A TALE-inspired computational screen for proteins that contain approximate tandem repeats.

Science.gov (United States)

Perycz, Malgorzata; Krwawicz, Joanna; Bochtler, Matthias

2017-01-01

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen.

Constructs for the expression of repeating triple-helical protein domains

International Nuclear Information System (INIS)

Peng, Yong Y; Werkmeister, Jerome A; Vaughan, Paul R; Ramshaw, John A M

2009-01-01

The development of novel scaffolds will be an important aspect in future success of tissue engineering. Scaffolds will preferably contain information that directs the cellular content of constructs so that the new tissue that is formed is closely aligned in structure, composition and function to the target natural tissue. One way of approaching this will be the development of novel protein-based constructs that contain one or more repeats of functional elements derived from various proteins. In the present case, we describe a strategy to make synthetic, recombinant triple-helical constructs that contain repeat segments of biologically relevant domains. Copies of a DNA fragment prepared by PCR from human type III collagen have been inserted in a co-linear contiguous fashion into the yeast expression vector YEpFlag-1, using sequential addition between selected restriction sites. Constructs containing 1, 2 and 3 repeats were designed to maintain the (Gly-X-Y) repeat, which is essential for the formation of an extended triple helix. All constructs gave expressed protein, with the best being the 3-repeat construct which was readily secreted. This material had the expected composition and N-terminal sequence. Incubation of the product at low temperature led to triple-helix formation, shown by reaction with a conformation dependent monoclonal antibody.

Constructs for the expression of repeating triple-helical protein domains

Energy Technology Data Exchange (ETDEWEB)

Peng, Yong Y; Werkmeister, Jerome A; Vaughan, Paul R; Ramshaw, John A M, E-mail: jerome.werkmeister@csiro.a [CSIRO Molecular and Health Technologies, Bag 10, Clayton South, VIC 3169 (Australia)

2009-02-15

The development of novel scaffolds will be an important aspect in future success of tissue engineering. Scaffolds will preferably contain information that directs the cellular content of constructs so that the new tissue that is formed is closely aligned in structure, composition and function to the target natural tissue. One way of approaching this will be the development of novel protein-based constructs that contain one or more repeats of functional elements derived from various proteins. In the present case, we describe a strategy to make synthetic, recombinant triple-helical constructs that contain repeat segments of biologically relevant domains. Copies of a DNA fragment prepared by PCR from human type III collagen have been inserted in a co-linear contiguous fashion into the yeast expression vector YEpFlag-1, using sequential addition between selected restriction sites. Constructs containing 1, 2 and 3 repeats were designed to maintain the (Gly-X-Y) repeat, which is essential for the formation of an extended triple helix. All constructs gave expressed protein, with the best being the 3-repeat construct which was readily secreted. This material had the expected composition and N-terminal sequence. Incubation of the product at low temperature led to triple-helix formation, shown by reaction with a conformation dependent monoclonal antibody.

Quantitative analysis and prediction of curvature in leucine-rich repeat proteins.

Science.gov (United States)

Hindle, K Lauren; Bella, Jordi; Lovell, Simon C

2009-11-01

Leucine-rich repeat (LRR) proteins form a large and diverse family. They have a wide range of functions most of which involve the formation of protein-protein interactions. All known LRR structures form curved solenoids, although there is large variation in their curvature. It is this curvature that determines the shape and dimensions of the inner space available for ligand binding. Unfortunately, large-scale parameters such as the overall curvature of a protein domain are extremely difficult to predict. Here, we present a quantitative analysis of determinants of curvature of this family. Individual repeats typically range in length between 20 and 30 residues and have a variety of secondary structures on their convex side. The observed curvature of the LRR domains correlates poorly with the lengths of their individual repeats. We have, therefore, developed a scoring function based on the secondary structure of the convex side of the protein that allows prediction of the overall curvature with a high degree of accuracy. We also demonstrate the effectiveness of this method in selecting a suitable template for comparative modeling. We have developed an automated, quantitative protocol that can be used to predict accurately the curvature of leucine-rich repeat proteins of unknown structure from sequence alone. This protocol is available as an online resource at http://www.bioinf.manchester.ac.uk/curlrr/.

DNA-binding proteins from marine bacteria expand the known sequence diversity of TALE-like repeats.

Science.gov (United States)

de Lange, Orlando; Wolf, Christina; Thiel, Philipp; Krüger, Jens; Kleusch, Christian; Kohlbacher, Oliver; Lahaye, Thomas

2015-11-16

Transcription Activator-Like Effectors (TALEs) of Xanthomonas bacteria are programmable DNA binding proteins with unprecedented target specificity. Comparative studies into TALE repeat structure and function are hindered by the limited sequence variation among TALE repeats. More sequence-diverse TALE-like proteins are known from Ralstonia solanacearum (RipTALs) and Burkholderia rhizoxinica (Bats), but RipTAL and Bat repeats are conserved with those of TALEs around the DNA-binding residue. We study two novel marine-organism TALE-like proteins (MOrTL1 and MOrTL2), the first to date of non-terrestrial origin. We have assessed their DNA-binding properties and modelled repeat structures. We found that repeats from these proteins mediate sequence specific DNA binding conforming to the TALE code, despite low sequence similarity to TALE repeats, and with novel residues around the BSR. However, MOrTL1 repeats show greater sequence discriminating power than MOrTL2 repeats. Sequence alignments show that there are only three residues conserved between repeats of all TALE-like proteins including the two new additions. This conserved motif could prove useful as an identifier for future TALE-likes. Additionally, comparing MOrTL repeats with those of other TALE-likes suggests a common evolutionary origin for the TALEs, RipTALs and Bats. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structure of thrombospondin type 3 repeats in bacterial outer membrane protein A reveals its intra-repeat disulfide bond-dependent calcium-binding capability

Energy Technology Data Exchange (ETDEWEB)

Dai, Shuyan; Sun, Cancan; Tan, Kemin; Ye, Sheng; Zhang, Rongguang

2017-09-01

Eukaryotic thrombospondin type 3 repeat (TT3R) is an efficient calcium ion (Ca2+) binding motif only found in mammalian thrombospondin family. TT3R has also been found in prokaryotic cellulase Cel5G, which was thought to forfeit the Ca2+-binding capability due to the formation of intra-repeat disulfide bonds, instead of the inter-repeat ones possessed by eukaryotic TT3Rs. In this study, we have identified an enormous number of prokaryotic TT3R-containing proteins belonging to several different protein families, including outer membrane protein A (OmpA), an important structural protein connecting the outer membrane and the periplasmic peptidoglycan layer in gram-negative bacteria. Here, we report the crystal structure of the periplasmic region of OmpA from Capnocytophaga gingivalis, which contains a linker region comprising five consecutive TT3Rs. The structure of OmpA-TT3R exhibits a well-ordered architecture organized around two tightly-coordinated Ca2+ and confirms the presence of abnormal intra-repeat disulfide bonds. Further mutagenesis studies showed that the Ca2+-binding capability of OmpA-TT3R is indeed dependent on the proper formation of intra-repeat disulfide bonds, which help to fix a conserved glycine residue at its proper position for Ca2+ coordination. Additionally, despite lacking inter repeat disulfide bonds, the interfaces between adjacent OmpA-TT3Rs are enhanced by both hydrophobic and conserved aromatic-proline interactions.

Alanine repeats influence protein localization in splicing speckles and paraspeckles.

Science.gov (United States)

Chang, Shuo-Hsiu; Chang, Wei-Lun; Lu, Chia-Chen; Tarn, Woan-Yuh

2014-12-16

Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated-fully or partially-from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Solution properties of the archaeal CRISPR DNA repeat-binding homeodomain protein Cbp2

DEFF Research Database (Denmark)

Kenchappa, Chandra; Heiðarsson, Pétur Orri; Kragelund, Birthe

2013-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) form the basis of diverse adaptive immune systems directed primarily against invading genetic elements of archaea and bacteria. Cbp1 of the crenarchaeal thermoacidophilic order Sulfolobales, carrying three imperfect repeats, binds...... specifically to CRISPR DNA repeats and has been implicated in facilitating production of long transcripts from CRISPR loci. Here, a second related class of CRISPR DNA repeat-binding protein, denoted Cbp2, is characterized that contains two imperfect repeats and is found amongst members of the crenarchaeal...... in facilitating high affinity DNA binding of Cbp2 by tethering the two domains. Structural studies on mutant proteins provide support for Cys(7) and Cys(28) enhancing high thermal stability of Cbp2(Hb) through disulphide bridge formation. Consistent with their proposed CRISPR transcriptional regulatory role, Cbp2...

Inferring repeat-protein energetics from evolutionary information.

Directory of Open Access Journals (Sweden)

Rocío Espada

2017-06-01

Full Text Available Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing covariations in extant sequences. Still, many natural proteins that fold into the same structural topology show different stabilization energies, and these are often related to their physiological behavior. We propose a description for the energetic variation given by sequence modifications in repeat proteins, systems for which the overall problem is simplified by their inherent symmetry. We explicitly account for single amino acid and pair-wise interactions and treat higher order correlations with a single term. We show that the resulting evolutionary field can be interpreted with structural detail. We trace the variations in the energetic scores of natural proteins and relate them to their experimental characterization. The resulting energetic evolutionary field allows the prediction of the folding free energy change for several mutants, and can be used to generate synthetic sequences that are statistically indistinguishable from the natural counterparts.

Myotonin protein-kinase [AGC]n trinucleotide repeat in seven nonhuman primates

Energy Technology Data Exchange (ETDEWEB)

Novelli, G.; Sineo, L.; Pontieri, E. [Catholic Univ. of Rome (Italy)]|[Univ. of Milan (Italy)]|[Univ. Florence (Italy)] [and others

1994-09-01

Myotonic dystrophy (DM) is due to a genomic instability of a trinucleotide [AGC]n motif, located at the 3{prime} UTR region of a protein-kinase gene (myotonin protein kinase, MT-PK). The [AGC] repeat is meiotically and mitotically unstable, and it is directly related to the manifestations of the disorder. Although a gene dosage effect of the MT-PK has been demonstrated n DM muscle, the mechanism(s) by which the intragenic repeat expansion leads to disease is largely unknown. This non-standard mutational event could reflect an evolutionary mechanism widespread among animal genomes. We have isolated and sequenced the complete 3{prime}UTR region of the MT-PK gene in seven primates (macaque, orangutan, gorilla, chimpanzee, gibbon, owl monkey, saimiri), and examined by comparative sequence nucleotide analysis the [AGC]n intragenic repeat and the surrounding nucleotides. The genomic organization, including the [AGC]n repeat structure, was conserved in all examined species, excluding the gibbon (Hylobates agilis), in which the [AGC]n upstream sequence (GGAA) is replaced by a GA dinucleotide. The number of [AGC]n in the examined species ranged between 7 (gorilla) and 13 repeats (owl monkeys), with a polymorphism informative content (PIC) similar to that observed in humans. These results indicate that the 3{prime}UTR [AGC] repeat within the MT-PK gene is evolutionarily conserved, supporting that this region has important regulatory functions.

Direct and inverted repeats elicit genetic instability by both exploiting and eluding DNA double-strand break repair systems in mycobacteria.

Directory of Open Access Journals (Sweden)

Ewelina A Wojcik

Full Text Available Repetitive DNA sequences with the potential to form alternative DNA conformations, such as slipped structures and cruciforms, can induce genetic instability by promoting replication errors and by serving as a substrate for DNA repair proteins, which may lead to DNA double-strand breaks (DSBs. However, the contribution of each of the DSB repair pathways, homologous recombination (HR, non-homologous end-joining (NHEJ and single-strand annealing (SSA, to this sort of genetic instability is not fully understood. Herein, we assessed the genome-wide distribution of repetitive DNA sequences in the Mycobacterium smegmatis, Mycobacterium tuberculosis and Escherichia coli genomes, and determined the types and frequencies of genetic instability induced by direct and inverted repeats, both in the presence and in the absence of HR, NHEJ, and SSA. All three genomes are strongly enriched in direct repeats and modestly enriched in inverted repeats. When using chromosomally integrated constructs in M. smegmatis, direct repeats induced the perfect deletion of their intervening sequences ~1,000-fold above background. Absence of HR further enhanced these perfect deletions, whereas absence of NHEJ or SSA had no influence, suggesting compromised replication fidelity. In contrast, inverted repeats induced perfect deletions only in the absence of SSA. Both direct and inverted repeats stimulated excision of the constructs from the attB integration sites independently of HR, NHEJ, or SSA. With episomal constructs, direct and inverted repeats triggered DNA instability by activating nucleolytic activity, and absence of the DSB repair pathways (in the order NHEJ>HR>SSA exacerbated this instability. Thus, direct and inverted repeats may elicit genetic instability in mycobacteria by 1 directly interfering with replication fidelity, 2 stimulating the three main DSB repair pathways, and 3 enticing L5 site-specific recombination.

Direct and inverted repeats elicit genetic instability by both exploiting and eluding DNA double-strand break repair systems in mycobacteria.

Science.gov (United States)

Wojcik, Ewelina A; Brzostek, Anna; Bacolla, Albino; Mackiewicz, Pawel; Vasquez, Karen M; Korycka-Machala, Malgorzata; Jaworski, Adam; Dziadek, Jaroslaw

2012-01-01

Repetitive DNA sequences with the potential to form alternative DNA conformations, such as slipped structures and cruciforms, can induce genetic instability by promoting replication errors and by serving as a substrate for DNA repair proteins, which may lead to DNA double-strand breaks (DSBs). However, the contribution of each of the DSB repair pathways, homologous recombination (HR), non-homologous end-joining (NHEJ) and single-strand annealing (SSA), to this sort of genetic instability is not fully understood. Herein, we assessed the genome-wide distribution of repetitive DNA sequences in the Mycobacterium smegmatis, Mycobacterium tuberculosis and Escherichia coli genomes, and determined the types and frequencies of genetic instability induced by direct and inverted repeats, both in the presence and in the absence of HR, NHEJ, and SSA. All three genomes are strongly enriched in direct repeats and modestly enriched in inverted repeats. When using chromosomally integrated constructs in M. smegmatis, direct repeats induced the perfect deletion of their intervening sequences ~1,000-fold above background. Absence of HR further enhanced these perfect deletions, whereas absence of NHEJ or SSA had no influence, suggesting compromised replication fidelity. In contrast, inverted repeats induced perfect deletions only in the absence of SSA. Both direct and inverted repeats stimulated excision of the constructs from the attB integration sites independently of HR, NHEJ, or SSA. With episomal constructs, direct and inverted repeats triggered DNA instability by activating nucleolytic activity, and absence of the DSB repair pathways (in the order NHEJ>HR>SSA) exacerbated this instability. Thus, direct and inverted repeats may elicit genetic instability in mycobacteria by 1) directly interfering with replication fidelity, 2) stimulating the three main DSB repair pathways, and 3) enticing L5 site-specific recombination.

Constraints and consequences of the emergence of amino acid repeats in eukaryotic proteins.

Science.gov (United States)

Chavali, Sreenivas; Chavali, Pavithra L; Chalancon, Guilhem; de Groot, Natalia Sanchez; Gemayel, Rita; Latysheva, Natasha S; Ing-Simmons, Elizabeth; Verstrepen, Kevin J; Balaji, Santhanam; Babu, M Madan

2017-09-01

Proteins with amino acid homorepeats have the potential to be detrimental to cells and are often associated with human diseases. Why, then, are homorepeats prevalent in eukaryotic proteomes? In yeast, homorepeats are enriched in proteins that are essential and pleiotropic and that buffer environmental insults. The presence of homorepeats increases the functional versatility of proteins by mediating protein interactions and facilitating spatial organization in a repeat-dependent manner. During evolution, homorepeats are preferentially retained in proteins with stringent proteostasis, which might minimize repeat-associated detrimental effects such as unregulated phase separation and protein aggregation. Their presence facilitates rapid protein divergence through accumulation of amino acid substitutions, which often affect linear motifs and post-translational-modification sites. These substitutions may result in rewiring protein interaction and signaling networks. Thus, homorepeats are distinct modules that are often retained in stringently regulated proteins. Their presence facilitates rapid exploration of the genotype-phenotype landscape of a population, thereby contributing to adaptation and fitness.

Comparison of serum leptin, glucose, total cholesterol and total protein levels in fertile and repeat breeder cows

Directory of Open Access Journals (Sweden)

Saime Guzel

2014-12-01

Full Text Available In the present study we measured serum glucose, leptin, total cholesterol and total protein concentrations in repeat breeder cows and compared them with fertile cows. For this aim, 20 repeat breeder cows and 20 fertile cows were used as material. Repeat breeder cows were found to have lower levels of leptin and glucose as compared with fertile ones. No significant differences in total cholesterol and total protein levels were observed between the two groups. No significant correlation of leptin with glucose, total cholesterol and total protein was observed in fertile and repeat breeder cows. Low concentrations of glucose and leptin can have some effects on reproductive problems as repeat breeder and help to understand potential mechanisms impairing fertility in repeat breeder cows.

A large complement of the predicted Arabidopsis ARM repeat proteins are members of the U-box E3 ubiquitin ligase family.

Science.gov (United States)

Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L; Salt, Jennifer N; Goring, Daphne R

2004-01-01

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis.

Superfamily of ankyrin repeat proteins in tomato.

Science.gov (United States)

Yuan, Xiaowei; Zhang, Shizhong; Qing, Xiaohe; Sun, Meihong; Liu, Shiyang; Su, Hongyan; Shu, Huairui; Li, Xinzheng

2013-07-10

The ankyrin repeat (ANK) protein family plays a crucial role in plant growth and development and in response to biotic and abiotic stresses. However, no detailed information concerning this family is available for tomato (Solanum lycopersicum) due to the limited information on whole genome sequences. In this study, we identified a total of 130 ANK genes in tomato genome (SlANK), and these genes were distributed across all 12 chromosomes at various densities. And chromosomal localizations of SlANK genes indicated 25 SlANK genes were involved in tandem duplications. Based on their domain composition, all of the SlANK proteins were grouped into 13 subgroups. A combined phylogenetic tree was constructed with the aligned SlANK protein sequences. This tree revealed that the SlANK proteins comprise five major groups. An analysis of the expression profiles of SlANK genes in tomato in different tissues and in response to stresses showed that the SlANK proteins play roles in plant growth, development and stress responses. To our knowledge, this is the first report of a genome-wide analysis of the tomato ANK gene family. This study provides valuable information regarding the classification and putative functions of SlANK genes in tomato. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Deletion of Repeats in the Alpha C Protein Enhances the Pathogenicity of Group B Streptococci in Immune Mice

OpenAIRE

Gravekamp, C.; Rosner, Bernard; Madoff, L. C.

1998-01-01

The alpha C protein is a protective surface-associated antigen of group B streptococci (GBS). The prototype alpha C protein of GBS (strain A909) contains nine identical tandem repeats, each comprising 82 amino acids, flanked by N- and C-terminal domains. Clinical isolates of GBS show variable numbers of repeats with a normal distribution and a median of 9 to 10 repeats. Here, we show that escape mutants of GBS expressing one-repeat alpha C protein were 100-fold more pathogenic than GBS expres...

Programmable DNA-binding proteins from Burkholderia provide a fresh perspective on the TALE-like repeat domain.

Science.gov (United States)

de Lange, Orlando; Wolf, Christina; Dietze, Jörn; Elsaesser, Janett; Morbitzer, Robert; Lahaye, Thomas

2014-06-01

The tandem repeats of transcription activator like effectors (TALEs) mediate sequence-specific DNA binding using a simple code. Naturally, TALEs are injected by Xanthomonas bacteria into plant cells to manipulate the host transcriptome. In the laboratory TALE DNA binding domains are reprogrammed and used to target a fused functional domain to a genomic locus of choice. Research into the natural diversity of TALE-like proteins may provide resources for the further improvement of current TALE technology. Here we describe TALE-like proteins from the endosymbiotic bacterium Burkholderia rhizoxinica, termed Bat proteins. Bat repeat domains mediate sequence-specific DNA binding with the same code as TALEs, despite less than 40% sequence identity. We show that Bat proteins can be adapted for use as transcription factors and nucleases and that sequence preferences can be reprogrammed. Unlike TALEs, the core repeats of each Bat protein are highly polymorphic. This feature allowed us to explore alternative strategies for the design of custom Bat repeat arrays, providing novel insights into the functional relevance of non-RVD residues. The Bat proteins offer fertile grounds for research into the creation of improved programmable DNA-binding proteins and comparative insights into TALE-like evolution. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

CRISPR/Cas9-Assisted Transformation-Efficient Reaction (CRATER) for Near-Perfect Selective Transformation

Science.gov (United States)

Rothschild, Lynn J.; Greenberg, Daniel T.; Takahashi, Jack R.; Thompson, Kirsten A.; Maheshwari, Akshay J.; Kent, Ryan E.; McCutcheon, Griffin; Shih, Joseph D.; Calvet, Charles; Devlin, Tyler D.;

A Large Complement of the Predicted Arabidopsis ARM Repeat Proteins Are Members of the U-Box E3 Ubiquitin Ligase Family1[w

Science.gov (United States)

Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L.; Salt, Jennifer N.; Goring, Daphne R.

2004-01-01

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis. PMID:14657406

Structure-Function Analysis of Cf-9, a Receptor-Like Protein with Extracytoplasmic Leucine-Rich Repeats

NARCIS (Netherlands)

Hoorn, van der R.A.L.; Wulff, B.B.H.; Rivas, S.; Durrant, M.C.; Ploeg, van der A.; Wit, de P.J.G.M.; Jones, J.D.G.

2005-01-01

The tomato (Lycopersicon pimpinellifolium) resistance protein Cf-9 belongs to a large class of plant proteins with extracytoplasmic Leu-rich repeats (eLRRs). eLRR proteins play key roles in plant defense and development, mainly as receptor-like proteins or receptor-like kinases, conferring

Identification of TTAGGG-binding proteins in Neurospora crassa, a fungus with vertebrate-like telomere repeats.

Science.gov (United States)

Casas-Vila, Núria; Scheibe, Marion; Freiwald, Anja; Kappei, Dennis; Butter, Falk

2015-11-17

To date, telomere research in fungi has mainly focused on Saccharomyces cerevisiae and Schizosaccharomyces pombe, despite the fact that both yeasts have degenerated telomeric repeats in contrast to the canonical TTAGGG motif found in vertebrates and also several other fungi. Using label-free quantitative proteomics, we here investigate the telosome of Neurospora crassa, a fungus with canonical telomeric repeats. We show that at least six of the candidates detected in our screen are direct TTAGGG-repeat binding proteins. While three of the direct interactors (NCU03416 [ncTbf1], NCU01991 [ncTbf2] and NCU02182 [ncTay1]) feature the known myb/homeobox DNA interaction domain also found in the vertebrate telomeric factors, we additionally show that a zinc-finger protein (NCU07846) and two proteins without any annotated DNA-binding domain (NCU02644 and NCU05718) are also direct double-strand TTAGGG binders. We further find two single-strand binders (NCU02404 [ncGbp2] and NCU07735 [ncTcg1]). By quantitative label-free interactomics we identify TTAGGG-binding proteins in Neurospora crassa, suggesting candidates for telomeric factors that are supported by phylogenomic comparison with yeast species. Intriguingly, homologs in yeast species with degenerated telomeric repeats are also TTAGGG-binding proteins, e.g. in S. cerevisiae Tbf1 recognizes the TTAGGG motif found in its subtelomeres. However, there is also a subset of proteins that is not conserved. While a rudimentary core TTAGGG-recognition machinery may be conserved across yeast species, our data suggests Neurospora as an emerging model organism with unique features.

The leucine-rich repeat structure.

Science.gov (United States)

Bella, J; Hindle, K L; McEwan, P A; Lovell, S C

2008-08-01

The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.

Pentapeptide-repeat proteins that act as topoisomerase poison resistance factors have a common dimer interface

International Nuclear Information System (INIS)

Vetting, Matthew W.; Hegde, Subray S.; Zhang, Yong; Blanchard, John S.

2011-01-01

The pentapeptide repeat protein AlbG, provides self-resistance to the nonribosomally encoded hybrid polyketide-peptide termed albicidin. Analysis of the AlbG three-dimensional structure and the sequences of other pentapeptide repeat proteins that confer resistance to topiosomerase poisons suggests they have a similar dimer interface which may be critical to their interaction with topoisomerases. The protein AlbG is a self-resistance factor against albicidin, a nonribosomally encoded hybrid polyketide-peptide with antibiotic and phytotoxic properties produced by Xanthomonas albilineans. Primary-sequence analysis indicates that AlbG is a member of the pentapeptide-repeat family of proteins (PRP). The structure of AlbG from X. albilineans was determined at 2.0 Å resolution by SAD phasing using data collected from a single trimethyllead acetate derivative on a home source. AlbG folds into a right-handed quadrilateral β-helix composed of approximately eight semi-regular coils. The regularity of the β-helix is blemished by a large loop/deviation in the β-helix between coils 4 and 5. The C-terminus of the β-helix is capped by a dimerization module, yielding a dimer with a 110 Å semi-collinear β-helical axis. This method of dimer formation appears to be common to all PRP proteins that confer resistance to topoisomerase poisons and contrasts with most PRP proteins, which are typically monomeric

Quantum perfect correlations

International Nuclear Information System (INIS)

Ozawa, Masanao

2006-01-01

The notion of perfect correlations between arbitrary observables, or more generally arbitrary POVMs, is introduced in the standard formulation of quantum mechanics, and characterized by several well-established statistical conditions. The transitivity of perfect correlations is proved to generally hold, and applied to a simple articulation for the failure of Hardy's nonlocality proof for maximally entangled states. The notion of perfect correlations between observables and POVMs is used for defining the notion of a precise measurement of a given observable in a given state. A longstanding misconception on the correlation made by the measuring interaction is resolved in the light of the new theory of quantum perfect correlations

Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes

LENUS (Irish Health Repository)

Whan, Vicki

2010-11-23

Abstract Background About forty human diseases are caused by repeat instability mutations. A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation is also apparent in human poly-Q encoding genes from normal individuals. As these coding sequence repeats are subject to selection in mammals, it has been suggested that normal variations in some of these typically highly conserved genes are implicated in morphological differences between species and phenotypic variations within species. At present, poly-Q encoding genes in non-human mammalian species are poorly documented, as are their functions and propensities for polymorphic variation. Results The current investigation identified 178 bovine poly-Q encoding genes (Q ≥ 5) and within this group, 26 genes with orthologs in both human and mouse that did not contain poly-Q repeats. The bovine poly-Q encoding genes typically had ubiquitous expression patterns although there was bias towards expression in epithelia, brain and testes. They were also characterised by unusually large sizes. Analysis of gene ontology terms revealed that the encoded proteins were strongly enriched for functions associated with transcriptional regulation and many contributed to physical interaction networks in the nucleus where they presumably act cooperatively in transcriptional regulatory complexes. In addition, the coding sequence CAG repeats in some bovine genes impacted mRNA splicing thereby generating unusual transcriptional diversity, which in at least one instance was tissue-specific. The poly-Q encoding genes were prioritised using multiple criteria for their likelihood of being polymorphic and then the highest ranking group was experimentally tested for polymorphic variation within a cattle diversity panel. Extensive and meiotically stable variation was identified

Repeated radiation injuries by fission products

International Nuclear Information System (INIS)

Vasilenko, I.Ya.

1986-01-01

Attention is given to repeated radiation injuries during internal irradiation of theoretical and practical interest, particularly in case of the intake into organism of young products of nuclear fission (PNF). The results of experiments with dogs with repeated radioactive iodine injury the isotopes of which (131-135sub(I)) constitute a considerable part of PNF activity are discussed. The blood reaction and protein metabolism state have been studied. Observations for dogs have been continued for about 4 years. The doses for thyroid, gastrointestinal tract and liver subjected to the most intensive irradiation consituted in the first series of experiments after the first intake about 3;0.3;0.05 Gy, after the second - 5;0.5;0.08 Gy and in the second series of experiments - 3;0.3;0.05 Gy and 0.6;0.06;0.01 Gy, respectively. Hematologic factors,thyroid function, changes in exchange and immunologic reactivity have been studied. The dogs have been under observation for 5 years. It is shown in case of repeated intake of Isup(131) PNF into animals organism in quantity which does not cause during the acute period a clinically outlined sickness, substantial differences in the organism reaction as compared with the first intake of radionuclides have not been found. The presence of residual radiation injuries did not cause charging action during the acute period during PNF and repeated intake which in the author's opinion testifies to perfection of compensator mechanisms in case of intake of such quantities of radioactive products. At the remote periods blastomogenic action manifested which is estimated as a result of general biological action of radionuclides administered to the organism. The necessity in subsequent investigations for obtaining the data on organism reactivity, clinic and pathogenesis with the aim of prophylaxis and treatment of such injuries is indicated

Not so bad after all: retroviruses and long terminal repeat retrotransposons as a source of new genes in vertebrates.

Science.gov (United States)

Naville, M; Warren, I A; Haftek-Terreau, Z; Chalopin, D; Brunet, F; Levin, P; Galiana, D; Volff, J-N

2016-04-01

Viruses and transposable elements, once considered as purely junk and selfish sequences, have repeatedly been used as a source of novel protein-coding genes during the evolution of most eukaryotic lineages, a phenomenon called 'molecular domestication'. This is exemplified perfectly in mammals and other vertebrates, where many genes derived from long terminal repeat (LTR) retroelements (retroviruses and LTR retrotransposons) have been identified through comparative genomics and functional analyses. In particular, genes derived from gag structural protein and envelope (env) genes, as well as from the integrase-coding and protease-coding sequences, have been identified in humans and other vertebrates. Retroelement-derived genes are involved in many important biological processes including placenta formation, cognitive functions in the brain and immunity against retroelements, as well as in cell proliferation, apoptosis and cancer. These observations support an important role of retroelement-derived genes in the evolution and diversification of the vertebrate lineage. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Overexpression of MIP2, a novel WD-repeat protein, promotes proliferation of H9c2 cells

International Nuclear Information System (INIS)

Wei, Xing; Song, Lan; Jiang, Lei; Wang, Guiliang; Luo, Xinjing; Zhang, Bin; Xiao, Xianzhong

2010-01-01

WD40 repeat proteins have a wide range of diverse biological functions including signal transduction, cell cycle regulation, RNA splicing, and transcription. Myocardial ischemic preconditioning up-regulated protein 2 (MIP2) is a novel member of the WD40 repeat proteins superfamily that contains five WD40 repeats. Little is known about its biological role, and the purpose of this study was to determine the role of MIP2 in regulating cellular proliferation. Transfection and constitutive expression of MIP2 in the rat cardiomyoblast cell line H9c2 results in enhanced growth of those cells as measured by cell number and is proportional to the amount of MIP2 expressed. Overexpression of MIP2 results in a shorter cell cycle, as measured by flow cytometry. Collectively, these data suggest that MIP2 may participate in the progression of cell proliferation in H9c2 cells.

Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic

Directory of Open Access Journals (Sweden)

Youn-Bok Lee

2013-12-01

Full Text Available The GGGGCC (G4C2 intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected cells. Only hnRNP-H binds directly to G4C2 repeats following RNA immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2 repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins. We propose that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration.

History, rare, and multiple events of mechanical unfolding of repeat proteins

Science.gov (United States)

Sumbul, Fidan; Marchesi, Arin; Rico, Felix

2018-03-01

Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.

Perfect imaging without negative refraction

OpenAIRE

Leonhardt, Ulf

2009-01-01

Perfect imaging has been believed to rely on negative refraction, but here we show that an ordinary positively-refracting optical medium may form perfect images as well. In particular, we establish a mathematical proof that Maxwell's fish eye in two-dimensional integrated optics makes a perfect instrument with a resolution not limited by the wavelength of light. We also show how to modify the fish eye such that perfect imaging devices can be made in practice. Our method of perfect focusing ma...

Identification of Pentatricopeptide Repeat Proteins in the Model Organism Dictyostelium discoideum

Directory of Open Access Journals (Sweden)

Sam Manna

2013-01-01

Full Text Available Pentatricopeptide repeat (PPR proteins are RNA binding proteins with functions in organelle RNA metabolism. They are found in all eukaryotes but have been most extensively studied in plants. We report on the identification of 12 PPR-encoding genes in the genome of the protist Dictyostelium discoideum, with potential homologs in other members of the same lineage and some predicted novel functions for the encoded gene products in protists. For one of the gene products, we show that it localizes to the mitochondria, and we also demonstrate that antisense inhibition of its expression leads to slower growth, a phenotype associated with mitochondrial dysfunction.

PERFECT DEMAND ILLUSION

Directory of Open Access Journals (Sweden)

Alexander Yu. Sulimov

2015-01-01

Full Text Available The article is devoted to technique «Perfect demand illusion», which allows to strengthen the competitive advantageof retailers. Also in the paper spells out the golden rules of visual merchandising.The definition of the method «Demand illusion», formulated the conditions of its functioning, and is determined by the mainhypothesis of the existence of this method.Furthermore, given the definition of the «Perfect demand illusion», and describes its additional conditions. Also spells out the advantages of the «Perfect demandillusion», before the «Demand illusion».

Learning, Teaching, and Turn Taking in the Repeated Assignment Game

OpenAIRE

Timothy N. Cason; Sau-Him Paul Lau; Vai-Lam Mui

2011-01-01

History-dependent strategies are often used to support cooperation in repeated game models. Using the indefinitely repeated common-pool resource assignment game and a perfect stranger experimental design, this paper reports novel evidence that players who have successfully used an efficiency-enhancing turn-taking strategy will teach other players in subsequent supergames to adopt this strategy. We find that subjects engage in turn taking frequently in both the Low Conflict and the High Confli...

Poly-dipeptides encoded by the C9ORF72 repeats block global protein translation.

Science.gov (United States)

Kanekura, Kohsuke; Yagi, Takuya; Cammack, Alexander J; Mahadevan, Jana; Kuroda, Masahiko; Harms, Matthew B; Miller, Timothy M; Urano, Fumihiko

2016-05-01

The expansion of the GGGGCC hexanucleotide repeat in the non-coding region of the Chromosome 9 open-reading frame 72 (C9orf72) gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This genetic alteration leads to the accumulation of five types of poly-dipeptides translated from the GGGGCC hexanucleotide repeat. Among these, poly-proline-arginine (poly-PR) and poly-glycine-arginine (poly-GR) peptides are known to be neurotoxic. However, the mechanisms of neurotoxicity associated with these poly-dipeptides are not clear. A proteomics approach identified a number of interacting proteins with poly-PR peptide, including mRNA-binding proteins, ribosomal proteins, translation initiation factors and translation elongation factors. Immunostaining of brain sections from patients with C9orf72 ALS showed that poly-GR was colocalized with a mRNA-binding protein, hnRNPA1. In vitro translation assays showed that poly-PR and poly-GR peptides made insoluble complexes with mRNA, restrained the access of translation factors to mRNA, and blocked protein translation. Our results demonstrate that impaired protein translation mediated by poly-PR and poly-GR peptides plays a role in neurotoxicity and reveal that the pathways altered by the poly-dipeptides-mRNA complexes are potential therapeutic targets for treatment of C9orf72 FTD/ALS. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Perfect imaging without negative refraction

Energy Technology Data Exchange (ETDEWEB)

Leonhardt, Ulf [School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews KY16 9SS (United Kingdom)], E-mail: ulf@st-andrews.ac.uk

2009-09-15

Perfect imaging has been believed to rely on negative refraction, but here we show that an ordinary positively refracting optical medium may form perfect images as well. In particular, we establish a mathematical proof that Maxwell's fish eye in two-dimensional (2D) integrated optics makes a perfect instrument with a resolution not limited by the wavelength of light. We also show how to modify the fish eye such that perfect imaging devices can be made in practice. Our method of perfect focusing may also find applications outside of optics, in acoustics, fluid mechanics or quantum physics, wherever waves obey the 2D Helmholtz equation.

DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing.

Science.gov (United States)

Saveliev, Alexander; Everett, Christopher; Sharpe, Tammy; Webster, Zoë; Festenstein, Richard

2003-04-24

Gene repression is crucial to the maintenance of differentiated cell types in multicellular organisms, whereas aberrant silencing can lead to disease. The organization of DNA into chromatin and heterochromatin is implicated in gene silencing. In chromatin, DNA wraps around histones, creating nucleosomes. Further condensation of chromatin, associated with large blocks of repetitive DNA sequences, is known as heterochromatin. Position effect variegation (PEV) occurs when a gene is located abnormally close to heterochromatin, silencing the affected gene in a proportion of cells. Here we show that the relatively short triplet-repeat expansions found in myotonic dystrophy and Friedreich's ataxia confer variegation of expression on a linked transgene in mice. Silencing was correlated with a decrease in promoter accessibility and was enhanced by the classical PEV modifier heterochromatin protein 1 (HP1). Notably, triplet-repeat-associated variegation was not restricted to classical heterochromatic regions but occurred irrespective of chromosomal location. Because the phenomenon described here shares important features with PEV, the mechanisms underlying heterochromatin-mediated silencing might have a role in gene regulation at many sites throughout the mammalian genome and modulate the extent of gene silencing and hence severity in several triplet-repeat diseases.

Interaction between a plasma membrane-localized ankyrin-repeat protein ITN1 and a nuclear protein RTV1

Energy Technology Data Exchange (ETDEWEB)

Sakamoto, Hikaru [Department of Bioproduction, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri-shi, Hokkaido 093-2422 (Japan); Sakata, Keiko; Kusumi, Kensuke [Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Kojima, Mikiko; Sakakibara, Hitoshi [RIKEN Plant Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 (Japan); Iba, Koh, E-mail: koibascb@kyushu-u.org [Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)

2012-06-29

Highlights: Black-Right-Pointing-Pointer ITN1, a plasma membrane ankyrin protein, interacts with a nuclear DNA-binding protein RTV1. Black-Right-Pointing-Pointer The nuclear transport of RTV1 is partially inhibited by interaction with ITN1. Black-Right-Pointing-Pointer RTV1 can promote the nuclear localization of ITN1. Black-Right-Pointing-Pointer Both overexpression of RTV1 and the lack of ITN1 increase salicylic acids sensitivity in plants. -- Abstract: The increased tolerance to NaCl 1 (ITN1) protein is a plasma membrane (PM)-localized protein involved in responses to NaCl stress in Arabidopsis. The predicted structure of ITN1 is composed of multiple transmembrane regions and an ankyrin-repeat domain that is known to mediate protein-protein interactions. To elucidate the molecular functions of ITN1, we searched for interacting partners using a yeast two-hybrid assay, and a nuclear-localized DNA-binding protein, RTV1, was identified as a candidate. Bimolecular fluorescence complementation analysis revealed that RTV1 interacted with ITN1 at the PM and nuclei in vivo. RTV1 tagged with red fluorescent protein localized to nuclei and ITN1 tagged with green fluorescent protein localized to PM; however, both proteins localized to both nuclei and the PM when co-expressed. These findings suggest that RTV1 and ITN1 regulate the subcellular localization of each other.

Perfect sequences over the real quaternions

OpenAIRE

Kuznetsov, Oleg

2017-01-01

In this Thesis, perfect sequences over the real quaternions are first considered. Definitions for the right and left periodic autocorrelation functions are given, and right and left perfect sequences introduced. It is shown that the right (left) perfection of any sequence implies the left (right) perfection, so concepts of right and left perfect sequences over the real quaternions are equivalent. Unitary transformations of the quaternion space ℍ are then considered. Using the equivalence of t...

The protein network surrounding the human telomere repeat binding factors TRF1, TRF2, and POT1.

Directory of Open Access Journals (Sweden)

Richard J Giannone

2010-08-01

Full Text Available Telomere integrity (including telomere length and capping is critical in overall genomic stability. Telomere repeat binding factors and their associated proteins play vital roles in telomere length regulation and end protection. In this study, we explore the protein network surrounding telomere repeat binding factors, TRF1, TRF2, and POT1 using dual-tag affinity purification in combination with multidimensional protein identification technology liquid chromatography--tandem mass spectrometry (MudPIT LC-MS/MS. After control subtraction and data filtering, we found that TRF2 and POT1 co-purified all six members of the telomere protein complex, while TRF1 identified five of six components at frequencies that lend evidence towards the currently accepted telomere architecture. Many of the known TRF1 or TRF2 interacting proteins were also identified. Moreover, putative associating partners identified for each of the three core components fell into functional categories such as DNA damage repair, ubiquitination, chromosome cohesion, chromatin modification/remodeling, DNA replication, cell cycle and transcription regulation, nucleotide metabolism, RNA processing, and nuclear transport. These putative protein-protein associations may participate in different biological processes at telomeres or, intriguingly, outside telomeres.

Identification of a novel Leucine-rich repeat protein and candidate PP1 regulatory subunit expressed in developing spermatids

Directory of Open Access Journals (Sweden)

Sperry Ann O

2008-01-01

Full Text Available Abstract Background Spermatogenesis is comprised of a series of highly regulated developmental changes that transform the precursor germ cell into a highly specialized spermatozoon. The last phase of spermatogenesis, termed spermiogenesis, involves dramatic morphological change including formation of the acrosome, elongation and condensation of the nucleus, formation of the flagella, and disposal of unnecessary cytoplasm. A prominent cytoskeletal component of the developing spermatid is the manchette, a unique microtubular structure that surrounds the nucleus of the developing spermatid and is thought to assist in both the reshaping of the nucleus and redistribution of spermatid cytoplasm. Although the molecular motor KIFC1 has been shown to associate with the manchette, its precise role in function of the manchette and the identity of its testis specific protein partners are unknown. The purpose of this study was to identify proteins in the testis that interact with KIFC1 using a yeast 2 hybrid screen of a testis cDNA library. Results Thirty percent of the interacting clones identified in our screen contain an identical cDNA encoding a 40 kD protein. This interacting protein has 4 leucine-rich repeats in its amino terminal half and is expressed primarily in the testis; therefore we have named this protein testis leucine-rich repeat protein or TLRR. TLRR was also found to associate tightly with the KIFC1 targeting domain using affinity chromatography. In addition to the leucine-rich repeats, TLRR contains a consensus-binding site for protein phosphatase-1 (PP1. Immunocytochemistry using a TLRR specific antibody demonstrates that this protein is found near the manchette of developing spermatids. Conclusion We have identified a previously uncharacterized leucine-rich repeat protein that is expressed abundantly in the testis and associates with the manchette of developing spermatids, possibly through its interaction with the KIFC1 molecular motor

Highly Stable Trypsin-Aggregate Coatings on Polymer Nanofibers for Repeated Protein Digestion

Energy Technology Data Exchange (ETDEWEB)

Kim, Byoung Chan; Lopez-Ferrer, Daniel; Lee, Sang-mok; Ahn, Hye-kyung; Nair, Sujith; Kim, Seong H.; Kim, Beom S.; Petritis, Konstantinos; Camp, David G.; Grate, Jay W.; Smith, Richard D.; Koo, Yoon-mo; Gu, Man Bock; Kim, Jungbae

2009-04-01

A stable and robust trypsin-based biocatalytic system was developed and demonstrated for proteomic applications. The system utilizes polymer nanofibers coated with trypsin aggregates for immobilized protease digestions. After covalently attaching an initial layer of trypsin to the polymer nanofibers, highly concentrated trypsin molecules are crosslinked to the layered trypsin by way of a glutaraldehyde treatment. This new process produced a 300-fold increase in trypsin activity compared with a conventional method for covalent trypsin immobilization and proved to be robust in that it still maintained a high level of activity after a year of repeated recycling. This highly stable form of immobilized trypsin was also resistant to autolysis, enabling repeated digestions of bovine serum albumin over 40 days and successful peptide identification by LC-MS/MS. Finally, the immobilized trypsin was resistant to proteolysis when exposed to other enzymes (i.e. chymotrypsin), which makes it suitable for use in “real-world” proteomic applications. Overall, the biocatalytic nanofibers with enzyme aggregate coatings proved to be an effective approach for repeated and automated protein digestion in proteomic analyses.

Genome-wide identification, sequence characterization, and protein-protein interaction properties of DDB1 (damaged DNA binding protein-1)-binding WD40-repeat family members in Solanum lycopersicum.

Science.gov (United States)

Zhu, Yunye; Huang, Shengxiong; Miao, Min; Tang, Xiaofeng; Yue, Junyang; Wang, Wenjie; Liu, Yongsheng

2015-06-01

One hundred DDB1 (damaged DNA binding protein-1)-binding WD40-repeat domain (DWD) family genes were identified in the S. lycopersicum genome. The DWD genes encode proteins presumably functioning as the substrate recognition subunits of the cullin4-ring ubiquitin E3 ligase complex. These findings provide candidate genes and a research platform for further gene functionality and molecular breeding study. A subclass of DDB1 (damaged DNA binding protein-1)-binding WD40-repeat domain (DWD) family proteins has been demonstrated to function as the substrate recognition subunits of the cullin4-ring ubiquitin E3 ligase complex. However, little information is available about the cognate subfamily genes in tomato (S. lycopersicum). In this study, based on the recently released tomato genome sequences, 100 tomato genes encoding DWD proteins that potentially interact with DDB1 were identified and characterized, including analyses of the detailed annotations, chromosome locations and compositions of conserved amino acid domains. In addition, a phylogenetic tree, which comprises of three main groups, of the subfamily genes was constructed. The physical interaction between tomato DDB1 and 14 representative DWD proteins was determined by yeast two-hybrid and co-immunoprecipitation assays. The subcellular localization of these 14 representative DWD proteins was determined. Six of them were localized in both nucleus and cytoplasm, seven proteins exclusively in cytoplasm, and one protein either in nucleus and cytoplasm, or exclusively in cytoplasm. Comparative genomic analysis demonstrated that the expansion of these subfamily members in tomato predominantly resulted from two whole-genome triplication events in the evolution history.

Perfect simulation of Hawkes processes

DEFF Research Database (Denmark)

Møller, Jesper; Rasmussen, Jakob Gulddahl

2005-01-01

Our objective is to construct a perfect simulation algorithm for unmarked and marked Hawkes processes. The usual straightforward simulation algorithm suffers from edge effects, whereas our perfect simulation algorithm does not. By viewing Hawkes processes as Poisson cluster processes and using...... their branching and conditional independence structures, useful approximations of the distribution function for the length of a cluster are derived. This is used to construct upper and lower processes for the perfect simulation algorithm. A tail-lightness condition turns out to be of importance...... for the applicability of the perfect simulation algorithm. Examples of applications and empirical results are presented....

Alternative Conformations of the Tau Repeat Domain in Complex with an Engineered Binding Protein*

Science.gov (United States)

Grüning, Clara S. R.; Mirecka, Ewa A.; Klein, Antonia N.; Mandelkow, Eckhard; Willbold, Dieter; Marino, Stephen F.; Stoldt, Matthias; Hoyer, Wolfgang

2014-01-01

The aggregation of Tau into paired helical filaments is involved in the pathogenesis of several neurodegenerative diseases, including Alzheimer disease. The aggregation reaction is characterized by conformational conversion of the repeat domain, which partially adopts a cross-β-structure in the resulting amyloid-like fibrils. Here, we report the selection and characterization of an engineered binding protein, β-wrapin TP4, targeting the Tau repeat domain. TP4 was obtained by phage display using the four-repeat Tau construct K18ΔK280 as a target. TP4 binds K18ΔK280 as well as the longest isoform of human Tau, hTau40, with nanomolar affinity. NMR spectroscopy identified two alternative TP4-binding sites in the four-repeat domain, with each including two hexapeptide motifs with high β-sheet propensity. Both binding sites contain the aggregation-determining PHF6 hexapeptide within repeat 3. In addition, one binding site includes the PHF6* hexapeptide within repeat 2, whereas the other includes the corresponding hexapeptide Tau(337–342) within repeat 4, denoted PHF6**. Comparison of TP4-binding with Tau aggregation reveals that the same regions of Tau are involved in both processes. TP4 inhibits Tau aggregation at substoichiometric concentration, demonstrating that it interferes with aggregation nucleation. This study provides residue-level insight into the interaction of Tau with an aggregation inhibitor and highlights the structural flexibility of Tau. PMID:24966331

Characterization of two-qubit perfect entanglers

International Nuclear Information System (INIS)

Rezakhani, A.T.

2004-01-01

Here we consider perfect entanglers from another perspective. It is shown that there are some special perfect entanglers which can maximally entangle a full product basis. We explicitly construct a one-parameter family of such entanglers together with the proper product basis that they maximally entangle. This special family of perfect entanglers contains some well-known operators such as controlled-NOT (CNOT) and double-CNOT, but not √(SWAP). In addition, it is shown that all perfect entanglers with entangling power equal to the maximal value (2/9) are also special perfect entanglers. It is proved that the one-parameter family is the only possible set of special perfect entanglers. Also we provide an analytic way to implement any arbitrary two-qubit gate, given a proper special perfect entangler supplemented with single-qubit gates. Such gates are shown to provide a minimum universal gate construction in that just two of them are necessary and sufficient in implementation of a generic two-qubit gate

Breast milk is conditionally perfect.

Science.gov (United States)

Erick, Miriam

2018-02-01

Breast milk is the universal preferred nutrition for the newborn human infant. New mother have been encouraged to exclusively breastfeed by health care professionals and consumer-advocacy forums for years, citing "breast milk is the perfect food". The benefits are numerous and include psychological, convenience, economical, ecological and nutritionally superior. Human milk is a composite of nutritional choices of the mother, commencing in the pre-conceptual era. Events influencing the eventual nutritional profile of breast milk for the neonate start with pre-conceptual dietary habits through pregnancy and finally to postpartum. Food choices do affect the nutritional profile of human breast milk. It is not known who coined the phrase "breast milk is the perfect food" but it is widely prevalent in the literature. While breast milk is highly nutritive, containing important immunological and growth factors, scientific investigation reveals a few short-falls. Overall, human breast milk has been found to be low in certain nutrients in developed countries: vitamin D, iodine, iron, and vitamin K. Additional nutrient deficiencies have been documented in resource-poor countries: vitamin A, vitamin B 12, zinc, and vitamin B 1/thiamin. Given these findings, isn't it more accurate to describe breast milk as "conditionally perfect"? Correcting the impression that breast milk is an inherently, automatically comprehensive enriched product would encourage women who plan to breastfeed an opportunity to concentrate on dietary improvement to optimizes nutrient benefits ultimately to the neonate. The more immediate result would improve pre-conceptual nutritional status. Here, we explore the nutritional status of groups of young women; some of whom will become pregnant and eventually produce breast milk. We will review the available literature profiling vitamin, mineral, protein and caloric content of breast milk. We highlight pre-existing situations needing correction to optimize

Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells

NARCIS (Netherlands)

Barker, N.; Clevers, H.

2010-01-01

Molecular markers are used to characterize and track adult stem cells. Colon cancer research has led to the identification of 2 related receptors, leucine-rich repeat-containing, G-protein-coupled receptors (Lgr)5 and Lgr6, that are expressed by small populations of cells in a variety of adult

Gender, obesity and repeated elevation of C-reactive protein: data from the CARDIA cohort.

Directory of Open Access Journals (Sweden)

Shinya Ishii

Full Text Available C-reactive Protein (CRP measurements above 10 mg/L have been conventionally treated as acute inflammation and excluded from epidemiologic studies of chronic inflammation. However, recent evidence suggest that such CRP elevations can be seen even with chronic inflammation. The authors assessed 3,300 participants in The Coronary Artery Risk Development in Young Adults study, who had two or more CRP measurements between 1992/3 and 2005/6 to a investigate characteristics associated with repeated CRP elevation above 10 mg/L; b identify subgroups at high risk of repeated elevation; and c investigate the effect of different CRP thresholds on the probability of an elevation being one-time rather than repeated. 225 participants (6.8% had one-time and 103 (3.1% had repeated CRP elevation above 10 mg/L. Repeated elevation was associated with obesity, female gender, low income, and sex hormone use. The probability of an elevation above 10 mg/L being one-time rather than repeated was lowest (51% in women with body mass index above 31 kg/m(2, compared to 82% in others. These findings suggest that CRP elevations above 10 mg/L in obese women are likely to be from chronic rather than acute inflammation, and that CRP thresholds above 10 mg/L may be warranted to distinguish acute from chronic inflammation in obese women.

The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

DEFF Research Database (Denmark)

Kolsum, Umme; Roy, Kay; Starkey, Cerys

2009-01-01

BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...... (CRP) over one year and examined the relationships between these systemic markers in COPD. METHODS: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

DEFF Research Database (Denmark)

Kolsum, Umme; Roy, Kay; Starkey, Cerys

2009-01-01

BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...... (CRP) over one year and examined the relationships between these systemic markers in COPD. METHODS: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth.

Science.gov (United States)

Draeger, Christian; Ndinyanka Fabrice, Tohnyui; Gineau, Emilie; Mouille, Grégory; Kuhn, Benjamin M; Moller, Isabel; Abdou, Marie-Therese; Frey, Beat; Pauly, Markus; Bacic, Antony; Ringli, Christoph

2015-06-24

Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. The importance of these LRX genes for plant development and particularly cell wall formation was investigated. Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development.

Modulation of CRISPR locus transcription by the repeat-binding protein Cbp1 in Sulfolobus

DEFF Research Database (Denmark)

Deng, Ling; Kenchappa, Chandra Shekar; Peng, Xu

2012-01-01

CRISPR loci are essential components of the adaptive immune system of archaea and bacteria. They consist of long arrays of repeats separated by DNA spacers encoding guide RNAs (crRNA), which target foreign genetic elements. Cbp1 (CRISPR DNA repeat binding protein) binds specifically to the multiple...... direct repeats of CRISPR loci of members of the acidothermophilic, crenarchaeal order Sulfolobales. cbp1 gene deletion from Sulfolobus islandicus REY15A produced a strong reduction in pre-crRNA yields from CRISPR loci but did not inhibit the foreign DNA targeting capacity of the CRISPR/Cas system....... Conversely, overexpression of Cbp1 in S. islandicus generated an increase in pre-crRNA yields while the level of reverse strand transcripts from CRISPR loci remained unchanged. It is proposed that Cbp1 modulates production of longer pre-crRNA transcripts from CRISPR loci. A possible mechanism...

The repeatability of interleukin-6, tumor necrosis factor-α, and C-reactive protein in COPD patients over one year

Directory of Open Access Journals (Sweden)

Umme Kolsum

2009-04-01

Full Text Available Umme Kolsum, Kay Roy, Cerys Starkey, Zoë Borrill, Nick Truman, Jørgen Vestbo, Dave SinghNorth West Lung Research Centre, University of Manchester, South Manchester University Hospitals Trust, Wythenshawe, Manchester, UKBackground: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and C-reactive protein (CRP over one year and examined the relationships between these systemic markers in COPD.Methods: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-α were measured. Repeatability was expressed by intraclass correlation coefficient (Ri and the Bland–Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits.Results: There was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001 between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α. CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively. There were no other significant associations between the systemic markers at either of the visits.Conclusions: Systemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients. We have also shown that a robust and repeatable association between IL-6 and CRP exists.Keywords: interleukin-6, tumor necrosis factor-α, C-reactive protein, repeatability, COPD   

Perfect simulation of Hawkes processes

DEFF Research Database (Denmark)

Møller, Jesper; Rasmussen, Jakob Gulddahl

This article concerns a perfect simulation algorithm for unmarked and marked Hawkes processes. The usual stratihtforward simulation algorithm suffers from edge effects, whereas our perfect simulation algorithm does not. By viewing Hawkes processes as Poisson cluster processes and using...... their branching and conditional independence structure, useful approximations of the distribution function for the length of a cluster are derived. This is used to construct upper and lower processes for the perfect simulation algorithm. Examples of applications and empirical results are presented....

Generating perfect fluid spheres in general relativity

Science.gov (United States)

Boonserm, Petarpa; Visser, Matt; Weinfurtner, Silke

2005-06-01

Ever since Karl Schwarzschild’s 1916 discovery of the spacetime geometry describing the interior of a particular idealized general relativistic star—a static spherically symmetric blob of fluid with position-independent density—the general relativity community has continued to devote considerable time and energy to understanding the general-relativistic static perfect fluid sphere. Over the last 90 years a tangle of specific perfect fluid spheres has been discovered, with most of these specific examples seemingly independent from each other. To bring some order to this collection, in this article we develop several new transformation theorems that map perfect fluid spheres into perfect fluid spheres. These transformation theorems sometimes lead to unexpected connections between previously known perfect fluid spheres, sometimes lead to new previously unknown perfect fluid spheres, and in general can be used to develop a systematic way of classifying the set of all perfect fluid spheres.

Generating perfect fluid spheres in general relativity

International Nuclear Information System (INIS)

Boonserm, Petarpa; Visser, Matt; Weinfurtner, Silke

2005-01-01

Ever since Karl Schwarzschild's 1916 discovery of the spacetime geometry describing the interior of a particular idealized general relativistic star--a static spherically symmetric blob of fluid with position-independent density--the general relativity community has continued to devote considerable time and energy to understanding the general-relativistic static perfect fluid sphere. Over the last 90 years a tangle of specific perfect fluid spheres has been discovered, with most of these specific examples seemingly independent from each other. To bring some order to this collection, in this article we develop several new transformation theorems that map perfect fluid spheres into perfect fluid spheres. These transformation theorems sometimes lead to unexpected connections between previously known perfect fluid spheres, sometimes lead to new previously unknown perfect fluid spheres, and in general can be used to develop a systematic way of classifying the set of all perfect fluid spheres

Characterization of tetratricopeptide repeat-containing proteins critical for cilia formation and function.

Directory of Open Access Journals (Sweden)

Yanan Xu

Full Text Available Cilia formation and function require a special set of trafficking machinery termed intraflagellar transport (IFT, consisting mainly of protein complexes IFT-A, IFT-B, BBSome, and microtubule-dependent molecular motors. Tetratricopeptide repeat-containing (TTC proteins are widely involved in protein complex formation. Nine of them are known to serve as components of the IFT or BBSome complexes. How many TTC proteins are cilia-related and how they function, however, remain unclear. Here we show that twenty TTC genes were upregulated by at least 2-fold during the differentiation of cultured mouse tracheal epithelial cells (MTECs into multiciliated cells. Our systematic screen in zebrafish identified four novel TTC genes, ttc4, -9c, -36, and -39c, that are critical for cilia formation and motility. Accordingly, their zebrafish morphants displayed typical ciliopathy-related phenotypes, including curved body, abnormal otolith, hydrocephalus, and defective left-right patterning. The morphants of ttc4 and ttc25, a known cilia-related gene, additionally showed pronephric cyst formation. Immunoprecipitation indicated associations of TTC4, -9c, -25, -36, and -39c with components or entire complexes of IFT-A, IFT-B, or BBSome, implying their participations in IFT or IFT-related activities. Our results provide a global view for the relationship between TTC proteins and cilia.

Creation and structure determination of an artificial protein with three complete sequence repeats

Energy Technology Data Exchange (ETDEWEB)

Adachi, Motoyasu, E-mail: adachi.motoyasu@jaea.go.jp; Shimizu, Rumi; Kuroki, Ryota [Japan Atomic Energy Agency, Shirakatashirane 2-4, Nakagun Tokaimura, Ibaraki 319-1195 (Japan); Blaber, Michael [Japan Atomic Energy Agency, Shirakatashirane 2-4, Nakagun Tokaimura, Ibaraki 319-1195 (Japan); Florida State University, Tallahassee, FL 32306-4300 (United States)

2013-11-01

An artificial protein with three complete sequence repeats was created and the structure was determined by X-ray crystallography. The structure showed threefold symmetry even though there is an amino- and carboxy-terminal. The artificial protein with threefold symmetry may be useful as a scaffold to capture small materials with C3 symmetry. Symfoil-4P is a de novo protein exhibiting the threefold symmetrical β-trefoil fold designed based on the human acidic fibroblast growth factor. First three asparagine–glycine sequences of Symfoil-4P are replaced with glutamine–glycine (Symfoil-QG) or serine–glycine (Symfoil-SG) sequences protecting from deamidation, and His-Symfoil-II was prepared by introducing a protease digestion site into Symfoil-QG so that Symfoil-II has three complete repeats after removal of the N-terminal histidine tag. The Symfoil-QG and SG and His-Symfoil-II proteins were expressed in Eschericha coli as soluble protein, and purified by nickel affinity chromatography. Symfoil-II was further purified by anion-exchange chromatography after removing the HisTag by proteolysis. Both Symfoil-QG and Symfoil-II were crystallized in 0.1 M Tris-HCl buffer (pH 7.0) containing 1.8 M ammonium sulfate as precipitant at 293 K; several crystal forms were observed for Symfoil-QG and II. The maximum diffraction of Symfoil-QG and II crystals were 1.5 and 1.1 Å resolution, respectively. The Symfoil-II without histidine tag diffracted better than Symfoil-QG with N-terminal histidine tag. Although the crystal packing of Symfoil-II is slightly different from Symfoil-QG and other crystals of Symfoil derivatives having the N-terminal histidine tag, the refined crystal structure of Symfoil-II showed pseudo-threefold symmetry as expected from other Symfoils. Since the removal of the unstructured N-terminal histidine tag did not affect the threefold structure of Symfoil, the improvement of diffraction quality of Symfoil-II may be caused by molecular characteristics of

Cardiac ankyrin repeat protein (CARP) expression in human and murine atherosclerotic lesions - Activin induces carp in smooth muscle cells

NARCIS (Netherlands)

de Waard, Vivian; van Achterberg, Tanja A. E.; Beauchamp, Nicholas J.; Pannekoek, Hans; de Vries, Carlie J. M.

2003-01-01

Objective-Cardiac ankyrin repeat protein (CARP) is a transcription factor-related protein that has been studied most extensively in the heart. In the present study, we investigated the expression and the potential function of CARP in human and murine atherosclerosis. Methods and Results-CARP

Explaining evolution via constrained persistent perfect phylogeny

Science.gov (United States)

2014-01-01

Background The perfect phylogeny is an often used model in phylogenetics since it provides an efficient basic procedure for representing the evolution of genomic binary characters in several frameworks, such as for example in haplotype inference. The model, which is conceptually the simplest, is based on the infinite sites assumption, that is no character can mutate more than once in the whole tree. A main open problem regarding the model is finding generalizations that retain the computational tractability of the original model but are more flexible in modeling biological data when the infinite site assumption is violated because of e.g. back mutations. A special case of back mutations that has been considered in the study of the evolution of protein domains (where a domain is acquired and then lost) is persistency, that is the fact that a character is allowed to return back to the ancestral state. In this model characters can be gained and lost at most once. In this paper we consider the computational problem of explaining binary data by the Persistent Perfect Phylogeny model (referred as PPP) and for this purpose we investigate the problem of reconstructing an evolution where some constraints are imposed on the paths of the tree. Results We define a natural generalization of the PPP problem obtained by requiring that for some pairs (character, species), neither the species nor any of its ancestors can have the character. In other words, some characters cannot be persistent for some species. This new problem is called Constrained PPP (CPPP). Based on a graph formulation of the CPPP problem, we are able to provide a polynomial time solution for the CPPP problem for matrices whose conflict graph has no edges. Using this result, we develop a parameterized algorithm for solving the CPPP problem where the parameter is the number of characters. Conclusions A preliminary experimental analysis shows that the constrained persistent perfect phylogeny model allows to

Differential interaction and aggregation of 3-repeat and 4-repeat tau isoforms with 14-3-3ζ protein

International Nuclear Information System (INIS)

Sadik, Golam; Tanaka, Toshihisa; Kato, Kiyoko; Yanagi, Kentaro; Kudo, Takashi; Takeda, Masatoshi

2009-01-01

Tau isoforms, 3-repeat (3R) and 4-repeat tau (4R), are differentially involved in neuronal development and in several tauopathies. 14-3-3 protein binds to tau and 14-3-3/tau association has been found both in the development and in tauopathies. To understand the role of 14-3-3 in the differential regulation of tau isoforms, we have performed studies on the interaction and aggregation of 3R-tau and 4R-tau, either phosphorylated or unphosphorylated, with 14-3-3ζ. We show by surface plasmon resonance studies that the interaction between unphosphorylated 3R-tau and 14-3-3ζ is ∼3-folds higher than that between unphosphorylated 4R-tau and 14-3-3ζ. Phosphorylation of tau by protein kinase A (PKA) increases the affinity of both 3R- and 4R-tau for 14-3-3ζ to a similar level. An in vitro aggregation assay employing both transmission electron microscopy and fluorescence spectroscopy revealed the aggregation of unphosphorylated 4R-tau to be significantly higher than that of unphosphorylated 3R-tau following the induction of 14-3-3ζ. The filaments formed from 3R- and 4R-tau were almost similar in morphology. In contrast, the aggregation of both 3R- and 4R-tau was reduced to a similar low level after phosphorylation with PKA. Taken together, these results suggest that 14-3-3ζ exhibits a similar role for tau isoforms after PKA-phosphorylation, but a differential role for unphosphorylated tau. The significant aggregation of 4R-tau by 14-3-3ζ suggests that 14-3-3 may act as an inducer in the generation of 4R-tau-predominant neurofibrillary tangles in tauopathies.

RRW: repeated random walks on genome-scale protein networks for local cluster discovery

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Can Tolga

2009-09-01

Full Text Available Abstract Background We propose an efficient and biologically sensitive algorithm based on repeated random walks (RRW for discovering functional modules, e.g., complexes and pathways, within large-scale protein networks. Compared to existing cluster identification techniques, RRW implicitly makes use of network topology, edge weights, and long range interactions between proteins. Results We apply the proposed technique on a functional network of yeast genes and accurately identify statistically significant clusters of proteins. We validate the biological significance of the results using known complexes in the MIPS complex catalogue database and well-characterized biological processes. We find that 90% of the created clusters have the majority of their catalogued proteins belonging to the same MIPS complex, and about 80% have the majority of their proteins involved in the same biological process. We compare our method to various other clustering techniques, such as the Markov Clustering Algorithm (MCL, and find a significant improvement in the RRW clusters' precision and accuracy values. Conclusion RRW, which is a technique that exploits the topology of the network, is more precise and robust in finding local clusters. In addition, it has the added flexibility of being able to find multi-functional proteins by allowing overlapping clusters.

The candidate phylum Poribacteria by single-cell genomics: new insights into phylogeny, cell-compartmentation, eukaryote-like repeat proteins, and other genomic features.

Directory of Open Access Journals (Sweden)

Janine Kamke

Full Text Available The candidate phylum Poribacteria is one of the most dominant and widespread members of the microbial communities residing within marine sponges. Cell compartmentalization had been postulated along with their discovery about a decade ago and their phylogenetic association to the Planctomycetes, Verrucomicrobia, Chlamydiae superphylum was proposed soon thereafter. In the present study we revised these features based on genomic data obtained from six poribacterial single cells. We propose that Poribacteria form a distinct monophyletic phylum contiguous to the PVC superphylum together with other candidate phyla. Our genomic analyses supported the possibility of cell compartmentalization in form of bacterial microcompartments. Further analyses of eukaryote-like protein domains stressed the importance of such proteins with features including tetratricopeptide repeats, leucin rich repeats as well as low density lipoproteins receptor repeats, the latter of which are reported here for the first time from a sponge symbiont. Finally, examining the most abundant protein domain family on poribacterial genomes revealed diverse phyH family proteins, some of which may be related to dissolved organic posphorus uptake.

Multi-channel coherent perfect absorbers

KAUST Repository

Bai, Ping

2016-05-18

The absorption efficiency of a coherent perfect absorber usually depends on the phase coherence of the incident waves on the surfaces. Here, we present a scheme to create a multi-channel coherent perfect absorber in which the constraint of phase coherence is loosened. The scheme has a multi-layer structure such that incident waves in different channels with different angular momenta can be simultaneously and perfectly absorbed. This absorber is robust in achieving high absorption efficiency even if the incident waves become "incoherent" and possess "random" wave fronts. Our work demonstrates a unique approach to designing highly efficient metamaterial absorbers. © CopyrightEPLA, 2016.

Multi-channel coherent perfect absorbers

KAUST Repository

Bai, Ping; Wu, Ying; Lai, Yun

2016-01-01

The absorption efficiency of a coherent perfect absorber usually depends on the phase coherence of the incident waves on the surfaces. Here, we present a scheme to create a multi-channel coherent perfect absorber in which the constraint of phase coherence is loosened. The scheme has a multi-layer structure such that incident waves in different channels with different angular momenta can be simultaneously and perfectly absorbed. This absorber is robust in achieving high absorption efficiency even if the incident waves become "incoherent" and possess "random" wave fronts. Our work demonstrates a unique approach to designing highly efficient metamaterial absorbers. © CopyrightEPLA, 2016.

Revisiting the TALE repeat.

Science.gov (United States)

Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

2014-04-01

Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

High-Pressure NMR and SAXS Reveals How Capping Modulates Folding Cooperativity of the pp32 Leucine-rich Repeat Protein.

Science.gov (United States)

Zhang, Yi; Berghaus, Melanie; Klein, Sean; Jenkins, Kelly; Zhang, Siwen; McCallum, Scott A; Morgan, Joel E; Winter, Roland; Barrick, Doug; Royer, Catherine A

2018-04-27

Many repeat proteins contain capping motifs, which serve to shield the hydrophobic core from solvent and maintain structural integrity. While the role of capping motifs in enhancing the stability and structural integrity of repeat proteins is well documented, their contribution to folding cooperativity is not. Here we examined the role of capping motifs in defining the folding cooperativity of the leucine-rich repeat protein, pp32, by monitoring the pressure- and urea-induced unfolding of an N-terminal capping motif (N-cap) deletion mutant, pp32-∆N-cap, and a C-terminal capping motif destabilization mutant pp32-Y131F/D146L, using residue-specific NMR and small-angle X-ray scattering. Destabilization of the C-terminal capping motif resulted in higher cooperativity for the unfolding transition compared to wild-type pp32, as these mutations render the stability of the C-terminus similar to that of the rest of the protein. In contrast, deletion of the N-cap led to strong deviation from two-state unfolding. In both urea- and pressure-induced unfolding, residues in repeats 1-3 of pp32-ΔN-cap lost their native structure first, while the C-terminal half was more stable. The residue-specific free energy changes in all regions of pp32-ΔN-cap were larger in urea compared to high pressure, indicating a less cooperative destabilization by pressure. Moreover, in contrast to complete structural disruption of pp32-ΔN-cap at high urea concentration, its pressure unfolded state remained compact. The contrasting effects of the capping motifs on folding cooperativity arise from the differential local stabilities of pp32, whereas the contrasting effects of pressure and urea on the pp32-ΔN-cap variant arise from their distinct mechanisms of action. Copyright © 2018 Elsevier Ltd. All rights reserved.

Plasmodium cysteine repeat modular proteins 1-4: complex proteins with roles throughout the malaria parasite life cycle.

Science.gov (United States)

Thompson, Joanne; Fernandez-Reyes, Delmiro; Sharling, Lisa; Moore, Sally G; Eling, Wijnand M; Kyes, Sue A; Newbold, Christopher I; Kafatos, Fotis C; Janse, Chris J; Waters, Andrew P

2007-06-01

The Cysteine Repeat Modular Proteins (PCRMP1-4) of Plasmodium, are encoded by a small gene family that is conserved in malaria and other Apicomplexan parasites. They are very large, predicted surface proteins with multipass transmembrane domains containing motifs that are conserved within families of cysteine-rich, predicted surface proteins in a range of unicellular eukaryotes, and a unique combination of protein-binding motifs, including a >100 kDa cysteine-rich modular region, an epidermal growth factor-like domain and a Kringle domain. PCRMP1 and 2 are expressed in life cycle stages in both the mosquito and vertebrate. They colocalize with PfEMP1 (P. falciparum Erythrocyte Membrane Antigen-1) during its export from P. falciparum blood-stage parasites and are exposed on the surface of haemolymph- and salivary gland-sporozoites in the mosquito, consistent with a role in host tissue targeting and invasion. Gene disruption of pcrmp1 and 2 in the rodent malaria model, P. berghei, demonstrated that both are essential for transmission of the parasite from the mosquito to the mouse and has established their discrete and important roles in sporozoite targeting to the mosquito salivary gland. The unprecedented expression pattern and structural features of the PCRMPs thus suggest a variety of roles mediating host-parasite interactions throughout the parasite life cycle.

Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage

International Nuclear Information System (INIS)

Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J.; Rudich, Yinon

2016-01-01

Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. - Highlights: • Repeated exposure to urban PM cause systemic inflammation and oxidative damage to lung tissue lipids and proteins. • Repeated exposure to these PM extracts decreased transcription of Nrf2 protective genes. • Single as opposed to repeated exposure, induced confined lung response accompanied by activated defense mechanisms. • Metals, potentially from break and tire wear, drive the pulmonary response with exposure to urban PM. - Repeated exposures to urban PM water extracts

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat expanded C9orf72 amyotrophic lateral sclerosis

Science.gov (United States)

Saberi, Shahram; Stauffer, Jennifer E.; Jiang, Jie; Garcia, Sandra Diaz; Taylor, Amy E; Schulte, Derek; Ohkubo, Takuya; Schloffman, Cheyenne L.; Maldonado, Marcus; Baughn, Michael; Rodriguez, Maria J; Pizzo, Don; Cleveland, Don; Ravits, John

2018-01-01

Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically-related and clinically-unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically-related areas compared to unrelated areas (p<0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p<0.0001). While most poly-GR dendritic inclusions were pTDP-43-positive, only 4% of pTDP-43 dendritic inclusions were poly-GR-positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically-related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to neurites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites. PMID:29196813

Imperfect DNA mirror repeats in the gag gene of HIV-1 (HXB2 identify key functional domains and coincide with protein structural elements in each of the mature proteins

Directory of Open Access Journals (Sweden)

Lang Dorothy M

2007-10-01

Full Text Available Abstract Background A DNA mirror repeat is a sequence segment delimited on the basis of its containing a center of symmetry on a single strand, e.g. 5'-GCATGGTACG-3'. It is most frequently described in association with a functionally significant site in a genomic sequence, and its occurrence is regarded as noteworthy, if not unusual. However, imperfect mirror repeats (IMRs having ≥ 50% symmetry are common in the protein coding DNA of monomeric proteins and their distribution has been found to coincide with protein structural elements – helices, β sheets and turns. In this study, the distribution of IMRs is evaluated in a polyprotein – to determine whether IMRs may be related to the position or order of protein cleavage or other hierarchal aspects of protein function. The gag gene of HIV-1 [GenBank:K03455] was selected for the study because its protein motifs and structural components are well documented. Results There is a highly specific relationship between IMRs and structural and functional aspects of the Gag polyprotein. The five longest IMRs in the polyprotein translate a key functional segment in each of the five cleavage products. Throughout the protein, IMRs coincide with functionally significant segments of the protein. A detailed annotation of the protein, which combines structural, functional and IMR data illustrates these associations. There is a significant statistical correlation between the ends of IMRs and the ends of PSEs in each of the mature proteins. Weakly symmetric IMRs (≥ 33% are related to cleavage positions and processes. Conclusion The frequency and distribution of IMRs in HIV-1 Gag indicates that DNA symmetry is a fundamental property of protein coding DNA and that different levels of symmetry are associated with different functional aspects of the gene and its protein. The interaction between IMRs and protein structure and function is precise and interwoven over the entire length of the polyprotein. The

On 4-critical t-perfect graphs

OpenAIRE

Benchetrit, Yohann

2016-01-01

It is an open question whether the chromatic number of $t$-perfect graphs is bounded by a constant. The largest known value for this parameter is 4, and the only example of a 4-critical $t$-perfect graph, due to Laurent and Seymour, is the complement of the line graph of the prism $\\Pi$ (a graph is 4-critical if it has chromatic number 4 and all its proper induced subgraphs are 3-colorable). In this paper, we show a new example of a 4-critical $t$-perfect graph: the complement of the line gra...

Picture perfect

DEFF Research Database (Denmark)

Pless, Mette; Sørensen, Niels Ulrik

’Picture perfect’ – when perfection becomes the new normal This paper draws on perspectives from three different studies. One study, which focuses on youth life and lack of well-being (Sørensen et al 2011), one study on youth life on the margins of society (Katznelson et al 2015) and one study...

Inter-Faith Reading of Perfect Man With Mystical Approach

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Fatemeh Musavi

2010-12-01

Full Text Available The expression Insan –e kamil (perfect man is often said to have first been used by Muhyiddin ibn 'Arabi (1165 -1240AD, though the concept of the term is much older. In his theosophical teaching, the doctrine of insan e- kamil, is held a prominent place. After him two other great Sufis, Aziz Nasafi (1300AD and 'Abd al- karim ibn Ibrahim al- Jili (1366 – 1424 AD, each wrote a work on this very issue. These works are regarded as explanations of Ibn Arabi’s teachings on human perfection. In Islamic mysticism, Perfect man is the one who within their soul possesses all God's names and attributes. Thus the perfect man’s existence, reality and inner might become a clear mirror and a complete reflection of the Perfection, Beauty and Glory of the Essence of the One, so that he becomes Godlike. However, the idea of human perfectibility going back to other religions and human schools even before Islam. In Abrahimic religions there are some joint teachings that could be considered as main statements for the doctrine of Perfect Man In Jewish scriptures the notion of human creation in God's image suggests that the human being is able to be God's like and the perfection is available to him. However, Jews do not believe a perfect man. They hold that even Moses is not a perfect man. In Christianity, Although Jesus encourages his followers to be perfect like their heavenly fathers, the doctrine of original sin to be considered as an obstacle for human perfectibility.This essay examines some significant element in human perfectibility from the view points of some scholars of Judaism, Christianity and Islam and presents some similarities and differences of their view points.

Inter-Faith Reading of Perfect Man With Mystical Approach

Directory of Open Access Journals (Sweden)

Mohammadkazem Shaker

2011-01-01

Full Text Available   The expression Insan –e kamil (perfect man is often said to have first been used by Muhyiddin ibn 'Arabi (1165 -1240AD, though the concept of the term is much older. In his theosophical teaching, the doctrine of insan e- kamil, is held a prominent place. After him two other great Sufis, Aziz Nasafi (1300AD and 'Abd al- karim ibn Ibrahim al- Jili (1366 – 1424 AD, each wrote a work on this very issue. These works are regarded as explanations of Ibn Arabi’s teachings on human perfection. In Islamic mysticism, Perfect man is the one who within their soul possesses all God's names and attributes. Thus the perfect man’s existence, reality and inner might become a clear mirror and a complete reflection of the Perfection, Beauty and Glory of the Essence of the One, so that he becomes Godlike. However, the idea of human perfectibility going back to other religions and human schools even before Islam. In Abrahimic religions there are some joint teachings that could be considered as main statements for the doctrine of Perfect Man In Jewish scriptures the notion of human creation in God's image suggests that the human being is able to be God's like and the perfection is available to him. However, Jews do not believe a perfect man. They hold that even Moses is not a perfect man. In Christianity, Although Jesus encourages his followers to be perfect like their heavenly fathers, the doctrine of original sin to be considered as an obstacle for human perfectibility.This essay examines some significant element in human perfectibility from the view points of some scholars of Judaism, Christianity and Islam and presents some similarities and differences of their view points.

Inter-Faith Reading of Perfect Man With Mystical Approach

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Shaker, M.K

2011-01-01

Full Text Available The expression Insan –e kamil (perfect man is often said to have first been used by Muhyiddin ibn 'Arabi (1165 -1240AD, though the concept of the term is much older. In his theosophical teaching, the doctrine of insan e- kamil, is held a prominent place. After him two other great Sufis, Aziz Nasafi (1300AD and 'Abd al- karim ibn Ibrahim al- Jili (1366 – 1424 AD, each wrote a work on this very issue. These works are regarded as explanations of Ibn Arabi’s teachings on human perfection. In Islamic mysticism, Perfect man is the one who within their soul possesses all God's names and attributes. Thus the perfect man’s existence, reality and inner might become a clear mirror and a complete reflection of the Perfection, Beauty and Glory of the Essence of the One, so that he becomes Godlike. However, the idea of human perfectibility going back to other religions and human schools even before Islam. In Abrahimic religions there are some joint teachings that could be considered as main statements for the doctrine of Perfect Man In Jewish scriptures the notion of human creation in God's image suggests that the human being is able to be God's like and the perfection is available to him. However, Jews do not believe a perfect man. They hold that even Moses is not a perfect man. In Christianity, Although Jesus encourages his followers to be perfect like their heavenly fathers, the doctrine of original sin to be considered as an obstacle for human perfectibility.This essay examines some significant element in human perfectibility from the view points of some scholars of Judaism, Christianity and Islam and presents some similarities and differences of their view points.

Perfect secure domination in graphs

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S.V. Divya Rashmi

2017-07-01

Full Text Available Let $G=(V,E$ be a graph. A subset $S$ of $V$ is a dominating set of $G$ if every vertex in $Vsetminus  S$ is adjacent to a vertex in $S.$ A dominating set $S$ is called a secure dominating set if for each $vin Vsetminus S$ there exists $uin S$ such that $v$ is adjacent to $u$ and $S_1=(Ssetminus{u}cup {v}$ is a dominating set. If further the vertex $uin S$ is unique, then $S$ is called a perfect secure dominating set. The minimum cardinality of a perfect secure dominating set of $G$ is called the perfect  secure domination number of $G$ and is denoted by $gamma_{ps}(G.$ In this paper we initiate a study of this parameter and present several basic results.

Critical phenomena at perfect and non-perfect surfaces

International Nuclear Information System (INIS)

Pleimling, M

2004-01-01

In the past, perfect surfaces have been shown to yield local critical behaviour that differs from bulk critical behaviour. On the other hand, surface defects, whether they are of natural origin or created artificially, are known to modify local quantities. It is therefore important to clarify whether these defects are relevant or irrelevant for the surface critical behaviour. The purpose of this review is two-fold. In the first part we summarize some of the important results on surface criticality at perfect surfaces. Special attention is thereby paid to new developments such as for example the study of the surface critical behaviour in systems with competing interactions or of surface critical dynamics. In the second part the effect of surface defects (presence of edges, steps, quenched randomness, lines of adatoms, regular geometric patterns) on local critical behaviour in semi-infinite systems and in thin films is discussed in detail. Whereas most of the defects commonly encountered are shown to be irrelevant, some notable exceptions are highlighted. It is shown furthermore that under certain circumstances non-universal local critical behaviour may be observed at surfaces. (topical review)

Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress.

Science.gov (United States)

Sonobe, Yoshifumi; Ghadge, Ghanashyam; Masaki, Katsuhisa; Sendoel, Ataman; Fuchs, Elaine; Roos, Raymond P

2018-08-01

Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS. Despite the location of the HRE in the non-coding region (with respect to the main C9ORF72 gene product), dipeptide repeat proteins (DPRs) that are thought to be toxic are translated from the HRE in all three reading frames from both the sense and antisense transcript. Here, we identified a CUG that has a good Kozak consensus sequence as the translation initiation codon. Mutation of this CTG significantly suppressed polyglycine-alanine (GA) translation. GA was translated when the G 4 C 2 construct was placed as the second cistron in a bicistronic construct. CRISPR/Cas9-induced knockout of a non-canonical translation initiation factor, eIF2A, impaired GA translation. Transfection of G 4 C 2 constructs induced an integrated stress response (ISR), while triggering the ISR led to a continuation of translation of GA with a decline in conventional cap-dependent translation. These in vitro observations were confirmed in chick embryo neural cells. The findings suggest that DPRs translated from an HRE in C9ORF72 aggregate and lead to an ISR that then leads to continuing DPR production and aggregation, thereby creating a continuing pathogenic cycle. Copyright © 2018 Elsevier Inc. All rights reserved.

High-temperature protein G is essential for activity of the Escherichia coli clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system.

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Yosef, Ido; Goren, Moran G; Kiro, Ruth; Edgar, Rotem; Qimron, Udi

2011-12-13

Prokaryotic DNA arrays arranged as clustered regularly interspaced short palindromic repeats (CRISPR), along with their associated proteins, provide prokaryotes with adaptive immunity by RNA-mediated targeting of alien DNA or RNA matching the sequences between the repeats. Here, we present a thorough screening system for the identification of bacterial proteins participating in immunity conferred by the Escherichia coli CRISPR system. We describe the identification of one such protein, high-temperature protein G (HtpG), a homolog of the eukaryotic chaperone heat-shock protein 90. We demonstrate that in the absence of htpG, the E. coli CRISPR system loses its suicidal activity against λ prophage and its ability to provide immunity from lysogenization. Transcomplementation of htpG restores CRISPR activity. We further show that inactivity of the CRISPR system attributable to htpG deficiency can be suppressed by expression of Cas3, a protein that is essential for its activity. Accordingly, we also find that the steady-state level of overexpressed Cas3 is significantly enhanced following HtpG expression. We conclude that HtpG is a newly identified positive modulator of the CRISPR system that is essential for maintaining functional levels of Cas3.

Modern problems of perfection of elite light athletic sportsmen’s technical skillfulness perfection

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A.V. Kolot

2016-04-01

Full Text Available Purpose: perfection of elite sportsmen’s technical skillfulness in competition kinds of light athletic. Material: the data of more than 60 literature sources were systemized. Expert questioning of 36 coaches, having experience of work with elite sportsmen, was carried out; documents of training process planning were analyzed as well as sportsmen’s diaries (n=244. Results: we have presented main principles of sportsmen’s technical skillfulness perfection and elucidated characteristics of technical training methodic. We have determined main priorities of technical training building for light athletes at every stage of many years’ perfection. Dynamic of competition practice volume has been found as well as main requirements to selection of training means of technical orientation. The data of bio-mechanical criteria of sportsmen’s technical skillfulness assessment have been supplemented. Conclusions: effectiveness of sportsmen’s training methodic is determined by realization of previous stages’ technical potential in final competition results. It can be achieved by determination of means of and methods of different orientation rational correlation.

Modern problems of perfection of elite light athletic sportsmen’s technical skillfulness perfection

Directory of Open Access Journals (Sweden)

Kolot A.V.

2016-02-01

Full Text Available Purpose: perfection of elite sportsmen’s technical skillfulness in competition kinds of light athletic. Material: the data of more than 60 literature sources were systemized. Expert questioning of 36 coaches, having experience of work with elite sportsmen, was carried out; documents of training process planning were analyzed as well as sportsmen’s diaries (n=244. Results: we have presented main principles of sportsmen’s technical skillfulness perfection and elucidated characteristics of technical training methodic. We have determined main priorities of technical training building for light athletes at every stage of many years’ perfection. Dynamic of competition practice volume has been found as well as main requirements to selection of training means of technical orientation. The data of bio-mechanical criteria of sportsmen’s technical skillfulness assessment have been supplemented. Conclusions: effectiveness of sportsmen’s training methodic is determined by realization of previous stages’ technical potential in final competition results. It can be achieved by determination of means of and methods of different orientation rational correlation.

ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.

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Ray, Hind; Moreau, Karen; Dizin, Eva; Callebaut, Isabelle; Venezia, Nicole Dalla

2006-06-16

The tumour suppressor gene BRCA1 encodes a 220 kDa protein that participates in multiple cellular processes. The BRCA1 protein contains a tandem of two BRCT repeats at its carboxy-terminal region. The majority of disease-associated BRCA1 mutations affect this region and provide to the BRCT repeats a central role in the BRCA1 tumour suppressor function. The BRCT repeats have been shown to mediate phospho-dependant protein-protein interactions. They recognize phosphorylated peptides using a recognition groove that spans both BRCT repeats. We previously identified an interaction between the tandem of BRCA1 BRCT repeats and ACCA, which was disrupted by germ line BRCA1 mutations that affect the BRCT repeats. We recently showed that BRCA1 modulates ACCA activity through its phospho-dependent binding to ACCA. To delineate the region of ACCA that is crucial for the regulation of its activity by BRCA1, we searched for potential phosphorylation sites in the ACCA sequence that might be recognized by the BRCA1 BRCT repeats. Using sequence analysis and structure modelling, we proposed the Ser1263 residue as the most favourable candidate among six residues, for recognition by the BRCA1 BRCT repeats. Using experimental approaches, such as GST pull-down assay with Bosc cells, we clearly showed that phosphorylation of only Ser1263 was essential for the interaction of ACCA with the BRCT repeats. We finally demonstrated by immunoprecipitation of ACCA in cells, that the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263.

A novel tetratricopeptide repeat (TPR containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum

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Adams Brian

2001-11-01

Full Text Available Abstract Background The malarial parasite, Plasmodium falciparum (Pf, is responsible for nearly 2 million deaths worldwide. However, the mechanisms of cellular signaling in the parasite remain largely unknown. Recent discovery of a few protein kinases and phosphatases point to a thriving reversible phosphorylation system in the parasite, although their function and regulation need to be determined. Results We provide biochemical and sequence evidence for a protein serine/threonine phosphatase type PP5 in Plasmodium falciparum, and named it PfPP5. The 594-amino acid polypeptide was encoded by a 1785 nucleotide long intronless gene in the parasite. The recombinant protein, expressed in bacteria, was indistinguishable from native PfPP5. Sequencing comparison indicated that the extra-long N-terminus of PfPP5 outside the catalytic core contained four tetratricopeptide repeats (TPRs, compared to three such repeats in other PP5 phosphatases. The PfPP5 N-terminus was required for stimulation of the phosphatase activity by polyunsaturated fatty acids. Co-immunoprecipitation demonstrated an interaction between native PfPP5 and Pf heat shock protein 90 (hsp90. PfPP5 was expressed in all the asexual erythrocytic stages of the parasite, and was moderately sensitive to okadaic acid. Conclusions This is the first example of a TPR-domain protein in the Apicomplexa family of parasites. Since TPR domains play important roles in protein-protein interaction, especially relevant to the regulation of PP5 phosphatases, PfPP5 is destined to have a definitive role in parasitic growth and signaling pathways. This is exemplified by the interaction between PfPP5 and the cognate chaperone hsp90.

Influence of training intensity on adaptations in acid/base transport proteins, muscle buffer capacity, and repeated-sprint ability in active men.

Science.gov (United States)

McGinley, Cian; Bishop, David J

2016-12-01

McGinley C, Bishop DJ. Influence of training intensity on adaptations in acid/base transport proteins, muscle buffer capacity, and repeated-sprint ability in active men. J Appl Physiol 121: 1290-1305, 2016. First published October 14, 2016; doi:10.1152/japplphysiol.00630.2016-This study measured the adaptive response to exercise training for each of the acid-base transport protein families, including providing isoform-specific evidence for the monocarboxylate transporter (MCT)1/4 chaperone protein basigin and for the electrogenic sodium-bicarbonate cotransporter (NBCe)1. We investigated whether 4 wk of work-matched, high-intensity interval training (HIIT), performed either just above the lactate threshold (HIITΔ20; n = 8), or close to peak aerobic power (HIITΔ90; n = 8), influenced adaptations in acid-base transport protein abundance, nonbicarbonate muscle buffer capacity (βm in vitro ), and exercise capacity in active men. Training intensity did not discriminate between adaptations for most proteins measured, with abundance of MCT1, sodium/hydrogen exchanger (NHE) 1, NBCe1, carbonic anhydrase (CA) II, and CAXIV increasing after 4 wk, whereas there was little change in CAIII and CAIV abundance. βm in vitro also did not change. However, MCT4 protein content only increased for HIITΔ20 [effect size (ES): 1.06, 90% confidence limits × / ÷ 0.77], whereas basigin protein content only increased for HIITΔ90 (ES: 1.49, × / ÷ 1.42). Repeated-sprint ability (5 × 6-s sprints; 24 s passive rest) improved similarly for both groups. Power at the lactate threshold only improved for HIITΔ20 (ES: 0.49; 90% confidence limits ± 0.38), whereas peak O 2 uptake did not change for either group. Detraining was characterized by the loss of adaptations for all of the proteins measured and for repeated-sprint ability 6 wk after removing the stimulus of HIIT. In conclusion, 4 wk of HIIT induced improvements in each of the acid-base transport protein families, but, remarkably, a 40

Tetratricopeptide repeat domain 9A is an interacting protein for tropomyosin Tm5NM-1

International Nuclear Information System (INIS)

Cao, Shenglan; Ho, Gay Hui; Lin, Valerie CL

2008-01-01

Tetratricopeptide repeat domain 9A (TTC9A) protein is a recently identified protein which contains three tetratricopeptide repeats (TPRs) on its C-terminus. In our previous studies, we have shown that TTC9A was a hormonally-regulated gene in breast cancer cells. In this study, we found that TTC9A was over-expressed in breast cancer tissues compared with the adjacent controls (P < 0.00001), suggesting it might be involved in the breast cancer development process. The aim of the current study was to further elucidate the function of TTC9A. Breast samples from 25 patients including the malignant breast tissues and the adjacent normal tissues were processed for Southern blot analysis. Yeast-two-hybrid assay, GST pull-down assay and co-immunoprecipitation were used to identify and verify the interaction between TTC9A and other proteins. Tropomyosin Tm5NM-1 was identified as one of the TTC9A partner proteins. The interaction between TTC9A and Tm5NM-1 was further confirmed by GST pull-down assay and co-immunoprecipitation in mammalian cells. TTC9A domains required for the interaction were also characterized in this study. The results suggested that the first TPR domain and the linker fragment between the first two TPR domains of TTC9A were important for the interaction with Tm5NM-1 and the second and the third TPR might play an inhibitory role. Since the primary function of tropomyosin is to stabilize actin filament, its interaction with TTC9A may play a role in cell shape and motility. In our previous results, we have found that progesterone-induced TTC9A expression was associated with increased cell motility and cell spreading. We speculate that TTC9A acts as a chaperone protein to facilitate the function of tropomyosins in stabilizing microfilament and it may play a role in cancer cell invasion and metastasis

Positive selection and propeptide repeats promote rapid interspecific divergence of a gastropod sperm protein.

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Hellberg, M E; Moy, G W; Vacquier, V D

2000-03-01

Male-specific proteins have increasingly been reported as targets of positive selection and are of special interest because of the role they may play in the evolution of reproductive isolation. We report the rapid interspecific divergence of cDNA encoding a major acrosomal protein of unknown function (TMAP) of sperm from five species of teguline gastropods. A mitochondrial DNA clock (calibrated by congeneric species divided by the Isthmus of Panama) estimates that these five species diverged 2-10 MYA. Inferred amino acid sequences reveal a propeptide that has diverged rapidly between species. The mature protein has diverged faster still due to high nonsynonymous substitution rates (> 25 nonsynonymous substitutions per site per 10(9) years). cDNA encoding the mature protein (89-100 residues) shows evidence of positive selection (Dn/Ds > 1) for 4 of 10 pairwise species comparisons. cDNA and predicted secondary-structure comparisons suggest that TMAP is neither orthologous nor paralogous to abalone lysin, and thus marks a second, phylogenetically independent, protein subject to strong positive selection in free-spawning marine gastropods. In addition, an internal repeat in one species (Tegula aureotincta) produces a duplicated cleavage site which results in two alternatively processed mature proteins differing by nine amino acid residues. Such alternative processing may provide a mechanism for introducing novel amino acid sequence variation at the amino-termini of proteins. Highly divergent TMAP N-termini from two other tegulines (Tegula regina and Norrisia norrisii) may have originated by such a mechanism.

Lattice-Like Total Perfect Codes

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Araujo Carlos

2014-02-01

Full Text Available A contribution is made to the classification of lattice-like total perfect codes in integer lattices Λn via pairs (G, Φ formed by abelian groups G and homomorphisms Φ: Zn → G. A conjecture is posed that the cited contribution covers all possible cases. A related conjecture on the unfinished work on open problems on lattice-like perfect dominating sets in Λn with induced components that are parallel paths of length > 1 is posed as well.

The 1.7 Å resolution structure of At2g44920, a pentapeptide-repeat protein in the thylakoid lumen of Arabidopsis thaliana

International Nuclear Information System (INIS)

Ni, Shuisong; McGookey, Michael E.; Tinch, Stuart L.; Jones, Alisha N.; Jayaraman, Seetharaman; Tong, Liang; Kennedy, Michael A.

2011-01-01

The crystal structure of At2g44920, a pentapeptide repeat protein (PRP) from Arabidopsis thaliana, has been determined at 1.7 Å resolution. The structure represents the first PRP protein whose subcellular localization has been experimentally confirmed to be the thylakoid lumen of a plant species. At2g44920 belongs to a diverse family (Pfam PF00805) of pentapeptide-repeat proteins (PRPs) that are present in all known organisms except yeast. PRPs contain at least eight tandem-repeating sequences of five amino acids with an approximate consensus sequence (STAV)(D/N)(L/F)(S/T/R)(X). Recent crystal structures show that PRPs adopt a highly regular four-sided right-handed β-helical structure consisting mainly of type II and type IV β-turns, sometimes referred to as a repeated five-residue (or Rfr) fold. Among sequenced genomes, PRP genes are most abundant in cyanobacteria, leading to speculation that PRPs play an important role in the unique lifestyle of photosynthetic cyanobacteria. Despite the recent structural characterization of several cyanobacterial PRPs, most of their functions remain unknown. Plants, whose chloroplasts are of cyanobacterial origin, have only four PRP genes in their genomes. At2g44920 is one of three PRPs located in the thylakoid lumen. Here, the crystal structure of a double methionine mutant of residues 81–224 of At2g44920, the naturally processed fragment of one of its full-length isoforms, is reported at 1.7 Å resolution. The structure of At2g44920 consists of the characteristic Rfr fold with five uninterrupted coils made up of 25 pentapeptide repeats and α-helical elements capping both termini. A disulfide bridge links the two α-helices with a conserved loop between the helical elements at its C-terminus. This structure represents the first structure of a PRP protein whose subcellular location has been experimentally confirmed to be the thylakoid lumen in a plant species

Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

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Kippert, Fred; Gerloff, Dietlind L

2009-09-24

HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high

Elfin: An algorithm for the computational design of custom three-dimensional structures from modular repeat protein building blocks.

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Yeh, Chun-Ting; Brunette, T J; Baker, David; McIntosh-Smith, Simon; Parmeggiani, Fabio

2018-02-01

Computational protein design methods have enabled the design of novel protein structures, but they are often still limited to small proteins and symmetric systems. To expand the size of designable proteins while controlling the overall structure, we developed Elfin, a genetic algorithm for the design of novel proteins with custom shapes using structural building blocks derived from experimentally verified repeat proteins. By combining building blocks with compatible interfaces, it is possible to rapidly build non-symmetric large structures (>1000 amino acids) that match three-dimensional geometric descriptions provided by the user. A run time of about 20min on a laptop computer for a 3000 amino acid structure makes Elfin accessible to users with limited computational resources. Protein structures with controlled geometry will allow the systematic study of the effect of spatial arrangement of enzymes and signaling molecules, and provide new scaffolds for functional nanomaterials. Copyright © 2017 Elsevier Inc. All rights reserved.

WD40-repeat proteins in plant cell wall formation: current evidence and research prospects

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Gea eGuerriero

2015-12-01

Full Text Available The metabolic complexity of living organisms relies on supramolecular protein structures which ensure vital processes, such as signal transduction, transcription, translation and cell wall synthesis. In eukaryotes WD40-repeat (WDR proteins often function as molecular hubs mediating supramolecular interactions. WDR proteins may display a variety of interacting partners and participate in the assembly of complexes involved in distinct cellular functions. In plants, the formation of lignocellulosic biomass involves extensive synthesis of cell wall polysaccharides, a process that requires the assembly of large transmembrane enzyme complexes, intensive vesicle trafficking, interactions with the cytoskeleton, and coordinated gene expression. Because of their function as supramolecular hubs, WDR proteins could participate in each or any of these steps, although to date only few WDR proteins have been linked to the cell wall by experimental evidence. Nevertheless, several potential cell wall-related WDR proteins were recently identified using in silico aproaches, such as analyses of co-expression, interactome and conserved gene neighbourhood. Notably, some WDR genes are frequently genomic neighbours of genes coding for GT2-family polysaccharide synthases in eukaryotes, and this WDR-GT2 collinear microsynteny is detected in diverse taxa. In angiosperms, two WDR genes are collinear to cellulose synthase genes, CESAs, whereas in ascomycetous fungi several WDR genes are adjacent to chitin synthase genes, chs. In this Perspective we summarize and discuss experimental and in silico studies on the possible involvement of WDR proteins in plant cell wall formation. The prospects of biotechnological engineering for enhanced biomass production are discussed.

Armadillo Repeat Containing 8α Binds to HRS and Promotes HRS Interaction with Ubiquitinated Proteins

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Tomaru, Koji; Ueda, Atsuhisa; Suzuki, Takeyuki; Kobayashi, Nobuaki; Yang, Jun; Yamamoto, Masaki; Takeno, Mitsuhiro; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

2010-01-01

Recently, we reported that a complex with an essential role in the degradation of Fructose-1,6-bisphosphatase in yeast is well conserved in mammalian cells; we named this mammalian complex C-terminal to the Lissencephaly type-1-like homology (CTLH) complex. Although the function of the CTLH complex remains unclear, here we used yeast two-hybrid screening to isolate Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) as a protein binding to a key component of CTLH complex, Armadillo repeat containing 8 (ARMc8) α. The association was confirmed by a yeast two-hybrid assay and a co-immunoprecipitation assay. The proline-rich domain of HRS was essential for the association. As demonstrated through immunofluorescence microscopy, ARMc8α co-localized with HRS. ARMc8α promoted the interaction of HRS with various ubiquitinated proteins through the ubiquitin-interacting motif. These findings suggest that HRS mediates protein endosomal trafficking partly through its interaction with ARMc8α. PMID:20224683

Repeated pulses of serotonin required for long-term facilitation activate mitogen-activated protein kinase in sensory neurons of Aplysia

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Michael, Dan; Martin, Kelsey C.; Seger, Rony; Ning, Ming-Ming; Baston, Rene; Kandel, Eric R.

1998-01-01

Long-term facilitation of the connections between the sensory and motor neurons of the gill-withdrawal reflex in Aplysia requires five repeated pulses of serotonin (5-HT). The repeated pulses of 5-HT initiate a cascade of gene activation that leads ultimately to the growth of new synaptic connections. Several genes in this process have been identified, including the transcriptional regulators apCREB-1, apCREB-2, apC/EBP, and the cell adhesion molecule apCAM, which is thought to be involved in the formation of new synaptic connections. Here we report that the transcriptional regulators apCREB-2 and apC/EBP, as well as a peptide derived from the cytoplasmic domain of apCAM, are phosphorylated in vitro by Aplysia mitogen-activated protein kinase (apMAPK). We have cloned the cDNA encoding apMAPK and show that apMAPK activity is increased in sensory neurons treated with repeated pulses of 5-HT and by the cAMP pathway. These results suggest that apMAPK may participate with cAMP-dependent protein kinase during long-term facilitation in sensory cells by modifying some of the key elements involved in the consolidation of short- to long-lasting changes in synaptic strength. PMID:9465108

Generating markers based on biotic stress of protein system in and tandem repeats sequence for Aquilaria sp

International Nuclear Information System (INIS)

Azhar Mohamad; Muhammad Hanif Azhari N; Siti Norhayati Ismail

2014-01-01

Aquilaria sp. belongs to the Thymelaeaceae family and is well distributed in Asia region. The species has multipurpose use from root to shoot and is an economically important crop, which generates wide interest in understanding genetic diversity of the species. Knowledge on DNA-based markers has become a prerequisite for more effective application of molecular marker techniques in breeding and mapping programs. In this work, both targeted genes and tandem repeat sequences were used for DNA fingerprinting in Aquilaria sp. A total of 100 ISSR (inter simple sequence repeat) primers and 50 combination pairs of specific primers derived from conserved region of a specific protein known as system in were optimized. 38 ISSR primers were found affirmative for polymorphism evaluation study and were generated from both specific and degenerate ISSR primers. And one utmost combination of system in primers showed significant results in distinguishing the Aquilaria sp. In conclusion, polymorphism derived from ISSR profiling and targeted stress genes of protein system in proved as a powerful approach for identification and molecular classification of Aquilaria sp. which will be useful for diversification in identifying any mutant lines derived from nature. (author)

Origin and diversification of leucine-rich repeat receptor-like protein kinase (LRR-RLK) genes in plants

OpenAIRE

Liu, Ping-Li; Du, Liang; Huang, Yuan; Gao, Shu-Min; Yu, Meng

2017-01-01

Background Leucine-rich repeat receptor-like protein kinases (LRR-RLKs) are the largest group of receptor-like kinases in plants and play crucial roles in development and stress responses. The evolutionary relationships among LRR-RLK genes have been investigated in flowering plants; however, no comprehensive studies have been performed for these genes in more ancestral groups. The subfamily classification of LRR-RLK genes in plants, the evolutionary history and driving force for the evolution...

PERFECTED enhanced recovery (PERFECT-ER) care versus standard acute care for patients admitted to acute settings with hip fracture identified as experiencing confusion: study protocol for a feasibility cluster randomized controlled trial.

Science.gov (United States)

Hammond, Simon P; Cross, Jane L; Shepstone, Lee; Backhouse, Tamara; Henderson, Catherine; Poland, Fiona; Sims, Erika; MacLullich, Alasdair; Penhale, Bridget; Howard, Robert; Lambert, Nigel; Varley, Anna; Smith, Toby O; Sahota, Opinder; Donell, Simon; Patel, Martyn; Ballard, Clive; Young, John; Knapp, Martin; Jackson, Stephen; Waring, Justin; Leavey, Nick; Howard, Gregory; Fox, Chris

2017-12-04

Health and social care provision for an ageing population is a global priority. Provision for those with dementia and hip fracture has specific and growing importance. Older people who break their hip are recognised as exceptionally vulnerable to experiencing confusion (including but not exclusively, dementia and/or delirium and/or cognitive impairment(s)) before, during or after acute admissions. Older people experiencing hip fracture and confusion risk serious complications, linked to delayed recovery and higher mortality post-operatively. Specific care pathways acknowledging the differences in patient presentation and care needs are proposed to improve clinical and process outcomes. This protocol describes a multi-centre, feasibility, cluster-randomised, controlled trial (CRCT) to be undertaken across ten National Health Service hospital trusts in the UK. The trial will explore the feasibility of undertaking a CRCT comparing the multicomponent PERFECTED enhanced recovery intervention (PERFECT-ER), which acknowledges the differences in care needs of confused older patients experiencing hip fracture, with standard care. The trial will also have an integrated process evaluation to explore how PERFECT-ER is implemented and interacts with the local context. The study will recruit 400 hip fracture patients identified as experiencing confusion and will also recruit "suitable informants" (individuals in regular contact with participants who will complete proxy measures). We will also recruit NHS professionals for the process evaluation. This mixed methods design will produce data to inform a definitive evaluation of the intervention via a large-scale pragmatic randomised controlled trial (RCT). The trial will provide a preliminary estimate of potential efficacy of PERFECT-ER versus standard care; assess service delivery variation, inform primary and secondary outcome selection, generate estimates of recruitment and retention rates, data collection difficulties, and

Human mismatch repair protein hMutLα is required to repair short slipped-DNAs of trinucleotide repeats.

Science.gov (United States)

Panigrahi, Gagan B; Slean, Meghan M; Simard, Jodie P; Pearson, Christopher E

2012-12-07

Mismatch repair (MMR) is required for proper maintenance of the genome by protecting against mutations. The mismatch repair system has also been implicated as a driver of certain mutations, including disease-associated trinucleotide repeat instability. We recently revealed a requirement of hMutSβ in the repair of short slip-outs containing a single CTG repeat unit (1). The involvement of other MMR proteins in short trinucleotide repeat slip-out repair is unknown. Here we show that hMutLα is required for the highly efficient in vitro repair of single CTG repeat slip-outs, to the same degree as hMutSβ. HEK293T cell extracts, deficient in hMLH1, are unable to process single-repeat slip-outs, but are functional when complemented with hMutLα. The MMR-deficient hMLH1 mutant, T117M, which has a point mutation proximal to the ATP-binding domain, is defective in slip-out repair, further supporting a requirement for hMLH1 in the processing of short slip-outs and possibly the involvement of hMHL1 ATPase activity. Extracts of hPMS2-deficient HEC-1-A cells, which express hMLH1, hMLH3, and hPMS1, are only functional when complemented with hMutLα, indicating that neither hMutLβ nor hMutLγ is sufficient to repair short slip-outs. The resolution of clustered short slip-outs, which are poorly repaired, was partially dependent upon a functional hMutLα. The joint involvement of hMutSβ and hMutLα suggests that repeat instability may be the result of aberrant outcomes of repair attempts.

Circuital model for the spherical geodesic waveguide perfect drain

Science.gov (United States)

González, Juan C.; Grabovičkić, Dejan; Benítez, Pablo; Miñano, Juan C.

2012-08-01

The perfect drain for the Maxwell fish eye (MFE) is a non-magnetic dissipative region placed in the focal point to absorb all the incident radiation without reflection or scattering. The perfect drain was recently designed as a material with complex permittivity that depends on frequency. However, this material is only a theoretical material, so it cannot be used in practical devices. The perfect drain has been claimed as necessary for achieving super-resolution (Leonhardt 2009 New J. Phys. 11 093040), which has increased the interest in practical perfect drains suitable for manufacturing. Here, we present a practical perfect drain that is designed using a simple circuit (made of a resistance and a capacitor) connected to the coaxial line. Moreover, we analyze the super-resolution properties of a device equivalent to the MFE, known as a spherical geodesic waveguide, loaded with this perfect drain. The super-resolution analysis for this device is carried out using COMSOL Multiphysics. The results of simulations predict a super-resolution of up to λ/3000.

Circuital model for the spherical geodesic waveguide perfect drain

International Nuclear Information System (INIS)

González, Juan C; Grabovičkić, Dejan; Benítez, Pablo; Miñano, Juan C

2012-01-01

The perfect drain for the Maxwell fish eye (MFE) is a non-magnetic dissipative region placed in the focal point to absorb all the incident radiation without reflection or scattering. The perfect drain was recently designed as a material with complex permittivity that depends on frequency. However, this material is only a theoretical material, so it cannot be used in practical devices. The perfect drain has been claimed as necessary for achieving super-resolution (Leonhardt 2009 New J. Phys. 11 093040), which has increased the interest in practical perfect drains suitable for manufacturing. Here, we present a practical perfect drain that is designed using a simple circuit (made of a resistance and a capacitor) connected to the coaxial line. Moreover, we analyze the super-resolution properties of a device equivalent to the MFE, known as a spherical geodesic waveguide, loaded with this perfect drain. The super-resolution analysis for this device is carried out using COMSOL Multiphysics. The results of simulations predict a super-resolution of up to λ/3000. (paper)

Repeatability and Reproducibility in Proteomic Identifications by Liquid Chromatography—Tandem Mass Spectrometry

Science.gov (United States)

Tabb, David L.; Vega-Montoto, Lorenzo; Rudnick, Paul A.; Variyath, Asokan Mulayath; Ham, Amy-Joan L.; Bunk, David M.; Kilpatrick, Lisa E.; Billheimer, Dean D.; Blackman, Ronald K.; Cardasis, Helene L.; Carr, Steven A.; Clauser, Karl R.; Jaffe, Jacob D.; Kowalski, Kevin A.; Neubert, Thomas A.; Regnier, Fred E.; Schilling, Birgit; Tegeler, Tony J.; Wang, Mu; Wang, Pei; Whiteaker, Jeffrey R.; Zimmerman, Lisa J.; Fisher, Susan J.; Gibson, Bradford W.; Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry; Stein, Steven E.; Tempst, Paul; Paulovich, Amanda G.; Liebler, Daniel C.; Spiegelman, Cliff

2009-01-01

The complexity of proteomic instrumentation for LC-MS/MS introduces many possible sources of variability. Data-dependent sampling of peptides constitutes a stochastic element at the heart of discovery proteomics. Although this variation impacts the identification of peptides, proteomic identifications are far from completely random. In this study, we analyzed interlaboratory data sets from the NCI Clinical Proteomic Technology Assessment for Cancer to examine repeatability and reproducibility in peptide and protein identifications. Included data spanned 144 LC-MS/MS experiments on four Thermo LTQ and four Orbitrap instruments. Samples included yeast lysate, the NCI-20 defined dynamic range protein mix, and the Sigma UPS 1 defined equimolar protein mix. Some of our findings reinforced conventional wisdom, such as repeatability and reproducibility being higher for proteins than for peptides. Most lessons from the data, however, were more subtle. Orbitraps proved capable of higher repeatability and reproducibility, but aberrant performance occasionally erased these gains. Even the simplest protein digestions yielded more peptide ions than LC-MS/MS could identify during a single experiment. We observed that peptide lists from pairs of technical replicates overlapped by 35–60%, giving a range for peptide-level repeatability in these experiments. Sample complexity did not appear to affect peptide identification repeatability, even as numbers of identified spectra changed by an order of magnitude. Statistical analysis of protein spectral counts revealed greater stability across technical replicates for Orbitraps, making them superior to LTQ instruments for biomarker candidate discovery. The most repeatable peptides were those corresponding to conventional tryptic cleavage sites, those that produced intense MS signals, and those that resulted from proteins generating many distinct peptides. Reproducibility among different instruments of the same type lagged behind

Detection, characterization and evolution of internal repeats in Chitinases of known 3-D structure.

Directory of Open Access Journals (Sweden)

Manigandan Sivaji

Full Text Available Chitinase proteins have evolved and diversified almost in all organisms ranging from prokaryotes to eukaryotes. During evolution, internal repeats may appear in amino acid sequences of proteins which alter the structural and functional features. Here we deciphered the internal repeats from Chitinase and characterized the structural similarities between them. Out of 24 diverse Chitinase sequences selected, six sequences (2CJL, 2DSK, 2XVP, 2Z37, 3EBV and 3HBE did not contain any internal repeats of amino acid sequences. Ten sequences contained repeats of length <50, and the remaining 8 sequences contained repeat length between 50 and 100 residues. Two Chitinase sequences, 1ITX and 3SIM, were found to be structurally similar when analyzed using secondary structure of Chitinase from secondary and 3-Dimensional structure database of Protein Data Bank. Internal repeats of 3N17 and 1O6I were also involved in the ligand-binding site of those Chitinase proteins, respectively. Our analyses enhance our understanding towards the identification of structural characteristics of internal repeats in Chitinase proteins.

The Perfect Text.

Science.gov (United States)

Russo, Ruth

1998-01-01

A chemistry teacher describes the elements of the ideal chemistry textbook. The perfect text is focused and helps students draw a coherent whole out of the myriad fragments of information and interpretation. The text would show chemistry as the central science necessary for understanding other sciences and would also root chemistry firmly in the…

Identification and function of leucine-rich repeat flightless-I-interacting protein 2 (LRRFIP2 in Litopenaeus vannamei.

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Shuang Zhang

Full Text Available Leucine-rich repeat flightless-I-interacting protein 2 (LRRFIP2 is a myeloid differentiation factor 88-interacting protein with a positive regulatory function in toll-like receptor signaling. In this study, seven LRRFIP2 protein variants (LvLRRFIP2A-G were identified in Litopenaeus vannamei. All the seven LvLRRFIP2 protein variants encode proteins with a DUF2051 domain. LvLRRFIP2s were upregulated in hemocytes after challenged with lipopolysaccharide, poly I:C, CpG-ODN2006, Vibrio parahaemolyticus, Staphylococcus aureus, and white spot syndrome virus (WSSV. Dual-luciferase reporter assays in Drosophila Schneider 2 cells revealed that LvLRRFIP2 activates the promoters of Drosophila and shrimp AMP genes. The knockdown of LvLRRFIP2 by RNA interference resulted in higher cumulative mortality of L. vannamei upon V. parahaemolyticus but not S. aureus and WSSV infections. The expression of L. vannamei AMP genes were reduced by dsLvLRRFIP2 interference. These results indicate that LvLRRFIP2 has an important function in antibacterials via the regulation of AMP gene expression.

Genome-wide analyses and functional classification of proline repeat-rich proteins: potential role of eIF5A in eukaryotic evolution.

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Ajeet Mandal

Full Text Available The eukaryotic translation factor, eIF5A has been recently reported as a sequence-specific elongation factor that facilitates peptide bond formation at consecutive prolines in Saccharomyces cerevisiae, as its ortholog elongation factor P (EF-P does in bacteria. We have searched the genome databases of 35 representative organisms from six kingdoms of life for PPP (Pro-Pro-Pro and/or PPG (Pro-Pro-Gly-encoding genes whose expression is expected to depend on eIF5A. We have made detailed analyses of proteome data of 5 selected species, Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Mus musculus and Homo sapiens. The PPP and PPG motifs are low in the prokaryotic proteomes. However, their frequencies markedly increase with the biological complexity of eukaryotic organisms, and are higher in newly derived proteins than in those orthologous proteins commonly shared in all species. Ontology classifications of S. cerevisiae and human genes encoding the highest level of polyprolines reveal their strong association with several specific biological processes, including actin/cytoskeletal associated functions, RNA splicing/turnover, DNA binding/transcription and cell signaling. Previously reported phenotypic defects in actin polarity and mRNA decay of eIF5A mutant strains are consistent with the proposed role for eIF5A in the translation of the polyproline-containing proteins. Of all the amino acid tandem repeats (≥3 amino acids, only the proline repeat frequency correlates with functional complexity of the five organisms examined. Taken together, these findings suggest the importance of proline repeat-rich proteins and a potential role for eIF5A and its hypusine modification pathway in the course of eukaryotic evolution.

m-Trifluoromethyl-diphenyl Diselenide Regulates Prefrontal Cortical MOR and KOR Protein Levels and Abolishes the Phenotype Induced by Repeated Forced Swim Stress in Mice.

Science.gov (United States)

Rosa, Suzan Gonçalves; Pesarico, Ana Paula; Martini, Franciele; Nogueira, Cristina Wayne

2018-04-05

The present study aimed to investigate the m-trifluoromethyl-diphenyl diselenide [(m-CF 3 -PhSe) 2 ] effects on prefrontal cortical MOR and KOR protein levels and phenotype induced by repeated forced swim stress (FSS) in mice. Adult Swiss mice were subjected to repeated FSS sessions, and after that, they performed the spontaneous locomotor/exploratory activity, tail suspension, and splash tests. (m-CF 3 -PhSe) 2 (0.1 to 5 mg/kg) was administered to mice 30 min before the first FSS session and 30 min before the subsequent repeated FSS. (m-CF 3 -PhSe) 2 abolished the phenotype induced by repeated FSS in mice. In addition, a single FSS session increased μ but reduced δ-opioid receptor contents, without changing the κ content. Mice subjected to repeated FSS had an increase in the μ content when compared to those of naïve group or subjected to single FSS. Repeated FSS induced an increase of δ-opioid receptor content compared to those mice subjected to single FSS. However, the δ-opioid receptor contents were lower than those found in the naïve group. The mice subjected to repeated FSS showed an increase in the κ-opioid receptor content when compared to that of the naïve mice. (m-CF 3 -PhSe) 2 regulated the protein contents of μ and κ receptors in mice subjected to repeated FSS. These findings demonstrate that (m-CF 3 -PhSe) 2 was effective to abolish the phenotype induced by FSS, which was accompanied by changes in the contents of cortical μ- and κ-opioid receptors.

Overlapped optics induced perfect coherent effects

Science.gov (United States)

Li, Jian Jie; Zang, Xiao Fei; Mao, Jun Fa; Tang, Min; Zhu, Yi Ming; Zhuang, Song Lin

2013-12-01

For traditional coherent effects, two separated identical point sources can be interfered with each other only when the optical path difference is integer number of wavelengths, leading to alternate dark and bright fringes for different optical path difference. For hundreds of years, such a perfect coherent condition seems insurmountable. However, in this paper, based on transformation optics, two separated in-phase identical point sources can induce perfect interference with each other without satisfying the traditional coherent condition. This shifting illusion media is realized by inductor-capacitor transmission line network. Theoretical analysis, numerical simulations and experimental results are performed to confirm such a kind of perfect coherent effect and it is found that the total radiation power of multiple elements system can be greatly enhanced. Our investigation may be applicable to National Ignition Facility (NIF), Inertial Confined Fusion (ICF) of China, LED lighting technology, terahertz communication, and so on.

A diverse host thrombospondin-type-1 repeat protein repertoire promotes symbiont colonization during establishment of cnidarian-dinoflagellate symbiosis.

Science.gov (United States)

Neubauer, Emilie-Fleur; Poole, Angela Z; Neubauer, Philipp; Detournay, Olivier; Tan, Kenneth; Davy, Simon K; Weis, Virginia M

2017-05-08

The mutualistic endosymbiosis between cnidarians and dinoflagellates is mediated by complex inter-partner signaling events, where the host cnidarian innate immune system plays a crucial role in recognition and regulation of symbionts. To date, little is known about the diversity of thrombospondin-type-1 repeat (TSR) domain proteins in basal metazoans or their potential role in regulation of cnidarian-dinoflagellate mutualisms. We reveal a large and diverse repertoire of TSR proteins in seven anthozoan species, and show that in the model sea anemone Aiptasia pallida the TSR domain promotes colonization of the host by the symbiotic dinoflagellate Symbiodinium minutum . Blocking TSR domains led to decreased colonization success, while adding exogenous TSRs resulted in a 'super colonization'. Furthermore, gene expression of TSR proteins was highest at early time-points during symbiosis establishment. Our work characterizes the diversity of cnidarian TSR proteins and provides evidence that these proteins play an important role in the establishment of cnidarian-dinoflagellate symbiosis.

A new characterization of trivially perfect graphs

Directory of Open Access Journals (Sweden)

Christian Rubio Montiel

2015-03-01

Full Text Available A graph $G$ is \\emph{trivially perfect} if for every induced subgraph the cardinality of the largest set of pairwise nonadjacent vertices (the stability number $\\alpha(G$ equals the number of (maximal cliques $m(G$. We characterize the trivially perfect graphs in terms of vertex-coloring and we extend some definitions to infinite graphs.

Lattice fluid dynamics from perfect discretizations of continuum flows

International Nuclear Information System (INIS)

Katz, E.; Wiese, U.

1998-01-01

We use renormalization group methods to derive equations of motion for large scale variables in fluid dynamics. The large scale variables are averages of the underlying continuum variables over cubic volumes and naturally exist on a lattice. The resulting lattice dynamics represents a perfect discretization of continuum physics, i.e., grid artifacts are completely eliminated. Perfect equations of motion are derived for static, slow flows of incompressible, viscous fluids. For Hagen-Poiseuille flow in a channel with a square cross section the equations reduce to a perfect discretization of the Poisson equation for the velocity field with Dirichlet boundary conditions. The perfect large scale Poisson equation is used in a numerical simulation and is shown to represent the continuum flow exactly. For nonsquare cross sections one can use a numerical iterative procedure to derive flow equations that are approximately perfect. copyright 1998 The American Physical Society

TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNA-binding proteins.

Science.gov (United States)

Zamiri, Bita; Reddy, Kaalak; Macgregor, Robert B; Pearson, Christopher E

2014-02-21

Certain DNA and RNA sequences can form G-quadruplexes, which can affect genetic instability, promoter activity, RNA splicing, RNA stability, and neurite mRNA localization. Amyotrophic lateral sclerosis and frontotemporal dementia can be caused by expansion of a (GGGGCC)n repeat in the C9orf72 gene. Mutant r(GGGGCC)n- and r(GGCCCC)n-containing transcripts aggregate in nuclear foci, possibly sequestering repeat-binding proteins such as ASF/SF2 and hnRNPA1, suggesting a toxic RNA pathogenesis, as occurs in myotonic dystrophy. Furthermore, the C9orf72 repeat RNA was recently demonstrated to undergo the noncanonical repeat-associated non-AUG translation (RAN translation) into pathologic dipeptide repeats in patient brains, a process that is thought to depend upon RNA structure. We previously demonstrated that the r(GGGGCC)n RNA forms repeat tract length-dependent G-quadruplex structures that bind the ASF/SF2 protein. Here we show that the cationic porphyrin (5,10,15,20-tetra(N-methyl-4-pyridyl) porphyrin (TMPyP4)), which can bind some G-quadruplex-forming sequences, can bind and distort the G-quadruplex formed by r(GGGGCC)8, and this ablates the interaction of either hnRNPA1 or ASF/SF2 with the repeat. These findings provide proof of concept that nucleic acid binding small molecules, such as TMPyP4, can distort the secondary structure of the C9orf72 repeat, which may beneficially disrupt protein interactions, which may ablate either protein sequestration and/or RAN translation into potentially toxic dipeptides. Disruption of secondary structure formation of the C9orf72 RNA repeats may be a viable therapeutic avenue, as well as a means to test the role of RNA structure upon RAN translation.

California's Perfect Storm

Science.gov (United States)

Bacon, David

2010-01-01

The United States today faces an economic crisis worse than any since the Great Depression of the 1930s. Nowhere is it sharper than in the nation's schools. Last year, California saw a perfect storm of protest in virtually every part of its education system. K-12 teachers built coalitions with parents and students to fight for their jobs and their…

Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

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Shanshan Huang

2015-10-01

Full Text Available In polyglutamine (polyQ diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17, we found that a large polyQ (105 glutamines in the TATA-box-binding protein (TBP preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.

Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

Science.gov (United States)

Huang, Shanshan; Yang, Su; Guo, Jifeng; Yan, Sen; Gaertig, Marta A.; Li, Shihua; Li, Xiao-Jiang

2015-01-01

SUMMARY In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knock-in mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases. PMID:26387956

Optimal simulation of a perfect entangler

International Nuclear Information System (INIS)

Yu Nengkun; Duan Runyao; Ying Mingsheng

2010-01-01

A 2 x 2 unitary operation is called a perfect entangler if it can generate a maximally entangled state from some unentangled input. We study the following question: How many runs of a given two-qubit entangling unitary operation are required to simulate some perfect entangler with one-qubit unitary operations as free resources? We completely solve this problem by presenting an analytical formula for the optimal number of runs of the entangling operation. Our result reveals an entanglement strength of two-qubit unitary operations.

Optically Modulated Multiband Terahertz Perfect Absorber

DEFF Research Database (Denmark)

Seren, Huseyin R.; Keiser, George R.; Cao, Lingyue

2014-01-01

response of resonant metamaterials continues to be a challengingendeavor. Resonant perfect absorbers have flourished as one of the mostpromising metamaterial devices with applications ranging from power har-vesting to terahertz imaging. Here, an optically modulated resonant perfectabsorber is presented....... Utilizing photo-excited free carriers in silicon padsplaced in the capacitive gaps of split ring resonators, a dynamically modu-lated perfect absorber is designed and fabricated to operate in reflection.Large modulation depth (38% and 91%) in two absorption bands (with 97%and 92% peak absorption...

Poxviral Ankyrin Proteins

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Michael H. Herbert

2015-02-01

Full Text Available Multiple repeats of the ankyrin motif (ANK are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range.

Everybody's Different Nobody's Perfect

Science.gov (United States)

... traten ni qué edad tengan — eso se llama “DISCAPACIDAD.” Some kids have a disability because their muscles ... have one? ¿Conoces a alguien que tenga una discapacidad? ¿Tienes una tú? Everybody’s different, nobody’s perfect. So ...

Visible light broadband perfect absorbers

Energy Technology Data Exchange (ETDEWEB)

Jia, X. L.; Meng, Q. X.; Yuan, C. X.; Zhou, Z. X.; Wang, X. O., E-mail: wxo@hit.edu.cn [School of Science, Harbin Institute of Technology, Harbin 150001 (China)

2016-03-15

The visible light broadband perfect absorbers based on the silver (Ag) nano elliptical disks and holes array are studied using finite difference time domain simulations. The semiconducting indium silicon dioxide thin film is introduced as the space layer in this sandwiched structure. Utilizing the asymmetrical geometry of the structures, polarization sensitivity for transverse electric wave (TE)/transverse magnetic wave (TM) and left circular polarization wave (LCP)/right circular polarization wave (RCP) of the broadband absorption are gained. The absorbers with Ag nano disks and holes array show several peaks absorbance of 100% by numerical simulation. These simple and flexible perfect absorbers are particularly desirable for various potential applications including the solar energy absorber.

Two-perfect fluid interpretation of an energy tensor

International Nuclear Information System (INIS)

Ferrando, J.J.; Morales, J.A.; Portilla, M.

1990-01-01

There are many topics in General Relativity where matter is represented by a mixture of two fluids. In fact, some astrophysical and cosmological situations need to be described by an energy tensor made up of the sum of two or more perfect fluids rather than that with only one. The paper contains the necessary and sufficient conditions for a given energy tensor to be interpreted as a sum of two perfect fluids. Given a tensor of this class, the decomposition in two perfect fluids (which is determined up to a couple of real functions) is obtained

A cross-linguistic discourse analysis of the perfect

NARCIS (Netherlands)

Swart, Henriëtte de

2007-01-01

Since Reichenbach (1947), the Present Perfect has been discussed in relation to the Simple Past. The Reichenbachian characterization E-R,S has led to the view that the English Present Perfect, with its restrictions on modification by time adverbials and its resistance to narrative structure is the

Enhanced Expression of WD Repeat-Containing Protein 35 via Nuclear Factor-Kappa B Activation in Bupivacaine-Treated Neuro2a Cells

Science.gov (United States)

Huang, Lei; Kondo, Fumio; Harato, Misako; Feng, Guo-Gang; Ishikawa, Naoshisa; Fujiwara, Yoshihiro; Okada, Shoshiro

2014-01-01

The family of WD repeat proteins comprises a large number of proteins and is involved in a wide variety of cellular processes such as signal transduction, cell growth, proliferation, and apoptosis. Bupivacaine is a sodium channel blocker administered for local infiltration, nerve block, epidural, and intrathecal anesthesia. Recently, we reported that bupivacaine induces reactive oxygen species (ROS) generation and p38 mitogen-activated protein kinase (MAPK) activation, resulting in an increase in the expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. It has been shown that ROS activate MAPK through phosphorylation, followed by activation of nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1). The present study was undertaken to test whether NF-κB and c-Jun/AP-1 are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Bupivacaine activated both NF-κB and c-Jun in Neuro2a cells. APDC, an NF-κB inhibitor, attenuated the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. GW9662, a selective peroxisome proliferator-activated receptor-γ antagonist, enhanced the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. In contrast, c-Jun siRNA did not inhibit the bupivacaine-induced increase in WDR35 mRNA expression. These results indicate that bupivacaine induces the activation of transcription factors NF-κB and c-Jun/AP-1 in Neuro2a cells, while activation of NF-κB is involved in bupivacaine-induced increases in WDR35 expression. PMID:24466034

Development of a perfect prognosis probabilistic model for ...

Indian Academy of Sciences (India)

A prediction model based on the perfect prognosis method was developed to predict the probability of lightning and probable time of its occurrence over the south-east Indian region. In the perfect prognosis method, statistical relationships are established using past observed data. For real time applications, the predictors ...

The diversity and evolution of Wolbachia ankyrin repeat domain genes.

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Stefanos Siozios

Full Text Available Ankyrin repeat domain-encoding genes are common in the eukaryotic and viral domains of life, but they are rare in bacteria, the exception being a few obligate or facultative intracellular Proteobacteria species. Despite having a reduced genome, the arthropod strains of the alphaproteobacterium Wolbachia contain an unusually high number of ankyrin repeat domain-encoding genes ranging from 23 in wMel to 60 in wPip strain. This group of genes has attracted considerable attention for their astonishing large number as well as for the fact that ankyrin proteins are known to participate in protein-protein interactions, suggesting that they play a critical role in the molecular mechanism that determines host-Wolbachia symbiotic interactions. We present a comparative evolutionary analysis of the wMel-related ankyrin repeat domain-encoding genes present in different Drosophila-Wolbachia associations. Our results show that the ankyrin repeat domain-encoding genes change in size by expansion and contraction mediated by short directly repeated sequences. We provide examples of intra-genic recombination events and show that these genes are likely to be horizontally transferred between strains with the aid of bacteriophages. These results confirm previous findings that the Wolbachia genomes are evolutionary mosaics and illustrate the potential that these bacteria have to generate diversity in proteins potentially involved in the symbiotic interactions.

Ternary WD40 repeat-containing protein complexes: evolution, composition and roles in plant immunity

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Jimi C. Miller

2016-01-01

Full Text Available Plants, like mammals, rely on their innate immune system to perceive and discriminate among the majority of their microbial pathogens. Unlike mammals, plants respond to this molecular dialogue by unleashing a complex chemical arsenal of defense metabolites to resist or evade pathogen infection. In basal or non-host resistance, plants utilize signal transduction pathways to detect non-self, damaged-self and altered-self-associated molecular patterns and translate these danger signals into largely inducible chemical defenses. The WD40 repeat (WDR-containing proteins Gβ and TTG1 are constituents of two independent ternary protein complexes functioning at opposite ends of a plant immune signaling pathway. Gβ and TTG1 are also encoded by single-copy genes that are ubiquitous in higher plants, implying the limited diversity and functional conservation of their respective complexes. In this review, we summarize what is currently known about the evolutionary history of these WDR-containing ternary complexes, their repertoire and combinatorial interactions, and their downstream effectors and pathways in plant defense.

A note on perfect scalar fields

International Nuclear Information System (INIS)

Unnikrishnan, Sanil; Sriramkumar, L.

2010-01-01

We derive a condition on the Lagrangian density describing a generic, single, noncanonical scalar field, by demanding that the intrinsic, nonadiabatic pressure perturbation associated with the scalar field vanishes identically. Based on the analogy with perfect fluids, we refer to such fields as perfect scalar fields. It is common knowledge that models that depend only on the kinetic energy of the scalar field (often referred to as pure kinetic models) possess no nonadiabatic pressure perturbation. While we are able to construct models that seemingly depend on the scalar field and also do not contain any nonadiabatic pressure perturbation, we find that all such models that we construct allow a redefinition of the field under which they reduce to pure kinetic models. We show that, if a perfect scalar field drives inflation, then, in such situations, the first slow roll parameter will always be a monotonically decreasing function of time. We point out that this behavior implies that these scalar fields cannot lead to features in the inflationary, scalar perturbation spectrum.

Forbidden Structures for Planar Perfect Consecutively Colourable Graphs

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Borowiecka-Olszewska Marta

2017-05-01

Full Text Available A consecutive colouring of a graph is a proper edge colouring with posi- tive integers in which the colours of edges incident with each vertex form an interval of integers. The idea of this colouring was introduced in 1987 by Asratian and Kamalian under the name of interval colouring. Sevast- janov showed that the corresponding decision problem is NP-complete even restricted to the class of bipartite graphs. We focus our attention on the class of consecutively colourable graphs whose all induced subgraphs are consecutively colourable, too. We call elements of this class perfect consecutively colourable to emphasise the conceptual similarity to perfect graphs. Obviously, the class of perfect consecutively colourable graphs is induced hereditary, so it can be characterized by the family of induced forbidden graphs. In this work we give a necessary and sufficient conditions that must be satisfied by the generalized Sevastjanov rosette to be an induced forbid- den graph for the class of perfect consecutively colourable graphs. Along the way, we show the exact values of the deficiency of all generalized Sevastjanov rosettes, which improves the earlier known estimating result. It should be mentioned that the deficiency of a graph measures its closeness to the class of consecutively colourable graphs. We motivate the investigation of graphs considered here by showing their connection to the class of planar perfect consecutively colourable graphs.

Wages and employment in a repeated game with revenue fluctuations

DEFF Research Database (Denmark)

Schultz, Christian

1997-01-01

Empirical investigations suggests that the real wage is surprisingly flat over the business cycle. This paper analyses a repeated game between a union and a firm which can contribute to explaining the flat wage. The parties cannot enter binding contracts, and revenue is fluctuating. The paper...... focuses on the best subgame-perfect equilibrium among those sharing the expected surplus in given fixed shares - e.g. equal shares. It is shown that (for moderate discount factors) this equilibrium has a more counter-cyclical wage, than what would be the case if the parties shared the surplus in each...

Perfect Power Prototype for Illinois Institute of Technology

Energy Technology Data Exchange (ETDEWEB)

Shahidehpour, Mohammad [Illinois Inst. Of Technology, Chicago, IL (United States)

2014-09-30

Starting in October 2008, Illinois Institute of Technology (IIT), in collaboration with over 20 participating members, led an extensive effort to develop, demonstrate, promote, and commercialize a microgrid system and offer supporting technologies that will achieve Perfect Power at the main campus of IIT. A Perfect Power system, as defined by the Galvin Electricity Initiative (GEI), is a system that cannot fail to meet the electric needs of the individual end-user. The Principle Investigator of this Perfect Power project was Dr. Mohammad Shahidehpour, Director of the Robert W. Galvin Center for Electricity Innovation at IIT. There were six overall objectives of the Perfect Power project: (1) Demonstrate the higher reliability introduced by the microgrid system at IIT; (2) Demonstrate the economics of microgrid operations; (3) Allow for a decrease of fifty percent (50%) of grid electricity load; (4) Create a permanent twenty percent (20%) decrease in peak load from 2007 level; (5) Defer planned substation through load reduction; (6) Offer a distribution system design that can be replicated in urban communities.

The Jasmonate-ZIM-domain proteins interact with the WD-Repeat/bHLH/MYB complexes to regulate Jasmonate-mediated anthocyanin accumulation and trichome initiation in Arabidopsis thaliana.

Science.gov (United States)

Qi, Tiancong; Song, Susheng; Ren, Qingcuo; Wu, Dewei; Huang, Huang; Chen, Yan; Fan, Meng; Peng, Wen; Ren, Chunmei; Xie, Daoxin

2011-05-01

Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)-based SCF(COI1) complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation.

Expression, purification, crystallization and preliminary X-ray diffraction studies of the human keratin 4-binding domain of serine-rich repeat protein 1 from Streptococcus agalactiae

International Nuclear Information System (INIS)

Sundaresan, Ramya; Samen, Ulrike; Ponnuraj, Karthe

2011-01-01

Expression, purification and crystallization of Srr-1-K4BD, a human keratin 4-binding domain of serine-rich repeat protein 1 from S. agalactiae, was carried out. Native crystals of Srr-1-K4BD diffracted to 3.8 Å resolution using synchrotron radiation. Serine-rich repeat protein 1 (Srr-1) is a surface protein from Streptococcus agalactiae. A 17 kDa region of this protein has been identified to bind to human keratin 4 (K4) and is termed the Srr-1 K4-binding domain (Srr-1-K4BD). Recombinant Srr-1-K4BD was overexpressed in Escherichia coli BL21 (DE3) cells. Native and selenomethionine-substituted proteins were prepared using Luria–Bertani (LB) and M9 minimal media, respectively. A two-step purification protocol was carried out to obtain a final homogenous sample of Srr-1-K4BD. Crystals of native Srr-1-K4BD were obtained using PEG 3350 as a precipitant. The crystals diffracted to 3.8 Å resolution using synchrotron radiation and belonged to space group P2 1 , with unit-cell parameters a = 47.56, b = 59.48, c = 94.71 Å, β = 93.95°

10 CFR 609.16 - Perfection of liens and preservation of collateral.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Perfection of liens and preservation of collateral. 609.16... THAT EMPLOY INNOVATIVE TECHNOLOGIES § 609.16 Perfection of liens and preservation of collateral. (a... to perfect and maintain liens, as applicable, on assets which are pledged as collateral for the...

Scheme for achieving coherent perfect absorption by anisotropic metamaterials

KAUST Repository

Zhang, Xiujuan

2017-02-22

We propose a unified scheme to achieve coherent perfect absorption of electromagnetic waves by anisotropic metamaterials. The scheme describes the condition on perfect absorption and offers an inverse design route based on effective medium theory in conjunction with retrieval method to determine practical metamaterial absorbers. The scheme is scalable to frequencies and applicable to various incident angles. Numerical simulations show that perfect absorption is achieved in the designed absorbers over a wide range of incident angles, verifying the scheme. By integrating these absorbers, we further propose an absorber to absorb energy from two coherent point sources.

Ten tandem repeats of β-hCG 109-118 enhance immunogenicity and anti-tumor effects of β-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65

International Nuclear Information System (INIS)

Zhang Yankai; Yan Rong; He Yi; Liu Wentao; Cao Rongyue; Yan Ming; Li Taiming; Liu Jingjing; Wu Jie

2006-01-01

The β-subunit of human chorionic gonadotropin (β-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of β-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with β-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-βhCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residue sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-βhCGCTP37 and HSP65-βhCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-βhCGCTP37 elicited much higher levels of specific anti-β-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-βhCGCTP37, which should suggest that HSP65-X10-βhCGCTP37 may be an effective protein vaccine for the treatment of β-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens

Conservative Sample Size Determination for Repeated Measures Analysis of Covariance.

Science.gov (United States)

Morgan, Timothy M; Case, L Douglas

2013-07-05

In the design of a randomized clinical trial with one pre and multiple post randomized assessments of the outcome variable, one needs to account for the repeated measures in determining the appropriate sample size. Unfortunately, one seldom has a good estimate of the variance of the outcome measure, let alone the correlations among the measurements over time. We show how sample sizes can be calculated by making conservative assumptions regarding the correlations for a variety of covariance structures. The most conservative choice for the correlation depends on the covariance structure and the number of repeated measures. In the absence of good estimates of the correlations, the sample size is often based on a two-sample t-test, making the 'ultra' conservative and unrealistic assumption that there are zero correlations between the baseline and follow-up measures while at the same time assuming there are perfect correlations between the follow-up measures. Compared to the case of taking a single measurement, substantial savings in sample size can be realized by accounting for the repeated measures, even with very conservative assumptions regarding the parameters of the assumed correlation matrix. Assuming compound symmetry, the sample size from the two-sample t-test calculation can be reduced at least 44%, 56%, and 61% for repeated measures analysis of covariance by taking 2, 3, and 4 follow-up measures, respectively. The results offer a rational basis for determining a fairly conservative, yet efficient, sample size for clinical trials with repeated measures and a baseline value.

Indefinite and Continuative Interpretations of the English Present Perfect

Directory of Open Access Journals (Sweden)

Katarina Dea Žetko

2005-06-01

Full Text Available The objective of our paper is to demonstrate that the English present perfect is not by inherent meaning either indefinite or continuative. Notions like indefinite and continuative are contextdependent interpretations of whole constructions and their broader context. However, continuative interpretation can also be triggered by certain adverbials, negative constructions and verbs in the progressive form. But, even these factors do not always guarantee continuative interpretations. Construction, continuative meaning can be cancelled by the context in a broader sense, this fact being a proof that this meaning is merely an implicature. We will demonstrate how different factors interact and trigger either indefinite or continuative interpretations which are not inherent in the present perfect itself. Our paper will attempt to provide sufficient evidence that there is no indefinite/continuative distinction in the English present perfect, the inherent meaning or function of the present perfect is merely to locate the situation somewhere within a period that starts before the time of utterance and leads up to it.

Perfect and Periphrastic Passive Constructions in Danish

DEFF Research Database (Denmark)

Bjerre, Tavs; Bjerre, Anne

2007-01-01

This paper gives an account of the event and argument structure of past participles and the linking between argument structure and valence structure. It further accounts for how participles form perfect and passiv constructions with auxiliaries. We assume that the same participle form is used...... in both types of construction. Our claim is that the valence structure of a past participle is predictable from its semantic type, and that the valence structure predicts with which auciliary a past participle combines in perfect constructions and whether the past participle may occur in passiv...

Perfect 800 Advanced Strategies for Top Students

CERN Document Server

Celenti, Dan

2010-01-01

Getting into the nation's most competitive universities requires more than a good SAT score, it requires a perfect score. Perfect 800: SAT Math gives advanced students the tools needed to master the SAT math test. Covering areas including arithmetic concepts; algebra; geometry; and additional topics such as probability and weighted average, the book offers exposure to a wide range of degrees of difficulty in a holistic approach that allows students to experience the "real thing," including the impact of time constraints on their performance. By emphasizing critical thinking and analytic skills

Elastic collisions of classical point particles on a finite frictionless linear track with perfectly reflecting endpoints

Science.gov (United States)

DeLuca, R.

2006-03-01

Repeated elastic collisions of point particles on a finite frictionless linear track with perfectly reflecting endpoints are considered. The problem is analysed by means of an elementary linear algebra approach. It is found that, starting with a state consisting of a projectile particle in motion at constant velocity and a target particle at rest in a fixed known position, the points at which collisions occur on track, when plotted versus progressive numerals, corresponding to the collisions themselves, show periodic patterns for a rather large choice of values of the initial position x(0) and on the mass ratio r. For certain values of these parameters, however, only regular behaviour over a large number of collisions is detected.

Protection against Syphilis Correlates with Specificity of Antibodies to the Variable Regions of Treponema pallidum Repeat Protein K

OpenAIRE

Morgan, Cecilia A.; Lukehart, Sheila A.; Van Voorhis, Wesley C.

2003-01-01

Syphilis has been recognized as a disease since the late 1400s, yet there is no practical vaccine available. One impediment to the development of a vaccine is the lack of understanding of multiple reinfections in humans despite the development of robust immune responses during the first episode. It has been shown that the Treponema pallidum repeat protein K (TprK) differs in seven discrete variable (V) regions in isolates and that the antibody response during infection is directed to these V ...

Repeatability of apparent diffusion coefficient and intravoxel incoherent motion parameters at 3.0 Tesla in orbital lesions

Energy Technology Data Exchange (ETDEWEB)

Lecler, Augustin [Fondation Ophtalmologique Adolphe de Rothschild, Department of Radiology, Paris (France); Cardiovascular Research Centre - PARCC, Universite Paris Descartes Sorbonne Paris Cite, INSERM UMR-S970, Paris (France); Savatovsky, Julien; Sadik, Jean-Claude; Charbonneau, Frederique; Berges, Olivier [Fondation Ophtalmologique Adolphe de Rothschild, Department of Radiology, Paris (France); Balvay, Daniel [Cardiovascular Research Centre - PARCC, Universite Paris Descartes Sorbonne Paris Cite, INSERM UMR-S970, Paris (France); Zmuda, Mathieu; Galatoire, Olivier [Fondation Ophtalmologique Adolphe de Rothschild, Department of Orbitopalpebral Surgery, Paris (France); Picard, Herve [Fondation Ophtalmologique Adolphe de Rothschild, Clinical Research Unit, Paris (France); Fournier, Laure [Cardiovascular Research Centre - PARCC, Universite Paris Descartes Sorbonne Paris Cite, INSERM UMR-S970, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Radiology Department, Paris (France)

2017-12-15

To evaluate repeatability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters in the orbit. From December 2015 to March 2016, 22 patients were scanned twice using an IVIM sequence with 15b values (0-2,000 s/mm{sup 2}) at 3.0T. Two readers independently delineated regions of interest in an orbital mass and in different intra-orbital and extra-orbital structures. Short-term test-retest repeatability and inter-observer agreement were assessed using the intra-class correlation coefficient (ICC), the coefficient of variation (CV) and Bland-Altman limits of agreements (BA-LA). Test-retest repeatability of IVIM parameters in the orbital mass was satisfactory for ADC and D (mean CV 12% and 14%, ICC 95% and 93%), poor for f and D*(means CV 43% and 110%, ICC 90% and 65%). Inter-observer repeatability agreement was almost perfect in the orbital mass for all the IVIM parameters (ICC = 95%, 93%, 94% and 90% for ADC, D, f and D*, respectively). IVIM appeared to be a robust tool to measure D in orbital lesions with good repeatability, but this approach showed a poor repeatability of f and D*. (orig.)

Repeatability of apparent diffusion coefficient and intravoxel incoherent motion parameters at 3.0 Tesla in orbital lesions

International Nuclear Information System (INIS)

Lecler, Augustin; Savatovsky, Julien; Sadik, Jean-Claude; Charbonneau, Frederique; Berges, Olivier; Balvay, Daniel; Zmuda, Mathieu; Galatoire, Olivier; Picard, Herve; Fournier, Laure

2017-01-01

To evaluate repeatability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters in the orbit. From December 2015 to March 2016, 22 patients were scanned twice using an IVIM sequence with 15b values (0-2,000 s/mm 2 ) at 3.0T. Two readers independently delineated regions of interest in an orbital mass and in different intra-orbital and extra-orbital structures. Short-term test-retest repeatability and inter-observer agreement were assessed using the intra-class correlation coefficient (ICC), the coefficient of variation (CV) and Bland-Altman limits of agreements (BA-LA). Test-retest repeatability of IVIM parameters in the orbital mass was satisfactory for ADC and D (mean CV 12% and 14%, ICC 95% and 93%), poor for f and D*(means CV 43% and 110%, ICC 90% and 65%). Inter-observer repeatability agreement was almost perfect in the orbital mass for all the IVIM parameters (ICC = 95%, 93%, 94% and 90% for ADC, D, f and D*, respectively). IVIM appeared to be a robust tool to measure D in orbital lesions with good repeatability, but this approach showed a poor repeatability of f and D*. (orig.)

Perfect 2-colorings of the generalized Petersen graph

Indian Academy of Sciences (India)

There are no perfect 2-colorings of GP(n, 2) with the matrix A3. Proof. Suppose, contrary to our claim, there is a perfect 2-coloring of GP(n, 2) with the matrix A3. By Lemma 3.4, there are 2 vertices ai and bi, for some 0 ≤ i ≤ n−1, such that they are the same color. By symmetry, without loss of generality, we can assume T (a0) ...

Thermodynamical stability for a perfect fluid

Energy Technology Data Exchange (ETDEWEB)

Fang, Xiongjun; Jing, Jiliang [Hunan Normal University, Department of Physics, Key Laboratory of Low Dimensional Quantum Structures and Quantum Control of Ministry of Education, and Synergetic Innovation Center for Quantum Effects and Applications, Changsha, Hunan (China); He, Xiaokai [Hunan Normal University, Department of Physics, Key Laboratory of Low Dimensional Quantum Structures and Quantum Control of Ministry of Education, and Synergetic Innovation Center for Quantum Effects and Applications, Changsha, Hunan (China); Hunan First Normal University, School of Mathematics and Computational Science, Changsha (China)

2017-12-15

According to the maximum entropy principle, it has been proved that the gravitational field equations could be derived by the extrema of the total entropy for a perfect fluid, which implies that thermodynamic relations contain information as regards gravity. In this manuscript, we obtain a criterion for the thermodynamical stability of an adiabatic, self-gravitating perfect fluid system by the second variation of the total entropy. We show, for Einstein's gravity with spherical symmetry spacetime, that the criterion is consistent with that for the dynamical stability derived by Chandrasekhar and Wald. We also find that the criterion could be applied to cases without spherical symmetry, or under general perturbations. The result further establishes the connection between thermodynamics and gravity. (orig.)

Stealing the spotlight: CUL4-DDB1 ubiquitin ligase docks WD40-repeat proteins to destroy

Directory of Open Access Journals (Sweden)

Zhang Hui

2007-02-01

Full Text Available Abstract Recent investigation of Cullin 4 (CUL4 has ushered this class of multiprotein ubiquitin E3 ligases to center stage as critical regulators of diverse processes including cell cycle regulation, developmental patterning, DNA replication, DNA damage and repair, and epigenetic control of gene expression. CUL4 associates with DNA Damage Binding protein 1 (DDB1 to assemble an ubiquitin E3 ligase that targets protein substrates for ubiquitin-dependent proteolysis. CUL4 ligase activity is also regulated by the covalent attachment of the ubiquitin-like protein NEDD8 to CUL4, or neddylation, and the COP9 signalosome complex (CSN that removes this important modification. Recently, multiple WD40-repeat proteins (WDR were found to interact with DDB1 and serve as the substrate-recognition subunits of the CUL4-DDB1 ubiquitin ligase. As more than 150–300 WDR proteins exist in the human genome, these findings impact a wide array of biological processes through CUL4 ligase-mediated proteolysis. Here, we review the recent progress in understanding the mechanism of CUL4 ubiquitin E3 ligase and discuss the architecture of CUL4-assembled E3 ubiquitin ligase complexes by comparison to CUL1-based E3s (SCF. Then, we will review several examples to highlight the critical roles of CUL4 ubiquitin ligase in genome stability, cell cycle regulation, and histone lysine methylation. Together, these studies provide insights into the mechanism of this novel ubiquitin ligase in the regulation of important biological processes.

Perfect 3-colorings of the cubic graphs of order 10

Directory of Open Access Journals (Sweden)

Mehdi Alaeiyan

2017-10-01

Full Text Available Perfect coloring is a generalization of the notion of completely regular codes, given by Delsarte. A perfect m-coloring of a graph G with m colors is a partition of the vertex set of G into m parts A_1, A_2, ..., A_m such that, for all $ i,j \\in \\lbrace 1, ... , m \\rbrace $, every vertex of A_i is adjacent to the same number of vertices, namely, a_{ij} vertices, of A_j. The matrix $A=(a_{ij}_{i,j\\in \\lbrace 1,... ,m\\rbrace }$, is called the parameter matrix. We study the perfect 3-colorings (also known as the equitable partitions into three parts of the cubic graphs of order 10. In particular, we classify all the realizable parameter matrices of perfect 3-colorings for the cubic graphs of order 10.

Computing a quasi-perfect equilibrium of a two-player game

DEFF Research Database (Denmark)

Miltersen, Peter Bro; Sørensen, Troels Bjerre

2010-01-01

Refining an algorithm due to Koller, Megiddo and von Stengel, we show how to apply Lemke's algorithm for solving linear complementarity programs to compute a quasi-perfect equilibrium in behavior strategies of a given two-player extensive-form game of perfect recall. A quasi-perfect equilibrium...... of a zero-sum game, we devise variants of the algorithm that rely on linear programming rather than linear complementarity programming and use the simplex algorithm or other algorithms for linear programming rather than Lemke's algorithm. We argue that these latter algorithms are relevant for recent...

A Hypergraph Dictatorship Test with Perfect Completeness

Science.gov (United States)

Chen, Victor

A hypergraph dictatorship test is first introduced by Samorodnitsky and Trevisan and serves as a key component in their unique games based {operatorname{PCP}} construction. Such a test has oracle access to a collection of functions and determines whether all the functions are the same dictatorship, or all their low degree influences are o(1). Their test makes q ≥ 3 queries, has amortized query complexity 1+Oleft(log q/qright), but has an inherent loss of perfect completeness. In this paper we give an (adaptive) hypergraph dictatorship test that achieves both perfect completeness and amortized query complexity 1+Oleft(log q/qright).

Optimization of Perfect Absorbers with Multilayer Structures

Science.gov (United States)

Li Voti, Roberto

2018-02-01

We study wide-angle and broadband perfect absorbers with compact multilayer structures made of a sequence of ITO and TiN layers deposited onto a silver thick layer. An optimization procedure is introduced for searching the optimal thicknesses of the layers so as to design a perfect broadband absorber from 400 nm to 750 nm, for a wide range of angles of incidence from 0{°} to 50{°}, for both polarizations and with a low emissivity in the mid-infrared. We eventually compare the performances of several optimal structures that can be very promising for solar thermal energy harvesting and collectors.

Electromagnetic Detection of a Perfect Invisibility Cloak

International Nuclear Information System (INIS)

Zhang Baile; Wu, Bae-Ian

2009-01-01

A perfect invisibility cloak is commonly believed to be undetectable from electromagnetic (EM) detection because it is equivalent to a curved but empty EM space created from coordinate transformation. Based on the intrinsic asymmetry of coordinate transformation applied to motions of photons and charges, we propose a method to detect this curved EM space by shooting a fast-moving charged particle through it. A broadband radiation generated in this process makes a cloak visible. Our method is the only known EM mechanism so far to detect an ideal perfect cloak (curved EM space) within its working band.

Apnea of prematurity--perfect storm.

Science.gov (United States)

Di Fiore, Juliann M; Martin, Richard J; Gauda, Estelle B

2013-11-01

With increased survival of preterm infants as young as 23 weeks gestation, maintaining adequate respiration and corresponding oxygenation represents a clinical challenge in this unique patient cohort. Respiratory instability characterized by apnea and periodic breathing occurs in premature infants because of immature development of the respiratory network. While short respiratory pauses and apnea may be of minimal consequence if oxygenation is maintained, they can be problematic if accompanied by chronic intermittent hypoxemia. Underdevelopment of the lung and the resultant lung injury that occurs in this population concurrent with respiratory instability creates the perfect storm leading to frequent episodes of profound and recurrent hypoxemia. Chronic intermittent hypoxemia contributes to the immediate and long term co-morbidities that occur in this population. In this review we discuss the pathophysiology leading to the perfect storm, diagnostic assessment of breathing instability in this unique population and therapeutic interventions that aim to stabilize breathing without contributing to tissue injury. Copyright © 2013. Published by Elsevier B.V.

Perfect Liberty or Natural Liberty?

DEFF Research Database (Denmark)

Jacobsen, Stefan Gaarsmand

2012-01-01

The article investigates the concept of natural order as it is used by François Quesnay and Adam Smith in their respective economic writings. While Smith used the concept only after having visited Quesnay and the Physiocrats in France in the 1760s, in The Wealth of Nations he sought to negotiate...... the meaning of what was “natural” about economic life. The Physiocrats believed it possible to identify a model or a perfect regime of natural order – an order that they in fact thought to exist and function in China due to a rigorous system of economic laws. Smith sided with contemporary critics...... of this metaphysical vision of economic perfection (and of Chinese governance), but he suggested that the economic mechanisms of the physiocratic theories would remain intact even with a minimum of control by state laws. However, Smith’s balancing act on these questions remained disputed even by his Scottish...

Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

Directory of Open Access Journals (Sweden)

Marsha eMailick

2014-09-01

Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

CD4-specific designed ankyrin repeat proteins are novel potent HIV entry inhibitors with unique characteristics.

Directory of Open Access Journals (Sweden)

Andreas Schweizer

2008-07-01

Full Text Available Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins-high physical stability, specificity and low production costs-with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development.

Immediate-early gene response to repeated immobilization: Fos protein and arc mRNA levels appear to be less sensitive than c-fos mRNA to adaptation.

Science.gov (United States)

Ons, Sheila; Rotllant, David; Marín-Blasco, Ignacio J; Armario, Antonio

2010-06-01

Stress exposure resulted in brain induction of immediate-early genes (IEGs), considered as markers of neuronal activation. Upon repeated exposure to the same stressor, reduction of IEG response (adaptation) has been often observed, but there are important discrepancies in literature that may be in part related to the particular IEG and methodology used. We studied the differential pattern of adaptation of the IEGs c-fos and arc (activity-regulated cytoskeleton-associated protein) after repeated exposure to a severe stressor: immobilization on wooden boards (IMO). Rats repeatedly exposed to IMO showed reduced c-fos mRNA levels in response to acute IMO in most brain areas studied: the medial prefrontal cortex (mPFC), lateral septum (LS), medial amygdala (MeA), paraventricular nucleus of the hypothalamus (PVN) and locus coeruleus. In contrast, the number of neurons showing Fos-like immunoreactivity was only reduced in the MeA and the various subregions of the PVN. IMO-induced increases in arc gene expression were restricted to telencephalic regions and reduced by repeated IMO only in the mPFC. Double-labelling in the LS of IMO-exposed rats revealed that arc was expressed in only one-third of Fos+ neurons, suggesting two populations of Fos+ neurons. These data suggest that c-fos mRNA levels are more affected by repeated IMO than corresponding protein, and that arc gene expression does not reflect adaptation in most brain regions, which may be related to its constitutive expression. Therefore, the choice of a particular IEG and the method of measurement are important for proper interpretation of the impact of chronic repeated stress on brain activation.

Jammer Type Estimation in LTE with a Smart Jammer Repeated Game

KAUST Repository

Aziz, Farhan

2017-02-22

LTE/LTE-Advanced networks are known to be vulnerable to denial-of-service (DOS) and loss-of-service attacks from smart jammers. The interaction between the network and the smart jammer has been modeled as an infinite-horizon general-sum (non-zero-sum) Bayesian game with asymmetric information, with the network being the uninformed player. Although significant work has been done on optimal strategy computation and control of information revelation of the informed player in repeated asymmetric information games, it has been limited to zero-sum games with perfect monitoring. Recent progress on the strategy computation of the uninformed player is also limited to zero-sum games with perfect monitoring and is focused on expected payoff formulations. Since the proposed formulation is a general-sum game with imperfect monitoring, existing formulations cannot be leveraged for estimating true state of nature (the jammer type). Hence, a threat-based mechanism is proposed for the uninformed player (the network) to estimate the informed player’s type (jammer type). The proposed mechanism helps the network resolve uncertainty about the state of nature (jammer type) so that it can compute a repeated-game strategy conditioned on its estimate. The proposed algorithm does not rely on the commonly assumed “full monitoring” premise, and uses a combination of threat-based mechanism and non-parametric estimation to estimate the jammer type. In addition, it does not require any explicit feedback from the network users nor does it rely on a specific distribution (e.g., Gaussian) of test statistic. It is shown that the proposed algorithm’s estimation performance is quite robust under realistic modeling and observational constraints despite all the aforementioned challenges.

Serine-rich repeat proteins and pili promote Streptococcus agalactiae colonization of the vaginal tract.

Science.gov (United States)

Sheen, Tamsin R; Jimenez, Alyssa; Wang, Nai-Yu; Banerjee, Anirban; van Sorge, Nina M; Doran, Kelly S

2011-12-01

Streptococcus agalactiae (group B streptococcus [GBS]) is a Gram-positive bacterium found in the female rectovaginal tract and is capable of producing severe disease in susceptible hosts, including newborns and pregnant women. The vaginal tract is considered a major reservoir for GBS, and maternal vaginal colonization poses a significant risk to the newborn; however, little is known about the specific bacterial factors that promote GBS colonization and persistence in the female reproductive tract. We have developed in vitro models of GBS interaction with the human female cervicovaginal tract using human vaginal and cervical epithelial cell lines. Analysis of isogenic mutant GBS strains deficient in cell surface organelles such as pili and serine-rich repeat (Srr) proteins shows that these factors contribute to host cell attachment. As Srr proteins are heavily glycosylated, we confirmed that carbohydrate moieties contribute to the effective interaction of Srr-1 with vaginal epithelial cells. Antibody inhibition assays identified keratin 4 as a possible host receptor for Srr-1. Our findings were further substantiated in an in vivo mouse model of GBS vaginal colonization, where mice inoculated with an Srr-1-deficient mutant exhibited decreased GBS vaginal persistence compared to those inoculated with the wild-type (WT) parental strain. Furthermore, competition experiments in mice showed that WT GBS exhibited a significant survival advantage over the ΔpilA or Δsrr-1 mutant in the vaginal tract. Our results suggest that these GBS surface proteins contribute to vaginal colonization and may offer new insights into the mechanisms of vaginal niche establishment.

Holographic perfect fluidity, Cotton energy-momentum duality and transport properties

Energy Technology Data Exchange (ETDEWEB)

Mukhopadhyay, Ayan [Centre de Physique Théorique, Ecole Polytechnique, CNRS UMR 7644,Route de Saclay, 91128 Palaiseau Cedex (France); Institut de Physique Théorique, CEA, CNRS URA 2306,91191 Gif-sur-Yvette (France); Petkou, Anastasios C. [Institute of Theoretical Physics, Department of Physics, Aristotle University of Thessaloniki,54124 Thessaloniki (Greece); Petropoulos, P. Marios; Pozzoli, Valentina [Centre de Physique Théorique, Ecole Polytechnique, CNRS UMR 7644,Route de Saclay, 91128 Palaiseau Cedex (France); Siampos, Konstadinos [Service de Mécanique et Gravitation, Université de Mons, UMONS,20 Place du Parc, 7000 Mons (Belgium)

2014-04-23

We investigate background metrics for 2+1-dimensional holographic theories where the equilibrium solution behaves as a perfect fluid, and admits thus a thermodynamic description. We introduce stationary perfect-Cotton geometries, where the Cotton-York tensor takes the form of the energy-momentum tensor of a perfect fluid, i.e. they are of Petrov type D{sub t}. Fluids in equilibrium in such boundary geometries have non-trivial vorticity. The corresponding bulk can be exactly reconstructed to obtain 3+1-dimensional stationary black-hole solutions with no naked singularities for appropriate values of the black-hole mass. It follows that an infinite number of transport coefficients vanish for holographic fluids. Our results imply an intimate relationship between black-hole uniqueness and holographic perfect equilibrium. They also point towards a Cotton/energy-momentum tensor duality constraining the fluid vorticity, as an intriguing boundary manifestation of the bulk mass/nut duality.

Holographic perfect fluidity, Cotton energy-momentum duality and transport properties

International Nuclear Information System (INIS)

Mukhopadhyay, Ayan; Petkou, Anastasios C.; Petropoulos, P. Marios; Pozzoli, Valentina; Siampos, Konstadinos

2014-01-01

We investigate background metrics for 2+1-dimensional holographic theories where the equilibrium solution behaves as a perfect fluid, and admits thus a thermodynamic description. We introduce stationary perfect-Cotton geometries, where the Cotton-York tensor takes the form of the energy-momentum tensor of a perfect fluid, i.e. they are of Petrov type D t . Fluids in equilibrium in such boundary geometries have non-trivial vorticity. The corresponding bulk can be exactly reconstructed to obtain 3+1-dimensional stationary black-hole solutions with no naked singularities for appropriate values of the black-hole mass. It follows that an infinite number of transport coefficients vanish for holographic fluids. Our results imply an intimate relationship between black-hole uniqueness and holographic perfect equilibrium. They also point towards a Cotton/energy-momentum tensor duality constraining the fluid vorticity, as an intriguing boundary manifestation of the bulk mass/nut duality

Leptospira borgpetersenii hybrid leucine-rich repeat protein: Cloning and expression, immunogenic identification and molecular docking evaluation.

Science.gov (United States)

Sritrakul, Tepyuda; Nitipan, Supachai; Wajjwalku, Worawidh; La-Ard, Anchalee; Suphatpahirapol, Chattip; Petkarnjanapong, Wimol; Ongphiphadhanakul, Boonsong; Prapong, Siriwan

2017-11-01

Leptospirosis is an important zoonotic disease, and the major outbreak of this disease in Thailand in 1999 was due largely to the Leptospira borgpetersenii serovar Sejroe. Identification of the leucine-rich repeat (LRR) LBJ_2271 protein containing immunogenic epitopes and the discovery of the LBJ_2271 ortholog in Leptospira serovar Sejroe, KU_Sej_R21_2271, led to further studies of the antigenic immune properties of KU_Sej_LRR_2271. The recombinant hybrid (rh) protein was created and expressed from a hybrid PCR fragment of KU_Sej_R21_2271 fused with DNA encoding the LBJ_2271 signal sequence for targeting protein as a membrane-anchoring protein. The fusion DNA was cloned into pET160/GW/D-TOPO® to form the pET160_hKU_R21_2271 plasmid. The plasmid was used to express the rhKU_Sej_LRR_2271 protein in Escherichia coli BL21 Star™ (DE3). The expressed protein was immunologically detected by Western blotting and immunoreactivity detection with hyperimmune sera, T cell epitope prediction by HLA allele and epitope peptide binding affinity, and potential T cell reactivity analysis. The immunogenic epitopes of the protein were evaluated and verified by HLA allele and epitope peptide complex structure molecular docking. Among fourteen best allele epitopes of this protein, binding affinity values of 12 allele epitopes remained unchanged compared to LBJ_2271. Two epitopes for alleles HLA-A0202 and -A0301 had higher IC 50 values, while T cell reactivity values of these peptides were better than values from LBJ_2271 epitopes. Eight of twelve epitope peptides had positive T-cell reactivity scores. Although the molecular docking of two epitopes, 3FPLLKEFLV11/47FPLLKEFLV55 and 50KLSTVPEGV58, into an HLA-A0202 model revealed a good fit in the docked structures, 50KLSTVPEGV58 and 94KLSTVPEEV102 are still considered as the proteins' best epitopes for allele HLA-A0202. The results of this study showed that rhKU_Sej_LRR_2271 protein contained natural immunological properties that should

Force Spectroscopy of the Plasmodium falciparum Vaccine Candidate Circumsporozoite Protein Suggests a Mechanically Pliable Repeat Region.

Science.gov (United States)

Patra, Aditya Prasad; Sharma, Shobhona; Ainavarapu, Sri Rama Koti

2017-02-10

The most effective vaccine candidate of malaria is based on the Plasmodium falciparum circumsporozoite protein (CSP), a major surface protein implicated in the structural strength, motility, and immune evasion properties of the infective sporozoites. It is suspected that reversible conformational changes of CSP are required for infection of the mammalian host, but the detailed structure and dynamic properties of CSP remain incompletely understood, limiting our understanding of its function in the infection. Here, we report the structural and mechanical properties of the CSP studied using single-molecule force spectroscopy on several constructs, one including the central region of CSP, which is rich in NANP amino acid repeats (CSP rep ), and a second consisting of a near full-length sequence without the signal and anchor hydrophobic domains (CSP ΔHP ). Our results show that the CSP rep is heterogeneous, with 40% of molecules requiring virtually no mechanical force to unfold (<10 piconewtons (pN)), suggesting that these molecules are mechanically compliant and perhaps act as entropic springs, whereas the remaining 60% are partially structured with low mechanical resistance (∼70 pN). CSP ΔHP having multiple force peaks suggests specifically folded domains, with two major populations possibly indicating the open and collapsed forms. Our findings suggest that the overall low mechanical resistance of the repeat region, exposed on the outer surface of the sporozoites, combined with the flexible full-length conformations of CSP, may provide the sporozoites not only with immune evasion properties, but also with lubricating capacity required during its navigation through the mosquito and vertebrate host tissues. We anticipate that these findings would further assist in the design and development of future malarial vaccines. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

KAUST Repository

Viterbo, David; Michoud, Gregoire; Mosbach, Valentine; Dujon, Bernard; Richard, Guy-Franck

2016-01-01

Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

KAUST Repository

Viterbo, David

2016-03-16

Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

The Potato Nucleotide-binding Leucine-rich Repeat (NLR) Immune Receptor Rx1 Is a Pathogen-dependent DNA-deforming Protein*

Science.gov (United States)

Fenyk, Stepan; Townsend, Philip D.; Dixon, Christopher H.; Spies, Gerhard B.; de San Eustaquio Campillo, Alba; Slootweg, Erik J.; Westerhof, Lotte B.; Gawehns, Fleur K. K.; Knight, Marc R.; Sharples, Gary J.; Goverse, Aska; Pålsson, Lars-Olof; Takken, Frank L. W.; Cann, Martin J.

2015-01-01

Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable cells to respond to pathogen attack. Several NLRs act in the nucleus; however, conserved nuclear targets that support their role in immunity are unknown. Previously, we noted a structural homology between the nucleotide-binding domain of NLRs and DNA replication origin-binding Cdc6/Orc1 proteins. Here we show that the NB-ARC (nucleotide-binding, Apaf-1, R-proteins, and CED-4) domain of the Rx1 NLR of potato binds nucleic acids. Rx1 induces ATP-dependent bending and melting of DNA in vitro, dependent upon a functional P-loop. In situ full-length Rx1 binds nuclear DNA following activation by its cognate pathogen-derived effector protein, the coat protein of potato virus X. In line with its obligatory nucleocytoplasmic distribution, DNA binding was only observed when Rx1 was allowed to freely translocate between both compartments and was activated in the cytoplasm. Immune activation induced by an unrelated NLR-effector pair did not trigger an Rx1-DNA interaction. DNA binding is therefore not merely a consequence of immune activation. These data establish a role for DNA distortion in Rx1 immune signaling and define DNA as a molecular target of an activated NLR. PMID:26306038

Zeroth Poisson Homology, Foliated Cohomology and Perfect Poisson Manifolds

Science.gov (United States)

Martínez-Torres, David; Miranda, Eva

2018-01-01

We prove that, for compact regular Poisson manifolds, the zeroth homology group is isomorphic to the top foliated cohomology group, and we give some applications. In particular, we show that, for regular unimodular Poisson manifolds, top Poisson and foliated cohomology groups are isomorphic. Inspired by the symplectic setting, we define what a perfect Poisson manifold is. We use these Poisson homology computations to provide families of perfect Poisson manifolds.

C-terminal low-complexity sequence repeats of Mycobacterium smegmatis Ku modulate DNA binding.

Science.gov (United States)

Kushwaha, Ambuj K; Grove, Anne

2013-01-24

Ku protein is an integral component of the NHEJ (non-homologous end-joining) pathway of DSB (double-strand break) repair. Both eukaryotic and prokaryotic Ku homologues have been characterized and shown to bind DNA ends. A unique feature of Mycobacterium smegmatis Ku is its basic C-terminal tail that contains several lysine-rich low-complexity PAKKA repeats that are absent from homologues encoded by obligate parasitic mycobacteria. Such PAKKA repeats are also characteristic of mycobacterial Hlp (histone-like protein) for which they have been shown to confer the ability to appose DNA ends. Unexpectedly, removal of the lysine-rich extension enhances DNA-binding affinity, but an interaction between DNA and the PAKKA repeats is indicated by the observation that only full-length Ku forms multiple complexes with a short stem-loop-containing DNA previously designed to accommodate only one Ku dimer. The C-terminal extension promotes DNA end-joining by T4 DNA ligase, suggesting that the PAKKA repeats also contribute to efficient end-joining. We suggest that low-complexity lysine-rich sequences have evolved repeatedly to modulate the function of unrelated DNA-binding proteins.

The Jasmonate-ZIM-Domain Proteins Interact with the WD-Repeat/bHLH/MYB Complexes to Regulate Jasmonate-Mediated Anthocyanin Accumulation and Trichome Initiation in Arabidopsis thaliana[C][W

Science.gov (United States)

Qi, Tiancong; Song, Susheng; Ren, Qingcuo; Wu, Dewei; Huang, Huang; Chen, Yan; Fan, Meng; Peng, Wen; Ren, Chunmei; Xie, Daoxin

2011-01-01

Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)–based SCFCOI1 complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation. PMID:21551388

Implementation of a perfect metamaterial absorber into multi-functional sensor applications

Science.gov (United States)

Akgol, O.; Karaaslan, M.; Unal, E.; Sabah, C.

2017-05-01

Perfect metamaterial absorber (MA)-based sensor applications are presented and investigated in the microwave frequency range. It is also experimentally analyzed and tested to verify the behavior of the MA. Suggested perfect MA-based sensor has a simple configuration which introduces flexibility to sense the dielectric properties of a material and the pressure of the medium. The investigated applications include pressure and density sensing. Besides, numerical simulations verify that the suggested sensor achieves good sensing capabilities for both applications. The proposed perfect MA-based sensor variations enable many potential applications in medical or food technologies.

Hamiltonian formalism for perfect fluids in general relativity

International Nuclear Information System (INIS)

Demaret, J.; Moncrief, V.

1980-01-01

Schutz's Hamiltonian theory of a relativistic perfect fluid, based on the velocity-potential version of classical perfect fluid hydrodynamics as formulated by Seliger and Whitham, is used to derive, in the framework of the Arnowitt, Deser, and Misner (ADM) method, a general partially reduced Hamiltonian for relativistic systems filled with a perfect fluid. The time coordinate is chosen, as in Lund's treatment of collapsing balls of dust, as minus the only velocity potential different from zero in the case of an irrotational and isentropic fluid. A ''semi-Dirac'' method can be applied to quantize astrophysical and cosmological models in the framework of this partially reduced formalism. If one chooses Taub's adapted comoving coordinate system, it is possible to derive a fully reduced ADM Hamiltonian, which is equal to minus the total baryon number of the fluid, generalizing a result previously obtained by Moncrief in the more particular framework of Taub's variational principle, valid for self-gravitating barotropic relativistic perfect fluids. An unconstrained Hamiltonian density is then explicitly derived for a fluid obeying the equation of state p=(gamma-1)rho (1 < or = γ < or = 2), which can adequately describe the phases of very high density attained in a catastrophic collapse or during the early stages of the Universe. This Hamiltonian density, shown to be equivalent to Moncrief's in the particular case of an isentropic fluid, can be simplified for fluid-filled class-A diagonal Bianchi-type cosmological models and appears as a suitable starting point for the study of the canonical quantization of these models

Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage.

Science.gov (United States)

Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J; Rudich, Yinon

2016-03-01

Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perfect transfer of arbitrary states in quantum spin networks

International Nuclear Information System (INIS)

Christandl, Matthias; Kay, Alastair; Datta, Nilanjana; Dorlas, Tony C.; Ekert, Artur; Landahl, Andrew J.

2005-01-01

We propose a class of qubit networks that admit perfect state transfer of any two-dimensional quantum state in a fixed period of time. We further show that such networks can distribute arbitrary entangled states between two distant parties, and can, by using such systems in parallel, transmit the higher-dimensional systems states across the network. Unlike many other schemes for quantum computation and communication, these networks do not require qubit couplings to be switched on and off. When restricted to N-qubit spin networks of identical qubit couplings, we show that 2 log 3 N is the maximal perfect communication distance for hypercube geometries. Moreover, if one allows fixed but different couplings between the qubits then perfect state transfer can be achieved over arbitrarily long distances in a linear chain. This paper expands and extends the work done by Christandl et al., Phys. Rev. Lett. 92, 187902 (2004)

Serine-Rich Repeat Proteins and Pili Promote Streptococcus agalactiae Colonization of the Vaginal Tract ▿

Science.gov (United States)

Sheen, Tamsin R.; Jimenez, Alyssa; Wang, Nai-Yu; Banerjee, Anirban; van Sorge, Nina M.; Doran, Kelly S.

2011-01-01

Streptococcus agalactiae (group B streptococcus [GBS]) is a Gram-positive bacterium found in the female rectovaginal tract and is capable of producing severe disease in susceptible hosts, including newborns and pregnant women. The vaginal tract is considered a major reservoir for GBS, and maternal vaginal colonization poses a significant risk to the newborn; however, little is known about the specific bacterial factors that promote GBS colonization and persistence in the female reproductive tract. We have developed in vitro models of GBS interaction with the human female cervicovaginal tract using human vaginal and cervical epithelial cell lines. Analysis of isogenic mutant GBS strains deficient in cell surface organelles such as pili and serine-rich repeat (Srr) proteins shows that these factors contribute to host cell attachment. As Srr proteins are heavily glycosylated, we confirmed that carbohydrate moieties contribute to the effective interaction of Srr-1 with vaginal epithelial cells. Antibody inhibition assays identified keratin 4 as a possible host receptor for Srr-1. Our findings were further substantiated in an in vivo mouse model of GBS vaginal colonization, where mice inoculated with an Srr-1-deficient mutant exhibited decreased GBS vaginal persistence compared to those inoculated with the wild-type (WT) parental strain. Furthermore, competition experiments in mice showed that WT GBS exhibited a significant survival advantage over the ΔpilA or Δsrr-1 mutant in the vaginal tract. Our results suggest that these GBS surface proteins contribute to vaginal colonization and may offer new insights into the mechanisms of vaginal niche establishment. PMID:21984789

The Perfect Glass Paradigm: Disordered Hyperuniform Glasses Down to Absolute Zero

Science.gov (United States)

Zhang, G.; Stillinger, F. H.; Torquato, S.

2016-11-01

Rapid cooling of liquids below a certain temperature range can result in a transition to glassy states. The traditional understanding of glasses includes their thermodynamic metastability with respect to crystals. However, here we present specific examples of interactions that eliminate the possibilities of crystalline and quasicrystalline phases, while creating mechanically stable amorphous glasses down to absolute zero temperature. We show that this can be accomplished by introducing a new ideal state of matter called a “perfect glass”. A perfect glass represents a soft-interaction analog of the maximally random jammed (MRJ) packings of hard particles. These latter states can be regarded as the epitome of a glass since they are out of equilibrium, maximally disordered, hyperuniform, mechanically rigid with infinite bulk and shear moduli, and can never crystallize due to configuration-space trapping. Our model perfect glass utilizes two-, three-, and four-body soft interactions while simultaneously retaining the salient attributes of the MRJ state. These models constitute a theoretical proof of concept for perfect glasses and broaden our fundamental understanding of glass physics. A novel feature of equilibrium systems of identical particles interacting with the perfect-glass potential at positive temperature is that they have a non-relativistic speed of sound that is infinite.

[INVITED] Coherent perfect absorption of electromagnetic wave in subwavelength structures

Science.gov (United States)

Yan, Chao; Pu, Mingbo; Luo, Jun; Huang, Yijia; Li, Xiong; Ma, Xiaoliang; Luo, Xiangang

2018-05-01

Electromagnetic (EM) absorption is a common process by which the EM energy is transformed into other kinds of energy in the absorber, for example heat. Perfect absorption of EM with structures at subwavelength scale is important for many practical applications, such as stealth technology, thermal control and sensing. Coherent perfect absorption arises from the interplay of interference and absorption, which can be interpreted as a time-reversed process of lasing or EM emitting. It provides a promising way for complete absorption in both nanophotonics and electromagnetics. In this review, we discuss basic principles and properties of a coherent perfect absorber (CPA). Various subwavelength structures including thin films, metamaterials and waveguide-based structures to realize CPAs are compared. We also discuss the potential applications of CPAs.

The Potato Nucleotide-binding Leucine-rich Repeat (NLR) Immune Receptor Rx1 Is a Pathogen-dependent DNA-deforming Protein.

Science.gov (United States)

Fenyk, Stepan; Townsend, Philip D; Dixon, Christopher H; Spies, Gerhard B; de San Eustaquio Campillo, Alba; Slootweg, Erik J; Westerhof, Lotte B; Gawehns, Fleur K K; Knight, Marc R; Sharples, Gary J; Goverse, Aska; Pålsson, Lars-Olof; Takken, Frank L W; Cann, Martin J

2015-10-09

Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable cells to respond to pathogen attack. Several NLRs act in the nucleus; however, conserved nuclear targets that support their role in immunity are unknown. Previously, we noted a structural homology between the nucleotide-binding domain of NLRs and DNA replication origin-binding Cdc6/Orc1 proteins. Here we show that the NB-ARC (nucleotide-binding, Apaf-1, R-proteins, and CED-4) domain of the Rx1 NLR of potato binds nucleic acids. Rx1 induces ATP-dependent bending and melting of DNA in vitro, dependent upon a functional P-loop. In situ full-length Rx1 binds nuclear DNA following activation by its cognate pathogen-derived effector protein, the coat protein of potato virus X. In line with its obligatory nucleocytoplasmic distribution, DNA binding was only observed when Rx1 was allowed to freely translocate between both compartments and was activated in the cytoplasm. Immune activation induced by an unrelated NLR-effector pair did not trigger an Rx1-DNA interaction. DNA binding is therefore not merely a consequence of immune activation. These data establish a role for DNA distortion in Rx1 immune signaling and define DNA as a molecular target of an activated NLR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural model for the interaction of a designed Ankyrin Repeat Protein with the human epidermal growth factor receptor 2.

Directory of Open Access Journals (Sweden)

V Chandana Epa

Full Text Available Designed Ankyrin Repeat Proteins are a class of novel binding proteins that can be selected and evolved to bind to targets with high affinity and specificity. We are interested in the DARPin H10-2-G3, which has been evolved to bind with very high affinity to the human epidermal growth factor receptor 2 (HER2. HER2 is found to be over-expressed in 30% of breast cancers, and is the target for the FDA-approved therapeutic monoclonal antibodies trastuzumab and pertuzumab and small molecule tyrosine kinase inhibitors. Here, we use computational macromolecular docking, coupled with several interface metrics such as shape complementarity, interaction energy, and electrostatic complementarity, to model the structure of the complex between the DARPin H10-2-G3 and HER2. We analyzed the interface between the two proteins and then validated the structural model by showing that selected HER2 point mutations at the putative interface with H10-2-G3 reduce the affinity of binding up to 100-fold without affecting the binding of trastuzumab. Comparisons made with a subsequently solved X-ray crystal structure of the complex yielded a backbone atom root mean square deviation of 0.84-1.14 Ångstroms. The study presented here demonstrates the capability of the computational techniques of structural bioinformatics in generating useful structural models of protein-protein interactions.

Telomerase Repeated Amplification Protocol (TRAP).

Science.gov (United States)

Mender, Ilgen; Shay, Jerry W

2015-11-20

Telomeres are found at the end of eukaryotic linear chromosomes, and proteins that bind to telomeres protect DNA from being recognized as double-strand breaks thus preventing end-to-end fusions (Griffith et al. , 1999). However, due to the end replication problem and other factors such as oxidative damage, the limited life span of cultured cells (Hayflick limit) results in progressive shortening of these protective structures (Hayflick and Moorhead, 1961; Olovnikov, 1973). The ribonucleoprotein enzyme complex telomerase-consisting of a protein catalytic component hTERT and a functional RNA component hTR or hTERC - counteracts telomere shortening by adding telomeric repeats to the end of chromosomes in ~90% of primary human tumors and in some transiently proliferating stem-like cells (Shay and Wright, 1996; Shay and Wright, 2001). This results in continuous proliferation of cells which is a hallmark of cancer. Therefore, telomere biology has a central role in aging, cancer progression/metastasis as well as targeted cancer therapies. There are commonly used methods in telomere biology such as Telomere Restriction Fragment (TRF) (Mender and Shay, 2015b), Telomere Repeat Amplification Protocol (TRAP) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this detailed protocol we describe Telomere Repeat Amplification Protocol (TRAP). The TRAP assay is a popular method to determine telomerase activity in mammalian cells and tissue samples (Kim et al. , 1994). The TRAP assay includes three steps: extension, amplification, and detection of telomerase products. In the extension step, telomeric repeats are added to the telomerase substrate (which is actually a non telomeric oligonucleotide, TS) by telomerase. In the amplification step, the extension products are amplified by the polymerase chain reaction (PCR) using specific primers (TS upstream primer and ACX downstream primer) and in the detection step, the presence or absence of telomerase is

Nonminimal coupling of perfect fluids to curvature

International Nuclear Information System (INIS)

Bertolami, Orfeu; Lobo, Francisco S. N.; Paramos, Jorge

2008-01-01

In this work, we consider different forms of relativistic perfect fluid Lagrangian densities that yield the same gravitational field equations in general relativity (GR). A particularly intriguing example is the case with couplings of the form [1+f 2 (R)]L m , where R is the scalar curvature, which induces an extra force that depends on the form of the Lagrangian density. It has been found that, considering the Lagrangian density L m =p, where p is the pressure, the extra-force vanishes. We argue that this is not the unique choice for the matter Lagrangian density, and that more natural forms for L m do not imply the vanishing of the extra force. Particular attention is paid to the impact on the classical equivalence between different Lagrangian descriptions of a perfect fluid.

Hydrogen can be used as a perfect fuel

International Nuclear Information System (INIS)

Aydin, E.

2005-01-01

At present, hydrogen is one of the new and clean energy production sources. Hydrogen is the perfect partner for electricity, and together they create an integrated energy system based on distributed power generation and use. Hydrogen and electricity are interchangeable using a fuel cell (to convert hydrogen to electricity) or an electrolyzer (for converting electricity to hydrogen). A regenerative fuel cell works either way, converting hydrogen to electricity and vice versa. Hydrogen and electricity are both energy carriers because, unlike naturally occurring hydrocarbon fuels, they must both be produced using a primary energy source. In this study, it will be discussed whether hydrogen is perfect fuel or not

MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection

Directory of Open Access Journals (Sweden)

Gelfi Jacqueline

2010-03-01

Full Text Available Abstract Myxoma virus (MYXV, a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus. Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has drawn considerable attention for its potential role in modulating the host ubiquitin-proteasome system during viral infection. To date, many members of this novel protein family have been shown to interact with SCF components, in vitro. Here, we focus on MNF gene, which has been shown to express a nuclear protein presenting nine ANK repeats, one of which has been identified as a nuclear localization signal. In transfection, MNF has been shown to colocalise with the transcription factor NF-κB in the nucleus of TNFα-stimulated cells. Functionally, MNF is a critical virulence factor since its deletion generates an almost apathogenic virus. In this study, to pursue the investigation of proteins interacting with MNF and of its mechanism of action, we engineered a recombinant MYXV expressing a GFP-linked MNF under the control of MNF native promoter. Infection of rabbits with MYXV-GFPMNF recombinant virus provided the evidence that the GFP fusion does not disturb the main function of MNF. Hence, cells were infected with MYXV-GFPMNF and immunoprecipitation of the GFPMNF fusion protein was performed to identify MNF's partners. For the first time, endogenous components of SCF (Cullin-1 and Skp1 were co-precipitated with an ANK myxoma virus protein, expressed in an infectious context, and without over-expression of any protein.

MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection

Science.gov (United States)

2010-01-01

Myxoma virus (MYXV), a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor) and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has drawn considerable attention for its potential role in modulating the host ubiquitin-proteasome system during viral infection. To date, many members of this novel protein family have been shown to interact with SCF components, in vitro. Here, we focus on MNF gene, which has been shown to express a nuclear protein presenting nine ANK repeats, one of which has been identified as a nuclear localization signal. In transfection, MNF has been shown to colocalise with the transcription factor NF-κB in the nucleus of TNFα-stimulated cells. Functionally, MNF is a critical virulence factor since its deletion generates an almost apathogenic virus. In this study, to pursue the investigation of proteins interacting with MNF and of its mechanism of action, we engineered a recombinant MYXV expressing a GFP-linked MNF under the control of MNF native promoter. Infection of rabbits with MYXV-GFPMNF recombinant virus provided the evidence that the GFP fusion does not disturb the main function of MNF. Hence, cells were infected with MYXV-GFPMNF and immunoprecipitation of the GFPMNF fusion protein was performed to identify MNF's partners. For the first time, endogenous components of SCF (Cullin-1 and Skp1) were co-precipitated with an ANK myxoma virus protein, expressed in an infectious context, and without over-expression of any protein. PMID:20211013

C-terminal sequences of hsp70 and hsp90 as non-specific anchors for tetratricopeptide repeat (TPR) proteins.

Science.gov (United States)

Ramsey, Andrew J; Russell, Lance C; Chinkers, Michael

2009-10-12

Steroid-hormone-receptor maturation is a multi-step process that involves several TPR (tetratricopeptide repeat) proteins that bind to the maturation complex via the C-termini of hsp70 (heat-shock protein 70) and hsp90 (heat-shock protein 90). We produced a random T7 peptide library to investigate the roles played by the C-termini of the two heat-shock proteins in the TPR-hsp interactions. Surprisingly, phages with the MEEVD sequence, found at the C-terminus of hsp90, were not recovered from our biopanning experiments. However, two groups of phages were isolated that bound relatively tightly to HsPP5 (Homo sapiens protein phosphatase 5) TPR. Multiple copies of phages with a C-terminal sequence of LFG were isolated. These phages bound specifically to the TPR domain of HsPP5, although mutation studies produced no evidence that they bound to the domain's hsp90-binding groove. However, the most abundant family obtained in the initial screen had an aspartate residue at the C-terminus. Two members of this family with a C-terminal sequence of VD appeared to bind with approximately the same affinity as the hsp90 C-12 control. A second generation pseudo-random phage library produced a large number of phages with an LD C-terminus. These sequences acted as hsp70 analogues and had relatively low affinities for hsp90-specific TPR domains. Unfortunately, we failed to identify residues near hsp90's C-terminus that impart binding specificity to individual hsp90-TPR interactions. The results suggest that the C-terminal sequences of hsp70 and hsp90 act primarily as non-specific anchors for TPR proteins.

10 CFR 611.108 - Perfection of liens and preservation of collateral.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Perfection of liens and preservation of collateral. 611... of collateral. (a) The Agreement and other documents related thereto shall provide that: (1) DOE and... necessary to perfect and maintain liens, as applicable, on assets which are pledged as collateral for the...

Building the perfect PC

CERN Document Server

Thompson, Robert Bruce

2006-01-01

This popular Build-It-Yourself (BIY) PC book covers everything you want to know about building your own system: Planning and picking out the right components, step-by-step instructions for assembling your perfect PC, and an insightful discussion of why you'd want to do it in the first place. Most big brand computers from HP, Dell and others use lower-quality components so they can meet their aggressive pricing targets. But component manufacturers also make high-quality parts that you can either purchase directly, or obtain through distributors and resellers. Consumers and corporations

Le Perfectionnement en Phonetique (Perfecting Phonetics)

Science.gov (United States)

Laroche-Bouvy, Danielle

1975-01-01

This article describes the programs of the Institut d'Etudes Linguistiques et Phonetiques, located in Paris. The program focuses on perfecting the students' phonetic production of French. Both curriculum and teaching methods are described, as well as a course in phonetics for future teachers of French. (Text is in French.) (CLK)

Do Musicians with Perfect Pitch Have More Autism Traits than Musicians without Perfect Pitch? An Empirical Study

DEFF Research Database (Denmark)

Dohn, Anders; Garza-Villarreal, Eduardo A.; Heaton, Pamela

2012-01-01

Perfect pitch, also known as absolute pitch (AP), refers to the rare ability to identify or produce a musical tone correctly without the benefit of an external reference. AP is often considered to reflect musical giftedness, but it has also been associated with certain disabilities due to increas...

Looking beyond the perfect lens

International Nuclear Information System (INIS)

Wee, W H; Pendry, J B

2010-01-01

The holy grail of imaging is the ability to see through anything. From the conservation of energy, we can easily see that to see through a lossy material would require lenses with gain. The aim of this paper therefore is to propose a simple scheme by which we can construct a general perfect lens, with gain-one that can restore both the phases and amplitudes of near and far fields.

The Present Perfect in World Englishes

Science.gov (United States)

Yao, Xinyue; Collins, Peter

2012-01-01

This paper reports on a comprehensive corpus-based study of regional and stylistic variation in the distribution of the English present perfect. The data represents ten English varieties of both the Inner Circle and Outer Circle, covering four major text types: conversation, news reportage, academic and fictional writing. The results are discussed…

Dual band metamaterial perfect absorber based on Mie resonances

Energy Technology Data Exchange (ETDEWEB)

Liu, Xiaoming; Lan, Chuwen; Li, Bo; Zhou, Ji, E-mail: zhouji@tsinghua.edu.cn [State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Bi, Ke [School of Science, Beijing University of Posts and Telecommunications, Beijing 100876 (China); Zhao, Qian [State Key Lab of Tribology, Department of Precision Instruments and Mechanology, Tsinghua University, Beijing 100084 (China)

2016-08-08

We numerically and experimentally demonstrated a polarization insensitive dual-band metamaterial perfect absorber working in wide incident angles based on the two magnetic Mie resonances of a single dielectric “atom” with simple structure. Two absorption bands with simulated absorptivity of 99% and 96%, experimental absorptivity of 97% and 94% at 8.45 and 11.97 GHz were achieved due to the simultaneous magnetic and electric resonances in dielectric “atom” and copper plate. Mie resonances of dielectric “atom” provide a simple way to design metamaterial perfect absorbers with high symmetry.

Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

Directory of Open Access Journals (Sweden)

Ana ePalomino

2014-03-01

Full Text Available Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression (CB1 receptors and enzymes that produce (DAGLα/β and NAPE-PLD and degrade (MAGL and FAAH eCB were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system (glutamate synthesizing enzymes LGA and KGA, mGluR3/5 metabotropic receptors, and NR1/2A/2B/2C-NMDA and GluR1/2/3/4-AMPA ionotropic receptor subunits and the gene expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-AG production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that

The perfect family: decision making in biparental care.

Science.gov (United States)

Akçay, Erol; Roughgarden, Joan

2009-10-13

Previous theoretical work on parental decisions in biparental care has emphasized the role of the conflict between evolutionary interests of parents in these decisions. A prominent prediction from this work is that parents should compensate for decreases in each other's effort, but only partially so. However, experimental tests that manipulate parents and measure their responses fail to confirm this prediction. At the same time, the process of parental decision making has remained unexplored theoretically. We develop a model to address the discrepancy between experiments and the theoretical prediction, and explore how assuming different decision making processes changes the prediction from the theory. We assume that parents make decisions in behavioral time. They have a fixed time budget, and allocate it between two parental tasks: provisioning the offspring and defending the nest. The proximate determinant of the allocation decisions are parents' behavioral objectives. We assume both parents aim to maximize the offspring production from the nest. Experimental manipulations change the shape of the nest production function. We consider two different scenarios for how parents make decisions: one where parents communicate with each other and act together (the perfect family), and one where they do not communicate, and act independently (the almost perfect family). The perfect family model is able to generate all the types of responses seen in experimental studies. The kind of response predicted depends on the nest production function, i.e. how parents' allocations affect offspring production, and the type of experimental manipulation. In particular, we find that complementarity of parents' allocations promotes matching responses. In contrast, the relative responses do not depend on the type of manipulation in the almost perfect family model. These results highlight the importance of the interaction between nest production function and how parents make decisions

The perfect family: decision making in biparental care.

Directory of Open Access Journals (Sweden)

Erol Akçay

Full Text Available Previous theoretical work on parental decisions in biparental care has emphasized the role of the conflict between evolutionary interests of parents in these decisions. A prominent prediction from this work is that parents should compensate for decreases in each other's effort, but only partially so. However, experimental tests that manipulate parents and measure their responses fail to confirm this prediction. At the same time, the process of parental decision making has remained unexplored theoretically. We develop a model to address the discrepancy between experiments and the theoretical prediction, and explore how assuming different decision making processes changes the prediction from the theory.We assume that parents make decisions in behavioral time. They have a fixed time budget, and allocate it between two parental tasks: provisioning the offspring and defending the nest. The proximate determinant of the allocation decisions are parents' behavioral objectives. We assume both parents aim to maximize the offspring production from the nest. Experimental manipulations change the shape of the nest production function. We consider two different scenarios for how parents make decisions: one where parents communicate with each other and act together (the perfect family, and one where they do not communicate, and act independently (the almost perfect family.The perfect family model is able to generate all the types of responses seen in experimental studies. The kind of response predicted depends on the nest production function, i.e. how parents' allocations affect offspring production, and the type of experimental manipulation. In particular, we find that complementarity of parents' allocations promotes matching responses. In contrast, the relative responses do not depend on the type of manipulation in the almost perfect family model. These results highlight the importance of the interaction between nest production function and how parents make

Tunable THz perfect absorber with two absorption peaks based on graphene microribbons

DEFF Research Database (Denmark)

Gu, Mingyue; Xiao, Binggang; Xiao, Sanshui

2018-01-01

Perfect absorption is characterised by the complete suppression of incident and reflected electromagnetic wave, and complete dissipation of the incident energy. A tunable perfect terahertz (THz) absorber with two absorption peaks based on graphene is presented. The proposed structure consists of ...

AN FDTD ALGORITHM WITH PERFECTLY MATCHED LAYERS FOR CONDUCTIVE MEDIA. (R825225)

Science.gov (United States)

We extend Berenger's perfectly matched layers (PML) to conductive media. A finite-difference-time-domain (FDTD) algorithm with PML as an absorbing boundary condition is developed for solutions of Maxwell's equations in inhomogeneous, conductive media. For a perfectly matched laye...

Whole genome association mapping by incompatibilities and local perfect phylogenies

DEFF Research Database (Denmark)

Mailund, Thomas; Besenbacher, Søren; Schierup, Mikkel Heide

2006-01-01

around each marker that is compatible with a single phylogenetic tree. This perfect phylogenetic tree is treated as a decision tree for determining disease status, and scored by its accuracy as a decision tree. The rationale for this is that the perfect phylogeny near a disease affecting mutation should...... a fast method for accurate localisation of disease causing variants in high density case-control association mapping experiments with large numbers of cases and controls. The method searches for significant clustering of case chromosomes in the "perfect" phylogenetic tree defined by the largest region...... provide more information about the affected/unaffected classification than random trees. If regions of compatibility contain few markers, due to e.g. large marker spacing, the algorithm can allow the inclusion of incompatibility markers in order to enlarge the regions prior to estimating their phylogeny...

Perfect commuting-operator strategies for linear system games

Science.gov (United States)

Cleve, Richard; Liu, Li; Slofstra, William

2017-01-01

Linear system games are a generalization of Mermin's magic square game introduced by Cleve and Mittal. They show that perfect strategies for linear system games in the tensor-product model of entanglement correspond to finite-dimensional operator solutions of a certain set of non-commutative equations. We investigate linear system games in the commuting-operator model of entanglement, where Alice and Bob's measurement operators act on a joint Hilbert space, and Alice's operators must commute with Bob's operators. We show that perfect strategies in this model correspond to possibly infinite-dimensional operator solutions of the non-commutative equations. The proof is based around a finitely presented group associated with the linear system which arises from the non-commutative equations.

Identification of histone H4-like TAF in Schizosaccharomyces pombe as a protein that interacts with WD repeat-containing TAF

OpenAIRE

Mitsuzawa, Hiroshi; Ishihama, Akira

2002-01-01

The general transcription factor TFIID consists of the TATA-binding protein (TBP) and multiple TBP-associated factors (TAFs). We previously identified two distinct WD repeat-containing TAFs, spTAF72 and spTAF73, in the fission yeast Schizosaccharomyces pombe. Here we report the identification of another S.pombe TAF, spTAF50, which is the S.pombe homolog of histone H4-like TAFs such as human TAF80, Drosophila TAF60 and Saccharomyces cerevisiae TAF60. spTAF50 was identified in a two-hybrid scre...

An Infinite Family of Circulant Graphs with Perfect State Transfer in Discrete Quantum Walks

OpenAIRE

Zhan, Hanmeng

2017-01-01

We study perfect state transfer in a discrete quantum walk. In particular, we show that there are infinitely many $4$-regular circulant graphs that admit perfect state transfer between antipodal vertices. To the best of our knowledge, previously there was no infinite family of $k$-regular graphs with perfect state transfer, for any $k\\ge 3$.

Repeatability indices for the Adams D-15 test for colour-normal and colour-defective adults.

Science.gov (United States)

Hovis, Jeffery K; Ramaswamy, Shankaran; Anderson, Matthew

2004-07-01

The Adams desaturated D-15 test was administered to individuals with normal colour vision or with congenital red-green colour vision defects to establish the repeatability of the test. One hundred subjects with normal colour vision and 64 subjects with defective colour vision participated in the study. Results were analysed from two different sessions to determine the repeatability of the test for different pass/fail criteria. The test was scored using both visual inspection of the score sheet and the modified Colour Difference Vector analysis (CDV) program. For both subject groups, the repeatability was lowest when a perfect arrangement was required for a pass and improved as more errors were allowed. The improvement in repeatability was greatest as the failure criterion changed from 'any mistake' to 'more than two crossings'. The kappa coefficient for the reliability of the defect classification was 0.38 for visual inspection and 0.59 for the CDV analysis. All the protans who failed the test at both sessions were classified correctly. Approximately 98 per cent of the colour-normals and 82 per cent of the colour-defectives would have the same pass/fail outcome on the Adams D-15 test conducted several days apart when the failure criterion was either one or more or two or more crossings. Individuals who make less than four crossings on the Adams D-15 should repeat the test to ensure confidence in the pass/fail result.

Robust Secure Authentication and Data Storage with Perfect Secrecy

Directory of Open Access Journals (Sweden)

Sebastian Baur

2018-04-01

Full Text Available We consider an authentication process that makes use of biometric data or the output of a physical unclonable function (PUF, respectively, from an information theoretical point of view. We analyse different definitions of achievability for the authentication model. For the secrecy of the key generated for authentication, these definitions differ in their requirements. In the first work on PUF based authentication, weak secrecy has been used and the corresponding capacity regions have been characterized. The disadvantages of weak secrecy are well known. The ultimate performance criteria for the key are perfect secrecy together with uniform distribution of the key. We derive the corresponding capacity region. We show that, for perfect secrecy and uniform distribution of the key, we can achieve the same rates as for weak secrecy together with a weaker requirement on the distribution of the key. In the classical works on PUF based authentication, it is assumed that the source statistics are known perfectly. This requirement is rarely met in applications. That is why the model is generalized to a compound model, taking into account source uncertainty. We also derive the capacity region for the compound model requiring perfect secrecy. Additionally, we consider results for secure storage using a biometric or PUF source that follow directly from the results for authentication. We also generalize known results for this problem by weakening the assumption concerning the distribution of the data that shall be stored. This allows us to combine source compression and secure storage.

Perfect lensing with phase-conjugating surfaces: toward practical realization

International Nuclear Information System (INIS)

Maslovski, Stanislav; Tretyakov, Sergei

2012-01-01

It is theoretically known that a pair of phase-conjugating surfaces can function as a perfect lens, focusing propagating waves and enhancing evanescent waves. However, the known experimental approaches based on thin sheets of nonlinear materials cannot fully realize the required phase conjugation boundary condition. In this paper, we show that the ideal phase-conjugating surface is, in principle, physically realizable and investigate the necessary properties of nonlinear and nonreciprocal particles which can be used to build a perfect lens system. The physical principle of the lens operation is discussed in detail and directions of possible experimental realizations are outlined. (paper)

Protein profiling of cerebrospinal fluid

DEFF Research Database (Denmark)

Simonsen, Anja H

2012-01-01

The cerebrospinal fluid (CSF) perfuses the brain and spinal cord. CSF contains proteins and peptides important for brain physiology and potentially also relevant for brain pathology. Hence, CSF is the perfect source to search for new biomarkers to improve diagnosis of neurological diseases as well...

A hybrid of monopoly and perfect competition model for hi-tech products

Science.gov (United States)

Yang, P. C.; Wee, H. M.; Pai, S.; Yang, H. J.; Wee, P. K. P.

2010-11-01

For Hi-tech products, the demand rate, the component cost as well as the selling price usually decline significantly with time. In the case of perfect competition, shortages usually result in lost sales; while in a monopoly, shortages will be completely backordered. However, neither perfect competition nor monopoly exists. Therefore, there is a need to develop a replenishment model considering a hybrid of perfect competition and monopoly when the cost, price and demand are decreasing simultaneously. A numerical example and sensitivity analysis are carried out to illustrate this model. The results show that a higher decline-rate in the component cost leads to a smaller service level and a larger replenishment interval. When the component cost decline rate increases and the selling price decline rate decreases simultaneously, the replenishment interval decreases. In perfect competition it is better to have a high service level, while for the case with monopoly, keeping a low service level is better due to complete backordering.

What is anthropological about The Perfect Human?

DEFF Research Database (Denmark)

Thomsen, Line Hassall

2015-01-01

Jørgen Leth has classified The Perfect Human as an anthropological film. But is the film anthropological at all? This article explores Leth’s connections with anthropology and finds that he is more inspired by anthropological framing than he is by anthropological research methods....

Diffraction of love waves by two staggered perfectly weak half-planes

International Nuclear Information System (INIS)

Asghar, S.; Zaman, F.D.; Sajida Asghar

1989-01-01

Love wave travelling in a layer of uniform thickness overlying a half-space is assumed to be incident on two parallel but staggered perfectly weak half-planes lying in the upper layer. The diffracted fields is calculated using the modified Wiener-Hopf technique and contour integration method. The diffracted waves satisfy the dispersion relations appropriate to different regions formed by the perfectly weak half-planes

Oxidative stress adaptation with acute, chronic, and repeated stress.

Science.gov (United States)

Pickering, Andrew M; Vojtovich, Lesya; Tower, John; A Davies, Kelvin J

2013-02-01

Oxidative stress adaptation, or hormesis, is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells and the fruit fly Drosophila melanogaster are capable of adapting to chronic or repeated stress by upregulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12-h or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the levels of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila nevertheless also caused significant reductions in life span for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life. Copyright © 2012 Elsevier Inc. All rights reserved.

Maxwell's fish-eye lens and the mirage of perfect imaging

International Nuclear Information System (INIS)

Merlin, R

2011-01-01

Recent claims that Maxwell's fish-eye is a perfect lens, capable of providing images with deep subwavelength resolution, are examined. We show that the imaging properties of a dispersionless fish-eye are very similar to those of an ideal spherical cavity. Using this correspondence, we prove that the correct solution to Maxwell equations in the fish-eye gives image sizes that are consistent with the standard diffraction limit. Perfect focusing is an optical illusion that results from placing a time-reversed source at the position of the geometrical image which, when combined with the field due to the primary (object) source, mimics the behavior of a perfect drain. Issues of causality are briefly discussed. We also demonstrate that passive outlets are not a good alternative to time-reversed sources for broadband drain-like behavior and that, even if they were, they could not do a better job than conventional optical systems at providing high resolution

Making perfect life : bio-engineering (in) the 21st century : interim study

NARCIS (Netherlands)

Est, van R.; Keulen, van I.; Geesink, I.; Schuiff, M.

2010-01-01

Reportnumber: PE 438.829; This document is the result of the preparatory phase of the STOA-project "Making perfect life", that defined the project focus. This resulted in the study document Making Perfect Life: Bio-engineering (in) the 21st century. A project plan for the next two phases was

Hit by a Perfect Storm? Art & Design in the National Student Survey

Science.gov (United States)

Yorke, Mantz; Orr, Susan; Blair, Bernadette

2014-01-01

There has long been the suspicion amongst staff in Art & Design that the ratings given to their subject disciplines in the UK's National Student Survey are adversely affected by a combination of circumstances--a "perfect storm". The "perfect storm" proposition is tested by comparing ratings for Art & Design with those…

Tie-breaking in games of perfect information

DEFF Research Database (Denmark)

Tranæs, Torben

1998-01-01

The paper suggests that ties in an extensive form game have strategic implications if they represent credible threats or promises. We consider a subset of subgame-perfect Nash equilibria obtained by breaking ties according to their strategic implications, and show that the subset is nonempty for ...

The near-symmetry of proteins.

Science.gov (United States)

Bonjack-Shterengartz, Maayan; Avnir, David

2015-04-01

The majority of protein oligomers form clusters which are nearly symmetric. Understanding of that imperfection, its origins, and perhaps also its advantages requires the conversion of the currently used vague qualitative descriptive language of the near-symmetry into an accurate quantitative measure that will allow to answer questions such as: "What is the degree of symmetry deviation of the protein?," "how do these deviations compare within a family of proteins?," and so on. We developed quantitative methods to answer this type of questions, which are capable of analyzing the whole protein, its backbone or selected portions of it, down to comparison of symmetry-related specific amino-acids, and which are capable of visualizing the various levels of symmetry deviations in the form of symmetry maps. We have applied these methods on an extensive list of homomers and heteromers and found that apparently all proteins never reach perfect symmetry. Strikingly, even homomeric protein clusters are never ideally symmetric. We also found that the main burden of symmetry distortion is on the amino-acids near the symmetry axis; that it is mainly the more hydrophilic amino-acids that take place in symmetry-distortive interactions; and more. The remarkable ability of heteromers to preserve near-symmetry, despite the different sequences, was also shown and analyzed. The comprehensive literature on the suggested advantages symmetric oligomerizations raises a yet-unsolved key question: If symmetry is so advantageous, why do proteins stop shy of perfect symmetry? Some tentative answers to be tested in further studies are suggested in a concluding outlook. © 2014 Wiley Periodicals, Inc.

A not-so-short description of the PERFECT platform

International Nuclear Information System (INIS)

Bugat, S.; Zeghadi, A.; Adjanor, G.

2010-01-01

This article describes the building of the so-called 'PERFECT platform', which main issue was to allow the development of the PERFECT end-products dedicated to the prediction of the degradation of material properties due to irradiation. First, the general principles used to build the platform are detailed. Such principles guided the choices of preferential development language, architecture, and operating system. The architecture of the platform is then described. It allows an easy development of the end-products, and a 'black-box' integration of the codes developed during the project. Each end-product can be seen as a sequence of modules, each module representing a physical phenomenon in time and space. The platform is very flexible, so that different methodologies can be tested and compared inside an end-product. The second part is devoted to the description of a classical PERFECT study, defined thanks to the graphical user interface developed in the project. Focus is made in particular on how a selection of modules is done, how the input data can be entered, and how the study execution is fully controlled by the user. A final description of the post-processing facilities on the results is exposed.

Effective high-order solver with thermally perfect gas model for hypersonic heating prediction

International Nuclear Information System (INIS)

Jiang, Zhenhua; Yan, Chao; Yu, Jian; Qu, Feng; Ma, Libin

2016-01-01

Highlights: • Design proper numerical flux for thermally perfect gas. • Line-implicit LUSGS enhances efficiency without extra memory consumption. • Develop unified framework for both second-order MUSCL and fifth-order WENO. • The designed gas model can be applied to much wider temperature range. - Abstract: Effective high-order solver based on the model of thermally perfect gas has been developed for hypersonic heat transfer computation. The technique of polynomial curve fit coupling to thermodynamics equation is suggested to establish the current model and particular attention has been paid to the design of proper numerical flux for thermally perfect gas. We present procedures that unify five-order WENO (Weighted Essentially Non-Oscillatory) scheme in the existing second-order finite volume framework and a line-implicit method that improves the computational efficiency without increasing memory consumption. A variety of hypersonic viscous flows are performed to examine the capability of the resulted high order thermally perfect gas solver. Numerical results demonstrate its superior performance compared to low-order calorically perfect gas method and indicate its potential application to hypersonic heating predictions for real-life problem.

The Perfect Eye A Novel Model for Teaching the Theory of Refraction.

Science.gov (United States)

Kurtz, Daniel

1999-01-01

The Perfect Eye model simplifies solutions to a wide variety of optometry instructional problems by facilitating student understanding of the interaction among lenses, objects, accommodation, and ametropia. The model is based on the premise that inside every eye is a perfect (emmetropic) eye, and that the physiological eye is a combination of the…

Computational study of the human dystrophin repeats: interaction properties and molecular dynamics.

Directory of Open Access Journals (Sweden)

Baptiste Legrand

Full Text Available Dystrophin is a large protein involved in the rare genetic disease Duchenne muscular dystrophy (DMD. It functions as a mechanical linker between the cytoskeleton and the sarcolemma, and is able to resist shear stresses during muscle activity. In all, 75% of the dystrophin molecule consists of a large central rod domain made up of 24 repeat units that share high structural homology with spectrin-like repeats. However, in the absence of any high-resolution structure of these repeats, the molecular basis of dystrophin central domain's functions has not yet been deciphered. In this context, we have performed a computational study of the whole dystrophin central rod domain based on the rational homology modeling of successive and overlapping tandem repeats and the analysis of their surface properties. Each tandem repeat has very specific surface properties that make it unique. However, the repeats share enough electrostatic-surface similarities to be grouped into four separate clusters. Molecular dynamics simulations of four representative tandem repeats reveal specific flexibility or bending properties depending on the repeat sequence. We thus suggest that the dystrophin central rod domain is constituted of seven biologically relevant sub-domains. Our results provide evidence for the role of the dystrophin central rod domain as a scaffold platform with a wide range of surface features and biophysical properties allowing it to interact with its various known partners such as proteins and membrane lipids. This new integrative view is strongly supported by the previous experimental works that investigated the isolated domains and the observed heterogeneity of the severity of dystrophin related pathologies, especially Becker muscular dystrophy.

Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).

Science.gov (United States)

Xu, Jin-Gen; Huang, Chunfeng; Yang, Zhengfeng; Jin, Mengmeng; Fu, Panhan; Zhang, Ni; Luo, Jian; Li, Dali; Liu, Mingyao; Zhou, Yan; Zhu, Yongqun

2015-01-23

Leucine-rich repeat G-protein-coupled receptors (LGRs) are a unique class of G-protein-coupled receptors characterized by a large extracellular domain to recognize ligands and regulate many important developmental processes. Among the three groups of LGRs, group B members (LGR4-6) recognize R-spondin family proteins (Rspo1-4) to stimulate Wnt signaling. In this study, we successfully utilized the "hybrid leucine-rich repeat technique," which fused LGR4 with the hagfish VLR protein, to obtain two recombinant human LGR4 proteins, LGR415 and LGR49. We determined the crystal structures of ligand-free LGR415 and the LGR49-Rspo1 complex. LGR4 exhibits a twisted horseshoe-like structure. Rspo1 adopts a flat and β-fold architecture and is bound in the concave surface of LGR4 in the complex through electrostatic and hydrophobic interactions. All the Rspo1-binding residues are conserved in LGR4-6, suggesting that LGR4-6 bind R-spondins through an identical surface. Structural analysis of our LGR4-Rspo1 complex with the previously determined LGR4 and LGR5 structures revealed that the concave surface of LGR4 is the sole binding site for R-spondins, suggesting a one-site binding model of LGR4-6 in ligand recognition. The molecular mechanism of LGR4-6 is distinct from the two-step mechanism of group A receptors LGR1-3 and the multiple-interface binding model of group C receptors LGR7-8, suggesting LGRs utilize the divergent mechanisms for ligand recognition. Our structures, together with previous reports, provide a comprehensive understanding of the ligand recognition by LGRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

On the Contribution of Slovenian Linguistics to the History of the Ancient Greek Perfect

Directory of Open Access Journals (Sweden)

Jerneja Kavčič

2010-12-01

Full Text Available An important contribution to the history of the Ancient Greek perfect is the study of Erika Mihevc-Gabrovec, The Disappearance of the Perfect in Late Greek (La disparition du parfait dans le grec de la basse époque. In terms of theory and content, her study continues the work of Pierre Chantraine, but somewhat diverges from her predecessor’s views on the issue of the merger between the aorist and the perfect, identifying examples of the use of the perfect even in an – according to Pierre Chantraine – relatively late period.  Some years after the publication of Erika Mihevc-Gabrovec’s book, the question of when the aorist and the perfect may have merged was raised again, to be addressed by McKay in a number of articles. Today, the views on the subject are strongly divided.   As argued by the author of this paper, one of the setbacks in examining the merger between the aorist and the perfect concerns the methodology, since researchers have tended to rely exclusively on their sense of language. A possible new approach is offered in the framework of the Slovenian theory of Natural Syntax, which has from the start paid considerable attention to English sentences of the I believe her to be intelligent type. The paper describes similar sentences in New Testament Greek, terming them “sentences of the λέγουσινἀνάστασινμὴεἶναι type”. In New Testament Greek, they display a tendency to use the present infinitive of stative verbs; relatively frequent is also the perfect infinitive (of non-stative verbs, while, as already noted in other studies, these sentences – at least in New Testament Greek – avoid the aorist infinitive. Such sentences thus bear witness to the fact that the aorist and the perfect were not fully interchangeable in New Testament Greek; the status of the aorist and perfect infinitives in sentences of the λέγουσινἀνάστασινμὴεἶναι type should also be taken into

Perfectly Secure Oblivious RAM without Random Oracles

DEFF Research Database (Denmark)

Damgård, Ivan Bjerre; Meldgaard, Sigurd Torkel; Nielsen, Jesper Buus

2011-01-01

We present an algorithm for implementing a secure oblivious RAM where the access pattern is perfectly hidden in the information theoretic sense, without assuming that the CPU has access to a random oracle. In addition we prove a lower bound on the amount of randomness needed for implementing...

The proliferation marker pKi-67 becomes masked to MIB-1 staining after expression of its tandem repeats.

Science.gov (United States)

Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Duchrow, Michael

2002-11-01

The Ki-67 antigen, pKi-67, is one of the most commonly used markers of proliferating cells. The protein can only be detected in dividing cells (G(1)-, S-, G(2)-, and M-phase) but not in quiescent cells (G(0)). The standard antibody to detect pKi-67 is MIB-1, which detects the so-called 'Ki-67 motif' FKELF in 9 of the protein's 16 tandem repeats. To investigate the function of these repeats we expressed three of them in an inducible gene expression system in HeLa cells. Surprisingly, addition of a nuclear localization sequence led to a complete absence of signal in the nuclei of MIB-1-stained cells. At the same time antibodies directed against different epitopes of pKi-67 did not fail to detect the protein. We conclude that the overexpression of the 'Ki-67 motif', which is present in the repeats, can lead to inability of MIB-1 to detect its antigen as demonstrated in adenocarcinoma tissue samples. Thereafter, in order to prevent the underestimation of Ki-67 proliferation indices in MIB-1-labeled preparations, additional antibodies (for example, MIB-21) should be used. Additionally, we could show in a mammalian two-hybrid assay that recombinant pKi-67 repeats are capable of self-associating with endogenous pKi-67. Speculating that the tandem repeats are intimately involved in its protein-protein interactions, this offers new insights in how access to these repeats is regulated by pKi-67 itself.

Perfect Fluid Theory and its Extensions

OpenAIRE

Jackiw, R.; Nair, V. P.; Pi, S. -Y.; Polychronakos, A. P.

2004-01-01

We review the canonical theory for perfect fluids, in Eulerian and Lagrangian formulations. The theory is related to a description of extended structures in higher dimensions. Internal symmetry and supersymmetry degrees of freedom are incorporated. Additional miscellaneous subjects that are covered include physical topics concerning quantization, as well as mathematical issues of volume preserving diffeomorphisms and representations of Chern-Simons terms (= vortex or magnetic helicity).

On the perfect hexagonal packing of rods

International Nuclear Information System (INIS)

Starostin, E L

2006-01-01

In most cases the hexagonal packing of fibrous structures or rods extremizes the energy of interaction between strands. If the strands are not straight, then it is still possible to form a perfect hexatic bundle. Conditions under which the perfect hexagonal packing of curved tubular structures may exist are formulated. Particular attention is given to closed or cycled arrangements of the rods like in the DNA toroids and spools. The closure or return constraints of the bundle result in an allowable group of automorphisms of the cross-sectional hexagonal lattice. The structure of this group is explored. Examples of open helical-like and closed toroidal-like bundles are presented. An expression for the elastic energy of a perfectly packed bundle of thin elastic rods is derived. The energy accounts for both the bending and torsional stiffnesses of the rods. It is shown that equilibria of the bundle correspond to solutions of a variational problem formulated for the curve representing the axis of the bundle. The functional involves a function of the squared curvature under the constraints on the total torsion and the length. The Euler-Lagrange equations are obtained in terms of curvature and torsion and due to the existence of the first integrals the problem is reduced to the quadrature. The three-dimensional shape of the bundle may be readily reconstructed by integration of the Ilyukhin-type equations in special cylindrical coordinates. The results are of universal nature and are applicable to various fibrous structures, in particular, to intramolecular liquid crystals formed by DNA condensed in toroids or packed inside the viral capsids

Perfect state of Cryptococcus neoformans, Filobasidiella neoformans, on pigeon manure filtrate agar

Energy Technology Data Exchange (ETDEWEB)

Staib, F.

1981-02-01

To enable studies of the dependence of Cryptococcus neoformans and its perfect and imperfect states upon bird manure as a habitat of this pathogen, a nutrient medium closely resembling natural conditions was prepared. As sole nutrient, the water soluble ingredients of manure from pigeons (Columbia livia) were used. There was no heat sterilization of the manure filtrate. Using a standard pair of C. neoformans strains for mating, it could be demonstrated that the perfect state of the fungus developed on this so called pigeon manure filtrate agar within 48 h at 26 degrees C. This medium is supposed to help in the elucidation of the epidemiological significance of the perfect and imperfect states of this pathogen.

Hyper-Achievement, Perfection, and College Student Resilience

Science.gov (United States)

Eells, Gregory T.

2017-01-01

Over the past decade, there has been considerable attention given to college students' experience of pressure to pursue perfection through hyper-achievement and the psychological and emotional toll this process takes on them. The popular press has highlighted this phenomenon and raised specific questions about some of the related consequences like…

Generalized magneto-thermoviscoelasticity in a perfectly conducting ...

Indian Academy of Sciences (India)

on the theory of generalized thermoelastic diffusion with one relaxation time. ... cavity is taken to be traction free and subjected to both heating and external constant ... problems on wave propagation in a linear viscoelas- ... Let us consider a perfect electric conductor medium ... The energy equation in the context of general-.

Concerted evolution of the tandemly repeated genes encoding primate U2 small nuclear RNA (the RNU2 locus) does not prevent rapid diversification of the (CT){sub n} {center_dot} (GA){sub n} microsatellite embedded within the U2 repeat unit

Energy Technology Data Exchange (ETDEWEB)

Liao, D.; Weiner, A.M. [Yale Univ., New Haven, CT (United States)

1995-12-10

The RNU2 locus encoding human U2 small nuclear RNA (snRNA) is organized as a nearly perfect tandem array containing 5 to 22 copies of a 5.8-kb repeat unit. Just downstream of the U2 snRNA gene in each 5.8-kb repeat unit lies a large (CT){sub n}{center_dot}(GA){sub n} dinucleotide repeat (n {approx} 70). This form of genomic organization, in which one repeat is embedded within another, provides an unusual opportunity to study the balance of forces maintaining the homogeneity of both kinds of repeats. Using a combination of field inversion gel electrophoresis and polymerase chain reaction, we have been able to study the CT microsatellites within individual U2 tandem arrays. We find that the CT microsatellites within an RNU2 allele exhibit significant length polymorphism, despite the remarkable homogeneity of the surrounding U2 repeat units. Length polymorphism is due primarily to loss or gain of CT dinucleotide repeats, but other types of deletions, insertions, and substitutions are also frequent. Polymorphism is greatly reduced in regions where pure (CT){sub n} tracts are interrupted by occasional G residues, suggesting that irregularities stabilize both the length and the sequence of the dinucleotide repeat. We further show that the RNU2 loci of other catarrhine primates (gorilla, chimpanzee, ogangutan, and baboon) contain orthologous CT microsatellites; these also exhibit length polymorphism, but are highly divergent from each other. Thus, although the CT microsatellite is evolving far more rapidly than the rest of the U2 repeat unit, it has persisted through multiple speciation events spanning >35 Myr. The persistence of the CT microsatellite, despite polymorphism and rapid evolution, suggests that it might play a functional role in concerted evolution of the RNU2 loci, perhaps as an initiation site for recombination and/or gene conversion. 70 refs., 5 figs.

Group B streptococcal serine-rich repeat proteins promote interaction with fibrinogen and vaginal colonization.

Science.gov (United States)

Wang, Nai-Yu; Patras, Kathryn A; Seo, Ho Seong; Cavaco, Courtney K; Rösler, Berenice; Neely, Melody N; Sullam, Paul M; Doran, Kelly S

2014-09-15

Group B streptococcus (GBS) can cause severe disease in susceptible hosts, including newborns, pregnant women, and the elderly. GBS serine-rich repeat (Srr) surface glycoproteins are important adhesins/invasins in multiple host tissues, including the vagina. However, exact molecular mechanisms contributing to their importance in colonization are unknown. We have recently determined that Srr proteins contain a fibrinogen-binding region (BR) and hypothesize that Srr-mediated fibrinogen binding may contribute to GBS cervicovaginal colonization. In this study, we observed that fibrinogen enhanced wild-type GBS attachment to cervical and vaginal epithelium, and that this was dependent on Srr1. Moreover, purified Srr1-BR peptide bound directly to host cells, and peptide administration in vivo reduced GBS recovery from the vaginal tract. Furthermore, a GBS mutant strain lacking only the Srr1 "latching" domain exhibited decreased adherence in vitro and decreased persistence in a mouse model of GBS vaginal colonization, suggesting the importance of Srr-fibrinogen interactions in the female reproductive tract. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

On a ''conformal'' perfect fluid in the classical vacuum

International Nuclear Information System (INIS)

Culetu, H.

1993-02-01

A possible existence of a conformal perfect fluid in the classical vacuum is investigated in this letter. It is shown, contrary to Madsen's opinion, that the scalar field stress tensor acquires a perfect fluid form even with a nonminimal coupling (ξ = 1/6) in the Einstein Lagrangian, provided the geometry is the Lorentzian analogue of the Euclidean Hawking wormhole. In addition, our T μν equals (up to a constant factor) the vacuum expectation value of the Fulling stress tensor for a massless scalar field and Visser's one concerning transversible wormholes. On the other side of the light cone, there is a coordinate system (the dimensionally reduced Witten bubble) where the stress tensor becomes diagonal. (author). 13 refs

Were protein internal repeats formed by "bricolage"?

Science.gov (United States)

Lavorgna, G; Patthy, L; Boncinelli, E

2001-03-01

Is evolution an engineer, or is it a tinkerer--a "bricoleur"--building up complex molecules in organisms by increasing and adapting the materials at hand? An analysis of completely sequenced genomes suggests the latter, showing that increasing repetition of modules within the proteins encoded by these genomes is correlated with increasing complexity of the organism.

Inequivalent quantizations and fundamentally perfect spaces

International Nuclear Information System (INIS)

Imbo, T.D.; Sudarshan, E.C.G.

1987-06-01

We investigate the problem of inequivalent quantizations of a physical system with multiply connected configuration space X. For scalar quantum theory on X we show that state vectors must be single-valued if and only if the first homology group H 1 (X) is trivial, or equivalently the fundamental group π 1 (X) is perfect. The θ-structure of quantum gauge and gravitational theories is discussed in light of this result

Zero-dynamics principle for perfect quantum memory in linear networks

International Nuclear Information System (INIS)

Yamamoto, Naoki; James, Matthew R

2014-01-01

In this paper, we study a general linear networked system that contains a tunable memory subsystem; that is, it is decoupled from an optical field for state transportation during the storage process, while it couples to the field during the writing or reading process. The input is given by a single photon state or a coherent state in a pulsed light field. We then completely and explicitly characterize the condition required on the pulse shape achieving the perfect state transfer from the light field to the memory subsystem. The key idea to obtain this result is the use of zero-dynamics principle, which in our case means that, for perfect state transfer, the output field during the writing process must be a vacuum. A useful interpretation of the result in terms of the transfer function is also given. Moreover, a four-node network composed of atomic ensembles is studied as an example, demonstrating how the input field state is transferred to the memory subsystem and what the input pulse shape to be engineered for perfect memory looks like. (paper)

Zero-dynamics principle for perfect quantum memory in linear networks

Science.gov (United States)

Yamamoto, Naoki; James, Matthew R.

2014-07-01

In this paper, we study a general linear networked system that contains a tunable memory subsystem; that is, it is decoupled from an optical field for state transportation during the storage process, while it couples to the field during the writing or reading process. The input is given by a single photon state or a coherent state in a pulsed light field. We then completely and explicitly characterize the condition required on the pulse shape achieving the perfect state transfer from the light field to the memory subsystem. The key idea to obtain this result is the use of zero-dynamics principle, which in our case means that, for perfect state transfer, the output field during the writing process must be a vacuum. A useful interpretation of the result in terms of the transfer function is also given. Moreover, a four-node network composed of atomic ensembles is studied as an example, demonstrating how the input field state is transferred to the memory subsystem and what the input pulse shape to be engineered for perfect memory looks like.

Interaction of Prevotella intermedia strain 17 leucine-rich repeat domain protein AdpF with eukaryotic cells promotes bacterial internalization.

Science.gov (United States)

Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K; Miyazaki, Hiroshi; Lewis, Janina P

2014-06-01

Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells.

Mechanical Energy Changes in Perfectly Inelastic Collisions

Science.gov (United States)

Mungan, Carl E.

2013-01-01

Suppose a block of mass "m"[subscript 1] traveling at speed "v"[subscript 1] makes a one-dimensional perfectly inelastic collision with another block of mass "m"[subscript 2]. What else does one need to know to calculate the fraction of the mechanical energy that is dissipated in the collision? (Contains 1 figure.)

Maple Explorations, Perfect Numbers, and Mersenne Primes

Science.gov (United States)

Ghusayni, B.

2005-01-01

Some examples from different areas of mathematics are explored to give a working knowledge of the computer algebra system Maple. Perfect numbers and Mersenne primes, which have fascinated people for a very long time and continue to do so, are studied using Maple and some questions are posed that still await answers.

Thermodynamics of perfect fluids from scalar field theory

CERN Document Server

Ballesteros, Guillermo; Pilo, Luigi

2016-01-01

The low-energy dynamics of relativistic continuous media is given by a shift-symmetric effective theory of four scalar fields. These scalars describe the embedding in spacetime of the medium and play the role of Stuckelberg fields for spontaneously broken spatial and time translations. Perfect fluids are selected imposing a stronger symmetry group or reducing the field content to a single scalar. We explore the relation between the field theory description of perfect fluids to thermodynamics. By drawing the correspondence between the allowed operators at leading order in derivatives and the thermodynamic variables, we find that a complete thermodynamic picture requires the four Stuckelberg fields. We show that thermodynamic stability plus the null energy condition imply dynamical stability. We also argue that a consistent thermodynamic interpretation is not possible if any of the shift symmetries is explicitly broken.

Double-stranded endonuclease activity in Bacillus halodurans clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas2 protein.

Science.gov (United States)

Nam, Ki Hyun; Ding, Fran; Haitjema, Charles; Huang, Qingqiu; DeLisa, Matthew P; Ke, Ailong

2012-10-19

The CRISPR (clustered regularly interspaced short palindromic repeats) system is a prokaryotic RNA-based adaptive immune system against extrachromosomal genetic elements. Cas2 is a universally conserved core CRISPR-associated protein required for the acquisition of new spacers for CRISPR adaptation. It was previously characterized as an endoribonuclease with preference for single-stranded (ss)RNA. Here, we show using crystallography, mutagenesis, and isothermal titration calorimetry that the Bacillus halodurans Cas2 (Bha_Cas2) from the subtype I-C/Dvulg CRISPR instead possesses metal-dependent endonuclease activity against double-stranded (ds)DNA. This activity is consistent with its putative function in producing new spacers for insertion into the 5'-end of the CRISPR locus. Mutagenesis and isothermal titration calorimetry studies revealed that a single divalent metal ion (Mg(2+) or Mn(2+)), coordinated by a symmetric Asp pair in the Bha_Cas2 dimer, is involved in the catalysis. We envision that a pH-dependent conformational change switches Cas2 into a metal-binding competent conformation for catalysis. We further propose that the distinct substrate preferences among Cas2 proteins may be determined by the sequence and structure in the β1-α1 loop.

Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease

DEFF Research Database (Denmark)

O'Doherty, Mark G; Jørgensen, Torben; Borglykke, Anders

2014-01-01

Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single 'baseline' measurement and such analyses cannot account for possible changes in these which...... may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between......, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity....

Optimization of preparation of skilled wrestlers by perfection of method of the special preparation

Directory of Open Access Journals (Sweden)

Ogar' G.O.

2009-12-01

Full Text Available The author method of the special physical preparation of skilled fighters is presented. A method carries stage-by-stage character. On the first stage effectively to conduct the accented power training. On the second stage - to perfect explosive force. Tasks of the third stage are perfection of speed force and lactate component of energy supply. On the fourth stage the special is perfected speed-power endurance. The fifth stage coincides with beginning of competition period of macrocycle.

On the perfectness of C^{∞,s}-diffeomorphism groups on a foliated manifold

OpenAIRE

Jacek Lech

2008-01-01

The notion of \\(C^{r,s}\\) and \\(C^{\\infty,s}\\)-diffeomorphisms is introduced. It is shown that the identity component of the group of leaf preserving \\(C^{\\infty,s}\\)-diffeomorphisms with compact supports is perfect. This result is a modification of the Mather and Epstein perfectness theorem.

Perfect imaging with positive refraction in three dimensions

International Nuclear Information System (INIS)

Leonhardt, Ulf; Philbin, Thomas G.

2010-01-01

Maxwell's fish eye has been known to be a perfect lens within the validity range of ray optics since 1854. Solving Maxwell's equations, we show that the fish-eye lens in three dimensions has unlimited resolution for electromagnetic waves.

NMR Analysis of Amide Hydrogen Exchange Rates in a Pentapeptide-Repeat Protein from A. thaliana.

Science.gov (United States)

Xu, Shenyuan; Ni, Shuisong; Kennedy, Michael A

2017-05-23

At2g44920 from Arabidopsis thaliana is a pentapeptide-repeat protein (PRP) composed of 25 repeats capped by N- and C-terminal α-helices. PRP structures are dominated by four-sided right-handed β-helices typically consisting of mixtures of type II and type IV β-turns. PRPs adopt repeated five-residue (Rfr) folds with an Rfr consensus sequence (STAV)(D/N)(L/F)(S/T/R)(X). Unlike other PRPs, At2g44920 consists exclusively of type II β-turns. At2g44920 is predicted to be located in the thylakoid lumen although its biochemical function remains unknown. Given its unusual structure, we investigated the biophysical properties of At2g44920 as a representative of the β-helix family to determine if it had exceptional global stability, backbone dynamics, or amide hydrogen exchange rates. Circular dichroism measurements yielded a melting point of 62.8°C, indicating unexceptional global thermal stability. Nuclear spin relaxation measurements indicated that the Rfr-fold core was rigid with order parameters ranging from 0.7 to 0.9. At2g44920 exhibited a striking range of amide hydrogen exchange rates spanning 10 orders of magnitude, with lifetimes ranging from minutes to several months. A weak correlation was found among hydrogen exchange rates, hydrogen bonding energies, and amino acid solvent-accessible areas. Analysis of contributions from fast (approximately picosecond to nanosecond) backbone dynamics to amide hydrogen exchange rates revealed that the average order parameter of amides undergoing fast exchange was significantly smaller compared to those undergoing slow exchange. Importantly, the activation energies for amide hydrogen exchange were found to be generally higher for the slowest exchanging amides in the central Rfr coil and decreased toward the terminal coils. This could be explained by assuming that the concerted motions of two preceding or following coils required for hydrogen bond disruption and amide hydrogen exchange have a higher activation energy

Structure of filamin A immunoglobulin-like repeat 10 from Homo sapiens

International Nuclear Information System (INIS)

Page, Richard C.; Clark, Jeffrey G.; Misra, Saurav

2011-01-01

The structure of immunoglobulin-like repeat 10 from human filamin A solved at 2.44 Å resolution suggests the potential effects of mutations correlated with otopalatodigital syndrome spectrum disorders. Filamin A (FlnA) plays a critical role in cytoskeletal organization, cell motility and cellular signaling. FlnA utilizes different binding sites on a series of 24 immunoglobulin-like domains (Ig repeats) to interact with diverse cytosolic proteins and with cytoplasmic portions of membrane proteins. Mutations in a specific domain, Ig10 (FlnA-Ig10), are correlated with two severe forms of the otopalatodigital syndrome spectrum disorders Melnick–Needles syndrome and frontometaphyseal dysplasia. The crystal structure of FlnA-Ig10 determined at 2.44 Å resolution provides insight into the perturbations caused by these mutations

A versatile palindromic amphipathic repeat coding sequence horizontally distributed among diverse bacterial and eucaryotic microbes

Directory of Open Access Journals (Sweden)

Glass John I

2010-07-01

Full Text Available Abstract Background Intragenic tandem repeats occur throughout all domains of life and impart functional and structural variability to diverse translation products. Repeat proteins confer distinctive surface phenotypes to many unicellular organisms, including those with minimal genomes such as the wall-less bacterial monoderms, Mollicutes. One such repeat pattern in this clade is distributed in a manner suggesting its exchange by horizontal gene transfer (HGT. Expanding genome sequence databases reveal the pattern in a widening range of bacteria, and recently among eucaryotic microbes. We examined the genomic flux and consequences of the motif by determining its distribution, predicted structural features and association with membrane-targeted proteins. Results Using a refined hidden Markov model, we document a 25-residue protein sequence motif tandemly arrayed in variable-number repeats in ORFs lacking assigned functions. It appears sporadically in unicellular microbes from disparate bacterial and eucaryotic clades, representing diverse lifestyles and ecological niches that include host parasitic, marine and extreme environments. Tracts of the repeats predict a malleable configuration of recurring domains, with conserved hydrophobic residues forming an amphipathic secondary structure in which hydrophilic residues endow extensive sequence variation. Many ORFs with these domains also have membrane-targeting sequences that predict assorted topologies; others may comprise reservoirs of sequence variants. We demonstrate expressed variants among surface lipoproteins that distinguish closely related animal pathogens belonging to a subgroup of the Mollicutes. DNA sequences encoding the tandem domains display dyad symmetry. Moreover, in some taxa the domains occur in ORFs selectively associated with mobile elements. These features, a punctate phylogenetic distribution, and different patterns of dispersal in genomes of related taxa, suggest that the

Emerging role for leucine-rich repeat-containing G-protein-coupled receptors LGR5 and LGR4 in cancer stem cells

International Nuclear Information System (INIS)

Nakata, Susumu; Phillips, Emma; Goidts, Violaine

2014-01-01

The concept of cancer stem cells has gained considerable interest in the last few decades, partly because of their potential implication in therapy resistance. However, the lack of specific cellular surface markers for these cells has impeded their isolation, making the characterization of this cellular subpopulation technically challenging. Recent studies have indicated that leucine-rich repeat-containing G-protein-coupled receptor 4 and 5 (LGR4 and LGR5) expression in multiple organs may represent a global marker of adult stem cells. This review aims to give an overview of LGR4 and LGR5 as cancer stem cell markers and their function in development

Expression, crystallization and preliminary crystallographic data analysis of filamin A repeats 14–16

International Nuclear Information System (INIS)

Aguda, Adeleke Halilu; Sakwe, Amos Malle; Rask, Lars; Robinson, Robert Charles

2007-01-01

The crystallization and crystallographic data analysis of filamin repeats 14–16 are reported. Human filamin A is a 280 kDa protein involved in actin-filament cross-linking. It is structurally divided into an actin-binding headpiece (ABD) and a rod domain containing 24 immunoglobulin-like (Ig) repeats. A fragment of human filamin A (Ig repeats 14–16) was cloned and expressed in Escherichia coli and the purified protein was crystallized in 1.6 M ammonium sulfate, 2% PEG 1000 and 100 mM HEPES pH 7.5. The crystals diffracted to 1.95 Å and belong to space group P2 1 2 1 2 1 , with unit-cell parameters a = 50.63, b = 52.10, c = 98.46 Å, α = β = γ = 90°

Study of simple sequence repeat (SSR) polymorphism for biotic ...

African Journals Online (AJOL)

home

2013-10-02

Oct 2, 2013 ... G. Siva Kumar1, K. Aruna Kumari1*, Ch. V. Durga Rani1, R. M. Sundaram2, S. Vanisree3, Md. ..... review by Jena and Mackill (2008) provided the list of .... repeat protein and is a member of a resistance gene cluster on rice.

Reshaping the perfect electrical conductor cylinder arbitrarily

International Nuclear Information System (INIS)

Chen Huanyang; Zhang Xiaohe; Luo Xudong; Ma Hongru; Chan Cheting

2008-01-01

A general method is proposed to design a cylindrical cloak, concentrator and superscatterer with an arbitrary cross section. The method is demonstrated by the design of a perfect electrical conductor (PEC) reshaper which is able to reshape a PEC cylinder arbitrarily by combining the concept of cloak, concentrator and superscatterer together. Numerical simulations are performed to demonstrate its properties.

PASTA repeats of the protein kinase StkP interconnect cell constriction and separation of Streptococcus pneumoniae.

Science.gov (United States)

Zucchini, Laure; Mercy, Chryslène; Garcia, Pierre Simon; Cluzel, Caroline; Gueguen-Chaignon, Virginie; Galisson, Frédéric; Freton, Céline; Guiral, Sébastien; Brochier-Armanet, Céline; Gouet, Patrice; Grangeasse, Christophe

2018-02-01

Eukaryotic-like serine/threonine kinases (eSTKs) with extracellular PASTA repeats are key membrane regulators of bacterial cell division. How PASTA repeats govern eSTK activation and function remains elusive. Using evolution- and structural-guided approaches combined with cell imaging, we disentangle the role of each PASTA repeat of the eSTK StkP from Streptococcus pneumoniae. While the three membrane-proximal PASTA repeats behave as interchangeable modules required for the activation of StkP independently of cell wall binding, they also control the septal cell wall thickness. In contrast, the fourth and membrane-distal PASTA repeat directs StkP localization at the division septum and encompasses a specific motif that is critical for final cell separation through interaction with the cell wall hydrolase LytB. We propose a model in which the extracellular four-PASTA domain of StkP plays a dual function in interconnecting the phosphorylation of StkP endogenous targets along with septal cell wall remodelling to allow cell division of the pneumococcus.

Double-chimera proteins to enhance recruitment of endothelial cells and their progenitor cells.

Science.gov (United States)

Behjati, M; Kazemi, M; Hashemi, M; Zarkesh-Esfahanai, S H; Bahrami, E; Hashemi-Beni, B; Ahmadi, R

2013-08-20

Enhanced attraction of selective vascular reparative cells is of great importance in order to increase vascular patency after endovascular treatments. We aimed to evaluate efficient attachment of endothelial cells and their progenitors on surfaces coated with mixture of specific antibodies, L-selectin and VE-cadherin, with prohibited platelet attachment. The most efficient conditions for coating of L-selectin-Fc chimera and VE-cadherin-Fc chimera proteins were first determined by protein coating on ELISA plates. The whole processes were repeated on titanium substrates, which are commonly used to coat stents. Endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs) were isolated and characterized by flow cytometry. Cell attachment, growth, proliferation, viability and surface cytotoxicity were evaluated using nuclear staining and MTT assay. Platelet and cell attachment were evaluated using scanning electron microscopy. Optimal concentration of each protein for surface coating was 50 ng/ml. The efficacy of protein coating was both heat and pH independent. Calcium ions had significant impact on simultaneous dual-protein coating (P<0.05). Coating stability data revealed more than one year stability for these coated proteins at 4°C. L-selectin and VE-cadherin (ratio of 50:50) coated surface showed highest EPC and HUVEC attachment, viability and proliferation compared to single protein coated and non-coated titanium surfaces (P<0.05). This double coated surface did not show any cytotoxic effect. Surfaces coated with L-selectin and VE-cadherin are friendly surface for EPC and endothelial cell attachment with less platelet attachment. These desirable factors make the L-selectin and VE-cadherin coated surfaces perfect candidate endovascular device. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Expression, purification and preliminary biochemical and structural characterization of the leucine rich repeat namesake domain of leucine rich repeat kinase 2.

Science.gov (United States)

Vancraenenbroeck, Renée; Lobbestael, Evy; Weeks, Stephen D; Strelkov, Sergei V; Baekelandt, Veerle; Taymans, Jean-Marc; De Maeyer, Marc

2012-03-01

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease. Much research effort has been directed towards the catalytic core region of LRRK2 composed of GTPase (ROC, Ras of complex proteins) and kinase domains and a connecting COR (C-terminus of ROC) domain. In contrast, the precise functions of the protein-protein interaction domains, such as the leucine-rich repeat (LRR) domain, are not known. In the present study, we modeled the LRRK2 LRR domain (LRR(LRRK2)) using a template assembly approach, revealing the presence of 14 LRRs. Next, we focused on the expression and purification of LRR(LRRK2) in Escherichia coli. Buffer optimization revealed that the protein requires the presence of a zwitterionic detergent, namely Empigen BB, during solubilization and the subsequent purification and characterization steps. This indicates that the detergent captures the hydrophobic surface patches of LRR(LRRK2) thereby suppressing its aggregation. Circular dichroism (CD) spectroscopy measured 18% α-helices and 21% β-sheets, consistent with predictions from the homology model. Size exclusion chromatography (SEC) and dynamic light scattering measurements showed the presence of a single species, with a Stokes radius corresponding to the model dimensions of a protein monomer. Furthermore, no obvious LRR(LRRK2) multimerization was detected via cross-linking studies. Finally, the LRR(LRRK2) clinical mutations did not influence LRR(LRRK2) secondary, tertiary or quaternary structure as determined via SEC and CD spectroscopy. We therefore conclude that these mutations are likely to affect putative LRR(LRRK2) inter- and intramolecular interactions. Copyright © 2011 Elsevier B.V. All rights reserved.

Mouse Models of C9orf72 Hexanucleotide Repeat Expansion in Amyotrophic Lateral Sclerosis/ Frontotemporal Dementia

Directory of Open Access Journals (Sweden)

Ranjan Batra

2017-07-01

Full Text Available The presence of hexanucleotide repeat expansion (HRE in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2 HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN translation mechanism, and on loss-of-function of the C9orf72 protein. Immense effort to elucidate these mechanisms has been put forth and toxic gain-of-function models have especially gained attention. Various mouse models that recapitulate distinct disease-related pathological, functional, and behavioral phenotypes have been generated and characterized. Although these models express the C9orf72 HRE mutation, there are numerous differences among them, including the transgenesis approach to introduce G4C2-repeat DNA, genomic coverage of C9orf72 features in the transgene, G4C2-repeat length after genomic stabilization, spatiotemporal expression profiles of RNA foci and RAN protein aggregates, neuropathological features, and neurodegeneration-related clinical symptoms. This review aims to (1 provide an overview of the key characteristics; (2 provide insights into potential pathological factors contributing to neurotoxicity and clinical phenotypes through systematic comparison of these models.

Repeat-associated plasticity in the Helicobacter pylori RD gene family.

Science.gov (United States)

Shak, Joshua R; Dick, Jonathan J; Meinersmann, Richard J; Perez-Perez, Guillermo I; Blaser, Martin J

2009-11-01

The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3' region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host.

Promoter Engineering Reveals the Importance of Heptameric Direct Repeats for DNA Binding by Streptomyces Antibiotic Regulatory Protein-Large ATP-Binding Regulator of the LuxR Family (SARP-LAL) Regulators in Streptomyces natalensis.

Science.gov (United States)

Barreales, Eva G; Vicente, Cláudia M; de Pedro, Antonio; Santos-Aberturas, Javier; Aparicio, Jesús F

2018-05-15

The biosynthesis of small-size polyene macrolides is ultimately controlled by a couple of transcriptional regulators that act in a hierarchical way. A Streptomyces antibiotic regulatory protein-large ATP-binding regulator of the LuxR family (SARP-LAL) regulator binds the promoter of a PAS-LuxR regulator-encoding gene and activates its transcription, and in turn, the gene product of the latter activates transcription from various promoters of the polyene gene cluster directly. The primary operator of PimR, the archetype of SARP-LAL regulators, contains three heptameric direct repeats separated by four-nucleotide spacers, but the regulator can also bind a secondary operator with only two direct repeats separated by a 3-nucleotide spacer, both located in the promoter region of its unique target gene, pimM A similar arrangement of operators has been identified for PimR counterparts encoded by gene clusters for different antifungal secondary metabolites, including not only polyene macrolides but peptidyl nucleosides, phoslactomycins, or cycloheximide. Here, we used promoter engineering and quantitative transcriptional analyses to determine the contributions of the different heptameric repeats to transcriptional activation and final polyene production. Optimized promoters have thus been developed. Deletion studies and electrophoretic mobility assays were used for the definition of DNA-binding boxes formed by 22-nucleotide sequences comprising two conserved heptameric direct repeats separated by four-nucleotide less conserved spacers. The cooperative binding of PimR SARP appears to be the mechanism involved in the binding of regulator monomers to operators, and at least two protein monomers are required for efficient binding. IMPORTANCE Here, we have shown that a modulation of the production of the antifungal pimaricin in Streptomyces natalensis can be accomplished via promoter engineering of the PAS-LuxR transcriptional activator pimM The expression of this gene is

A linear construction of perfect secret sharing schemes

NARCIS (Netherlands)

Dijk, van M.; Santis, De A.

1995-01-01

In this paper, we generalize the vector space construction due to Brickell [5]. This generalization, introduced by Bertilsson [1], leads to perfect secret sharing schemes with rational information rates in which the secret can be computed efficiently by each qualified group. A one to one

Perfect pitch reconsidered.

Science.gov (United States)

Moulton, Calum

2014-10-01

Perfect pitch, or absolute pitch (AP), is defined as the ability to identify or produce the pitch of a sound without need for a reference pitch, and is generally regarded as a valuable asset to the musician. However, there has been no recent review of the literature examining its aetiology and its utility taking into account emerging scientific advances in AP research, notably in functional imaging. This review analyses the key empirical research on AP, focusing on genetic and neuroimaging studies. The review concludes that: AP probably has a genetic predisposition, although this is based on limited evidence; early musical training is almost certainly essential for AP acquisition; and, although there is evidence that it may be relevant to speech processing, AP can interfere with relative pitch, an ability on which humans rely to communicate effectively. The review calls into question the value of AP to musicians and non-musicians alike. © 2014 Royal College of Physicians.

On the Galois cohomology of unipotent groups and extensions of non-perfect fields

International Nuclear Information System (INIS)

Nguyen Duy Tan; Nguyen Quoc Thang

2006-12-01

In this note we discuss, in the case of unipotent groups over non-perfect fields, an analog of Serre's conjectures for unipotent algebraic group schemes, which relates properties of Galois (or flat) cohomology of unipotent group schemes to finite extensions of non-perfect fields, and Russel's defining equations of one-dimensional unipotent groups. (author)

Crystallization and preliminary crystallographic analysis of merohedrally twinned crystals of MJ0729, a CBS-domain protein from Methanococcus jannaschii

International Nuclear Information System (INIS)

Fernández-Millán, Pablo; Kortazar, Danel; Lucas, María; Martínez-Chantar, María Luz; Astigarraga, Egoitz; Fernández, José Andrés; Sabas, Olatz; Albert, Armando; Mato, Jose M.; Martínez-Cruz, Luis Alfonso

2008-01-01

Trigonal crystals of MJ0729 showing different degrees of merohedral twinning that may vary from perfect hemihedral twinning to perfect tetartohedral twinning were obtained upon slight variation of the pH. CBS domains are small protein motifs, usually associated in tandem, that are implicated in binding to adenosyl groups. Several genetic diseases in humans have been associated with mutations in CBS sequences, which has made them very promising targets for rational drug design. Trigonal crystals of the CBS-domain protein MJ0729 from Methanococcus jannaschii were grown by the vapour-diffusion method at acidic pH. Preliminary analysis of nine X-ray diffraction data sets using Yeates statistics and Britton plots showed that slight variation in the pH as well as in the buffer used in the crystallization experiments led to crystals with different degrees of merohedral twinning that may vary from perfect hemihedral twinning to perfect tetartohedral twinning

Physicotechnical potentialities of perfecting roentgenographic research

International Nuclear Information System (INIS)

Chikirdin, Eh.G.; Mishkinis, B.Ya.

1991-01-01

Physicotechnical potentialities of perfecting image quality in X-ray examinations are enumerated. Realization of these potentialities demands interrelated decision of two problems: substantiation of optimizing conditions of survey (postures of a patient, geometry of investigation, image converters, electric regimes), creation of adequate hardware and software components. It is shown that introduction of X-ray feeding device with microprocessor control permits to upgrade the quality of X-ray images and to reduce radiation loads of a patient

Molecular Characterization of Respiratory Syncytial Virus in Children with Repeated Infections with Subgroup B in the Philippines.

Science.gov (United States)

Okamoto, Michiko; Dapat, Clyde P; Sandagon, Ann Marie D; Batangan-Nacion, Leilanie P; Lirio, Irene C; Tamaki, Raita; Saito, Mayuko; Saito-Obata, Mariko; Lupisan, Socorro P; Oshitani, Hitoshi

2018-05-02

Human respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes. We conducted a cohort study for children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between prior and subsequent RSV infections. We examined 1,802 children from May 2014 to January 2016 and collected 3,471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein. Amino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.

Random mutagenesis of the nucleotide-binding domain of NRC1 (NB-LRR Required for Hypersensitive Response-Associated Cell Death-1), a downstream signalling nucleotide-binding, leucine-rich repeat (NB-LRR) protein, identifies gain-of-function mutations in the nucleotide-binding pocket

NARCIS (Netherlands)

Sueldo, D.J.; Shimels, M.Z.; Spiridon, L.N.; Caldararu, O.; Petrescu, A.J.; Joosten, M.H.A.J.; Tameling, W.I.L.

2015-01-01

•Plant nucleotide-binding, leucine-rich repeat (NB-LRR) proteins confer immunity to pathogens possessing the corresponding avirulence proteins. Activation of NB-LRR proteins is often associated with induction of the hypersensitive response (HR), a form of programmed cell death. •NRC1 (NB-LRR

The last half-repeat of transcription activator-like effector (TALE) is dispensable and thereby TALE-based technology can be simplified.

Science.gov (United States)

Zheng, Chong-Ke; Wang, Chun-Lian; Zhang, Xiao-Ping; Wang, Fu-Jun; Qin, Teng-Fei; Zhao, Kai-Jun

2014-09-01

To activate the expression of host genes that contribute to pathogen growth, pathogenic Xanthomonas bacteria inject their transcription activator-like effectors (TALEs) into plant cells and the TALEs bind to target gene promoters by the central repeat region consisting of near-perfect 34-amino-acid repeats (34-aa repeats). Based on the recognition codes between the 34-aa repeats and the targeted nucleotides, TALE-based technologies, such as designer TALEs (dTALEs) and TALE nucleases (TALENs), have been developed. Amazingly, every natural TALE invariantly has a truncated last half-repeat (LHR) at the end of the 34-aa repeats. Consequently, all the reported dTALEs and TALENs also harbour their LHRs. Here, we show that the LHRs in dTALEs are dispensable for the function of gene activation by both transient expression assays in Nicotiana benthamiana and gene-specific targeting in the rice genome, indicating that TALEs might originate from a single progenitor. In the light of this finding, we demonstrate that dTALEs can be constructed through two simple steps. Moreover, the activation strengths of dTALEs lacking the LHR are comparable with those of dTALEs harbouring the LHR. Our results provide new insights into the origin of natural TALEs, and will facilitate the simplification of the design and assembly of TALE-based tools, such as dTALEs and TALENs, in the near future. © 2014 BSPP AND JOHN WILEY & SONS LTD.

The Perfect Storm--Genetic Engineering, Science, and Ethics

Science.gov (United States)

Rollin, Bernard E.

2014-01-01

Uncertainty about ethics has been a major factor in societal rejection of biotechnology. Six factors help create a societal "perfect storm" regarding ethics and biotechnology: Social demand for ethical discussion; societal scientific illiteracy; poor social understanding of ethics; a "Gresham's Law for Ethics;" Scientific…

Quantum private query with perfect user privacy against a joint-measurement attack

Energy Technology Data Exchange (ETDEWEB)

Yang, Yu-Guang, E-mail: yangyang7357@bjut.edu.cn [College of Computer Science and Technology, Beijing University of Technology, Beijing 100124 (China); State Key Laboratory of Information Security, Institute of Information Engineering, Chinese Academy of Sciences, Beijing 100093 (China); Liu, Zhi-Chao [College of Computer Science and Technology, Beijing University of Technology, Beijing 100124 (China); Li, Jian [School of Computer, Beijing University of Posts and Telecommunications, Beijing 100876 (China); Chen, Xiu-Bo [Information Security Center, State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing, 100876 (China); Zuo, Hui-Juan [College of Mathematics and Information Science, Hebei Normal University, Shijiazhuang 050024 (China); Zhou, Yi-Hua; Shi, Wei-Min [College of Computer Science and Technology, Beijing University of Technology, Beijing 100124 (China)

2016-12-16

The joint-measurement (JM) attack is the most powerful threat to the database security for existing quantum-key-distribution (QKD)-based quantum private query (QPQ) protocols. Wei et al. (2016) [28] proposed a novel QPQ protocol against the JM attack. However, their protocol relies on two-way quantum communication thereby affecting its real implementation and communication efficiency. Moreover, it cannot ensure perfect user privacy. In this paper, we present a new one-way QPQ protocol in which the special way of classical post-processing of oblivious key ensures the security against the JM attack. Furthermore, it realizes perfect user privacy and lower complexity of communication. - Highlights: • A special classical post-processing ensures the security against the JM attack. • It ensures perfect user privacy. • It ensures lower complexity of communication. Alice's conclusive key rate is 1/6.

Quantum private query with perfect user privacy against a joint-measurement attack

International Nuclear Information System (INIS)

Yang, Yu-Guang; Liu, Zhi-Chao; Li, Jian; Chen, Xiu-Bo; Zuo, Hui-Juan; Zhou, Yi-Hua; Shi, Wei-Min

2016-01-01

The joint-measurement (JM) attack is the most powerful threat to the database security for existing quantum-key-distribution (QKD)-based quantum private query (QPQ) protocols. Wei et al. (2016) [28] proposed a novel QPQ protocol against the JM attack. However, their protocol relies on two-way quantum communication thereby affecting its real implementation and communication efficiency. Moreover, it cannot ensure perfect user privacy. In this paper, we present a new one-way QPQ protocol in which the special way of classical post-processing of oblivious key ensures the security against the JM attack. Furthermore, it realizes perfect user privacy and lower complexity of communication. - Highlights: • A special classical post-processing ensures the security against the JM attack. • It ensures perfect user privacy. • It ensures lower complexity of communication. Alice's conclusive key rate is 1/6.

Analysis of experience of feet functions perfection in rhythmic gymnastic exercises

Directory of Open Access Journals (Sweden)

Nesterova T.V.

2009-10-01

Full Text Available Trainers and gymnasts take the problem of the special preparation feet and developments of method of its perfection to the number of the actual. The results of the pedagogical testing are shown that basic (basic, pushed, amortisation and specific (aesthetic, manipulation, integral functions feet have a different degree of display. They will be realized in exercises on all of the stages of long-term preparation of sportswomen. Most dynamic perfection of functions feet gymnasts take place on the stages of initial and preliminary base preparation.

Identification and characterization of short tandem repeats in the Tibetan macaque genome based on resequencing data.

Science.gov (United States)

Liu, San-Xu; Hou, Wei; Zhang, Xue-Yan; Peng, Chang-Jun; Yue, Bi-Song; Fan, Zhen-Xin; Li, Jing

2018-07-18

The Tibetan macaque, which is endemic to China, is currently listed as a Near Endangered primate species by the International Union for Conservation of Nature (IUCN). Short tandem repeats (STRs) refer to repetitive elements of genome sequence that range in length from 1-6 bp. They are found in many organisms and are widely applied in population genetic studies. To clarify the distribution characteristics of genome-wide STRs and understand their variation among Tibetan macaques, we conducted a genome-wide survey of STRs with next-generation sequencing of five macaque samples. A total of 1 077 790 perfect STRs were mined from our assembly, with an N50 of 4 966 bp. Mono-nucleotide repeats were the most abundant, followed by tetra- and di-nucleotide repeats. Analysis of GC content and repeats showed consistent results with other macaques. Furthermore, using STR analysis software (lobSTR), we found that the proportion of base pair deletions in the STRs was greater than that of insertions in the five Tibetan macaque individuals (Pgenome showed good amplification efficiency and could be used to study population genetics in Tibetan macaques. The neighbor-joining tree classified the five macaques into two different branches according to their geographical origin, indicating high genetic differentiation between the Huangshan and Sichuan populations. We elucidated the distribution characteristics of STRs in the Tibetan macaque genome and provided an effective method for screening polymorphic STRs. Our results also lay a foundation for future genetic variation studies of macaques.

The number of genes encoding repeat domain-containing proteins positively correlates with genome size in amoebal giant viruses

Science.gov (United States)

Shukla, Avi; Chatterjee, Anirvan

2018-01-01

Abstract Curiously, in viruses, the virion volume appears to be predominantly driven by genome length rather than the number of proteins it encodes or geometric constraints. With their large genome and giant particle size, amoebal viruses (AVs) are ideally suited to study the relationship between genome and virion size and explore the role of genome plasticity in their evolutionary success. Different genomic regions of AVs exhibit distinct genealogies. Although the vertically transferred core genes and their functions are universally conserved across the nucleocytoplasmic large DNA virus (NCLDV) families and are essential for their replication, the horizontally acquired genes are variable across families and are lineage-specific. When compared with other giant virus families, we observed a near–linear increase in the number of genes encoding repeat domain-containing proteins (RDCPs) with the increase in the genome size of AVs. From what is known about the functions of RDCPs in bacteria and eukaryotes and their prevalence in the AV genomes, we envisage important roles for RDCPs in the life cycle of AVs, their genome expansion, and plasticity. This observation also supports the evolution of AVs from a smaller viral ancestor by the acquisition of diverse gene families from the environment including RDCPs that might have helped in host adaption. PMID:29308275

Spherically symmetric Einstein-aether perfect fluid models

Energy Technology Data Exchange (ETDEWEB)

Coley, Alan A.; Latta, Joey [Department of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Leon, Genly [Instituto de Física, Pontificia Universidad Católica de Valparaíso, Casilla 4950, Valparaíso (Chile); Sandin, Patrik, E-mail: aac@mathstat.dal.ca, E-mail: genly.leon@ucv.cl, E-mail: patrik.sandin@aei.mpg.de, E-mail: lattaj@mathstat.dal.ca [Max-Planck-Institut für Gravitationsphysik (Albert-Einstein-Institut), Am Mühlenberg 1, D-14476 Potsdam (Germany)

2015-12-01

We investigate spherically symmetric cosmological models in Einstein-aether theory with a tilted (non-comoving) perfect fluid source. We use a 1+3 frame formalism and adopt the comoving aether gauge to derive the evolution equations, which form a well-posed system of first order partial differential equations in two variables. We then introduce normalized variables. The formalism is particularly well-suited for numerical computations and the study of the qualitative properties of the models, which are also solutions of Horava gravity. We study the local stability of the equilibrium points of the resulting dynamical system corresponding to physically realistic inhomogeneous cosmological models and astrophysical objects with values for the parameters which are consistent with current constraints. In particular, we consider dust models in (β−) normalized variables and derive a reduced (closed) evolution system and we obtain the general evolution equations for the spatially homogeneous Kantowski-Sachs models using appropriate bounded normalized variables. We then analyse these models, with special emphasis on the future asymptotic behaviour for different values of the parameters. Finally, we investigate static models for a mixture of a (necessarily non-tilted) perfect fluid with a barotropic equations of state and a scalar field.

Multi-mode competition in an FEL oscillator at perfect synchronism of an optical cavity

CERN Document Server

Dong, Z W; Kii, T; Yamazaki, T; Yoshikawa, K

2002-01-01

The sustained saturation in a short pulse free electron laser (FEL) oscillator at perfect synchronism of an optical cavity has been observed recently by Japan Atomic Energy Research Institute (JAERI) FEL group by using their super-conducting linac (Phys. Rev. Lett., in preparation). The experiments have clearly shown that FEL efficiency becomes maximum at perfect synchronism, although it has been considered that only a transient state exists at perfect synchronism due to the lethargy effect. Through careful analyses of the experimental condition of JAERI FEL, we found that, in spite of the short length of the electron micro-bunch, the saturation appears due to the following features, which were different from other FEL experiments: (1) very large ratio of the small signal gain to losses, (2) very long electron macro-bunch which can tolerate a slow start up. The saturation and high efficiency at perfect synchronism were benefited from the contribution of the weak sideband instability. In order to analyse these...

Scheme for achieving coherent perfect absorption by anisotropic metamaterials

KAUST Repository

Zhang, Xiujuan; Wu, Ying

2017-01-01

in conjunction with retrieval method to determine practical metamaterial absorbers. The scheme is scalable to frequencies and applicable to various incident angles. Numerical simulations show that perfect absorption is achieved in the designed absorbers over a

Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene

Energy Technology Data Exchange (ETDEWEB)

Goldfarb, L.G.; Brown, P.; McCombie, W.R.; Gibbs, C.J. Jr.; Gajdusek, D.C. (National Inst. of Health, Bethesda, MD (United States)); Goldgaber, D. (State Univ. of New York, Stony Brook (United States)); Swergold, G.D. (National Inst. of Health, Bethesda, MD (United States)); Wills, P.R. (Univ. of Auckland (New Zealand)); Cervenakova, L. (Inst. of Preventive and Clinical Medicine, Bratislava (Czechoslovakia)); Baron, H. (Searle Pharmaceuticals, Paris (France))

1991-12-01

The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of five variant tandem octapeptide coding repeats between codons 51 and 91. The authors screened a total of 535 individuals for the presence of extra repeats in this region, including patients with sporadic and familial forms of spongiform encephalopathy, members of their families, other neurological and non-neurological patients, and normal controls. They identified three CJD families (in each of which the proband's disease was neuropathologically confirmed and experimentally transmitted to primates) that were heterozygous for alleles with 10, 12, or 13 repeats, some of which had wobble nucleotide substitutions. They also found one individual with 9 repeats and no nucleotide substitutions who had no evidence of neurological disease. These observations, together with data on published British patients with 11 and 14 repeats, strongly suggest that the occurrence of 10 or more octapeptide repeats in the encoded amyloid precursor protein predisposes to CJD.

Perfect fluid cosmology with geodesic world lines

International Nuclear Information System (INIS)

Raychaudhuri, A.K.; Maity, S.R.

1978-01-01

It is shown that for a perfect fluid with an equation of state p = p (rho), if the world lines are geodesics, then they are hypersurface orthogonal and the scalars p, rho, sigma 2 , and theta 2 are all constants over these hypersurfaces, irrespective of any spatial-homogeneity assumption. However, an examination of some simple cases does not reveal any spatially nonhomogeneous solution with these properties

Another Class of Perfect Nonlinear Polynomial Functions

Directory of Open Access Journals (Sweden)

Menglong Su

2013-01-01

Full Text Available Perfect nonlinear (PN functions have been an interesting subject of study for a long time and have applications in coding theory, cryptography, combinatorial designs, and so on. In this paper, the planarity of the trinomials xpk+1+ux2+vx2pk over GF(p2k are presented. This class of PN functions are all EA-equivalent to x2.

INVESTIGATION OF MICROPROCESSOR CURRENT PROTECTION LINES WITH IMPROVED INDICES OF TECHNICAL PERFECTION

Directory of Open Access Journals (Sweden)

E. V. Buloichyk

2014-01-01

Full Text Available Technical perfection improvement of microprocessor current protection of distribution networks lines is provided by introduction of asymmetrical fault mode determination and fault location functions in the algorithm of its functioning. As a result of computing experiment the basic indices of the technical perfection of current protection have been obtained in the paper. The paper proves high efficiency of the proposed methods that ensure selective and proper operation in the different modes of the controlled line.

A novel seven-octapeptide repeat insertion in the prion protein gene (PRNP) in a Dutch pedigree with Gerstmann-Sträussler-Scheinker disease phenotype: comparison with similar cases from the literature

NARCIS (Netherlands)

Jansen, Casper; Voet, Willem; Head, Mark W.; Parchi, Piero; Yull, Helen; Verrips, Aad; Wesseling, Pieter; Meulstee, Jan; Baas, Frank; van Gool, Willem A.; Ironside, James W.; Rozemuller, Annemieke J. M.

2011-01-01

Human prion diseases can be sporadic, inherited or acquired by infection and show considerable phenotypic heterogeneity. We describe the clinical, histopathological and pathological prion protein (PrP(Sc)) characteristics of a Dutch family with a novel 7-octapeptide repeat insertion (7-OPRI) in

Selfish DNA in protein-coding genes of Rickettsia.

Science.gov (United States)

Ogata, H; Audic, S; Barbe, V; Artiguenave, F; Fournier, P E; Raoult, D; Claverie, J M

2000-10-13

Rickettsia conorii, the aetiological agent of Mediterranean spotted fever, is an intracellular bacterium transmitted by ticks. Preliminary analyses of the nearly complete genome sequence of R. conorii have revealed 44 occurrences of a previously undescribed palindromic repeat (150 base pairs long) throughout the genome. Unexpectedly, this repeat was found inserted in-frame within 19 different R. conorii open reading frames likely to encode functional proteins. We found the same repeat in proteins of other Rickettsia species. The finding of a mobile element inserted in many unrelated genes suggests the potential role of selfish DNA in the creation of new protein sequences.

Identification of the centromeric repeat in the threespine stickleback fish (Gasterosteus aculeatus).

Science.gov (United States)

Cech, Jennifer N; Peichel, Catherine L

2015-12-01

Centromere sequences exist as gaps in many genome assemblies due to their repetitive nature. Here we take an unbiased approach utilizing centromere protein A (CENP-A) chomatin immunoprecipitation followed by high-throughput sequencing to identify the centromeric repeat sequence in the threespine stickleback fish (Gasterosteus aculeatus). A 186-bp, AT-rich repeat was validated as centromeric using both fluorescence in situ hybridization (FISH) and immunofluorescence combined with FISH (IF-FISH) on interphase nuclei and metaphase spreads. This repeat hybridizes strongly to the centromere on all chromosomes, with the exception of weak hybridization to the Y chromosome. Together, our work provides the first validated sequence information for the threespine stickleback centromere.

Simulation of MILD combustion using Perfectly Stirred Reactor model

KAUST Repository

Chen, Z.; Vanteru, Mahendra Reddy; Ruan, S.; Doan, N. A K; Roberts, William L.; Swaminathan, N.

2016-01-01

A simple model based on a Perfectly Stirred Reactor (PSR) is proposed for moderate or intense low-oxygen dilution (MILD) combustion. The PSR calculation is performed covering the entire flammability range and the tabulated chemistry approach is used

Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms.

Science.gov (United States)

Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R

2015-01-01

Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called "repeat-swap modeling" to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport also

Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms

Directory of Open Access Journals (Sweden)

Cristina eFenollar Ferrer

2015-09-01

Full Text Available Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to either the outside or inside of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (asymmetry of these systems has been successfully used as a bioinformatic tool, called repeat-swap modeling to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that

Understanding A.M. Iqbal’s Vision on Perfect Man

Directory of Open Access Journals (Sweden)

Imam Bahroni

2013-12-01

Full Text Available This article tries to elucidate A.M Iqbal’s vision on the concept of perfectman. Its significance is at the point that Man can transform both his being andhis surroundings according to his own desires and aspirations. He actually makesimprovements upon what is created by God. God created night, he inventedthe lamp; God created clay, and from it he made the cup; God created deserts,mountains, forests, orchards, gardens, and groves. He makes glass out of stoneand turns poison into an antidote. God created the world, but he made it morebeautiful.Iqbal’s reasoning amply justifies belief in the ascendancy of man overthe universe and his predicted perfection. The perfect man is the ultimate endof the revolutionary process, and he is developed out of the present man, justas the full moon is developed from the crescent.

Microsatellite instability at a tetranucleotide repeat in type I endometrial carcinoma

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Choi Ho

2008-12-01

Full Text Available Abstract Background Microsatellite instability (MSI at tri- or tetranucleotide repeat markers (elevated microsatellite alterations at selected tetranucleotide repeat, EMAST has been recently described. But, the underlying genetic mechanism of EMAST is unclear. This study was to investigate the prevalence of EMAST, in type I endometrial carcinoma, and to determine the correlation between the MSI status and mismatch repair genes (MMR or p53. Methods We examined the 3 mono-, 3 di-, and 6 tetranucleotide repeat markers by PCR in 39 cases of type I endometrial carcinoma and performed the immunohistochemistry of hMSH2, hMLH1, and p53 protein. Results More than two MSI at mono- and dinucleotide repeat markers was noted in 8 cases (MSI-H, 20.5%. MSI, at a tetranucleotide repeat, was detected in 15 cases (EMAST, 38.5%. In remaining 16 cases, any MSI was not observed. (MSS, 42.1%, MSI status was not associated with FIGO stage, grade or depth of invasion. The absence of expression of either one of both hMSH2 or hMLH1 was noted in seven (87.5% of eight MSI-H tumors, one (6.3% of 16 MSS tumors, and five (33.3% of 15 EMAST tumors. (p = 0.010 The expression of p53 protein was found in one (12.5% of eight MSI-H tumors, five (31.3% of 16 MSS tumors, and seven of 15 EMAST tumors. (p = 0.247 Conclusion Our results showed that about 38.5% of type I endometrial carcinomas exhibited EMAST, and that EMAST was rarely associated with alteration of hMSH2 or hMLH1.

Diamagnetic expansions for perfect quantum gases

DEFF Research Database (Denmark)

Briet, Philippe; Cornean, Horia; Louis, Delphine

2006-01-01

In this work we study the diamagnetic properties of a perfect quantum gas in the presence of a constant magnetic field of intensity B. We investigate the Gibbs semigroup associated with the one particle operator at finite volume, and study its Taylor series with respect to the field parameter ome......:=eB/c in different topologies. This allows us to prove the existence of the thermodynamic limit for the pressure and for all its derivatives with respect to omega (the so-called generalized susceptibilities)....

Simulation of a perfect CVD diamond Schottky diode steep forward current–voltage characteristic

Energy Technology Data Exchange (ETDEWEB)

Kukushkin, V.A., E-mail: vakuk@appl.sci-nnov.ru [Institute of Applied Physics of the Russian Academy of Science, 46 Ulyanov St., 603950 Nizhny Novgorod (Russian Federation); Nizhny Novgorod State University named after N.I. Lobachevsky, 23 Gagarin pr., 603950 Nizhny Novgorod (Russian Federation)

2016-10-01

The kinetic equation approach to the simulation of the perfect CVD diamond Schottky diode current–voltage characteristic is considered. In result it is shown that the latter has a significantly steeper forward branch than that of perfect devices of such a type on usual semiconductors. It means that CVD diamond-based Schottky diodes have an important potential advantage over analogous devices on conventional materials.

Crystal structure of clustered regularly interspaced short palindromic repeats (CRISPR)-associated Csn2 protein revealed Ca2+-dependent double-stranded DNA binding activity.

Science.gov (United States)

Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong

2011-09-02

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 Å tetrameric ring structure. The inner circle of the Csn2 tetrameric ring is ∼26 Å wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an α/β domain and an α-helical domain; significant hinge motion was observed between these two domains. Ca(2+) was located at strategic positions in the oligomerization interface. We further showed that removal of Ca(2+) ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca(2+) ions.

Perfect coupling of light to a periodic dielectric/metal/dielectric structure

Science.gov (United States)

Wang, Zhengling; Li, Shiqiang; Chang, R. P. H.; Ketterson, John B.

2014-07-01

Using the finite difference time domain method, it is demonstrated that perfect coupling can be achieved between normally incident light and a periodic dielectric/metal/dielectric structure. The structure serves as a diffraction grating that excites modes related to the long range surface plasmon and short range surface plasmon modes that propagate on continuous metallic films. By optimizing the structural dimensions, perfect coupling is achieved between the incident light and these modes. A high Q of 697 and an accompanying ultrasharp linewidth of 0.8 nm are predicted for a 10 nm silver film for optimal conditions.

Perfect 2-colorings of the generalized Petersen graph

Indian Academy of Sciences (India)

It is obvious that GP(n, k) is a 3-regular connected graph. DEFINITION 2.2 ... vertex of color i, the number of its neighbors of color j is equal to aij . ... By the given conditions, we can see that a parameter matrix of a perfect 2-coloring of. GP(n, k) ...

Unraveling the Role of RNA Mediated Toxicity of C9orf72 Repeats in C9-FTD/ALS

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Vijay Kumar

2017-12-01

Full Text Available The most frequent genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD is intronic hexanucleotide (G4C2 repeat expansions (HRE in the C9orf72 gene. The non-exclusive pathogenic mechanisms by which C9orf72 repeat expansions contribute to these neurological disorders include loss of C9orf72 function and gain-of-function determined by toxic RNA molecules and dipeptides repeats protein toxicity. The expanded repeats are transcribed bidirectionally and forms RNA foci in the central nervous system, and sequester key RNA-binding proteins (RBPs leading to impairment in RNA processing events. Many studies report widespread transcriptome changes in ALS carrying a C9orf72 repeat expansion. Here we review the contribution of RNA foci interaction with RBPs as well as transcriptome changes involved in the pathogenesis of C9orf72- associated FTD/ALS. These informations are essential to elucidate the pathology and therapeutic intervention of ALS and/or FTD.

Repeat-Associated Plasticity in the Helicobacter pylori RD Gene Family▿ †

Science.gov (United States)

Shak, Joshua R.; Dick, Jonathan J.; Meinersmann, Richard J.; Perez-Perez, Guillermo I.; Blaser, Martin J.

2009-01-01

The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3′ region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5′ region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host. PMID:19749042

Upon Infection the Cellular WD Repeat-containing Protein 5 (WDR5) Localizes to Cytoplasmic Inclusion Bodies and Enhances Measles Virus Replication.

Science.gov (United States)

Ma, Dzwokai; George, Cyril X; Nomburg, Jason; Pfaller, Christian K; Cattaneo, Roberto; Samuel, Charles E

2017-12-13

Replication of negative-strand RNA viruses occurs in association with discrete cytoplasmic foci called inclusion bodies. Whereas inclusion bodies represent a prominent subcellular structure induced by viral infection, our knowledge of the cellular protein components involved in inclusion body formation and function is limited. Using measles virus-infected HeLa cells, we found that the WD repeat-containing protein 5 (WDR5), a subunit of histone H3 lysine 4 methyltransferases, was selectively recruited to virus-induced inclusion bodies. Furthermore, WDR5 was found in complexes containing viral proteins associated with RNA replication. WDR5 was not detected with mitochondria, stress granules, or other known secretory or endocytic compartments of infected cells. WDR5 deficiency decreased both viral protein production and infectious virus yields. Interferon production was modestly increased in WDR5 deficient cells. Thus, our study identifies WDR5 as a novel viral inclusion body-associated cellular protein and suggests a role for WDR5 in promoting viral replication. IMPORTANCE Measles virus is a human pathogen that remains a global concern with more than 100,000 measles-related deaths annually despite the availability of an effective vaccine. As measles continues to cause significant morbidity and mortality, understanding the virus-host interactions at the molecular level that affect virus replication efficiency is important for development and optimization of treatment procedures. Measles virus is an RNA virus that encodes six genes and replicates in the cytoplasm of infected cells in discrete cytoplasmic replication bodies, though little is known of the biochemical nature of these structures. Here we show that the cellular protein WDR5 is enriched in the cytoplasmic viral replication factories and enhances virus growth. WDR5-containing protein complex includes viral proteins responsible for viral RNA replication. Thus, we have identified WDR5 as a host factor that

Fas-associated factor 1 is a scaffold protein that promotes β-transducin repeat-containing protein (β-TrCP)-mediated β-catenin ubiquitination and degradation.

Science.gov (United States)

Zhang, Long; Zhou, Fangfang; Li, Yihao; Drabsch, Yvette; Zhang, Juan; van Dam, Hans; ten Dijke, Peter

2012-08-31

FAS-associated factor 1 (FAF1) antagonizes Wnt signaling by stimulating β-catenin degradation. However, the molecular mechanism underlying this effect is unknown. Here, we demonstrate that the E3 ubiquitin ligase β-transducin repeat-containing protein (β-TrCP) is required for FAF1 to suppress Wnt signaling and that FAF1 specifically associates with the SCF (Skp1-Cul1-F-box protein)-β-TrCP complex. Depletion of β-TrCP reduced FAF1-mediated β-catenin polyubiquitination and impaired FAF1 in antagonizing Wnt/β-catenin signaling. FAF1 was shown to act as a scaffold for β-catenin and β-TrCP and thereby to potentiate β-TrCP-mediated β-catenin ubiquitination and degradation. Data mining revealed that FAF1 expression is statistically down-regulated in human breast carcinoma compared with normal breast tissue. Consistent with this, FAF1 expression is higher in epithelial-like MCF7 than mesenchymal-like MDA-MB-231 human breast cancer cells. Depletion of FAF1 in MCF7 cells resulted in increased β-catenin accumulation and signaling. Importantly, FAF1 knockdown promoted a decrease in epithelial E-cadherin and an increase in mesenchymal vimentin expression, indicative for an epithelial to mesenchymal transition. Moreover, ectopic FAF1 expression reduces breast cancer cell migration in vitro and invasion/metastasis in vivo. Thus, our studies strengthen a tumor-suppressive function for FAF1.

Metamaterials for perfect absorption

CERN Document Server

Lee, Young Pak; Yoo, Young Joon; Kim, Ki Won

2016-01-01

This book provides a comprehensive overview of the theory and practical development of metamaterial-based perfect absorbers (MMPAs). It begins with a brief history of MMPAs which reviews the various theoretical and experimental milestones in their development. The theoretical background and fundamental working principles of MMPAs are then discussed, providing the necessary background on how MMPAs work and are constructed. There then follows a section describing how different MMPAs are designed and built according to the operating frequency of the electromagnetic wave, and how their behavior is changed. Methods of fabricating and characterizing MMPAs are then presented. The book elaborates on the performance and characteristics of MMPAs, including electromagnetically-induced transparency (EIT). It also covers recent advances in MMPAs and their applications, including multi-band, broadband, tunability, polarization independence and incidence independence. Suitable for graduate students in optical sciences and e...

Scalar-metric quantum cosmology with Chaplygin gas and perfect fluid

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Saumya; Panigrahi, Prasanta K. [Indian Institute of Science Education and Research Kolkata, Nadia, West Bengal (India); Gangopadhyay, Sunandan [Indian Institute of Science Education and Research Kolkata, Nadia, West Bengal (India); S.N. Bose National Centre for Basic Sciences, Kolkata (India)

2018-01-15

In this paper we consider the flat FRW cosmology with a scalar field coupled with the metric along with generalized Chaplygin gas and perfect fluid comprising the matter sector. We use the Schutz's formalism to deal with the generalized Chaplygin gas sector. The full theory is then quantized canonically using the Wheeler-DeWitt Hamiltonian formalism. We then solve the WD equation with appropriate boundary conditions. Then by defining a proper completeness relation for the self-adjointness of the WD equation we arrive at the wave packet for the universe. It is observed that the peak in the probability density gets affected due to both fluids in the matter sector, namely, the Chaplygin gas and perfect fluid. (orig.)

Tunable enhanced optical absorption of graphene using plasmonic perfect absorbers

Energy Technology Data Exchange (ETDEWEB)

Cai, Yijun [Institute of Optoelectronic Technology, Department of Electronic Engineering, Xiamen University, Xiamen 361005 (China); Institute of Electromagnetics and Acoustics, Department of Electronic Science, Xiamen University, Xiamen 361005 (China); Zhu, Jinfeng, E-mail: nanoantenna@hotmail.com [Institute of Electromagnetics and Acoustics, Department of Electronic Science, Xiamen University, Xiamen 361005 (China); Liu, Qing Huo [Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States)

2015-01-26

Enhancement and manipulation of light absorption in graphene is a significant issue for applications of graphene-based optoelectronic devices. In order to achieve this purpose in the visible region, we demonstrate a design of a graphene optical absorber inspired by metal-dielectric-metal metamaterial for perfect absorption of electromagnetic waves. The optical absorbance ratios of single and three atomic layer graphene are enhanced up to 37.5% and 64.8%, respectively. The graphene absorber shows polarization-dependence and tolerates a wide range of incident angles. Furthermore, the peak position and bandwidth of graphene absorption spectra are tunable in a wide wavelength range through a specific structural configuration. These results imply that graphene in combination with plasmonic perfect absorbers have a promising potential for developing advanced nanophotonic devices.

Functional and genomic analyses of alpha-solenoid proteins.

Science.gov (United States)

Fournier, David; Palidwor, Gareth A; Shcherbinin, Sergey; Szengel, Angelika; Schaefer, Martin H; Perez-Iratxeta, Carol; Andrade-Navarro, Miguel A

2013-01-01

Alpha-solenoids are flexible protein structural domains formed by ensembles of alpha-helical repeats (Armadillo and HEAT repeats among others). While homology can be used to detect many of these repeats, some alpha-solenoids have very little sequence homology to proteins of known structure and we expect that many remain undetected. We previously developed a method for detection of alpha-helical repeats based on a neural network trained on a dataset of protein structures. Here we improved the detection algorithm and updated the training dataset using recently solved structures of alpha-solenoids. Unexpectedly, we identified occurrences of alpha-solenoids in solved protein structures that escaped attention, for example within the core of the catalytic subunit of PI3KC. Our results expand the current set of known alpha-solenoids. Application of our tool to the protein universe allowed us to detect their significant enrichment in proteins interacting with many proteins, confirming that alpha-solenoids are generally involved in protein-protein interactions. We then studied the taxonomic distribution of alpha-solenoids to discuss an evolutionary scenario for the emergence of this type of domain, speculating that alpha-solenoids have emerged in multiple taxa in independent events by convergent evolution. We observe a higher rate of alpha-solenoids in eukaryotic genomes and in some prokaryotic families, such as Cyanobacteria and Planctomycetes, which could be associated to increased cellular complexity. The method is available at http://cbdm.mdc-berlin.de/~ard2/.

Genome-wide cloning and sequence analysis of leucine-rich repeat receptor-like protein kinase genes in Arabidopsis thaliana

Directory of Open Access Journals (Sweden)

Yuan Tong

2010-01-01

Full Text Available Abstract Background Transmembrane receptor kinases play critical roles in both animal and plant signaling pathways regulating growth, development, differentiation, cell death, and pathogenic defense responses. In Arabidopsis thaliana, there are at least 223 Leucine-rich repeat receptor-like kinases (LRR-RLKs, representing one of the largest protein families. Although functional roles for a handful of LRR-RLKs have been revealed, the functions of the majority of members in this protein family have not been elucidated. Results As a resource for the in-depth analysis of this important protein family, the complementary DNA sequences (cDNAs of 194 LRR-RLKs were cloned into the GatewayR donor vector pDONR/ZeoR and analyzed by DNA sequencing. Among them, 157 clones showed sequences identical to the predictions in the Arabidopsis sequence resource, TAIR8. The other 37 cDNAs showed gene structures distinct from the predictions of TAIR8, which was mainly caused by alternative splicing of pre-mRNA. Most of the genes have been further cloned into GatewayR destination vectors with GFP or FLAG epitope tags and have been transformed into Arabidopsis for in planta functional analysis. All clones from this study have been submitted to the Arabidopsis Biological Resource Center (ABRC at Ohio State University for full accessibility by the Arabidopsis research community. Conclusions Most of the Arabidopsis LRR-RLK genes have been isolated and the sequence analysis showed a number of alternatively spliced variants. The generated resources, including cDNA entry clones, expression constructs and transgenic plants, will facilitate further functional analysis of the members of this important gene family.

Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome

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Karen Kelley

2012-01-01

Full Text Available The majority of the human genome is comprised of non-coding DNA, which frequently contains redundant microsatellite-like trinucleotide repeats. Many of these trinucleotide repeats are involved in triplet repeat expansion diseases (TREDs such as fragile X syndrome (FXS. After transcription, the trinucleotide repeats can fold into RNA hairpins and are further processed by Dicer endoribonuclases to form microRNA (miRNA-like molecules that are capable of triggering targeted gene-silencing effects in the TREDs. However, the function of these repeat-associated miRNAs (ramRNAs is unclear. To solve this question, we identified the first native ramRNA in FXS and successfully developed a transgenic zebrafish model for studying its function. Our studies showed that ramRNA-induced DNA methylation of the FMR1 5′-UTR CGG trinucleotide repeat expansion is responsible for both pathological and neurocognitive characteristics linked to the transcriptional FMR1 gene inactivation and the deficiency of its protein product FMRP. FMRP deficiency often causes synapse deformity in the neurons essential for cognition and memory activities, while FMR1 inactivation augments metabotropic glutamate receptor (mGluR-activated long-term depression (LTD, leading to abnormal neuronal responses in FXS. Using this novel animal model, we may further dissect the etiological mechanisms of TREDs, with the hope of providing insights into new means for therapeutic intervention.

MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review of the literature.

Science.gov (United States)

Dumitrescu, Laura; Popescu, Bogdan O

2015-01-01

MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.

Single Strand Annealing Plays a Major Role in RecA-Independent Recombination between Repeated Sequences in the Radioresistant Deinococcus radiodurans Bacterium.

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Solenne Ithurbide

2015-10-01

Full Text Available The bacterium Deinococcus radiodurans is one of the most radioresistant organisms known. It is able to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Our work aims to highlight the genes involved in recombination between 438 bp direct repeats separated by intervening sequences of various lengths ranging from 1,479 bp to 10,500 bp to restore a functional tetA gene in the presence or absence of radiation-induced DNA double strand breaks. The frequency of spontaneous deletion events between the chromosomal direct repeats were the same in recA+ and in ΔrecA, ΔrecF, and ΔrecO bacteria, whereas recombination between chromosomal and plasmid DNA was shown to be strictly dependent on the RecA and RecF proteins. The presence of mutations in one of the repeated sequence reduced, in a MutS-dependent manner, the frequency of the deletion events. The distance between the repeats did not influence the frequencies of deletion events in recA+ as well in ΔrecA bacteria. The absence of the UvrD protein stimulated the recombination between the direct repeats whereas the absence of the DdrB protein, previously shown to be involved in DNA double strand break repair through a single strand annealing (SSA pathway, strongly reduces the frequency of RecA- (and RecO- independent deletions events. The absence of the DdrB protein also increased the lethal sectoring of cells devoid of RecA or RecO protein. γ-irradiation of recA+ cells increased about 10-fold the frequencies of the deletion events, but at a lesser extend in cells devoid of the DdrB protein. Altogether, our results suggest a major role of single strand annealing in DNA repeat deletion events in bacteria devoid of the RecA protein, and also in recA+ bacteria exposed to ionizing radiation.

The Perfect Storm—Genetic Engineering, Science, and Ethics

Science.gov (United States)

Rollin, Bernard E.

2014-02-01

Uncertainty about ethics has been a major factor in societal rejection of biotechnology. Six factors help create a societal "perfect storm" regarding ethics and biotechnology: Social demand for ethical discussion; societal scientific illiteracy; poor social understanding of ethics; a "Gresham's Law for Ethics;" Scientific Ideology; vested interests dominating ethical discussion. How this can be remedied is discussed.

A Lightweight Anonymous Authentication Protocol with Perfect Forward Secrecy for Wireless Sensor Networks

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Ling Xiong

2017-11-01

Full Text Available Due to their frequent use in unattended and hostile deployment environments, the security in wireless sensor networks (WSNs has attracted much interest in the past two decades. However, it remains a challenge to design a lightweight authentication protocol for WSNs because the designers are confronted with a series of desirable security requirements, e.g., user anonymity, perfect forward secrecy, resistance to de-synchronization attack. Recently, the authors presented two authentication schemes that attempt to provide user anonymity and to resist various known attacks. Unfortunately, in this work we shall show that user anonymity of the two schemes is achieved at the price of an impractical search operation—the gateway node may search for every possible value. Besides this defect, they are also prone to smart card loss attacks and have no provision for perfect forward secrecy. As our main contribution, a lightweight anonymous authentication scheme with perfect forward secrecy is designed, and what we believe the most interesting feature is that user anonymity, perfect forward secrecy, and resistance to de-synchronization attack can be achieved at the same time. As far as we know, it is extremely difficult to meet these security features simultaneously only using the lightweight operations, such as symmetric encryption/decryption and hash functions.

A Lightweight Anonymous Authentication Protocol with Perfect Forward Secrecy for Wireless Sensor Networks.

Science.gov (United States)

Xiong, Ling; Peng, Daiyuan; Peng, Tu; Liang, Hongbin; Liu, Zhicai

2017-11-21

Due to their frequent use in unattended and hostile deployment environments, the security in wireless sensor networks (WSNs) has attracted much interest in the past two decades. However, it remains a challenge to design a lightweight authentication protocol for WSNs because the designers are confronted with a series of desirable security requirements, e.g., user anonymity, perfect forward secrecy, resistance to de-synchronization attack. Recently, the authors presented two authentication schemes that attempt to provide user anonymity and to resist various known attacks. Unfortunately, in this work we shall show that user anonymity of the two schemes is achieved at the price of an impractical search operation-the gateway node may search for every possible value. Besides this defect, they are also prone to smart card loss attacks and have no provision for perfect forward secrecy. As our main contribution, a lightweight anonymous authentication scheme with perfect forward secrecy is designed, and what we believe the most interesting feature is that user anonymity, perfect forward secrecy, and resistance to de-synchronization attack can be achieved at the same time. As far as we know, it is extremely difficult to meet these security features simultaneously only using the lightweight operations, such as symmetric encryption/decryption and hash functions.

Recurrent network models for perfect temporal integration of fluctuating correlated inputs.

Directory of Open Access Journals (Sweden)

Hiroshi Okamoto

2009-06-01

Full Text Available Temporal integration of input is essential to the accumulation of information in various cognitive and behavioral processes, and gradually increasing neuronal activity, typically occurring within a range of seconds, is considered to reflect such computation by the brain. Some psychological evidence suggests that temporal integration by the brain is nearly perfect, that is, the integration is non-leaky, and the output of a neural integrator is accurately proportional to the strength of input. Neural mechanisms of perfect temporal integration, however, remain largely unknown. Here, we propose a recurrent network model of cortical neurons that perfectly integrates partially correlated, irregular input spike trains. We demonstrate that the rate of this temporal integration changes proportionately to the probability of spike coincidences in synaptic inputs. We analytically prove that this highly accurate integration of synaptic inputs emerges from integration of the variance of the fluctuating synaptic inputs, when their mean component is kept constant. Highly irregular neuronal firing and spike coincidences are the major features of cortical activity, but they have been separately addressed so far. Our results suggest that the efficient protocol of information integration by cortical networks essentially requires both features and hence is heterotic.

Methodic of perfection of higher pedagogical educational establishments girl students’ rhythm

Directory of Open Access Journals (Sweden)

A.N. Kolumbet

2016-06-01

Full Text Available Purpose: to study influence of methodic of rhythm perfection on girl students’ coordination abilities. Material: in the research 264 girl students participated. We assessed individual and collective rhythm, internal and external motor rhythm; rhythm in exercises with musical accompaniment. Results: we have determined that creative motor tasks require variable conditions for their realization. We have proved demand in appropriate criteria for their assessment. It is noted that there is a demand in development of rhythm, considering its main kinds and manifestations, which are formed with some peculiarities. Individual rhythm is determined by activation of attention and its level. It is perfected more successfully rather with stimulated development than with natural. It was found that with age the character of natural progressing of rhythm preserves. Conclusions: it is recommended to develop rhythm in compliance with its kinds and manifestations. Progressing and perfection of rhythm is a long lasted process and shall be realized during all period of girl students’ studying. Such approach forms girl students’ demand in finding of purposeful motor rhythm in all their new motor actions. It ensures optimality of their fulfillment.

A corrugated perfect magnetic conductor surface supporting spoof surface magnon polaritons.

Science.gov (United States)

Liu, Liang-liang; Li, Zhuo; Gu, Chang-qing; Ning, Ping-ping; Xu, Bing-zheng; Niu, Zhen-yi; Zhao, Yong-jiu

2014-05-05

In this paper, we demonstrate that spoof surface magnon polaritons (SSMPs) can propagate along a corrugated perfect magnetic conductor (PMC) surface. From duality theorem, the existence of surface electromagnetic modes on corrugated PMC surfaces are manifest to be transverse electric (TE) mode compared with the transverse magnetic (TM) mode of spoof surface plasmon plaritons (SSPPs) excited on corrugated perfect electric conductor surfaces. Theoretical deduction through modal expansion method and simulation results clearly verify that SSMPs share the same dispersion relationship with the SSPPs. It is worth noting that this metamaterial will have more similar properties and potential applications as the SSPPs in large number of areas.

Characterization of α-isopropylmalate synthases containing different copy numbers of tandem repeats in Mycobacterium tuberculosis

Directory of Open Access Journals (Sweden)

Palittapongarnpim Prasit

2009-06-01

Full Text Available Abstract Background Alpha-isopropylmalate synthase (α-IPMS is the key enzyme that catalyzes the first committed step in the leucine biosynthetic pathway. The gene encoding α-IPMS in Mycobacterium tuberculosis, leuA, is polymorphic due to the insertion of 57-bp repeat units referred to as Variable Number of Tandem Repeats (VNTR. The role of the VNTR found within the M. tuberculosis genome is unclear. To investigate the role of the VNTR in leuA, we compared two α-IPMS proteins with different numbers of amino acid repeats, one with two copies and the other with 14 copies. We have cloned leuA with 14 copies of the repeat units into the pET15b expression vector with a His6-tag at the N-terminus, as was previously done for the leuA gene with two copies of the repeat units. Results The recombinant His6-α-IPMS proteins with two and 14 copies (α-IPMS-2CR and α-IPMS-14CR, respectively of the repeat units were purified by immobilized metal ion affinity chromatography and gel filtration. Both enzymes were found to be dimers by gel filtration. Both enzymes work well at pH values of 7–8.5 and temperatures of 37–42°C. However, α-IPMS-14CR tolerates pH values and temperatures outside of this range better than α-IPMS-2CR does. α-IPMS-14CR has higher affinity than α-IPMS-2CR for the two substrates, α-ketoisovalerate and acetyl CoA. Furthermore, α-IPMS-2CR was feedback inhibited by the end product l-leucine, whereas α-IPMS-14CR was not. Conclusion The differences in the kinetic properties and the l-leucine feedback inhibition between the two M. tuberculosis α-IPMS proteins containing low and high numbers of VNTR indicate that a large VNTR insertion affects protein structure and function. Demonstration of l-leucine binding to α-IPMS-14CR would confirm whether or not α-IPMS-14CR responds to end-product feedback inhibition.

Rhoptry-associated protein (rap-1) genes in the sheep pathogen Babesia sp. Xinjiang: Multiple transcribed copies differing by 3' end repeated sequences.

Science.gov (United States)

Niu, Qingli; Marchand, Jordan; Yang, Congshan; Bonsergent, Claire; Guan, Guiquan; Yin, Hong; Malandrin, Laurence

2015-07-30

Sheep babesiosis occurs mainly in tropical and subtropical areas. The sheep parasite Babesia sp. Xinjiang is widespread in China, and our goal is to characterize rap-1 (rhoptry-associated protein 1) gene diversity and expression as a first step of a long term goal aiming at developing a recombinant subunit vaccine. Seven different rap-1a genes were amplified in Babesia sp. Xinjiang, using degenerate primers designed from conserved motifs. Rap-1b and rap-1c gene types could not be identified. In all seven rap-1a genes, the 5' regions exhibited identical sequences over 936 nt, and the 3' regions differed at 28 positions over 147 nt, defining two types of genes designated α and β. The remaining 3' part varied from 72 to 360 nt in length, depending on the gene. This region consists of a succession of two to ten 36 nt repeats, which explains the size differences. Even if the nucleotide sequences varied, 6 repeats encoded the same stretch of amino acids. Transcription of at least four α and two β genes was demonstrated by standard RT-PCR. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced Expression of WD Repeat-Containing Protein 35 via CaMKK/AMPK Activation in Bupivacaine-Treated Neuro2a Cells

Science.gov (United States)

Huang, Lei; Kondo, Fumio; Gosho, Masahiko; Feng, Guo-Gang; Harato, Misako; Xia, Zhong-yuan; Ishikawa, Naohisa; Fujiwara, Yoshihiro; Okada, Shoshiro

2014-01-01

We previously reported that bupivacaine induces reactive oxygen species (ROS) generation, p38 mitogen-activated protein kinase (MAPK) activation and nuclear factor-kappa B activation, resulting in an increase in expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. However, the identity of signaling upstream of p38 MAPK pathways to WDR35 expression remains unclear. It has been shown that AMP-activated protein kinase (AMPK) can activate p38 MAPK through diverse mechanisms. In addition, several kinases acting upstream of AMPK have been identified including Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Recent studies reported that AMPK may be involved in bupivacaine-induced cytotoxicity in Schwann cells and in human neuroblastoma SH-SY5Y cells. The present study was undertaken to test whether CaMKK and AMPK are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Our results showed that bupivacaine induced activation of AMPK and p38 MAPK in Neuro2a cells. The AMPK inhibitors, compound C and iodotubercidin, attenuated the bupivacaine-induced activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine-induced increase in WDR35 expression. Treatment with the CaMKK inhibitor STO-609 also attenuated the bupivacaine-induced activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine-induced increase in WDR35 expression. These results suggest that bupivacaine activates AMPK and p38 MAPK via CaMKK in Neuro2a cells, and that the CaMKK/AMPK/p38 MAPK pathway is involved in regulating WDR35 expression. PMID:24859235

Perfect Worlds : Utopian Fiction in China and the West

NARCIS (Netherlands)

Fokkema, Douwe

2011-01-01

Perfect Worlds biedt een uitgebreide historische analyse van utopische verhalen in de Chinese en Euro-Amerikaanse traditie. Aan bod komen onder meer de kritiek van Thomas More op Plato, de Europese oriëntalistische speurtocht naar utopieën in China en Chinese schrijvers die hun confucianistische

Perfect Worlds : Utopian Fiction in China and the West

NARCIS (Netherlands)

Fokkema, Douwe

2011-01-01

Perfect Worlds biedt een uitgebreide historische analyse van utopische verhalen in de Chinese en Euro-Amerikaanse traditie. Verschillende hoofdstukken gaan onder meer in op de kritiek van Thomas More op Plato, de Europese oriëntalistische speurtocht naar utopieën in China, Dostoevsky’s reactie op

The periphrastic perfect of Old Persian revisited (slides) [Dataset

NARCIS (Netherlands)

Bavant, M.J.J.

2011-01-01

The voice of the periphrastic perfect of Old Persian has long been a controversial issue. This document is a slide set to present the matter. It illustrates the contents of an article on the same theme: "Retour sur le parfait périphrastique du vieux perse".

Gauge freedom in perfect fluid spatially homogeneous spacetimes

International Nuclear Information System (INIS)

Jantzen, R.T.

1983-01-01

The class of reference systems compatible with the symmetry of a spatially homogeneous perfect fluid spacetime is discussed together with the associated class of symmetry adapted comoving ADM frames (or computational frames). The fluid equations of motion are related to the four functions on the space of fluid flow lines discovered by Taub and which characterize an isentropic flow. (Auth.)

Comment on 'Perfect imaging without negative refraction'

Science.gov (United States)

Blaikie, R. J.

2010-05-01

The prediction of 'perfect' imaging without negative refraction for Maxwell's fish-eye lens (Leonhardt U 2009 New J. Phys. 11 093040) is a consequence of imposing an active localized 'drain' at the image point rather than being a general property of the lens. This work then becomes analogous to other work using time-reversal symmetry and/or structured antennae to achieve super-resolution, which can be applied to many types of imaging system beyond the fish-eye lens.

Comment on 'Perfect imaging without negative refraction'

International Nuclear Information System (INIS)

Blaikie, R J

2010-01-01

The prediction of 'perfect' imaging without negative refraction for Maxwell's fish-eye lens (Leonhardt U 2009 New J. Phys. 11 093040) is a consequence of imposing an active localized 'drain' at the image point rather than being a general property of the lens. This work then becomes analogous to other work using time-reversal symmetry and/or structured antennae to achieve super-resolution, which can be applied to many types of imaging system beyond the fish-eye lens.

Interrogating Key Positions of Size-Reduced TALE Repeats Reveals a Programmable Sensor of 5-Carboxylcytosine.

Science.gov (United States)

Maurer, Sara; Giess, Mario; Koch, Oliver; Summerer, Daniel

2016-12-16

Transcription-activator-like effector (TALE) proteins consist of concatenated repeats that recognize consecutive canonical nucleobases of DNA via the major groove in a programmable fashion. Since this groove displays unique chemical information for the four human epigenetic cytosine nucleobases, TALE repeats with epigenetic selectivity can be engineered, with potential to establish receptors for the programmable decoding of all human nucleobases. TALE repeats recognize nucleobases via key amino acids in a structurally conserved loop whose backbone is positioned very close to the cytosine 5-carbon. This complicates the engineering of selectivities for large 5-substituents. To interrogate a more promising structural space, we engineered size-reduced repeat loops, performed saturation mutagenesis of key positions, and screened a total of 200 repeat-nucleobase interactions for new selectivities. This provided insight into the structural requirements of TALE repeats for affinity and selectivity, revealed repeats with improved or relaxed selectivity, and resulted in the first selective sensor of 5-carboxylcytosine.

Protection against syphilis correlates with specificity of antibodies to the variable regions of Treponema pallidum repeat protein K.

Science.gov (United States)

Morgan, Cecilia A; Lukehart, Sheila A; Van Voorhis, Wesley C

2003-10-01

Syphilis has been recognized as a disease since the late 1400s, yet there is no practical vaccine available. One impediment to the development of a vaccine is the lack of understanding of multiple reinfections in humans despite the development of robust immune responses during the first episode. It has been shown that the Treponema pallidum repeat protein K (TprK) differs in seven discrete variable (V) regions in isolates and that the antibody response during infection is directed to these V regions. Immunization with TprK confers significant protection against infection with the homologous strain. We hypothesize that the antigenic diversity of TprK is involved in immune evasion, which contributes to the lack of heterologous protection. Here, using the rabbit model, we show a correlation between limited heterologous protection and tprK diversity in the challenge inoculum. We demonstrate that antibody responses to the V regions of one TprK molecule show limited cross-reactivity with heterologous TprK V regions.

Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits

Directory of Open Access Journals (Sweden)

Saul Herranz-Martin

2017-07-01

Full Text Available Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Two major pathologies stemming from the hexanucleotide RNA expansions (HREs have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN dipeptides, although it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here, we describe two novel lines of mice that overexpress either 10 pure or 102 interrupted GGGGCC repeats mediated by adeno-associated virus (AAV and recapitulate the relevant human pathology and disease-related behavioural phenotypes. Similar levels of intracellular RNA foci developed in both lines of mice, but only mice expressing 102 repeats generated C9orf72 RAN pathology, neuromuscular junction (NMJ abnormalities, dispersal of the hippocampal CA1, enhanced apoptosis, and deficits in gait and cognition. Neither line of mice, however, showed extensive TAR DNA-binding protein 43 (TDP-43 pathology or neurodegeneration. Our data suggest that RNA foci pathology is not a good predictor of C9orf72 RAN dipeptide formation, and that RAN dipeptides and NMJ dysfunction are drivers of C9orf72 disease pathogenesis. These AAV-mediated models of C9orf72-associated ALS/FTD will be useful tools for studying disease pathophysiology and developing new therapeutic approaches.

Overemphasis on Perfectly Competitive Markets in Microeconomics Principles Textbooks

Science.gov (United States)

Hill, Roderick; Myatt, Anthony

2007-01-01

Microeconomic principles courses focus on perfectly competitive markets far more than other market structures. The authors examine five possible reasons for this but find none of them sufficiently compelling. They conclude that textbook authors should place more emphasis on how economists select appropriate models and test models' predictions…

Hypersurface-homogeneous Universe filled with perfect fluid in f ( R ...

Indian Academy of Sciences (India)

homogeneous Universe filled with perfect fluid in the framework of f ( R , T ) theory of gravity (Harko et al, \\emph{Phys. Rev.} D 84, 024020 (2011)) is derived. The physical behaviour of the cosmological model is studied.

Identification of genes containing expanded purine repeats in the human genome and their apparent protective role against cancer.

Science.gov (United States)

Singh, Himanshu Narayan; Rajeswari, Moganty R

2016-01-01

Purine repeat sequences present in a gene are unique as they have high propensity to form unusual DNA-triple helix structures. Friedreich's ataxia is the only human disease that is well known to be associated with DNA-triplexes formed by purine repeats. The purpose of this study was to recognize the expanded purine repeats (EPRs) in human genome and find their correlation with cancer pathogenesis. We developed "PuRepeatFinder.pl" algorithm to identify non-overlapping EPRs without pyrimidine interruptions in the human genome and customized for searching repeat lengths, n ≥ 200. A total of 1158 EPRs were identified in the genome which followed Wakeby distribution. Two hundred and ninety-six EPRs were found in geneic regions of 282 genes (EPR-genes). Gene clustering of EPR-genes was done based on their cellular function and a large number of EPR-genes were found to be enzymes/enzyme modulators. Meta-analysis of 282 EPR-genes identified only 63 EPR-genes in association with cancer, mostly in breast, lung, and blood cancers. Protein-protein interaction network analysis of all 282 EPR-genes identified proteins including those in cadherins and VEGF. The two observations, that EPRs can induce mutations under malignant conditions and that identification of some EPR-gene products in vital cell signaling-mediated pathways, together suggest the crucial role of EPRs in carcinogenesis. The new link between EPR-genes and their functionally interacting proteins throws a new dimension in the present understanding of cancer pathogenesis and can help in planning therapeutic strategies. Validation of present results using techniques like NGS is required to establish the role of the EPR genes in cancer pathology.

Generation and characterization of a perfect vortex beam with a large topological charge through a digital micromirror device.

Science.gov (United States)

Chen, Yue; Fang, Zhao-Xiang; Ren, Yu-Xuan; Gong, Lei; Lu, Rong-De

2015-09-20

Optical vortices are associated with a spatial phase singularity. Such a beam with a vortex is valuable in optical microscopy, hyper-entanglement, and optical levitation. In these applications, vortex beams with a perfect circle shape and a large topological charge are highly desirable. But the generation of perfect vortices with high topological charges is challenging. We present a novel method to create perfect vortex beams with large topological charges using a digital micromirror device (DMD) through binary amplitude modulation and a narrow Gaussian approximation. The DMD with binary holograms encoding both the spatial amplitude and the phase could generate fast switchable, reconfigurable optical vortex beams with significantly high quality and fidelity. With either the binary Lee hologram or the superpixel binary encoding technique, we were able to generate the corresponding hologram with high fidelity and create a perfect vortex with topological charge as large as 90. The physical properties of the perfect vortex beam produced were characterized through measurements of propagation dynamics and the focusing fields. The measurements show good consistency with the theoretical simulation. The perfect vortex beam produced satisfies high-demand utilization in optical manipulation and control, momentum transfer, quantum computing, and biophotonics.

The Ideology of the Perfect Dictionary: How Efficient Can a ...

African Journals Online (AJOL)

friendly material which will improve both their fluency in and understanding of the target language, and embed acquired lexis in their long-term memory. Lexicographers, in their search for perfection and in compliance with users' wishes, are ...

Cognitive Learning Styles: Can You Engineer a "Perfect" Match?

Science.gov (United States)

Khuzzan, Sharifah Mazlina Syed; Goulding, Jack Steven

2016-01-01

Education and training is widely acknowledged as being one of the key factors for leveraging organisational success. However, it is equally acknowledged that skills development and the acquisition of learning through managed cognitive approaches has yet to provide a "perfect" match. Whilst it is argued that an ideal learning scenario…

Perfect and imperfect states

Directory of Open Access Journals (Sweden)

Nikitović Aleksandar

2013-01-01

Full Text Available Early Greek ethics embodied in Cretan and Spartan mores, served as a model for Plato`s political theory. Plato theorized the contents of early Greek ethics, aspiring to justify and revitalize the fundamental principles of a traditional view of the world. However, according to Plato`s new insight, deed is further from the truth than a thought i.e. theory. The dorian model had to renounce its position to the perfect prototype of a righteous state, which is a result of the inner logic of philosophical theorizing in early Greek ethics. Prototype and model of philosophical reflection, in comparison to philosophical theory, becomes minor and deficient. Philosophical theorizing of early Greek ethics philosophically formatted Greek heritage, initiating substantial changes to the content of traditional ethics. Replacement of the myth with ontology, as a new foundation of politics, transformed early Greek ethics in various relevant ways. [Projekat Ministarstva nauke Republike Srbije, br. 179049

Novel beam bunching methods by perfect crystals and electromagnetic means

International Nuclear Information System (INIS)

Rauch, H.

1985-01-01

The use of perfect crystals for installing new neutron small-angle scattering cameras provides advantages for measurements in the small Q-range and for real-time experiments. A neutron resonator is proposed which is based on the combination of perfect crystal back-reflections in Zeman energy splitting. The neutron magnetic resonance system in combination with gated crystals can act as a pumping unit for neutrons and as a new pulse-shaping unit. It is shown how travelling magnetic waves can act as powerful neutron bunching units. The achievable velocity changes are around 5 m/s and, therefore, by a factor of 100 larger than in the case of neutron magnetic resonance systems. The advantage of expanding potentials for focusing neutrons from a source with a long pulse duration becomes obvious. Real gain factors higher than 10 are expected for properly designed systems. (author)

Ultra-broadband and wide-angle perfect absorber based on composite metal-semiconductor grating

Science.gov (United States)

Li, Xu; Wang, Zongpeng; Hou, Yumin

2018-01-01

In this letter, we present an ultra-broadband and wide-angle perfect absorber based on composite Ge-Ni grating. Near perfect absorption above 90% is achieved in a wide frequency range from 150 nm to 4200 nm, which covers almost the full spectrum of solar radiation. The absorption keeps robust in a wide range of incident angle from 0º to 60º. The upper triangle Ge grating works as an antireflection coating. The lower Ni grating works as a reflector and an effective energy trapper. The guided modes inside Ge grating are excited due to reflection of the lower Ni grating surface. In longer wavelength band, gap surface plasmons (GSPs) in the Ni grating are excited and couple with the guided modes inside the Ge grating. The coupled modes extend the perfect absorption band to the near-infrared region (150 nm-4200 nm). This design has potential application in photovoltaic devices and thermal emitters.

The Gaze of the Perfect Search Engine: Google as an Infrastructure of Dataveillance

Science.gov (United States)

Zimmer, M.

Web search engines have emerged as a ubiquitous and vital tool for the successful navigation of the growing online informational sphere. The goal of the world's largest search engine, Google, is to "organize the world's information and make it universally accessible and useful" and to create the "perfect search engine" that provides only intuitive, personalized, and relevant results. While intended to enhance intellectual mobility in the online sphere, this chapter reveals that the quest for the perfect search engine requires the widespread monitoring and aggregation of a users' online personal and intellectual activities, threatening the values the perfect search engines were designed to sustain. It argues that these search-based infrastructures of dataveillance contribute to a rapidly emerging "soft cage" of everyday digital surveillance, where they, like other dataveillance technologies before them, contribute to the curtailing of individual freedom, affect users' sense of self, and present issues of deep discrimination and social justice.

Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats

Directory of Open Access Journals (Sweden)

Daniël O. Warmerdam

2016-03-01

Full Text Available rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of breaks in 45S rDNA, and this results in repeat loss. We identify the structural maintenance of chromosomes protein 5 (SMC5 as contributing to recombination-mediated repair of rDNA breaks. Together, our data demonstrate that SMC5-mediated recombination can lead to error-prone repair of 45S rDNA repeats, resulting in their loss and thereby reducing cellular viability.

Designed ankyrin repeat proteins: a new approach to mimic complex antigens for diagnostic purposes?

Directory of Open Access Journals (Sweden)

Stefanie Hausammann

Full Text Available Inhibitory antibodies directed against coagulation factor VIII (FVIII can be found in patients with acquired and congenital hemophilia A. Such FVIII-inhibiting antibodies are routinely detected by the functional Bethesda Assay. However, this assay has a low sensitivity and shows a high inter-laboratory variability. Another method to detect antibodies recognizing FVIII is ELISA, but this test does not allow the distinction between inhibitory and non-inhibitory antibodies. Therefore, we aimed at replacing the intricate antigen FVIII by Designed Ankyrin Repeat Proteins (DARPins mimicking the epitopes of FVIII inhibitors. As a model we used the well-described inhibitory human monoclonal anti-FVIII antibody, Bo2C11, for the selection on DARPin libraries. Two DARPins were selected binding to the antigen-binding site of Bo2C11, which mimic thus a functional epitope on FVIII. These DARPins inhibited the binding of the antibody to its antigen and restored FVIII activity as determined in the Bethesda assay. Furthermore, the specific DARPins were able to recognize the target antibody in human plasma and could therefore be used to test for the presence of Bo2C11-like antibodies in a large set of hemophilia A patients. These data suggest, that our approach might be used to isolate epitopes from different sets of anti-FVIII antibodies in order to develop an ELISA-based screening assay allowing the distinction of inhibitory and non-inhibitory anti-FVIII antibodies according to their antibody signatures.

C9orf72 nucleotide repeat structures initiate molecular cascades of disease.

Science.gov (United States)

Haeusler, Aaron R; Donnelly, Christopher J; Periz, Goran; Simko, Eric A J; Shaw, Patrick G; Kim, Min-Sik; Maragakis, Nicholas J; Troncoso, Juan C; Pandey, Akhilesh; Sattler, Rita; Rothstein, Jeffrey D; Wang, Jiou

2014-03-13

A hexanucleotide repeat expansion (HRE), (GGGGCC)n, in C9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we identify a molecular mechanism by which structural polymorphism of the HRE leads to ALS/FTD pathology and defects. The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA•DNA hybrids (R-loops). The structural polymorphism causes a repeat-length-dependent accumulation of transcripts aborted in the HRE region. These transcribed repeats bind to ribonucleoproteins in a conformation-dependent manner. Specifically, nucleolin, an essential nucleolar protein, preferentially binds the HRE G-quadruplex, and patient cells show evidence of nucleolar stress. Our results demonstrate that distinct C9orf72 HRE structural polymorphism at both DNA and RNA levels initiates molecular cascades leading to ALS/FTD pathologies, and provide the basis for a mechanistic model for repeat-associated neurodegenerative diseases.

Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.

Directory of Open Access Journals (Sweden)

Yao Song

Full Text Available AIMS: It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo. METHODS AND RESULTS: We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis. CONCLUSION: CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.

A simple route to scalable fabrication of perfectly ordered ZnO nanorod arrays

International Nuclear Information System (INIS)

Liu, D F; Xiang, Y J; Liao, Q; Zhang, J P; Wu, X C; Zhang, Z X; Liu, L F; Ma, W J; Shen, J; Zhou, W Y; Xie, S S

2007-01-01

ZnO nanorod arrays with perfect order and uniformity were prepared using a simple, low-cost, commonly available and scalable nanosphere lithography for patterning gold catalyst particles and a successive bottom-up growth technique in a tube furnace chemical vapor deposition system. Each rod in the arrays had perfect surface facets, sharp edges and uniform size. For all of the rods, their sides were oriented the same. This bottom-up assembly method may accelerate the use of ZnO nanorods in real device applications

Polytropic solutions of a perfect fluid in spatial n-dimensions

International Nuclear Information System (INIS)

Luiz, Fabricio Casarejos Lopes; Rocha, Jaime F. Villas da

2005-01-01

We found all the solutions of a polytropic state equation for a n-dimensional metric associated to a perfect fluid. Some of them represent gravitational collapse with black hole or naked singularity formation. We found also an accelerating cosmological model. (author)

An improved perfectly matched layer in the eigenmode expansion technique

DEFF Research Database (Denmark)

Gregersen, Niels; Mørk, Jesper

2008-01-01

When employing the eigenmode expansion technique (EET), parasitic reflections at the boundary of the computational domain can be suppressed by introducing a perfectly matched layer (PML). However, the traditional PML, suffers from an artificial field divergence limiting its usefulness. We propose...

Comparison among perfect-C®, zero-P®, and plates with a cage in single-level cervical degenerative disc disease.

Science.gov (United States)

Noh, Sung Hyun; Zhang, Ho Yeol

2018-01-25

We intended to analyze the efficacy of a new integrated cage and plate device called Perfect-C for anterior cervical discectomy and fusion (ACDF) to cure single-level cervical degenerative disc disease. We enrolled 148 patients who were subjected to single-level ACDF with one of the following three surgical devices: a Perfect-C implant (41 patients), a Zero-P implant (36 patients), or a titanium plate with a polyetheretherketone (PEEK) cage (71 patients). We conducted a retrospective study to compare the clinical and radiological results among the three groups. The length of the operation, intraoperative blood loss, and duration of hospitalization were significantly lower in the Perfect-C group than in the Zero-P and plate-with-cage groups (P Zero-P groups but was noted in 21 cases (30%) in the plate-with-cage group. The cephalad and caudal plate-to-disc distance (PDD) and the cephalad and caudal PDD/anterior body height (ABH) were significantly greater in the Perfect-C and Zero-P groups than in the plate-with-cage group (P Zero-P group, and in 15 cases (21%) in the plate-with-cage group. Fusion occurred in 37 cases (90%) in the Perfect-C group, in 31 cases (86%) in the Zero-P group, and in 68 cases (95%) in the plate-with-cage group. The Perfect-C, Zero-P, and plate-with-cage devices are effective for treating single-level cervical degenerative disc disease. However, the Perfect-C implant has many advantages over both the Zero-P implant and conventional plate-cage treatments. The Perfect-C implant was associated with shorter operation times and hospitalization durations, less blood loss, and lower subsidence rates compared with the Zero-P implant or the titanium plate with a PEEK cage.

Dipeptide repeat protein inclusions are rare in the spinal cord and almost absent from motor neurons in C9ORF72 mutant amyotrophic lateral sclerosis and are unlikely to cause their degeneration.

Science.gov (United States)

Gomez-Deza, Jorge; Lee, Youn-Bok; Troakes, Claire; Nolan, Matthew; Al-Sarraj, Safa; Gallo, Jean-Marc; Shaw, Christopher E

2015-06-25

Cytoplasmic TDP-43 inclusions are the pathological hallmark of amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal lobar dementia (FTLD). The G4C2 repeat mutation in C9ORF72 is the most common cause of ALS and FTLD in which, in addition to TDP-43 inclusions, five different di-peptide repeat (DPR) proteins have been identified. Di-peptide repeat proteins are translated in a non-canonical fashion from sense and antisense transcripts of the G4C2 repeat (GP, GA, GR, PA, PR). DPR inclusions are abundant in the cerebellum, as well as in the frontal and temporal lobes of ALS and FTLD patients and some are neurotoxic in a range of cellular and animal models, implying that DPR aggregation directly contributes to disease pathogenesis. Here we sought to quantify inclusions for each DPR and TDP-43 in ALS cases with and without the C9ORF72 mutation. We characterised the abundance of DPRs and their cellular location and compared this to cytoplasmic TDP-43 inclusions in order to explore the role of each inclusion in lower motor neuron degeneration. Spinal cord sections from ten cases positive for the C9ORF72 repeat expansion (ALS-C9+ve) and five cases that were not were probed by double immunofluorescence staining for individual DPRs and TDP-43. Inclusions immunoreactive for each of the DPRs were present in the spinal cord but they were rare or very rare in abundance (in descending order of frequency: GA, GP, GR, PA and PR). TDP-43 cytoplasmic inclusions were 45- to 750-fold more frequent than any DPR, and fewer than 4 % of DPR inclusions colocalized with TDP-43 inclusions. In motor neurons, a single cytoplasmic DPR inclusion was detected (0.1 %) in contrast to the 34 % of motor neurons that contained cytoplasmic TDP-43 inclusions. Furthermore, the number of TDP-43 inclusions in ALS cases with and without the C9ORF72 mutation was nearly identical. For all other neurodegenerative diseases, the neurotoxic protein aggregates are detected in the affected

A novel multiple locus variable number of tandem repeat (VNTR) analysis (MLVA) method for Propionibacterium acnes.

Science.gov (United States)

Hauck, Yolande; Soler, Charles; Gérôme, Patrick; Vong, Rithy; Macnab, Christine; Appere, Géraldine; Vergnaud, Gilles; Pourcel, Christine

2015-07-01

Propionibacterium acnes plays a central role in the pathogenesis of acne and is responsible for severe opportunistic infections. Numerous typing schemes have been developed that allow the identification of phylotypes, but they are often insufficient to differentiate subtypes. To better understand the genetic diversity of this species and to perform epidemiological analyses, high throughput discriminant genotyping techniques are needed. Here we describe the development of a multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) method. Thirteen VNTRs were identified in the genome of P. acnes and were used to genotype a collection of clinical isolates. In addition, publically available sequencing data for 102 genomes were analyzed in silico, providing an MLVA genotype. The clustering of MLVA data was in perfect congruence with whole genome based clustering. Analysis of the clustered regularly interspaced short palindromic repeat (CRISPR) element uncovered new spacers, a supplementary source of genotypic information. The present MLVA13 scheme and associated internet database represents a first line genotyping assay to investigate large number of isolates. Particular strains may then be submitted to full genome sequencing in order to better analyze their pathogenic potential. Copyright © 2015 Elsevier B.V. All rights reserved.

Repeatability of Computerized Tomography-Based Anthropomorphic Measurements of Frailty in Patients With Pulmonary Fibrosis Undergoing Lung Transplantation.

Science.gov (United States)

McClellan, Taylor; Allen, Brian C; Kappus, Matthew; Bhatti, Lubna; Dafalla, Randa A; Snyder, Laurie D; Bashir, Mustafa R

To determine interreader and intrareader repeatability and correlations among measurements of computerized tomography-based anthropomorphic measurements in patients with pulmonary fibrosis undergoing lung transplantation. This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study of 23 randomly selected subjects (19 male and 4 female; median age = 69 years; range: 66-77 years) with idiopathic pulmonary fibrosis undergoing pulmonary transplantation, who had also undergone preoperative thoracoabdominal computerized tomography. Five readers of varying imaging experience independently performed the following cross-sectional area measurements at the inferior endplate of the L3 vertebral body: right and left psoas muscles, right and left paraspinal muscles, total abdominal musculature, and visceral and subcutaneous fat. The following measurements were obtained at the inferior endplate of T6: right and left paraspinal muscles with and without including the trapezius muscles and subcutaneous fat. Three readers repeated all measurements to assess intrareader repeatability. Intrareader repeatability was nearly perfect (interclass correlation coefficients = 0.99, P < 0.001). Interreader agreement was excellent across all 5 readers (interclass correlation coefficients: 0.71-0.99, P < 0.001). Coefficients of variance between measures ranged from 3.2%-6.8% for abdominal measurements, but were higher for thoracic measurements, up to 23.9%. Correlation between total paraspinal and total psoas muscle area was strong (r 2 = 0.67, P < 0.001). Thoracic and abdominal musculature had a weaker correlation (r 2 = 0.35-0.38, P < 0.001). Measures of thoracic and abdominal muscle and fat area are highly repeatable in patients with pulmonary fibrosis undergoing lung transplantation. Measures of muscle area are strongly correlated among abdominal locations, but inversely correlated between abdominal and thoracic locations

Characterization of the variable-number tandem repeats in vrrA from different Bacillus anthracis isolates

Energy Technology Data Exchange (ETDEWEB)

Jackson, P.J.; Walthers, E.A.; Richmond, K.L. [Los Alamos National Lab., NM (United States)] [and others

1997-04-01

PCR analysis of 198 Bacillus anthracis isolates revealed a variable region of DNA sequence differing in length among the isolates. Five Polymorphisms differed by the presence Of two to six copies of the 12-bp tandem repeat 5{prime}-CAATATCAACAA-3{prime}. This variable-number tandem repeat (VNTR) region is located within a larger sequence containing one complete open reading frame that encodes a putative 30-kDa protein. Length variation did not change the reading frame of the encoded protein and only changed the copy number of a 4-amino-acid sequence (QYQQ) from 2 to 6. The structure of the VNTR region suggests that these multiple repeats are generated by recombination or polymerase slippage. Protein structures predicted from the reverse-translated DNA sequence suggest that any structural changes in the encoded protein are confined to the region encoded by the VNTR sequence. Copy number differences in the VNTR region were used to define five different B. anthracis alleles. Characterization of 198 isolates revealed allele frequencies of 6.1, 17.7, 59.6, 5.6, and 11.1% sequentially from shorter to longer alleles. The high degree of polymorphism in the VNTR region provides a criterion for assigning isolates to five allelic categories. There is a correlation between categories and geographic distribution. Such molecular markers can be used to monitor the epidemiology of anthrax outbreaks in domestic and native herbivore populations. 22 refs., 4 figs., 3 tabs.

Crystal Structure of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated Csn2 Protein Revealed Ca[superscript 2+]-dependent Double-stranded DNA Binding Activity

Energy Technology Data Exchange (ETDEWEB)

Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong (Cornell); (NWU)

2012-05-22

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 {angstrom} tetrameric ring structure. The inner circle of the Csn2 tetrameric ring is {approx}26 {angstrom} wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an {alpha}/{beta} domain and an {alpha}-helical domain; significant hinge motion was observed between these two domains. Ca{sup 2+} was located at strategic positions in the oligomerization interface. We further showed that removal of Ca{sup 2+} ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca{sup 2+} ions.

Small glutamine-rich tetratricopeptide repeat-containing protein alpha is present in human ovaries but may not be differentially expressed in relation to polycystic ovary syndrome.

Science.gov (United States)

Butler, Miriam S; Yang, Xing; Ricciardelli, Carmela; Liang, Xiaoyan; Norman, Robert J; Tilley, Wayne D; Hickey, Theresa E

2013-06-01

To evaluate the expression and function of small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA), an androgen receptor (AR) molecular chaperone, in human ovarian tissues. Examine the effect of SGTA on AR subcellular localization in granulosa tumor cells (KGN) and SGTA expression in ovarian tissues. University-based research laboratory. Archived tissues from premenopausal women and granulosa cells from infertile women receiving assisted reproduction. None. AR subcellular localization and SGTA protein or mRNA levels. SGTA and AR proteins were expressed in the cytoplasm of KGN cells and exposure to androgen stimulated AR nuclear localization. SGTA protein knockdown increased AR nuclear localization at low (0-0.1 nmol/L) but not high (1-10 nmol/L) concentrations of androgen hormone. In ovarian tissues, SGTA was localized to the cytoplasm of granulosa cells at all stages of folliculogenesis and in thecal cells of antral follicles. SGTA protein levels were similar when comparing primordial and primary follicles within core biopsies (n = 40) from women with and without polycystic ovary syndrome (PCOS). Likewise, SGTA mRNA levels were not significantly different in granulosa cells from preovulatory follicles after hyperstimulation of women with and without PCOS. SGTA is present in human ovaries and has the potential to modulate AR signalling, but it may not be differentially expressed in PCOS. Copyright © 2013 American Society for Reproductive Medicine. All rights reserved.

Exceptionally long 5' UTR short tandem repeats specifically linked to primates.

Science.gov (United States)

Namdar-Aligoodarzi, P; Mohammadparast, S; Zaker-Kandjani, B; Talebi Kakroodi, S; Jafari Vesiehsari, M; Ohadi, M

2015-09-10

We have previously reported genome-scale short tandem repeats (STRs) in the core promoter interval (i.e. -120 to +1 to the transcription start site) of protein-coding genes that have evolved identically in primates vs. non-primates. Those STRs may function as evolutionary switch codes for primate speciation. In the current study, we used the Ensembl database to analyze the 5' untranslated region (5' UTR) between +1 and +60 of the transcription start site of the entire human protein-coding genes annotated in the GeneCards database, in order to identify "exceptionally long" STRs (≥5-repeats), which may be of selective/adaptive advantage. The importance of this critical interval is its function as core promoter, and its effect on transcription and translation. In order to minimize ascertainment bias, we analyzed the evolutionary status of the human 5' UTR STRs of ≥5-repeats in several species encompassing six major orders and superorders across mammals, including primates, rodents, Scandentia, Laurasiatheria, Afrotheria, and Xenarthra. We introduce primate-specific STRs, and STRs which have expanded from mouse to primates. Identical co-occurrence of the identified STRs of rare average frequency between 0.006 and 0.0001 in primates supports a role for those motifs in processes that diverged primates from other mammals, such as neuronal differentiation (e.g. APOD and FGF4), and craniofacial development (e.g. FILIP1L). A number of the identified STRs of ≥5-repeats may be human-specific (e.g. ZMYM3 and DAZAP1). Future work is warranted to examine the importance of the listed genes in primate/human evolution, development, and disease. Copyright © 2015 Elsevier B.V. All rights reserved.

A quantitative comparison of corrective and perfective maintenance

Science.gov (United States)

Henry, Joel; Cain, James

1994-01-01

This paper presents a quantitative comparison of corrective and perfective software maintenance activities. The comparison utilizes basic data collected throughout the maintenance process. The data collected are extensive and allow the impact of both types of maintenance to be quantitatively evaluated and compared. Basic statistical techniques test relationships between and among process and product data. The results show interesting similarities and important differences in both process and product characteristics.

16 CFR 23.12 - Misuse of the words “flawless,” “perfect,” etc.

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Misuse of the words âflawless,â âperfect,â... GUIDES FOR THE JEWELRY, PRECIOUS METALS, AND PEWTER INDUSTRIES § 23.12 Misuse of the words “flawless,” “perfect,” etc. (a) It is unfair or deceptive to use the word “flawless” to describe any diamond that...

16 CFR 23.26 - Misuse of the words “flawless,” “perfect,” etc.

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Misuse of the words âflawless,â âperfect,â... GUIDES FOR THE JEWELRY, PRECIOUS METALS, AND PEWTER INDUSTRIES § 23.26 Misuse of the words “flawless,” “perfect,” etc. (a) It is unfair or deceptive to use the word “flawless” as a quality description of any...

The role of Slr0151, a tetratricopeptide repeat protein from Synechocystis sp. PCC 6803, during Photosystem II assembly and repair

Directory of Open Access Journals (Sweden)

Anna eRast

2016-05-01

Full Text Available The assembly and repair of photosystem II (PSII is facilitated by a variety of assembly factors. Among those, the tetratricopeptide repeat (TPR protein Slr0151 from Synechocystis sp. PCC 6803 (hereafter Synechocystis has previously been assigned a repair function under high light conditions (Yang et al., 2014, J. Integr. Plant Biol. 56, 1136-50. Here, we show that inactivation of Slr0151 affects thylakoid membrane ultrastructure even under normal light conditions. Moreover, the level and localization of Slr0151 are affected in a variety of PSII-related mutants. In particular, the data suggest a close functional relationship between Slr0151 and Sll0933, which interacts with Ycf48 during PSII assembly and is homologous to PAM68 in Arabidopsis thaliana. Immunofluorescence analysis revealed a punctate distribution of Slr0151 within several different membrane types in Synechocystis cells.

Repeating and non-repeating fast radio bursts from binary neutron star mergers

Science.gov (United States)

Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

2018-04-01

Most fast radio bursts (FRB) do not show evidence of repetition, and such non-repeating FRBs may be produced at the time of a merger of binary neutron stars (BNS), provided that the BNS merger rate is close to the high end of the currently possible range. However, the merger environment is polluted by dynamical ejecta, which may prohibit the radio signal from propagating. We examine this by using a general-relativistic simulation of a BNS merger, and show that the ejecta appears about 1 ms after the rotation speed of the merged star becomes the maximum. Therefore there is a time window in which an FRB signal can reach outside, and the short duration of non-repeating FRBs can be explained by screening after ejecta formation. A fraction of BNS mergers may leave a rapidly rotating and stable neutron star, and such objects may be the origin of repeating FRBs like FRB 121102. We show that a merger remnant would appear as a repeating FRB on a time scale of ˜1-10 yr, and expected properties are consistent with the observations of FRB 121102. We construct an FRB rate evolution model that includes these two populations of repeating and non-repeating FRBs from BNS mergers, and show that the detection rate of repeating FRBs relative to non-repeating ones rapidly increases with improving search sensitivity. This may explain why only the repeating FRB 121102 was discovered by the most sensitive FRB search with Arecibo. Several predictions are made, including the appearance of a repeating FRB 1-10 yr after a BNS merger that is localized by gravitational waves and subsequent electromagnetic radiation.

Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats.

Science.gov (United States)

Warmerdam, Daniël O; van den Berg, Jeroen; Medema, René H

2016-03-22

rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of breaks in 45S rDNA, and this results in repeat loss. We identify the structural maintenance of chromosomes protein 5 (SMC5) as contributing to recombination-mediated repair of rDNA breaks. Together, our data demonstrate that SMC5-mediated recombination can lead to error-prone repair of 45S rDNA repeats, resulting in their loss and thereby reducing cellular viability. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Repeatability and Reproducibility of Compression Strength Measurements Conducted According to ASTM E9

Science.gov (United States)

Luecke, William E.; Ma, Li; Graham, Stephen M.; Adler, Matthew A.

2010-01-01

Ten commercial laboratories participated in an interlaboratory study to establish the repeatability and reproducibility of compression strength tests conducted according to ASTM International Standard Test Method E9. The test employed a cylindrical aluminum AA2024-T351 test specimen. Participants measured elastic modulus and 0.2 % offset yield strength, YS(0.2 % offset), using an extensometer attached to the specimen. The repeatability and reproducibility of the yield strength measurement, expressed as coefficient of variations were cv(sub r)= 0.011 and cv(sub R)= 0.020 The reproducibility of the test across the laboratories was among the best that has been reported for uniaxial tests. The reported data indicated that using diametrically opposed extensometers, instead of a single extensometer doubled the precision of the test method. Laboratories that did not lubricate the ends of the specimen measured yield stresses and elastic moduli that were smaller than those measured in laboratories that lubricated the specimen ends. A finite element analysis of the test specimen deformation for frictionless and perfect friction could not explain the discrepancy, however. The modulus measured from stress-strain data were reanalyzed using a technique that finds the optimal fit range, and applies several quality checks to the data. The error in modulus measurements from stress-strain curves generally increased as the fit range decreased to less than 40 % of the stress range.

Perfect independent sets with respect to infinitely many relations

Czech Academy of Sciences Publication Activity Database

Doležal, Martin; Kubiś, Wieslaw

2016-01-01

Roč. 55, č. 7 (2016), s. 847-856 ISSN 0933-5846 R&D Projects: GA ČR(CZ) GA14-07880S Institutional support: RVO:67985840 Keywords : perfect clique * free subgroup * open relation Subject RIV: BA - General Mathematics Impact factor: 0.394, year: 2016 http://link.springer.com/article/10.1007%2Fs00153-016-0498-3

t2prhd: a tool to study the patterns of repeat evolution

Directory of Open Access Journals (Sweden)

Pénzes Zsolt

2008-01-01

Full Text Available Abstract Background The models developed to characterize the evolution of multigene families (such as the birth-and-death and the concerted models have also been applied on the level of sequence repeats inside a gene/protein. Phylogenetic reconstruction is the method of choice to study the evolution of gene families and also sequence repeats in the light of these models. The characterization of the gene family evolution in view of the evolutionary models is done by the evaluation of the clustering of the sequences with the originating loci in mind. As the locus represents positional information, it is straightforward that in the case of the repeats the exact position in the sequence should be used, as the simple numbering according to repeat order can be misleading. Results We have developed a novel rapid visual approach to study repeat evolution, that takes into account the exact repeat position in a sequence. The "pairwise repeat homology diagram" visualizes sequence repeats detected by a profile HMM in a pair of sequences and highlights their homology relations inferred by a phylogenetic tree. The method is implemented in a Perl script (t2prhd available for downloading at http://t2prhd.sourceforge.net and is also accessible as an online tool at http://t2prhd.brc.hu. The power of the method is demonstrated on the EGF-like and fibronectin-III-like (Fn-III domain repeats of three selected mammalian Tenascin sequences. Conclusion Although pairwise repeat homology diagrams do not carry all the information provided by the phylogenetic tree, they allow a rapid and intuitive assessment of repeat evolution. We believe, that t2prhd is a helpful tool with which to study the pattern of repeat evolution. This method can be particularly useful in cases of large datasets (such as large gene families, as the command line interface makes it possible to automate the generation of pairwise repeat homology diagrams with the aid of scripts.

A global conformal extension theorem for perfect fluid Bianchi space-times

International Nuclear Information System (INIS)

Luebbe, Christian; Tod, Paul

2008-01-01

A global extension theorem is established for isotropic singularities in polytropic perfect fluid Bianchi space-times. When an extension is possible, the limiting behaviour of the physical space-time near the singularity is analysed

The equivalence of perfect fluid space-times and viscous magnetohydrodynamic space-times in general relativity

International Nuclear Information System (INIS)

Tupper, B.O.J.

1983-01-01

The work of a previous article is extended to show that space-times which are the exact solutions of the field equations for a perfect fluid also may be exact solutions of the field equations for a viscous magnetohydrodynamic fluid. Conditions are found for this equivalence to exist and viscous magnetohydrodynamic solutions are found for a number of known perfect fluid space-times. (author)

Feasibilty of zein proteins, simple sequence repeats and phenotypic ...

African Journals Online (AJOL)

Widespread adoption of quality protein maize (QPM), especially among tropical farming systems has been slow mainly due to the slow process of generating varieties with acceptable kernel quality and adaptability to different agroecological contexts. A molecular based foreground selection system for opaque 2 (o2), the ...

A perfect Fresnel acoustic reflector implemented by a Fano-resonant metascreen

KAUST Repository

Amin, M.

2018-04-10

We propose a perfectly reflecting acoustic metasurface which is designed by replacing the curved segments of the traditional Fresnel reflector by flat Fano-resonant sub-wavelength unit cells. To preserve the original Fresnel focusing mechanism, the unit cell phase follows a specific phase profile which is obtained by applying the generalized Snell\\'s law and Fermat\\'s principle. The reflected curved phase fronts are thus created at the air-metasurface boundary by tailoring the metasurface dispersion as dictated by Huygens\\' principle. Since the unit cells are implemented by sub-wavelength double slit-shaped cavity resonators, the impinging sound waves are perfectly reflected producing acoustic focusing with negligible absorption. We use plane-wave solution and full-wave simulations to demonstrate the focusing effects. The simulation results closely follow the analytical predictions.

A perfect Fresnel acoustic reflector implemented by a Fano-resonant metascreen

KAUST Repository

Amin, M.; Siddiqui, O.; Farhat, Mohamed; Khelif, A.

2018-01-01

We propose a perfectly reflecting acoustic metasurface which is designed by replacing the curved segments of the traditional Fresnel reflector by flat Fano-resonant sub-wavelength unit cells. To preserve the original Fresnel focusing mechanism, the unit cell phase follows a specific phase profile which is obtained by applying the generalized Snell's law and Fermat's principle. The reflected curved phase fronts are thus created at the air-metasurface boundary by tailoring the metasurface dispersion as dictated by Huygens' principle. Since the unit cells are implemented by sub-wavelength double slit-shaped cavity resonators, the impinging sound waves are perfectly reflected producing acoustic focusing with negligible absorption. We use plane-wave solution and full-wave simulations to demonstrate the focusing effects. The simulation results closely follow the analytical predictions.

A perfect Fresnel acoustic reflector implemented by a Fano-resonant metascreen

Science.gov (United States)

Amin, M.; Siddiqui, O.; Farhat, M.; Khelif, A.

2018-04-01

We propose a perfectly reflecting acoustic metasurface which is designed by replacing the curved segments of the traditional Fresnel reflector by flat Fano-resonant sub-wavelength unit cells. To preserve the original Fresnel focusing mechanism, the unit cell phase follows a specific phase profile which is obtained by applying the generalized Snell's law and Fermat's principle. The reflected curved phase fronts are thus created at the air-metasurface boundary by tailoring the metasurface dispersion as dictated by Huygens' principle. Since the unit cells are implemented by sub-wavelength double slit-shaped cavity resonators, the impinging sound waves are perfectly reflected producing acoustic focusing with negligible absorption. We use plane-wave solution and full-wave simulations to demonstrate the focusing effects. The simulation results closely follow the analytical predictions.

A psychogenic dystonia perfect responsive to antidepressant treatment.

OpenAIRE

Volkan Solmaz; Durdane Aksoy; Betul Cevik; Semiha Gulsum Kurt; Elmas Pekdas; Sema inanir

2014-01-01

After ruling out of organic causes, movement disorders are named as psychogenic movement disorders, it can mimic perfectly Organic movement disorders, but with a good history, clinical observations and detailed examination is very helpful in the diagnosis of this disease. In here we will present a 15 years old male patient, he was complaining of urinary incontinence at night, emerging dystonic posture especially in crowded environments, eating, and during activities that require attention, fo...

Dissecting the critical factors for thermodynamic stability of modular proteins using molecular modeling approach.

Directory of Open Access Journals (Sweden)

Yuno Lee

Full Text Available Repeat proteins have recently attracted much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural and biophysical features. In particular, repeat proteins show high stability against temperature and chaotic agents. Despite many studies, structural features for the stability of repeat proteins remain poorly understood. Here we present an interesting result from in silico analyses pursuing the factors which affect the stability of repeat proteins. Previously developed repebody structure based on variable lymphocytes receptors (VLRs which consists of leucine-rich repeat (LRR modules was used as initial structure for the present study. We constructed extra six repebody structures with varying numbers of repeat modules and those structures were used for molecular dynamics simulations. For the structures, the intramolecular interactions including backbone H-bonds, van der Waals energy, and hydrophobicity were investigated and then the radius of gyration, solvent-accessible surface area, ratio of secondary structure, and hydration free energy were also calculated to find out the relationship between the number of LRR modules and stability of the protein. Our results show that the intramolecular interactions lead to more compact structure and smaller surface area of the repebodies, which are critical for the stability of repeat proteins. The other features were also well compatible with the experimental results. Based on our observations, the repebody-5 was proposed as the best structure from the all repebodies in structure optimization process. The present study successfully demonstrated that our computer-based molecular modeling approach can significantly contribute to the experiment-based protein engineering challenge.

Enhanced expression of WD repeat-containing protein 35 (WDR35 stimulated by domoic acid in rat hippocampus: involvement of reactive oxygen species generation and p38 mitogen-activated protein kinase activation

Directory of Open Access Journals (Sweden)

Tsunekawa Koji

2013-01-01

Full Text Available Abstract Background Domoic acid (DA is an excitatory amino acid analogue of kainic acid (KA that acts via activation of glutamate receptors to elicit a rapid and potent excitotoxic response, resulting in neuronal cell death. Recently, DA was shown to elicit reactive oxygen species (ROS production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK in vitro. We have reported that WDR35, a WD-repeat protein, may mediate apoptosis in several animal models. In the present study, we administered DA to rats intraperitoneally, then used liquid chromatography/ion trap tandem mass spectrometry (LC-MS/MS to identify and quantify DA in the brains of the rats and performed histological examinations of the hippocampus. We further investigated the potential involvement of glutamate receptors, ROS, p38 MAPK, and WDR35 in DA-induced toxicity in vivo. Results Our results showed that intraperitoneally administered DA was present in the brain and induced neurodegenerative changes including apoptosis in the CA1 region of the hippocampus. DA also increased the expression of WDR35 mRNA and protein in a dose- and time-dependent manner in the hippocampus. In experiments using glutamate receptor antagonists, the AMPA/KA receptor antagonist NBQX significantly attenuated the DA-induced increase in WDR35 protein expression, but the NMDA receptor antagonist MK-801 did not. In addition, the radical scavenger edaravone significantly attenuated the DA-induced increase in WDR35 protein expression. Furthermore, NBQX and edaravone significantly attenuated the DA-induced increase in p38 MAPK phosphorylation. Conclusion In summary, our results indicated that DA activated AMPA/KA receptors and induced ROS production and p38 MAPK phosphorylation, resulting in an increase in the expression of WDR35 in vivo.

Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

Directory of Open Access Journals (Sweden)

Hua Wan

2016-01-01

Full Text Available TAL effectors (TALEs contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE.

Protein (Cyanobacteria): 175822 [PGDBj - Ortholog DB

Lifescience Database Archive (English)

Full Text Available agen triple helix repeat-containing protein 'Nostoc azollae' 0708 MRLIEDGEDGEDGEDGEDGEDGEDGEDGEDGEDGEDGEDGEDGGEIFLMPYALCPMPYALCPMPYALCPMPYALCPMPYALCPMPYAQNQDFSHPNRESSVKLFSSVAPKP ...

Clinical Results After Prostatic Artery Embolization Using the PErFecTED Technique: A Single-Center Study

International Nuclear Information System (INIS)

Amouyal, Gregory; Thiounn, Nicolas; Pellerin, Olivier; Yen-Ting, Lin; Giudice, Costantino Del; Dean, Carole; Pereira, Helena; Chatellier, Gilles; Sapoval, Marc

2016-01-01

BackgroundProstatic artery embolization (PAE) has been performed for a few years, but there is no report on PAE using the PErFecTED technique outside from the team that initiated this approach.ObjectiveThis single-center retrospective open label study reports our experience and clinical results on patients suffering from symptomatic BPH, who underwent PAE aiming at using the PErFecTED technique.Materials and MethodsWe treated 32 consecutive patients, mean age 65 (52–84 years old) between December 2013 and January 2015. Patients were referred for PAE after failure of medical treatment and refusal or contra-indication to surgery. They were treated using the PErFecTED technique, when feasible, with 300–500 µm calibrated microspheres (two-night hospital stay or outpatient procedure). Follow-up was performed at 3, 6, and 12 months.ResultsWe had a 100 % immediate technical success of embolization (68 % of feasibility of the PErFecTED technique) with no immediate complications. After a mean follow-up of 7.7 months, we observed a 78 % rate of clinical success. Mean IPSS decreased from 15.3 to 4.2 (p = .03), mean QoL from 5.4 to 2 (p = .03), mean Qmax increased from 9.2 to 19.2 (p = .25), mean prostatic volume decreased from 91 to 62 (p = .009) mL. There was no retrograde ejaculation and no major complication.ConclusionPAE using the PErFecTED technique is a safe and efficient technique to treat bothersome LUTS related to BPH. It is of interest to note that the PErFecTED technique cannot be performed in some cases for anatomical reasons

Clinical Results After Prostatic Artery Embolization Using the PErFecTED Technique: A Single-Center Study

Energy Technology Data Exchange (ETDEWEB)

Amouyal, Gregory, E-mail: gregamouyal@hotmail.com; Thiounn, Nicolas, E-mail: nicolas.thiounn@aphp.fr; Pellerin, Olivier, E-mail: olivier.pellerin@aphp.fr [Université Paris Descartes - Sorbonne - Paris - Cité, Faculté de Médecine (France); Yen-Ting, Lin, E-mail: ymerically@gmail.com [Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Interventional Radiology Department (France); Giudice, Costantino Del, E-mail: costantino.delgiudice@aphp.fr [Université Paris Descartes - Sorbonne - Paris - Cité, Faculté de Médecine (France); Dean, Carole, E-mail: carole.dean@aphp.fr [Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Interventional Radiology Department (France); Pereira, Helena, E-mail: helena.pereira@aphp.fr [Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Clinical Research Unit (France); Chatellier, Gilles, E-mail: gilles.chatellier@aphp.fr; Sapoval, Marc, E-mail: marc.sapoval2@aphp.fr [Université Paris Descartes - Sorbonne - Paris - Cité, Faculté de Médecine (France)

2016-03-15

BackgroundProstatic artery embolization (PAE) has been performed for a few years, but there is no report on PAE using the PErFecTED technique outside from the team that initiated this approach.ObjectiveThis single-center retrospective open label study reports our experience and clinical results on patients suffering from symptomatic BPH, who underwent PAE aiming at using the PErFecTED technique.Materials and MethodsWe treated 32 consecutive patients, mean age 65 (52–84 years old) between December 2013 and January 2015. Patients were referred for PAE after failure of medical treatment and refusal or contra-indication to surgery. They were treated using the PErFecTED technique, when feasible, with 300–500 µm calibrated microspheres (two-night hospital stay or outpatient procedure). Follow-up was performed at 3, 6, and 12 months.ResultsWe had a 100 % immediate technical success of embolization (68 % of feasibility of the PErFecTED technique) with no immediate complications. After a mean follow-up of 7.7 months, we observed a 78 % rate of clinical success. Mean IPSS decreased from 15.3 to 4.2 (p = .03), mean QoL from 5.4 to 2 (p = .03), mean Qmax increased from 9.2 to 19.2 (p = .25), mean prostatic volume decreased from 91 to 62 (p = .009) mL. There was no retrograde ejaculation and no major complication.ConclusionPAE using the PErFecTED technique is a safe and efficient technique to treat bothersome LUTS related to BPH. It is of interest to note that the PErFecTED technique cannot be performed in some cases for anatomical reasons.

An improved perfectly matched layer for the eigenmode expansion technique

DEFF Research Database (Denmark)

Gregersen, Niels; Mørk, Jesper

2008-01-01

be suppressed by introducing a perfectly matched layer (PML) using e.g. complex coordinate stretching of the cylinder radius. However, the traditional PML suffers from an artificial field divergence limiting its usefulness. We show that the choice of a constant cylinder radius leads to mode profiles...

Functionalization of protein-based nanocages for drug delivery applications.

Science.gov (United States)

Schoonen, Lise; van Hest, Jan C M

2014-07-07

Traditional drug delivery strategies involve drugs which are not targeted towards the desired tissue. This can lead to undesired side effects, as normal cells are affected by the drugs as well. Therefore, new systems are now being developed which combine targeting functionalities with encapsulation of drug cargo. Protein nanocages are highly promising drug delivery platforms due to their perfectly defined structures, biocompatibility, biodegradability and low toxicity. A variety of protein nanocages have been modified and functionalized for these types of applications. In this review, we aim to give an overview of different types of modifications of protein-based nanocontainers for drug delivery applications.

The pursuit of perfect packing

CERN Document Server

Weaire, Denis

2000-01-01

In 1998 Thomas Hales dramatically announced the solution of a problem that has long teased eminent mathematicians: what is the densest possible arrangement of identical spheres? The Pursuit of Perfect Packing recounts the story of this problem and many others that have to do with packing things together. The examples are taken from mathematics, physics, biology, and engineering, including the arrangement of soap bubbles in foam, atoms in a crystal, the architecture of the bee''s honeycomb, and the structure of the Giant''s Causeway. Using an informal style and with key references, the book also includes brief accounts of the lives of many of the scientists who devoted themselves to problems of packing over many centuries, together with wry comments on their efforts. It is an entertaining introduction to the field for both specialists and the more general public.

Hybrid Sterility in Rice (Oryza sativa L.) Involves the Tetratricopeptide Repeat Domain Containing Protein.

Science.gov (United States)

Yu, Yang; Zhao, Zhigang; Shi, Yanrong; Tian, Hua; Liu, Linglong; Bian, Xiaofeng; Xu, Yang; Zheng, Xiaoming; Gan, Lu; Shen, Yumin; Wang, Chaolong; Yu, Xiaowen; Wang, Chunming; Zhang, Xin; Guo, Xiuping; Wang, Jiulin; Ikehashi, Hiroshi; Jiang, Ling; Wan, Jianmin

2016-07-01

Intersubspecific hybrid sterility is a common form of reproductive isolation in rice (Oryza sativa L.), which significantly hampers the utilization of heterosis between indica and japonica varieties. Here, we elucidated the mechanism of S7, which specially causes Aus-japonica/indica hybrid female sterility, through cytological and genetic analysis, map-based cloning, and transformation experiments. Abnormal positioning of polar nuclei and smaller embryo sac were observed in F1 compared with male and female parents. Female gametes carrying S7(cp) and S7(i) were aborted in S7(ai)/S7(cp) and S7(ai)/S7(i), respectively, whereas they were normal in both N22 and Dular possessing a neutral allele, S7(n) S7 was fine mapped to a 139-kb region in the centromere region on chromosome 7, where the recombination was remarkably suppressed due to aggregation of retrotransposons. Among 16 putative open reading frames (ORFs) localized in the mapping region, ORF3 encoding a tetratricopeptide repeat domain containing protein was highly expressed in the pistil. Transformation experiments demonstrated that ORF3 is the candidate gene: downregulated expression of ORF3 restored spikelet fertility and eliminated absolutely preferential transmission of S7(ai) in heterozygote S7(ai)/S7(cp); sterility occurred in the transformants Cpslo17-S7(ai) Our results may provide implications for overcoming hybrid embryo sac sterility in intersubspecific hybrid rice and utilization of hybrid heterosis for cultivated rice improvement. Copyright © 2016 by the Genetics Society of America.

Perfect-absorption graphene metamaterials for surface-enhanced molecular fingerprint spectroscopy

Science.gov (United States)

Guo, Xiangdong; Hu, Hai; Liao, Baoxin; Zhu, Xing; Yang, Xiaoxia; Dai, Qing

2018-05-01

Graphene plasmon with extremely strong light confinement and tunable resonance frequency represents a promising surface-enhanced infrared absorption (SEIRA) sensing platform. However, plasmonic absorption is relatively weak (approximately 1%-9%) in monolayer graphene nanostructures, which would limit its sensitivity. Here, we theoretically propose a hybrid plasmon-metamaterial structure that can realize perfect absorption in graphene with a low carrier mobility of 1000 cm2 V-1 s-1. This structure combines a gold reflector and a gold grating to the graphene plasmon structures, which introduce interference effect and the lightning-rod effect, respectively, and largely enhance the coupling of light to graphene. The vibration signal of trace molecules can be enhanced up to 2000-fold at the hotspot of the perfect-absorption structure, enabling the SEIRA sensing to reach the molecular level. This hybrid metal-graphene structure provides a novel path to generate high sensitivity in nanoscale molecular recognition for numerous applications.

Perfect simulation and moment properties for the Matérn type III process

DEFF Research Database (Denmark)

Møller, Jesper; Huber, Mark L.; Wolpert, Robert L.

2010-01-01

In a seminal work, Bertil Matérn introduced several types of processes for modeling repulsive point processes. In this paper an algorithm is presented for the perfect simulation of the Matérn III process within a bounded window in , fully accounting for edge effects. A simple upper bound on the m......In a seminal work, Bertil Matérn introduced several types of processes for modeling repulsive point processes. In this paper an algorithm is presented for the perfect simulation of the Matérn III process within a bounded window in , fully accounting for edge effects. A simple upper bound...

Effects of Perfectly Correlated and Anti-Correlated Noise in a Logistic Growth Model

International Nuclear Information System (INIS)

Zhang Li; Cao Li

2011-01-01

The logistic growth model with correlated additive and multiplicative Gaussian white noise is used to analyze tumor cell population. The effects of perfectly correlated and anti-correlated noise on the stationary properties of tumor cell population are studied. As in both cases the diffusion coefficient has zero point in real number field, some special features of the system are arisen. It is found that in both cases, the increase of the multiplicative noise intensity cause tumor cell extinction. In the perfectly anti-correlated case, the stationary probability distribution as a function of tumor cell population exhibit two extrema. (general)

Helicity and other conservation laws in perfect fluid motion

Science.gov (United States)

Serre, Denis

2018-03-01

In this review paper, we discuss helicity from a geometrical point of view and see how it applies to the motion of a perfect fluid. We discuss its relation with the Hamiltonian structure, and then its extension to arbitrary space dimensions. We also comment about the existence of additional conservation laws for the Euler equation, and its unlikely integrability in Liouville's sense.

Repeat-mediated epigenetic dysregulation of the FMR1 gene in the fragile X-related disorders.

Science.gov (United States)

Usdin, Karen; Kumari, Daman

2015-01-01

The fragile X-related disorders are members of the Repeat Expansion Diseases, a group of genetic conditions resulting from an expansion in the size of a tandem repeat tract at a specific genetic locus. The repeat responsible for disease pathology in the fragile X-related disorders is CGG/CCG and the repeat tract is located in the 5' UTR of the FMR1 gene, whose protein product FMRP, is important for the proper translation of dendritic mRNAs in response to synaptic activation. There are two different pathological FMR1 allele classes that are distinguished only by the number of repeats. Premutation alleles have 55-200 repeats and confer risk of fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Full mutation alleles on the other hand have >200 repeats and result in fragile X syndrome, a disorder that affects learning and behavior. Different symptoms are seen in carriers of premutation and full mutation alleles because the repeat number has paradoxical effects on gene expression: Epigenetic changes increase transcription from premutation alleles and decrease transcription from full mutation alleles. This review will cover what is currently known about the mechanisms responsible for these changes in FMR1 expression and how they may relate to other Repeat Expansion Diseases that also show repeat-mediated changes in gene expression.

Sequestration of DROSHA and DGCR8 by Expanded CGG RNA Repeats Alters MicroRNA Processing in Fragile X-Associated Tremor/Ataxia Syndrome

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Chantal Sellier

2013-03-01

Full Text Available Fragile X-associated tremor/ataxia syndrome (FXTAS is an inherited neurodegenerative disorder caused by the expansion of 55–200 CGG repeats in the 5′ UTR of FMR1. These expanded CGG repeats are transcribed and accumulate in nuclear RNA aggregates that sequester one or more RNA-binding proteins, thus impairing their functions. Here, we have identified that the double-stranded RNA-binding protein DGCR8 binds to expanded CGG repeats, resulting in the partial sequestration of DGCR8 and its partner, DROSHA, within CGG RNA aggregates. Consequently, the processing of microRNAs (miRNAs is reduced, resulting in decreased levels of mature miRNAs in neuronal cells expressing expanded CGG repeats and in brain tissue from patients with FXTAS. Finally, overexpression of DGCR8 rescues the neuronal cell death induced by expression of expanded CGG repeats. These results support a model in which a human neurodegenerative disease originates from the alteration, in trans, of the miRNA-processing machinery.

A Unified Model for Repeating and Non-repeating Fast Radio Bursts

International Nuclear Information System (INIS)

Bagchi, Manjari

2017-01-01

The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

A Unified Model for Repeating and Non-repeating Fast Radio Bursts

Energy Technology Data Exchange (ETDEWEB)

Bagchi, Manjari, E-mail: manjari@imsc.res.in [The Institute of Mathematical Sciences (IMSc-HBNI), 4th Cross Road, CIT Campus, Taramani, Chennai 600113 (India)

2017-04-01

The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

Repeatability of Cryogenic Multilayer Insulation

Science.gov (United States)

Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

2017-12-01

Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation (MLI) has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five Glenn Research Center (GRC) provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons has been fabricated by Yetispace and tested by Florida State University, the repeatability between coupons has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

A tensegrity model for hydrogen bond networks in proteins.

Science.gov (United States)

Bywater, Robert P

2017-05-01

Hydrogen-bonding networks in proteins considered as structural tensile elements are in balance separately from any other stabilising interactions that may be in operation. The hydrogen bond arrangement in the network is reminiscent of tensegrity structures in architecture and sculpture. Tensegrity has been discussed before in cells and tissues and in proteins. In contrast to previous work only hydrogen bonds are studied here. The other interactions within proteins are either much stronger - covalent bonds connecting the atoms in the molecular skeleton or weaker forces like the so-called hydrophobic interactions. It has been demonstrated that the latter operate independently from hydrogen bonds. Each category of interaction must, if the protein is to have a stable structure, balance out. The hypothesis here is that the entire hydrogen bond network is in balance without any compensating contributions from other types of interaction. For sidechain-sidechain, sidechain-backbone and backbone-backbone hydrogen bonds in proteins, tensegrity balance ("closure") is required over the entire length of the polypeptide chain that defines individually folding units in globular proteins ("domains") as well as within the repeating elements in fibrous proteins that consist of extended chain structures. There is no closure to be found in extended structures that do not have repeating elements. This suggests an explanation as to why globular domains, as well as the repeat units in fibrous proteins, have to have a defined number of residues. Apart from networks of sidechain-sidechain hydrogen bonds there are certain key points at which this closure is achieved in the sidechain-backbone hydrogen bonds and these are associated with demarcation points at the start or end of stretches of secondary structure. Together, these three categories of hydrogen bond achieve the closure that is necessary for the stability of globular protein domains as well as repeating elements in fibrous proteins.

Selection pressure on human STR loci and its relevance in repeat expansion disease

KAUST Repository

Shimada, Makoto K.

2016-06-11

Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat-number variation according to selection pressure. However, the remaining questions include: Why are STRs causing repeat expansion diseases maintained in the human population; and why are these limited to neurodegenerative diseases? By evaluating the genome-wide selection pressure on STRs using the database we constructed, we identified two different patterns of relationship in repeat-number polymorphisms between DNA and amino-acid sequences, although both patterns are evolutionary consequences of avoiding the formation of harmful long STRs. First, a mixture of degenerate codons is represented in poly-proline (poly-P) repeats. Second, long poly-glutamine (poly-Q) repeats are favored at the protein level; however, at the DNA level, STRs encoding long poly-Qs are frequently divided by synonymous SNPs. Furthermore, significant enrichments of apoptosis and neurodevelopment were biological processes found specifically in genes encoding poly-Qs with repeat polymorphism. This suggests the existence of a specific molecular function for polymorphic and/or long poly-Q stretches. Given that the poly-Qs causing expansion diseases were longer than other poly-Qs, even in healthy subjects, our results indicate that the evolutionary benefits of long and/or polymorphic poly-Q stretches outweigh the risks of long CAG repeats predisposing to pathological hyper-expansions. Molecular pathways in neurodevelopment requiring long and polymorphic poly-Q stretches may provide a clue to understanding why poly-Q expansion diseases are limited to neurodegenerative diseases. © 2016, Springer-Verlag Berlin Heidelberg.

Coordinate transformations make perfect invisibility cloaks with arbitrary shape

International Nuclear Information System (INIS)

Yan Wei; Yan Min; Ruan Zhichao; Qiu Min

2008-01-01

By investigating wave properties at cloak boundaries, invisibility cloaks with arbitrary shape constructed by general coordinate transformations are confirmed to be perfectly invisible to the external incident wave. The differences between line transformed cloaks and point transformed cloaks are discussed. The fields in the cloak medium are found analytically to be related to the fields in the original space via coordinate transformation functions. At the exterior boundary of the cloak, it is shown that no reflection is excited even though the permittivity and permeability do not always have a perfectly matched layer form, whereas at the inner boundary, no reflection is excited either, and in particular no field can penetrate into the cloaked region. However, for the inner boundary of any line transformed cloak, the permittivity and permeability in a specific tangential direction are always required to be infinitely large. Furthermore, the field discontinuity at the inner boundary always exists; the surface current is induced to make this discontinuity self-consistent. A point transformed cloak does not experience such problems. The tangential fields at the inner boundary are all zero, implying that no field discontinuity exists

Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients.

Science.gov (United States)

Yin, Shanye; Lopez-Gonzalez, Rodrigo; Kunz, Ryan C; Gangopadhyay, Jaya; Borufka, Carl; Gygi, Steven P; Gao, Fen-Biao; Reed, Robin

2017-06-13

Hexanucleotide repeat expansion in the C9ORF72 gene results in production of dipeptide repeat (DPR) proteins that may disrupt pre-mRNA splicing in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. At present, the mechanisms underlying this mis-splicing are not understood. Here, we show that addition of proline-arginine (PR) and glycine-arginine (GR) toxic DPR peptides to nuclear extracts blocks spliceosome assembly and splicing, but not other types of RNA processing. Proteomic and biochemical analyses identified the U2 small nuclear ribonucleoprotein particle (snRNP) as a major interactor of PR and GR peptides. In addition, U2 snRNP, but not other splicing factors, mislocalizes from the nucleus to the cytoplasm both in C9ORF72 patient induced pluripotent stem cell (iPSC)-derived motor neurons and in HeLa cells treated with the toxic peptides. Bioinformatic studies support a specific role for U2-snRNP-dependent mis-splicing in C9ORF72 patient brains. Together, our data indicate that DPR-mediated dysfunction of U2 snRNP could account for as much as ∼44% of the mis-spliced cassette exons in C9ORF72 patient brains. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients

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Shanye Yin

2017-06-01

Full Text Available Hexanucleotide repeat expansion in the C9ORF72 gene results in production of dipeptide repeat (DPR proteins that may disrupt pre-mRNA splicing in amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD patients. At present, the mechanisms underlying this mis-splicing are not understood. Here, we show that addition of proline-arginine (PR and glycine-arginine (GR toxic DPR peptides to nuclear extracts blocks spliceosome assembly and splicing, but not other types of RNA processing. Proteomic and biochemical analyses identified the U2 small nuclear ribonucleoprotein particle (snRNP as a major interactor of PR and GR peptides. In addition, U2 snRNP, but not other splicing factors, mislocalizes from the nucleus to the cytoplasm both in C9ORF72 patient induced pluripotent stem cell (iPSC-derived motor neurons and in HeLa cells treated with the toxic peptides. Bioinformatic studies support a specific role for U2-snRNP-dependent mis-splicing in C9ORF72 patient brains. Together, our data indicate that DPR-mediated dysfunction of U2 snRNP could account for as much as ∼44% of the mis-spliced cassette exons in C9ORF72 patient brains.

A short note on nearly perfect maps of locales | Razafindrakoto ...

African Journals Online (AJOL)

We characterise compact locales in terms of nearly perfect maps. We show in particular that these maps are the natural pointfree version of Bourbaki's proper maps - when defined via any ultrafillter - and that they extend Herrlich's notion of nearly closed sublocales [10]. Mathematics Subject Classication (2010): 06A15, ...

Inhomogeneous generalizations of Bianchi type VIh models with perfect fluid

Science.gov (United States)

Roy, S. R.; Prasad, A.

1991-07-01

Inhomogeneous universes admitting an Abelian G2 of isometry and filled with perfect fluid have been derived. These contain as special cases exact homogeneous universes of Bianchi type VIh. Many of these universes asymptotically tend to homogeneous Bianchi VIh universes. The models have been discussed for their physical and kinematical behaviors.

Zero-point energy of N perfectly conducting concentric cylindrical shells

International Nuclear Information System (INIS)

Tatur, K.; Woods, L.M.

2008-01-01

The zero-point (Casimir) energy of N perfectly conducting, infinitely long, concentric cylindrical shells is calculated utilizing the mode summation technique. The obtained convergent expression is studied as a function of size, curvature and number of shells. Limiting cases, such as infinitely close shells or infinite radius shells are also investigated

Deployment Repeatability

Science.gov (United States)

2016-04-01

evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

Protein (Cyanobacteria): 479132094 [PGDBj - Ortholog DB

Lifescience Database Archive (English)

Full Text Available 30 696747:230 ... WD-40 repeat protein Arthrospira platensis NIES-39 MVIASGGASLFNLATGEAVWEIDCPALGGAVSADGRLLALRSNKDIYLWDLSTGQLLRQLTGHTST...VNSVRFSRRGQTLASGSGDNTVRLWDVATGRELRQLTGHTSTVNSVRFSRRGQTLASGSGDNTVRLWDVATGRELRQLTGHTSTVYSVSFSRRGQTLASGSDDGVVRLWRVGF

Identification and expression analysis of the interferon-induced protein with tetratricopeptide repeats 5 (IFIT5 gene in duck (Anas platyrhynchos domesticus.

Directory of Open Access Journals (Sweden)

Bin Wang

Full Text Available The interferon-induced proteins with tetratricopeptide repeats (IFITs protein family mediates antiviral effects by inhibiting translation initiation, cell proliferation, and migration in the interferon (IFN dependent innate immune system. Several members of this family, including IFIT1, IFIT2, IFIT3 and IFIT5, have been heavily studied in mammals. Avian species contain only one family member, IFIT5, and little is known about the role of this protein in birds. In this study, duck IFIT5 (duIFIT5 full-length mRNA was cloned by reverse transcription polymerase chain reaction (RT-PCR and rapid amplification of the cDNA ends (RACE. Based on the sequence obtained, we performed a series of bioinformatics analyses, and found that duIFIT5 was most similar to homologs in other avian species. Also, duIFIT5 contained eight conserved TPR motifs and two conserved multi-domains (TPR_11 and TPR_12. Finally, we used duck hepatitis virus type 1 (DHV-1 and polyriboinosinicpolyribocytidylic acid (poly (I:C as a pathogen or a pathogen-associated molecular pattern induction to infect three-day-old domestic ducklings. The liver and spleen were collected to detect the change in duIFIT5 transcript level upon infection by quantitative real-time PCR (qRT-PCR. DuIFIT5 expression rapidly increased after DHV-1 infection and maintained a high level, while the transcripts of duIFIT5 peaked at 8h after poly (I:C infection and then returned to normal. Taken together, these results provide a greater understanding of avian IFIT5.

Identification and Expression Analysis of the Interferon-Induced Protein with Tetratricopeptide Repeats 5 (IFIT5) Gene in Duck (Anas platyrhynchos domesticus)

Science.gov (United States)

Mu, Chunyu; Su, Yanhui; Liu, Ran; Huang, Zhengyang; Li, Yang; Yu, Qingming; Chang, Guobin; Xu, Qi; Chen, Guohong

2015-01-01

The interferon-induced proteins with tetratricopeptide repeats (IFITs) protein family mediates antiviral effects by inhibiting translation initiation, cell proliferation, and migration in the interferon (IFN) dependent innate immune system. Several members of this family, including IFIT1, IFIT2, IFIT3 and IFIT5, have been heavily studied in mammals. Avian species contain only one family member, IFIT5, and little is known about the role of this protein in birds. In this study, duck IFIT5 (duIFIT5) full-length mRNA was cloned by reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of the cDNA ends (RACE). Based on the sequence obtained, we performed a series of bioinformatics analyses, and found that duIFIT5 was most similar to homologs in other avian species. Also, duIFIT5 contained eight conserved TPR motifs and two conserved multi-domains (TPR_11 and TPR_12). Finally, we used duck hepatitis virus type 1 (DHV-1) and polyriboinosinicpolyribocytidylic acid (poly (I:C)) as a pathogen or a pathogen-associated molecular pattern induction to infect three-day-old domestic ducklings. The liver and spleen were collected to detect the change in duIFIT5 transcript level upon infection by quantitative real-time PCR (qRT-PCR). DuIFIT5 expression rapidly increased after DHV-1 infection and maintained a high level, while the transcripts of duIFIT5 peaked at 8h after poly (I:C) infection and then returned to normal. Taken together, these results provide a greater understanding of avian IFIT5. PMID:25816333

The pursuit of perfect packing

CERN Document Server

Weaire, Denis

2008-01-01

Coauthored by one of the creators of the most efficient space packing solution, the Weaire-Phelan structure, The Pursuit of Perfect Packing, Second Edition explores a problem of importance in physics, mathematics, chemistry, biology, and engineering: the packing of structures. Maintaining its mathematical core, this edition continues and revises some of the stories from its predecessor while adding several new examples and applications. The book focuses on both scientific and everyday problems ranging from atoms to honeycombs. It describes packing models, such as the Kepler conjecture, Voronoï decomposition, and Delaunay decomposition, as well as actual structure models, such as the Kelvin cell and the Weaire-Phelan structure. The authors discuss numerous historical aspects and provide biographical details on influential contributors to the field, including emails from Thomas Hales and Ken Brakke. With examples from physics, crystallography, engineering, and biology, this accessible and whimsical bo...

Quality strategies implemented within the tourism agency Perfect Tour

Directory of Open Access Journals (Sweden)

Madar, A.

2012-01-01

Full Text Available The paper presents the quality strategies adopted by the tourism agency Perfect Tour. The most important advantages of the Romanian agency in comparison with its competitors are: the focus on high quality services, cooperation with other international agencies, entering new fields like medical tourism and sole representative of Disneyland Paris. The strategies adopted explain the good financial results even in the period of crisis.

Schizosaccharomyces pombe MutSα and MutLα Maintain Stability of Tetra-Nucleotide Repeats and Msh3 of Hepta-Nucleotide Repeats

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Desirée Villahermosa

2017-05-01

Full Text Available Defective mismatch repair (MMR in humans is associated with colon cancer and instability of microsatellites, that is, DNA sequences with one or several nucleotides repeated. Key factors of eukaryotic MMR are the heterodimers MutSα (Msh2-Msh6, which recognizes base-base mismatches and unpaired nucleotides in DNA, and MutLα (Mlh1-Pms1, which facilitates downstream steps. In addition, MutSβ (Msh2-Msh3 recognizes DNA loops of various sizes, although our previous data and the data presented here suggest that Msh3 of Schizosaccharomyces pombe does not play a role in MMR. To test microsatellite stability in S. pombe and hence DNA loop repair, we have inserted tetra-, penta-, and hepta-nucleotide repeats in the ade6 gene and determined their Ade+ reversion rates and spectra in wild type and various mutants. Our data indicate that loops with four unpaired nucleotides in the nascent and the template strand are the upper limit of MutSα- and MutLα-mediated MMR in S. pombe. Stability of hepta-nucleotide repeats requires Msh3 and Exo1 in MMR-independent processes as well as the DNA repair proteins Rad50, Rad51, and Rad2FEN1. Most strikingly, mutation rates in the double mutants msh3 exo1 and msh3 rad51 were decreased when compared to respective single mutants, indicating that Msh3 prevents error prone processes carried out by Exo1 and Rad51. We conclude that Msh3 has no obvious function in MMR in S. pombe, but contributes to DNA repeat stability in MMR-independent processes.

Computational study of ammonia adsorption on the perfect and rippled graphene sheet

International Nuclear Information System (INIS)

Seyed-Talebi, Seyedeh Mozhgan; Beheshtian, Javad

2013-01-01

Adsorption of an ammonia molecule onto perfect and rippled graphene is studied using molecular mechanics calculations. The most stable orientation of an ammonia molecule and equilibrium distance of this molecule over graphene surface (motivated by the recent realization of graphene sensors to detect individual gas molecules) is determined using DFT calculation. This result is in agreement with the predicted molecular mechanics calculation result. It also has been found that (i) the ammonia molecule is weakly adsorbed onto the graphene sheet; (ii) the periodic nature of the potential energy stored between ammonia and perfect graphene is altered due to the sinusoidal ripples; and (iii) the effect of amplitude and wavelength of the one-dimensional created ripple on different energy modes is reported

Computational study of ammonia adsorption on the perfect and rippled graphene sheet

Energy Technology Data Exchange (ETDEWEB)

Seyed-Talebi, Seyedeh Mozhgan [Department of Physics, Shahid Rajaee Teacher Training University, Tehran (Iran, Islamic Republic of); Beheshtian, Javad, E-mail: J.Beheshtian@Srttu.edu [Department of Chemistry, Shahid Rajaee Teacher Training University, Tehran (Iran, Islamic Republic of)

2013-11-15

Adsorption of an ammonia molecule onto perfect and rippled graphene is studied using molecular mechanics calculations. The most stable orientation of an ammonia molecule and equilibrium distance of this molecule over graphene surface (motivated by the recent realization of graphene sensors to detect individual gas molecules) is determined using DFT calculation. This result is in agreement with the predicted molecular mechanics calculation result. It also has been found that (i) the ammonia molecule is weakly adsorbed onto the graphene sheet; (ii) the periodic nature of the potential energy stored between ammonia and perfect graphene is altered due to the sinusoidal ripples; and (iii) the effect of amplitude and wavelength of the one-dimensional created ripple on different energy modes is reported.

Reconfigurable multiport EPON repeater

Science.gov (United States)

Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

2009-11-01

An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

Mirror-backed Dark Alumina: A Nearly Perfect Absorber for Thermoelectronics and Thermophotovotaics

KAUST Repository

Farhat, Mohamed; Cheng, Tsung-Chieh; Le, Khai. Q.; Cheng, Mark Ming-Cheng; Bagci, Hakan; Chen, Pai-Yen

2016-01-01

We present here a broadband, wide-angle, and polarization-independent nearly perfect absorber consisting of mirror-backed nanoporous alumina. By electrochemically anodizing the disordered multicomponent aluminum and properly tailoring the thickness

WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family.

Science.gov (United States)

Chevanne, Damien; Saupe, Sven J; Clavé, Corinne; Paoletti, Mathieu

2010-05-06

Genes involved in non-self recognition and host defence are typically capable of rapid diversification and exploit specialized genetic mechanism to that end. Fungi display a non-self recognition phenomenon termed heterokaryon incompatibility that operates when cells of unlike genotype fuse and leads to the cell death of the fusion cell. In the fungus Podospora anserina, three genes controlling this allorecognition process het-d, het-e and het-r are paralogs belonging to the same hnwd gene family. HNWD proteins are STAND proteins (signal transduction NTPase with multiple domains) that display a WD-repeat domain controlling recognition specificity. Based on genomic sequence analysis of different P. anserina isolates, it was established that repeat regions of all members of the gene family are extremely polymorphic and undergoing concerted evolution arguing for frequent recombination within and between family members. Herein, we directly analyzed the genetic instability and diversification of this allorecognition gene family. We have constituted a collection of 143 spontaneous mutants of the het-R (HNWD2) and het-E (hnwd5) genes with altered recognition specificities. The vast majority of the mutants present rearrangements in the repeat arrays with deletions, duplications and other modifications as well as creation of novel repeat unit variants. We investigate the extreme genetic instability of these genes and provide a direct illustration of the diversification strategy of this eukaryotic allorecognition gene family.

The perfect man in the literary opus of John Climacus and Ibn Arabi

Directory of Open Access Journals (Sweden)

Rašić Dunja

2015-01-01

Full Text Available In search of the perfect man of the Islamic and Christian mysticisms, this paper also discusses the nature of mystical knowledge, to whose domain the perfect man, as the highest model of human existence and spiritual life, indisputably belongs. This study belongs to the philosophical discipline of comparative philosophy. Hence, searching for the lost paradise of human existence, still remembering the taste of bliss of residence filled only with infinite happiness, this paper will consider the extent to which the methodology of Paul Masson-Oursel and Henry Corbin, as two well-known comparative philosophy research methods can try to measure their strength with cryptic teachings of mysticism.

HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment

NARCIS (Netherlands)

Kappei, D.; Butter, F.; Benda, C.; Scheibe, M.; Draskovic, Irena; Stevense, M.; Novo, C.L.; Basquin, C.; Araki, M.; Araki, K.; Krastev, D.B.; Kittler, R.; Jessberger, R.; Londono-Vallejo, J.A.; Mann, M.; Buchholz, F.

2013-01-01

Telomeres are repetitive DNA structures that, together with the shelterin and the CST complex, protect the ends of chromosomes. Telomere shortening is mitigated in stem and cancer cells through the de novo addition of telomeric repeats by telomerase. Telomere elongation requires the delivery of the

Changes in Liver Proteome Expression of Senegalese Sole (Solea senegalensis) in Response to Repeated Handling Stress

DEFF Research Database (Denmark)

Cordeiro, O. D.; Silva, Tomé Santos; Alves, R. N.

2012-01-01

The Senegalese sole, a high-value flatfish, is a good candidate for aquaculture production. Nevertheless, there are still issues regarding this species’ sensitivity to stress in captivity. We aimed to characterize the hepatic proteome expression for this species in response to repeated handling...... and identify potential molecular markers that indicate a physiological response to chronic stress. Two groups of fish were reared in duplicate for 28 days, one of them weekly exposed to handling stress (including hypoxia) for 3 min, and the other left undisturbed. Two-dimensional electrophoresis enabled...... the detection of 287 spots significantly affected by repeated handling stress (Wilcoxon–Mann–Whitney U test, p stress seems to have affected protein synthesis, folding and turnover (40S ribosomal protein S12...

Bianchi Type-V model with a perfect fluid and Λ-term

Indian Academy of Sciences (India)

A self-consistent system of gravitational field with a binary mixture of perfect ... a form of quintessence, may explain the coincidence, adding a new motivation for .... hand, with the expansion of the universe, i.e., with the increase of V , the ...

β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat.

Science.gov (United States)

Wohleb, Eric S; Hanke, Mark L; Corona, Angela W; Powell, Nicole D; Stiner, La'Tonia M; Bailey, Michael T; Nelson, Randy J; Godbout, Jonathan P; Sheridan, John F

2011-04-27

Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.

Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel leu-rich repeats-containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster

DEFF Research Database (Denmark)

Eriksen, Kathrine Krageskov; Hauser, Frank; Schiøtt, Morten

2000-01-01

After screening the Berkeley Drosophila Genome Project database with sequences from a recently characterized Leu-rich repeats-containing G protein-coupled receptor (LGR) fromDrosophila (DLGR-1), we identified a second gene for a different LGR (DLGR-2) and cloned its cDNA. DLGR-2 is 1360 amino aci...... knock-out mutants, where the DLGR-2 gene is interrupted by a P element insertion, die around the time of hatching. This finding, together with the expression data, strongly suggests that DLGR-2 is exclusively involved in development....

Unity and Duality in Barack Obama's "A More Perfect Union"

Science.gov (United States)

Terrill, Robert E.

2009-01-01

Faced with a racialized political crisis that threatened to derail his campaign to become the first African American president of the United States, Barack Obama delivered a speech on race titled "A More Perfect Union." He begins by portraying himself as an embodiment of double consciousness, but then invites his audience to share his…

Structural and biochemical analysis of nuclease domain of clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 3 (Cas3).

Science.gov (United States)

Mulepati, Sabin; Bailey, Scott

2011-09-09

RNA transcribed from clustered regularly interspaced short palindromic repeats (CRISPRs) protects many prokaryotes from invasion by foreign DNA such as viruses, conjugative plasmids, and transposable elements. Cas3 (CRISPR-associated protein 3) is essential for this CRISPR protection and is thought to mediate cleavage of the foreign DNA through its N-terminal histidine-aspartate (HD) domain. We report here the 1.8 Å crystal structure of the HD domain of Cas3 from Thermus thermophilus HB8. Structural and biochemical studies predict that this enzyme binds two metal ions at its active site. We also demonstrate that the single-stranded DNA endonuclease activity of this T. thermophilus domain is activated not by magnesium but by transition metal ions such as manganese and nickel. Structure-guided mutagenesis confirms the importance of the metal-binding residues for the nuclease activity and identifies other active site residues. Overall, these results provide a framework for understanding the role of Cas3 in the CRISPR system.

Perfect-use and typical-use Pearl Index of a contraceptive mobile app.

Science.gov (United States)

Berglund Scherwitzl, E; Lundberg, O; Kopp Kallner, H; Gemzell Danielsson, K; Trussell, J; Scherwitzl, R

2017-12-01

The Natural Cycles application is a fertility awareness-based contraceptive method that uses dates of menstruation and basal body temperature to inform couples whether protected intercourse is needed to prevent pregnancies. Our purpose with this study is to investigate the contraceptive efficacy of the mobile application by evaluating the perfect- and typical-use Pearl Index. In this prospective observational study, 22,785 users of the application logged a total of 18,548 woman-years of data into the application. We used these data to calculate typical- and perfect-use Pearl Indexes, as well as 13-cycle pregnancy rates using life-table analysis. We found a typical-use Pearl Index of 6.9 pregnancies per 100 woman-years [95% confidence interval (CI): 6.5-7.2], corrected to 6.8 (95% CI: 6.4-7.2) when truncating users after 12months. We estimated a 13-cycle typical-use failure rate of 8.3% (95% CI: 7.8-8.9). We found that the perfect-use Pearl Index was 1.0 pregnancy per 100 woman-years (95% CI: 0.5-1.5). Finally, we estimated that the rate of pregnancies from cycles where the application erroneously flagged a fertile day as infertile was 0.5 (95% CI: 0.4-0.7) per 100 woman-years. We estimated a discontinuation rate over 12months of 54%. This study shows that the efficacy of a contraceptive mobile application is higher than usually reported for traditional fertility awareness-based methods. The application may contribute to reducing the unmet need for contraception. The measured typical- and perfect-use efficacies of the mobile application Natural Cycles are important parameters for women considering their contraceptive options as well as for the clinicians advising them. The large available data set in this paper allows for future studies on acceptability, for example, by studying the efficacy for different cohorts and geographic regions. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

[Bioinformatics Analysis of Clustered Regularly Interspaced Short Palindromic Repeats in the Genomes of Shigella].

Science.gov (United States)

Wang, Pengfei; Wang, Yingfang; Duan, Guangcai; Xue, Zerun; Wang, Linlin; Guo, Xiangjiao; Yang, Haiyan; Xi, Yuanlin

2015-04-01

This study was aimed to explore the features of clustered regularly interspaced short palindromic repeats (CRISPR) structures in Shigella by using bioinformatics. We used bioinformatics methods, including BLAST, alignment and RNA structure prediction, to analyze the CRISPR structures of Shigella genomes. The results showed that the CRISPRs existed in the four groups of Shigella, and the flanking sequences of upstream CRISPRs could be classified into the same group with those of the downstream. We also found some relatively conserved palindromic motifs in the leader sequences. Repeat sequences had the same group with corresponding flanking sequences, and could be classified into two different types by their RNA secondary structures, which contain "stem" and "ring". Some spacers were found to homologize with part sequences of plasmids or phages. The study indicated that there were correlations between repeat sequences and flanking sequences, and the repeats might act as a kind of recognition mechanism to mediate the interaction between foreign genetic elements and Cas proteins.

Defending perfectionism: Some comments on Quong’s liberalism without perfection

Directory of Open Access Journals (Sweden)

Kulenović Enes

2014-01-01

Full Text Available The article offers a defense of liberal perfectionism in the light of criticism of perfectionist politics stated in Jonathan Quong’s book Liberalism without Perfection. It argues against Quong’s claims that perfectionism is incompatible with demands of individual autonomy and non-paternalism as requirements of liberal commitment of treating all persons as free and equal.

Bianchi type-I massive string magnetized barotropic perfect fluid

Indian Academy of Sciences (India)

Bianchi type-I massive string cosmological model for perfect fluid distribution in the presence of magnetic field is investigated in Rosen's [Gen. Relativ. Gravit. 4, 435 (1973)] bimetric theory of gravitation. To obtain the deterministic model in terms of cosmic time, we have used the condition A = ( B C ) n , where n is a constant, ...

The C9orf72 repeat expansion disrupts nucleocytoplasmic transport.

Science.gov (United States)

Zhang, Ke; Donnelly, Christopher J; Haeusler, Aaron R; Grima, Jonathan C; Machamer, James B; Steinwald, Peter; Daley, Elizabeth L; Miller, Sean J; Cunningham, Kathleen M; Vidensky, Svetlana; Gupta, Saksham; Thomas, Michael A; Hong, Ingie; Chiu, Shu-Ling; Huganir, Richard L; Ostrow, Lyle W; Matunis, Michael J; Wang, Jiou; Sattler, Rita; Lloyd, Thomas E; Rothstein, Jeffrey D

2015-09-03

The hexanucleotide repeat expansion (HRE) GGGGCC (G4C2) in C9orf72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies support an HRE RNA gain-of-function mechanism of neurotoxicity, and we previously identified protein interactors for the G4C2 RNA including RanGAP1. A candidate-based genetic screen in Drosophila expressing 30 G4C2 repeats identified RanGAP (Drosophila orthologue of human RanGAP1), a key regulator of nucleocytoplasmic transport, as a potent suppressor of neurodegeneration. Enhancing nuclear import or suppressing nuclear export of proteins also suppresses neurodegeneration. RanGAP physically interacts with HRE RNA and is mislocalized in HRE-expressing flies, neurons from C9orf72 ALS patient-derived induced pluripotent stem cells (iPSC-derived neurons), and in C9orf72 ALS patient brain tissue. Nuclear import is impaired as a result of HRE expression in the fly model and in C9orf72 iPSC-derived neurons, and these deficits are rescued by small molecules and antisense oligonucleotides targeting the HRE G-quadruplexes. Nucleocytoplasmic transport defects may be a fundamental pathway for ALS and FTD that is amenable to pharmacotherapeutic intervention.

Nonlinear analysis of sequence repeats of multi-domain proteins

Energy Technology Data Exchange (ETDEWEB)

Huang Yanzhao [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Li Mingfeng [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Xiao Yi [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China)]. E-mail: lmf_bill@sina.com

2007-11-15

Many multi-domain proteins have repetitive three-dimensional structures but nearly-random amino acid sequences. In the present paper, by using a modified recurrence plot proposed by us previously, we show that these amino acid sequences have hidden repetitions in fact. These results indicate that the repetitive domain structures are encoded by the repetitive sequences. This also gives a method to detect the repetitive domain structures directly from amino acid sequences.

Identification of a novel receptor-like protein kinase that interacts with a geminivirus nuclear shuttle protein

International Nuclear Information System (INIS)

Mariano, Andrea C.; Andrade, Maxuel O.; Santos, Anesia A.; Carolino, Sonia M.B.; Oliveira, Marli L.; Baracat-Pereira, Maria Cristina; Brommonshenkel, Sergio H.; Fontes, Elizabeth P.B.

2004-01-01

Despite extensive studies in plant virus-host interactions, the molecular mechanisms of geminivirus movement and interactions with host components remain largely unknown. A tomato kinase protein and its soybean homolog were found to interact specifically with the nuclear shuttle protein (NSP) of Tomato golden mosaic virus (TGMV) and Tomato crinkle leaf yellows virus (TCrLYV) through yeast two-hybrid screening and in vitro protein binding assays. These proteins, designated LeNIK (Lycopersicon esculentum NSP-Interacting Kinase) and GmNIK (Glycine max NIK), belong to the LRR-RLK (leucine rich-repeat receptor-like kinase) family that is involved in plant developmental processes and/or resistance response. As such, NIK is structurally organized into characteristic domains, including a serine/threonine kinase domain with a nucleotide binding site at the C-terminal region, an internal transmembrane segment and leucine-rich repeats (LRR) at the N-terminal portion. The potential significance of the NSP-NIK interaction is discussed

Thermal stability of chicken brain {alpha}-spectrin repeat 17: a spectroscopic study

Energy Technology Data Exchange (ETDEWEB)

Brenner, Annette K. [University of Bergen, Department of Chemistry (Norway); Kieffer, Bruno [Ecole Superieure de Biotechnologie de Strasbourg, IGBMC Biomolecular NMR Group, CNRS UMR 7104 (France); Trave, Gilles [Ecole Superieure de Biotechnologie de Strasbourg, Equipe Oncoproteines, IREBS, UMR 7242 (France); Froystein, Nils Age [University of Bergen, Department of Chemistry (Norway); Raae, Arnt J., E-mail: arnt.raae@mbi.uib.no [University of Bergen, Department of Molecular Biology (Norway)

2012-06-15

Spectrin is a rod-like multi-modular protein that is mainly composed of triple-helical repeats. These repeats show very similar 3D-structures but variable conformational and thermodynamical stabilities, which may be of great importance for the flexibility and dynamic behaviour of spectrin in the cell. For instance, repeat 17 (R17) of the chicken brain spectrin {alpha}-chain is four times less stable than neighbouring repeat 16 (R16) in terms of Increment G. The structure of spectrin repeats has mainly been investigated by X-ray crystallography, but the structures of a few repeats, e.g. R16, have also been determined by NMR spectroscopy. Here, we undertook a detailed characterization of the neighbouring R17 by NMR spectroscopy. We assigned most backbone resonances and observed NOE restraints, relaxation values and coupling constants that all indicated that the fold of R17 is highly similar to that of R16, in agreement with previous X-ray analysis of a tandem repeat of the two domains. However, {sup 15}N heteronuclear NMR spectra measured at different temperatures revealed particular features of the R17 domain that might contribute to its lower stability. Conformational exchange appeared to alter the linker connecting R17 to R16 as well as the BC-loop in close proximity. In addition, heat-induced splitting was observed for backbone resonances of a few spatially related residues including V99 of helix C, which in R16 is replaced by the larger hydrophobic tryptophan residue that is relatively conserved among other spectrin repeats. These data support the view that the substitution of tryptophan by valine at this position may contribute to the lower stability of R17.

Individualization of psychological training and its importance at different stages of many years’ perfection in tennis

Directory of Open Access Journals (Sweden)

N.L. Vysochina

2015-08-01

Full Text Available Purpose: to determine significance of individualized approach during psychological training at different stages of many years’ perfection in tennis. The tasks of the research were studying of place and role of psychological component in general system of tennis players’ sport training as well as determination of specificities of individualized approach during 14-15 years old and elite tennis players’ psychological training. Material: In the research 24 experts, coaches of combined teams and clubs, elite tennis players took part. Results: Role of psychological training in general system of many years’ perfection has been determined. We also found out that individualization of psychological training in modern tennis is not paid sufficient attention to at present. Most of the questioned respondents pointed, that such training is conducted mainly with elite sportsmen (42%. Only 14% noted that individual psychological training is carried out at basic stages of many years’ perfection. Conclusions: Principle of individualization is a determining one in the course of sportsmen’s training at stages of many years’ perfection. About 86% of experts stressed on significance of application of individualized approach in work with tennis players. Consideration of tennis players’ individual features during psychological training is a compulsory matter in increasing of effectiveness of sportsmen’s training and competition functioning.

Collapsing a perfect superposition to a chosen quantum state without measurement.

Directory of Open Access Journals (Sweden)

Ahmed Younes

Full Text Available Given a perfect superposition of [Formula: see text] states on a quantum system of [Formula: see text] qubits. We propose a fast quantum algorithm for collapsing the perfect superposition to a chosen quantum state [Formula: see text] without applying any measurements. The basic idea is to use a phase destruction mechanism. Two operators are used, the first operator applies a phase shift and a temporary entanglement to mark [Formula: see text] in the superposition, and the second operator applies selective phase shifts on the states in the superposition according to their Hamming distance with [Formula: see text]. The generated state can be used as an excellent input state for testing quantum memories and linear optics quantum computers. We make no assumptions about the used operators and applied quantum gates, but our result implies that for this purpose the number of qubits in the quantum register offers no advantage, in principle, over the obvious measurement-based feedback protocol.

A New Compact Octagonal Shape Perfect Metamaterial Absorber for Microwave Applications

Directory of Open Access Journals (Sweden)

Mohammad Jakir Hossain

2017-12-01

Full Text Available A new compact octagonal shape perfect metamaterial absorber (PMA design, numerical simulation, fabrication, and investigational verification of unit cell that is based on a simple structure are presented in this paper. The suggested structure comprised of three layers, in which interact to produce the plasmonic resonances. The finite-integration technique (FIT based Computer Simulation Technology (CST microwave electromagnetic simulator was utilized to examine the design parameters and conduct absorption analysis. The design structure exhibited peak absorption values as 99.64% and 99.95% at frequencies 8.08 GHz and 11.41 GHz, respectively. The absorption characteristics were analysed using the polarization angle of the structure, layer thickness, PMA with resistive load, and number of rings. An N5227A vector network analyser was used for the measurement. The measured results of the fabricated prototype were in good agreement with the simulation results. The suggested perfect absorber structure enables innumerable application aimed at X-band for applications like, defence, security, and stealth technology.

P-Finder: Reconstruction of Signaling Networks from Protein-Protein Interactions and GO Annotations.

Science.gov (United States)

Young-Rae Cho; Yanan Xin; Speegle, Greg

2015-01-01

Because most complex genetic diseases are caused by defects of cell signaling, illuminating a signaling cascade is essential for understanding their mechanisms. We present three novel computational algorithms to reconstruct signaling networks between a starting protein and an ending protein using genome-wide protein-protein interaction (PPI) networks and gene ontology (GO) annotation data. A signaling network is represented as a directed acyclic graph in a merged form of multiple linear pathways. An advanced semantic similarity metric is applied for weighting PPIs as the preprocessing of all three methods. The first algorithm repeatedly extends the list of nodes based on path frequency towards an ending protein. The second algorithm repeatedly appends edges based on the occurrence of network motifs which indicate the link patterns more frequently appearing in a PPI network than in a random graph. The last algorithm uses the information propagation technique which iteratively updates edge orientations based on the path strength and merges the selected directed edges. Our experimental results demonstrate that the proposed algorithms achieve higher accuracy than previous methods when they are tested on well-studied pathways of S. cerevisiae. Furthermore, we introduce an interactive web application tool, called P-Finder, to visualize reconstructed signaling networks.

Use of the perfect electric conductor boundary conditions to discretize a diffractor in FDTD/PML environment

OpenAIRE

Calderón-Ramón, C.; Gómez-Aguilar, J. F.; Rodríguez-Achach, M.; Morales- Mendoza, L. J.; Laguna-Camacho, J. R.; Benavides-Cruz, M.; Cruz-Orduna, M. I.; González-Lee, M.; Pérez-Meana, H.; Enciso-Aguilar, M.; Chávez-Pérez, R.; Martínez-García, H.

2015-01-01

In this paper we present a computational electromagnetic simulation of a multiform diffractor placed at the center of an antenna array. Our approach is to solve Maxwell's differential equations with a discrete space-time formulation, using the Finite Difference Time Domain (FDTD) method. The Perfectly Matched Layers (PML) method is used as an absorbing boundary condition, to prevent further spread of the electromagnetic wave to the outside of the calculation region. The Perfect Electric Condu...

A tensegrity model for hydrogen bond networks in proteins

Directory of Open Access Journals (Sweden)

Robert P. Bywater

2017-05-01

Full Text Available Hydrogen-bonding networks in proteins considered as structural tensile elements are in balance separately from any other stabilising interactions that may be in operation. The hydrogen bond arrangement in the network is reminiscent of tensegrity structures in architecture and sculpture. Tensegrity has been discussed before in cells and tissues and in proteins. In contrast to previous work only hydrogen bonds are studied here. The other interactions within proteins are either much stronger − covalent bonds connecting the atoms in the molecular skeleton or weaker forces like the so-called hydrophobic interactions. It has been demonstrated that the latter operate independently from hydrogen bonds. Each category of interaction must, if the protein is to have a stable structure, balance out. The hypothesis here is that the entire hydrogen bond network is in balance without any compensating contributions from other types of interaction. For sidechain-sidechain, sidechain-backbone and backbone-backbone hydrogen bonds in proteins, tensegrity balance (“closure” is required over the entire length of the polypeptide chain that defines individually folding units in globular proteins (“domains” as well as within the repeating elements in fibrous proteins that consist of extended chain structures. There is no closure to be found in extended structures that do not have repeating elements. This suggests an explanation as to why globular domains, as well as the repeat units in fibrous proteins, have to have a defined number of residues. Apart from networks of sidechain-sidechain hydrogen bonds there are certain key points at which this closure is achieved in the sidechain-backbone hydrogen bonds and these are associated with demarcation points at the start or end of stretches of secondary structure. Together, these three categories of hydrogen bond achieve the closure that is necessary for the stability of globular protein domains as well as repeating

Comparative and functional characterization of intragenic tandem repeats in 10 Aspergillus genomes.

Science.gov (United States)

Gibbons, John G; Rokas, Antonis

2009-03-01

Intragenic tandem repeats (ITRs) are consecutive repeats of three or more nucleotides found in coding regions. ITRs are the underlying cause of several human genetic diseases and have been associated with phenotypic variation, including pathogenesis, in several clades of the tree of life. We have examined the evolution and functional role of ITRs in 10 genomes spanning the fungal genus Aspergillus, a clade of relevance to medicine, agriculture, and industry. We identified several hundred ITRs in each of the species examined. ITR content varied extensively between species, with an average 79% of ITRs unique to a given species. For the fraction of conserved ITR regions, sequence comparisons within species and between close relatives revealed that they were highly variable. ITR-containing proteins were evolutionarily less conserved, compositionally distinct, and overrepresented for domains associated with cell-surface localization and function relative to the rest of the proteome. Furthermore, ITRs were preferentially found in proteins involved in transcription, cellular communication, and cell-type differentiation but were underrepresented in proteins involved in metabolism and energy. Importantly, although ITRs were evolutionarily labile, their functional associations appeared. To be remarkably conserved across eukaryotes. Fungal ITRs likely participate in a variety of developmental processes and cell-surface-associated functions, suggesting that their contribution to fungal lifestyle and evolution may be more general than previously assumed.

Bioengineered protein-based nanocage for drug delivery.

Science.gov (United States)

Lee, Eun Jung; Lee, Na Kyeong; Kim, In-San

2016-11-15

Nature, in its wonders, presents and assembles the most intricate and delicate protein structures and this remarkable phenomenon occurs in all kingdom and phyla of life. Of these proteins, cage-like multimeric proteins provide spatial control to biological processes and also compartmentalizes compounds that may be toxic or unstable and avoids their contact with the environment. Protein-based nanocages are of particular interest because of their potential applicability as drug delivery carriers and their perfect and complex symmetry and ideal physical properties, which have stimulated researchers to engineer, modify or mimic these qualities. This article reviews various existing types of protein-based nanocages that are used for therapeutic purposes, and outlines their drug-loading mechanisms and bioengineering strategies via genetic and chemical functionalization. Through a critical evaluation of recent advances in protein nanocage-based drug delivery in vitro and in vivo, an outlook for de novo and in silico nanocage design, and also protein-based nanocage preclinical and future clinical applications will be presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

Science.gov (United States)

Battes, Linda C; Caliskan, Kadir; Rizopoulos, Dimitris; Constantinescu, Alina A; Robertus, Jan L; Akkerhuis, Martijn; Manintveld, Olivier C; Boersma, Eric; Kardys, Isabella

2015-03-01

Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.

The superfamily of C3b/C4b-binding proteins

DEFF Research Database (Denmark)

Kristensen, Torsten; D'Eustachio, P; Ogata, R T

1987-01-01

The determination of primary structures by amino acid and nucleotide sequencing for the C3b-and/or C4b-binding proteins H, C4BP, CR1, B, and C2 has revealed the presence of a common structural element. This element is approximately 60 amino acids long and is repeated in a tandem fashion, commencing...... at the amino-terminal end of each molecule. Two other complement components, C1r and C1s, have two of these repeating units in the carboxy-terminal region of their noncatalytic A chains. Three noncomplement proteins, beta 2-glycoprotein I (beta 2I), the interleukin 2 receptor (IL 2 receptor), and the b chain...... of factor XIII, have 4, 2 and 10 of these repeating units, respectively. These proteins obviously belong to the above family, although there is no evidence that they interact with C3b and/or C4b. Human haptoglobin and rat leukocyte common antigen also contain two and three repeating units, respectively...

Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

Science.gov (United States)

Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

2014-02-01

The Gd5Ge2Si2 alloy and the off-stoichiometric Ni50Mn35In15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd5Ge2Si2 and Ni50Mn35In15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

International Nuclear Information System (INIS)

Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

2014-01-01

The Gd 5 Ge 2 Si 2 alloy and the off-stoichiometric Ni 50 Mn 35 In 15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd 5 Ge 2 Si 2 and Ni 50 Mn 35 In 15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis

Repeated treatment with nitric oxide synthase inhibitor attenuates learned helplessness development in rats and increases hippocampal BDNF expression.

Science.gov (United States)

Stanquini, Laura Alves; Biojone, Caroline; Guimarães, Francisco Silveira; Joca, Sâmia Regiane

2017-11-20

Nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects in animal models sensitive to acute drug treatment such as the forced swimming test. However, it is not yet clear if repeated treatment with these drugs is required to induce antidepressant-like effects in preclinical models. The aim of this study was to test the effect induced by acute or repeated (7 days) treatment with 7-nitroindazole (7-NI), a preferential inhibitor of neuronal NOS, in rats submitted to the learned helplessness (LH) model. In addition, we aimed at investigating if 7-NI treatment would increase brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus, similarly to the effect of prototype antidepressants. Animals were submitted to a pre-test (PT) session with inescapable footshocks or habituation (no shocks) to the experimental shuttle box. Six days later they were exposed to a test with escapable footshocks. Independent groups received acute (a single injection after PT or before test) or repeated (once a day for 7 days) treatment with vehicle or 7-NI (30 mg/kg). Repeated, but not acute, treatment with 7-NI attenuated LH development. The effect was similar to repeated imipramine treatment. Moreover, in an independent experimental group, only repeated treatment with 7-NI and imipramine increased BDNF protein levels in the hippocampus. The results suggest the nitrergic system could be a target for the treatment of depressive-like conditions. They also indicate that, similar to the positive control imipramine, the antidepressant-like effects of NOS inhibition could involve an increase in hippocampal BDNF levels.

FURTHER NOTES FOR A CONTRASTIVE AND DIDACTIC APPROACH TO THE USE OF THE PRESENT PERFECT TENSE VS. THE PAST TENSE

Directory of Open Access Journals (Sweden)

Constantin MANEA

2010-11-01

Full Text Available The Present Perfect Tense is a notable instance of the many quirks, “pitfalls” and inherent intricacies that can make the acquisition of English grammar quite a challenge, even with advanced students. Its dissimilarity from its possible counterparts in most European languages (including Romanian is patent. The present contribution continues the author’s preoccupation with such “False Friends” that teaching is called upon to overcome (at least, to an acceptable degree. Since the Present Perfect Tense closely incorporates tense and aspect information, while also being highly context-, and attitude-dependent, it requires conscious communicative adjustment on the part of the nonnative speaker, including the students of EFL. The grammatical category of Aspect often emerges as a linguistic “trap” for foreign learners of English, since, in Romanian, it is rendered unsystematically, mainly through specialized words, phrases, or derivational morphemes, being, in most cases, rather lexicalized (and comparatively syntax-dependent; in English aspect is a grammatical category mainly – and essentially – subordinated to the category of tense, and is usually taught as such. In this presentation, very much as in the previous one dealing with the Present Perfect and Past Tense, we considered that the most serious grammatical “trap” with respect to the use and definition of the two tenses under consideration is laid by the notion of perfectivity. The contribution presents the main tenses involved in the broader picture of the English tenses and verbal structures related, in a way or other, to the past – viz. the Past Tense Simple, the Past Tense Progressive, the Present Perfect Simple Tense, and the Present Perfect Progressive Tense –, as well as the main differences (in meaning, grammatical collocation and communicative implications between the Present Perfect Tense and the Past Tense. The author’s remarks could hopefully contribute to

FURTHER NOTES FOR A CONTRASTIVE AND DIDACTIC APPROACH TO THE USE OF THE PRESENT PERFECT TENSE VS. THE PAST TENSE

Directory of Open Access Journals (Sweden)

Constantin MANEA

2008-09-01

Full Text Available The Present Perfect Tense is a notable instance of the many quirks, “pitfalls” and inherent intricacies that can make the acquisition of English grammar quite a challenge, even with advanced students. Its dissimilarity from its possible counterparts in most European languages (including Romanian is patent. The present contribution continues the author’s preoccupation with such “False Friends” that teaching is called upon to overcome (at least, to an acceptable degree. Since the Present Perfect Tense closely incorporates tense and aspect information, while also being highly context-, and attitude-dependent, it requires conscious communicative adjustment on the part of the non-native speaker, including the students of EFL. The grammatical category of Aspect often emerges as a linguistic “trap” for foreign learners of English, since, in Romanian, it is rendered unsystematically, mainly through specialized words, phrases, or derivational morphemes, being, in most cases, rather lexicalized (and comparatively syntax-dependent; in English aspect is a grammatical category mainly – and essentially – subordinated to the category of tense, and is usually taught as such. In this presentation, very much as in the previous one dealing with the Present Perfect and Past Tense, we considered that the most serious grammatical “trap” with respect to the use and definition of the two tenses under consideration is laid by the notion of perfectivity. The contribution presents the main tenses involved in the broader picture of the English tenses and verbal structures related, in a way or other, to the past – viz. the Past Tense Simple, the Past Tense Progressive, the Present Perfect Simple Tense, and the Present Perfect Progressive Tense –, as well as the main differences (in meaning, grammatical collocation and communicative implications between the Present Perfect Tense and the Past Tense. The author’s remarks could hopefully contribute

Linearization of the bradford protein assay.

Science.gov (United States)

Ernst, Orna; Zor, Tsaffrir

2010-04-12

Determination of microgram quantities of protein in the Bradford Coomassie brilliant blue assay is accomplished by measurement of absorbance at 590 nm. This most common assay enables rapid and simple protein quantification in cell lysates, cellular fractions, or recombinant protein samples, for the purpose of normalization of biochemical measurements. However, an intrinsic nonlinearity compromises the sensitivity and accuracy of this method. It is shown that under standard assay conditions, the ratio of the absorbance measurements at 590 nm and 450 nm is strictly linear with protein concentration. This simple procedure increases the accuracy and improves the sensitivity of the assay about 10-fold, permitting quantification down to 50 ng of bovine serum albumin. Furthermore, the interference commonly introduced by detergents that are used to create the cell lysates is greatly reduced by the new protocol. A linear equation developed on the basis of mass action and Beer's law perfectly fits the experimental data.

CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression

DEFF Research Database (Denmark)

Zaghloul, Eman M; Gissberg, Olof; Moreno, Pedro M D

2017-01-01

Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not significantly alter the disease progression or increase life expectancy. HD is caused by expansion....... Thus, reduction of both muHTT mRNA and protein levels would ideally be the most useful therapeutic option. We herein present a novel strategy for HD treatment using oligonucleotides (ONs) directly targeting the HTT trinucleotide repeat DNA. A partial, but significant and potentially long-term, HTT...

All-photonic quantum repeaters

Science.gov (United States)

Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

2015-01-01

Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

Complement system proteins which interact with C3b or C4b A superfamily of structurally related proteins

DEFF Research Database (Denmark)

Reid, K B M; Bentley, D R; Campbell, R D

1986-01-01

Recent cDNA sequencing data has allowed the prediction of the entire amino acid sequences of complement components factor B and C2, the complement control proteins factor H and C4b-binding protein and a partial sequence for the Cab/C4b receptor CR1. These proteins all contain internal repeating u...

Binary Mixture of Perfect Fluid and Dark Energy in Modified Theory of Gravity

Science.gov (United States)

Shaikh, A. Y.

2016-07-01

A self consistent system of Plane Symmetric gravitational field and a binary mixture of perfect fluid and dark energy in a modified theory of gravity are considered. The gravitational field plays crucial role in the formation of soliton-like solutions, i.e., solutions with limited total energy, spin, and charge. The perfect fluid is taken to be the one obeying the usual equation of state, i.e., p = γρ with γ∈ [0, 1] whereas, the dark energy is considered to be either the quintessence like equation of state or Chaplygin gas. The exact solutions to the corresponding field equations are obtained for power-law and exponential volumetric expansion. The geometrical and physical parameters for both the models are studied.

Diffraction of love waves by two parallel perfectly weak half planes

International Nuclear Information System (INIS)

Asghar, S.; Zaman, F.D.; Ayub, M.

1986-04-01

We consider the diffraction of Love waves by two parallel perfectly weak half planes in a layer overlying a half space. The problem is formulated in terms of the Wiener-Hopf equations in the transformed plane. The transmitted waves are then calculated using the Wiener-Hopf procedure and inverse transforms. (author)

Amino acid sequence analysis of the annexin super-gene family of proteins.

Science.gov (United States)

Barton, G J; Newman, R H; Freemont, P S; Crumpton, M J

1991-06-15

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of

A THz plasmonics perfect absorber and Fabry-Perot cavity mechanism (Conference Presentation)

Science.gov (United States)

Zhou, Jiangfeng; Bhattarai, Khagendra; Silva, Sinhara; Jeon, Jiyeon; Kim, Junoh; Lee, Sang Jun; Ku, Zahyun

2016-10-01

The plasmonic metamaterial perfect absorber (MPA) is a recently developed branch of metamaterial which exhibits nearly unity absorption within certain frequency range.[1-6] The optically thin MPA possesses characteristic features of angular-independence, high Q-factor and strong field localization that have inspired a wide range of applications including electromagnetic wave absorption,[3, 7, 8] spatial[6] and spectral[5] modulation of light,[9] selective thermal emission,[9] thermal detecting[10] and refractive index sensing for gas[11] and liquid[12, 13] targets. In this work, we demonstrate a MPA working at terahertz (THz) regime and characterize it using an ultrafast THz time-domain spectroscopy (THz-TDS). Our study reveal an ultra-thin Fabry-Perot cavity mechanism compared to the impedance matching mechanism widely adopted in previous study [1-6]. Our results also shows higher-order resonances when the cavities length increases. These higher order modes exhibits much larger Q-factor that can benefit potential sensing and imaging applications. [1] C. M. Watts, X. L. Liu, and W. J. Padilla, "Metamaterial Electromagnetic Wave Absorbers," Advanced Materials, vol. 24, pp. 98-120, Jun 19 2012. [2] M. Hedayati, F. Faupel, and M. Elbahri, "Review of Plasmonic Nanocomposite Metamaterial Absorber," Materials, vol. 7, pp. 1221-1248, 2014. [3] N. I. Landy, S. Sajuyigbe, J. J. Mock, D. R. Smith, and W. J. Padilla, "Perfect metamaterial absorber," Physical Review Letters, vol. 100, p. 207402, May 23 2008. [4] H. R. Seren, G. R. Keiser, L. Cao, J. Zhang, A. C. Strikwerda, K. Fan, et al., "Optically Modulated Multiband Terahertz Perfect Absorber," Advanced Optical Materials, vol. 2, pp. 1221-1226, 2014. [5] D. Shrekenhamer, J. Montoya, S. Krishna, and W. J. Padilla, "Four-Color Metamaterial Absorber THz Spatial Light Modulator," Advanced Optical Materials, vol. 1, pp. 905-909, 2013. [6] S. Savo, D. Shrekenhamer, and W. J. Padilla, "Liquid Crystal Metamaterial Absorber Spatial

Black hole formation in perfect fluid collapse