether; Smit, Vincent Thbm; Bosse, Tjalling; Graham, Trevor A; Church, David N; Tomlinson, Ian

    2018-03-31

    Genomic instability, which is a hallmark of cancer, is generally thought to occur in the middle to late stages of tumourigenesis, following the acquisition of permissive molecular aberrations such as TP53 mutation or whole genome doubling. Tumours with somatic POLE exonuclease domain mutations are notable for their extreme genomic instability (their mutation burden is among the highest in human cancer), distinct mutational signature, lymphocytic infiltrate, and excellent prognosis. To what extent these characteristics are determined by the timing of POLE mutations in oncogenesis is unknown. Here, we have shown that pathogenic POLE mutations are detectable in non-malignant precursors of endometrial and colorectal cancer. Using genome and exome sequencing, we found that multiple driver mutations in POLE-mutant cancers show the characteristic POLE mutational signature, including those in genes conventionally regarded as initiators of tumourigenesis. In POLE-mutant cancers, the proportion of monoclonal predicted neoantigens was similar to that in other cancers, but the absolute number was much greater. We also found that the prominent CD8 + T-cell infiltrate present in POLE-mutant cancers was evident in their precursor lesions. Collectively, these data indicate that somatic POLE mutations are early, quite possibly initiating, events in the endometrial and colorectal cancers in which they occur. The resulting early onset of genomic instability may account for the striking immune response and excellent prognosis of these tumours, as well as their early presentation. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  11. MOCASSIN-prot: a multi-objective clustering approach for protein similarity networks.

    PubMed

    Keel, Brittney N; Deng, Bo; Moriyama, Etsuko N

    2018-04-15

    Proteins often include multiple conserved domains. Various evolutionary events including duplication and loss of domains, domain shuffling, as well as sequence divergence contribute to generating complexities in protein structures, and consequently, in their functions. The evolutionary history of proteins is hence best modeled through networks that incorporate information both from the sequence divergence and the domain content. Here, a game-theoretic approach proposed for protein network construction is adapted into the framework of multi-objective optimization, and extended to incorporate clustering refinement procedure. The new method, MOCASSIN-prot, was applied to cluster multi-domain proteins from ten genomes. The performance of MOCASSIN-prot was compared against two protein clustering methods, Markov clustering (TRIBE-MCL) and spectral clustering (SCPS). We showed that compared to these two methods, MOCASSIN-prot, which uses both domain composition and quantitative sequence similarity information, generates fewer false positives. It achieves more functionally coherent protein clusters and better differentiates protein families. MOCASSIN-prot, implemented in Perl and Matlab, is freely available at http://bioinfolab.unl.edu/emlab/MOCASSINprot. emoriyama2@unl.edu. Supplementary data are available at Bioinformatics online.

  12. Fungal-type carbohydrate binding modules from the coccolithophore Emiliania huxleyi show binding affinity to cellulose and chitin

    PubMed Central

    Rooijakkers, Bart J. M.

    2018-01-01

    Six fungal-type cellulose binding domains were found in the genome of the coccolithophore Emiliania huxleyi and cloned and expressed in Escherichia coli. Sequence comparison indicate high similarity to fungal cellulose binding domains, raising the question of why these domains exist in coccolithophores. The proteins were tested for binding with cellulose and chitin as ligands, which resulted in the identification of two functional carbohydrate binding modules: EHUX2 and EHUX4. Compared to benchmark fungal cellulose binding domain Cel7A-CBM1 from Trichoderma reesei, these proteins showed slightly lower binding to birch and bacterial cellulose, but were more efficient chitin binders. Finally, a set of cellulose binding domains was created based on the shuffling of one well-functioning and one non-functional domain. These were characterized in order to get more information of the binding domain’s sequence–function relationship, indicating characteristic differences between the molecular basis of cellulose versus chitin recognition. As previous reports have showed the presence of cellulose in coccoliths and here we find functional cellulose binding modules, a possible connection is discussed. PMID:29782536

  13. Inspecting School Social Quality: Assessing and Improving School Effectiveness in the Social Domain

    ERIC Educational Resources Information Center

    Dijkstra, Anne Bert; Daas, Remmert; De la Motte, Per Ingvar; Ehren, Melanie

    2017-01-01

    Purpose: School inspection of school social quality is, in contrast to inspection in the cognitive domain, still in its early phase of development. While schools are shown to affect social outcomes, the interplay of mechanisms makes it difficult to isolate the effect of the school. This paper aims to evaluate different approaches to inspecting…

  14. Reconstituting protein interaction networks using parameter-dependent domain-domain interactions

    PubMed Central

    2013-01-01

    Background We can describe protein-protein interactions (PPIs) as sets of distinct domain-domain interactions (DDIs) that mediate the physical interactions between proteins. Experimental data confirm that DDIs are more consistent than their corresponding PPIs, lending support to the notion that analyses of DDIs may improve our understanding of PPIs and lead to further insights into cellular function, disease, and evolution. However, currently available experimental DDI data cover only a small fraction of all existing PPIs and, in the absence of structural data, determining which particular DDI mediates any given PPI is a challenge. Results We present two contributions to the field of domain interaction analysis. First, we introduce a novel computational strategy to merge domain annotation data from multiple databases. We show that when we merged yeast domain annotations from six annotation databases we increased the average number of domains per protein from 1.05 to 2.44, bringing it closer to the estimated average value of 3. Second, we introduce a novel computational method, parameter-dependent DDI selection (PADDS), which, given a set of PPIs, extracts a small set of domain pairs that can reconstruct the original set of protein interactions, while attempting to minimize false positives. Based on a set of PPIs from multiple organisms, our method extracted 27% more experimentally detected DDIs than existing computational approaches. Conclusions We have provided a method to merge domain annotation data from multiple sources, ensuring large and consistent domain annotation for any given organism. Moreover, we provided a method to extract a small set of DDIs from the underlying set of PPIs and we showed that, in contrast to existing approaches, our method was not biased towards DDIs with low or high occurrence counts. Finally, we used these two methods to highlight the influence of the underlying annotation density on the characteristics of extracted DDIs. Although

  15. Attitudes of young african american fathers toward early childbearing.

    PubMed

    Davies, Susan L; Dix, Emily S; Rhodes, Scott D; Harrington, Kathleen F; Frison, Sonja; Willis, Leigh

    2004-01-01

    To qualitatively examine the perceptions of young fathers toward issues related to early childbearing. Focus groups were held with male partners of adolescent females who had become pregnant while participating in an HIV-prevention trial. Primary domains that emerged included young male's desire for pregnancy, their attitudes toward father/child involvement, and their perceived social support as young fathers. Findings may help in developing gender-appropriate interventions to delay early childbearing and prevent HIV/STD transmission.

  16. Hybridisations of Variable Neighbourhood Search and Modified Simplex Elements to Harmony Search and Shuffled Frog Leaping Algorithms for Process Optimisations

    NASA Astrophysics Data System (ADS)

    Aungkulanon, P.; Luangpaiboon, P.

    2010-10-01

    Nowadays, the engineering problem systems are large and complicated. An effective finite sequence of instructions for solving these problems can be categorised into optimisation and meta-heuristic algorithms. Though the best decision variable levels from some sets of available alternatives cannot be done, meta-heuristics is an alternative for experience-based techniques that rapidly help in problem solving, learning and discovery in the hope of obtaining a more efficient or more robust procedure. All meta-heuristics provide auxiliary procedures in terms of their own tooled box functions. It has been shown that the effectiveness of all meta-heuristics depends almost exclusively on these auxiliary functions. In fact, the auxiliary procedure from one can be implemented into other meta-heuristics. Well-known meta-heuristics of harmony search (HSA) and shuffled frog-leaping algorithms (SFLA) are compared with their hybridisations. HSA is used to produce a near optimal solution under a consideration of the perfect state of harmony of the improvisation process of musicians. A meta-heuristic of the SFLA, based on a population, is a cooperative search metaphor inspired by natural memetics. It includes elements of local search and global information exchange. This study presents solution procedures via constrained and unconstrained problems with different natures of single and multi peak surfaces including a curved ridge surface. Both meta-heuristics are modified via variable neighbourhood search method (VNSM) philosophy including a modified simplex method (MSM). The basic idea is the change of neighbourhoods during searching for a better solution. The hybridisations proceed by a descent method to a local minimum exploring then, systematically or at random, increasingly distant neighbourhoods of this local solution. The results show that the variant of HSA with VNSM and MSM seems to be better in terms of the mean and variance of design points and yields.

  17. Diagnostic capability of spectral-domain optical coherence tomography for glaucoma.

    PubMed

    Wu, Huijuan; de Boer, Johannes F; Chen, Teresa C

    2012-05-01

    To determine the diagnostic capability of spectral-domain optical coherence tomography in glaucoma patients with visual field defects. Prospective, cross-sectional study. Participants were recruited from a university hospital clinic. One eye of 85 normal subjects and 61 glaucoma patients with average visual field mean deviation of -9.61 ± 8.76 dB was selected randomly for the study. A subgroup of the glaucoma patients with early visual field defects was calculated separately. Spectralis optical coherence tomography (Heidelberg Engineering, Inc) circular scans were performed to obtain peripapillary retinal nerve fiber layer (RNFL) thicknesses. The RNFL diagnostic parameters based on the normative database were used alone or in combination for identifying glaucomatous RNFL thinning. To evaluate diagnostic performance, calculations included areas under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. Overall RNFL thickness had the highest area under the receiver operating characteristic curve values: 0.952 for all patients and 0.895 for the early glaucoma subgroup. For all patients, the highest sensitivity (98.4%; 95% confidence interval, 96.3% to 100%) was achieved by using 2 criteria: ≥ 1 RNFL sectors being abnormal at the < 5% level and overall classification of borderline or outside normal limits, with specificities of 88.9% (95% confidence interval, 84.0% to 94.0%) and 87.1% (95% confidence interval, 81.6% to 92.5%), respectively, for these 2 criteria. Statistical parameters for evaluating the diagnostic performance of the Spectralis spectral-domain optical coherence tomography were good for early perimetric glaucoma and were excellent for moderately advanced perimetric glaucoma. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Fairness influences early signatures of reward-related neural processing.

    PubMed

    Massi, Bart; Luhmann, Christian C

    2015-12-01

    Many humans exhibit a strong preference for fairness during decision-making. Although there is evidence that social factors influence reward-related and affective neural processing, it is unclear if this effect is mediated by compulsory outcome evaluation processes or results from slower deliberate cognition. Here we show that the feedback-related negativity (FRN) and late positive potential (LPP), two signatures of early hedonic processing, are modulated by the fairness of rewards during a passive rating task. We find that unfair payouts elicit larger FRNs than fair payouts, whereas fair payouts elicit larger LPPs than unfair payouts. This is true both in the time-domain, where the FRN and LPP are related, and in the time-frequency domain, where the two signals are largely independent. Ultimately, this work demonstrates that fairness affects the early stages of reward and affective processing, suggesting a common biological mechanism for social and personal reward evaluation.

  19. Early Terrestrial Mantle Differentiation Recorded in Paleoarchean Komatiites

    NASA Astrophysics Data System (ADS)

    Puchtel, I. S.; Blichert-Toft, J.; Touboul, M.; Horan, M. F.; Walker, R. J.

    2016-12-01

    Geochmical signatures generated in the manle as a result of radioactive decay of short- and long-lived nuclides can be used to constrain the timing of formation and the nature of now mostly vanished early terrestrial reservoirs. The 3.55 Ga komatiites from the Schapenburg Greenstone Remnant (SGR) located in the Barberton Greenstone Belt in South Africa have a unique combination of trace element abundances and isotopic compositions that place strong constraints on the origin of these reservoirs. The SGR komatiites define a Re-Os isochron with an age of 3550±87 Ma and an initial γ187Os = +3.7±0.2 (2SD). The absolute HSE abundances in the mantle source of the SGR komatiite system are estimated to be only 29±5% of those in the present-day bulk silicate Earth (BSE) estimates. The SGR komatiites show coupled depletion, relative to the modern mantle, in 142Nd and 182W (μ142Nd = -5.0±2.8, μ182W = -8.4±4.5), the decay products of the short-lived 146Sm and 182Hf nuclides, respectively, indicating derivation from a mantle domain that was enriched in incompatible elements 30 Ma after Solar System formation. Early Hadean contributors to this mantle domain could include high-pressure fractionates from a primordial magma ocean. By contrast, the long-lived Sm-Nd and Lu-Hf isotope systems (ɛ143Nd = +2.4±0.1, ɛ176Hf = +5.7±0.3) indicate that the mantle domain that the SGR komatiites were ultimately derived from underwent additional processing after the early Hadean, including melt depletion at lower pressures. The preservation of early-formed 182W and 142Nd anomalies in the mantle until at least 3.55 Ga indicates that the products of early planetary differentiation survived both later planetary accretion and convective mantle mixing during the Hadean. This study lends further support to the notion that variable late accretion, by itself, cannot account for all of the observed W isotope and absolute and relative HSE abundance variations in the Archean mantle recorded by

  20. Structure and electrostatic property of cytoplasmic domain of ZntB transporter

    PubMed Central

    Tan, Kemin; Sather, Alicia; Robertson, Janice L; Moy, Shiu; Roux, Benoît; Joachimiak, Andrzej

    2009-01-01

    ZntB is the distant homolog of CorA Mg2+ transporter within the metal ion transporter superfamily. It was early reported that the ZntB from Salmonella typhimurium facilitated efflux of Zn2+ and Cd2+, but not Mg2+. Here, we report the 1.90 Å crystal structure of the intracellular domain of ZntB from Vibrio parahemolyticus. The domain forms a funnel-shaped homopentamer that is similar to the full-length CorA from Thermatoga maritima, but differs from two previously reported dimeric structures of truncated CorA intracellular domains. However, no Zn2+ or Cd2+ binding sites were identified in the high-resolution structure. Instead, 25 well-defined Cl− ions were observed and some of these binding sites are highly conserved within the ZntB family. Continuum electrostatics calculations suggest that the central pore of the funnel is highly attractive for cations, especially divalents. The presence of the bound Cl− ions increases the stability of cations along the pore suggesting they could be important in enhancing cation transport. PMID:19653298

  1. Automating gene library synthesis by structure-based combinatorial protein engineering: examples from plant sesquiterpene synthases.

    PubMed

    Dokarry, Melissa; Laurendon, Caroline; O'Maille, Paul E

    2012-01-01

    Structure-based combinatorial protein engineering (SCOPE) is a homology-independent recombination method to create multiple crossover gene libraries by assembling defined combinations of structural elements ranging from single mutations to domains of protein structure. SCOPE was originally inspired by DNA shuffling, which mimics recombination during meiosis, where mutations from parental genes are "shuffled" to create novel combinations in the resulting progeny. DNA shuffling utilizes sequence identity between parental genes to mediate template-switching events (the annealing and extension of one parental gene fragment on another) in PCR reassembly reactions to generate crossovers and hence recombination between parental genes. In light of the conservation of protein structure and degeneracy of sequence, SCOPE was developed to enable the "shuffling" of distantly related genes with no requirement for sequence identity. The central principle involves the use of oligonucleotides to encode for crossover regions to choreograph template-switching events during PCR assembly of gene fragments to create chimeric genes. This approach was initially developed to create libraries of hybrid DNA polymerases from distantly related parents, and later developed to create a combinatorial mutant library of sesquiterpene synthases to explore the catalytic landscapes underlying the functional divergence of related enzymes. This chapter presents a simplified protocol of SCOPE that can be integrated with different mutagenesis techniques and is suitable for automation by liquid-handling robots. Two examples are presented to illustrate the application of SCOPE to create gene libraries using plant sesquiterpene synthases as the model system. In the first example, we outline how to create an active-site library as a series of complex mixtures of diverse mutants. In the second example, we outline how to create a focused library as an array of individual clones to distil minimal combinations of

  2. Early career professional development issues for military academic psychiatrists.

    PubMed

    Warner, Christopher H; Bobo, William V; Flynn, Julianne

    2005-01-01

    Academically motivated graduates of military psychiatric residency programs confront serious challenges. In this article, the authors present a junior faculty development model organized around four overlapping domains: mentorship, scholarship, research, and career planning/development. Using these four domains as a platform for discussion, the authors focus on challenges facing academically oriented early-career military psychiatrists and provide guidance. The authors believe that a proactive stance, skillful mentoring, self-awareness through conscious planning and effort, ability to capitalize on existing opportunities for growth, and attention to detail are all vital to the junior military psychiatrist.

  3. Assembly of oligomeric death domain complexes during Toll receptor signaling.

    PubMed

    Moncrieffe, Martin C; Grossmann, J Günter; Gay, Nicholas J

    2008-11-28

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling.

  4. Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

    PubMed Central

    Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

    2008-01-01

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling. PMID:18829464

  5. Early Indications of Delayed Cognitive Development in Preschool Children Born Very Preterm: Evidence from Domain-General and Domain-Specific Tasks

    ERIC Educational Resources Information Center

    Pitchford, Nicola; Johnson, Samantha; Scerif, Gaia; Marlow, Neil

    2011-01-01

    Cognitive impairment often follows preterm birth but its early underlying nature is not well understood. We used a novel approach by investigating the development of colour cognition in 54 very preterm children born less than or equal to 30 weeks gestational age without severe neurosensory impairment and 37 age-matched term-born controls, aged 2-5…

  6. Cancer-specific self-efficacy and psychosocial and functional adaptation to early stage breast cancer.

    PubMed

    Manne, Sharon L; Ostroff, Jamie S; Norton, Tina R; Fox, Kevin; Grana, Generosa; Goldstein, Lori

    2006-04-01

    Although self-efficacy is considered a key psychological resource in adapting to chronic physical illness, this construct has received less attention among individuals coping with cancer. To examine changes in cancer self-efficacy over time among women with early stage breast cancer and associations between task-specific domains of self-efficacy and specific psychological, relationship, and functional outcomes. Ninety-five women diagnosed with early stage breast cancer completed surveys postsurgery and 1 year later. Cancer-related self-efficacy was relatively stable over 1 year, with only 2 domains of efficacy-(a) Activity Management and (b) Self-Satisfaction-evidencing significant increases over the 1-year time period. Cross-sectional findings were relatively consistent with predictions and suggested that specific domains of self-efficacy were more strongly related to relevant domains of adaptation. Longitudinal findings were not as consistent with the domain-specificity hypothesis but did suggest several predictive associations between self-efficacy and outcomes. Personal Management self-efficacy was associated with higher relationship satisfaction, higher Communication Self-Efficacy was associated with less functional impairment, and higher Affective Management self-efficacy was associated with higher self-esteem 1 year later. Specific domains of cancer-related self-efficacy are most closely related to relevant areas of adaptation when considered cross-sectionally, but further study is needed to clarify the nature of these relationships over time.

  7. Internationalized Domain Names.

    ERIC Educational Resources Information Center

    Wielansky, Marc D.

    2002-01-01

    Reports on an investigation of what may appear at first to be an arcane topic--the internationalization of domain names on the Internet. Concludes that expanding domain names internationally poses challenges to the inherent open structure of the Internet; to its ease of use for those accustomed to Latin-alphabet-only domain names; and to corporate…

  8. Comparison of frequency-domain and time-domain rotorcraft vibration control methods

    NASA Technical Reports Server (NTRS)

    Gupta, N. K.

    1984-01-01

    Active control of rotor-induced vibration in rotorcraft has received significant attention recently. Two classes of techniques have been proposed. The more developed approach works with harmonic analysis of measured time histories and is called the frequency-domain approach. The more recent approach computes the control input directly using the measured time history data and is called the time-domain approach. The report summarizes the results of a theoretical investigation to compare the two approaches. Five specific areas were addressed: (1) techniques to derive models needed for control design (system identification methods), (2) robustness with respect to errors, (3) transient response, (4) susceptibility to noise, and (5) implementation difficulties. The system identification methods are more difficult for the time-domain models. The time-domain approach is more robust (e.g., has higher gain and phase margins) than the frequency-domain approach. It might thus be possible to avoid doing real-time system identification in the time-domain approach by storing models at a number of flight conditions. The most significant error source is the variation in open-loop vibrations caused by pilot inputs, maneuvers or gusts. The implementation requirements are similar except that the time-domain approach can be much simpler to implement if real-time system identification were not necessary.

  9. Age-Related Differences in Longitudinal Structural Change by Spectral-Domain Optical Coherence Tomography in Early Experimental Glaucoma

    PubMed Central

    Yang, Hongli; He, Lin; Gardiner, Stuart K.; Reynaud, Juan; Williams, Galen; Hardin, Christy; Strouthidis, Nicholas G.; Downs, J. Crawford; Fortune, Brad; Burgoyne, Claude F.

    2014-01-01

    Purpose. To characterize age-related differences in the magnitude of spectral-domain optical coherence tomography (SD-OCT) structural change in early experimental glaucoma (EG). Methods. Both eyes from four young (1.4–2.6 years) and four old (18.6–21.9 years) rhesus monkeys were imaged at least three times at baseline, and then every 2 weeks after laser-induced, chronic, unilateral IOP elevation until the onset of EG (confocal scanning laser tomographic surface change confirmed twice). Two to 20 weeks after EG onset, animals were euthanized and optic nerve axon counts for all eyes were performed. Masked operators delineated retinal and ONH landmarks in 40 radial B-scans from each eye and imaging session to quantify change from baseline in five SD-OCT neural and connective tissue parameters. The effects of EG, age, and EG × age interactions on the magnitude, rate (magnitude per postlaser time), and IOP responsiveness (magnitude per cumulative IOP insult) of postlaser parameter change were individually assessed using general estimating equation models. Results. Presac SD-OCT RNFLT and minimum rim width change and postmortem axon loss was not significantly different in old compared with young EG eyes. The rate of change and IOP responsiveness of the parameters anterior lamina cribrosa surface depth relative to Bruch's membrane opening (BMO) and BMO depth relative to peripheral Bruch's membrane were significantly lower (P < 0.05) in the old compared with the young EG eyes. Conclusions. At similar postlaser times, levels of cumulative IOP insult and axonal damage, SD-OCT–detected ONH connective tissue structural change is greater in young compared with old monkey EG eyes. PMID:25190652

  10. Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry.

    PubMed

    Rhein, Bethany A; Brouillette, Rachel B; Schaack, Grace A; Chiorini, John A; Maury, Wendy

    2016-07-01

    , including EBOV. TIM family member TIM-4 is expressed on macrophages and dendritic cells, which are early cellular targets during EBOV infection. Here, we performed a mutagenesis screening of the IgV domain of murine and human TIM-4 to identify residues that are critical for EBOV entry. Surprisingly, we identified more human than murine TIM-4 IgV domain residues that are required for EBOV entry. Defining the TIM IgV residues needed for EBOV entry clarifies the virus-receptor interactions and paves the way for the development of novel therapeutics targeting virus binding to this cell surface receptor. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry

    PubMed Central

    Rhein, Bethany A.; Brouillette, Rachel B.; Schaack, Grace A.; Chiorini, John A.

    2016-01-01

    enveloped viruses, including EBOV. TIM family member TIM-4 is expressed on macrophages and dendritic cells, which are early cellular targets during EBOV infection. Here, we performed a mutagenesis screening of the IgV domain of murine and human TIM-4 to identify residues that are critical for EBOV entry. Surprisingly, we identified more human than murine TIM-4 IgV domain residues that are required for EBOV entry. Defining the TIM IgV residues needed for EBOV entry clarifies the virus-receptor interactions and paves the way for the development of novel therapeutics targeting virus binding to this cell surface receptor. PMID:27122575

  12. Early-onset lymphoma and extensive embryonic apoptosis in two domain-specific Fen1 mice mutants.

    PubMed

    Larsen, Elisabeth; Kleppa, Liv; Meza, Trine J; Meza-Zepeda, Leonardo A; Rada, Christina; Castellanos, Cesilie G; Lien, Guro F; Nesse, Gaute J; Neuberger, Michael S; Laerdahl, Jon K; William Doughty, Richard; Klungland, Arne

    2008-06-15

    Flap endonuclease 1 (FEN1) processes Okazaki fragments in lagging strand DNA synthesis, and FEN1 is involved in several DNA repair pathways. The interaction of FEN1 with the proliferating cell nuclear antigen (PCNA) processivity factor is central to the function of FEN1 in both DNA replication and repair. Here we present two gene-targeted mice with mutations in FEN1. The first mutant mouse carries a single amino acid point mutation in the active site of the nuclease domain of FEN1 (Fen1(E160D/E160D)), and the second mutant mouse contains two amino acid substitutions in the highly conserved PCNA interaction domain of FEN1 (Fen1(DeltaPCNA/DeltaPCNA)). Fen1(E160D/E160D) mice develop a considerably elevated incidence of B-cell lymphomas beginning at 6 months of age, particularly in females. By 16 months of age, more than 90% of the Fen1(E160D/E160D) females have tumors, primarily lymphomas. By contrast, Fen1(DeltaPCNA/DeltaPCNA) mouse embryos show extensive apoptosis in the forebrain and vertebrae area and die around stage E9.5 to E11.5.

  13. Nowa, a novel protein with minicollagen Cys-rich domains, is involved in nematocyst formation in Hydra.

    PubMed

    Engel, Ulrike; Ozbek, Suat; Streitwolf-Engel, Ruth; Petri, Barbara; Lottspeich, Friedrich; Holstein, Thomas W; Oezbek, Suat; Engel, Ruth

    2002-10-15

    The novel protein Nowa was identified in nematocysts, explosive organelles of Hydra, jellyfish, corals and other CNIDARIA: Biogenesis of these organelles is complex and involves assembly of proteins inside a post-Golgi vesicle to form a double-layered capsule with a long tubule. Nowa is the major component of the outer wall, which is formed very early in morphogenesis. The high molecular weight glycoprotein has a modular structure with an N-terminal sperm coating glycoprotein domain, a central C-type lectin-like domain, and an eightfold repeated cysteine-rich domain at the C-terminus. Interestingly, the cysteine-rich domains are homologous to the cysteine-rich domains of minicollagens. We have previously shown that the cysteines of these minicollagen cysteine-rich domains undergo an isomerization process from intra- to intermolecular disulfide bonds, which mediates the crosslinking of minicollagens to networks in the inner wall of the capsule. The minicollagen cysteine-rich domains present in both proteins provide a potential link between Nowa in the outer wall and minicollagens in the inner wall. We propose a model for nematocyst formation that integrates cytoskeleton rearrangements around the post-Golgi vesicle and protein assembly inside the vesicle to generate a complex structure that is stabilized by intermolecular disulfide bonds.

  14. Analyzing Teacher Narratives in Early Childhood Garden-Based Education

    ERIC Educational Resources Information Center

    Murakami, Christopher Daniel; Su-Russell, Chang; Manfra, Louis

    2018-01-01

    Learning gardens can provide dynamic learning and developmental experiences for young children. This case study of 12 early childhood teachers explores how teachers describe (1) learning across numerous school readiness domains and (2) how to support this learning by promoting opportunities for autonomy, relatedness, and competence. Participants…

  15. Housing First: exploring participants' early support needs.

    PubMed

    Stergiopoulos, Vicky; Gozdzik, Agnes; O'Campo, Patricia; Holtby, Alixandra R; Jeyaratnam, Jeyagobi; Tsemberis, Sam

    2014-04-13

    Housing First has become a popular treatment model for homeless adults with mental illness, yet little is known about program participants' early experiences or trajectories. This study used a mixed methods design to examine participant changes in selected domains 6 months after enrollment in a Canadian field trial of Housing First. The study sample included 301 participants receiving the Housing First intervention at the Toronto site of the At Home/Chez Soi project. This study used a pre-post design to compare quantitative 6-month outcome data to baseline values in key domains and multivariate regression to identify baseline demographic, clinical or service use variables associated with observed changes in these domains. In addition, qualitative data exploring participant and service provider perspectives and experiences was collected via stakeholder interviews and focus groups, and analyzed using thematic analysis. The majority (60 to 72%) of participants followed the expected trajectory of improvement, with the remaining experiencing difficulties in community integration, mental health symptom severity, substance use, community functioning and quality of life 6 months after program enrollment. Diagnosis of psychotic disorder was associated with a reduction in quality of life from baseline to 6-months, while substance use disorders were associated with reduced mental illness symptoms and substance use related problems and an improvement in quality of life. Participants housed in independent housing at 6-months had greater improvements in community integration and quality of life, and greater reduction in mental illness symptoms, compared to those not independently housed. The quality of the working alliance was positively associated with improvements in physical and psychological community integration and quality of life. Qualitative data provided a unique window into the loneliness and isolation experienced by Housing First participants, as well as problems

  16. Housing First: exploring participants’ early support needs

    PubMed Central

    2014-01-01

    Background Housing First has become a popular treatment model for homeless adults with mental illness, yet little is known about program participants’ early experiences or trajectories. This study used a mixed methods design to examine participant changes in selected domains 6 months after enrolment in a Canadian field trial of Housing First. Methods The study sample included 301 participants receiving the Housing First intervention at the Toronto site of the At Home/Chez Soi project. This study used a pre-post design to compare quantitative 6-month outcome data to baseline values in key domains and multivariate regression to identify baseline demographic, clinical or service use variables associated with observed changes in these domains. In addition, qualitative data exploring participant and service provider perspectives and experiences was collected via stakeholder interviews and focus groups, and analyzed using thematic analysis. Results The majority (60 to 72%) of participants followed the expected trajectory of improvement, with the remaining experiencing difficulties in community integration, mental health symptom severity, substance use, community functioning and quality of life 6 months after program enrolment. Diagnosis of psychotic disorder was associated with a reduction in quality of life from baseline to 6-months, while substance use disorders were associated with reduced mental illness symptoms and substance use related problems and an improvement in quality of life. Participants housed in independent housing at 6-months had greater improvements in community integration and quality of life, and greater reduction in mental illness symptoms, compared to those not independently housed. The quality of the working alliance was positively associated with improvements in physical and psychological community integration and quality of life. Qualitative data provided a unique window into the loneliness and isolation experienced by Housing First

  17. Initiation of continental accretion in the Betic-Rif domain

    NASA Astrophysics Data System (ADS)

    Maxime, Daudet; Frederic, Mouthereau; Stéphanie, Brichau; Ana, Crespo-Blanc; Arnaud, Vacherat

    2017-04-01

    The Betic - Rif cordillera in southern Spain and northern Morocco, respectively, form one of the tightest orogenic arc on Earth. The formation of this arcuate orogenic belt resulted from the westward migration of the Alboran crustal domain, constituted by the internal zone of the orogeny and the basement of the Alboran back-arc basin, that collided with the rifted margins of Iberia and Africa at least since the early Miocene. This collision is intimately linked to the post-35-30Ma regional slab roll-back and back-arc extension in the western Mediterranean region. The geodynamics of the Betic-Rif domain, which is of great importance for the paleogeographic reconstructions of the Tethys-Altantic and the Mediterranean sea, is still largely debated. Answers will come from a more detailed structural analyses, including refinement of the time-temperature paths and kinematics of the main structural units, which is one of the main objectives of the OROGEN research project, co-financed by BRGM, TOTAL & CNRS. In this study, we focus on the well-developed flysch-type sediments now accreted in the Betics-Rif but initially deposited in a basin, north of the african margin and on the iberian margin from the Early Cretaceous to the Early Miocene. Using low-temperature thermochronology (fission-track and (U-Th)/He analyses) combined with zircon U-Pb geochronology on the flyschs deposited on the most distal part of the margin, we aim to constrain the thermal history of both the source rocks and accreted thrust sheets at the earliest stages of continental accretion. Sample have been collected in flyschs series ranging from Mesozoic, Paleogene to Neogene ages. Additional samples have been collected in the Rif where Cretaceous series are more developed. Combined with a detailed structural analysis, LT thermochronological constraints will refine the kinematics of thrust units when continental accretion started before the final thrust emplacement occurred in the Early Miocene

  18. A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway

    PubMed Central

    Erdmann, Kai S.; Mao, Yuxin; McCrea, Heather J.; Zoncu, Roberto; Lee, Sangyoon; Paradise, Summer; Modregger, Jan; Biemesderfer, Daniel; Toomre, Derek; De Camilli, Pietro

    2007-01-01

    Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome, whose manifestations include mental retardation and renal Fanconi syndrome. OCRL has been implicated in membrane traffic, but disease mechanisms remain unclear. We show that OCRL visits late stage endocytic clathrin coated pits and binds the Rab5 effector APPL1 on peripheral early endosomes. The interaction with APPL1, which is mediated by the ASH-RhoGAP-like domains of OCRL and is abolished by disease mutations, provides a link to protein networks implicated in the reabsorptive function of kidney and in traffic and signaling of growth factor receptors in brain. Crystallographic studies reveal a role of the ASH-RhoGAP-like domains in positioning the phosphatase domain at the membrane interface and a clathrin box protruding from the RhoGAP-like domain. Our results support a role of OCRL in the early endocytic pathway consistent with the predominant localization of its preferred substrates, PI(4,5)P2 and PI(3,4,5)P3, at the cell surface. PMID:17765681

  19. Gratitude From Early Adulthood to Old Age.

    PubMed

    Allemand, Mathias; Hill, Patrick L

    2016-02-01

    Are there age differences in gratitude from early adulthood to old age? The current studies tested several ways by which an association between age and dispositional gratitude may present, by considering multiple measures on both fronts. We used data from three cross-sectional studies (total N = 1,736; total age range: 19-94). The results indicated that (a) age effects in gratitude are more likely to occur for subjective age in terms of future time perspective (i.e., people's perceptions of their remaining opportunities and time) than chronological age; (b) chronological age effects are more domain specific than general in nature; and (c) they are more likely to occur for the instrumental domain as compared to the interpersonal domain. Finally, the results indicated that (d) perceived future time, particularly with respect to remaining opportunities, mediates the relation between chronological age and general gratitude. Overall, the findings suggest that gratitude is subject to a variety of developmental influences across adulthood. © 2014 Wiley Periodicals, Inc.

  20. Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling.

    PubMed

    Mas, Caroline; Norwood, Suzanne J; Bugarcic, Andrea; Kinna, Genevieve; Leneva, Natalya; Kovtun, Oleksiy; Ghai, Rajesh; Ona Yanez, Lorena E; Davis, Jasmine L; Teasdale, Rohan D; Collins, Brett M

    2014-10-10

    Sorting nexins (SNXs) or phox homology (PX) domain containing proteins are central regulators of cell trafficking and signaling. A subfamily of PX domain proteins possesses two unique PX-associated domains, as well as a regulator of G protein-coupled receptor signaling (RGS) domain that attenuates Gαs-coupled G protein-coupled receptor signaling. Here we delineate the structural organization of these RGS-PX proteins, revealing a protein family with a modular architecture that is conserved in all eukaryotes. The one exception to this is mammalian SNX19, which lacks the typical RGS structure but preserves all other domains. The PX domain is a sensor of membrane phosphoinositide lipids and we find that specific sequence alterations in the PX domains of the mammalian RGS-PX proteins, SNX13, SNX14, SNX19, and SNX25, confer differential phosphoinositide binding preferences. Although SNX13 and SNX19 PX domains bind the early endosomal lipid phosphatidylinositol 3-phosphate, SNX14 shows no membrane binding at all. Crystal structures of the SNX19 and SNX14 PX domains reveal key differences, with alterations in SNX14 leading to closure of the binding pocket to prevent phosphoinositide association. Our findings suggest a role for alternative membrane interactions in spatial control of RGS-PX proteins in cell signaling and trafficking. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers

    PubMed Central

    Finnerty, John R; Mazza, Maureen E; Jezewski, Peter A

    2009-01-01

    Background Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs. Results Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades. The sister-group relationship between MSX1 and MSX2 reflects their derivation from the 4p/5q chromosomal paralogon, a derivative of the original "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox genes (Hmx, NK1, Emx) in a cnidarian. Seven conserved domains, including two Groucho repression domains (N- and C-terminal), were present in the ancestral Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1, the N-terminal Groucho domain is conserved, while the C-terminal domain diverged substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C-terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or orofacial clefting disorders map to conserved domains in a non-random fashion. Conclusion Msx originated from a MetaHox ancestor that also gave rise to Tlx, Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or loss of domains played a central role in the functional evolution of Msx. Duplicated domains allow pleiotropically expressed proteins to evolve new functions without disrupting existing interaction networks. Human missense sequence variants reside within evolutionarily conserved domains, likely disrupting protein function. This phylogenomic evaluation of candidate disease markers will inform clinical and functional studies. PMID:19154605

  2. Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers.

    PubMed

    Finnerty, John R; Mazza, Maureen E; Jezewski, Peter A

    2009-01-20

    Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs. Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades. The sister-group relationship between MSX1 and MSX2 reflects their derivation from the 4p/5q chromosomal paralogon, a derivative of the original "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox genes (Hmx, NK1, Emx) in a cnidarian. Seven conserved domains, including two Groucho repression domains (N- and C-terminal), were present in the ancestral Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1, the N-terminal Groucho domain is conserved, while the C-terminal domain diverged substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C-terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or orofacial clefting disorders map to conserved domains in a non-random fashion. Msx originated from a MetaHox ancestor that also gave rise to Tlx, Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or loss of domains played a central role in the functional evolution of Msx. Duplicated domains allow pleiotropically expressed proteins to evolve new functions without disrupting existing interaction networks. Human missense sequence variants reside within evolutionarily conserved domains, likely disrupting protein function. This phylogenomic evaluation of candidate disease markers will inform clinical and functional studies.

  3. Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics

    NASA Astrophysics Data System (ADS)

    Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.

    2018-01-01

    The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

  4. Early Parental Adjustment and Bereavement after Childhood Cancer Death

    ERIC Educational Resources Information Center

    Barrera, Maru; O'connor, Kathleen; D'Agostino, Norma Mammone; Spencer, Lynlee; Nicholas, David; Jovcevska, Vesna; Tallet, Susan; Schneiderman, Gerald

    2009-01-01

    This study comprehensively explored parental bereavement and adjustment at 6 months post-loss due to childhood cancer. Interviews were conducted with 18 mothers and 13 fathers. Interviews were transcribed verbatim and analyzed based on qualitative methodology. A model describing early parental bereavement and adaptation emerged with 3 domains:…

  5. Attitudes of Young African American Fathers Toward Early Childbearing

    ERIC Educational Resources Information Center

    Davies, Susan L.; Dix, Emily S.; Rhodes, Scott D.; Harrington, Kathleen F.; Frison, Sonja; Willis, Leigh

    2004-01-01

    Objective : To qualitatively examine the perceptions of young fathers toward issues related to early childbearing. Methods : Focus groups were held with male partners of adolescent females who had become pregnant while participating in an HIV-prevention trial. Results : Primary domains that emerged included young male's desire for pregnancy, their…

  6. MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

    PubMed

    Shelby, Shameka J; Colwill, Karen; Dhe-Paganon, Sirano; Pawson, Tony; Thompson, Debra A

    2013-01-01

    The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE). A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999)), purified and phosphorylated. Ni(2+)-NTA pull downs were performed using 6xHis-rMERTK(571-999) in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999) and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α), VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS), siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

  7. The Role of Deliberate Practice and Play in Career Progression in Sport: The Early Engagement Hypothesis

    ERIC Educational Resources Information Center

    Ford, Paul R.; Ward, Paul; Hodges, Nicola J.; Williams, A. Mark

    2009-01-01

    Experts acquire domain-specific skills as a result of the activities in which they participate throughout their development. We examine the domain-specific activities in which two groups of elite youth soccer players participated between six and 12 years of age. Our goal was to examine early participation differences between those who progressed…

  8. Domain-Generality versus Domain-Specificity: The Life and Impending Death of a False Dichotomy.

    ERIC Educational Resources Information Center

    Sternberg, Robert J.

    1989-01-01

    Argues that the question of whether information representation and processing are domain-general or domain-specific is neither meaningful nor answerable. Researchers should be asking questions about ways in which representation and processing are domain-general and ways in which they are domain-specific. (RH)

  9. Replication domains are self-interacting structural chromatin units of human chromosomes

    NASA Astrophysics Data System (ADS)

    Arneodo, Alain

    2011-03-01

    In higher eukaryotes, the absence of specific sequence motifs marking the origins of replication has been a serious hindrance to the understanding of the mechanisms that regulate the initiation and the maintenance of the replication program in different cell types. In silico analysis of nucleotide compositional skew has predicted the existence, in the germline, of replication N-domains bordered by putative replication origins and where the skew decreases rather linearly as the signature of a progressive inversion of the average fork polarity. Here, from the demonstration that the average fork polarity can be directly extracted from the derivative of replication timing profiles, we develop a wavelet-based pattern recognition methodology to delineate replication U-domains where the replication timing profile is shaped as a U and its derivative as a N. Replication U-domains are robustly found in seven cell lines as covering a significant portion (40-50%) of the human genome where the replication timing data actually displays some plasticity between cell lines. The early replication initiation zones at U-domains borders are found to be hypersensitive to DNase I cleavage, to be associated with transcriptional activity and to present a significant enrichment in insular-binding proteins CTCF, the hallmark of an open chromatin structure. A comparative analysis of genome-wide chromatin interaction (HiC) data shows that replication-U domains correspond to self-interacting structural high order chromatin units of megabase characteristic size. Taken together, these findings provide evidence that the epigenetic compartmentalization of the human genome into autonomous replication U-domains comes along with an extensive remodelling of the threedimensional chromosome architecture during development or in specific diseases. The observed cell specific conservation of the replication timing between the human and mouse genomes strongly suggests that this chromosome organization into

  10. Between-domain relations of students' academic emotions and their judgments of school domain similarity

    PubMed Central

    Goetz, Thomas; Haag, Ludwig; Lipnevich, Anastasiya A.; Keller, Melanie M.; Frenzel, Anne C.; Collier, Antonie P. M.

    2014-01-01

    With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual) emotions reflected students' judgments of domain similarities, whereas between-domain relations of state (i.e., momentary) emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals' beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics of academic domains from students' perspective. In Study 2 (N = 1709; 8th and 11th graders) the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English) using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders) by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed. PMID:25374547

  11. Inference of domain-disease associations from domain-protein, protein-disease and disease-disease relationships.

    PubMed

    Zhang, Wangshu; Coba, Marcelo P; Sun, Fengzhu

    2016-01-11

    Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease

  12. Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

    PubMed

    Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

    2018-04-01

    Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

  13. Ultrasonic force microscopy: detection and imaging of ultra-thin molecular domains.

    PubMed

    Dinelli, Franco; Albonetti, Cristiano; Kolosov, Oleg V

    2011-03-01

    The analysis of the formation of ultra-thin organic films is a very important issue. In fact, it is known that the properties of organic light emitting diodes and field effect transistors are strongly affected by the early growth stages. For instance, in the case of sexithiophene, the presence of domains made of molecules with the backbone parallel to the substrate surface has been indirectly evidenced by photoluminescence spectroscopy and confocal microscopy. On the contrary, conventional scanning force microscopy both in contact and intermittent contact modes have failed to detect such domains. In this paper, we show that Ultrasonic Force Microscopy (UFM), sensitive to nanomechanical properties, allows one to directly identify the structure of sub-monolayer thick films. Sexithiophene flat domains have been imaged for the first time with nanometer scale spatial resolution. A comparison with lateral force and intermittent contact modes has been carried out in order to explain the origins of the UFM contrast and its advantages. In particular, it indicates that UFM is highly suitable for investigations where high sensitivity to material properties, low specimen damage and high spatial resolution are required. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Improving the Effectiveness of Speaker Verification Domain Adaptation With Inadequate In-Domain Data

    DTIC Science & Technology

    2017-08-20

    Improving the Effectiveness of Speaker Verification Domain Adaptation With Inadequate In-Domain Data Bengt J. Borgström1, Elliot Singer1, Douglas...ll.mit.edu.edu, dar@ll.mit.edu, es@ll.mit.edu, omid.sadjadi@nist.gov Abstract This paper addresses speaker verification domain adaptation with...contain speakers with low channel diversity. Existing domain adaptation methods are reviewed, and their shortcomings are discussed. We derive an

  15. Evolution of domain promiscuity in eukaryotic genomes—a perspective from the inferred ancestral domain architectures†

    PubMed Central

    Cohen-Gihon, Inbar; Fong, Jessica H.; Sharan, Roded; Nussinov, Ruth

    2012-01-01

    Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution. PMID:21127809

  16. Gabor domain optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Murali, Supraja

    to this technology all of which have been demonstrated in full functional hardware conceived and built during the course of this research. First, it has been demonstrated that the coherence gate created by the femtosecond laser can be coupled into a scanning optical microscope using optical design methods to include liquid lens technology that enables scanning below the surface of skin with no moving parts and at high resolution throughout a 2x2x2 mm imaging cube. Second, the integration the variable-focus liquid lens technology within a fixed-optics microscope custom optical design helped increase the working NA by an order of magnitude over the limitation imposed by the liquid lens alone. Thus, this design has enabled homogenous axial and lateral resolution at the micron-level (i.e., 2 mum) while imaging in the spectral domain, and still maintaining in vivo speeds. The latest images in biological specimens clearly demonstrate sub-cellular resolution in all dimensions throughout the imaging volume. Third, this new modality for data collection has been integrated with an automated Gabor domain image registration and fusion algorithm to provide full resolution images across the data cube in real-time. We refer to this overall OCM method as Gabor domain OCM (GD-OCM). These advantages place GD-OCM in a unique position with respect to the diagnosis of cancer, because when fully developed, it promises to enable fast and accurate screening for early symptoms that could lead to prevention. The next step for this technology is to apply it directly, in a clinical environment. This step is underway and is expected to be reported by the next generation of researchers within this group.

  17. Domain-specific perceptual causality in children depends on the spatio-temporal configuration, not motion onset

    PubMed Central

    Schlottmann, Anne; Cole, Katy; Watts, Rhianna; White, Marina

    2013-01-01

    Humans, even babies, perceive causality when one shape moves briefly and linearly after another. Motion timing is crucial in this and causal impressions disappear with short delays between motions. However, the role of temporal information is more complex: it is both a cue to causality and a factor that constrains processing. It affects ability to distinguish causality from non-causality, and social from mechanical causality. Here we study both issues with 3- to 7-year-olds and adults who saw two computer-animated squares and chose if a picture of mechanical, social or non-causality fit each event best. Prior work fit with the standard view that early in development, the distinction between the social and physical domains depends mainly on whether or not the agents make contact, and that this reflects concern with domain-specific motion onset, in particular, whether the motion is self-initiated or not. The present experiments challenge both parts of this position. In Experiments 1 and 2, we showed that not just spatial, but also animacy and temporal information affect how children distinguish between physical and social causality. In Experiments 3 and 4 we showed that children do not seem to use spatio-temporal information in perceptual causality to make inferences about self- or other-initiated motion onset. Overall, spatial contact may be developmentally primary in domain-specific perceptual causality in that it is processed easily and is dominant over competing cues, but it is not the only cue used early on and it is not used to infer motion onset. Instead, domain-specific causal impressions may be automatic reactions to specific perceptual configurations, with a complex role for temporal information. PMID:23874308

  18. Disciplinary knowledge of K-3 teachers and their knowledge calibration in the domain of early literacy.

    PubMed

    Cunningham, Anne E; Perry, Kathryn E; Stanovich, Keith E; Stanovich, Paula J

    2004-06-01

    Recently, investigators have begun to pay increasing attention to the role of teachers' domain specific knowledge in the area of reading, and its implications for both classroom practice and student learning. The aims of the present study were to assess kindergarten to third-grade teachers' actual and perceived reading-related subject matter knowledge, and to investigate the extent to which teachers calibrate their reading related subject matter knowledge by examining relationships between actual and perceived knowledge. Results indicated that while teachers demonstrated limited knowledge of children's literature, phoneme awareness, and phonics, the majority of these same teachers evaluated their knowledge levels quite positively. Teachers demonstrated some ability to calibrate their own knowledge levels in the area of children's literature, yet they were poorly calibrated in the domains of phoneme awareness and phonics. These findings suggest that teachers tend to overestimate their reading related subject matter knowledge and are often unaware of what they know and do not know. Implications for the design of teacher education at both the preservice and inservice levels are discussed.

  19. Spectral domain polarization-sensitive optical coherence tomography at 850 nm

    NASA Astrophysics Data System (ADS)

    Cense, Barry; Chen, Teresa C.; Mujat, Mircea; Joo, Chulmin; Akkin, Taner; Park, B. H.; Pierce, Mark C.; Yun, Andy; Bouma, Brett E.; Tearney, Guillermo J.; de Boer, Johannes F.

    2005-04-01

    Spectral-Domain Polarization-Sensitive Optical Coherence Tomography (SD-PS-OCT) is a technique developed to measure the thickness and birefringence of the nerve fiber layer in vivo as a tool for the early diagnosis of glaucoma. A clinical SD-PS-OCT system was developed and scans were made around the optic nerve head (ONH) using ten concentric circles of increasing diameter. One healthy volunteer was imaged. Retinal nerve fiber layer thickness and birefringence information was extracted from the data. Polarization-sensitive OCT images were acquired at video rate (29 frames per second (fps), 1000 A-lines / frame) and at 7 fps (1000 A-lines / frame). The last setting improved the signal to noise ratio by approximately 6 dB. Birefringence measurements on the healthy volunteer gave similar results as earlier reported values that were obtained with a time-domain setup. The measurement time was reduced from more than a minute to less than a second.

  20. Direct Ethanol Production from Lignocellulosic Sugars and Sugarcane Bagasse by a Recombinant Trichoderma reesei Strain HJ48

    PubMed Central

    Huang, Jun; Chen, Dong; Wei, Yutuo; Wang, Qingyan; Li, Zhenchong; Chen, Ying; Huang, Ribo

    2014-01-01

    Trichoderma reesei can be considered as a candidate for consolidated bioprocessing (CBP) microorganism. However, its ethanol yield needs to be improved significantly. Here the ethanol production of T. reesei CICC 40360 was improved by genome shuffling while simultaneously enhancing the ethanol resistance. The initial mutant population was generated by nitrosoguanidine treatment of the spores, and an improved population producing more than fivefold ethanol than wild type was obtained by genome shuffling. The results show that the shuffled strain HJ48 can efficiently convert lignocellulosic sugars to ethanol under aerobic conditions. Furthermore, it was able to produce ethanol directly from sugarcane bagasse, demonstrating that the shuffled strain HJ48 is a suitable microorganism for consolidated bioprocessing. PMID:24995362

  1. Direct ethanol production from lignocellulosic sugars and sugarcane bagasse by a recombinant Trichoderma reesei strain HJ48.

    PubMed

    Huang, Jun; Chen, Dong; Wei, Yutuo; Wang, Qingyan; Li, Zhenchong; Chen, Ying; Huang, Ribo

    2014-01-01

    Trichoderma reesei can be considered as a candidate for consolidated bioprocessing (CBP) microorganism. However, its ethanol yield needs to be improved significantly. Here the ethanol production of T. reesei CICC 40360 was improved by genome shuffling while simultaneously enhancing the ethanol resistance. The initial mutant population was generated by nitrosoguanidine treatment of the spores, and an improved population producing more than fivefold ethanol than wild type was obtained by genome shuffling. The results show that the shuffled strain HJ48 can efficiently convert lignocellulosic sugars to ethanol under aerobic conditions. Furthermore, it was able to produce ethanol directly from sugarcane bagasse, demonstrating that the shuffled strain HJ48 is a suitable microorganism for consolidated bioprocessing.

  2. [Autism: An early neurodevelopmental disorder].

    PubMed

    Bonnet-Brilhault, F

    2017-04-01

    With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Structure of the E2 DNA-binding domain from human papillomavirus serotype 31 at 2.4 A.

    PubMed

    Bussiere, D E; Kong, X; Egan, D A; Walter, K; Holzman, T F; Lindh, F; Robins, T; Giranda, V L

    1998-11-01

    The papillomaviruses are a family of small double-stranded DNA viruses which exclusively infect epithelial cells and stimulate the proliferation of those cells. A key protein within the papillomavirus life-cycle is known as the E2 (Early 2) protein and is responsible for regulating viral transcription from all viral promoters as well as for replication of the papillomavirus genome in tandem with another protein known as E1. The E2 protein itself consists of three functional domains: an N-terminal trans-activation domain, a proline-rich linker, and a C-terminal DNA-binding domain. The first crystal structure of the human papillomavirus, serotype 31 (HPV-31), E2 DNA-binding domain has been determined at 2.4 A resolution. The HPV DNA-binding domain monomer consists of two beta-alpha-beta repeats of approximately equal length and is arranged as to have an anti-parallel beta-sheet flanked by the two alpha-helices. The monomers form the functional in vivo dimer by association of the beta-sheets of each monomer so as to form an eight-stranded anti-parallel beta-barrel at the center of the dimer, with the alpha-helices lining the outside of the barrel. The overall structure of HVP-31 E2 DNA-binding domain is similar to both the bovine papillomavirus E2-binding domain and the Epstein-Barr nuclear antigen-1 DNA-binding domain.

  4. Identifying Domains of Ideas to Influence Early Childhood Teachers' Beliefs in Globalisation: A Mixed-Method Study

    ERIC Educational Resources Information Center

    Tzuo, Pei-Wen; Tan, Liang See; Yang, Chien-Hui

    2013-01-01

    In the age of globalisation, it has been understood that teachers' beliefs revolve between old--new and local--foreign ideas of teaching and learning. The purpose of this study is to identify the domains of the various ideas that influence teachers' beliefs in globalisation, compare them to the strengths of influence, and explore the meanings of…

  5. Traumatic Brain Injury in Early Childhood: Developmental Effects and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara; Lowenthal, Barbara

    1998-01-01

    Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)

  6. Basic-Level and Superordinate-like Categorical Representations in Early Infancy.

    ERIC Educational Resources Information Center

    Behl-Chadha, Gundeep

    1996-01-01

    Examined three- to four-month-old infants' ability to form perceptually based categorical representation in the domains of natural kinds and artifacts. By showing the availability of perceptually driven basic and superordinate-like representations in early infancy that closely correspond to adult conceptual categories, findings underscored the…

  7. Simplicity and Specificity in Language: Domain-General Biases Have Domain-Specific Effects

    PubMed Central

    Culbertson, Jennifer; Kirby, Simon

    2016-01-01

    The extent to which the linguistic system—its architecture, the representations it operates on, the constraints it is subject to—is specific to language has broad implications for cognitive science and its relation to evolutionary biology. Importantly, a given property of the linguistic system can be “specific” to the domain of language in several ways. For example, if the property evolved by natural selection under the pressure of the linguistic function it serves then the property is domain-specific in the sense that its design is tailored for language. Equally though, if that property evolved to serve a different function or if that property is domain-general, it may nevertheless interact with the linguistic system in a way that is unique. This gives a second sense in which a property can be thought of as specific to language. An evolutionary approach to the language faculty might at first blush appear to favor domain-specificity in the first sense, with individual properties of the language faculty being specifically linguistic adaptations. However, we argue that interactions between learning, culture, and biological evolution mean any domain-specific adaptations that evolve will take the form of weak biases rather than hard constraints. Turning to the latter sense of domain-specificity, we highlight a very general bias, simplicity, which operates widely in cognition and yet interacts with linguistic representations in domain-specific ways. PMID:26793132

  8. A Novel Kinesin-Like Protein with a Calmodulin-Binding Domain

    NASA Technical Reports Server (NTRS)

    Wang, W.; Takezawa, D.; Narasimhulu, S. B.; Reddy, A. S. N.; Poovaiah, B. W.

    1996-01-01

    Calcium regulates diverse developmental processes in plants through the action of calmodulin. A cDNA expression library from developing anthers of tobacco was screened with S-35-labeled calmodulin to isolate cDNAs encoding calmodulin-binding proteins. Among several clones isolated, a kinesin-like gene (TCK1) that encodes a calmodulin-binding kinesin-like protein was obtained. The TCK1 cDNA encodes a protein with 1265 amino acid residues. Its structural features are very similar to those of known kinesin heavy chains and kinesin-like proteins from plants and animals, with one distinct exception. Unlike other known kinesin-like proteins, TCK1 contains a calmodulin-binding domain which distinguishes it from all other known kinesin genes. Escherichia coli-expressed TCK1 binds calmodulin in a Ca(2+)-dependent manner. In addition to the presence of a calmodulin-binding domain at the carboxyl terminal, it also has a leucine zipper motif in the stalk region. The amino acid sequence at the carboxyl terminal of TCK1 has striking homology with the mechanochemical motor domain of kinesins. The motor domain has ATPase activity that is stimulated by microtubules. Southern blot analysis revealed that TCK1 is coded by a single gene. Expression studies indicated that TCKI is expressed in all of the tissues tested. Its expression is highest in the stigma and anther, especially during the early stages of anther development. Our results suggest that Ca(2+)/calmodulin may play an important role in the function of this microtubule-associated motor protein and may be involved in the regulation of microtubule-based intracellular transport.

  9. Emergence of novel domains in proteins

    PubMed Central

    2013-01-01

    Background Proteins are composed of a combination of discrete, well-defined, sequence domains, associated with specific functions that have arisen at different times during evolutionary history. The emergence of novel domains is related to protein functional diversification and adaptation. But currently little is known about how novel domains arise and how they subsequently evolve. Results To gain insights into the impact of recently emerged domains in protein evolution we have identified all human young protein domains that have emerged in approximately the past 550 million years. We have classified them into vertebrate-specific and mammalian-specific groups, and compared them to older domains. We have found 426 different annotated young domains, totalling 995 domain occurrences, which represent about 12.3% of all human domains. We have observed that 61.3% of them arose in newly formed genes, while the remaining 38.7% are found combined with older domains, and have very likely emerged in the context of a previously existing protein. Young domains are preferentially located at the N-terminus of the protein, indicating that, at least in vertebrates, novel functional sequences often emerge there. Furthermore, young domains show significantly higher non-synonymous to synonymous substitution rates than older domains using human and mouse orthologous sequence comparisons. This is also true when we compare young and old domains located in the same protein, suggesting that recently arisen domains tend to evolve in a less constrained manner than older domains. Conclusions We conclude that proteins tend to gain domains over time, becoming progressively longer. We show that many proteins are made of domains of different age, and that the fastest evolving parts correspond to the domains that have been acquired more recently. PMID:23425224

  10. Application of Feature-Oriented Domain Analysis to the Army Movement Control Domain (Appendices A-I)

    DTIC Science & Technology

    1992-06-01

    Cohen, James A. Hess, William E. Novak, & A. Spen- cer Peterson. Feature-Oriented Domain Analysis ( FODA ) Feasibility Study (CMU/SEI-90- TR-21...Oriented Domain Analysis to the Army Movement Control Domain (Appendices A -1) Sholom G. Cohen Jay L. Stanley, Jr. A. Spencer Peterson Robert W...Appendices) June 1992 Application of Feature-Oriented Domain Analysis to the Army Movement Control Domain (Appendices A -1) Sholom G. Cohen Jay L

  11. Transverse instabilities of stripe domains in magnetic thin films with perpendicular magnetic anisotropy

    NASA Astrophysics Data System (ADS)

    Ruth, Max E.; Iacocca, Ezio; Kevrekidis, Panayotis G.; Hoefer, Mark A.

    2018-03-01

    Stripe domains are narrow, elongated, reversed regions that exist in magnetic materials with perpendicular magnetic anisotropy. They appear as a pair of domain walls that can exhibit topology with a nonzero chirality. Recent experimental and numerical investigations identify an instability of stripe domains along the long direction as a means of nucleating isolated magnetic skyrmions. Here, the onset and nonlinear evolution of transverse instabilities for a dynamic stripe domain known as the bion stripe are investigated. Both nontopological and topological variants of the bion stripe are shown to exhibit a long-wavelength transverse instability with different characteristic features. In the former, small transverse variations in the stripe's width lead to a neck instability that eventually pinches the nontopological stripe into a chain of two-dimensional breathers composed of droplet soliton pairs. In the latter case, small variations in the stripe's center result in a snake instability whose topological structure leads to the nucleation of dynamic magnetic skyrmions and antiskyrmions as well as perimeter-modulated droplets. Quantitative, analytical predictions for both the early, linear evolution and the long-time, nonlinear evolution are achieved using an averaged Lagrangian approach that incorporates both exchange (dispersion) and anisotropy (nonlinearity). The method of analysis is general and can be applied to other filamentary structures.

  12. Adult Neuropsychological Performance Following Prenatal and Early Postnatal Exposure to Tetrachloroethylene (PCE)-contaminated Drinking Water

    PubMed Central

    Janulewicz, Patricia A; White, Roberta F; Martin, Brett M; Winter, Michael R; Weinberg, Janice M; Vieira, Veronica; Aschengrau, Ann

    2012-01-01

    This population-based retrospective cohort study examined adult performance on a battery of neuropsychological tests in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using pipe network information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Results of crude and multivariate analyses among 35 exposed and 28 unexposed subjects showed no association between prenatal and early postnatal exposure and decrements on tests that assess abilities in the domains of omnibus intelligence, academic achievement or language. The results were suggestive of an association between prenatal and early postnatal PCE exposure and diminished performance on tests that assessed abilities in the domains of visuospatial functioning, learning and memory, motor, attention and mood. Because the sample size was small, most findings were not statistically significant. Future studies with larger sample sizes should be conducted to further define the neuropsychological consequences of early developmental PCE exposure. PMID:22522125

  13. Trimeric Transmembrane Domain Interactions in Paramyxovirus Fusion Proteins

    PubMed Central

    Smith, Everett Clinton; Smith, Stacy E.; Carter, James R.; Webb, Stacy R.; Gibson, Kathleen M.; Hellman, Lance M.; Fried, Michael G.; Dutch, Rebecca Ellis

    2013-01-01

    Paramyxovirus fusion (F) proteins promote membrane fusion between the viral envelope and host cell membranes, a critical early step in viral infection. Although mutational analyses have indicated that transmembrane (TM) domain residues can affect folding or function of viral fusion proteins, direct analysis of TM-TM interactions has proved challenging. To directly assess TM interactions, the oligomeric state of purified chimeric proteins containing the Staphylococcal nuclease (SN) protein linked to the TM segments from three paramyxovirus F proteins was analyzed by sedimentation equilibrium analysis in detergent and buffer conditions that allowed density matching. A monomer-trimer equilibrium best fit was found for all three SN-TM constructs tested, and similar fits were obtained with peptides corresponding to just the TM region of two different paramyxovirus F proteins. These findings demonstrate for the first time that class I viral fusion protein TM domains can self-associate as trimeric complexes in the absence of the rest of the protein. Glycine residues have been implicated in TM helix interactions, so the effect of mutations at Hendra F Gly-508 was assessed in the context of the whole F protein. Mutations G508I or G508L resulted in decreased cell surface expression of the fusogenic form, consistent with decreased stability of the prefusion form of the protein. Sedimentation equilibrium analysis of TM domains containing these mutations gave higher relative association constants, suggesting altered TM-TM interactions. Overall, these results suggest that trimeric TM interactions are important driving forces for protein folding, stability and membrane fusion promotion. PMID:24178297

  14. Early parental adjustment and bereavement after childhood cancer death.

    PubMed

    Barrera, Maru; O'Connor, Kathleen; D'Agostino, Norma Mammone; Spencer, Lynlee; Nicholas, David; Jovcevska, Vesna; Tallet, Susan; Schneiderman, Gerald

    2009-07-01

    This study comprehensively explored parental bereavement and adjustment at 6 months post-loss due to childhood cancer. Interviews were conducted with 18 mothers and 13 fathers. Interviews were transcribed verbatim and analyzed based on qualitative methodology. A model describing early parental bereavement and adaptation emerged with 3 domains: (1) Perception of the Child, describing bereavement and adjustment prior to and after the loss; (2) Perception of Others, including relationships with partners, surviving children, and their social network; and (3) Perception of the World, exploring parents' perceived meanings of the experience in the context of their worldview. Domains are illustrated by quotes. Profiles of parental bereavement emerged.

  15. Developing a Shuffled Complex-Self Adaptive Hybrid Evolution (SC-SAHEL) Framework for Water Resources Management and Water-Energy System Optimization

    NASA Astrophysics Data System (ADS)

    Rahnamay Naeini, M.; Sadegh, M.; AghaKouchak, A.; Hsu, K. L.; Sorooshian, S.; Yang, T.

    2017-12-01

    Meta-Heuristic optimization algorithms have gained a great deal of attention in a wide variety of fields. Simplicity and flexibility of these algorithms, along with their robustness, make them attractive tools for solving optimization problems. Different optimization methods, however, hold algorithm-specific strengths and limitations. Performance of each individual algorithm obeys the "No-Free-Lunch" theorem, which means a single algorithm cannot consistently outperform all possible optimization problems over a variety of problems. From users' perspective, it is a tedious process to compare, validate, and select the best-performing algorithm for a specific problem or a set of test cases. In this study, we introduce a new hybrid optimization framework, entitled Shuffled Complex-Self Adaptive Hybrid EvoLution (SC-SAHEL), which combines the strengths of different evolutionary algorithms (EAs) in a parallel computing scheme, and allows users to select the most suitable algorithm tailored to the problem at hand. The concept of SC-SAHEL is to execute different EAs as separate parallel search cores, and let all participating EAs to compete during the course of the search. The newly developed SC-SAHEL algorithm is designed to automatically select, the best performing algorithm for the given optimization problem. This algorithm is rigorously effective in finding the global optimum for several strenuous benchmark test functions, and computationally efficient as compared to individual EAs. We benchmark the proposed SC-SAHEL algorithm over 29 conceptual test functions, and two real-world case studies - one hydropower reservoir model and one hydrological model (SAC-SMA). Results show that the proposed framework outperforms individual EAs in an absolute majority of the test problems, and can provide competitive results to the fittest EA algorithm with more comprehensive information during the search. The proposed framework is also flexible for merging additional EAs, boundary

  16. Recovering Protein-Protein and Domain-Domain Interactions from Aggregation of IP-MS Proteomics of Coregulator Complexes

    PubMed Central

    Mazloom, Amin R.; Dannenfelser, Ruth; Clark, Neil R.; Grigoryan, Arsen V.; Linder, Kathryn M.; Cardozo, Timothy J.; Bond, Julia C.; Boran, Aislyn D. W.; Iyengar, Ravi; Malovannaya, Anna; Lanz, Rainer B.; Ma'ayan, Avi

    2011-01-01

    Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/. PMID:22219718

  17. Full waveform inversion in the frequency domain using classified time-domain residual wavefields

    NASA Astrophysics Data System (ADS)

    Son, Woohyun; Koo, Nam-Hyung; Kim, Byoung-Yeop; Lee, Ho-Young; Joo, Yonghwan

    2017-04-01

    We perform the acoustic full waveform inversion in the frequency domain using residual wavefields that have been separated in the time domain. We sort the residual wavefields in the time domain according to the order of absolute amplitudes. Then, the residual wavefields are separated into several groups in the time domain. To analyze the characteristics of the residual wavefields, we compare the residual wavefields of conventional method with those of our residual separation method. From the residual analysis, the amplitude spectrum obtained from the trace before separation appears to have little energy at the lower frequency bands. However, the amplitude spectrum obtained from our strategy is regularized by the separation process, which means that the low-frequency components are emphasized. Therefore, our method helps to emphasize low-frequency components of residual wavefields. Then, we generate the frequency-domain residual wavefields by taking the Fourier transform of the separated time-domain residual wavefields. With these wavefields, we perform the gradient-based full waveform inversion in the frequency domain using back-propagation technique. Through a comparison of gradient directions, we confirm that our separation method can better describe the sub-salt image than the conventional approach. The proposed method is tested on the SEG/EAGE salt-dome model. The inversion results show that our algorithm is better than the conventional gradient based waveform inversion in the frequency domain, especially for deeper parts of the velocity model.

  18. Evolution of EF-hand calcium-modulated proteins. III. Exon sequences confirm most dendrograms based on protein sequences: calmodulin dendrograms show significant lack of parallelism

    NASA Technical Reports Server (NTRS)

    Nakayama, S.; Kretsinger, R. H.

    1993-01-01

    In the first report in this series we presented dendrograms based on 152 individual proteins of the EF-hand family. In the second we used sequences from 228 proteins, containing 835 domains, and showed that eight of the 29 subfamilies are congruent and that the EF-hand domains of the remaining 21 subfamilies have diverse evolutionary histories. In this study we have computed dendrograms within and among the EF-hand subfamilies using the encoding DNA sequences. In most instances the dendrograms based on protein and on DNA sequences are very similar. Significant differences between protein and DNA trees for calmodulin remain unexplained. In our fourth report we evaluate the sequences and the distribution of introns within the EF-hand family and conclude that exon shuffling did not play a significant role in its evolution.

  19. Apoplastic domains and sub-domains in the shoots of etiolated corn seedlings

    NASA Technical Reports Server (NTRS)

    Epel, B. L.; Bandurski, R. S.

    1990-01-01

    Light Green, an apoplastic probe, was applied to the cut mesocotyl base or to the cut coleoptile apex of etiolated seedlings of Zea mays L. cv. Silver Queen. Probe transport was measured and its tissue distribution determined. In the mesocotyl, there is an apoplastic barrier between cortex and stele. This barrier creates two apoplastic domains which are non-communicating. A kinetic barrier exists between the apoplast of the mesocotyl stele and that of the coleoptile. This kinetic barrier is not absolute and there is limited communication between the apoplasts of the two regions. This kinetic barrier effectively creates two sub-domains. In the coleoptile, there is communication between the apoplast of the vascular strands and that of the surrounding cortical tissue. No apoplastic communication was observed between the coleoptile cortex and the mesocotyl cortex. Thus, the apoplastic space of the coleoptile cortex is a sub-domain of the integrated coleoptile domain and is separate from that of the apoplastic domain of the mesocotyl cortex.

  20. Domains in Ferroelectric Nanostructures

    NASA Astrophysics Data System (ADS)

    Gregg, Marty

    2010-03-01

    Ferroelectric materials have great potential in influencing the future of small scale electronics. At a basic level, this is because ferroelectric surfaces are charged, and so interact strongly with charge-carrying metals and semiconductors - the building blocks for all electronic systems. Since the electrical polarity of the ferroelectric can be reversed, surfaces can both attract and repel charges in nearby materials, and can thereby exert complete control over both charge distribution and movement. It should be no surprise, therefore, that microelectronics industries have already looked very seriously at harnessing ferroelectric materials in a variety of applications, from solid state memory chips (FeRAMs) to field effect transistors (FeFETs). In all such applications, switching the direction of the polarity of the ferroelectric is a key aspect of functional behavior. The mechanism for switching involves the field-induced nucleation and growth of domains. Domain coarsening, through domain wall propagation, eventually causes the entire ferroelectric to switch its polar direction. It is thus the existence and behavior of domains that determine the switching response, and ultimately the performance of the ferroelectric device. A major issue, associated with the integration of ferroelectrics into microelectronic devices, has been that the fundamental properties associated with ferroelectrics, when in bulk form, appear to change quite dramatically and unpredictably when at the nanoscale: new modes of behaviour, and different functional characteristics from those seen in bulk appear. For domains, in particular, the proximity of surfaces and boundaries have a dramatic effect: surface tension and depolarizing fields both serve to increase the equilibrium density of domains, such that minor changes in scale or morphology can have major ramifications for domain redistribution. Given the importance of domains in dictating the overall switching characteristics of a device

  1. Target of Rapamycin Regulates Development and Ribosomal RNA Expression through Kinase Domain in Arabidopsis1[W][OA

    PubMed Central

    Ren, Maozhi; Qiu, Shuqing; Venglat, Prakash; Xiang, Daoquan; Feng, Li; Selvaraj, Gopalan; Datla, Raju

    2011-01-01

    Target of rapamycin (TOR) is a central regulator of cell growth, cell death, nutrition, starvation, hormone, and stress responses in diverse eukaryotes. However, very little is known about TOR signaling and the associated functional domains in plants. We have taken a genetic approach to dissect TOR functions in Arabidopsis (Arabidopsis thaliana) and report here that the kinase domain is essential for the role of TOR in embryogenesis and 45S rRNA expression. Twelve new T-DNA insertion mutants, spanning 14.2 kb of TOR-encoding genomic region, have been characterized. Nine of these share expression of defective kinase domain and embryo arrest at 16 to 32 cell stage. However, three T-DNA insertion lines affecting FATC domain displayed normal embryo development, indicating that FATC domain was dispensable in Arabidopsis. Genetic complementation showed that the TOR kinase domain alone in tor-10/tor-10 mutant background can rescue early embryo lethality and restore normal development. Overexpression of full-length TOR or kinase domain in Arabidopsis displayed developmental abnormalities in meristem, leaf, root, stem, flowering time, and senescence. We further show that TOR, especially the kinase domain, plays a role in ribosome biogenesis by activating 45S rRNA production. Of the six putative nuclear localization sequences in the kinase domain, nuclear localization sequence 6 was identified to confer TOR nuclear targeting in transient expression assays. Chromatin immunoprecipitation studies revealed that the HEAT repeat domain binds to 45S rRNA promoter and the 5′ external transcribed spacer elements motif. Together, these results show that TOR controls the embryogenesis, postembryonic development, and 45S rRNA production through its kinase domain in Arabidopsis. PMID:21266656

  2. Institutionalizing the Human Domain: Achieving Cross Domain Synergy for Every Day Missions

    DTIC Science & Technology

    2017-04-06

    AIR WAR COLLEGE AIR UNIVERSITY INSTITUTIONALIZING THE HUMAN DOMAIN: ACHIEVING CROSS DOMAIN SYNERGY FOR “EVERY DAY ” MISSIONS by...war. Next, this paper will focus on the importance of the Human Domain as it relates to success within every day missions of the U.S. Military and...socially complex environment. History demonstrates that the U.S. Military has and will continue to conduct these every day missions amongst the

  3. DIMA 3.0: Domain Interaction Map.

    PubMed

    Luo, Qibin; Pagel, Philipp; Vilne, Baiba; Frishman, Dmitrij

    2011-01-01

    Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46,900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software.

  4. Genome-Wide Prediction and Analysis of 3D-Domain Swapped Proteins in the Human Genome from Sequence Information.

    PubMed

    Upadhyay, Atul Kumar; Sowdhamini, Ramanathan

    2016-01-01

    3D-domain swapping is one of the mechanisms of protein oligomerization and the proteins exhibiting this phenomenon have many biological functions. These proteins, which undergo domain swapping, have acquired much attention owing to their involvement in human diseases, such as conformational diseases, amyloidosis, serpinopathies, proteionopathies etc. Early realisation of proteins in the whole human genome that retain tendency to domain swap will enable many aspects of disease control management. Predictive models were developed by using machine learning approaches with an average accuracy of 78% (85.6% of sensitivity, 87.5% of specificity and an MCC value of 0.72) to predict putative domain swapping in protein sequences. These models were applied to many complete genomes with special emphasis on the human genome. Nearly 44% of the protein sequences in the human genome were predicted positive for domain swapping. Enrichment analysis was performed on the positively predicted sequences from human genome for their domain distribution, disease association and functional importance based on Gene Ontology (GO). Enrichment analysis was also performed to infer a better understanding of the functional importance of these sequences. Finally, we developed hinge region prediction, in the given putative domain swapped sequence, by using important physicochemical properties of amino acids.

  5. Domain fusion analysis by applying relational algebra to protein sequence and domain databases.

    PubMed

    Truong, Kevin; Ikura, Mitsuhiko

    2003-05-06

    Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at http://calcium.uhnres.utoronto.ca/pi. As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time.

  6. Domain fusion analysis by applying relational algebra to protein sequence and domain databases

    PubMed Central

    Truong, Kevin; Ikura, Mitsuhiko

    2003-01-01

    Background Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. Results This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at . Conclusion As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time. PMID:12734020

  7. Academic Achievement and Risk Factors for Adolescents with Attention-Deficit Hyperactivity Disorder in Middle School and Early High School.

    PubMed

    Zendarski, Nardia; Sciberras, Emma; Mensah, Fiona; Hiscock, Harriet

    Examine academic achievement of students with attention-deficit hyperactivity disorder (ADHD) during the early high school period and identify potentially modifiable risk factors for low achievement. Data were collected through surveys (adolescent, parent, and teacher) and direct assessment of Australian adolescents (12-15 yr; n = 130) with ADHD in early high school (i.e., US middle and high school grades). Academic achievement outcomes were measured by linking to individual performance on the National Assessment Program-Literacy and Numeracy (NAPLAN) tests, direct assessment of reading and math, and teacher report of academic competence. Linear regression models examined associations between adolescent, parent/family, and school factors and NAPLAN domain scores. Students with ADHD had lower NAPLAN scores on all domains and fewer met minimum academic standards in comparison with state benchmarks. The poorest results were for persuasive writing. Poor achievement was associated with lower intelligence quotient across all academic domains. Adolescent inattention, bullying, poor family management, male sex, and attending a low socioeconomic status school were associated with lower achievement on specific domains. Students with ADHD are at increased academic risk during the middle school and early high school period. In addition to academic support, interventions targeting modifiable factors including inattention, bullying, and poor family management may improve academic achievement across this critical period.

  8. Domain-General and Domain-Specific Patterns of Activity Supporting Metacognition in Human Prefrontal Cortex

    PubMed Central

    2018-01-01

    Metacognition is the capacity to evaluate the success of one's own cognitive processes in various domains; for example, memory and perception. It remains controversial whether metacognition relies on a domain-general resource that is applied to different tasks or if self-evaluative processes are domain specific. Here, we investigated this issue directly by examining the neural substrates engaged when metacognitive judgments were made by human participants of both sexes during perceptual and memory tasks matched for stimulus and performance characteristics. By comparing patterns of fMRI activity while subjects evaluated their performance, we revealed both domain-specific and domain-general metacognitive representations. Multivoxel activity patterns in anterior prefrontal cortex predicted levels of confidence in a domain-specific fashion, whereas domain-general signals predicting confidence and accuracy were found in a widespread network in the frontal and posterior midline. The demonstration of domain-specific metacognitive representations suggests the presence of a content-rich mechanism available to introspection and cognitive control. SIGNIFICANCE STATEMENT We used human neuroimaging to investigate processes supporting memory and perceptual metacognition. It remains controversial whether metacognition relies on a global resource that is applied to different tasks or if self-evaluative processes are specific to particular tasks. Using multivariate decoding methods, we provide evidence that perceptual- and memory-specific metacognitive representations coexist with generic confidence signals. Our findings reconcile previously conflicting results on the domain specificity/generality of metacognition and lay the groundwork for a mechanistic understanding of metacognitive judgments. PMID:29519851

  9. Evidence of reduced recombination rate in human regulatory domains.

    PubMed

    Liu, Yaping; Sarkar, Abhishek; Kheradpour, Pouya; Ernst, Jason; Kellis, Manolis

    2017-10-20

    Recombination rate is non-uniformly distributed across the human genome. The variation of recombination rate at both fine and large scales cannot be fully explained by DNA sequences alone. Epigenetic factors, particularly DNA methylation, have recently been proposed to influence the variation in recombination rate. We study the relationship between recombination rate and gene regulatory domains, defined by a gene and its linked control elements. We define these links using expression quantitative trait loci (eQTLs), methylation quantitative trait loci (meQTLs), chromatin conformation from publicly available datasets (Hi-C and ChIA-PET), and correlated activity links that we infer across cell types. Each link type shows a "recombination rate valley" of significantly reduced recombination rate compared to matched control regions. This recombination rate valley is most pronounced for gene regulatory domains of early embryonic development genes, housekeeping genes, and constitutive regulatory elements, which are known to show increased evolutionary constraint across species. Recombination rate valleys show increased DNA methylation, reduced doublestranded break initiation, and increased repair efficiency, specifically in the lineage leading to the germ line. Moreover, by using only the overlap of functional links and DNA methylation in germ cells, we are able to predict the recombination rate with high accuracy. Our results suggest the existence of a recombination rate valley at regulatory domains and provide a potential molecular mechanism to interpret the interplay between genetic and epigenetic variations.

  10. Topological domain walls in helimagnets

    NASA Astrophysics Data System (ADS)

    Schoenherr, P.; Müller, J.; Köhler, L.; Rosch, A.; Kanazawa, N.; Tokura, Y.; Garst, M.; Meier, D.

    2018-05-01

    Domain walls naturally arise whenever a symmetry is spontaneously broken. They interconnect regions with different realizations of the broken symmetry, promoting structure formation from cosmological length scales to the atomic level1,2. In ferroelectric and ferromagnetic materials, domain walls with unique functionalities emerge, holding great promise for nanoelectronics and spintronics applications3-5. These walls are usually of Ising, Bloch or Néel type and separate homogeneously ordered domains. Here we demonstrate that a wide variety of new domain walls occurs in the presence of spatially modulated domain states. Using magnetic force microscopy and micromagnetic simulations, we show three fundamental classes of domain walls to arise in the near-room-temperature helimagnet iron germanium. In contrast to conventional ferroics, the domain walls exhibit a well-defined inner structure, which—analogous to cholesteric liquid crystals—consists of topological disclination and dislocation defects. Similar to the magnetic skyrmions that form in the same material6,7, the domain walls can carry a finite topological charge, permitting an efficient coupling to spin currents and contributions to a topological Hall effect. Our study establishes a new family of magnetic nano-objects with non-trivial topology, opening the door to innovative device concepts based on helimagnetic domain walls.

  11. Age of acquisition in sport: starting early matters.

    PubMed

    Hernandez, Arturo E; Mattarella-Micke, Andrew; Redding, Richard W T; Woods, Elizabeth A; Beilock, Sian

    2011-01-01

    Although the age at which a skill is learned (age of acquisition [AoA]) is one of the most studied predictors of success in domains ranging from language to music, very little work has focused on this factor in sports. In order to uncover how the age at which a skill is learned relates to how athletes cognitively represent that skill, we asked a group of skilled golfers who learned to play golf before (early learners) or after (late learners) the age of 10 to take a series of putts on an indoor putting green. Golfers putted in isolation (single-task condition), while monitoring a stream of words presented over a loudspeaker (dual-task condition), or while being instructed to attend to specific aspects of their golf swing (skill-focused condition). Early and late learners putted equally well in the single-task and dual-task conditions. However, in the skill-focused condition, golfers who learned earlier performed worse than those who learned later. The results are consistent with the notion that AoA influences the manner in which sports, like other domains such as language and music, are represented in memory.

  12. The Origin and Early Evolution of Membrane Proteins

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Schweighofter, Karl; Wilson, Michael A.

    2006-01-01

    The origin and early evolution of membrane proteins, and in particular ion channels, are considered from the point of view that the transmembrane segments of membrane proteins are structurally quite simple and do not require specific sequences to fold. We argue that the transport of solute species, especially ions, required an early evolution of efficient transport mechanisms, and that the emergence of simple ion channels was protobiologically plausible. We also argue that, despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. These properties can be subtly modulated by local modifications to the sequence rather than global changes in molecular architecture. In order to address the evolution and development of ion channels, we focus on identifying those protein domains that are commonly associated with ion channel proteins and are conserved throughout the three main domains of life (Eukarya, Prokarya, and Archaea). We discuss the potassium-sodium-calcium superfamily of voltage-gated ion channels, mechanosensitive channels, porins, and ABC-transporters and argue that these families of membrane channels have sufficiently universal architectures that they can readily adapt to the diverse functional demands arising during evolution.

  13. Reading Acquisition Enhances an Early Visual Process of Contour Integration

    ERIC Educational Resources Information Center

    Szwed, Marcin; Ventura, Paulo; Querido, Luis; Cohen, Laurent; Dehaene, Stanislas

    2012-01-01

    The acquisition of reading has an extensive impact on the developing brain and leads to enhanced abilities in phonological processing and visual letter perception. Could this expertise also extend to early visual abilities outside the reading domain? Here we studied the performance of illiterate, ex-illiterate and literate adults closely matched…

  14. Applying Technology to Inquiry-Based Learning in Early Childhood Education

    ERIC Educational Resources Information Center

    Wang, Feng; Kinzie, Mable B.; McGuire, Patrick; Pan, Edward

    2009-01-01

    Children naturally explore and learn about their environments through inquiry, and computer technologies offer an accessible vehicle for extending the domain and range of this inquiry. Over the past decade, a growing number of interactive games and educational software packages have been implemented in early childhood education and addressed a…

  15. Integration of color, orientation, and size functional domains in the ventral pathway

    PubMed Central

    Ghose, Geoffrey M.; Ts’o, Daniel Y.

    2017-01-01

    Abstract. Functional specialization within the extrastriate areas of the ventral pathway associated with visual form analysis is poorly understood. Studies comparing the functional selectivities of neurons within the early visual areas have found that there are more similar than different between the areas. We simultaneously imaged visually evoked activation over regions of V2 and V4 and parametrically varied three visual attributes for which selectivity exists in both areas: color, orientation, and size. We found that color selective regions were observed in both areas and were of similar size and spatial distribution. However, two major areal distinctions were observed: V4 contained a greater number and diversity of color-specific regions than V2 and exhibited a higher degree of overlap between domains for different functional attributes. In V2, size and color regions were largely segregated from orientation domains, whereas in V4 both color and size regions overlapped considerably with orientation regions. Our results suggest that higher-order composite selectivities in the extrastriate cortex may arise organically from the interactions afforded by an overlap of functional domains for lower order selectivities. PMID:28573155

  16. Impairment in proverb interpretation as an executive function deficit in patients with amnestic mild cognitive impairment and early Alzheimer's disease.

    PubMed

    Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W; Milian, Monika

    2011-01-01

    Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD.

  17. Microtubule-Actin Cross-Linking Factor 1: Domains, Interaction Partners, and Tissue-Specific Functions.

    PubMed

    Goryunov, Dmitry; Liem, Ronald K H

    2016-01-01

    The cytoskeleton of most eukaryotic cells is composed of three principal filamentous components: actin filaments, microtubules (MTs), and intermediate filaments. It is a highly dynamic system that plays crucial roles in a wide range of cellular processes, including migration, adhesion, cytokinesis, morphogenesis, intracellular traffic and signaling, and structural flexibility. Among the large number of cytoskeleton-associated proteins characterized to date, microtubule-actin cross-linking factor 1 (MACF1) is arguably the most versatile integrator and modulator of cytoskeleton-related processes. MACF1 belongs to the plakin family of proteins, and within it, to the spectraplakin subfamily. These proteins are characterized by the ability to bridge MT and actin cytoskeletal networks in a dynamic fashion, which underlies their involvement in the regulation of cell migration, axonal extension, and vesicular traffic. Studying MACF1 functions has provided insights not only into the regulation of the cytoskeleton but also into molecular mechanisms of both normal cellular physiology and cellular pathology. Multiple MACF1 isoforms exist, composed of a large variety of alternatively spliced domains. Each of these domains mediates a specific set of interactions and functions. These functions are manifested in tissue and cell-specific phenotypes observed in conditional MACF1 knockout mice. The conditional models described to date reveal critical roles of MACF1 in mammalian skin, nervous system, heart muscle, and intestinal epithelia. Complete elimination of MACF1 is early embryonic lethal, indicating an essential role for MACF1 in early development. Further studies of MACF1 domains and their interactions will likely reveal multiple new roles of this protein in various tissues. © 2016 Elsevier Inc. All rights reserved.

  18. A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.

    PubMed

    Li-Smerin, Y; Hackos, D H; Swartz, K J

    2000-02-01

    Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.

  19. PERIPARTUM DEPRESSION AND ANXIETY AS AN INTEGRATIVE CROSS DOMAIN TARGET FOR PSYCHIATRIC PREVENTATIVE MEASURES

    PubMed Central

    Babb, Jessica A.; Deligiannidis, Kristina M.; Murgatroyd, Christopher A.

    2014-01-01

    Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety. PMID:24709228

  20. Critical domain interactions for type A RNase P RNA catalysis with and without the specificity domain

    PubMed Central

    Mao, Guanzhong; Srivastava, Abhishek S.; Wu, Shiying; Kosek, David; Lindell, Magnus

    2018-01-01

    The natural trans-acting ribozyme RNase P RNA (RPR) is composed of two domains in which the catalytic (C-) domain mediates cleavage of various substrates. The C-domain alone, after removal of the second specificity (S-) domain, catalyzes this reaction as well, albeit with reduced efficiency. Here we provide experimental evidence indicating that efficient cleavage mediated by the Escherichia coli C-domain (Eco CP RPR) with and without the C5 protein likely depends on an interaction referred to as the "P6-mimic". Moreover, the P18 helix connects the C- and S-domains between its loop and the P8 helix in the S-domain (the P8/ P18-interaction). In contrast to the "P6-mimic", the presence of P18 does not contribute to the catalytic performance by the C-domain lacking the S-domain in cleavage of an all ribo model hairpin loop substrate while deletion or disruption of the P8/ P18-interaction in full-size RPR lowers the catalytic efficiency in cleavage of the same model hairpin loop substrate in keeping with previously reported data using precursor tRNAs. Consistent with that P18 is not required for cleavage mediated by the C-domain we show that the archaeal Pyrococcus furiosus RPR C-domain, which lacks the P18 helix, is catalytically active in trans without the S-domain and any protein. Our data also suggest that the S-domain has a larger impact on catalysis for E. coli RPR compared to P. furiosus RPR. Finally, we provide data indicating that the absence of the S-domain and P18, or the P8/ P18-interaction in full-length RPR influences the charge distribution near the cleavage site in the RPR-substrate complex to a small but reproducible extent. PMID:29509761

  1. Expert Views on TPACK for Early Literacy: Priorities for Teacher Education

    ERIC Educational Resources Information Center

    McKenney, Susan; Voogt, Joke

    2017-01-01

    Technology applications can make important contributions to improving learning outcomes in the domain of early literacy. However, to fully exploit the potential of educational technologies, teachers must have specific knowledge and skills. This study aimed to articulate the technological pedagogical content knowledge teachers need to make…

  2. Can Early Years Professionals Determine Which Preschoolers Have Comprehension Delays? A Comparison of Two Screening Tools

    ERIC Educational Resources Information Center

    Seager, Emily; Abbot-Smith, Kirsten

    2017-01-01

    Language comprehension delays in pre-schoolers are predictive of difficulties in a range of developmental domains. In England, early years practitioners are required to assess the language comprehension of 2-year-olds in their care. Many use a format based on the Early Years Foundation Stage Unique Child Communication Sheet (EYFS:UCCS) in which…

  3. Domain adaptation via transfer component analysis.

    PubMed

    Pan, Sinno Jialin; Tsang, Ivor W; Kwok, James T; Yang, Qiang

    2011-02-01

    Domain adaptation allows knowledge from a source domain to be transferred to a different but related target domain. Intuitively, discovering a good feature representation across domains is crucial. In this paper, we first propose to find such a representation through a new learning method, transfer component analysis (TCA), for domain adaptation. TCA tries to learn some transfer components across domains in a reproducing kernel Hilbert space using maximum mean miscrepancy. In the subspace spanned by these transfer components, data properties are preserved and data distributions in different domains are close to each other. As a result, with the new representations in this subspace, we can apply standard machine learning methods to train classifiers or regression models in the source domain for use in the target domain. Furthermore, in order to uncover the knowledge hidden in the relations between the data labels from the source and target domains, we extend TCA in a semisupervised learning setting, which encodes label information into transfer components learning. We call this extension semisupervised TCA. The main contribution of our work is that we propose a novel dimensionality reduction framework for reducing the distance between domains in a latent space for domain adaptation. We propose both unsupervised and semisupervised feature extraction approaches, which can dramatically reduce the distance between domain distributions by projecting data onto the learned transfer components. Finally, our approach can handle large datasets and naturally lead to out-of-sample generalization. The effectiveness and efficiency of our approach are verified by experiments on five toy datasets and two real-world applications: cross-domain indoor WiFi localization and cross-domain text classification.

  4. MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

    PubMed Central

    Perlman, Elizabeth J.; Gadd, Samantha; Arold, Stefan T.; Radhakrishnan, Anand; Gerhard, Daniela S.; Jennings, Lawrence; Huff, Vicki; Guidry Auvil, Jaime M.; Davidsen, Tanja M.; Dome, Jeffrey S.; Meerzaman, Daoud; Hsu, Chih Hao; Nguyen, Cu; Anderson, James; Ma, Yussanne; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Gastier-Foster, Julie M.; Ross, Nicole; Smith, Malcolm A.

    2015-01-01

    Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour. PMID:26635203

  5. Formative Evaluation of the Early Development Instrument: Progress and Prospects

    ERIC Educational Resources Information Center

    Keating, Daniel P.

    2007-01-01

    This article is a commentary for the special issue on the Early Development Instrument (EDI), a community tool to assess children's school readiness and developmental outcomes at a group level. The EDI is administered by kindergarten teachers, who assess their kindergarten students on 5 developmental domains: physical health and well-being, social…

  6. Early Childhood Care and Education and School Readiness in Zambia

    ERIC Educational Resources Information Center

    McCoy, Dana Charles; Zuilkowski, Stephanie Simmons; Yoshikawa, Hirokazu; Fink, Günther

    2017-01-01

    Despite increased investment in early childhood care and education (ECCE) globally, little is known about its effectiveness in low-income countries. Using kernel exact matching within a national sample of 1,623 Zambian 6-year-olds, we test the associations between ECCE participation and seven domains of children's school readiness. We find ECCE…

  7. Who I Am: The Meaning of Early Adolescents' Most Valued Activities and Relationships, and Implications for Self-Concept Research

    ERIC Educational Resources Information Center

    Tatlow-Golden, Mimi; Guerin, Suzanne

    2017-01-01

    Self-concept research in early adolescence typically measures young people's self-perceptions of competence in specific, adult-defined domains. However, studies have rarely explored young people's own views of valued self-concept factors and their meanings. For two major self domains, the active and the social self, this mixed-methods study…

  8. Multifunctionalities driven by ferroic domains

    NASA Astrophysics Data System (ADS)

    Yang, J. C.; Huang, Y. L.; He, Q.; Chu, Y. H.

    2014-08-01

    Considerable attention has been paid to ferroic systems in pursuit of advanced applications in past decades. Most recently, the emergence and development of multiferroics, which exhibit the coexistence of different ferroic natures, has offered a new route to create functionalities in the system. In this manuscript, we step from domain engineering to explore a roadmap for discovering intriguing phenomena and multifunctionalities driven by periodic domain patters. As-grown periodic domains, offering exotic order parameters, periodic local perturbations and the capability of tailoring local spin, charge, orbital and lattice degrees of freedom, are introduced as modeling templates for fundamental studies and novel applications. We discuss related significant findings on ferroic domain, nanoscopic domain walls, and conjunct heterostructures based on the well-organized domain patterns, and end with future prospects and challenges in the field.

  9. Early Stages of Sea-Level Rise Lead To Decreased Salt Marsh Plant Diversity through Stronger Competition in Mediterranean-Climate Marshes.

    PubMed

    Noto, Akana E; Shurin, Jonathan B

    2017-01-01

    Climate change shuffles species ranges and creates novel interactions that may either buffer communities against climate change or exacerbate its effect. For instance, facilitation can become more prevalent in salt marshes under stressful conditions while competition is stronger in benign environments. Sea-level rise (SLR) is a consequence of climate change that affects the distribution of stress from inundation and salinity. To determine how interactions early in SLR are affected by changes in these two stressors in Mediterranean-climate marshes, we transplanted marsh turfs to lower elevations to simulate SLR and manipulated cover of the dominant plant species, Salicornia pacifica (formerly Salicornia virginica). We found that both S. pacifica and the subordinate species were affected by inundation treatments, and that subordinate species cover and diversity were lower at low elevations in the presence of S. pacifica than when it was removed. These results suggest that the competitive effect of S. pacifica on other plants is stronger at lower tidal elevations where we also found that salinity is reduced. As sea levels rise, stronger competition by the dominant plant will likely reduce diversity and cover of subordinate species, suggesting that stronger species interactions will exacerbate the effects of climate change on the plant community.

  10. The uses of outcome measures within multidisciplinary early childhood intervention services: a systematic review.

    PubMed

    Calder, Samuel; Ward, Roslyn; Jones, Megan; Johnston, Jenelle; Claessen, Mary

    2017-07-18

    Purpose of the article: To review the use of outcome measures, across the domains of activity, participation, and environment, within multidisciplinary early childhood intervention services. A systematic literature search was undertaken that included four electronic databases: Medline, CINAHL, EMBASE, and the Cochrane Library and Cochrane Database of Systematic Review. Inclusion criteria were age 0-24 months, having or at risk of a developmental disability, in receipt of multidisciplinary early childhood intervention services, and included outcome measures across all domains of the International Classification of Functioning-Child & Youth (ICF-CY). Only peer-reviewed journal articles were considered. Eligible studies were coded using the Oxford Levels of Evidence. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) Scale for randomised controlled trials and the QualSyst for non-randomised control trials. Of the total of 5764 records identified, 10 were considered to meet inclusion criteria. Fourteen outcome measures were identified, addressing the domains of activity, participation, and environment. Of these, eight have been recommended in the early intervention literature. While the methodological quality of the 10 studies varied, these papers make a contribution to the body of research that acknowledges the role of routine and enriched environments. Implications for Rehabilitation Core practice elements of multidisciplinary early childhood intervention services indicate it is necessary to select outcome measures framed within the International Classification of Functioning-Child & Youth to inform clinical decision-making for measuring intervention effectiveness across the domains of activity, participation and environment. Of the identified measures, three (Canadian Occupational Performance Measure, Pediatric Evaluation of Disability Inventory, and Goal Attainment Scaling) are well-established and identified in the literature as

  11. Text Processing of Domain-Related Information for Individuals with High and Low Domain Knowledge.

    ERIC Educational Resources Information Center

    Spilich, George J.; And Others

    1979-01-01

    The way in which previously acquired knowledge affects the processing on new domain-related information was investigated. Text processing was studied in two groups differing in knowledge of the domain of baseball. A knowledge structure for the domain was constructed, and text propositions were classified. (SW)

  12. A Novel Domain Assembly Routine for Creating Full-Length Models of Membrane Proteins from Known Domain Structures.

    PubMed

    Koehler Leman, Julia; Bonneau, Richard

    2018-04-03

    Membrane proteins composed of soluble and membrane domains are often studied one domain at a time. However, to understand the biological function of entire protein systems and their interactions with each other and drugs, knowledge of full-length structures or models is required. Although few computational methods exist that could potentially be used to model full-length constructs of membrane proteins, none of these methods are perfectly suited for the problem at hand. Existing methods require an interface or knowledge of the relative orientations of the domains or are not designed for domain assembly, and none of them are developed for membrane proteins. Here we describe the first domain assembly protocol specifically designed for membrane proteins that assembles intra- and extracellular soluble domains and the transmembrane domain into models of the full-length membrane protein. Our protocol does not require an interface between the domains and samples possible domain orientations based on backbone dihedrals in the flexible linker regions, created via fragment insertion, while keeping the transmembrane domain fixed in the membrane. For five examples tested, our method mp_domain_assembly, implemented in RosettaMP, samples domain orientations close to the known structure and is best used in conjunction with experimental data to reduce the conformational search space.

  13. The C-Terminal Domain of the Virulence Factor MgtC Is a Divergent ACT Domain

    PubMed Central

    Yang, Yinshan; Labesse, Gilles; Carrère-Kremer, Séverine; Esteves, Kevin; Kremer, Laurent

    2012-01-01

    MgtC is a virulence factor of unknown function important for survival inside macrophages in several intracellular bacterial pathogens, including Mycobacterium tuberculosis. It is also involved in adaptation to Mg2+ deprivation, but previous work suggested that MgtC is not a Mg2+ transporter. In this study, we demonstrated that the amount of the M. tuberculosis MgtC protein is not significantly increased by Mg2+ deprivation. Members of the MgtC protein family share a conserved membrane N-terminal domain and a more divergent cytoplasmic C-terminal domain. To get insights into MgtC functional and structural organization, we have determined the nuclear magnetic resonance (NMR) structure of the C-terminal domain of M. tuberculosis MgtC. This structure is not affected by the Mg2+ concentration, indicating that it does not bind Mg2+. The structure of the C-terminal domain forms a βαββαβ fold found in small molecule binding domains called ACT domains. However, the M. tuberculosis MgtC ACT domain differs from canonical ACT domains because it appears to lack the ability to dimerize and to bind small molecules. We have shown, using a bacterial two-hybrid system, that the M. tuberculosis MgtC protein can dimerize and that the C-terminal domain somehow facilitates this dimerization. Taken together, these results indicate that M. tuberculosis MgtC does not have an intrinsic function related to Mg2+ uptake or binding but could act as a regulatory factor based on protein-protein interaction that could be facilitated by its ACT domain. PMID:22984256

  14. The Early Development Instrument: An Examination of Convergent and Discriminant Validity

    ERIC Educational Resources Information Center

    Hymel, Shelley; LeMare, Lucy; McKee, William

    2011-01-01

    The convergent and discriminant validity of the Early Development Instrument (EDI), a teacher-rated assessment of children's "school readiness", was investigated in a multicultural sample of 267 kindergarteners (53% male). Teachers evaluations on the EDI, both overall and in five domains (physical health/well-being, social competence,…

  15. Discussion summary: Fictitious domain methods

    NASA Technical Reports Server (NTRS)

    Glowinski, Rowland; Rodrigue, Garry

    1991-01-01

    Fictitious Domain methods are constructed in the following manner: Suppose a partial differential equation is to be solved on an open bounded set, Omega, in 2-D or 3-D. Let R be a rectangle domain containing the closure of Omega. The partial differential equation is first solved on R. Using the solution on R, the solution of the equation on Omega is then recovered by some procedure. The advantage of the fictitious domain method is that in many cases the solution of a partial differential equation on a rectangular region is easier to compute than on a nonrectangular region. Fictitious domain methods for solving elliptic PDEs on general regions are also very efficient when used on a parallel computer. The reason is that one can use the many domain decomposition methods that are available for solving the PDE on the fictitious rectangular region. The discussion on fictitious domain methods began with a talk by R. Glowinski in which he gave some examples of a variational approach to ficititious domain methods for solving the Helmholtz and Navier-Stokes equations.

  16. Phanerozoic geological evolution of the Equatorial Atlantic domain

    NASA Astrophysics Data System (ADS)

    Basile, Christophe; Mascle, Jean; Guiraud, René

    2005-10-01

    The Phanerozoic geological evolution of the Equatorial Atlantic domain has been controlled since the end of Early Cretaceous by the Romanche and Saint Paul transform faults. These faults did not follow the PanAfrican shear zones, but were surimposed on Palæozoic basins. From Neocomian to Barremian, the Central Atlantic rift propagated southward in Cassiporé and Marajó basins, and the South Atlantic rift propagated northward in Potiguar and Benue basins. During Aptian times, the Equatorial Atlantic transform domain appeared as a transfer zone between the northward propagating tip of South Atlantic and the Central Atlantic. Between the transform faults, oceanic accretion started during Late Aptian in small divergent segments, from south to north: Benin-Mundaú, deep Ivorian basin-Barreirinhas, Liberia-Cassiporé. From Late Aptian to Late Albian, the Togo-Ghana-Ceará basins appeared along the Romanche transform fault, and Côte d'Ivoire-Parà-Maranhão basins along Saint Paul transform fault. They were rapidly subsiding in intra-continental settings. During Late Cretaceous, these basins became active transform continental margins, and passive margins since Santonian times. In the same time, the continental edge uplifted leading either to important erosion on the shelf or to marginal ridges parallel to the transform faults in deeper settings.

  17. Role of distal arginine in early sensing intermediates in the heme domain of the oxygen sensor FixL.

    PubMed

    Jasaitis, Audrius; Hola, Klara; Bouzhir-Sima, Latifa; Lambry, Jean-Christophe; Balland, Veronique; Vos, Marten H; Liebl, Ursula

    2006-05-16

    FixL is a bacterial heme-based oxygen sensor, in which release of oxygen from the sensing PAS domain leads to activation of an associated kinase domain. Static structural studies have suggested an important role of the conserved residue arginine 220 in signal transmission at the level of the heme domain. To assess the role of this residue in the dynamics and properties of the initial intermediates in ligand release, we have investigated the effects of R220X (X = I, Q, E, H, or A) mutations in the FixLH heme domain on the dynamics and spectral properties of the heme upon photolysis of O(2), NO, and CO using femtosecond transient absorption spectroscopy. Comparison of transient spectra for CO and NO dissociation with steady-state spectra indicated less strain on the heme in the ligand dissociation species for all mutants compared to the wild type (WT). For CO and NO, the kinetics were similar to those of the wild type, with the exception of (1) a relatively low yield of picosecond NO rebinding to R220A, presumably related to the increase in the free volume of the heme pocket, and (2) substantial pH-dependent picosecond to nanosecond rebinding of CO to R220H, related to formation of a hydrogen bond between CO and histidine 220. Upon excitation of the complex bound with the physiological sensor ligand O(2), a 5-8 ps decay phase and a nondecaying (>4 ns) phase were observed for WT and all mutants. The strong distortion of the spectrum associated with the decay phase in WT is substantially diminished in all mutant proteins, indicating an R220-induced role of the heme in the primary intermediate in signal transmission. Furthermore, the yield of dissociated oxygen after this phase ( approximately 10% in WT) is increased in all mutants, up to almost unity in R220A, indicating a key role of R220 in caging the oxygen near the heme through hydrogen bonding. Molecular dynamics simulations corroborate these findings and suggest motions of O(2) and arginine 220 away from the heme

  18. Rethinking Research in Early Care and Education: Joining Sally's Quest

    ERIC Educational Resources Information Center

    New, Rebecca S.

    2008-01-01

    The article considers three domains of Sally Lubeck's scholarship as illustrations of her orientation to research on early care and education: her critique of positivism in general and the field of developmental psychology (and the sub-discipline of child development) specifically as the primary source of a "knowledge base" for the field of early…

  19. Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments.

    PubMed

    Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter

    2017-01-01

    Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments - one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.

  20. Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins

    PubMed Central

    Crisci, Angela; Raleff, Flore; Bagdiul, Ivona; Raabe, Monika; Urlaub, Henning; Rain, Jean-Christophe; Krämer, Angela

    2015-01-01

    Splicing factor 1 (SF1) recognizes the branch point sequence (BPS) at the 3′ splice site during the formation of early complex E, thereby pre-bulging the BPS adenosine, thought to facilitate subsequent base-pairing of the U2 snRNA with the BPS. The 65-kDa subunit of U2 snRNP auxiliary factor (U2AF65) interacts with SF1 and was shown to recruit the U2 snRNP to the spliceosome. Co-immunoprecipitation experiments of SF1-interacting proteins from HeLa cell extracts shown here are consistent with the presence of SF1 in early splicing complexes. Surprisingly almost all U2 snRNP proteins were found associated with SF1. Yeast two-hybrid screens identified two SURP domain-containing U2 snRNP proteins as partners of SF1. A short, evolutionarily conserved region of SF1 interacts with the SURP domains, stressing their role in protein–protein interactions. A reduction of A complex formation in SF1-depleted extracts could be rescued with recombinant SF1 containing the SURP-interaction domain, but only partial rescue was observed with SF1 lacking this sequence. Thus, SF1 can initially recruit the U2 snRNP to the spliceosome during E complex formation, whereas U2AF65 may stabilize the association of the U2 snRNP with the spliceosome at later times. In addition, these findings may have implications for alternative splicing decisions. PMID:26420826

  1. Impairment in Proverb Interpretation as an Executive Function Deficit in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease

    PubMed Central

    Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W.; Milian, Monika

    2011-01-01

    Background/Aims Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. Methods We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). Results The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Conclusions Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD. PMID:22163233

  2. Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication

    PubMed Central

    Gu, Haidong

    2016-01-01

    Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced “conquer and compromise” strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host. PMID:26870669

  3. Low performance on mathematical tasks in preschoolers: the importance of domain-general and domain-specific abilities.

    PubMed

    Costa, H M; Nicholson, B; Donlan, C; Van Herwegen, J

    2018-04-01

    Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether this also holds for preschool low achievers (LAs) and how domain-specific and domain-general abilities contribute to mathematical difficulties at a young age. The aim of this study was to explore the cognitive characteristics of a sample of preschool LAs and identify sub-types of LAs. 81 children were identified as LAs from 283 preschoolers aged 3 to 5 years old and were assessed on a number of domain-general and domain-specific tasks. Cluster analysis revealed four subgroups of LAs in mathematics: (1) a weak processing sub-type; (2) a general mathematical LAs sub-type; (3) a mixed abilities sub-type; and (4) a visuo-spatial deficit sub-type. Whilst two of the groups showed specific domain-general difficulties, none showed only domain-specific difficulties. Current findings suggest that preschool LAs constitute a heterogeneous group and stress the importance of domain-general factors for the development of mathematical abilities during the preschool years. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  4. Polar Domain Discovery with Sparkler

    NASA Astrophysics Data System (ADS)

    Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

    2017-12-01

    The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

  5. Early-life predictors of leisure-time physical inactivity in midadulthood: findings from a prospective British birth cohort.

    PubMed

    Pinto Pereira, Snehal M; Li, Leah; Power, Chris

    2014-12-01

    Much adult physical inactivity research ignores early-life factors from which later influences may originate. In the 1958 British birth cohort (followed from 1958 to 2008), leisure-time inactivity, defined as activity frequency of less than once a week, was assessed at ages 33, 42, and 50 years (n = 12,776). Early-life factors (at ages 0-16 years) were categorized into 3 domains (i.e., physical, social, and behavioral). We assessed associations of adult inactivity 1) with factors within domains, 2) with the 3 domains combined, and 3) allowing for adult factors. At each age, approximately 32% of subjects were inactive. When domains were combined, factors associated with inactivity (e.g., at age 50 years) were prepubertal stature (5% lower odds per 1-standard deviation higher height), hand control/coordination problems (14% higher odds per 1-point increase on a 4-point scale), cognition (10% lower odds per 1-standard deviation greater ability), parental divorce (21% higher odds), institutional care (29% higher odds), parental social class at child's birth (9% higher odds per 1-point reduction on a 4-point scale), minimal parental education (13% higher odds), household amenities (2% higher odds per increase (representing poorer amenities) on a 19-point scale), inactivity (8% higher odds per 1-point reduction in activity on a 4-point scale), low sports aptitude (13% higher odds), and externalizing behaviors (i.e., conduct problems) (5% higher odds per 1-standard deviation higher score). Adjustment for adult covariates weakened associations slightly. Factors from early life were associated with adult leisure-time inactivity, allowing for early identification of groups vulnerable to inactivity. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Investigating the Incremental Validity of Cognitive Variables in Early Mathematics Screening

    ERIC Educational Resources Information Center

    Clarke, Ben; Shanley, Lina; Kosty, Derek; Baker, Scott K.; Cary, Mari Strand; Fien, Hank; Smolkowski, Keith

    2018-01-01

    The purpose of this study was to investigate the incremental validity of a set of domain general cognitive measures added to a traditional screening battery of early numeracy measures. The sample consisted of 458 kindergarten students of whom 285 were designated as severely at-risk for mathematics difficulty. Hierarchical multiple regression…

  7. Peripartum depression and anxiety as an integrative cross domain target for psychiatric preventative measures.

    PubMed

    Babb, Jessica A; Deligiannidis, Kristina M; Murgatroyd, Christopher A; Nephew, Benjamin C

    2015-01-01

    Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Modeling software systems by domains

    NASA Technical Reports Server (NTRS)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

    The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.

  9. Ferroelectric negative capacitance domain dynamics

    NASA Astrophysics Data System (ADS)

    Hoffmann, Michael; Khan, Asif Islam; Serrao, Claudy; Lu, Zhongyuan; Salahuddin, Sayeef; Pešić, Milan; Slesazeck, Stefan; Schroeder, Uwe; Mikolajick, Thomas

    2018-05-01

    Transient negative capacitance effects in epitaxial ferroelectric Pb(Zr0.2Ti0.8)O3 capacitors are investigated with a focus on the dynamical switching behavior governed by domain nucleation and growth. Voltage pulses are applied to a series connection of the ferroelectric capacitor and a resistor to directly measure the ferroelectric negative capacitance during switching. A time-dependent Ginzburg-Landau approach is used to investigate the underlying domain dynamics. The transient negative capacitance is shown to originate from reverse domain nucleation and unrestricted domain growth. However, with the onset of domain coalescence, the capacitance becomes positive again. The persistence of the negative capacitance state is therefore limited by the speed of domain wall motion. By changing the applied electric field, capacitor area or external resistance, this domain wall velocity can be varied predictably over several orders of magnitude. Additionally, detailed insights into the intrinsic material properties of the ferroelectric are obtainable through these measurements. A new method for reliable extraction of the average negative capacitance of the ferroelectric is presented. Furthermore, a simple analytical model is developed, which accurately describes the negative capacitance transient time as a function of the material properties and the experimental boundary conditions.

  10. Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase: regulation by autoinhibitory and visinin-like domains

    NASA Technical Reports Server (NTRS)

    Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.

    1997-01-01

    A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.

  11. Folding pathway of a multidomain protein depends on its topology of domain connectivity

    PubMed Central

    Inanami, Takashi; Terada, Tomoki P.; Sasai, Masaki

    2014-01-01

    How do the folding mechanisms of multidomain proteins depend on protein topology? We addressed this question by developing an Ising-like structure-based model and applying it for the analysis of free-energy landscapes and folding kinetics of an example protein, Escherichia coli dihydrofolate reductase (DHFR). DHFR has two domains, one comprising discontinuous N- and C-terminal parts and the other comprising a continuous middle part of the chain. The simulated folding pathway of DHFR is a sequential process during which the continuous domain folds first, followed by the discontinuous domain, thereby avoiding the rapid decrease in conformation entropy caused by the association of the N- and C-terminal parts during the early phase of folding. Our simulated results consistently explain the observed experimental data on folding kinetics and predict an off-pathway structural fluctuation at equilibrium. For a circular permutant for which the topological complexity of wild-type DHFR is resolved, the balance between energy and entropy is modulated, resulting in the coexistence of the two folding pathways. This coexistence of pathways should account for the experimentally observed complex folding behavior of the circular permutant. PMID:25267632

  12. Translocation of the Catalytic Domain of Diphtheria Toxin across Planar Phospholipid Bilayers by Its Own T Domain

    NASA Astrophysics Data System (ADS)

    Oh, Kyoung Joon; Senzel, Lisa; Collier, R. John; Finkelstein, Alan

    1999-07-01

    The T domain of diphtheria toxin is known to participate in the pH-dependent translocation of the catalytic C domain of the toxin across the endosomal membrane, but how it does so, and whether cellular proteins are also required for this process, remain unknown. Here, we report results showing that the T domain alone is capable of translocating the entire C domain across model, planar phospholipid bilayers in the absence of other proteins. The T domain therefore contains the entire molecular machinery for mediating transfer of the catalytic domain of diphtheria toxin across membranes.

  13. Scientific Reasoning across Different Domains.

    ERIC Educational Resources Information Center

    Glaser, Robert; And Others

    This study seeks to establish which scientific reasoning skills are primarily domain-general and which appear to be domain-specific. The subjects, 12 university undergraduates, each participated in self-directed experimentation with three different content domains. The experimentation contexts were computer-based laboratories in d.c. circuits…

  14. Detecting atypical examples of known domain types by sequence similarity searching: the SBASE domain library approach.

    PubMed

    Dhir, Somdutta; Pacurar, Mircea; Franklin, Dino; Gáspári, Zoltán; Kertész-Farkas, Attila; Kocsor, András; Eisenhaber, Frank; Pongor, Sándor

    2010-11-01

    SBASE is a project initiated to detect known domain types and predicting domain architectures using sequence similarity searching (Simon et al., Protein Seq Data Anal, 5: 39-42, 1992, Pongor et al, Nucl. Acids. Res. 21:3111-3115, 1992). The current approach uses a curated collection of domain sequences - the SBASE domain library - and standard similarity search algorithms, followed by postprocessing which is based on a simple statistics of the domain similarity network (http://hydra.icgeb.trieste.it/sbase/). It is especially useful in detecting rare, atypical examples of known domain types which are sometimes missed even by more sophisticated methodologies. This approach does not require multiple alignment or machine learning techniques, and can be a useful complement to other domain detection methodologies. This article gives an overview of the project history as well as of the concepts and principles developed within this the project.

  15. Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign).

    PubMed

    Chen, Eric; Brown, David M; Benz, Matthew S; Fish, Richard H; Wong, Tien P; Kim, Rosa Y; Major, James C

    2010-10-21

    While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage. Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers. Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the "flying saucer" sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none. Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.

  16. Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II.

    PubMed

    Chang, A; Cheang, S; Espanel, X; Sudol, M

    2000-07-07

    RSP5 is an essential gene in Saccharomyces cerevisiae and was recently shown to form a physical and functional complex with RNA polymerase II (RNA pol II). The amino-terminal half of Rsp5 consists of four domains: a C2 domain, which binds membrane phospholipids; and three WW domains, which are protein interaction modules that bind proline-rich ligands. The carboxyl-terminal half of Rsp5 contains a HECT (homologous to E6-AP carboxyl terminus) domain that catalytically ligates ubiquitin to proteins and functionally classifies Rsp5 as an E3 ubiquitin-protein ligase. The C2 and WW domains are presumed to act as membrane localization and substrate recognition modules, respectively. We report that the second (and possibly third) Rsp5 WW domain mediates binding to the carboxyl-terminal domain (CTD) of the RNA pol II large subunit. The CTD comprises a heptamer (YSPTSPS) repeated 26 times and a PXY core that is critical for interaction with a specific group of WW domains. An analysis of synthetic peptides revealed a minimal CTD sequence that is sufficient to bind to the second Rsp5 WW domain (Rsp5 WW2) in vitro and in yeast two-hybrid assays. Furthermore, we found that specific "imperfect" CTD repeats can form a complex with Rsp5 WW2. In addition, we have shown that phosphorylation of this minimal CTD sequence on serine, threonine and tyrosine residues acts as a negative regulator of the Rsp5 WW2-CTD interaction. In view of the recent data pertaining to phosphorylation-driven interactions between the RNA pol II CTD and the WW domain of Ess1/Pin1, we suggest that CTD dephosphorylation may be a prerequisite for targeted RNA pol II degradation.

  17. Illumination discrimination in the absence of a fixed surface-reflectance layout

    PubMed Central

    Radonjić, Ana; Ding, Xiaomao; Krieger, Avery; Aston, Stacey; Hurlbert, Anya C.; Brainard, David H.

    2018-01-01

    Previous studies have shown that humans can discriminate spectral changes in illumination and that this sensitivity depends both on the chromatic direction of the illumination change and on the ensemble of surfaces in the scene. These studies, however, always used stimulus scenes with a fixed surface-reflectance layout. Here we compared illumination discrimination for scenes in which the surface reflectance layout remains fixed (fixed-surfaces condition) to those in which surface reflectances were shuffled randomly across scenes, but with the mean scene reflectance held approximately constant (shuffled-surfaces condition). Illumination discrimination thresholds in the fixed-surfaces condition were commensurate with previous reports. Thresholds in the shuffled-surfaces condition, however, were considerably elevated. Nonetheless, performance in the shuffled-surfaces condition exceeded that attainable through random guessing. Analysis of eye fixations revealed that in the fixed-surfaces condition, low illumination discrimination thresholds (across observers) were predicted by low overall fixation spread and high consistency of fixation location and fixated surface reflectances across trial intervals. Performance in the shuffled-surfaces condition was not systematically related to any of the eye-fixation characteristics we examined for that condition, but was correlated with performance in the fixed-surfaces condition. PMID:29904786

  18. Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments

    PubMed Central

    Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter

    2018-01-01

    Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments — one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.† PMID:29457801

  19. Do People Who Became Blind Early in Life Develop a Better Sense of Smell? A Psychophysical Study

    ERIC Educational Resources Information Center

    Cuevas, Isabel; Plaza, Paula; Rombaux, Phillippe; Collignon, Olivier; De Volder, Anne G.; Renier, Laurent

    2010-01-01

    Using a set of psychophysical tests, we compared the olfactory abilities of 8 persons who became blind early in life and 16 sighted persons in a control group who were matched for age, sex, and handedness. The results indicated that those who became blind early in life developed compensatory perceptual mechanisms in the olfactory domain that…

  20. Time-domain imaging

    NASA Technical Reports Server (NTRS)

    Tolliver, C. L.

    1989-01-01

    The quest for the highest resolution microwave imaging and principle of time-domain imaging has been the primary motivation for recent developments in time-domain techniques. With the present technology, fast time varying signals can now be measured and recorded both in magnitude and in-phase. It has also enhanced our ability to extract relevant details concerning the scattering object. In the past, the interface of object geometry or shape for scattered signals has received substantial attention in radar technology. Various scattering theories were proposed to develop analytical solutions to this problem. Furthermore, the random inversion, frequency swept holography, and the synthetic radar imaging, have two things in common: (1) the physical optic far-field approximation, and (2) the utilization of channels as an extra physical dimension, were also advanced. Despite the inherent vectorial nature of electromagnetic waves, these scalar treatments have brought forth some promising results in practice with notable examples in subsurface and structure sounding. The development of time-domain techniques are studied through the theoretical aspects as well as experimental verification. The use of time-domain imaging for space robotic vision applications has been suggested.

  1. The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

    PubMed Central

    Dilworth, David; Bonnafous, Pierre; Edoo, Amiirah Bibi; Bourbigot, Sarah; Pesek-Jardim, Francy; Gudavicius, Geoff; Serpa, Jason J.; Petrotchenko, Evgeniy V.; Borchers, Christoph H.

    2017-01-01

    Abstract Prolyl isomerases are defined by a catalytic domain that facilitates the cis–trans interconversion of proline residues. In most cases, additional domains in these enzymes add important biological function, including recruitment to a set of protein substrates. Here, we report that the N-terminal basic tilted helix bundle (BTHB) domain of the human prolyl isomerase FKBP25 confers specific binding to double-stranded RNA (dsRNA). This binding is selective over DNA as well as single-stranded oligonucleotides. We find that FKBP25 RNA-association is required for its nucleolar localization and for the vast majority of its protein interactions, including those with 60S pre-ribosome and early ribosome biogenesis factors. An independent mobility of the BTHB and FKBP catalytic domains supports a model by which the N-terminus of FKBP25 is anchored to regions of dsRNA, whereas the FKBP domain is free to interact with neighboring proteins. Apart from the identification of the BTHB as a new dsRNA-binding module, this domain adds to the growing list of auxiliary functions used by prolyl isomerases to define their primary cellular targets. PMID:29036638

  2. Macular micropseudocysts in early stages of diabetic retinopathy.

    PubMed

    Tremolada, Gemma; Pierro, Luisa; de Benedetto, Umberto; Margari, Sergio; Gagliardi, Marco; Maestranzi, Gisella; Calori, Giliola; Lorenzi, Mara; Lattanzio, Rosangela

    2011-01-01

    To identify by noninvasive means early retinal abnormalities that may predict diabetic macular edema. The authors analyzed retrospectively data from consecutive patients with Type 1 (n = 16) or Type 2 (n = 23) diabetes who presented for routine follow-up of early retinopathy, had no clinical signs or symptoms of diabetic macular edema, and were evaluated with spectral-domain optical coherence tomography. Age- and gender-matched nondiabetic subjects provided normative data. Spectral-domain optical coherence tomography revealed in the macular region of diabetic patients small hyporeflective areas (median diameter, 55 μm) contained within discrete retinal layers that we named micropseudocysts (MPCs). Micropseudocysts are associated with vascular leakage. The patients showing MPCs had more frequently systemic hypertension and increased central foveal thickness than those without MPCs. The association with increased central foveal thickness was only in the patients with Type 2 diabetes. Macular MPCs in patients with mild diabetic retinopathy appear to reflect leakage and can precede macular thickening. The association of MPCs with increased central foveal thickness in patients with Type 2 diabetes, but not in patients with Type 1 diabetes, points to a greater tendency to retinal fluid accumulation in patients with Type 2 diabetes. Studies in larger cohorts will determine the usefulness of MPCs in strategies to abort diabetic macular edema.

  3. Domain Hierarchy and closed Loops (DHcL): a server for exploring hierarchy of protein domain structure

    PubMed Central

    Koczyk, Grzegorz; Berezovsky, Igor N.

    2008-01-01

    Domain hierarchy and closed loops (DHcL) (http://sitron.bccs.uib.no/dhcl/) is a web server that delineates energy hierarchy of protein domain structure and detects domains at different levels of this hierarchy. The server also identifies closed loops and van der Waals locks, which constitute a structural basis for the protein domain hierarchy. The DHcL can be a useful tool for an express analysis of protein structures and their alternative domain decompositions. The user submits a PDB identifier(s) or uploads a 3D protein structure in a PDB format. The results of the analysis are the location of domains at different levels of hierarchy, closed loops, van der Waals locks and their interactive visualization. The server maintains a regularly updated database of domains, closed loop and van der Waals locks for all X-ray structures in PDB. DHcL server is available at: http://sitron.bccs.uib.no/dhcl. PMID:18502776

  4. Two conformations of the integrin A-domain (I-domain): a pathway for activation?

    PubMed

    Lee, J O; Bankston, L A; Arnaout, M A; Liddington, R C

    1995-12-15

    Integrins are plasma membrane proteins that mediate adhesion to other cells and to components of the extracellular matrix. Most integrins are constitutively inactive in resting cells, but are rapidly and reversibly activated in response to agonists, leading to highly regulated cell adhesion. This activation is associated with conformational changes in their extracellular portions, but the nature of the structural changes that lead to a change in adhesiveness is not understood. The interactions of several integrins with their extracellular ligands are mediated by an A-type domain (generally called the I-domain in integrins). Binding of the I-domain to protein ligands is dependent on divalent cations. We have described previously the structure of the I-domain from complement receptor 3 with bound Mg2+, in which the glutamate side chain from a second I-domain completes the octahedral coordination sphere of the metal, acting as a ligand mimetic. We now describe a new crystal form of the I-domain with bound Mn2+, in which water completes the metal coordination sphere and there is no equivalent of the glutamate ligand. Comparison of the two crystal forms reveals a change in metal coordination which is linked to a large (10 A) shift of the C-terminal helix and the burial of two phenylalanine residues into the hydrophobic core of the Mn2+ form. These structural changes, analogous to those seen in the signal-transducing G-proteins, alter the electrophilicity of the metal, reducing its ability to bind ligand-associated acidic residues, and dramatically alter the surface of the protein implicated in binding ligand. Our observations provide the first atomic resolution view of conformational changes in an integrin domain, and suggest how these changes are linked to a change in integrin adhesiveness. We propose that the Mg2+ form represents the conformation of the domain in the active state and the Mn2+ form the conformation in the inactive state of the integrin.

  5. Comparative analysis of barophily-related amino acid content in protein domains of Pyrococcus abyssi and Pyrococcus furiosus.

    PubMed

    Yafremava, Liudmila S; Di Giulio, Massimo; Caetano-Anollés, Gustavo

    2013-01-01

    Amino acid substitution patterns between the nonbarophilic Pyrococcus furiosus and its barophilic relative P. abyssi confirm that hydrostatic pressure asymmetry indices reflect the extent to which amino acids are preferred by barophilic archaeal organisms. Substitution patterns in entire protein sequences, shared protein domains defined at fold superfamily level, domains in homologous sequence pairs, and domains of very ancient and very recent origin now provide further clues about the environment that led to the genetic code and diversified life. The pyrococcal proteomes are very similar and share a very early ancestor. Relative amino acid abundance analyses showed that biases in the use of amino acids are due to their shared fold superfamilies. Within these repertoires, only two of the five amino acids that are preferentially barophilic, aspartic acid and arginine, displayed this preference significantly and consistently across structure and in domains appearing in the ancestor. The more primordial asparagine, lysine and threonine displayed a consistent preference for nonbarophily across structure and in the ancestor. Since barophilic preferences are already evident in ancient domains that are at least ~3 billion year old, we conclude that barophily is a very ancient trait that unfolded concurrently with genetic idiosyncrasies in convergence towards a universal code.

  6. Domain Adaptation with Conditional Transferable Components

    PubMed Central

    Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard

    2017-01-01

    Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components T(X) that have similar P(T(X)) on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if P(Y∣T(X)) in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution P(T(X)∣Y) is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method. PMID:28239433

  7. Protective and compensatory factors mitigating the influence of deviant friends on delinquent behaviours during early adolescence.

    PubMed

    Fergusson, David M; Vitaro, Frank; Wanner, Brigitte; Brendgen, Mara

    2007-02-01

    This study examined factors that could moderate or compensate the link between exposure to deviant friends and delinquent behaviours in a sample of 265 early adolescents. The putative moderating or compensatory factors referred to the behavioural domain (i.e. novelty seeking, harm avoidance), the biological domain (i.e. physical maturation), the sociofamily domain (i.e. sociofamily adversity, parental practices), the school domain (i.e. academic performance), and the social domain (i.e. peer acceptance). A series of regression analyses showed that novelty seeking and puberty status moderated the link between friends' self-reported delinquency and participants' self-reported delinquency. In addition, all the factors except peer acceptance also had main effects that, cumulatively, reduced the association between friends' delinquency and self-rated delinquency through compensatory main effects. These results are discussed in light of the differential roles of moderating and of compensatory factors.

  8. Laurie R. Santos: Award for Distinguished Scientific Early Career Contributions to Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the winners of the American Psychological Association's Award for Distinguished Scientific Early Career Contributions to Psychology. The 2012 winner is Laurie R. Santos for creative and insightful investigations of cognition across a broad range of species and psychological domains, illuminating cognitive…

  9. Similarity between Early and Middle Adolescent Close Friends' Beliefs about Personal Jurisdiction

    ERIC Educational Resources Information Center

    Daddis, Christopher

    2008-01-01

    Similarity in close friends' beliefs about personal jurisdiction was examined using questionnaires and interviews with 162 early (M[subscript age] = 11.82) and middle (M[subscript age] = 15.68) adolescents who were matched with reciprocally nominated close friends. Using the framework of social domain theory, beliefs about personal jurisdiction…

  10. Monte Carlo simulation of ferroelectric domain growth

    NASA Astrophysics Data System (ADS)

    Li, B. L.; Liu, X. P.; Fang, F.; Zhu, J. L.; Liu, J.-M.

    2006-01-01

    The kinetics of two-dimensional isothermal domain growth in a quenched ferroelectric system is investigated using Monte Carlo simulation based on a realistic Ginzburg-Landau ferroelectric model with cubic-tetragonal (square-rectangle) phase transitions. The evolution of the domain pattern and domain size with annealing time is simulated, and the stability of trijunctions and tetrajunctions of domain walls is analyzed. It is found that in this much realistic model with strong dipole alignment anisotropy and long-range Coulomb interaction, the powerlaw for normal domain growth still stands applicable. Towards the late stage of domain growth, both the average domain area and reciprocal density of domain wall junctions increase linearly with time, and the one-parameter dynamic scaling of the domain growth is demonstrated.

  11. Domain-Specific Control of Selective Attention

    PubMed Central

    Lin, Szu-Hung; Yeh, Yei-Yu

    2014-01-01

    Previous research has shown that loading information on working memory affects selective attention. However, whether the load effect on selective attention is domain-general or domain-specific remains unresolved. The domain-general effect refers to the findings that load in one content (e.g. phonological) domain in working memory influences processing in another content (e.g., visuospatial) domain. Attentional control supervises selection regardless of information domain. The domain-specific effect refers to the constraint of influence only when maintenance and processing operate in the same domain. Selective attention operates in a specific content domain. This study is designed to resolve this controversy. Across three experiments, we manipulated the type of representation maintained in working memory and the type of representation upon which the participants must exert control to resolve conflict and select a target into the focus of attention. In Experiments 1a and 1b, participants maintained digits and nonverbalized objects, respectively, in working memory while selecting a target in a letter array. In Experiment 2, we presented auditory digits with a letter flanker task to exclude the involvement of resource competition within the same input modality. In Experiments 3a and 3b, we replaced the letter flanker task with an object flanker task while manipulating the memory load on object and digit representation, respectively. The results consistently showed that memory load modulated distractibility only when the stimuli of the two tasks were represented in the same domain. The magnitude of distractor interference was larger under high load than under low load, reflecting a lower efficacy of information prioritization. When the stimuli of the two tasks were represented in different domains, memory load did not modulate distractibility. Control of processing priority in selective attention demands domain-specific resources. PMID:24866977

  12. International Field Experience as an Impetus for Personal and Professional Transformation: Through the Lens of Early Childhood Postsecondary Students

    ERIC Educational Resources Information Center

    Bonnett, Tina Heather

    2015-01-01

    Research exploring preservice postsecondary students' experiences participating in an international field placement is a relatively new area of study in the domains of Early Childhood Education (ECE) and Early Childhood Leadership (ECL). While there is a growing body of literature offering merit to the profound transformations that can occur for…

  13. Structure of a double-domain phosphagen kinase reveals an asymmetric arrangement of the tandem domains.

    PubMed

    Wang, Zhiming; Qiao, Zhu; Ye, Sheng; Zhang, Rongguang

    2015-04-01

    Tandem duplications and fusions of single genes have led to magnificent expansions in the divergence of protein structures and functions over evolutionary timescales. One of the possible results is polydomain enzymes with interdomain cooperativities, few examples of which have been structurally characterized at the full-length level to explore their innate synergistic mechanisms. This work reports the crystal structures of a double-domain phosphagen kinase in both apo and ligand-bound states, revealing a novel asymmetric L-shaped arrangement of the two domains. Unexpectedly, the interdomain connections are not based on a flexible hinge linker but on a rigid secondary-structure element: a long α-helix that tethers the tandem domains in relatively fixed positions. Besides the connective helix, the two domains also contact each other directly and form an interdomain interface in which hydrogen bonds and hydrophobic interactions further stabilize the L-shaped domain arrangement. Molecular-dynamics simulations show that the interface is generally stable, suggesting that the asymmetric domain arrangement crystallographically observed in the present study is not a conformational state simply restrained by crystal-packing forces. It is possible that the asymmetrically arranged tandem domains could provide a structural basis for further studies of the interdomain synergy.

  14. A Fast, Efficient Domain Adaptation Technique for Cross-Domain Electroencephalography(EEG)-Based Emotion Recognition.

    PubMed

    Chai, Xin; Wang, Qisong; Zhao, Yongping; Li, Yongqiang; Liu, Dan; Liu, Xin; Bai, Ou

    2017-05-03

    Electroencephalography (EEG)-based emotion recognition is an important element in psychiatric health diagnosis for patients. However, the underlying EEG sensor signals are always non-stationary if they are sampled from different experimental sessions or subjects. This results in the deterioration of the classification performance. Domain adaptation methods offer an effective way to reduce the discrepancy of marginal distribution. However, for EEG sensor signals, both marginal and conditional distributions may be mismatched. In addition, the existing domain adaptation strategies always require a high level of additional computation. To address this problem, a novel strategy named adaptive subspace feature matching (ASFM) is proposed in this paper in order to integrate both the marginal and conditional distributions within a unified framework (without any labeled samples from target subjects). Specifically, we develop a linear transformation function which matches the marginal distributions of the source and target subspaces without a regularization term. This significantly decreases the time complexity of our domain adaptation procedure. As a result, both marginal and conditional distribution discrepancies between the source domain and unlabeled target domain can be reduced, and logistic regression (LR) can be applied to the new source domain in order to train a classifier for use in the target domain, since the aligned source domain follows a distribution which is similar to that of the target domain. We compare our ASFM method with six typical approaches using a public EEG dataset with three affective states: positive, neutral, and negative. Both offline and online evaluations were performed. The subject-to-subject offline experimental results demonstrate that our component achieves a mean accuracy and standard deviation of 80.46% and 6.84%, respectively, as compared with a state-of-the-art method, the subspace alignment auto-encoder (SAAE), which achieves values

  15. Evolution of the Ferric Reductase Domain (FRD) Superfamily: Modularity, Functional Diversification, and Signature Motifs

    PubMed Central

    Zhang, Xuezhi; Krause, Karl-Heinz; Xenarios, Ioannis; Soldati, Thierry; Boeckmann, Brigitte

    2013-01-01

    A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria. PMID:23505460

  16. Evolution of the ferric reductase domain (FRD) superfamily: modularity, functional diversification, and signature motifs.

    PubMed

    Zhang, Xuezhi; Krause, Karl-Heinz; Xenarios, Ioannis; Soldati, Thierry; Boeckmann, Brigitte

    2013-01-01

    A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria.

  17. POLE and POLD1 screening in 155 patients with multiple polyps and early-onset colorectal cancer

    PubMed Central

    Esteban-Jurado, Clara; Giménez-Zaragoza, David; Muñoz, Jenifer; Franch-Expósito, Sebastià; Álvarez-Barona, Miriam; Ocaña, Teresa; Cuatrecasas, Miriam; Carballal, Sabela; López-Cerón, María; Marti-Solano, Maria; Díaz-Gay, Marcos; van Wezel, Tom; Castells, Antoni; Bujanda, Luis; Balmaña, Judith; Gonzalo, Victoria; Llort, Gemma; Ruiz-Ponte, Clara; Cubiella, Joaquín; Balaguer, Francesc; Aligué, Rosa; Castellví-Bel, Sergi

    2017-01-01

    Germline mutations in POLE and POLD1 have been shown to cause predisposition to colorectal multiple polyposis and a wide range of neoplasms, early-onset colorectal cancer being the most prevalent. In order to find additional mutations affecting the proofreading activity of these polymerases, we sequenced its exonuclease domain in 155 patients with multiple polyps or an early-onset colorectal cancer phenotype without alterations in the known hereditary colorectal cancer genes. Interestingly, none of the previously reported mutations in POLE and POLD1 were found. On the other hand, among the genetic variants detected, only two of them stood out as putative pathogenic in the POLE gene, c.1359 + 46del71 and c.1420G > A (p.Val474Ile). The first variant, detected in two families, was not proven to alter correct RNA splicing. Contrarily, c.1420G > A (p.Val474Ile) was detected in one early-onset colorectal cancer patient and located right next to the exonuclease domain. The pathogenicity of this change was suggested by its rarity and bioinformatics predictions, and it was further indicated by functional assays in Schizosaccharomyces pombe. This is the first study to functionally analyze a POLE genetic variant outside the exonuclease domain and widens the spectrum of genetic changes in this DNA polymerase that could lead to colorectal cancer predisposition. PMID:28423643

  18. Phylogeny of the TRAF/MATH domain.

    PubMed

    Zapata, Juan M; Martínez-García, Vanesa; Lefebvre, Sophie

    2007-01-01

    The TNF-receptor associated factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel p-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated with a discrete set of protein-domains. Virtually all protein families encompassing a TRAF/MATH domain seem to be involved in the regulation of protein processing and ubiquitination, strongly suggesting a parallel evolution of the TRAF/MATH domain and certain proteolysis pathways in eukaryotes. The restricted number of living organisms for which we have information of their genetic and protein make-up limits the scope and analysis of the MATH domain in evolution. However, the available information allows us to get a glimpse on the origins, distribution and evolution of the TRAF/MATH domain, which will be overviewed in this chapter.

  19. Evolution of light domain walls interacting with dark matter, part 1

    NASA Technical Reports Server (NTRS)

    Massarotti, Alessandro

    1990-01-01

    The evolution of domain walls generated in the early Universe is discussed considering an interaction between the walls and a major gaseous component of the dark matter. The walls are supposed able to reflect the particles elastically and with a reflection coefficient of unity. A toy Lagrangian that could give rise to such a phenomenon is discussed. In the simple model studied, highly non-relativistic and slowly varying speeds are obtained for the domain walls (approximately 10 (exp -2)(1+z)(exp -1)) and negligible distortions of the microwave background. In addition, these topological defects may provide a mechanism of forming the large scale structure of the Universe, by creating fluctuations in the dark matter (delta rho/rho approximately O(1)) on a scale comparable with the distance the walls move from the formation (in the model d less than 20 h(exp -1) Mpc). The characteristic scale of the wall separation can be easily chosen to be of the order of 100 Mpc instead of being restricted to the horizon scale, as usually obtained.

  20. A probabilistic model for the persistence of early planar fabrics in polydeformed pelitic schists

    USGS Publications Warehouse

    Ferguson, C.C.

    1984-01-01

    Although early planar fabrics are commonly preserved within microlithons in low-grade pelites, in higher-grade (amphibolite facies) pelitic schists fabric regeneration often appears complete. Evidence for early fabrics may be preserved within porphyroblasts but, within the matrix, later deformation often appears to totally obliterate or reorient earlier fabrics. However, examination of several hundred Dalradian pelites from Connemara, western Ireland, reveals that preservation of early fabrics is by no means uncommon; relict matrix domains, although volumetrically insignificant, are remarkably persistent even when inferred later strains are very large and fabric regeneration appears, at first sight, complete. Deterministic plasticity theories are ill-suited to the analysis of such an inhomogeneous material response, and a probabilistic model is proposed instead. It assumes that ductile polycrystal deformation is controlled by elementary flow units which can be activated once their associated stress barrier is overcome. Bulk flow propensity is related to the proportion of simultaneous activations, and a measure of this is derived from the probabilistic interaction between a stress-barrier spectrum and an internal stress spectrum (the latter determined by the external loading and the details of internal stress transfer). The spectra are modelled as Gaussian distributions although the treatment is very general and could be adapted for other distributions. Using the time rate of change of activation probability it is predicted that, initially, fabric development will be rapid but will then slow down dramatically even though stress increases at a constant rate. This highly non-linear response suggests that early fabrics persist because they comprise unfavourable distributions of stress-barriers which remain unregenerated at the time bulk stress is stabilized by steady-state flow. Relict domains will, however, bear the highest stress and are potential upper

  1. Complexity multiscale asynchrony measure and behavior for interacting financial dynamics

    NASA Astrophysics Data System (ADS)

    Yang, Ge; Wang, Jun; Niu, Hongli

    2016-08-01

    A stochastic financial price process is proposed and investigated by the finite-range multitype contact dynamical system, in an attempt to study the nonlinear behaviors of real asset markets. The viruses spreading process in a finite-range multitype system is used to imitate the interacting behaviors of diverse investment attitudes in a financial market, and the empirical research on descriptive statistics and autocorrelation behaviors of return time series is performed for different values of propagation rates. Then the multiscale entropy analysis is adopted to study several different shuffled return series, including the original return series, the corresponding reversal series, the random shuffled series, the volatility shuffled series and the Zipf-type shuffled series. Furthermore, we propose and compare the multiscale cross-sample entropy and its modification algorithm called composite multiscale cross-sample entropy. We apply them to study the asynchrony of pairs of time series under different time scales.

  2. Domain and Specification Models for Software Engineering

    NASA Technical Reports Server (NTRS)

    Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui

    1992-01-01

    This paper discusses our approach to representing application domain knowledge for specific software engineering tasks. Application domain knowledge is embodied in a domain model. Domain models are used to assist in the creation of specification models. Although many different specification models can be created from any particular domain model, each specification model is consistent and correct with respect to the domain model. One aspect of the system-hierarchical organization is described in detail.

  3. A non-chromatographic protein purification strategy using Src 3 homology domains as generalized capture domains.

    PubMed

    Kim, Heejae; Chen, Wilfred

    2016-09-20

    Protein purification using inverse phase transition of elastin-like polypeptide (ELP) domains is a useful alternative to chromatography. Genetic fusions of ELP domains to various proteins have the ability to reversibly transition between soluble monomers and micron-sized aggregates and this has been used to selectively purify many ELP fusions. Affinity domains can enhance this technology by using specific protein binding domains to enable ELP mediated affinity capture (EMAC) of proteins of interest (POI) that have been fused to corresponding affinity ligands. In this paper, we highlight the use of Src homology 3 (SH3) domains and corresponding peptide ligands in EMAC that have differential binding affinities towards SH3 for efficient capture and elution of proteins. Furthermore, differences between capture and elution of a monomeric and a multimeric protein were also studied. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Multiple graph regularized protein domain ranking.

    PubMed

    Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin

    2012-11-19

    Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.

  5. A New Artificial Neural Network Enhanced by the Shuffled Complex Evolution Optimization with Principal Component Analysis (SP-UCI) for Water Resources Management

    NASA Astrophysics Data System (ADS)

    Hayatbini, N.; Faridzad, M.; Yang, T.; Akbari Asanjan, A.; Gao, X.; Sorooshian, S.

    2016-12-01

    The Artificial Neural Networks (ANNs) are useful in many fields, including water resources engineering and management. However, due to the non-linear and chaotic characteristics associated with natural processes and human decision making, the use of ANNs in real-world applications is still limited, and its performance needs to be further improved for a broader practical use. The commonly used Back-Propagation (BP) scheme and gradient-based optimization in training the ANNs have already found to be problematic in some cases. The BP scheme and gradient-based optimization methods are associated with the risk of premature convergence, stuck in local optimums, and the searching is highly dependent on initial conditions. Therefore, as an alternative to BP and gradient-based searching scheme, we propose an effective and efficient global searching method, termed the Shuffled Complex Evolutionary Global optimization algorithm with Principal Component Analysis (SP-UCI), to train the ANN connectivity weights. Large number of real-world datasets are tested with the SP-UCI-based ANN, as well as various popular Evolutionary Algorithms (EAs)-enhanced ANNs, i.e., Particle Swarm Optimization (PSO)-, Genetic Algorithm (GA)-, Simulated Annealing (SA)-, and Differential Evolution (DE)-enhanced ANNs. Results show that SP-UCI-enhanced ANN is generally superior over other EA-enhanced ANNs with regard to the convergence and computational performance. In addition, we carried out a case study for hydropower scheduling in the Trinity Lake in the western U.S. In this case study, multiple climate indices are used as predictors for the SP-UCI-enhanced ANN. The reservoir inflows and hydropower releases are predicted up to sub-seasonal to seasonal scale. Results show that SP-UCI-enhanced ANN is able to achieve better statistics than other EAs-based ANN, which implies the usefulness and powerfulness of proposed SP-UCI-enhanced ANN for reservoir operation, water resources engineering and management

  6. Time-Domain Stability Margin Assessment

    NASA Technical Reports Server (NTRS)

    Clements, Keith

    2016-01-01

    The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

  7. Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain

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

    Murphy, James M.; Korzhnev, Dmitry M.; Ceccarelli, Derek F.

    2012-10-23

    The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studiesmore » of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.« less

  8. Sperm 1: a POU-domain gene transiently expressed immediately before meiosis I in the male germ cell.

    PubMed Central

    Andersen, B; Pearse, R V; Schlegel, P N; Cichon, Z; Schonemann, M D; Bardin, C W; Rosenfeld, M G

    1993-01-01

    Members of the POU-domain gene family encode for transcriptional regulatory molecules that are important for terminal differentiation of several organ systems, including anterior pituitary, sensory neurons, and B lymphocytes. We have identified a POU-domain factor, referred to as sperm 1 (Sprm-1). This factor is most related to the transactivator Oct-3/4, which is expressed in the early embryo, primordial germ cells, and the egg. However, in contrast with Oct-3/4, rat Sprm-1 is selectively expressed during a 36- to 48-hr period immediately preceding meiosis I in male germ cells. Although the POU-domain of Sprm-1 is divergent from the POU-domains of Oct-1 and Oct-2, random-site-selection assay reveals that Sprm-1 preferentially binds to a specific variant of the classic octamer DNA-response element in which the optimal sequence differs from that preferred by Oct-1 and Pit-1. These data suggest that the Sprm-1 gene encodes a DNA-binding protein that may exert a regulatory function in meiotic events that are required for terminal differentiation of the male germ cell. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7902581

  9. A Fast, Efficient Domain Adaptation Technique for Cross-Domain Electroencephalography(EEG)-Based Emotion Recognition

    PubMed Central

    Chai, Xin; Wang, Qisong; Zhao, Yongping; Li, Yongqiang; Liu, Dan; Liu, Xin; Bai, Ou

    2017-01-01

    Electroencephalography (EEG)-based emotion recognition is an important element in psychiatric health diagnosis for patients. However, the underlying EEG sensor signals are always non-stationary if they are sampled from different experimental sessions or subjects. This results in the deterioration of the classification performance. Domain adaptation methods offer an effective way to reduce the discrepancy of marginal distribution. However, for EEG sensor signals, both marginal and conditional distributions may be mismatched. In addition, the existing domain adaptation strategies always require a high level of additional computation. To address this problem, a novel strategy named adaptive subspace feature matching (ASFM) is proposed in this paper in order to integrate both the marginal and conditional distributions within a unified framework (without any labeled samples from target subjects). Specifically, we develop a linear transformation function which matches the marginal distributions of the source and target subspaces without a regularization term. This significantly decreases the time complexity of our domain adaptation procedure. As a result, both marginal and conditional distribution discrepancies between the source domain and unlabeled target domain can be reduced, and logistic regression (LR) can be applied to the new source domain in order to train a classifier for use in the target domain, since the aligned source domain follows a distribution which is similar to that of the target domain. We compare our ASFM method with six typical approaches using a public EEG dataset with three affective states: positive, neutral, and negative. Both offline and online evaluations were performed. The subject-to-subject offline experimental results demonstrate that our component achieves a mean accuracy and standard deviation of 80.46% and 6.84%, respectively, as compared with a state-of-the-art method, the subspace alignment auto-encoder (SAAE), which achieves values

  10. Dual-domain point diffraction interferometer

    DOEpatents

    Naulleau, Patrick P.; Goldberg, Kenneth Alan

    2000-01-01

    A hybrid spatial/temporal-domain point diffraction interferometer (referred to as the dual-domain PS/PDI) that is capable of suppressing the scattered-reference-light noise that hinders the conventional PS/PDI is provided. The dual-domain PS/PDI combines the separate noise-suppression capabilities of the widely-used phase-shifting and Fourier-transform fringe pattern analysis methods. The dual-domain PS/PDI relies on both a more restrictive implementation of the image plane PS/PDI mask and a new analysis method to be applied to the interferograms generated and recorded by the modified PS/PDI. The more restrictive PS/PDI mask guarantees the elimination of spatial-frequency crosstalk between the signal and the scattered-light noise arising from scattered-reference-light interfering with the test beam. The new dual-domain analysis method is then used to eliminate scattered-light noise arising from both the scattered-reference-light interfering with the test beam and the scattered-reference-light interfering with the "true" pinhole-diffracted reference light. The dual-domain analysis method has also been demonstrated to provide performance enhancement when using the non-optimized standard PS/PDI design. The dual-domain PS/PDI is essentially a three-tiered filtering system composed of lowpass spatial-filtering the test-beam electric field using the more restrictive PS/PDI mask, bandpass spatial-filtering the individual interferogram irradiance frames making up the phase-shifting series, and bandpass temporal-filtering the phase-shifting series as a whole.

  11. Domain decomposition and matching for time-domain analysis of motions of ships advancing in head sea

    NASA Astrophysics Data System (ADS)

    Tang, Kai; Zhu, Ren-chuan; Miao, Guo-ping; Fan, Ju

    2014-08-01

    A domain decomposition and matching method in the time-domain is outlined for simulating the motions of ships advancing in waves. The flow field is decomposed into inner and outer domains by an imaginary control surface, and the Rankine source method is applied to the inner domain while the transient Green function method is used in the outer domain. Two initial boundary value problems are matched on the control surface. The corresponding numerical codes are developed, and the added masses, wave exciting forces and ship motions advancing in head sea for Series 60 ship and S175 containership, are presented and verified. A good agreement has been obtained when the numerical results are compared with the experimental data and other references. It shows that the present method is more efficient because of the panel discretization only in the inner domain during the numerical calculation, and good numerical stability is proved to avoid divergence problem regarding ships with flare.

  12. Physical self-esteem--a ten-year follow-up study from early adolescence to early adulthood.

    PubMed

    Raustorp, Anders; Lindwall, Magnus

    2015-02-01

    One variable that has been consistently associated with adolescents' physical activity is perceived activity competence. Perceived physical (or sport) competence is considered a sub-domain to the physical self-esteem or self-worth (i.e., a person's valuation of what is good and worthy in their self-description). This study aimed to describe levels of and inter-correlations among physical self-esteem, physical activity, and body mass index in a longitudinal design spanning adolescence to early adulthood. At mean ages of 12.7, 15.7, 17.7 and 22.7 years, we measured perceived physical self-esteem in 39 (22 boys) Swedish adolescents. Physical activity (steps/day) for four consecutive schooldays, height, and weight were also measured. No significant difference between the four time points for any variable of perceived physical self-esteem was seen, neither in boys nor girls. In general, all physical self-variables revealed non-linear trajectories across time, where the general trend was an increase during the younger ages followed by a decrease during older ages. At ages 12 and 15 years in boys and girls physical condition and physical strength as well as body attractiveness and physical strength, respectively, had the strongest correlations to physical self-esteem. At age 17 and 22 years sports competence had the strongest correlation to self-esteem in girls, while body attractiveness and physical strength had the strongest correlation to self-esteem in boys. An overall stability in physical self-esteem was found. However the impact of a sub-domain upon physical self-esteem vary during adolescence and early adulthood. Such information may be useful when creating physical activity programs that support and develop physical self-esteem.

  13. Preschool Ontology: The Role of Beliefs about Category Boundaries in Early Categorization

    ERIC Educational Resources Information Center

    Rhodes, Marjorie; Gelman, Susan A.; Karuza, J. Christopher

    2014-01-01

    These studies examined the role of ontological beliefs about category boundaries in early categorization. Study 1 found that preschool-age children (N = 48, aged 3-4 years old) have domain-specific beliefs about the meaning of category boundaries; children judged the boundaries of natural kind categories (animal species, human gender) as discrete…

  14. Early auditory evoked potential is modulated by selective attention and related to individual differences in visual working memory capacity.

    PubMed

    Giuliano, Ryan J; Karns, Christina M; Neville, Helen J; Hillyard, Steven A

    2014-12-01

    A growing body of research suggests that the predictive power of working memory (WM) capacity for measures of intellectual aptitude is due to the ability to control attention and select relevant information. Crucially, attentional mechanisms implicated in controlling access to WM are assumed to be domain-general, yet reports of enhanced attentional abilities in individuals with larger WM capacities are primarily within the visual domain. Here, we directly test the link between WM capacity and early attentional gating across sensory domains, hypothesizing that measures of visual WM capacity should predict an individual's capacity to allocate auditory selective attention. To address this question, auditory ERPs were recorded in a linguistic dichotic listening task, and individual differences in ERP modulations by attention were correlated with estimates of WM capacity obtained in a separate visual change detection task. Auditory selective attention enhanced ERP amplitudes at an early latency (ca. 70-90 msec), with larger P1 components elicited by linguistic probes embedded in an attended narrative. Moreover, this effect was associated with greater individual estimates of visual WM capacity. These findings support the view that domain-general attentional control mechanisms underlie the wide variation of WM capacity across individuals.

  15. Low Performance on Mathematical Tasks in Preschoolers: The Importance of Domain-General and Domain-Specific Abilities

    ERIC Educational Resources Information Center

    Costa, H. M.; Nicholson, B.; Donlan, C.; Van Herwegen, J.

    2018-01-01

    Background: Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether…

  16. Spectral identification of topological domains

    PubMed Central

    Chen, Jie; Hero, Alfred O.; Rajapakse, Indika

    2016-01-01

    Motivation: Topological domains have been proposed as the backbone of interphase chromosome structure. They are regions of high local contact frequency separated by sharp boundaries. Genes within a domain often have correlated transcription. In this paper, we present a computational efficient spectral algorithm to identify topological domains from chromosome conformation data (Hi-C data). We consider the genome as a weighted graph with vertices defined by loci on a chromosome and the edge weights given by interaction frequency between two loci. Laplacian-based graph segmentation is then applied iteratively to obtain the domains at the given compactness level. Comparison with algorithms in the literature shows the advantage of the proposed strategy. Results: An efficient algorithm is presented to identify topological domains from the Hi-C matrix. Availability and Implementation: The Matlab source code and illustrative examples are available at http://bionetworks.ccmb.med.umich.edu/ Contact: indikar@med.umich.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153657

  17. Multiple graph regularized protein domain ranking

    PubMed Central

    2012-01-01

    Background Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. Results To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. Conclusion The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. PMID:23157331

  18. The Vanderbilt Expertise Test Reveals Domain-General and Domain-Specific Sex Effects in Object Recognition

    PubMed Central

    McGugin, Rankin W.; Richler, Jennifer J.; Herzmann, Grit; Speegle, Magen; Gauthier, Isabel

    2012-01-01

    Individual differences in face recognition are often contrasted with differences in object recognition using a single object category. Likewise, individual differences in perceptual expertise for a given object domain have typically been measured relative to only a single category baseline. In Experiment 1, we present a new test of object recognition, the Vanderbilt Expertise Test (VET), which is comparable in methods to the Cambridge Face Memory Task (CFMT) but uses eight different object categories. Principal component analysis reveals that the underlying structure of the VET can be largely explained by two independent factors, which demonstrate good reliability and capture interesting sex differences inherent in the VET structure. In Experiment 2, we show how the VET can be used to separate domain-specific from domain-general contributions to a standard measure of perceptual expertise. While domain-specific contributions are found for car matching for both men and women and for plane matching in men, women in this sample appear to use more domain-general strategies to match planes. In Experiment 3, we use the VET to demonstrate that holistic processing of faces predicts face recognition independently of general object recognition ability, which has a sex-specific contribution to face recognition. Overall, the results suggest that the VET is a reliable and valid measure of object recognition abilities and can measure both domain-general skills and domain-specific expertise, which were both found to depend on the sex of observers. PMID:22877929

  19. Human-computer interface incorporating personal and application domains

    DOEpatents

    Anderson, Thomas G [Albuquerque, NM

    2011-03-29

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  20. Human-computer interface incorporating personal and application domains

    DOEpatents

    Anderson, Thomas G.

    2004-04-20

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  1. Creating and Manipulating a Domain-Specific Formal Object Base to Support a Domain-Oriented Application Composition System

    DTIC Science & Technology

    1992-12-01

    and add new attributes as needed (11:129). 2.2.3.2 Feature Oriented Domain Analysis In their Feature-Oriented Domain Analysis ( FODA ) study, the...dissertation, The University of Texas at Austin, Austin Texas, 1990. 12. Kang, Kyo C. and others. Feature-Oriented Domain Analysis ( FODA ) Feasibil- ity Study...2-1 2.2.2 Requirements Languages ..................... 2-2 2.2.3 Domain Analysis ............................ 2-3 2.2.4

  2. Effects of biases in domain wall network evolution. II. Quantitative analysis

    NASA Astrophysics Data System (ADS)

    Correia, J. R. C. C. C.; Leite, I. S. C. R.; Martins, C. J. A. P.

    2018-04-01

    Domain walls form at phase transitions which break discrete symmetries. In a cosmological context, they often overclose the Universe (contrary to observational evidence), although one may prevent this by introducing biases or forcing anisotropic evolution of the walls. In a previous work [Correia et al., Phys. Rev. D 90, 023521 (2014), 10.1103/PhysRevD.90.023521], we numerically studied the evolution of various types of biased domain wall networks in the early Universe, confirming that anisotropic networks ultimately reach scaling while those with a biased potential or biased initial conditions decay. We also found that the analytic decay law obtained by Hindmarsh was in good agreement with simulations of biased potentials, but not of biased initial conditions, and suggested that the difference was related to the Gaussian approximation underlying the analytic law. Here, we extend our previous work in several ways. For the cases of biased potential and biased initial conditions, we study in detail the field distributions in the simulations, confirming that the validity (or not) of the Gaussian approximation is the key difference between the two cases. For anisotropic walls, we carry out a more extensive set of numerical simulations and compare them to the canonical velocity-dependent one-scale model for domain walls, finding that the model accurately predicts the linear scaling regime after isotropization. Overall, our analysis provides a quantitative description of the cosmological evolution of these networks.

  3. Clinical Research Informatics: Challenges, Opportunities and Definition for an Emerging Domain

    PubMed Central

    Embi, Peter J.; Payne, Philip R.O.

    2009-01-01

    Objectives Clinical Research Informatics, an emerging sub-domain of Biomedical Informatics, is currently not well defined. A formal description of CRI including major challenges and opportunities is needed to direct progress in the field. Design Given the early stage of CRI knowledge and activity, we engaged in a series of qualitative studies with key stakeholders and opinion leaders to determine the range of challenges and opportunities facing CRI. These phases employed complimentary methods to triangulate upon our findings. Measurements Study phases included: 1) a group interview with key stakeholders, 2) an email follow-up survey with a larger group of self-identified CRI professionals, and 3) validation of our results via electronic peer-debriefing and member-checking with a group of CRI-related opinion leaders. Data were collected, transcribed, and organized for formal, independent content analyses by experienced qualitative investigators, followed by an iterative process to identify emergent categorizations and thematic descriptions of the data. Results We identified a range of challenges and opportunities facing the CRI domain. These included 13 distinct themes spanning academic, practical, and organizational aspects of CRI. These findings also informed the development of a formal definition of CRI and supported further representations that illustrate areas of emphasis critical to advancing the domain. Conclusions CRI has emerged as a distinct discipline that faces multiple challenges and opportunities. The findings presented summarize those challenges and opportunities and provide a framework that should help inform next steps to advance this important new discipline. PMID:19261934

  4. Unraveling Mixed Hydrate Formation: Microscopic Insights into Early Stage Behavior.

    PubMed

    Hall, Kyle Wm; Zhang, Zhengcai; Kusalik, Peter G

    2016-12-29

    The molecular-level details of mixed hydrate nucleation remain unclear despite the broad implications of this process for a variety of scientific domains. Through analysis of mixed hydrate nucleation in a prototypical CH 4 /H 2 S/H 2 O system, we demonstrate that high-level kinetic similarities between mixed hydrate systems and corresponding pure hydrate systems are not a reliable basis for estimating the composition of early stage mixed hydrate nuclei. Moreover, we show that solution compositions prior to and during nucleation are not necessarily effective proxies for the composition of early stage mixed hydrate nuclei. Rather, microscopic details, (e.g., guest-host interactions and previously neglected cage types) apparently play key roles in determining early stage behavior of mixed hydrates. This work thus provides key foundational concepts and insights for understanding mixed hydrate nucleation.

  5. Maternal Work Early in the Lives of Children and Its Distal Associations with Achievement and Behavior Problems: A Meta-Analysis

    ERIC Educational Resources Information Center

    Lucas-Thompson, Rachel G.; Goldberg, Wendy A.; Prause, JoAnn

    2010-01-01

    This meta-analysis of 69 studies (1,483 effect sizes) used random effects models to examine maternal employment during infancy/early childhood in relation to 2 major domains of child functioning: achievement and behavior problems. Analyses of studies that spanned 5 decades indicated that, with a few exceptions, early employment was not…

  6. Tell Me a Story: A Literacy-Based Intervention to Help Children, Early Care Providers, and Parents Talk about Difficult Topics

    ERIC Educational Resources Information Center

    Beardslee, William R.; Bartlett, Jessica Dym; Ayoub, Catherine

    2014-01-01

    The use of storytelling and discussion about difficult topics naturally lends itself to early skill development in both social-emotional and academic (i.e., emergent literacy) domains. In this article, the authors present initial information on the efficacy and feasibility of Tell Me A Story (TMAS), a program focused on supporting early childhood…

  7. Modeling Protein Domain Function

    ERIC Educational Resources Information Center

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

    2007-01-01

    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  8. Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains.

    PubMed

    Herbig, Eric; Warfield, Linda; Fish, Lisa; Fishburn, James; Knutson, Bruce A; Moorefield, Beth; Pacheco, Derek; Hahn, Steven

    2010-05-01

    Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking. The individual Gcn4 activation domains cross-link to three common targets, Gal11/Med15, Taf12, and Tra1, which are subunits of four conserved coactivator complexes, Mediator, SAGA, TFIID, and NuA4. The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from synergistic to less than additive. Gcn4-dependent genes had a requirement for Gal11 ranging from 10-fold dependence to complete Gal11 independence, while the Gcn4-Taf12 interaction did not significantly contribute to the expression of any gene studied. Complementary methods identified three conserved Gal11 activator-binding domains that bind each Gcn4 activation domain with micromolar affinity. These Gal11 activator-binding domains contribute additively to transcription activation and Mediator recruitment at Gcn4- and Gal11-dependent genes. Although we found that the conserved Gal11 KIX domain contributes to Gal11 function, we found no evidence of specific Gcn4-KIX interaction and conclude that the Gal11 KIX domain does not function by specific interaction with Gcn4. Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions.

  9. Early maladaptive schemas and personality disorder traits in perpetrators of intimate partner violence.

    PubMed

    Corral, Carmen; Calvete, Esther

    2014-01-01

    Personality disorders (PDs) are highly prevalent among perpetrators of intimate partner violence (IPV). Schema Therapy proposes a number of early maladaptive schemas (EMSs) that are involved in the development of PDs. This study examined the prevalence of PD traits in a sample of men who committed violence against their partners and the relationship between EMSs domains and PD traits. With this aim, a sample of 119 convicted men completed the Young Schema Questionnaire-Short Form (YSQ-SF; Young & Brown, 1994) and the Millon Clinical Multiaxial Inventory (MCMI-III; Millon, Millon, & Davis, 1994). The results showed that the most prevalent PD traits were narcissistic (24.6%), obsessive-compulsive (21.9%), and paranoid (17.5%). These PD traits were linked to several EMSs in ways consistent with the Schema Therapy model. Namely, narcissistic PD traits were positively associated with schemas of the impaired limits domain and were negatively associated with the other-directedness domain. The paranoid PD traits were associated with the disconnection and rejection domain and the impaired autonomy and performance domain. Finally, both borderline and antisocial PD traits were associated with the disconnection and rejection domain and the impaired limits domain. These findings suggest that the assessment and modification of EMSs should be a factor to consider for inclusion in the treatment programs for perpetrators of IPV in order to provide comprehensive intervention of this population.

  10. From higher order thinking to higher order behavior: exploring the relationship between early cognitive skills and social competence in black boys.

    PubMed

    Scott, Kristin M; Barbarin, Oscar A; Brown, Jeffrey M

    2013-01-01

    This study examines the relations of higher order (i.e., abstract) thinking (HOT) skills to specific domains of social competence in Black boys (n = 108) attending publicly sponsored prekindergarten (pre-K) programs. Data for the study were collected as part of the National Center for Early Development and Learning (NCEDL) Multi-State Study, a national, longitudinal study examining the quality and outcomes in a representative sample of publicly sponsored pre-K programs in six states (N = 240). Pre-K and kindergarten teachers rated randomly selected children on measures of abstract thinking, self-regulation, and social functioning at the beginning and end of each school year. Applying structural equation modeling, compared with earlier time points, HOT measured in the fall of kindergarten significantly predicted each of the domains of social competence in the spring of kindergarten, with the exception of peer social skills, while controlling for general cognitive ability. Results suggest that early intervention to improve HOT may be an effective and more focused approach to address concerns about Black boys' early social competencies in specific domains and potentially reduce the risk of later social difficulties. © 2013 American Orthopsychiatric Association.

  11. Generic domain models in software engineering

    NASA Technical Reports Server (NTRS)

    Maiden, Neil

    1992-01-01

    This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.

  12. Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study.

    PubMed

    Frazier, Jean A; Giuliano, Anthony J; Johnson, Jacqueline L; Yakutis, Lauren; Youngstrom, Eric A; Breiger, David; Sikich, Linmarie; Findling, Robert L; McClellan, Jon; Hamer, Robert M; Vitiello, Benedetto; Lieberman, Jeffrey A; Hooper, Stephen R

    2012-05-01

    To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site, randomized, double-blind clinical trial comparing molindone, olanzapine, and risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses. Of 116 TEOSS participants, 77 (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores. Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. Clinical trial registry information-Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS); http://www.clinicaltrials.gov; NCT00053703. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published

  13. Interaction Between the Biotin Carboxyl Carrier Domain and the Biotin Carboxylase Domain in Pyruvate Carboxylase from Rhizobium etli†

    PubMed Central

    Lietzan, Adam D.; Menefee, Ann L.; Zeczycki, Tonya N.; Kumar, Sudhanshu; Attwood, Paul V.; Wallace, John C.; Cleland, W. Wallace; Maurice, Martin St.

    2011-01-01

    Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in mammalian tissues. To effect catalysis, the tethered biotin of PC must gain access to active sites in both the biotin carboxylase domain and the carboxyl transferase domain. Previous studies have demonstrated that a mutation of threonine 882 to alanine in PC from Rhizobium etli renders the carboxyl transferase domain inactive and favors the positioning of biotin in the biotin carboxylase domain. We report the 2.4 Å resolution X-ray crystal structure of the Rhizobium etli PC T882A mutant which reveals the first high-resolution description of the domain interaction between the biotin carboxyl carrier protein domain and the biotin carboxylase domain. The overall quaternary arrangement of Rhizobium etli PC remains highly asymmetrical and is independent of the presence of allosteric activator. While biotin is observed in the biotin carboxylase domain, its access to the active site is precluded by the interaction between Arg353 and Glu248, revealing a mechanism for regulating carboxybiotin access to the BC domain active site. The binding location for the biotin carboxyl carrier protein domain demonstrates that tethered biotin cannot bind in the biotin carboxylase domain active site in the same orientation as free biotin, helping to explain the difference in catalysis observed between tethered biotin and free biotin substrates in biotin carboxylase enzymes. Electron density located in the biotin carboxylase domain active site is assigned to phosphonoacetate, offering a probable location for the putative carboxyphosphate intermediate formed during biotin carboxylation. The insights gained from the T882A Rhizobium etli PC crystal structure provide a new series of catalytic snapshots in PC and offer a revised perspective on catalysis in the biotin-dependent enzyme family. PMID:21958016

  14. Critical role of domain crystallinity, domain purity and domain interface sharpness for reduced bimolecular recombination in polymer solar cells

    DOE PAGES

    Venkatesan, Swaminathan; Chen, Jihua; Ngo, Evan C.; ...

    2014-12-31

    In this study, inverted bulk heterojunction solar cells were fabricated using poly(3-hexylthiophene) (P3HT) blended with two different fullerene derivatives namely phenyl-C61-butyric acid methyl ester (PC 60BM) and indene-C 60 bis-adduct (IC 60BA). The effects of annealing temperatures on the morphology, optical and structural properties were studied and correlated to differences in photovoltaic device performance. It was observed that annealing temperature significantly improved the performance of P3HT:IC 60BA solar cells while P3HT:PC 60BM cells showed relatively less improvement. The performance improvement is attributed to the extent of fullerene mixing with polymer domains. Energy filtered transmission electron microscopy (EFTEM) and x-ray diffractionmore » (XRD) results showed that ICBA mixes with disordered P3HT much more readily than PC 60BM which leads to lower short circuit current density and fill factor for P3HT:IC 60BA cells annealed below 120°C. Annealing above 120°C improves the crystallinity of P3HT in case of P3HT:IC 60BA whereas in P3HT:PC 60BM films, annealing above 80°C leads to negligible change in crystallinity. Crystallization of P3HT also leads to higher domain purity as seen EFTEM. Further it is seen that cells processed with additive nitrobenzene (NB) showed enhanced short circuit current density and power conversion efficiency regardless of the fullerene derivative used. Addition of NB led to nanoscale phase separation between purer polymer and fullerene domains. Kelvin probe force microscopy (KPFM) images showed that enhanced domain purity in additive casted films led to a sharper interface between polymer and fullerene. Lastly, enhanced domain purity and interfacial sharpness led to lower bimolecular recombination and higher mobility and charge carrier lifetime in NB modified devices.« less

  15. A thermodynamic definition of protein domains.

    PubMed

    Porter, Lauren L; Rose, George D

    2012-06-12

    Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earliest crystal structures. Numerous disparate domain identification algorithms have been proposed, all involving some combination of visual intuition and/or structure-based decomposition. Instead, we present a rigorous, thermodynamically-based approach that redefines domains as cooperative chain segments. In greater detail, most small proteins fold with high cooperativity, meaning that the equilibrium population is dominated by completely folded and completely unfolded molecules, with a negligible subpopulation of partially folded intermediates. Here, we redefine structural domains in thermodynamic terms as cooperative folding units, based on m-values, which measure the cooperativity of a protein or its substructures. In our analysis, a domain is equated to a contiguous segment of the folded protein whose m-value is largely unaffected when that segment is excised from its parent structure. Defined in this way, a domain is a self-contained cooperative unit; i.e., its cooperativity depends primarily upon intrasegment interactions, not intersegment interactions. Implementing this concept computationally, the domains in a large representative set of proteins were identified; all exhibit consistency with experimental findings. Specifically, our domain divisions correspond to the experimentally determined equilibrium folding intermediates in a set of nine proteins. The approach was also proofed against a representative set of 71 additional proteins, again with confirmatory results. Our reframed interpretation of a protein domain transforms an indeterminate structural phenomenon into a quantifiable molecular property grounded in solution thermodynamics.

  16. [Analysis of time domain and frequency domain heart rate variability in fighter pilot before and after upright tilt].

    PubMed

    Wang, L; Wu, L; Ji, G; Zhang, X; Chen, T; Wang, L

    1998-12-01

    Effects of upright tilt on mechanism of autonomic nervous regulation of cardiovascular system and characteristics of heart rate variability (HRV) were observed in sixty healthy male pilots. Relation between time domain and frequency domain indexes of short-time HRV (5 min) were analysed before and after upright tilt. The results showed that there are significant difference in short time HRV parameters before and after upright tilt. Significant relationship was formed between time domain and frequency domain indexes of HRV. It suggests that time domain and frequency domain HRV analysis is capable of revealing certain informations embedded in a short series of R-R intervals and can help to evaluate the status of autonomic regulation of cardiovascular function in pilots.

  17. Early maladaptive schemas and aggressive sexual behavior: a preliminary study with male college students.

    PubMed

    Sigre-Leirós, Vera Lúcia; Carvalho, Joana; Nobre, Pedro

    2013-07-01

    The influence of adverse early attachment experiences on the development of aggressive sexual behavior has been demonstrated. Nonetheless, there is a gap in the literature regarding the conceptualization of this behavior according to developmental psychopathology models. The purpose of the present study was to investigate a potential association between Early Maladaptive Schemas (EMSs) and aggressive sexual behavior. A total of 166 male college students participated in the study. Participants were divided into two comparative groups according to data from the Sexual Experiences Survey-Short Form Perpetration (SES-SFP): Group of individuals with history of aggressive sexual behavior (N = 37) and Group of individuals without history of aggressive sexual behavior (N = 129). Aggressive sexual behavior was measured by the SES-SFP, and EMSs were measured by the Young Schema Questionnaire (YSQ-S3). Results showed that students who have committed any form of sexually aggressive behavior exhibited significantly higher levels of EMSs from the Disconnection and Rejection domain (namely, Mistrust/Abuse schema), from the Impaired Autonomy and Performance domain (namely, Dependence/Incompetence schema), and from the Overvigilance and Inhibition domain (namely, Negativity/Pessimism schema). These preliminary findings suggest that the EMSs were associated with aggressive sexual behavior, but further investigation is warranted. © 2012 International Society for Sexual Medicine.

  18. Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease.

    PubMed

    Lonie, Jane A; Herrmann, Lucie L; Tierney, Kevin M; Donaghey, Claire; O'Carroll, Ronan; Lee, Andrew; Ebmeier, Klaus P

    2009-03-01

    Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out-patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.

  19. Socio-cognitive influences on the domain-specificity of prosocial behavior in the second year.

    PubMed

    Kärtner, Joscha; Schuhmacher, Nils; Collard, Jenny

    2014-11-01

    The main aim of this study was to explain the domain-specificity of early prosocial behavior in different domains (i.e., helping, comforting, and cooperation) by simultaneously assessing specific socio-cognitive factors (i.e., self-other-differentiation and joint attentional skills) that were hypothesized to be differentially related to the three domains of prosocial behavior. Based on a longitudinal study design, observational and parental report data were collected when toddlers (N=42) from German urban middle-class families were 15 and 18 months of age. At 15 months, regression analyses indicated differential relationships between socio-cognitive development and prosocial behavior (i.e., joint attentional skills were positively related with helping and, as hypothesized, both joint attentional skills and self-other differentiation were positively related with cooperation). Furthermore, self-other differentiation at 15 months predicted increases in coordination between 15 and 18 months. Finally, between 15 and 18 months, parental reports of socio-cognitive measures increased significantly while behavioral measures of both socio-cognitive concepts and prosocial behavior were stable across time. In sum, these results support the theoretical assumption of domain-specific socio-cognitive influences that constitute differential development of prosocial behavior. Implications of the results for theory and future studies are discussed from different perspectives with a focus on an interference interpretation calling for the integration of socialization approaches to the study of prosocial development. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Early Rehabilitation After Stroke: a Narrative Review

    PubMed Central

    Moudgal, Rohitha; Lang, Kathryn; Hyacinth, Hyacinth I.; Awosika, Oluwole O.; Kissela, Brett M.; Feng, Wuwei

    2018-01-01

    Purpose of Review Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain’s dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Recent Findings Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. Summary The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful. PMID:29116473

  1. Early Rehabilitation After Stroke: a Narrative Review.

    PubMed

    Coleman, Elisheva R; Moudgal, Rohitha; Lang, Kathryn; Hyacinth, Hyacinth I; Awosika, Oluwole O; Kissela, Brett M; Feng, Wuwei

    2017-11-07

    Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain's dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful.

  2. Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase.

    PubMed

    Karamzadeh, Razieh; Karimi-Jafari, Mohammad Hossein; Sharifi-Zarchi, Ali; Chitsaz, Hamidreza; Salekdeh, Ghasem Hosseini; Moosavi-Movahedi, Ali Akbar

    2017-06-16

    The human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.

  3. Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains.

    PubMed Central

    Tell, G; Perrone, L; Fabbro, D; Pellizzari, L; Pucillo, C; De Felice, M; Acquaviva, R; Formisano, S; Damante, G

    1998-01-01

    The thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor involved in the development of thyroid and lung. TTF-1 contains two transcriptional activation domains (N and C domain). The primary amino acid sequence of the N domain does not show any typical characteristic of known transcriptional activation domains. In aqueous solution the N domain exists in a random-coil conformation. The increase of the milieu hydrophobicity, by the addition of trifluoroethanol, induces a considerable gain of alpha-helical structure. Acidic transcriptional activation domains are largely unstructured in solution, but, under hydrophobic conditions, folding into alpha-helices or beta-strands can be induced. Therefore our data indicate that the inducibility of alpha-helix by hydrophobic conditions is a property not restricted to acidic domains. Co-transfections experiments indicate that the acidic domain of herpes simplex virus protein VP16 (VP16) and the TTF-1 N domain are interchangeable and that a chimaeric protein, which combines VP16 linked to the DNA-binding domain of TTF-1, undergoes the same regulatory constraints that operate for the wild-type TTF-1. In addition, we demonstrate that the TTF-1 N domain possesses two typical properties of acidic activation domains: TBP (TATA-binding protein) binding and ability to activate transcription in yeast. Accordingly, the TTF-1 N domain is able to squelch the activity of the p65 acidic domain. Altogether, these structural and functional data suggest that a non-acidic transcriptional activation domain (TTF-1 N domain) activates transcription by using molecular mechanisms similar to those used by acidic domains. TTF-1 N domain and acidic domains define a family of proteins whose common property is to activate transcription through the use of mechanisms largely conserved during evolutionary development. PMID:9425125

  4. Characteristics of microbial community involved in early biofilms formation under the influence of wastewater treatment plant effluent.

    PubMed

    Peng, Yuke; Li, Jie; Lu, Junling; Xiao, Lin; Yang, Liuyan

    2018-04-01

    Effluents from wastewater treatment plants (WWTPs) containing microorganisms and residual nutrients can influence the biofilm formation. Although the process and mechanism of bacterial biofilm formation have been well characterized, little is known about the characteristics and interaction of bacteria, archaea and eukaryotes in the early colonization, especially under the influence of WWTP effluent. The aim of this study was to characterize the important bacterial, archaeal and eukaryotic species in the early stage of biofilm formation downstream of the WWTP outlet. Water and biofilm samples were collected 24 and 48hr after the deposition of bio-cords in the stream. Illumina Miseq sequencing of the 16S and 18S rDNA showed that, among the three domains, the bacterial biofilm community had the largest alpha and beta diversity. The early bacterial colonizers appeared to be "biofilm-specific", with only a few dominant operational taxonomic units (OTUs) shared between the biofilm and the ambient water environment. Alpha-proteobacteria and Ciliophora tended to dominate the bacterial and eukaryotic communities, respectively, of the early biofilm already at 24hr, whereas archaea played only a minor role during the early stage of colonization. The network analysis showed that the three domains of microbial community connected highly during the early colonization and it might be a characteristic of the microbial communities in the biofilm formation process where co-occurrence relationships could drive coexistence and diversity maintenance within the microbial communities. Copyright © 2017. Published by Elsevier B.V.

  5. Mechanical switching of ferroelectric domains beyond flexoelectricity

    NASA Astrophysics Data System (ADS)

    Chen, Weijin; Liu, Jianyi; Ma, Lele; Liu, Linjie; Jiang, G. L.; Zheng, Yue

    2018-02-01

    The resurgence of interest in flexoelectricity has prompted discussions on the feasibility of switching ferroelectric domains 'non-electrically'. In this work, we perform three-dimensional thermodynamic simulations in combination with ab initio calculations and effective Hamiltonian simulations to demonstrate the great effects of surface screening and surface bonding on ferroelectric domain switching triggered by local tip loading. A three-dimensional simulation scheme has been developed to capture the tip-induced domain switching behavior in ferroelectric thin films by adequately taking into account the surface screening effect and surface bonding effect of the ferroelectric film, as well as the finite elastic stiffness of the substrate and the electrode layers. The major findings are as follows. (i) Compared with flexoelectricity, surface effects can be overwhelming and lead to much more efficient mechanical switching caused by tip loading. (ii) The surface-assisted mechanical switching can be bi-directional without the necessity of reversing strain gradients. (iii) A mode transition from local to propagating domain switching occurs when the screening below a critical value. A ripple effect of domain switching appears with the formation of concentric loop domains. (iv) The ripple effect can lead to 'domain interference' and a deterministic writing of confined loop domain patterns by local excitations. Our study reveals the hidden switching mechanisms of ferroelectric domains and the possible roles of surface in mechanical switching. The ripple effect of domain switching, which is believed to be general in dipole systems, broadens our current knowledge of domain engineering.

  6. Investigating Key Psychometric Properties of the French Version of the Early Years Evaluation-Teacher Assessment

    ERIC Educational Resources Information Center

    Laurie, Robert; Sloat, Elizabeth

    2016-01-01

    This research investigates key psychometric properties of the French Early Years Evaluation-Teacher Assessment measure designed to systematically assess kindergarten children across five social and academic developmental domains: awareness of self and environment, social skills and behaviour, cognitive abilities, language and communication, and…

  7. An Adaptable Spectrin/Ankyrin-Based Mechanism for Long-Range Organization of Plasma Membranes in Vertebrate Tissues.

    PubMed

    Bennett, Vann; Lorenzo, Damaris N

    2016-01-01

    Ankyrins are membrane-associated proteins that together with their spectrin partners are responsible for micron-scale organization of vertebrate plasma membranes, including those of erythrocytes, excitable membranes of neurons and heart, lateral membrane domains of columnar epithelial cells, and striated muscle. Ankyrins coordinate functionally related membrane transporters and cell adhesion proteins (15 protein families identified so far) within plasma membrane compartments through independently evolved interactions of intrinsically disordered sequences with a highly conserved peptide-binding groove formed by the ANK repeat solenoid. Ankyrins are coupled to spectrins, which are elongated organelle-sized proteins that form mechanically resilient arrays through cross-linking by specialized actin filaments. In addition to protein interactions, cellular targeting and assembly of spectrin/ankyrin domains also critically depend on palmitoylation of ankyrin-G by aspartate-histidine-histidine-cysteine 5/8 palmitoyltransferases, as well as interaction of beta-2 spectrin with phosphoinositide lipids. These lipid-dependent spectrin/ankyrin domains are not static but are locally dynamic and determine membrane identity through opposing endocytosis of bulk lipids as well as specific proteins. A partnership between spectrin, ankyrin, and cell adhesion molecules first emerged in bilaterians over 500 million years ago. Ankyrin and spectrin may have been recruited to plasma membranes from more ancient roles in organelle transport. The basic bilaterian spectrin-ankyrin toolkit markedly expanded in vertebrates through gene duplications combined with variation in unstructured intramolecular regulatory sequences as well as independent evolution of ankyrin-binding activity by ion transporters involved in action potentials and calcium homeostasis. In addition, giant vertebrate ankyrins with specialized roles in axons acquired new coding sequences by exon shuffling. We speculate that

  8. Requirements analysis, domain knowledge, and design

    NASA Technical Reports Server (NTRS)

    Potts, Colin

    1988-01-01

    Two improvements to current requirements analysis practices are suggested: domain modeling, and the systematic application of analysis heuristics. Domain modeling is the representation of relevant application knowledge prior to requirements specification. Artificial intelligence techniques may eventually be applicable for domain modeling. In the short term, however, restricted domain modeling techniques, such as that in JSD, will still be of practical benefit. Analysis heuristics are standard patterns of reasoning about the requirements. They usually generate questions of clarification or issues relating to completeness. Analysis heuristics can be represented and therefore systematically applied in an issue-based framework. This is illustrated by an issue-based analysis of JSD's domain modeling and functional specification heuristics. They are discussed in the context of the preliminary design of simple embedded systems.

  9. When a domain isn’t a domain, and why it’s important to properly filter proteins in databases

    PubMed Central

    Towse, Clare-Louise; Daggett, Valerie

    2013-01-01

    Summary Membership in a protein domain database does not a domain make; a feature we realized when generating a consensus view of protein fold space with our Consensus Domain Dictionary (CDD). This dictionary was used to select representative structures for characterization of the protein dynameome: the Dynameomics initiative. Through this endeavor we rejected a surprising 40% of the 1695 folds in the CDD as being non-autonomous folding units. Although some of this was due to the challenges of grouping similar fold topologies, the dissonance between the cataloguing and structural qualification of protein domains remains surprising. Another potential factor is previously overlooked intrinsic disorder; predicted estimates suggest 40% of proteins to have either local or global disorder. One thing is clear, filtering a structural database and ensuring a consistent definition for protein domains is crucial, and caution is prescribed when generalizations of globular domains are drawn from unfiltered protein domain datasets. PMID:23108912

  10. Structure-function correlations in glaucoma using matrix and standard automated perimetry versus time-domain and spectral-domain OCT devices.

    PubMed

    Pinto, Luciano Moreira; Costa, Elaine Fiod; Melo, Luiz Alberto S; Gross, Paula Blasco; Sato, Eduardo Toshio; Almeida, Andrea Pereira; Maia, Andre; Paranhos, Augusto

    2014-04-10

    We examined the structure-function relationship between two perimetric tests, the frequency doubling technology (FDT) matrix and standard automated perimetry (SAP), and two optical coherence tomography (OCT) devices (time-domain and spectral-domain). This cross-sectional study included 97 eyes from 29 healthy individuals, and 68 individuals with early, moderate, or advanced primary open-angle glaucoma. The correlations between overall and sectorial parameters of retinal nerve fiber layer thickness (RNFL) measured with Stratus and Spectralis OCT, and the visual field sensitivity obtained with FDT matrix and SAP were assessed. The relationship also was evaluated using a previously described linear model. The correlation coefficients for the threshold sensitivity measured with SAP and Stratus OCT ranged from 0.44 to 0.79, and those for Spectralis OCT ranged from 0.30 to 0.75. Regarding FDT matrix, the correlation ranged from 0.40 to 0.79 with Stratus OCT and from 0.39 to 0.79 with Spectralis OCT. Stronger correlations were found in the overall measurements and the arcuate sectors for both visual fields and OCT devices. A linear relationship was observed between FDT matrix sensitivity and the OCT devices. The previously described linear model fit the data from SAP and the OCT devices well, particularly in the inferotemporal sector. The FDT matrix and SAP visual sensitivities were related strongly to the RNFL thickness measured with the Stratus and Spectralis OCT devices, particularly in the overall and arcuate sectors. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  11. Origin and Evolution of the Sponge Aggregation Factor Gene Family

    PubMed Central

    Grice, Laura F.; Gauthier, Marie E.A.; Roper, Kathrein E.; Fernàndez-Busquets, Xavier; Degnan, Sandie M.

    2017-01-01

    Although discriminating self from nonself is a cardinal animal trait, metazoan allorecognition genes do not appear to be homologous. Here, we characterize the Aggregation Factor (AF) gene family, which encodes putative allorecognition factors in the demosponge Amphimedon queenslandica, and trace its evolution across 24 sponge (Porifera) species. The AF locus in Amphimedon is comprised of a cluster of five similar genes that encode Calx-beta and Von Willebrand domains and a newly defined Wreath domain, and are highly polymorphic. Further AF variance appears to be generated through individualistic patterns of RNA editing. The AF gene family varies between poriferans, with protein sequences and domains diagnostic of the AF family being present in Amphimedon and other demosponges, but absent from other sponge classes. Within the demosponges, AFs vary widely with no two species having the same AF repertoire or domain organization. The evolution of AFs suggests that their diversification occurs via high allelism, and the continual and rapid gain, loss and shuffling of domains over evolutionary time. Given the marked differences in metazoan allorecognition genes, we propose the rapid evolution of AFs in sponges provides a model for understanding the extensive diversification of self–nonself recognition systems in the animal kingdom. PMID:28104746

  12. C-terminal activating and inhibitory domains determine the transactivation potential of BSAP (Pax-5), Pax-2 and Pax-8.

    PubMed Central

    Dörfler, P; Busslinger, M

    1996-01-01

    Pax-5 encodes the transcription factor BSAP which plays an essential role in early B cell development and midbrain patterning. In this study we have analysed the structural requirements for transcriptional activation by BSAP. In vitro mutagenesis and transient transfection experiments indicate that the C-terminal serine/threonine/proline-rich region of BSAP contains a potent transactivation domain of 55 amino acids which is active from promoter and enhancer positions. This transactivation domain was found to be inactivated by a naturally occurring frameshift mutation in one PAX-5 allele of the acute lymphoblastic leukemia cell line REH. The function of the transactivation domain is negatively regulated by adjacent sequences from the extreme C-terminus. The activating and inhibitory domains function together as an independent regulatory module in different cell types as shown by fusion to the GAL4 DNA binding domain. The same arrangement of positively and negatively acting sequences has been conserved in the mammalian Pax-2 and Pax-8, the zebrafish Pax-b as well as the sea urchin Pax-258 proteins. These data demonstrate that the transcriptional competence of a subfamily of Pax proteins is determined by a C-terminal regulatory module composed of activating and inhibitory sequences. Images PMID:8617244

  13. Finite element simulation of ultrasonic waves in corroded reinforced concrete for early-stage corrosion detection

    NASA Astrophysics Data System (ADS)

    Tang, Qixiang; Yu, Tzuyang

    2017-04-01

    In reinforced concrete (RC) structures, corrosion of steel rebar introduces internal stress at the interface between rebar and concrete, ultimately leading to debonding and separation between rebar and concrete. Effective early-stage detection of steel rebar corrosion can significantly reduce maintenance costs and enable early-stage repair. In this paper, ultrasonic detection of early-stage steel rebar corrosion inside concrete is numerically investigated using the finite element method (FEM). Commercial FEM software (ABAQUS) was used in all simulation cases. Steel rebar was simplified and modeled by a cylindrical structure. 1MHz ultrasonic elastic waves were generated at the interface between rebar and concrete. Two-dimensional plain strain element was adopted in all FE models. Formation of surface rust in rebar was modeled by changing material properties and expanding element size in order to simulate the rust interface between rebar and concrete and the presence of interfacial stress. Two types of surface rust (corroded regions) were considered. Time domain and frequency domain responses of displacement were studied. From our simulation result, two corrosion indicators, baseline (b) and center frequency (fc) were proposed for detecting and quantifying corrosion.

  14. Imaging genetics in attention-deficit/hyperactivity disorder and related neurodevelopmental domains: state of the art.

    PubMed

    Vilor-Tejedor, Natàlia; Cáceres, Alejandro; Pujol, Jesús; Sunyer, Jordi; González, Juan R

    2017-12-01

    Joint analysis of genetic and neuroimaging data, known as Imaging Genetics (IG), offers an opportunity to deepen our knowledge of the biological mechanisms of neurodevelopmental domains. There has been exponential growth in the literature on IG studies, which challenges the standardization of analysis methods in this field. In this review we give a complete up-to-date account of IG studies on attention deficit hyperactivity disorder (ADHD) and related neurodevelopmental domains, which serves as a reference catalog for researchers working on this neurological disorder. We searched MEDLINE/Pubmed and identified 37 articles on IG of ADHD that met our eligibility criteria. We carefully cataloged these articles according to imaging technique, genes and brain region, and summarized the main results and characteristics of each study. We found that IG studies on ADHD generally focus on dopaminergic genes and the structure of basal ganglia using structural Magnetic Resonance Imaging (MRI). We found little research involving multiple genetic factors and brain regions because of the scarce use of multivariate strategies in data analysis. IG of ADHD and related neurodevelopmental domains is still in its early stages, and a lack of replicated findings is one of the most pressing challenges in the field.

  15. Multi-material micro-electromechanical fibers with bendable functional domains

    NASA Astrophysics Data System (ADS)

    Nguyen-Dang, Tung; Page, Alexis G.; Qu, Yunpeng; Volpi, Marco; Yan, Wei; Sorin, Fabien

    2017-04-01

    The integration of increasingly complex functionalities within thermally drawn multi-material fibers is heralding a novel path towards advanced soft electronics and smart fabrics. Fibers capable of electronic, optoelectronic, piezoelectric or energy harvesting functions are created by assembling new materials in intimate contact within increasingly complex architectures. Thus far, however, the opportunities associated with the integration of cantilever-like structures with freely moving functional domains within multi-material fibers have not been explored. Used extensively in the micro-electromechanical system (MEMS) technology, electro-mechanical transductance from moving and bendable domains is used in a myriad of applications. In this article we demonstrate the thermal drawing of micro-electromechanical fibers (MEMF) that can detect and localize pressure with high accuracy along their entire length. This ability results from an original cantilever-like design where a freestanding electrically conductive polymer composite film bends under an applied pressure. As it comes into contact with another conducting domain, placed at a prescribed position in the fiber cross-section, an electrical signal is generated. We show that by a judicious choice of materials and electrical connectivity, this signal can be uniquely related to a position along the fiber axis. We establish a model that predicts the position of a local touch from the measurement of currents generated in the 1D MEMF device, and demonstrate an excellent agreement with the experimental data. This ability to detect and localize touch over large areas, curved surfaces and textiles holds significant opportunities in robotics and prosthetics, flexible electronic interfaces, and medical textiles. , which features invited work from the best early-career researchers working within the scope of J. Phys. D. This project is part of the Journal of Physics series’ 50th anniversary celebrations in 2017. Fabien Sorin

  16. Cache domains that are homologous to, but different from PAS domains comprise the largest superfamily of extracellular sensors in prokaryotes

    DOE PAGES

    Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; ...

    2016-04-06

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less

  17. Cache domains that are homologous to, but different from PAS domains comprise the largest superfamily of extracellular sensors in prokaryotes

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

    Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less

  18. Evolutionary dynamics of protein domain architecture in plants

    PubMed Central

    2012-01-01

    Background Protein domains are the structural, functional and evolutionary units of the protein. Protein domain architectures are the linear arrangements of domain(s) in individual proteins. Although the evolutionary history of protein domain architecture has been extensively studied in microorganisms, the evolutionary dynamics of domain architecture in the plant kingdom remains largely undefined. To address this question, we analyzed the lineage-based protein domain architecture content in 14 completed green plant genomes. Results Our analyses show that all 14 plant genomes maintain similar distributions of species-specific, single-domain, and multi-domain architectures. Approximately 65% of plant domain architectures are universally present in all plant lineages, while the remaining architectures are lineage-specific. Clear examples are seen of both the loss and gain of specific protein architectures in higher plants. There has been a dynamic, lineage-wise expansion of domain architectures during plant evolution. The data suggest that this expansion can be largely explained by changes in nuclear ploidy resulting from rounds of whole genome duplications. Indeed, there has been a decrease in the number of unique domain architectures when the genomes were normalized into a presumed ancestral genome that has not undergone whole genome duplications. Conclusions Our data show the conservation of universal domain architectures in all available plant genomes, indicating the presence of an evolutionarily conserved, core set of protein components. However, the occurrence of lineage-specific domain architectures indicates that domain architecture diversity has been maintained beyond these core components in plant genomes. Although several features of genome-wide domain architecture content are conserved in plants, the data clearly demonstrate lineage-wise, progressive changes and expansions of individual protein domain architectures, reinforcing the notion that plant

  19. MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours | Office of Cancer Genomics

    Cancer.gov

    Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails.

  20. Nature and the Outdoor Learning Environment: The Forgotten Resource in Early Childhood Education

    ERIC Educational Resources Information Center

    Cooper, Allen

    2015-01-01

    Longitudinal studies now confirm the economic, academic, and social importance of high-quality early childhood education. At the same time, a substantial body of research indicates that an outdoor learning and play environment with diverse natural elements advances and enriches all of the domains relevant to the development, health, and well-being…