Guide-substrate base-pairing requirement for box H/ACA RNA-guided RNA pseudouridylation.

PubMed

De Zoysa, Meemanage D; Wu, Guowei; Katz, Raviv; Yu, Yi-Tao

2018-06-05

Box H/ACA RNAs are a group of small RNAs found in abundance in eukaryotes (as well as in archaea). Although their sequences differ, eukaryotic box H/ACA RNAs all share the same unique hairpin-hinge-hairpin-tail structure. Almost all of them function as guides that primarily direct pseudouridylation of rRNAs and spliceosomal snRNAs at specific sites. Although box H/ACA RNA-guided pseudouridylation has been extensively studied, the detailed rules governing this reaction, especially those concerning the guide RNA-substrate RNA base-pairing interactions that determine the specificity and efficiency of pseudouridylation, are still not exactly clear. This is particularly relevant given that the lengths of the guide sequences involved in base-pairing vary from one box H/ACA RNA to another. Here, we carry out a detailed investigation into guide-substrate base-pairing interactions, and identify the minimum number of base-pairs (8), required for RNA-guided pseudouridylation. In addition, we find that the pseudouridylation pocket, present in each hairpin of box H/ACA RNA, exhibits flexibility in fitting slightly different substrate sequences. Our results are consistent across three independent pseudouridylation pockets tested, suggesting that our findings are generally applicable to box H/ACA RNA-guided RNA pseudouridylation. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Accommodation of an N-(deoxyguanosin-8-yl)-2-acetylaminofluorene adduct in the active site of human DNA polymerase ι: Hoogsteen or Watson-Crick base pairing?†

PubMed Central

Donny-Clark, Kerry; Shapiro, Robert; Broyde, Suse

2009-01-01

Bypass across DNA lesions by specialized polymerases is essential for maintenance of genomic stability. Human DNA polymerase ι (polι) is a bypass polymerase of the Y family. Crystal structures of polι suggest that Hoogsteen base pairing is employed to bypass minor groove DNA lesions, placing them on the spacious major groove side of the enzyme. Primer extension studies have shown that polι is also capable of error-free nucleotide incorporation opposite the bulky major groove adduct N-(deoxyguanosin-8-yl)-2-acetyl-aminofluorene (dG-AAF). We present molecular dynamics simulations and free energy calculations suggesting that Watson-Crick base pairing could be employed in polι for bypass of dG-AAF. In polι with Hoogsteen paired dG-AAF the bulky AAF moiety would reside on the cramped minor groove side of the template. The Hoogsteen-capable conformation distorts the active site, disrupting interactions necessary for error-free incorporation of dC opposite the lesion. Watson-Crick pairing places the AAF rings on the spacious major groove side, similar to the position of minor groove adducts observed with Hoogsteen pairing. Watson-Crick paired structures show a well-ordered active site, with a near reaction-ready ternary complex. Thus our results suggest that polι would utilize the same spacious region for lesion bypass of both major and minor groove adducts. Therefore, purine adducts with bulk on the minor groove side would use Hoogsteen pairing, while adducts with the bulky lesion on the major groove side would utilize Watson-Crick base pairing as indicated by our MD simulations for dG-AAF. This suggests the possibility of an expanded role for polι in lesion bypass. PMID:19072536

Accommodation of an N-(deoxyguanosin-8-yl)-2-acetylaminofluorene adduct in the active site of human DNA polymerase iota: Hoogsteen or Watson-Crick base pairing?

PubMed

Donny-Clark, Kerry; Shapiro, Robert; Broyde, Suse

2009-01-13

Bypass across DNA lesions by specialized polymerases is essential for maintenance of genomic stability. Human DNA polymerase iota (poliota) is a bypass polymerase of the Y family. Crystal structures of poliota suggest that Hoogsteen base pairing is employed to bypass minor groove DNA lesions, placing them on the spacious major groove side of the enzyme. Primer extension studies have shown that poliota is also capable of error-free nucleotide incorporation opposite the bulky major groove adduct N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF). We present molecular dynamics simulations and free energy calculations suggesting that Watson-Crick base pairing could be employed in poliota for bypass of dG-AAF. In poliota with Hoogsteen-paired dG-AAF the bulky AAF moiety would reside on the cramped minor groove side of the template. The Hoogsteen-capable conformation distorts the active site, disrupting interactions necessary for error-free incorporation of dC opposite the lesion. Watson-Crick pairing places the AAF rings on the spacious major groove side, similar to the position of minor groove adducts observed with Hoogsteen pairing. Watson-Crick-paired structures show a well-ordered active site, with a near reaction-ready ternary complex. Thus our results suggest that poliota would utilize the same spacious region for lesion bypass of both major and minor groove adducts. Therefore, purine adducts with bulk on the minor groove side would use Hoogsteen pairing, while adducts with the bulky lesion on the major groove side would utilize Watson-Crick base pairing as indicated by our MD simulations for dG-AAF. This suggests the possibility of an expanded role for poliota in lesion bypass.

Influence of Hydration on Proton Transfer in the Guanine-Cytosine Radical Cation (G•+-C) Base Pair: A Density Functional Theory Study

PubMed Central

Kumar, Anil; Sevilla, Michael D.

2009-01-01

On one-electron oxidation all molecules including DNA bases become more acidic in nature. For the GC base pair experiments suggest that a facile proton transfer takes place in the G•+-C base pair from N1 of G•+ to N3 of cytosine. This intra-base pair proton transfer reaction has been extensively considered using theoretical methods for the gas phase and it is predicted that the proton transfer is slightly unfavorable in disagreement with experiment. In the present study, we consider the effect of the first hydration layer on the proton transfer reaction in G•+-C by the use of density functional theory (DFT), B3LYP/6-31+G** calculations of the G•+-C base pair in the presence of 6 and 11 water molecules. Under the influence of hydration of 11 waters, a facile proton transfer from N1 of G•+ to N3 of C is predicted. The zero point energy (ZPE) corrected forward and backward energy barriers, for the proton transfer from N1 of G•+ to N3 of C, was found to be 1.4 and 2.6 kcal/mol, respectively. The proton transferred G•-(H+)C + 11H2O was found to be 1.2 kcal/mol more stable than G•+-C + 11H2O in agreement with experiment. The present calculation demonstrates that the inclusion of the first hydration shell around G•+-C base pair has an important effect on the internal proton transfer energetics. PMID:19485319

Extensive dispersal of Roanoke logperch (Percina rex) inferred from genetic marker data

USGS Publications Warehouse

Roberts, James H.; Angermeier, Paul; Hallerman, Eric M.

2016-01-01

The dispersal ecology of most stream fishes is poorly characterised, complicating conservation efforts for these species. We used microsatellite DNA marker data to characterise dispersal patterns and effective population size (Ne) for a population of Roanoke logperchPercina rex, an endangered darter (Percidae). Juveniles and candidate parents were sampled for 2 years at sites throughout the Roanoke River watershed. Dispersal was inferred via genetic assignment tests (ATs), pedigree reconstruction (PR) and estimation of lifetime dispersal distance under a genetic isolation-by-distance model. Estimates of Ne varied from 105 to 1218 individuals, depending on the estimation method. Based on PR, polygamy was frequent in parents of both sexes, with individuals spawning with an average of 2.4 mates. The sample contained 61 half-sibling pairs, but only one parent–offspring pair and no full-sib pairs, which limited our ability to discriminate natal dispersal of juveniles from breeding dispersal of their parents between spawning events. Nonetheless, all methods indicated extensive dispersal. The AT indicated unrestricted dispersal among sites ≤15 km apart, while siblings inferred by the PR were captured an average of 14 km and up to 55 km apart. Model-based estimates of median lifetime dispersal distance (6–24 km, depending on assumptions) bracketed AT and PR estimates, indicating that widely dispersed individuals do, on average, contribute to gene flow. Extensive dispersal of P. rex suggests that darters and other small benthic stream fishes may be unexpectedly mobile. Monitoring and management activities for such populations should encompass entire watersheds to fully capture population dynamics.

All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3' terminus.

PubMed Central

Klobutcher, L A; Swanton, M T; Donini, P; Prescott, D M

1981-01-01

In hypotrichous ciliates, all of the macronuclear DNA is in the form of low molecular weight molecules with an average size of approximately 2200 base pairs. Total macronuclear DNA from four hypotrichs has been shown to have inverted terminal repeats by direct sequence analysis. In Oxytricha nova, Oxytricha sp., and Stylonychia pustulata, this terminal sequence may be written as 5'-C4A4C4A4C4 ... 3'-G4T4G4T4G4T4G4T4G4 ... In Euplotes aediculatus, the sequences is similar but differs in the lengths of the duplex region (28 base pairs) and of the putative 3' extension (14 base pairs). Also in Euplotes, a second common sequence of 5 base pairs (A-A-C-T-T-T-T-G-A-A) occurs internal to the terminal repeat and a 17-base-pair heterogeneous region: 5'-C4A4C4A4C4A4C4(X)17T-T-G-A-A ... 3'-G2T4G4T4G4T4G4T4G4T4G4(X)17A-A-C-T-T ... The length of the terminal repeat sequence for O. nova was confirmed in cloned macronuclear DNA molecules. Images PMID:6265931

Sequence-based evidence for major histocompatibility complex-disassortative mating in a colonial seabird.

PubMed

Juola, Frans A; Dearborn, Donald C

2012-01-07

The major histocompatibility complex (MHC) is a polymorphic gene family associated with immune defence, and it can play a role in mate choice. Under the genetic compatibility hypothesis, females choose mates that differ genetically from their own MHC genotypes, avoiding inbreeding and/or enhancing the immunocompetence of their offspring. We tested this hypothesis of disassortative mating based on MHC genotypes in a population of great frigatebirds (Fregata minor) by sequencing the second exon of MHC class II B. Extensive haploid cloning yielded two to four alleles per individual, suggesting the amplification of two genes. MHC similarity between mates was not significantly different between pairs that did (n = 4) or did not (n = 42) exhibit extra-pair paternity. Comparing all 46 mated pairs to a distribution based on randomized re-pairings, we observed the following (i): no evidence for mate choice based on maximal or intermediate levels of MHC allele sharing (ii), significantly disassortative mating based on similarity of MHC amino acid sequences, and (iii) no evidence for mate choice based on microsatellite alleles, as measured by either allele sharing or similarity in allele size. This suggests that females choose mates that differ genetically from themselves at MHC loci, but not as an inbreeding-avoidance mechanism.

Sample size considerations for paired experimental design with incomplete observations of continuous outcomes.

PubMed

Zhu, Hong; Xu, Xiaohan; Ahn, Chul

2017-01-01

Paired experimental design is widely used in clinical and health behavioral studies, where each study unit contributes a pair of observations. Investigators often encounter incomplete observations of paired outcomes in the data collected. Some study units contribute complete pairs of observations, while the others contribute either pre- or post-intervention observations. Statistical inference for paired experimental design with incomplete observations of continuous outcomes has been extensively studied in literature. However, sample size method for such study design is sparsely available. We derive a closed-form sample size formula based on the generalized estimating equation approach by treating the incomplete observations as missing data in a linear model. The proposed method properly accounts for the impact of mixed structure of observed data: a combination of paired and unpaired outcomes. The sample size formula is flexible to accommodate different missing patterns, magnitude of missingness, and correlation parameter values. We demonstrate that under complete observations, the proposed generalized estimating equation sample size estimate is the same as that based on the paired t-test. In the presence of missing data, the proposed method would lead to a more accurate sample size estimate comparing with the crude adjustment. Simulation studies are conducted to evaluate the finite-sample performance of the generalized estimating equation sample size formula. A real application example is presented for illustration.

A comparative review of methods for comparing means using partially paired data.

PubMed

Guo, Beibei; Yuan, Ying

2017-06-01

In medical experiments with the objective of testing the equality of two means, data are often partially paired by design or because of missing data. The partially paired data represent a combination of paired and unpaired observations. In this article, we review and compare nine methods for analyzing partially paired data, including the two-sample t-test, paired t-test, corrected z-test, weighted t-test, pooled t-test, optimal pooled t-test, multiple imputation method, mixed model approach, and the test based on a modified maximum likelihood estimate. We compare the performance of these methods through extensive simulation studies that cover a wide range of scenarios with different effect sizes, sample sizes, and correlations between the paired variables, as well as true underlying distributions. The simulation results suggest that when the sample size is moderate, the test based on the modified maximum likelihood estimator is generally superior to the other approaches when the data is normally distributed and the optimal pooled t-test performs the best when the data is not normally distributed, with well-controlled type I error rates and high statistical power; when the sample size is small, the optimal pooled t-test is to be recommended when both variables have missing data and the paired t-test is to be recommended when only one variable has missing data.

Pair 2-electron reduced density matrix theory using localized orbitals

NASA Astrophysics Data System (ADS)

Head-Marsden, Kade; Mazziotti, David A.

2017-08-01

Full configuration interaction (FCI) restricted to a pairing space yields size-extensive correlation energies but its cost scales exponentially with molecular size. Restricting the variational two-electron reduced-density-matrix (2-RDM) method to represent the same pairing space yields an accurate lower bound to the pair FCI energy at a mean-field-like computational scaling of O (r3) where r is the number of orbitals. In this paper, we show that localized molecular orbitals can be employed to generate an efficient, approximately size-extensive pair 2-RDM method. The use of localized orbitals eliminates the substantial cost of optimizing iteratively the orbitals defining the pairing space without compromising accuracy. In contrast to the localized orbitals, the use of canonical Hartree-Fock molecular orbitals is shown to be both inaccurate and non-size-extensive. The pair 2-RDM has the flexibility to describe the spectra of one-electron RDM occupation numbers from all quantum states that are invariant to time-reversal symmetry. Applications are made to hydrogen chains and their dissociation, n-acene from naphthalene through octacene, and cadmium telluride 2-, 3-, and 4-unit polymers. For the hydrogen chains, the pair 2-RDM method recovers the majority of the energy obtained from similar calculations that iteratively optimize the orbitals. The localized-orbital pair 2-RDM method with its mean-field-like computational scaling and its ability to describe multi-reference correlation has important applications to a range of strongly correlated phenomena in chemistry and physics.

On-time reliability impacts of advanced traveler information services (ATIS). Volume II, Extensions and applications of the simulated yoked study concept

DOT National Transportation Integrated Search

2002-03-01

In a simulated yoke study, estimates of roadway travel times are archived from web-based Advanced Traveler Information Systems (ATIS) and used to recreate hypothetical, retrospective paired driving trials between travelers with and without ATIS. Prev...

ClaRNA: a classifier of contacts in RNA 3D structures based on a comparative analysis of various classification schemes

PubMed Central

Waleń, Tomasz; Chojnowski, Grzegorz; Gierski, Przemysław; Bujnicki, Janusz M.

2014-01-01

The understanding of folding and function of RNA molecules depends on the identification and classification of interactions between ribonucleotide residues. We developed a new method named ClaRNA for computational classification of contacts in RNA 3D structures. Unique features of the program are the ability to identify imperfect contacts and to process coarse-grained models. Each doublet of spatially close ribonucleotide residues in a query structure is compared to clusters of reference doublets obtained by analysis of a large number of experimentally determined RNA structures, and assigned a score that describes its similarity to one or more known types of contacts, including pairing, stacking, base–phosphate and base–ribose interactions. The accuracy of ClaRNA is 0.997 for canonical base pairs, 0.983 for non-canonical pairs and 0.961 for stacking interactions. The generalized squared correlation coefficient (GC2) for ClaRNA is 0.969 for canonical base pairs, 0.638 for non-canonical pairs and 0.824 for stacking interactions. The classifier can be easily extended to include new types of spatial relationships between pairs or larger assemblies of nucleotide residues. ClaRNA is freely available via a web server that includes an extensive set of tools for processing and visualizing structural information about RNA molecules. PMID:25159614

Nine pairs of megastigmane enantiomers from the leaves of Eucommia ulmoides Oliver.

PubMed

Yan, Jiankun; Shi, Xuliu; Donkor, Paul Owusu; Zhu, Huajie; Gao, Xiumei; Ding, Liqin; Qiu, Feng

2017-10-01

Nine pairs of megastigmane enantiomers (1a/1b-9a/9b), comprising two new compounds (6S,9R)-blumenol C (7b), (6S,9S)-blumenol C (8b), two pairs of enantiomers (+)-(6R)-eucomegastigmane A (1a), (-)-(6S)-eucomegastigmane A (1b), (+)-(3S,4S)-eucomegastigmane B (5a), (-)-(3R,4R)-eucomegastigmane B (5b) isolated by chiral resolution firstly, and twelve known compounds, were isolated from the leaves of Eucommia ulmoides Oliver. Their structures were elucidated based on extensive spectroscopic analysis. Absolute configurations of the megastigmane enantiomers were assigned by comparing experimental ECD and OR with calculated ECD and OR. Docking-based virtual screening of all compounds showed that megastigmane enantiomers have weak intermolecular interactions with the binding site residues of angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT 1 R).

Outcomes of Stay Strong, Stay Healthy in community settings.

PubMed

Ball, Stephen; Gammon, Robin; Kelly, Patricia J; Cheng, An-Lin; Chertoff, Keyna; Kaume, Lydia; Abreu, Eduardo L; Brotto, Marco

2013-12-01

Loss of muscle strength, flexibility, and balance are strong predictors of falls in the elderly. The goal of this research was to investigate the effectiveness of a 10-week, strength-based exercise program delivered by Extension professionals. Matched pair t tests were used to compare differences in five measures of fitness collected from 808 participants (mean age = 65.4 years) at the start and finish of the exercise program. Following programming, participants significantly improved strength, flexibility, and balance. Results indicate that an evidence-based program can be translated into a community Extension program that is able to improve the fitness level of seniors.

Two-Stage Categorization in Brand Extension Evaluation: Electrophysiological Time Course Evidence

PubMed Central

Wang, Xiaoyi

2014-01-01

A brand name can be considered a mental category. Similarity-based categorization theory has been used to explain how consumers judge a new product as a member of a known brand, a process called brand extension evaluation. This study was an event-related potential study conducted in two experiments. The study found a two-stage categorization process reflected by the P2 and N400 components in brand extension evaluation. In experiment 1, a prime–probe paradigm was presented in a pair consisting of a brand name and a product name in three conditions, i.e., in-category extension, similar-category extension, and out-of-category extension. Although the task was unrelated to brand extension evaluation, P2 distinguished out-of-category extensions from similar-category and in-category ones, and N400 distinguished similar-category extensions from in-category ones. In experiment 2, a prime–probe paradigm with a related task was used, in which product names included subcategory and major-category product names. The N400 elicited by subcategory products was more significantly negative than that elicited by major-category products, with no salient difference in P2. We speculated that P2 could reflect the early low-level and similarity-based processing in the first stage, whereas N400 could reflect the late analytic and category-based processing in the second stage. PMID:25438152

Nucleotide sequence and transcriptional start site of the Methylobacterium organophilum XX methanol dehydrogenase structural gene

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

Machlin, S.M.; Hanson, R.S.

The nucleotide sequence of a cloned 2.5-kilobase-pair SmaI fragment containing the methanol dehydrogenase (MDH) structural gene from Methylobacterium organophilum XX was determined. A single open reading frame with a coding capacity of 626 amino acids (molecular weight, 66,000) was identified on one stand, and N-terminal sequencing of purified MDH revealed that 27 of these residues constituted a putative signal peptide. Primer extension mapping of in vivo transcripts indicated that the start of mRNA synthesis was 160 to 170 base pairs upstream of the ATG codon. Northern (RNA) blot analysis further demonstrated that the transcript was 2.1 kilobase pairs in lengthmore » and therefore appeared to encode only MDH.« less

From SHAPE Signatures to 3-D Structures | Center for Cancer Research

Cancer.gov

RNAs undergo extensive folding to form sophisticated based-paired secondary structures that are, in part, indicators of more complex three-dimensional structures.  These 3-D shapes are an integral part of the cellular gene-expression machinery. Deconstructing these structures is no small matter, yet it is critical to understanding their function.

Blind prediction of noncanonical RNA structure at atomic accuracy.

PubMed

Watkins, Andrew M; Geniesse, Caleb; Kladwang, Wipapat; Zakrevsky, Paul; Jaeger, Luc; Das, Rhiju

2018-05-01

Prediction of RNA structure from nucleotide sequence remains an unsolved grand challenge of biochemistry and requires distinct concepts from protein structure prediction. Despite extensive algorithmic development in recent years, modeling of noncanonical base pairs of new RNA structural motifs has not been achieved in blind challenges. We report a stepwise Monte Carlo (SWM) method with a unique add-and-delete move set that enables predictions of noncanonical base pairs of complex RNA structures. A benchmark of 82 diverse motifs establishes the method's general ability to recover noncanonical pairs ab initio, including multistrand motifs that have been refractory to prior approaches. In a blind challenge, SWM models predicted nucleotide-resolution chemical mapping and compensatory mutagenesis experiments for three in vitro selected tetraloop/receptors with previously unsolved structures (C7.2, C7.10, and R1). As a final test, SWM blindly and correctly predicted all noncanonical pairs of a Zika virus double pseudoknot during a recent community-wide RNA-Puzzle. Stepwise structure formation, as encoded in the SWM method, enables modeling of noncanonical RNA structure in a variety of previously intractable problems.

The combination of direct and paired link graphs can boost repetitive genome assembly

PubMed Central

Shi, Wenyu; Ji, Peifeng

2017-01-01

Abstract Currently, most paired link based scaffolding algorithms intrinsically mask the sequences between two linked contigs and bypass their direct link information embedded in the original de Bruijn assembly graph. Such disadvantage substantially complicates the scaffolding process and leads to the inability of resolving repetitive contig assembly. Here we present a novel algorithm, inGAP-sf, for effectively generating high-quality and continuous scaffolds. inGAP-sf achieves this by using a new strategy based on the combination of direct link and paired link graphs, in which direct link is used to increase graph connectivity and to decrease graph complexity and paired link is employed to supervise the traversing process on the direct link graph. Such advantage greatly facilitates the assembly of short-repeat enriched regions. Moreover, a new comprehensive decision model is developed to eliminate the noise routes accompanying with the introduced direct link. Through extensive evaluations on both simulated and real datasets, we demonstrated that inGAP-sf outperforms most of the genome scaffolding algorithms by generating more accurate and continuous assembly, especially for short repetitive regions. PMID:27924003

A more powerful exact test of noninferiority from binary matched-pairs data.

PubMed

Lloyd, Chris J; Moldovan, Max V

2008-08-15

Assessing the therapeutic noninferiority of one medical treatment compared with another is often based on the difference in response rates from a matched binary pairs design. This paper develops a new exact unconditional test for noninferiority that is more powerful than available alternatives. There are two new elements presented in this paper. First, we introduce the likelihood ratio statistic as an alternative to the previously proposed score statistic of Nam (Biometrics 1997; 53:1422-1430). Second, we eliminate the nuisance parameter by estimation followed by maximization as an alternative to the partial maximization of Berger and Boos (Am. Stat. Assoc. 1994; 89:1012-1016) or traditional full maximization. Based on an extensive numerical study, we recommend tests based on the score statistic, the nuisance parameter being controlled by estimation followed by maximization. 2008 John Wiley & Sons, Ltd

Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension

PubMed Central

Tetley, Robert J; Blanchard, Guy B; Fletcher, Alexander G; Adams, Richard J; Sanson, Bénédicte

2016-01-01

Convergence and extension movements elongate tissues during development. Drosophila germ-band extension (GBE) is one example, which requires active cell rearrangements driven by Myosin II planar polarisation. Here, we develop novel computational methods to analyse the spatiotemporal dynamics of Myosin II during GBE, at the scale of the tissue. We show that initial Myosin II bipolar cell polarization gives way to unipolar enrichment at parasegmental boundaries and two further boundaries within each parasegment, concomitant with a doubling of cell number as the tissue elongates. These boundaries are the primary sites of cell intercalation, behaving as mechanical barriers and providing a mechanism for how cells remain ordered during GBE. Enrichment at parasegment boundaries during GBE is independent of Wingless signaling, suggesting pair-rule gene control. Our results are consistent with recent work showing that a combinatorial code of Toll-like receptors downstream of pair-rule genes contributes to Myosin II polarization via local cell-cell interactions. We propose an updated cell-cell interaction model for Myosin II polarization that we tested in a vertex-based simulation. DOI: http://dx.doi.org/10.7554/eLife.12094.001 PMID:27183005

Loblolly pine karyotype using FISH and DAPI positive banding

Treesearch

M. Nurul Islam-Faridi; C. Dana Nelson; Thomas L. Kubisiak; M.V. Gullirmo; V.H. McNamara; S. Ramakrishnan; H.J. Price; D.M. Stelly

2003-01-01

The pines (Pinus, 2n = 2x = 24) include many commercially important timber species. Pinus spp. have 12 pairs of chromosomes, with 10 or 11 pairs of long metacentric chromosomes and one pair of short sub-metacentric chromosomes (Sax and Sax 1933). The pines have been studied extensively with...

Characterization of the IMF By-dependent field-aligned currents in the cleft region based on DE 2 observations

NASA Technical Reports Server (NTRS)

Taguchi, S.; Sugiura, M.; Winningham, J. D.; Slavin, J. A.

1993-01-01

The magnetic field and plasma data from 47 passes of DE-2 are used to study the IMF By-dependent distribution of field-aligned currents in the cleft region. It is proposed that the low-latitude cleft current (LCC) region is not an extension of the region 1 or region 2 current system and that a pair of LCCs and high-latitude cleft currents (HCCs) constitutes the cleft field-aligned current regime. The proposed pair of cleft field-aligned currents is explained with a qualitative model in which this pair of currents is generated on open field lines that have just been reconnected on the dayside magnetopause. The electric fields are transmitted along the field lines to the ionosphere, creating a poleward electric field and a pair of field-aligned currents when By is positive; the pair of field-aligned currents consists of a downward current at lower latitudes and an upward current at higher latitudes. In the By negative case, the model explains the reversal of the field-aligned current direction in the LCC and HCC regions.

Characterization of a highly polymorphic region 5′ to JH in the human immunoglobulin heavy chain

PubMed Central

Silva, Alcino J.; Johnson, John P.; White, Raymond L.

1987-01-01

A cloned DNA segment 1.25 kilobases (kb) upstream from the joining segments of the human heavy chain immunoglobulin gene revealed extensive polymorphic variation at this locus, and the polymorphic pattern was stably transmitted to the next generation. Genomic restriction analysis showed that the polymorphism was caused by insertions/deletions within an MspI/BamHI fragment. Sequencing of one allele, 848 base pairs (bp) long, revealed eleven 50-base-pair tandem repeats. A second allele, 648 bp long, was cloned from a human genomic cosmid library, sequenced, and found to contain four fewer repeats than the first allele. A survey of 186 chromosomes from unrelated individuals of primarily northern European descent revealed at least six alleles. Images PMID:2884636

Capturing RNA Folding Free Energy with Coarse-Grained Molecular Dynamics Simulations

PubMed Central

Bell, David R.; Cheng, Sara Y.; Salazar, Heber; Ren, Pengyu

2017-01-01

We introduce a coarse-grained RNA model for molecular dynamics simulations, RACER (RnA CoarsE-gRained). RACER achieves accurate native structure prediction for a number of RNAs (average RMSD of 2.93 Å) and the sequence-specific variation of free energy is in excellent agreement with experimentally measured stabilities (R2 = 0.93). Using RACER, we identified hydrogen-bonding (or base pairing), base stacking, and electrostatic interactions as essential driving forces for RNA folding. Also, we found that separating pairing vs. stacking interactions allowed RACER to distinguish folded vs. unfolded states. In RACER, base pairing and stacking interactions each provide an approximate stability of 3–4 kcal/mol for an A-form helix. RACER was developed based on PDB structural statistics and experimental thermodynamic data. In contrast with previous work, RACER implements a novel effective vdW potential energy function, which led us to re-parameterize hydrogen bond and electrostatic potential energy functions. Further, RACER is validated and optimized using a simulated annealing protocol to generate potential energy vs. RMSD landscapes. Finally, RACER is tested using extensive equilibrium pulling simulations (0.86 ms total) on eleven RNA sequences (hairpins and duplexes). PMID:28393861

Paired Comparisons.

DTIC Science & Technology

1982-05-01

including multidimensional scaling. Applications have arisen in many areas, but most notably in food technolog, marketing research, and sports ... competition .- An extensive bibliography on paired comparisons by Davidson and Farquhar (1976) contains some 400 references. - Paired comparisons have been...consideration of chess competition . Ford (1957) pro- posed the model independently. Both Zermelo and Ford concentrated on solution of normal equations for

Heterospecific pairing and hybridization between Nasutitermes corniger and N. ephratae

NASA Astrophysics Data System (ADS)

Hartke, Tamara R.; Rosengaus, Rebeca B.

2011-09-01

The sympatric neotropical termites Nasutitermes corniger and Nasutitermes ephratae are clearly distinguishable based on morphology, nest architecture, defensive secretion composition, and molecular markers. However, given the extensive ecological, geographical, and behavioral overlap of these closely related species, the potential for interbreeding may exist. To explore this possibility, heterospecific pairs were formed experimentally to examine courtship and colony-establishment behaviors, and reproductive potential. Courtship and nest construction behavior occurred in heterospecific pairs in a similar manner to that of conspecific pairs. Survival of pairs depended upon the species of the female partner. N. ephratae females paired with N. corniger males produced as many offspring as conspecific pairs. N. corniger females mated to N. ephratae males, however, produced significantly fewer offspring at 60 days post-establishment than the reciprocal cross or conspecific N. ephratae or N. corniger pairs. This was also the only pairing in which any aggression was observed. Heterospecific pairs and groups formed in mate choice mesocosms, suggesting that species recognition between these two termites is not an important aspect of mate choice. Overall, species mismatch tolerance and hybrid offspring viability are high. The present data, together with previous evidence from defensive secretions and isozyme analysis, suggest that hybridization may periodically occur in nature, and that reproductive barriers between these two species may be incomplete. Hybridization could provide a rare but important source of genetic diversity and may ensure mating opportunities for the more abundant sex of alates in each species.

Video-based data acquisition system for use in eye blink classical conditioning procedures in sheep.

PubMed

Nation, Kelsey; Birge, Adam; Lunde, Emily; Cudd, Timothy; Goodlett, Charles; Washburn, Shannon

2017-10-01

Pavlovian eye blink conditioning (EBC) has been extensively studied in humans and laboratory animals, providing one of the best-understood models of learning in neuroscience. EBC has been especially useful in translational studies of cerebellar and hippocampal function. We recently reported a novel extension of EBC procedures for use in sheep, and now describe new advances in a digital video-based system. The system delivers paired presentations of conditioned stimuli (CSs; a tone) and unconditioned stimuli (USs; an air puff to the eye), or CS-alone "unpaired" trials. This system tracks the linear distance between the eyelids to identify blinks occurring as either unconditioned (URs) or conditioned (CRs) responses, to a resolution of 5 ms. A separate software application (Eye Blink Reviewer) is used to review and autoscore the trial CRs and URs, on the basis of a set of predetermined rules, permitting an operator to confirm (or rescore, if needed) the autoscore results, thereby providing quality control for accuracy of scoring. Learning curves may then be quantified in terms of the frequencies of CRs over sessions, both on trials with paired CS-US presentations and on CS-alone trials. The latency to CR onset, latency to CR peak, and occurrence of URs are also obtained. As we demonstrated in two example cases, this video-based system provides efficient automated means to conduct EBC in sheep and can facilitate fully powered studies with multigroup designs that involve paired and unpaired training. This can help extend new studies in sheep, a species well suited for translational studies of neurodevelopmental disorders resulting from gestational exposure to drugs, toxins, or intrauterine distress.

Model for an RNA tertiary interaction from the structure of an intermolecular complex between a GAAA tetraloop and an RNA helix.

PubMed

Pley, H W; Flaherty, K M; McKay, D B

1994-11-03

In large structured RNAs, RNA hairpins in which the strands of the duplex stem are connected by a tetraloop of the consensus sequence 5'-GNRA (where N is any nucleotide, and R is either G or A) are unusually frequent. In group I introns there is a covariation in sequence between nucleotides in the third and fourth positions of the loop with specific distant base pairs in putative RNA duplex stems: GNAA loops correlate with successive 5'-C-C.G-C base pairs in stems, whereas GNGA loops correlate with 5'-C-U.G-A. This has led to the suggestion that GNRA tetraloops may be involved in specific long-range tertiary interactions, with each A in position 3 or 4 of the loop interacting with a C-G base pair in the duplex, and G in position 3 interacting with a U-A base pair. This idea is supported experimentally for the GAAA loop of the P5b extension of the group I intron of Tetrahymena thermophila and the L9 GUGA terminal loop of the td intron of bacteriophage T4 (ref. 4). NMR has revealed the overall structure of the tetraloop for 12-nucleotide hairpins with GCAA and GAAA loops and models have been proposed for the interaction of GNRA tetraloops with base pairs in the minor groove of A-form RNA. Here we describe the crystal structure of an intermolecular complex between a GAAA tetraloop and an RNA helix. The interactions we observe correlate with the specificity of GNRA tetraloops inferred from phylogenetic studies, suggesting that this complex is a legitimate model for intramolecular tertiary interactions mediated by GNRA tetraloops in large structured RNAs.

A bivariate contaminated binormal model for robust fitting of proper ROC curves to a pair of correlated, possibly degenerate, ROC datasets.

PubMed

Zhai, Xuetong; Chakraborty, Dev P

2017-06-01

The objective was to design and implement a bivariate extension to the contaminated binormal model (CBM) to fit paired receiver operating characteristic (ROC) datasets-possibly degenerate-with proper ROC curves. Paired datasets yield two correlated ratings per case. Degenerate datasets have no interior operating points and proper ROC curves do not inappropriately cross the chance diagonal. The existing method, developed more than three decades ago utilizes a bivariate extension to the binormal model, implemented in CORROC2 software, which yields improper ROC curves and cannot fit degenerate datasets. CBM can fit proper ROC curves to unpaired (i.e., yielding one rating per case) and degenerate datasets, and there is a clear scientific need to extend it to handle paired datasets. In CBM, nondiseased cases are modeled by a probability density function (pdf) consisting of a unit variance peak centered at zero. Diseased cases are modeled with a mixture distribution whose pdf consists of two unit variance peaks, one centered at positive μ with integrated probability α, the mixing fraction parameter, corresponding to the fraction of diseased cases where the disease was visible to the radiologist, and one centered at zero, with integrated probability (1-α), corresponding to disease that was not visible. It is shown that: (a) for nondiseased cases the bivariate extension is a unit variances bivariate normal distribution centered at (0,0) with a specified correlation ρ 1 ; (b) for diseased cases the bivariate extension is a mixture distribution with four peaks, corresponding to disease not visible in either condition, disease visible in only one condition, contributing two peaks, and disease visible in both conditions. An expression for the likelihood function is derived. A maximum likelihood estimation (MLE) algorithm, CORCBM, was implemented in the R programming language that yields parameter estimates and the covariance matrix of the parameters, and other statistics. A limited simulation validation of the method was performed. CORCBM and CORROC2 were applied to two datasets containing nine readers each contributing paired interpretations. CORCBM successfully fitted the data for all readers, whereas CORROC2 failed to fit a degenerate dataset. All fits were visually reasonable. All CORCBM fits were proper, whereas all CORROC2 fits were improper. CORCBM and CORROC2 were in agreement (a) in declaring only one of the nine readers as having significantly different performances in the two modalities; (b) in estimating higher correlations for diseased cases than for nondiseased ones; and (c) in finding that the intermodality correlation estimates for nondiseased cases were consistent between the two methods. All CORCBM fits yielded higher area under curve (AUC) than the CORROC2 fits, consistent with the fact that a proper ROC model like CORCBM is based on a likelihood-ratio-equivalent decision variable, and consequently yields higher performance than the binormal model-based CORROC2. The method gave satisfactory fits to four simulated datasets. CORCBM is a robust method for fitting paired ROC datasets, always yielding proper ROC curves, and able to fit degenerate datasets. © 2017 American Association of Physicists in Medicine.

The Use and Efficacy of Capacity-Building Assistance for Low-Performing Districts: The Case of California's District Assistance and Intervention Teams

ERIC Educational Resources Information Center

Strunk, Katharine O.; McEachin, Andrew; Westover, Theresa N.

2014-01-01

The theory of action upon which high-stakes accountability policies are based calls for systemic reforms in educational systems that will emerge by pairing incentives for improvement with extensive and targeted technical assistance (TA) to build the capacity of low-performing schools and districts. To this end, a little discussed and often…

AUCTSP: an improved biomarker gene pair class predictor.

PubMed

Kagaris, Dimitri; Khamesipour, Alireza; Yiannoutsos, Constantin T

2018-06-26

The Top Scoring Pair (TSP) classifier, based on the concept of relative ranking reversals in the expressions of pairs of genes, has been proposed as a simple, accurate, and easily interpretable decision rule for classification and class prediction of gene expression profiles. The idea that differences in gene expression ranking are associated with presence or absence of disease is compelling and has strong biological plausibility. Nevertheless, the TSP formulation ignores significant available information which can improve classification accuracy and is vulnerable to selecting genes which do not have differential expression in the two conditions ("pivot" genes). We introduce the AUCTSP classifier as an alternative rank-based estimator of the magnitude of the ranking reversals involved in the original TSP. The proposed estimator is based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) and as such, takes into account the separation of the entire distribution of gene expression levels in gene pairs under the conditions considered, as opposed to comparing gene rankings within individual subjects as in the original TSP formulation. Through extensive simulations and case studies involving classification in ovarian, leukemia, colon, breast and prostate cancers and diffuse large b-cell lymphoma, we show the superiority of the proposed approach in terms of improving classification accuracy, avoiding overfitting and being less prone to selecting non-informative (pivot) genes. The proposed AUCTSP is a simple yet reliable and robust rank-based classifier for gene expression classification. While the AUCTSP works by the same principle as TSP, its ability to determine the top scoring gene pair based on the relative rankings of two marker genes across all subjects as opposed to each individual subject results in significant performance gains in classification accuracy. In addition, the proposed method tends to avoid selection of non-informative (pivot) genes as members of the top-scoring pair.

Scalar entrainment in the mixing layer

NASA Technical Reports Server (NTRS)

Sandham, N. D.; Mungal, M. G.; Broadwell, J. E.; Reynolds, W. C.

1988-01-01

New definitions of entrainment and mixing based on the passive scalar field in the plane mixing layer are proposed. The definitions distinguish clearly between three fluid states: (1) unmixed fluid, (2) fluid engulfed in the mixing layer, trapped between two scalar contours, and (3) mixed fluid. The difference betwen (2) and (3) is the amount of fluid which has been engulfed during the pairing process, but has not yet mixed. Trends are identified from direct numerical simulations and extensions to high Reynolds number mixing layers are made in terms of the Broadwell-Breidenthal mixing model. In the limit of high Peclet number (Pe = ReSc) it is speculated that engulfed fluid rises in steps associated with pairings, introducing unmixed fluid into the large scale structures, where it is eventually mixed at the Kolmogorov scale. From this viewpoint, pairing is a prerequisite for mixing in the turbulent plane mixing layer.

The cyc1-11 mutation in yeast reverts by recombination with a nonallelic gene: composite genes determining the iso-cytochromes c.

PubMed Central

Ernst, J F; Stewart, J W; Sherman, F

1981-01-01

DNA sequence analysis of a cloned fragment directly established that the cyc1-11 mutation of iso-1-cytochrome c in the yeast Saccharomyces cerevisiae is a two-base-pair substitution that changes the CCA proline codon at amino acid position 76 to a UAA nonsense codon. Analysis of 11 revertant proteins and one cloned revertant gene showed that reversion of the cyc1-11 mutation can occur in three ways: a single base-pair substitution, which produces a serine replacement at position 76; recombination with the nonallelic CYC7 gene of iso-2-cytochrome c, which causes replacement of a segment in the cyc1-11 gene by the corresponding segment of the CYC7 gene; and either a two-base-pair substitution or recombination with the CYC7 gene, which causes the formation of the normal iso-1-cytochrome c sequence. These results demonstrate the occurrence of low frequencies of recombination between nonallelic genes having extensive but not complete homology. The formation of composite genes that share sequences from nonallelic genes may be an evolutionary mechanism for producing protein diversities and for maintaining identical sequences at different loci. Images PMID:6273865

Statistical exchange-coupling errors and the practicality of scalable silicon donor qubits

NASA Astrophysics Data System (ADS)

Song, Yang; Das Sarma, S.

2016-12-01

Recent experimental efforts have led to considerable interest in donor-based localized electron spins in Si as viable qubits for a scalable silicon quantum computer. With the use of isotopically purified 28Si and the realization of extremely long spin coherence time in single-donor electrons, the recent experimental focus is on two-coupled donors with the eventual goal of a scaled-up quantum circuit. Motivated by this development, we simulate the statistical distribution of the exchange coupling J between a pair of donors under realistic donor placement straggles, and quantify the errors relative to the intended J value. With J values in a broad range of donor-pair separation ( 5 <|R |<60 nm), we work out various cases systematically, for a target donor separation R0 along the [001], [110] and [111] Si crystallographic directions, with |R0|=10 ,20 or 30 nm and standard deviation σR=1 ,2 ,5 or 10 nm. Our extensive theoretical results demonstrate the great challenge for a prescribed J gate even with just a donor pair, a first step for any scalable Si-donor-based quantum computer.

A contact photo-cross-linking investigation of the active site of the 8-17 deoxyribozyme.

PubMed

Liu, Yong; Sen, Dipankar

2008-09-12

The small RNA-cleaving 8-17 deoxyribozyme (DNAzyme) has been the subject of extensive mechanistic and structural investigation, including a number of recent single-molecule studies of its global folding. Little detailed insight exists, however, into this DNAzyme's active site; for instance, the identity of specific nucleotides that are proximal to or in contact with the scissile site in the substrate. Here, we report a systematic replacement of a number of bases within the magnesium-folded DNAzyme-substrate complex with thio- and halogen-substituted base analogues, which were then photochemically activated to generate contact cross-links within the complex. Mapping of the cross-links revealed a striking pattern of DNAzyme-substrate cross-links but an absence of significant intra-DNAzyme cross-links. Notably, the two nucleotides directly flanking the scissile phosphodiester cross-linked strongly with functionally important elements within the DNAzyme, the thymine of a G.T wobble base pair, a WCGR bulge loop, and a terminal AGC loop. Mutation of the wobble base pair to a G-C pair led to a significant folding instability of the DNAzyme-substrate complex. The cross-linking patterns obtained were used to generate a model for the DNAzyme's active site that had the substrate's scissile phosphodiester sandwiched between the DNAzyme's wobble thymine and its AGC and WCGR loops.

Thermodynamic characterization of a triple-helical three-way junction containing a Hoogsteen branch point.

PubMed

Hüsler, P L; Klump, H H

1995-09-10

We have designed a Hoogsteen (HG) triple-helical three-way junction (ternary complex) constructed from three 33-mer oligonucleotides based on the same subset of sequences used for the Watson-Crick (WC) triple-helical three-way junction, characterized previously (P. L. Hüsler and H. H. Klump (1994) Arch. Biochem. Biophys., 313, 29-38). The junction differs primarily in the assembly of the branch point and the ends of the arms. The three oligonucleotides can each fold into a WC hairpin, linked by a four-member cytosine loop, each containing a homo-pyrimidine 10-mer single-strand extension. On lowering the pH (between 6 and 4), the extensions mutually associate to one of the other hairpins via Hoogsteen (HG) hydrogen bonding. Collectively, this process results in the formation of the branch point and the triple-helical arms. The HG triple-helical three-way junction is characterized by gel electrophoresis, circular dichroism, uv melting, and differential scanning calorimetry. The junction undergoes thermal unfolding in two distinct temperature regions. In the temperature range 15 to 50 degrees C loss of HG base pairing results in the dissociation of the three-way junction. Between 55 and 95 degrees C the resulting hairpins undergo further successive unfolding. The overall calorimetric unfolding enthalpy and entropy changes associated with the loss of HG base pairing are approximately equal to the sum of the enthalpy and entropy changes associated with the dissociation of the HG base pairing in the isolated arms (170.6 kcal.mol-1; 540.1 cal.mol-1.K-1). It is apparent from these results that in the proximity of the branch point the structure is not perturb or strain. This result is contrary to the results obtained for the WC triple-helical three-way and for three-way junctions constructed from canonical double-helical DNA. Complete folding of the junction requires either high Na+ (600 mM) ion concentrations or 40-60 mM Mg2+.

SSR_pipeline--computer software for the identification of microsatellite sequences from paired-end Illumina high-throughput DNA sequence data

USGS Publications Warehouse

Miller, Mark P.; Knaus, Brian J.; Mullins, Thomas D.; Haig, Susan M.

2013-01-01

SSR_pipeline is a flexible set of programs designed to efficiently identify simple sequence repeats (SSRs; for example, microsatellites) from paired-end high-throughput Illumina DNA sequencing data. The program suite contains three analysis modules along with a fourth control module that can be used to automate analyses of large volumes of data. The modules are used to (1) identify the subset of paired-end sequences that pass quality standards, (2) align paired-end reads into a single composite DNA sequence, and (3) identify sequences that possess microsatellites conforming to user specified parameters. Each of the three separate analysis modules also can be used independently to provide greater flexibility or to work with FASTQ or FASTA files generated from other sequencing platforms (Roche 454, Ion Torrent, etc). All modules are implemented in the Python programming language and can therefore be used from nearly any computer operating system (Linux, Macintosh, Windows). The program suite relies on a compiled Python extension module to perform paired-end alignments. Instructions for compiling the extension from source code are provided in the documentation. Users who do not have Python installed on their computers or who do not have the ability to compile software also may choose to download packaged executable files. These files include all Python scripts, a copy of the compiled extension module, and a minimal installation of Python in a single binary executable. See program documentation for more information.

The pair-production channel in atomic processes

NASA Astrophysics Data System (ADS)

Belkacem, Ali; Sørensen, Allan H.

2006-06-01

Assisted by the creation of electron-positron pairs, new channels for ionization, excitation, and charge transfer open in atomic collisions when the energy is raised to relativistic values. At extreme energies these pair-production channels usually dominate the "traditional" contributions to cross sections that involve only "positive-energy" electrons. An extensive body of theoretical and experimental work has been performed over the last two decades to investigate charge-changing processes catalyzed by pair production in relativistic heavy ion collisions. We review some of these studies.

Friedrichs systems in a Hilbert space framework: Solvability and multiplicity

NASA Astrophysics Data System (ADS)

Antonić, N.; Erceg, M.; Michelangeli, A.

2017-12-01

The Friedrichs (1958) theory of positive symmetric systems of first order partial differential equations encompasses many standard equations of mathematical physics, irrespective of their type. This theory was recast in an abstract Hilbert space setting by Ern, Guermond and Caplain (2007), and by Antonić and Burazin (2010). In this work we make a further step, presenting a purely operator-theoretic description of abstract Friedrichs systems, and proving that any pair of abstract Friedrichs operators admits bijective extensions with a signed boundary map. Moreover, we provide sufficient and necessary conditions for existence of infinitely many such pairs of spaces, and by the universal operator extension theory (Grubb, 1968) we get a complete identification of all such pairs, which we illustrate on two concrete one-dimensional examples.

Similarity from multi-dimensional scaling: solving the accuracy and diversity dilemma in information filtering.

PubMed

Zeng, Wei; Zeng, An; Liu, Hao; Shang, Ming-Sheng; Zhang, Yi-Cheng

2014-01-01

Recommender systems are designed to assist individual users to navigate through the rapidly growing amount of information. One of the most successful recommendation techniques is the collaborative filtering, which has been extensively investigated and has already found wide applications in e-commerce. One of challenges in this algorithm is how to accurately quantify the similarities of user pairs and item pairs. In this paper, we employ the multidimensional scaling (MDS) method to measure the similarities between nodes in user-item bipartite networks. The MDS method can extract the essential similarity information from the networks by smoothing out noise, which provides a graphical display of the structure of the networks. With the similarity measured from MDS, we find that the item-based collaborative filtering algorithm can outperform the diffusion-based recommendation algorithms. Moreover, we show that this method tends to recommend unpopular items and increase the global diversification of the networks in long term.

Robustness and Reliability of Synergy-Based Myocontrol of a Multiple Degree of Freedom Robotic Arm.

PubMed

Lunardini, Francesca; Casellato, Claudia; d'Avella, Andrea; Sanger, Terence D; Pedrocchi, Alessandra

2016-09-01

In this study, we test the feasibility of the synergy- based approach for application in the realistic and clinically oriented framework of multi-degree of freedom (DOF) robotic control. We developed and tested online ten able-bodied subjects in a semi-supervised method to achieve simultaneous, continuous control of two DOFs of a robotic arm, using muscle synergies extracted from upper limb muscles while performing flexion-extension movements of the elbow and shoulder joints in the horizontal plane. To validate the efficacy of the synergy-based approach in extracting reliable control signals, compared to the simple muscle-pair method typically used in commercial applications, we evaluated the repeatability of the algorithm over days, the effect of the arm dynamics on the control performance, and the robustness of the control scheme to the presence of co-contraction between pairs of antagonist muscles. Results showed that, without the need for a daily calibration, all subjects were able to intuitively and easily control the synergy-based myoelectric interface in different scenarios, using both dynamic and isometric muscle contractions. The proposed control scheme was shown to be robust to co-contraction between antagonist muscles, providing better performance compared to the traditional muscle-pair approach. The current study is a first step toward user-friendly application of synergy-based myocontrol of assistive robotic devices.

Extending the Fellegi-Sunter probabilistic record linkage method for approximate field comparators.

PubMed

DuVall, Scott L; Kerber, Richard A; Thomas, Alun

2010-02-01

Probabilistic record linkage is a method commonly used to determine whether demographic records refer to the same person. The Fellegi-Sunter method is a probabilistic approach that uses field weights based on log likelihood ratios to determine record similarity. This paper introduces an extension of the Fellegi-Sunter method that incorporates approximate field comparators in the calculation of field weights. The data warehouse of a large academic medical center was used as a case study. The approximate comparator extension was compared with the Fellegi-Sunter method in its ability to find duplicate records previously identified in the data warehouse using different demographic fields and matching cutoffs. The approximate comparator extension misclassified 25% fewer pairs and had a larger Welch's T statistic than the Fellegi-Sunter method for all field sets and matching cutoffs. The accuracy gain provided by the approximate comparator extension grew as less information was provided and as the matching cutoff increased. Given the ubiquity of linkage in both clinical and research settings, the incremental improvement of the extension has the potential to make a considerable impact.

Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

PubMed Central

Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P.; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

2015-01-01

Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of “lethal mutagenesis” that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

PubMed

Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

2015-01-02

Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

RNA Structural Analysis by Evolving SHAPE Chemistry

PubMed Central

Spitale, Robert C.; Flynn, Ryan A.; Torre, Eduardo A.; Kool, Eric T.; Chang, Howard Y.

2017-01-01

RNA is central to the flow of biological information. From transcription to splicing, RNA localization, translation, and decay, RNA is intimately involved in regulating every step of the gene expression program, and is thus essential for health and understanding disease. RNA has the unique ability to base-pair with itself and other nucleic acids to form complex structures. Hence the information content in RNA is not simply its linear sequence of bases, but is also encoded in complex folding of RNA molecules. A general chemical functionality that all RNAs have is a 2’-hydroxyl group in the ribose ring, and the reactivity of the 2'-hydroxyl in RNA is gated by local nucleotide flexibility. In other words, the 2'-hydroxyl is reactive at single-stranded and conformationally flexible positions but is unreactive at nucleotides constrained by base pairing. Recent efforts have been focused on developing reagents that modify RNA as a function of RNA 2’ hydroxyl group flexibility. Such RNA structure probing techniques can be read out by primer extension in experiments termed RNA SHAPE (Selective 2’ Hydroxyl Acylation and Primer Extension). Herein we describe the efforts devoted to the design and utilization of SHAPE probes for characterizing RNA structure. We also describe current technological advances that are being used to utilize SHAPE chemistry with deep sequencing to probe many RNAs in parallel. The merger of chemistry with genomics is sure to open the door to genome-wide exploration of RNA structure and function. PMID:25132067

Mechanisms of Insertion of dCTP and dTTP Opposite the DNA Lesion O6-Methyl-2'-deoxyguanosine by Human DNA Polymerase η.

PubMed

Patra, Amitraj; Zhang, Qianqian; Guengerich, F Peter; Egli, Martin

2016-11-11

O 6 -Methyl-2'-deoxyguanosine (O 6 -MeG) is a ubiquitous DNA lesion, formed not only by xenobiotic carcinogens but also by the endogenous methylating agent S-adenosylmethionine. It can introduce mutations during DNA replication, with different DNA polymerases displaying different ratios of correct or incorrect incorporation opposite this nucleoside. Of the "translesion" Y-family human DNA polymerases (hpols), hpol η is most efficient in incorporating equal numbers of correct and incorrect C and T bases. However, the mechanistic basis for this specific yet indiscriminate activity is not known. To explore this question, we report biochemical and structural analysis of the catalytic core of hpol η. Activity assays showed the truncated form displayed similar misincorporation properties as the full-length enzyme, incorporating C and T equally and extending from both. X-ray crystal structures of both dC and dT paired with O 6 -MeG were solved in both insertion and extension modes. The structures revealed a Watson-Crick-like pairing between O 6 -MeG and 2"-deoxythymidine-5"-[(α, β)-imido]triphosphate (approximating dT) at both the insertion and extension stages with formation of two H-bonds. Conversely, both the structures with O 6 - MeG opposite dCTP and dC display sheared configuration of base pairs but to different degrees, with formation of two bifurcated H-bonds and two single H-bonds in the structures trapped in the insertion and extension states, respectively. The structural data are consistent with the observed tendency of hpol η to insert both dC and dT opposite the O 6 -MeG lesion with similar efficiencies. Comparison of the hpol η active site configurations with either O 6 -MeG:dC or O 6 -MeG:dT bound compared with the corresponding situations in structures of complexes of Sulfolobus solfataricus Dpo4, a bypass pol that favors C relative to T by a factor of ∼4, helps rationalize the more error-prone synthesis opposite the lesion by hpol η. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanisms of Insertion of dCTP and dTTP Opposite the DNA Lesion O6-Methyl-2′-deoxyguanosine by Human DNA Polymerase η*

PubMed Central

Patra, Amitraj; Zhang, Qianqian; Guengerich, F. Peter; Egli, Martin

2016-01-01

O6-Methyl-2′-deoxyguanosine (O6-MeG) is a ubiquitous DNA lesion, formed not only by xenobiotic carcinogens but also by the endogenous methylating agent S-adenosylmethionine. It can introduce mutations during DNA replication, with different DNA polymerases displaying different ratios of correct or incorrect incorporation opposite this nucleoside. Of the “translesion” Y-family human DNA polymerases (hpols), hpol η is most efficient in incorporating equal numbers of correct and incorrect C and T bases. However, the mechanistic basis for this specific yet indiscriminate activity is not known. To explore this question, we report biochemical and structural analysis of the catalytic core of hpol η. Activity assays showed the truncated form displayed similar misincorporation properties as the full-length enzyme, incorporating C and T equally and extending from both. X-ray crystal structures of both dC and dT paired with O6-MeG were solved in both insertion and extension modes. The structures revealed a Watson-Crick-like pairing between O6-MeG and 2"-deoxythymidine-5"-[(α, β)-imido]triphosphate (approximating dT) at both the insertion and extension stages with formation of two H-bonds. Conversely, both the structures with O6- MeG opposite dCTP and dC display sheared configuration of base pairs but to different degrees, with formation of two bifurcated H-bonds and two single H-bonds in the structures trapped in the insertion and extension states, respectively. The structural data are consistent with the observed tendency of hpol η to insert both dC and dT opposite the O6-MeG lesion with similar efficiencies. Comparison of the hpol η active site configurations with either O6-MeG:dC or O6-MeG:dT bound compared with the corresponding situations in structures of complexes of Sulfolobus solfataricus Dpo4, a bypass pol that favors C relative to T by a factor of ∼4, helps rationalize the more error-prone synthesis opposite the lesion by hpol η. PMID:27694439

Multiple re-encounter approach to radical pair reactions and the role of nonlinear master equations.

PubMed

Clausen, Jens; Guerreschi, Gian Giacomo; Tiersch, Markus; Briegel, Hans J

2014-08-07

We formulate a multiple-encounter model of the radical pair mechanism that is based on a random coupling of the radical pair to a minimal model environment. These occasional pulse-like couplings correspond to the radical encounters and give rise to both dephasing and recombination. While this is in agreement with the original model of Haberkorn and its extensions that assume additional dephasing, we show how a nonlinear master equation may be constructed to describe the conditional evolution of the radical pairs prior to the detection of their recombination. We propose a nonlinear master equation for the evolution of an ensemble of independently evolving radical pairs whose nonlinearity depends on the record of the fluorescence signal. We also reformulate Haberkorn's original argument on the physicality of reaction operators using the terminology of quantum optics/open quantum systems. Our model allows one to describe multiple encounters within the exponential model and connects this with the master equation approach. We include hitherto neglected effects of the encounters, such as a separate dephasing in the triplet subspace, and predict potential new effects, such as Grover reflections of radical spins, that may be observed if the strength and time of the encounters can be experimentally controlled.

Efficient and Scalable Graph Similarity Joins in MapReduce

PubMed Central

Chen, Yifan; Zhang, Weiming; Tang, Jiuyang

2014-01-01

Along with the emergence of massive graph-modeled data, it is of great importance to investigate graph similarity joins due to their wide applications for multiple purposes, including data cleaning, and near duplicate detection. This paper considers graph similarity joins with edit distance constraints, which return pairs of graphs such that their edit distances are no larger than a given threshold. Leveraging the MapReduce programming model, we propose MGSJoin, a scalable algorithm following the filtering-verification framework for efficient graph similarity joins. It relies on counting overlapping graph signatures for filtering out nonpromising candidates. With the potential issue of too many key-value pairs in the filtering phase, spectral Bloom filters are introduced to reduce the number of key-value pairs. Furthermore, we integrate the multiway join strategy to boost the verification, where a MapReduce-based method is proposed for GED calculation. The superior efficiency and scalability of the proposed algorithms are demonstrated by extensive experimental results. PMID:25121135

Efficient and scalable graph similarity joins in MapReduce.

PubMed

Chen, Yifan; Zhao, Xiang; Xiao, Chuan; Zhang, Weiming; Tang, Jiuyang

2014-01-01

Along with the emergence of massive graph-modeled data, it is of great importance to investigate graph similarity joins due to their wide applications for multiple purposes, including data cleaning, and near duplicate detection. This paper considers graph similarity joins with edit distance constraints, which return pairs of graphs such that their edit distances are no larger than a given threshold. Leveraging the MapReduce programming model, we propose MGSJoin, a scalable algorithm following the filtering-verification framework for efficient graph similarity joins. It relies on counting overlapping graph signatures for filtering out nonpromising candidates. With the potential issue of too many key-value pairs in the filtering phase, spectral Bloom filters are introduced to reduce the number of key-value pairs. Furthermore, we integrate the multiway join strategy to boost the verification, where a MapReduce-based method is proposed for GED calculation. The superior efficiency and scalability of the proposed algorithms are demonstrated by extensive experimental results.

Combined quantum mechanics and molecular mechanics simulation of Ca2+/ammonia solution based on the ONIOM-XS method: Octahedral coordination and implication to biology

NASA Astrophysics Data System (ADS)

Kerdcharoen, Teerakiat; Morokuma, Keiji

2003-05-01

An extension of the ONIOM (Own N-layered Integrated molecular Orbital and molecular Mechanics) method [M. Svensson, S. Humbel, R. D. J. Froese, T. Mutsubara, S. Sieber, and K. Morokuma, J. Phys. Chem. 100, 19357 (1996)] for simulation in the condensed phase, called ONIOM-XS (XS=eXtension to Solvation) [T. Kerdcharoen and K. Morokuma, Chem. Phys. Lett. 355, 257 (2002)], was applied to investigate the coordination of Ca2+ in liquid ammonia. A coordination number of 6 is found. Previous simulations based on pair potential or pair potential plus three-body correction gave values of 9 and 8.2, respectively. The new value is the same as the coordination number most frequently listed in the Cambridge Structural Database (CSD) and Protein Data Bank (PDB). N-Ca-N angular distribution reveals a near-octahedral coordination structure. Inclusion of many-body interactions (which amounts to 25% of the pair interactions) into the potential energy surface is essential for obtaining reasonable coordination number. Analyses of the metal coordination in water, water-ammonia mixture, and in proteins reveals that cation/ammonia solution can be used to approximate the coordination environment in proteins.

Genetic and Environmental Etiologies of Reading Difficulties: DeFries-Fulker Analysis of Reading Performance Data from Twin Pairs and Their Non-Twin Siblings

ERIC Educational Resources Information Center

Astrom, Raven L.; Wadsworth, Sally J.; Olson, Richard K.; Willcutt, Erik G.; DeFries, John C.

2012-01-01

Reading performance data from 254 pairs of identical (MZ) and 420 pairs of fraternal (DZ) twins, 8.0 to 20.0 years of age, were subjected to multiple regression analyses. An extension of the DeFries-Fulker (DF) analysis (DeFries & Fulker, 1985, 1988) that facilitated inclusion of data from 303 of their nontwin siblings was employed. In addition to…

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

Banerjee, Surajit; Christov, Plamen P.; Kozekova, Albena

trans-4-Hydroxynonenal (HNE) is the major peroxidation product of {omega}-6 polyunsaturated fatty acids in vivo. Michael addition of the N{sub 2}-amino group of dGuo to HNE followed by ring closure of N1 onto the aldehyde results in four diastereomeric 1,N{sub 2}-dGuo (1,N{sub 2}-HNE-dGuo) adducts. The (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct was incorporated into the 18-mer templates 5'-d(TCATXGAATCCTTCCCCC)-3' and d(TCACXGAATCCTTCCCCC)-3', where X = (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct. These differed in the identity of the template 5'-neighbor base, which was either Thy or Cyt, respectively. Each of these templates was annealed with either a 13-mer primer 5'-d(GGGGGAAGGATTC)-3' or a 14-mer primer 5'-d(GGGGGAAGGATTCC)-3'. The addition of dNTPsmore » to the 13-mer primer allowed analysis of dNTP insertion opposite to the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct, whereas the 14-mer primer allowed analysis of dNTP extension past a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair. The Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) belongs to the Y-family of error-prone polymerases. Replication bypass studies in vitro reveal that this polymerase inserted dNTPs opposite the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct in a sequence-specific manner. If the template 5'-neighbor base was dCyt, the polymerase inserted primarily dGTP, whereas if the template 5'-neighbor base was dThy, the polymerase inserted primarily dATP. The latter event would predict low levels of Gua {yields} Thy mutations during replication bypass when the template 5'-neighbor base is dThy. When presented with a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair, the polymerase conducted full-length primer extension. Structures for ternary (Dpo4-DNA-dNTP) complexes with all four template-primers were obtained. For the 18-mer:13-mer template-primers in which the polymerase was confronted with the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct, the (6S,8R,11S)-1,N{sub 2}-dGuo lesion remained in the ring-closed conformation at the active site. The incoming dNTP, either dGTP or dATP, was positioned with Watson-Crick pairing opposite the template 5'-neighbor base, dCyt or dThy, respectively. In contrast, for the 18-mer:14-mer template-primers with a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair, ring opening of the adduct to the corresponding N{sub 2}-dGuo aldehyde species occurred. This allowed Watson-Crick base pairing at the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair.« less

Development of a clinician reputation metric to identify appropriate problem-medication pairs in a crowdsourced knowledge base.

PubMed

McCoy, Allison B; Wright, Adam; Rogith, Deevakar; Fathiamini, Safa; Ottenbacher, Allison J; Sittig, Dean F

2014-04-01

Correlation of data within electronic health records is necessary for implementation of various clinical decision support functions, including patient summarization. A key type of correlation is linking medications to clinical problems; while some databases of problem-medication links are available, they are not robust and depend on problems and medications being encoded in particular terminologies. Crowdsourcing represents one approach to generating robust knowledge bases across a variety of terminologies, but more sophisticated approaches are necessary to improve accuracy and reduce manual data review requirements. We sought to develop and evaluate a clinician reputation metric to facilitate the identification of appropriate problem-medication pairs through crowdsourcing without requiring extensive manual review. We retrieved medications from our clinical data warehouse that had been prescribed and manually linked to one or more problems by clinicians during e-prescribing between June 1, 2010 and May 31, 2011. We identified measures likely to be associated with the percentage of accurate problem-medication links made by clinicians. Using logistic regression, we created a metric for identifying clinicians who had made greater than or equal to 95% appropriate links. We evaluated the accuracy of the approach by comparing links made by those physicians identified as having appropriate links to a previously manually validated subset of problem-medication pairs. Of 867 clinicians who asserted a total of 237,748 problem-medication links during the study period, 125 had a reputation metric that predicted the percentage of appropriate links greater than or equal to 95%. These clinicians asserted a total of 2464 linked problem-medication pairs (983 distinct pairs). Compared to a previously validated set of problem-medication pairs, the reputation metric achieved a specificity of 99.5% and marginally improved the sensitivity of previously described knowledge bases. A reputation metric may be a valuable measure for identifying high quality clinician-entered, crowdsourced data. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of a clinician reputation metric to identify appropriate problem-medication pairs in a crowdsourced knowledge base

PubMed Central

McCoy, Allison B.; Wright, Adam; Rogith, Deevakar; Fathiamini, Safa; Ottenbacher, Allison J.; Sittig, Dean F.

2014-01-01

Background Correlation of data within electronic health records is necessary for implementation of various clinical decision support functions, including patient summarization. A key type of correlation is linking medications to clinical problems; while some databases of problem-medication links are available, they are not robust and depend on problems and medications being encoded in particular terminologies. Crowdsourcing represents one approach to generating robust knowledge bases across a variety of terminologies, but more sophisticated approaches are necessary to improve accuracy and reduce manual data review requirements. Objective We sought to develop and evaluate a clinician reputation metric to facilitate the identification of appropriate problem-medication pairs through crowdsourcing without requiring extensive manual review. Approach We retrieved medications from our clinical data warehouse that had been prescribed and manually linked to one or more problems by clinicians during e-prescribing between June 1, 2010 and May 31, 2011. We identified measures likely to be associated with the percentage of accurate problem-medication links made by clinicians. Using logistic regression, we created a metric for identifying clinicians who had made greater than or equal to 95% appropriate links. We evaluated the accuracy of the approach by comparing links made by those physicians identified as having appropriate links to a previously manually validated subset of problem-medication pairs. Results Of 867 clinicians who asserted a total of 237,748 problem-medication links during the study period, 125 had a reputation metric that predicted the percentage of appropriate links greater than or equal to 95%. These clinicians asserted a total of 2464 linked problem-medication pairs (983 distinct pairs). Compared to a previously validated set of problem-medication pairs, the reputation metric achieved a specificity of 99.5% and marginally improved the sensitivity of previously described knowledge bases. Conclusion A reputation metric may be a valuable measure for identifying high quality clinician-entered, crowdsourced data. PMID:24321170

High resolution 2D numerical models from rift to break-up: Crustal hyper-extension, Margin asymmetry, Sequential faulting

NASA Astrophysics Data System (ADS)

Brune, Sascha; Heine, Christian; Pérez-Gussinyé, Marta; Sobolev, Stephan

2013-04-01

Numerical modelling is a powerful tool to integrate a multitude of geological and geophysical data while addressing fundamental questions of passive margin formation such as the occurrence of crustal hyper-extension, (a-)symmetries between conjugate margin pairs, and the sometimes significant structural differences between adjacent margin segments. This study utilises knowledge gathered from two key examples of non-magmatic, asymmetric, conjugate margin pairs, i.e. Iberia-New Foundland and Southern Africa-Brazil, where many published seismic lines provide solid knowledge on individual margin geometry. While both margins involve crustal hyper-extension, it is much more pronounced in the South Atlantic. We investigate the evolution of these two margin pairs by carefully constraining our models with detailed plate kinematic history, laboratory-based rheology, and melt fraction evaluation of mantle upwelling. Our experiments are consistent with observed fault patterns, crustal thickness, and basin stratigraphy. We conduct 2D thermomechanical rift models using the finite element code SLIM3D that operates with nonlinear stress- and temperature-dependent elasto-visco-plastic rheology, with parameters provided by laboratory experiments on major crustal and upper mantle rocks. In our models we also calculate the melt fraction within the upwelling asthenosphere, which allows us to control whether the model indeed corresponds to the non-magmatic margin type or not. Our modelling highlights two processes as fundamental for the formation of hyper-extension and margin asymmetry at non-magmatic margins: (1) Strain hardening in the rift center due to cooling of upwelling mantle material (2) The formation of a weak crustal domain adjacent to the rift center caused by localized viscous strain softening and heat transfer from the mantle. Simultaneous activity of both processes promotes lateral rift migration in a continuous way that generates a wide layer of hyper-extended crust on one side of the rift basin. This mechanism implies that syn-rift deformation at the distal margin postdates faulting at the proximal margin by several million years. The succession of events holds intriguing implications not only for peak heat flow migration but also for processes like serpentinization and magmatic underplating.

Construction of a magnetostrictive hysteresis operator using a tripod-like primitive hopfield neural network

NASA Astrophysics Data System (ADS)

Adly, A. A.; Abd-El-Hafiz, S. K.

2018-05-01

It is well known that accurate modeling of magnetostrictive hysteresis is crucial to different industrial applications. Although several magnetostrictive models have been developed in the past, the accuracy-efficiency balance has always been crucial. Recently, the possibility of constructing a primitive vector hysteresis operator using a tri-node Hopfield Neural Network (HNN) was demonstrated. Based upon the fact that mechanical stress along a certain direction results in dimensional deformation, this paper introduces a novel extension to the aforementioned recently developed approach. More specifically, a stress-driven evolution of a tri-node HNN hysteresis operator pair is proposed, thus yielding a tripod-like HNN pair having different input offset values. Model identification, sample simulation results and comparison with experimental measurements are given in the paper.

Biochemical behavior of N-oxidized cytosine and adenine bases in DNA polymerase-mediated primer extension reactions

PubMed Central

Tsunoda, Hirosuke; Kudo, Tomomi; Masaki, Yoshiaki; Ohkubo, Akihiro; Seio, Kohji; Sekine, Mitsuo

2011-01-01

To clarify the biochemical behavior of 2′-deoxyribonucleoside 5′-triphosphates and oligodeoxyribonucleotides (ODNs) containing cytosine N-oxide (Co) and adenine N-oxide (Ao), we examined their base recognition ability in DNA duplex formation using melting temperature (Tm) experiments and their substrate specificity in DNA polymerase-mediated replication. As the result, it was found that the Tm values of modified DNA–DNA duplexes incorporating 2′-deoxyribonucleoside N-oxide derivatives significantly decreased compared with those of the unmodified duplexes. However, single insertion reactions by DNA polymerases of Klenow fragment (KF) (exo−) and Vent (exo−) suggested that Co and Ao selectively recognized G and T, respectively. Meanwhile, the kinetic study showed that the incorporation efficiencies of the modified bases were lower than those of natural bases. Ab initio calculations suggest that these modified bases can form the stable base pairs with the original complementary bases. These results indicate that the modified bases usually recognize the original bases as partners for base pairing, except for misrecognition of dATP by the action of KF (exo−) toward Ao on the template, and the primers could be extended on the template DNA. When they misrecognized wrong bases, the chain could not be elongated so that the modified base served as the chain terminator. PMID:21300642

Biochemical behavior of N-oxidized cytosine and adenine bases in DNA polymerase-mediated primer extension reactions.

PubMed

Tsunoda, Hirosuke; Kudo, Tomomi; Masaki, Yoshiaki; Ohkubo, Akihiro; Seio, Kohji; Sekine, Mitsuo

2011-04-01

To clarify the biochemical behavior of 2'-deoxyribonucleoside 5'-triphosphates and oligodeoxyribonucleotides (ODNs) containing cytosine N-oxide (C(o)) and adenine N-oxide (A(o)), we examined their base recognition ability in DNA duplex formation using melting temperature (T(m)) experiments and their substrate specificity in DNA polymerase-mediated replication. As the result, it was found that the T(m) values of modified DNA-DNA duplexes incorporating 2'-deoxyribonucleoside N-oxide derivatives significantly decreased compared with those of the unmodified duplexes. However, single insertion reactions by DNA polymerases of Klenow fragment (KF) (exo(-)) and Vent (exo(-)) suggested that C(o) and A(o) selectively recognized G and T, respectively. Meanwhile, the kinetic study showed that the incorporation efficiencies of the modified bases were lower than those of natural bases. Ab initio calculations suggest that these modified bases can form the stable base pairs with the original complementary bases. These results indicate that the modified bases usually recognize the original bases as partners for base pairing, except for misrecognition of dATP by the action of KF (exo(-)) toward A(o) on the template, and the primers could be extended on the template DNA. When they misrecognized wrong bases, the chain could not be elongated so that the modified base served as the chain terminator.

Unconventional Cooper pairing results in a pseudogap-like phase in s-wave superconductors

NASA Astrophysics Data System (ADS)

Springer, Daniel; Cheong, Siew Ann

2015-10-01

The impact of disorder on the superconducting (SC) pairing mechanism is the centre of much debate. Some evidence suggests a loss of phase coherence of pairs while others point towards the formation of a competing phase. In our work we show that the two perspectives may be different sides of the same coin. Using an extension of the perturbative renormalization group approach we compare the impact of different disorder-induced interactions on a SC ground state. We find that in the strongly disordered regime an interaction between paired fermions and their respective disordered environment replaces conventional Cooper pairing. For these unconventional Cooper pairs the phase coherence condition, required for the formation of a SC condensate, is not satisfied.

Efficient simultaneous reverse Monte Carlo modeling of pair-distribution functions and extended x-ray-absorption fine structure spectra of crystalline disordered materials.

PubMed

Németh, Károly; Chapman, Karena W; Balasubramanian, Mahalingam; Shyam, Badri; Chupas, Peter J; Heald, Steve M; Newville, Matt; Klingler, Robert J; Winans, Randall E; Almer, Jonathan D; Sandi, Giselle; Srajer, George

2012-02-21

An efficient implementation of simultaneous reverse Monte Carlo (RMC) modeling of pair distribution function (PDF) and EXAFS spectra is reported. This implementation is an extension of the technique established by Krayzman et al. [J. Appl. Cryst. 42, 867 (2009)] in the sense that it enables simultaneous real-space fitting of x-ray PDF with accurate treatment of Q-dependence of the scattering cross-sections and EXAFS with multiple photoelectron scattering included. The extension also allows for atom swaps during EXAFS fits thereby enabling modeling the effects of chemical disorder, such as migrating atoms and vacancies. Significant acceleration of EXAFS computation is achieved via discretization of effective path lengths and subsequent reduction of operation counts. The validity and accuracy of the approach is illustrated on small atomic clusters and on 5500-9000 atom models of bcc-Fe and α-Fe(2)O(3). The accuracy gains of combined simultaneous EXAFS and PDF fits are pointed out against PDF-only and EXAFS-only RMC fits. Our modeling approach may be widely used in PDF and EXAFS based investigations of disordered materials. © 2012 American Institute of Physics

Correlation in photon pairs generated using four-wave mixing in a cold atomic ensemble

NASA Astrophysics Data System (ADS)

Ferdinand, Andrew Richard; Manjavacas, Alejandro; Becerra, Francisco Elohim

2017-04-01

Spontaneous four-wave mixing (FWM) in atomic ensembles can be used to generate narrowband entangled photon pairs at or near atomic resonances. While extensive research has been done to investigate the quantum correlations in the time and polarization of such photon pairs, the study and control of high dimensional quantum correlations contained in their spatial degrees of freedom has not been fully explored. In our work we experimentally investigate the generation of correlated light from FWM in a cold ensemble of cesium atoms as a function of the frequencies of the pump fields in the FWM process. In addition, we theoretically study the spatial correlations of the photon pairs generated in the FWM process, specifically the joint distribution of their orbital angular momentum (OAM). We investigate the width of the distribution of the OAM modes, known as the spiral bandwidth, and the purity of OAM correlations as a function of the properties of the pump fields, collected photons, and the atomic ensemble. These studies will guide experiments involving high dimensional entanglement of photons generated from this FWM process and OAM-based quantum communication with atomic ensembles. This work is supported by AFORS Grant FA9550-14-1-0300.

Field Model: An Object-Oriented Data Model for Fields

NASA Technical Reports Server (NTRS)

Moran, Patrick J.

2001-01-01

We present an extensible, object-oriented data model designed for field data entitled Field Model (FM). FM objects can represent a wide variety of fields, including fields of arbitrary dimension and node type. FM can also handle time-series data. FM achieves generality through carefully selected topological primitives and through an implementation that leverages the potential of templated C++. FM supports fields where the nodes values are paired with any cell type. Thus FM can represent data where the field nodes are paired with the vertices ("vertex-centered" data), fields where the nodes are paired with the D-dimensional cells in R(sup D) (often called "cell-centered" data), as well as fields where nodes are paired with edges or other cell types. FM is designed to effectively handle very large data sets; in particular FM employs a demand-driven evaluation strategy that works especially well with large field data. Finally, the interfaces developed for FM have the potential to effectively abstract field data based on adaptive meshes. We present initial results with a triangular adaptive grid in R(sup 2) and discuss how the same design abstractions would work equally well with other adaptive-grid variations, including meshes in R(sup 3).

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases*

PubMed Central

Zhao, Linlin; Pence, Matthew G.; Christov, Plamen P.; Wawrzak, Zdzislaw; Choi, Jeong-Yun; Rizzo, Carmelo J.; Egli, Martin; Guengerich, F. Peter

2012-01-01

N2,3-Ethenoguanine (N2,3-ϵG) is one of the exocyclic DNA adducts produced by endogenous processes (e.g. lipid peroxidation) and exposure to bioactivated vinyl monomers such as vinyl chloride, which is a known human carcinogen. Existing studies exploring the miscoding potential of this lesion are quite indirect because of the lability of the glycosidic bond. We utilized a 2′-fluoro isostere approach to stabilize this lesion and synthesized oligonucleotides containing 2′-fluoro-N2,3-ϵ-2′-deoxyarabinoguanosine to investigate the miscoding potential of N2,3-ϵG by Y-family human DNA polymerases (pols). In primer extension assays, pol η and pol κ replicated through N2,3-ϵG, whereas pol ι and REV1 yielded only 1-base incorporation. Steady-state kinetics revealed that dCTP incorporation is preferred opposite N2,3-ϵG with relative efficiencies in the order of pol κ > REV1 > pol η ≈ pol ι, and dTTP misincorporation is the major miscoding event by all four Y-family human DNA pols. Pol ι had the highest dTTP misincorporation frequency (0.71) followed by pol η (0.63). REV1 misincorporated dTTP and dGTP with much lower frequencies. Crystal structures of pol ι with N2,3-ϵG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms. Two hydrogen bonds were observed in the N2,3-ϵG:dCTP base pair, whereas only one appears to be present in the case of the N2,3-ϵG:dTTP pair. Base pairing mechanisms derived from the crystal structures explain the slightly favored dCTP insertion for pol ι in steady-state kinetic analysis. Taken together, these results provide a basis for the mutagenic potential of N2,3-ϵG. PMID:22910910

Method and apparatus for setting precise nozzle/belt and nozzle/edge dam block gaps

DOEpatents

Carmichael, Robert J.; Dykes, Charles D.; Woodrow, Ronald

1989-05-16

A pair of guide pins are mounted on sideplate extensions of the caster and mating roller pairs are mounted on the nozzle assembly. The nozzle is advanced toward the caster so that the roller pairs engage the guide pins. Both guide pins are remotely adjustable in the vertical direction by hydraulic cylinders acting through eccentrics. This moves the nozzle vertically. The guide pin on the inboard side of the caster is similarly horizontally adjustable. The nozzle roller pair which engage the inboard guide pin are flanged so that the nozzle moves horizontally with the inboard guide pin.

MOCC: A Fast and Robust Correlation-Based Method for Interest Point Matching under Large Scale Changes

NASA Astrophysics Data System (ADS)

Zhao, Feng; Huang, Qingming; Wang, Hao; Gao, Wen

2010-12-01

Similarity measures based on correlation have been used extensively for matching tasks. However, traditional correlation-based image matching methods are sensitive to rotation and scale changes. This paper presents a fast correlation-based method for matching two images with large rotation and significant scale changes. Multiscale oriented corner correlation (MOCC) is used to evaluate the degree of similarity between the feature points. The method is rotation invariant and capable of matching image pairs with scale changes up to a factor of 7. Moreover, MOCC is much faster in comparison with the state-of-the-art matching methods. Experimental results on real images show the robustness and effectiveness of the proposed method.

Calculating the Bending Modulus for Multicomponent Lipid Membranes in Different Thermodynamic Phases

PubMed Central

2013-01-01

We establish a computational approach to extract the bending modulus, KC, for lipid membranes from relatively small-scale molecular simulations. Fluctuations in the splay of individual pairs of lipids faithfully inform on KC in multicomponent membranes over a large range of rigidities in different thermodynamic phases. Predictions are validated by experiments even where the standard spectral analysis-based methods fail. The local nature of this method potentially allows its extension to calculations of KC in protein-laden membranes. PMID:24039553

Neolasioptera pantaneira, a new species of Cecidomyiidae (Diptera) associated with Aeschynomene denticulata (Fabaceae) from Brazil.

PubMed

Maia, V C; Catian, G; Leme, F M

2017-03-01

A new species of gall midge that induces stem galls on Aeschynomene denticulata (Fabaceae) is described based on material collected in Pantanal (Mato Grosso do Sul, Brazil). This species is unique among the Brazilian congeners in having spatula with three convex teeth, cruciate, with defined anterolateral extensions, four lateral papillae on each side of the spatula, and three pairs of terminal papillae (larva), four-segmented palpi (adult), 17 flagellomeres (female), ovipositor about 11 times length of seventh tergite.

Designing heteropolymers to fold into unique structures via water-mediated interactions.

PubMed

Jamadagni, Sumanth N; Bosoy, Christian; Garde, Shekhar

2010-10-28

Hydrophobic homopolymers collapse into globular structures in water driven by hydrophobic interactions. Here we employ extensive molecular dynamics simulations to study the collapse of heteropolymers containing one or two pairs of oppositely charged monomers. We show that charging a pair of monomers can dramatically alter the most stable conformations from compact globular to more open hairpin-like. We systematically explore a subset of the sequence space of one- and two-charge-pair polymers, focusing on the locations of the charge pairs. Conformational stability is governed by a balance of hydrophobic interactions, hydration and interactions of charge groups, water-mediated charged-hydrophobic monomer repulsions, and other factors. As a result, placing charge pairs in the middle, away from the hairpin ends, leads to stable hairpin-like structures. Turning off the monomer-water attractions enhances hydrophobic interactions significantly leading to a collapse into compact globular structures even for two-charge-pair heteropolymers. In contrast, the addition of salt leads to open and extended structures, suggesting that solvation of charged monomer sites by salt ions dominates the salt-induced enhancement of hydrophobic interactions. We also test the ability of a predictive scheme based on the additivity of free energy of contact formation. The success of the scheme for symmetric two-charge-pair sequences and the failure for their flipped versions highlight the complexity of the heteropolymer conformation space and of the design problem. Collectively, our results underscore the ability of tuning water-mediated interactions to design stable nonglobular structures in water and present model heteropolymers for further studies in the extended thermodynamic space and in inhomogeneous environments.

Boosting compound-protein interaction prediction by deep learning.

PubMed

Tian, Kai; Shao, Mingyu; Wang, Yang; Guan, Jihong; Zhou, Shuigeng

2016-11-01

The identification of interactions between compounds and proteins plays an important role in network pharmacology and drug discovery. However, experimentally identifying compound-protein interactions (CPIs) is generally expensive and time-consuming, computational approaches are thus introduced. Among these, machine-learning based methods have achieved a considerable success. However, due to the nonlinear and imbalanced nature of biological data, many machine learning approaches have their own limitations. Recently, deep learning techniques show advantages over many state-of-the-art machine learning methods in some applications. In this study, we aim at improving the performance of CPI prediction based on deep learning, and propose a method called DL-CPI (the abbreviation of Deep Learning for Compound-Protein Interactions prediction), which employs deep neural network (DNN) to effectively learn the representations of compound-protein pairs. Extensive experiments show that DL-CPI can learn useful features of compound-protein pairs by a layerwise abstraction, and thus achieves better prediction performance than existing methods on both balanced and imbalanced datasets. Copyright © 2016 Elsevier Inc. All rights reserved.

Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing.

PubMed

Ghadie, Mohamed Ali; Lambourne, Luke; Vidal, Marc; Xia, Yu

2017-08-01

Alternative splicing is known to remodel protein-protein interaction networks ("interactomes"), yet large-scale determination of isoform-specific interactions remains challenging. We present a domain-based method to predict the isoform interactome from the reference interactome. First, we construct the domain-resolved reference interactome by mapping known domain-domain interactions onto experimentally-determined interactions between reference proteins. Then, we construct the isoform interactome by predicting that an isoform loses an interaction if it loses the domain mediating the interaction. Our prediction framework is of high-quality when assessed by experimental data. The predicted human isoform interactome reveals extensive network remodeling by alternative splicing. Protein pairs interacting with different isoforms of the same gene tend to be more divergent in biological function, tissue expression, and disease phenotype than protein pairs interacting with the same isoforms. Our prediction method complements experimental efforts, and demonstrates that integrating structural domain information with interactomes provides insights into the functional impact of alternative splicing.

Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing

PubMed Central

Lambourne, Luke; Vidal, Marc

2017-01-01

Alternative splicing is known to remodel protein-protein interaction networks (“interactomes”), yet large-scale determination of isoform-specific interactions remains challenging. We present a domain-based method to predict the isoform interactome from the reference interactome. First, we construct the domain-resolved reference interactome by mapping known domain-domain interactions onto experimentally-determined interactions between reference proteins. Then, we construct the isoform interactome by predicting that an isoform loses an interaction if it loses the domain mediating the interaction. Our prediction framework is of high-quality when assessed by experimental data. The predicted human isoform interactome reveals extensive network remodeling by alternative splicing. Protein pairs interacting with different isoforms of the same gene tend to be more divergent in biological function, tissue expression, and disease phenotype than protein pairs interacting with the same isoforms. Our prediction method complements experimental efforts, and demonstrates that integrating structural domain information with interactomes provides insights into the functional impact of alternative splicing. PMID:28846689

Similarity from Multi-Dimensional Scaling: Solving the Accuracy and Diversity Dilemma in Information Filtering

PubMed Central

Zeng, Wei; Zeng, An; Liu, Hao; Shang, Ming-Sheng; Zhang, Yi-Cheng

2014-01-01

Recommender systems are designed to assist individual users to navigate through the rapidly growing amount of information. One of the most successful recommendation techniques is the collaborative filtering, which has been extensively investigated and has already found wide applications in e-commerce. One of challenges in this algorithm is how to accurately quantify the similarities of user pairs and item pairs. In this paper, we employ the multidimensional scaling (MDS) method to measure the similarities between nodes in user-item bipartite networks. The MDS method can extract the essential similarity information from the networks by smoothing out noise, which provides a graphical display of the structure of the networks. With the similarity measured from MDS, we find that the item-based collaborative filtering algorithm can outperform the diffusion-based recommendation algorithms. Moreover, we show that this method tends to recommend unpopular items and increase the global diversification of the networks in long term. PMID:25343243

The structure of the human interferon alpha/beta receptor gene.

PubMed

Lutfalla, G; Gardiner, K; Proudhon, D; Vielh, E; Uzé, G

1992-02-05

Using the cDNA coding for the human interferon alpha/beta receptor (IFNAR), the IFNAR gene has been physically mapped relative to the other loci of the chromosome 21q22.1 region. 32,906 base pairs covering the IFNAR gene have been cloned and sequenced. Primer extension and solution hybridization-ribonuclease protection have been used to determine that the transcription of the gene is initiated in a broad region of 20 base pairs. Some aspects of the polymorphism of the gene, including noncoding sequences, have been analyzed; some are allelic differences in the coding sequence that induce amino acid variations in the resulting protein. The exon structure of the IFNAR gene and of that of the available genes for the receptors of the cytokine/growth hormone/prolactin/interferon receptor family have been compared with the predictions for the secondary structure of those receptors. From this analysis, we postulate a common origin and propose an hypothesis for the divergence from the immunoglobulin superfamily.

A DNA methylation map of human cancer at single base-pair resolution.

PubMed

Vidal, E; Sayols, S; Moran, S; Guillaumet-Adkins, A; Schroeder, M P; Royo, R; Orozco, M; Gut, M; Gut, I; Lopez-Bigas, N; Heyn, H; Esteller, M

2017-10-05

Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination.

Olfactory Interference during Inhibitory Backward Pairing in Honey Bees

PubMed Central

Dacher, Matthieu; Smith, Brian H.

2008-01-01

Background Restrained worker honey bees are a valuable model for studying the behavioral and neural bases of olfactory plasticity. The proboscis extension response (PER; the proboscis is the mouthpart of honey bees) is released in response to sucrose stimulation. If sucrose stimulation is preceded one or a few times by an odor (forward pairing), the bee will form a memory for this association, and subsequent presentations of the odor alone are sufficient to elicit the PER. However, backward pairing between the two stimuli (sucrose, then odor) has not been studied to any great extent in bees, although the vertebrate literature indicates that it elicits a form of inhibitory plasticity. Methodology/Principal Findings If hungry bees are fed with sucrose, they will release a long lasting PER; however, this PER can be interrupted if an odor is presented 15 seconds (but not 7 or 30 seconds) after the sucrose (backward pairing). We refer to this previously unreported process as olfactory interference. Bees receiving this 15 second backward pairing show reduced performance after a subsequent single forward pairing (excitatory conditioning) trial. Analysis of the results supported a relationship between olfactory interference and a form of backward pairing-induced inhibitory learning/memory. Injecting the drug cimetidine into the deutocerebrum impaired olfactory interference. Conclusions/Significance Olfactory interference depends on the associative link between odor and PER, rather than between odor and sucrose. Furthermore, pairing an odor with sucrose can lead either to association of this odor to PER or to the inhibition of PER by this odor. Olfactory interference may provide insight into processes that gate how excitatory and inhibitory memories for odor-PER associations are formed. PMID:18946512

Features of Superconducting Gaps Revealed by STM/STS in Iron Based Superconductors With and Without Hole Pockets

NASA Astrophysics Data System (ADS)

Wen, Hai-Hu; Hai-Hu Wen Team

The pairing mechanism and gap structure in iron based superconductors (IBS) remains unresolved. We have conducted extensive STM/STS study on the Na(Fe1-xTx) As (T =Co, Cu, Mn), Ba1-xKxFe2As2KFe2As2, and Li1-xFexOHFeSe single crystals. We found the clear evidence of the in-gap quasi-particle states induced by the non-magnetic Cu impurities in Na(Fe0.97- x Co0.03Cux) As, giving strong evidence of the S+/- pairing. Furthermore, we show the presence of the bosonic mode with the energy identical to that of the neutron resonance and a simple linear relation Ω/kBTc ~ 4.3, being explained a consequence of the S+/-pairing. The STS spectrum in Li1-x FexOHFeSe clearly indicates the presence of double superconducting gaps with Δ1 ~ 14.3 meV and Δ2 ~ 8.6 meV. Further analysis based on QPI allows us to assign the larger (smaller) gap to the outer (inner) hybridized electron pockets. The huge value 2Δ1/kBTc = 8.7 discovered here undoubtedly proves the strong coupling mechanism. This work was supported by the Ministry of Science and Technology of China, National Natural Science Foundation of China.

A tractable and accurate electronic structure method for static correlations: The perfect hextuples model

NASA Astrophysics Data System (ADS)

Parkhill, John A.; Head-Gordon, Martin

2010-07-01

We present the next stage in a hierarchy of local approximations to complete active space self-consistent field (CASSCF) model in an active space of one active orbital per active electron based on the valence orbital-optimized coupled-cluster (VOO-CC) formalism. Following the perfect pairing (PP) model, which is exact for a single electron pair and extensive, and the perfect quadruples (PQ) model, which is exact for two pairs, we introduce the perfect hextuples (PH) model, which is exact for three pairs. PH is an approximation to the VOO-CC method truncated at hextuples containing all correlations between three electron pairs. While VOO-CCDTQ56 requires computational effort scaling with the 14th power of molecular size, PH requires only sixth power effort. Our implementation also introduces some techniques which reduce the scaling to fifth order and has been applied to active spaces roughly twice the size of the CASSCF limit without any symmetry. Because PH explicitly correlates up to six electrons at a time, it can faithfully model the static correlations of molecules with up to triple bonds in a size-consistent fashion and for organic reactions usually reproduces CASSCF with chemical accuracy. The convergence of the PP, PQ, and PH hierarchy is demonstrated on a variety of examples including symmetry breaking in benzene, the Cope rearrangement, the Bergman reaction, and the dissociation of fluorine.

Activation energies for dissociation of double strand oligonucleotide anions: evidence for watson-crick base pairing in vacuo.

PubMed

Schnier, P D; Klassen, J S; Strittmatter, E F; Williams, E R

1998-09-23

The dissociation kinetics of a series of complementary and noncomplementary DNA duplexes, (TGCA)(2) (3-), (CCGG)(2) (3-), (AATTAAT)(2) (3-), (CCGGCCG)(2) (3-), A(7)*T(7) (3-), A(7)*A(7) (3-), T(7)*T(7) (3-), and A(7)*C(7) (3-) were investigated using blackbody infrared radiative dissociation in a Fourier transform mass spectrometer. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained. Activation energies range from 1.2 to 1.7 eV, and preexponential factors range from 10(13) to 10(19) s(-1). Dissociation of the duplexes results in cleavage of the noncovalent bonds and/or cleavage of covalent bonds leading to loss of a neutral nucleobase followed by backbone cleavage producing sequence-specific (a - base) and w ions. Four pieces of evidence are presented which indicate that Watson-Crick (WC) base pairing is preserved in complementary DNA duplexes in the gas phase: i. the activation energy for dissociation of the complementary dimer, A(7)*T(7) (3-), to the single strands is significantly higher than that for the related noncomplementary A(7)*A(7) (3-) and T(7)*T(7) (3-) dimers, indicating a stronger interaction between strands with a specific base sequence, ii. extensive loss of neutral adenine occurs for A(7)*A(7) (3-) and A(7)*C(7) (3-) but not for A(7)*T(7) (3-) consistent with this process being shut down by WC hydrogen bonding, iii. a correlation is observed between the measured activation energy for dissociation to single strands and the dimerization enthalpy (-DeltaH(d)) in solution, and iv. molecular dynamics carried out at 300 and 400 K indicate that WC base pairing is preserved for A(7)*T(7) (3-) duplex, although the helical structure is essentially lost. In combination, these results provide strong evidence that WC base pairing can exist in the complete absence of solvent.

Deformable image registration using convolutional neural networks

NASA Astrophysics Data System (ADS)

Eppenhof, Koen A. J.; Lafarge, Maxime W.; Moeskops, Pim; Veta, Mitko; Pluim, Josien P. W.

2018-03-01

Deformable image registration can be time-consuming and often needs extensive parameterization to perform well on a specific application. We present a step towards a registration framework based on a three-dimensional convolutional neural network. The network directly learns transformations between pairs of three-dimensional images. The outputs of the network are three maps for the x, y, and z components of a thin plate spline transformation grid. The network is trained on synthetic random transformations, which are applied to a small set of representative images for the desired application. Training therefore does not require manually annotated ground truth deformation information. The methodology is demonstrated on public data sets of inspiration-expiration lung CT image pairs, which come with annotated corresponding landmarks for evaluation of the registration accuracy. Advantages of this methodology are its fast registration times and its minimal parameterization.

Quantum Theory of Three-Dimensional Superresolution Using Rotating-PSF Imagery

NASA Astrophysics Data System (ADS)

Prasad, S.; Yu, Z.

The inverse of the quantum Fisher information (QFI) matrix (and extensions thereof) provides the ultimate lower bound on the variance of any unbiased estimation of a parameter from statistical data, whether of intrinsically quantum mechanical or classical character. We calculate the QFI for Poisson-shot-noise-limited imagery using the rotating PSF that can localize and resolve point sources fully in all three dimensions. We also propose an experimental approach based on the use of computer generated hologram and projective measurements to realize the QFI-limited variance for the problem of super-resolving a closely spaced pair of point sources at a highly reduced photon cost. The paper presents a preliminary analysis of quantum-limited three-dimensional (3D) pair optical super-resolution (OSR) problem with potential applications to astronomical imaging and 3D space-debris localization.

Symmetry-Enforced Line Nodes in Unconventional Superconductors [Nodal-Line Superconductors and Band-Sticking

DOE PAGES

Micklitz, T.; Norman, M. R.

2017-05-18

We classify line nodes in superconductors with strong spin-orbit interactions and time-reversal symmetry, where the latter may include nonprimitive translations in the magnetic Brillouin zone to account for coexistence with antiferromagnetic order. We find four possible combinations of irreducible representations of the order parameter on high-symmetry planes, two of which allow for line nodes in pseudospin-triplet pairs and two that exclude conventional fully gapped pseudospin-singlet pairs. We show that the former can only be realized in the presence of band-sticking degeneracies, and we verify their topological stability using arguments based on Clifford algebra extensions. Lastly, our classification exhausts all possiblemore » symmetry protected line nodes in the presence of spin-orbit coupling and a (generalized) time-reversal symmetry. Implications for existing nonsymmorphic and antiferromagnetic superconductors are discussed.« less

Morphological Feature Extraction for Automatic Registration of Multispectral Images

NASA Technical Reports Server (NTRS)

Plaza, Antonio; LeMoigne, Jacqueline; Netanyahu, Nathan S.

2007-01-01

The task of image registration can be divided into two major components, i.e., the extraction of control points or features from images, and the search among the extracted features for the matching pairs that represent the same feature in the images to be matched. Manual extraction of control features can be subjective and extremely time consuming, and often results in few usable points. On the other hand, automated feature extraction allows using invariant target features such as edges, corners, and line intersections as relevant landmarks for registration purposes. In this paper, we present an extension of a recently developed morphological approach for automatic extraction of landmark chips and corresponding windows in a fully unsupervised manner for the registration of multispectral images. Once a set of chip-window pairs is obtained, a (hierarchical) robust feature matching procedure, based on a multiresolution overcomplete wavelet decomposition scheme, is used for registration purposes. The proposed method is validated on a pair of remotely sensed scenes acquired by the Advanced Land Imager (ALI) multispectral instrument and the Hyperion hyperspectral instrument aboard NASA's Earth Observing-1 satellite.

Detailed analysis of stem I and its 5' and 3' neighbor regions in the trans-acting HDV ribozyme.

PubMed Central

Nishikawa, F; Roy, M; Fauzi, H; Nishikawa, S

1999-01-01

To determine the stem I structure of the human hepatitis delta virus (HDV) ribozyme, which is related to the substrate sequence in the trans -acting system, we kinetically studied stem I length and sequences. Stem I extension from 7 to 8 or 9 bp caused a loss of activity and a low amount of active complex with 9 bp in the trans -acting system. In a previous report, we presented cleavage in a 6 bp stem I. The observed reaction rates indicate that the original 7 bp stem I is in the most favorable location for catalytic reaction among the possible 6-8 bp stems. To test base specificity, we replaced the original GC-rich sequence in stem I with AU-rich sequences containing six AU or UA base pairs with the natural +1G.U wobble base pair at the cleavage site. The cis -acting AU-rich molecules demonstrated similar catalytic activity to that of the wild-type. In trans -acting molecules, due to stem I instability, reaction efficiency strongly depended on the concentration of the ribozyme-substrate complex and reaction temperature. Multiple turnover was observed at 37 degreesC, strongly suggesting that stem I has no base specificity and more efficient activity can be expected under multiple turnover conditions by substituting several UA or AU base pairs into stem I. We also studied the substrate damaging sequences linked to both ends of stem I for its development in therapeutic applications and confirmed the functions of the unique structure. PMID:9862958

Crystallographic observation of nonenzymatic RNA primer extension.

PubMed

Zhang, Wen; Walton, Travis; Li, Li; Szostak, Jack W

2018-05-31

The importance of genome replication has inspired detailed crystallographic studies of enzymatic DNA/RNA polymerization. In contrast, the mechanism of nonenzymatic polymerization is less well understood, despite its critical role in the origin of life. Here we report the direct observation of nonenzymatic RNA primer extension through time-resolved crystallography. We soaked crystals of an RNA primer-template-dGMP complex with guanosine-5'-phosphoro-2-aminoimidazolide for increasing times. At early times we see the activated ribonucleotides bound to the template, followed by formation of the imidazolium-bridged dinucleotide intermediate. At later times, we see a new phosphodiester bond forming between the primer and the incoming nucleotide. The intermediate is pre-organized because of the constraints of base-pairing with the template and hydrogen bonding between the imidazole amino group and both flanking phosphates. Our results provide atomic-resolution insight into the mechanism of nonenzymatic primer extension, and set the stage for further structural dissection and optimization of the RNA copying process. © 2018, Zhang et al.

In Vivo Patellofemoral Contact Mechanics During Active Extension Using a Novel Dynamic MRI-based Methodology

PubMed Central

Borotikar, Bhushan S.; Sheehan, Frances T.

2017-01-01

Objectives To establish an in vivo, normative patellofemoral cartilage contact mechanics database acquired during voluntary muscle control using a novel dynamic magnetic resonance (MR) imaging-based computational methodology and validate the contact mechanics sensitivity to the known sub-millimeter methodological inaccuracies. Design Dynamic cine phase-contrast and multi-plane cine images were acquired while female subjects (n=20, sample of convenience) performed an open kinetic chain (knee flexion-extension) exercise inside a 3-Tesla MR scanner. Static cartilage models were created from high resolution three-dimensional static MR data and accurately placed in their dynamic pose at each time frame based on the cine-PC data. Cartilage contact parameters were calculated based on the surface overlap. Statistical analysis was performed using paired t-test and a one-sample repeated measures ANOVA. The sensitivity of the contact parameters to the known errors in the patellofemoral kinematics was determined. Results Peak mean patellofemoral contact area was 228.7±173.6mm2 at 40° knee angle. During extension, contact centroid and peak strain locations tracked medially on the femoral and patellar cartilage and were not significantly different from each other. At 30°, 35°, and 40° of knee extension, contact area was significantly different. Contact area and centroid locations were insensitive to rotational and translational perturbations. Conclusion This study is a first step towards unfolding the biomechanical pathways to anterior patellofemoral pain and OA using dynamic, in vivo, and accurate methodologies. The database provides crucial data for future studies and for validation of, or as an input to, computational models. PMID:24012620

Complementarity to an miRNA seed region is sufficient to induce moderate repression of a target transcript in the unicellular green alga Chlamydomonas reinhardtii.

PubMed

Yamasaki, Tomohito; Voshall, Adam; Kim, Eun-Jeong; Moriyama, Etsuko; Cerutti, Heriberto; Ohama, Takeshi

2013-12-01

MicroRNAs (miRNAs) are 20-24 nt non-coding RNAs that play important regulatory roles in a broad range of eukaryotes by pairing with mRNAs to direct post-transcriptional repression. The mechanistic details of miRNA-mediated post-transcriptional regulation have been well documented in multicellular model organisms. However, this process remains poorly studied in algae such as Chlamydomonas reinhardtii, and specific features of miRNA biogenesis, target mRNA recognition and subsequent silencing are not well understood. In this study, we report on the characterization of a Chlamydomonas miRNA, cre-miR1174.2, which is processed from a near-perfect hairpin RNA. Using Gaussia luciferase (gluc) reporter genes, we have demonstrated that cre-miR1174.2 is functional in Chlamydomonas and capable of triggering site-specific cleavage at the center of a perfectly complementary target sequence. A mismatch tolerance test assay, based on pools of transgenic strains, revealed that target hybridization to nucleotides of the seed region, at the 5' end of an miRNA, was sufficient to induce moderate repression of expression. In contrast, pairing to the 3' region of the miRNA was not critical for silencing. Our results suggest that the base-pairing requirements for small RNA-mediated repression in C. reinhardtii are more similar to those of metazoans compared with the extensive complementarity that is typical of land plants. Individual Chlamydomonas miRNAs may potentially modulate the expression of numerous endogenous targets as a result of these relaxed base-pairing requirements. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Representation of planar motion of complex joints by means of rolling pairs. Application to neck motion.

PubMed

Page, Alvaro; de Rosario, Helios; Gálvez, José A; Mata, Vicente

2011-02-24

We propose to model planar movements between two human segments by means of rolling-without-slipping kinematic pairs. We compute the path traced by the instantaneous center of rotation (ICR) as seen from the proximal and distal segments, thus obtaining the fixed and moving centrodes, respectively. The joint motion is then represented by the rolling-without-slipping of one centrode on the other. The resulting joint kinematic model is based on the real movement and accounts for nonfixed axes of rotation; therefore it could improve current models based on revolute pairs in those cases where joint movement implies displacement of the ICR. Previous authors have used the ICR to characterize human joint motion, but they only considered the fixed centrode. Such an approach is not adequate for reproducing motion because the fixed centrode by itself does not convey information about body position. The combination of the fixed and moving centrodes gathers the kinematic information needed to reproduce the position and velocities of moving bodies. To illustrate our method, we applied it to the flexion-extension movement of the head relative to the thorax. The model provides a good estimation of motion both for position variables (mean R(pos)=0.995) and for velocities (mean R(vel)=0.958). This approach is more realistic than other models of neck motion based on revolute pairs, such as the dual-pivot model. The geometry of the centrodes can provide some information about the nature of the movement. For instance, the ascending and descending curves of the fixed centrode suggest a sequential movement of the cervical vertebrae. Copyright © 2010 Elsevier Ltd. All rights reserved.

Molecular cloning and nucleotide sequence of the alpha and beta subunits of allophycocyanin from the cyanelle genome of Cyanophora paradoxa.

PubMed Central

Bryant, D A; de Lorimier, R; Lambert, D H; Dubbs, J M; Stirewalt, V L; Stevens, S E; Porter, R D; Tam, J; Jay, E

1985-01-01

The genes for the alpha- and beta-subunit apoproteins of allophycocyanin (AP) were isolated from the cyanelle genome of Cyanophora paradoxa and subjected to nucleotide sequence analysis. The AP beta-subunit apoprotein gene was localized to a 7.8-kilobase-pair Pst I restriction fragment from cyanelle DNA by hybridization with a tetradecameric oligonucleotide probe. Sequence analysis using that oligonucleotide and its complement as primers for the dideoxy chain-termination sequencing method confirmed the presence of both AP alpha- and beta-subunit genes on this restriction fragment. Additional oligonucleotide primers were synthesized as sequencing progressed and were used to determine rapidly the nucleotide sequence of a 1336-base-pair region of this cloned fragment. This strategy allowed the sequencing to be completed without a detailed restriction map and without extensive and time-consuming subcloning. The sequenced region contains two open reading frames whose deduced amino acid sequences are 81-85% homologous to cyanobacterial and red algal AP subunits whose amino acid sequences have been determined. The two open reading frames are in the same orientation and are separated by 39 base pairs. AP alpha is 5' to AP beta and both coding sequences are preceded by a polypurine, Shine-Dalgarno-type sequence. Sequences upstream from AP alpha closely resemble the Escherichia coli consensus promoter sequences and also show considerable homology to promoter sequences for several chloroplast-encoded psbA genes. A 56-base-pair palindromic sequence downstream from the AP beta gene could play a role in the termination of transcription or translation. The allophycocyanin apoprotein subunit genes are located on the large single-copy region of the cyanelle genome. PMID:2987916

CAMPways: constrained alignment framework for the comparative analysis of a pair of metabolic pathways.

PubMed

Abaka, Gamze; Bıyıkoğlu, Türker; Erten, Cesim

2013-07-01

Given a pair of metabolic pathways, an alignment of the pathways corresponds to a mapping between similar substructures of the pair. Successful alignments may provide useful applications in phylogenetic tree reconstruction, drug design and overall may enhance our understanding of cellular metabolism. We consider the problem of providing one-to-many alignments of reactions in a pair of metabolic pathways. We first provide a constrained alignment framework applicable to the problem. We show that the constrained alignment problem even in a primitive setting is computationally intractable, which justifies efforts for designing efficient heuristics. We present our Constrained Alignment of Metabolic Pathways (CAMPways) algorithm designed for this purpose. Through extensive experiments involving a large pathway database, we demonstrate that when compared with a state-of-the-art alternative, the CAMPways algorithm provides better alignment results on metabolic networks as far as measures based on same-pathway inclusion and biochemical significance are concerned. The execution speed of our algorithm constitutes yet another important improvement over alternative algorithms. Open source codes, executable binary, useful scripts, all the experimental data and the results are freely available as part of the Supplementary Material at http://code.google.com/p/campways/. Supplementary data are available at Bioinformatics online.

Pairing phase diagram of three holes in the generalized Hubbard model

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

Navarro, O.; Espinosa, J.E.

Investigations of high-{Tc} superconductors suggest that the electronic correlation may play a significant role in the formation of pairs. Although the main interest is on the physic of two-dimensional highly correlated electron systems, the one-dimensional models related to high temperature superconductivity are very popular due to the conjecture that properties of the 1D and 2D variants of certain models have common aspects. Within the models for correlated electron systems, that attempt to capture the essential physics of high-temperature superconductors and parent compounds, the Hubbard model is one of the simplest. Here, the pairing problem of a three electrons system hasmore » been studied by using a real-space method and the generalized Hubbard Hamiltonian. This method includes the correlated hopping interactions as an extension of the previously proposed mapping method, and is based on mapping the correlated many body problem onto an equivalent site- and bond-impurity tight-binding one in a higher dimensional space, where the problem was solved in a non-perturbative way. In a linear chain, the authors analyzed the pairing phase diagram of three correlated holes for different values of the Hamiltonian parameters. For some value of the hopping parameters they obtain an analytical solution for all kind of interactions.« less

Electron attraction mediated by Coulomb repulsion.

PubMed

Hamo, A; Benyamini, A; Shapir, I; Khivrich, I; Waissman, J; Kaasbjerg, K; Oreg, Y; von Oppen, F; Ilani, S

2016-07-21

One of the defining properties of electrons is their mutual Coulomb repulsion. However, in solids this basic property may change; for example, in superconductors, the coupling of electrons to lattice vibrations makes the electrons attract one another, leading to the formation of bound pairs. Fifty years ago it was proposed that electrons can be made attractive even when all of the degrees of freedom in the solid are electronic, by exploiting their repulsion from other electrons. This attraction mechanism, termed 'excitonic', promised to achieve stronger and more exotic superconductivity. Yet, despite an extensive search, experimental evidence for excitonic attraction has yet to be found. Here we demonstrate this attraction by constructing, from the bottom up, the fundamental building block of the excitonic mechanism. Our experiments are based on quantum devices made from pristine carbon nanotubes, combined with cryogenic precision manipulation. Using this platform, we demonstrate that two electrons can be made to attract each other using an independent electronic system as the 'glue' that mediates attraction. Owing to its tunability, our system offers insights into the underlying physics, such as the dependence of the emergent attraction on the underlying repulsion, and the origin of the pairing energy. We also demonstrate transport signatures of excitonic pairing. This experimental demonstration of excitonic pairing paves the way for the design of exotic states of matter.

Electron attraction mediated by Coulomb repulsion

NASA Astrophysics Data System (ADS)

Hamo, A.; Benyamini, A.; Shapir, I.; Khivrich, I.; Waissman, J.; Kaasbjerg, K.; Oreg, Y.; von Oppen, F.; Ilani, S.

2016-07-01

One of the defining properties of electrons is their mutual Coulomb repulsion. However, in solids this basic property may change; for example, in superconductors, the coupling of electrons to lattice vibrations makes the electrons attract one another, leading to the formation of bound pairs. Fifty years ago it was proposed that electrons can be made attractive even when all of the degrees of freedom in the solid are electronic, by exploiting their repulsion from other electrons. This attraction mechanism, termed ‘excitonic’, promised to achieve stronger and more exotic superconductivity. Yet, despite an extensive search, experimental evidence for excitonic attraction has yet to be found. Here we demonstrate this attraction by constructing, from the bottom up, the fundamental building block of the excitonic mechanism. Our experiments are based on quantum devices made from pristine carbon nanotubes, combined with cryogenic precision manipulation. Using this platform, we demonstrate that two electrons can be made to attract each other using an independent electronic system as the ‘glue’ that mediates attraction. Owing to its tunability, our system offers insights into the underlying physics, such as the dependence of the emergent attraction on the underlying repulsion, and the origin of the pairing energy. We also demonstrate transport signatures of excitonic pairing. This experimental demonstration of excitonic pairing paves the way for the design of exotic states of matter.

Karyotype divergence and spreading of 5S rDNA sequences between genomes of two species: darter and emerald gobies ( Ctenogobius , Gobiidae).

PubMed

Lima-Filho, P A; Bertollo, L A C; Cioffi, M B; Costa, G W W F; Molina, W F

2014-01-01

Karyotype analyses of the cryptobenthic marine species Ctenogobius boleosoma and C. smaragdus were performed by means of classical and molecular cytogenetics, including physical mapping of the multigene 18S and 5S rDNA families. C. boleosoma has 2n = 44 chromosomes (2 submetacentrics + 42 acrocentrics; FN = 46) with a single chromosome pair each carrying 18S and 5S ribosomal sites; whereas C. smaragdus has 2n = 48 chromosomes (2 submetacentrics + 46 acrocentrics; FN = 50), also with a single pair bearing 18S rDNA, but an extensive increase in the number of GC-rich 5S rDNA sites in 21 chromosome pairs. The highly divergent karyotypes among Ctenogobius species contrast with observations in several other marine fish groups, demonstrating an accelerated rate of chromosomal evolution mediated by both chromosomal rearrangements and the extensive dispersion of 5S rDNA sequences in the genome. © 2014 S. Karger AG, Basel.

Structural variability and the nature of intermolecular interactions in Watson-Crick B-DNA base pairs.

PubMed

Czyznikowska, Z; Góra, R W; Zaleśny, R; Lipkowski, P; Jarzembska, K N; Dominiak, P M; Leszczynski, J

2010-07-29

A set of nearly 100 crystallographic structures was analyzed using ab initio methods in order to verify the effect of the conformational variability of Watson-Crick guanine-cytosine and adenine-thymine base pairs on the intermolecular interaction energy and its components. Furthermore, for the representative structures, a potential energy scan of the structural parameters describing mutual orientation of the base pairs was carried out. The results were obtained using the hybrid variational-perturbational interaction energy decomposition scheme. The electron correlation effects were estimated by means of the second-order Møller-Plesset perturbation theory and coupled clusters with singles and doubles method adopting AUG-cc-pVDZ basis set. Moreover, the characteristics of hydrogen bonds in complexes, mimicking those appearing in B-DNA, were evaluated using topological analysis of the electron density. Although the first-order electrostatic energy is usually the largest stabilizing component, it is canceled out by the associated exchange repulsion in majority of the studied crystallographic structures. Therefore, the analyzed complexes of the nucleic acid bases appeared to be stabilized mainly by the delocalization component of the intermolecular interaction energy which, in terms of symmetry adapted perturbation theory, encompasses the second- and higher-order induction and exchange-induction terms. Furthermore, it was found that the dispersion contribution, albeit much smaller in terms of magnitude, is also a vital stabilizing factor. It was also revealed that the intermolecular interaction energy and its components are strongly influenced by four (out of six) structural parameters describing mutual orientation of bases in Watson-Crick pairs, namely shear, stagger, stretch, and opening. Finally, as a part of a model study, much of the effort was devoted to an extensive testing of the UBDB databank. It was shown that the databank quite successfully reproduces the electrostatic energy determined with the aid of ab initio methods.

Mining protein database using machine learning techniques.

PubMed

Camargo, Renata da Silva; Niranjan, Mahesan

2008-08-25

With a large amount of information relating to proteins accumulating in databases widely available online, it is of interest to apply machine learning techniques that, by extracting underlying statistical regularities in the data, make predictions about the functional and evolutionary characteristics of unseen proteins. Such predictions can help in achieving a reduction in the space over which experiment designers need to search in order to improve our understanding of the biochemical properties. Previously it has been suggested that an integration of features computable by comparing a pair of proteins can be achieved by an artificial neural network, hence predicting the degree to which they may be evolutionary related and homologous.
We compiled two datasets of pairs of proteins, each pair being characterised by seven distinct features. We performed an exhaustive search through all possible combinations of features, for the problem of separating remote homologous from analogous pairs, we note that significant performance gain was obtained by the inclusion of sequence and structure information. We find that the use of a linear classifier was enough to discriminate a protein pair at the family level. However, at the superfamily level, to detect remote homologous pairs was a relatively harder problem. We find that the use of nonlinear classifiers achieve significantly higher accuracies.
In this paper, we compare three different pattern classification methods on two problems formulated as detecting evolutionary and functional relationships between pairs of proteins, and from extensive cross validation and feature selection based studies quantify the average limits and uncertainties with which such predictions may be made. Feature selection points to a \\"knowledge gap\\" in currently available functional annotations. We demonstrate how the scheme may be employed in a framework to associate an individual protein with an existing family of evolutionarily related proteins.

The evolutionary history of bears is characterized by gene flow across species

PubMed Central

Kumar, Vikas; Lammers, Fritjof; Bidon, Tobias; Pfenninger, Markus; Kolter, Lydia; Nilsson, Maria A.; Janke, Axel

2017-01-01

Bears are iconic mammals with a complex evolutionary history. Natural bear hybrids and studies of few nuclear genes indicate that gene flow among bears may be more common than expected and not limited to polar and brown bears. Here we present a genome analysis of the bear family with representatives of all living species. Phylogenomic analyses of 869 mega base pairs divided into 18,621 genome fragments yielded a well-resolved coalescent species tree despite signals for extensive gene flow across species. However, genome analyses using different statistical methods show that gene flow is not limited to closely related species pairs. Strong ancestral gene flow between the Asiatic black bear and the ancestor to polar, brown and American black bear explains uncertainties in reconstructing the bear phylogeny. Gene flow across the bear clade may be mediated by intermediate species such as the geographically wide-spread brown bears leading to large amounts of phylogenetic conflict. Genome-scale analyses lead to a more complete understanding of complex evolutionary processes. Evidence for extensive inter-specific gene flow, found also in other animal species, necessitates shifting the attention from speciation processes achieving genome-wide reproductive isolation to the selective processes that maintain species divergence in the face of gene flow. PMID:28422140

The evolutionary history of bears is characterized by gene flow across species.

PubMed

Kumar, Vikas; Lammers, Fritjof; Bidon, Tobias; Pfenninger, Markus; Kolter, Lydia; Nilsson, Maria A; Janke, Axel

2017-04-19

Bears are iconic mammals with a complex evolutionary history. Natural bear hybrids and studies of few nuclear genes indicate that gene flow among bears may be more common than expected and not limited to polar and brown bears. Here we present a genome analysis of the bear family with representatives of all living species. Phylogenomic analyses of 869 mega base pairs divided into 18,621 genome fragments yielded a well-resolved coalescent species tree despite signals for extensive gene flow across species. However, genome analyses using different statistical methods show that gene flow is not limited to closely related species pairs. Strong ancestral gene flow between the Asiatic black bear and the ancestor to polar, brown and American black bear explains uncertainties in reconstructing the bear phylogeny. Gene flow across the bear clade may be mediated by intermediate species such as the geographically wide-spread brown bears leading to large amounts of phylogenetic conflict. Genome-scale analyses lead to a more complete understanding of complex evolutionary processes. Evidence for extensive inter-specific gene flow, found also in other animal species, necessitates shifting the attention from speciation processes achieving genome-wide reproductive isolation to the selective processes that maintain species divergence in the face of gene flow.

Spontaneous Recovery after Extinction of the Conditioned Proboscis Extension Response in the Honeybee

ERIC Educational Resources Information Center

Sandoz, Jean-Christophe; Pham-Delegue, Minh-Ha

2004-01-01

In honeybees, the proboscis extension response (PER) can be conditioned by associating an odor stimulus (CS) to a sucrose reward (US). Conditioned responses to the CS, which are acquired by most bees after a single CS-US pairing, disappear after repeated unrewarded presentations of the CS, a process called extinction. Extinction is usually thought…

Morphological and molecular genetic diversity of Strongyluris calotis (Nematoda: Ascaridida: Heterakidae) in South East and East Asian lizards.

PubMed

Tran, Binh Thi; Ong, An Vinh; Luc, Pham Van; Sato, Hiroshi

2016-07-01

Strongyluris calotis is a heterakid nematode in the large intestine of agamid lizards (Reptilia: Sauria: Agamidae) from the Oriental Region. The standard light microscopic definition of the species counts the "caudal papillae" as 10 pairs on male worms. However, previous work from our group using scanning electron microscopy (SEM) on the heterakid from agamid lizards in Japan, Taiwan, and Singapore revealed that this counting contained a pair of phasmids and that two pairs of postcloacal papillae were completely fused to form a pair of united papillae, thus resulting in "10 pairs." In the present study, we examined S. calotis specimens from the Emma Gray's forest lizard, Calotes emma (Agamidae), living in the plain forest at low altitude, and the Vietnam false bloodsucker, Pseudocalotes brevipes (Agamidae), living in the mountainous forest at high altitude in the northern part of Vietnam. Using SEM, the arrangement of caudal papillae in male worms from an Emma Gray's forest lizard was found to be comparable to classical S. calotis specimens from agamid lizards collected in Japan, Taiwan, and Singapore. However, male worms from Vietnam false bloodsuckers did not have a pair of united papillae but had 10 pairs of independent caudal papillae with a pair of phasmids. Molecular genetic analyses of the ribosomal RNA gene (rDNA) of worms of the classical S. calotis morphotype from Japan and Singapore and two S. calotis morphotypes from Vietnam demonstrated absolutely identical nucleotide sequences of partial 18S rDNA (at least 1764 base pairs (bp)) and 5.8S rDNA (158 bp). However, intraspecific differences were detected in other regions of the rDNA, related to the geographical distribution of hosts regardless of morphotype: 97.8-98.5 % identity (443-446 bp/453 bp) in the internal transcribed spacer (ITS)-1 region, 96.6-98.0 % identity (425-431 bp/440 bp) in the ITS-2 region, and 99.6-99.7 % identity (1149-1151 bp/1154 bp) in the 28S rDNA. Thus, in the future, taxonomic relationships of S. calotis distributed widely in the Oriental Region as well as other nominal Oriental Strongyluris spp., currently six in number, need to be extensively explored based on molecular genetic analyses in addition to intensive morphological characterization.

Universal Profile of the Vortex Condensate in Two-Dimensional Turbulence

NASA Astrophysics Data System (ADS)

Laurie, Jason; Boffetta, Guido; Falkovich, Gregory; Kolokolov, Igor; Lebedev, Vladimir

2014-12-01

An inverse turbulent cascade in a restricted two-dimensional periodic domain creates a condensate—a pair of coherent system-size vortices. We perform extensive numerical simulations of this system and carry out theoretical analysis based on momentum and energy exchanges between the turbulence and the vortices. We show that the vortices have a universal internal structure independent of the type of small-scale dissipation, small-scale forcing, and boundary conditions. The theory predicts not only the vortex inner region profile, but also the amplitude, which both perfectly agree with the numerical data.

Indirect estimation of signal-dependent noise with nonadaptive heterogeneous samples.

PubMed

Azzari, Lucio; Foi, Alessandro

2014-08-01

We consider the estimation of signal-dependent noise from a single image. Unlike conventional algorithms that build a scatterplot of local mean-variance pairs from either small or adaptively selected homogeneous data samples, our proposed approach relies on arbitrarily large patches of heterogeneous data extracted at random from the image. We demonstrate the feasibility of our approach through an extensive theoretical analysis based on mixture of Gaussian distributions. A prototype algorithm is also developed in order to validate the approach on simulated data as well as on real camera raw images.

Flexion and extension gaps created by the navigation-assisted gap technique show small acceptable mismatches and close mutual correlations.

PubMed

Lee, Dae-Hee; Shin, Young-Soo; Jeon, Jin-Ho; Suh, Dong-Won; Han, Seung-Beom

2014-08-01

The aim of this study was to investigate the mechanism underlying the development of gap differences in total knee arthroplasty using the navigation-assisted gap technique and to assess whether these gap differences have statistical significance. Ninety-two patients (105 knees) implanted with cruciate-retaining prostheses using the navigation-assisted gap balancing technique were prospectively analysed. Medial extension and flexion gaps and lateral extension and flexion gaps were measured at full extension and at 90° of flexion. Repeated measures analysis of variance was used to compare the mean values of these four gaps. The correlation coefficient between each pair of gaps was assessed using Pearson's correlation analysis. Mean intra-operative medial and lateral extension gaps were 20.6 ± 2.1 and 21.7 ± 2.2 mm, respectively, and mean intra-operative medial and lateral flexion gaps were 21.6 ± 2.7 and 22.1 ± 2.5 mm, respectively. The pairs of gaps differed significantly (P < 0.05 each), except for the difference between the medial flexion and lateral extension gaps (n.s.). All four gaps were significantly correlated with each other, with the highest correlation between the medial and lateral flexion gaps (r = 0.890, P < 0.001) and the lowest between the medial flexion and lateral extension gaps (r = 0.701, P < 0.001). Medial and lateral flexion and extension gaps created using the navigation-assisted gap technique differed significantly, although the differences between them were <2 mm, and the gaps were closely correlated. These narrow ranges of statistically acceptable gap differences and the strong correlations between gaps should be considered by surgeons, as should the risks of soft tissue over-release or unintentional increases in extension or flexion gap after preparation of the other gap.

Extending or creating a new brand: evidence from a study on event-related potentials.

PubMed

Jin, Jia; Wang, Cuicui; Yu, Liping; Ma, Qingguo

2015-07-08

Brand strategy is a critical problem in new product promotion. In relation to this, producers typically have two main options, namely, brand extension and new brand creation. The current study investigated the neural basis of evaluating these brand strategies at the brain level by using event-related potentials. The experiment used a word-pair paradigm, in which the first word was either a famous beverage brand name or a newly created brand, and the second word was a product name from one of the two product categories (beverage or household appliance). Therefore, four conditions existed as follows: a famous beverage brand paired with a beverage product (BB) or with a household appliance (BH) and a newly created brand paired with a beverage product (NB) or with a household appliance (NH). Behavioral results showed that brand extension obtained a higher acceptance rate than new brand creation under the beverage product category; however, a lower acceptance rate was observed under the household appliance category. Moreover, at the brain level, BB elicited lower N400 mean amplitude than the new brand product NB, whereas BH led to higher N400 amplitude than the new brand product NH. These results showed that the likelihood of accepting a product depended on the association between the brand name and product name, and that the N400 could serve as an index of brand strategy evaluation. In addition, this study also confirmed that brand extension is not always the best brand strategy; an inappropriate extension sometimes performed worse than the creation of a new brand.

Overcoming Sequence Misalignments with Weighted Structural Superposition

PubMed Central

Khazanov, Nickolay A.; Damm-Ganamet, Kelly L.; Quang, Daniel X.; Carlson, Heather A.

2012-01-01

An appropriate structural superposition identifies similarities and differences between homologous proteins that are not evident from sequence alignments alone. We have coupled our Gaussian-weighted RMSD (wRMSD) tool with a sequence aligner and seed extension (SE) algorithm to create a robust technique for overlaying structures and aligning sequences of homologous proteins (HwRMSD). HwRMSD overcomes errors in the initial sequence alignment that would normally propagate into a standard RMSD overlay. SE can generate a corrected sequence alignment from the improved structural superposition obtained by wRMSD. HwRMSD’s robust performance and its superiority over standard RMSD are demonstrated over a range of homologous proteins. Its better overlay results in corrected sequence alignments with good agreement to HOMSTRAD. Finally, HwRMSD is compared to established structural alignment methods: FATCAT, SSM, CE, and Dalilite. Most methods are comparable at placing residue pairs within 2 Å, but HwRMSD places many more residue pairs within 1 Å, providing a clear advantage. Such high accuracy is essential in drug design, where small distances can have a large impact on computational predictions. This level of accuracy is also needed to correct sequence alignments in an automated fashion, especially for omics-scale analysis. HwRMSD can align homologs with low sequence identity and large conformational differences, cases where both sequence-based and structural-based methods may fail. The HwRMSD pipeline overcomes the dependency of structural overlays on initial sequence pairing and removes the need to determine the best sequence-alignment method, substitution matrix, and gap parameters for each unique pair of homologs. PMID:22733542

Insights to primitive replication derived from structures of small oligonucleotides

NASA Technical Reports Server (NTRS)

Smith, G. K.; Fox, G. E.

1995-01-01

Available information on the structure of small oligonucleotides is surveyed. It is observed that even small oligomers typically exhibit defined structures over a wide range of pH and temperature. These structures rely on a plethora of non-standard base-base interactions in addition to the traditional Watson-Crick pairings. Stable duplexes, though typically antiparallel, can be parallel or staggered and perfect complementarity is not essential. These results imply that primitive template directed reactions do not require high fidelity. Hence, the extensive use of Watson-Crick complementarity in genes rather than being a direct consequence of the primitive condensation process, may instead reflect subsequent selection based on the advantage of accuracy in maintaining the primitive genetic machinery once it arose.

Improving detection of copy-number variation by simultaneous bias correction and read-depth segmentation.

PubMed

Szatkiewicz, Jin P; Wang, WeiBo; Sullivan, Patrick F; Wang, Wei; Sun, Wei

2013-02-01

Structural variation is an important class of genetic variation in mammals. High-throughput sequencing (HTS) technologies promise to revolutionize copy-number variation (CNV) detection but present substantial analytic challenges. Converging evidence suggests that multiple types of CNV-informative data (e.g. read-depth, read-pair, split-read) need be considered, and that sophisticated methods are needed for more accurate CNV detection. We observed that various sources of experimental biases in HTS confound read-depth estimation, and note that bias correction has not been adequately addressed by existing methods. We present a novel read-depth-based method, GENSENG, which uses a hidden Markov model and negative binomial regression framework to identify regions of discrete copy-number changes while simultaneously accounting for the effects of multiple confounders. Based on extensive calibration using multiple HTS data sets, we conclude that our method outperforms existing read-depth-based CNV detection algorithms. The concept of simultaneous bias correction and CNV detection can serve as a basis for combining read-depth with other types of information such as read-pair or split-read in a single analysis. A user-friendly and computationally efficient implementation of our method is freely available.

A tale of two sequences: microRNA-target chimeric reads.

PubMed

Broughton, James P; Pasquinelli, Amy E

2016-04-04

In animals, a functional interaction between a microRNA (miRNA) and its target RNA requires only partial base pairing. The limited number of base pair interactions required for miRNA targeting provides miRNAs with broad regulatory potential and also makes target prediction challenging. Computational approaches to target prediction have focused on identifying miRNA target sites based on known sequence features that are important for canonical targeting and may miss non-canonical targets. Current state-of-the-art experimental approaches, such as CLIP-seq (cross-linking immunoprecipitation with sequencing), PAR-CLIP (photoactivatable-ribonucleoside-enhanced CLIP), and iCLIP (individual-nucleotide resolution CLIP), require inference of which miRNA is bound at each site. Recently, the development of methods to ligate miRNAs to their target RNAs during the preparation of sequencing libraries has provided a new tool for the identification of miRNA target sites. The chimeric, or hybrid, miRNA-target reads that are produced by these methods unambiguously identify the miRNA bound at a specific target site. The information provided by these chimeric reads has revealed extensive non-canonical interactions between miRNAs and their target mRNAs, and identified many novel interactions between miRNAs and noncoding RNAs.

U14 small nucleolar RNA makes multiple contacts with the pre-ribosomal RNA.

PubMed

Morrissey, J P; Tollervey, D

1997-06-01

The small nucleolar RNA (snoRNA) U14 has two regions of extended primary sequence complementarity to the 18S rRNA. The 3' region (domain B) shows the consensus structure for the methylation guide class of snoRNAs, whereas base-pairing between the 5' region (domain A) and the 18S rRNA sequence is required for the formation of functional ribosomes. Between domains A and B lies another essential region (domain Y). Here we report that yeast U14 can be cross-linked in vivo to the pre-rRNA; cross-linking is detected exclusively with the 35S primary transcript. Many nucleotides in U14 that lie outside of domains A and B are cross-linked to the pre-rRNA; in particular the essential domain Y region is cross-linked at several sites. U14 is, therefore, in far more extensive contact with the pre-rRNA than predicted from simple base-pairing models. Moreover, U14 can be cross-linked to other small RNA species. The functional interactions made by U14 during ribosome synthesis are likely to be very complex.

SELEX and SHAPE reveal that sequence motifs and an extended hairpin in the 5' portion of Turnip crinkle virus satellite RNA C mediate fitness in plants.

PubMed

Bayne, Charlie F; Widawski, Max E; Gao, Feng; Masab, Mohammed H; Chattopadhyay, Maitreyi; Murawski, Allison M; Sansevere, Robert M; Lerner, Bryan D; Castillo, Rinaldys J; Griesman, Trevor; Fu, Jiantao; Hibben, Jennifer K; Garcia-Perez, Alma D; Simon, Anne E; Kushner, David B

2018-07-01

Noncoding RNAs use their sequence and/or structure to mediate function(s). The 5' portion (166 nt) of the 356-nt noncoding satellite RNA C (satC) of Turnip crinkle virus (TCV) was previously modeled to contain a central region with two stem-loops (H6 and H7) and a large connecting hairpin (H2). We now report that in vivo functional selection (SELEX) experiments assessing sequence/structure requirements in H2, H6, and H7 reveal that H6 loop sequence motifs were recovered at nonrandom rates and only some residues are proposed to base-pair with accessible complementary sequences within the 5' central region. In vitro SHAPE of SELEX winners indicates that the central region is heavily base-paired, such that along with the lower stem and H2 region, one extensive hairpin exists composing the entire 5' region. As these SELEX winners are highly fit, these characteristics facilitate satRNA amplification in association with TCV in plants. Copyright © 2018 Elsevier Inc. All rights reserved.

A DNA methylation map of human cancer at single base-pair resolution

PubMed Central

Vidal, E; Sayols, S; Moran, S; Guillaumet-Adkins, A; Schroeder, M P; Royo, R; Orozco, M; Gut, M; Gut, I; Lopez-Bigas, N; Heyn, H; Esteller, M

2017-01-01

Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination. PMID:28581523

Pyrvinium pamoate changes alternative splicing of the serotonin receptor 2C by influencing its RNA structure

PubMed Central

Shen, Manli; Bellaousov, Stanislav; Hiller, Michael; de La Grange, Pierre; Creamer, Trevor P.; Malina, Orit; Sperling, Ruth; Mathews, David H.; Stoilov, Peter; Stamm, Stefan

2013-01-01

The serotonin receptor 2C plays a central role in mood and appetite control. It undergoes pre-mRNA editing as well as alternative splicing. The RNA editing suggests that the pre-mRNA forms a stable secondary structure in vivo. To identify substances that promote alternative exons inclusion, we set up a high-throughput screen and identified pyrvinium pamoate as a drug-promoting exon inclusion without editing. Circular dichroism spectroscopy indicates that pyrvinium pamoate binds directly to the pre-mRNA and changes its structure. SHAPE (selective 2′-hydroxyl acylation analysed by primer extension) assays show that part of the regulated 5′-splice site forms intramolecular base pairs that are removed by this structural change, which likely allows splice site recognition and exon inclusion. Genome-wide analyses show that pyrvinium pamoate regulates >300 alternative exons that form secondary structures enriched in A–U base pairs. Our data demonstrate that alternative splicing of structured pre-mRNAs can be regulated by small molecules that directly bind to the RNA, which is reminiscent to an RNA riboswitch. PMID:23393189

Evaluation of Controlled Vocabulary Resources for Development of a Consumer Entry Vocabulary for Diabetes

PubMed Central

Monga, Harpreet K; Sievert, MaryEllen C; Hall, Joan Houston; Longo, Daniel R

2001-01-01

Background Digital information technology can facilitate informed decision making by individuals regarding their personal health care. The digital divide separates those who do and those who do not have access to or otherwise make use of digital information. To close the digital divide, health care communications research must address a fundamental issue, the consumer vocabulary problem: consumers of health care, at least those who are laypersons, are not always familiar with the professional vocabulary and concepts used by providers of health care and by providers of health care information, and, conversely, health care and health care information providers are not always familiar with the vocabulary and concepts used by consumers. One way to address this problem is to develop a consumer entry vocabulary for health care communications. Objectives To evaluate the potential of controlled vocabulary resources for supporting the development of consumer entry vocabulary for diabetes. Methods We used folk medical terms from the Dictionary of American Regional English project to create exended versions of 3 controlled vocabulary resources: the Unified Medical Language System Metathesaurus, the Eurodicautom of the European Commission's Translation Service, and the European Commission Glossary of popular and technical medical terms. We extracted consumer terms from consumer-authored materials, and physician terms from physician-authored materials. We used our extended versions of the vocabulary resources to link diabetes-related terms used by health care consumers to synonymous, nearly-synonymous, or closely-related terms used by family physicians. We also examined whether retrieval of diabetes-related World Wide Web information sites maintained by nonprofit health care professional organizations, academic organizations, or governmental organizations can be improved by substituting a physician term for its related consumer term in the query. Results The Dictionary of American Regional English extension of the Metathesaurus provided coverage, either direct or indirect, of approximately 23% of the natural language consumer-term-physician-term pairs. The Dictionary of American Regional English extension of the Eurodicautom provided coverage for 16% of the term pairs. Both the Metathesaurus and the Eurodicautom indirectly related more terms than they directly related. A high percentage of covered term pairs, with more indirectly covered pairs than directly covered pairs, might be one way to make the most out of expensive controlled vocabulary resources. We compared retrieval of diabetes-related Web information sites using the physician terms to retrieval using related consumer terms We based the comparison on retrieval of sites maintained by non-profit healthcare professional organizations, academic organizations, or governmental organizations. The number of such sites in the first 20 results from a search was increased by substituting a physician term for its related consumer term in the query. This suggests that the Dictionary of American Regional English extensions of the Metathesaurus and Eurodicautom may be used to provide useful links from natural language consumer terms to natural language physician terms. Conclusions The Dictionary of American Regional English extensions of the Metathesaurus and Eurodicautom should be investigated further for support of consumer entry vocabulary for diabetes. PMID:11720966

a Norm Pairing in Formal Modules

NASA Astrophysics Data System (ADS)

Vostokov, S. V.

1980-02-01

A pairing of the multiplicative group of a local field (a finite extension of the field of p-adic numbers Qp) with the group of points of a Lubin-Tate formal group is defined explicitly. The values of the pairing are roots of an isogeny of the formal group. The main properties of this pairing are established: bilinearity, invariance under the choice of a local uniformizing element, and independence of the method of expanding elements into series with respect to this uniformizing element. These properties of the pairing are used to prove that it agrees with the generalized Hilbert norm residue symbol when the field over whose ring of integers the formal group is defined is totally ramified over Qp. This yields an explicit expression for the generalized Hilbert symbol on the group of points of the formal group. Bibliography: 12 titles.

A MULTICORE BASED PARALLEL IMAGE REGISTRATION METHOD

PubMed Central

Yang, Lin; Gong, Leiguang; Zhang, Hong; Nosher, John L.; Foran, David J.

2012-01-01

Image registration is a crucial step for many image-assisted clinical applications such as surgery planning and treatment evaluation. In this paper we proposed a landmark based nonlinear image registration algorithm for matching 2D image pairs. The algorithm was shown to be effective and robust under conditions of large deformations. In landmark based registration, the most important step is establishing the correspondence among the selected landmark points. This usually requires an extensive search which is often computationally expensive. We introduced a nonregular data partition algorithm using the K-means clustering algorithm to group the landmarks based on the number of available processing cores. The step optimizes the memory usage and data transfer. We have tested our method using IBM Cell Broadband Engine (Cell/B.E.) platform. PMID:19964921

Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

PubMed Central

Banda, Yambazi; Kvale, Mark N.; Hoffmann, Thomas J.; Hesselson, Stephanie E.; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A.; Dispensa, Brad P.; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H.; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P.; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C.; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P.; Van Den Eeden, Stephen K.; Walter, Lawrence; Whitmer, Rachel A.; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

2015-01-01

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian–European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent–child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent–child pairs was largely due to intermarriage. The parent–child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. PMID:26092716

Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.

PubMed

Banda, Yambazi; Kvale, Mark N; Hoffmann, Thomas J; Hesselson, Stephanie E; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A; Dispensa, Brad P; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P; Van Den Eeden, Stephen K; Walter, Lawrence; Whitmer, Rachel A; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

2015-08-01

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to intermarriage. The parent-child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. Copyright © 2015 by the Genetics Society of America.

Monitoring of surface deformation in open pit mine using DInSAR time-series: a case study in the N5W iron mine (Carajás, Brazil) using TerraSAR-X data

NASA Astrophysics Data System (ADS)

Mura, José C.; Paradella, Waldir R.; Gama, Fabio F.; Santos, Athos R.; Galo, Mauricio; Camargo, Paulo O.; Silva, Arnaldo Q.; Silva, Guilherme G.

2014-10-01

We present an investigation of surface deformation using Differential SAR Interferometry (DInSAR) time-series carried out in an active open pit iron mine, the N5W, located in the Carajás Mineral Province (Brazilian Amazon region), using 33 TerraSAR-X (TSX-1) scenes. This mine has presented a historical of instability and surface monitoring measurements over sectors of the mine (pit walls) have been done based on ground based radar. Two complementary approaches were used: the standard DInSAR configuration, as an early warning of the slope instability conditions, and the DInSAR timeseries analysis. In order to decrease the topographic phase error a high resolution DEM was generated based on a stereo GeoEye-1 pair. Despite the fact that a DinSAR contains atmospheric and topographic phase artifacts and noise, it was possible to detect deformation in some interferometric pairs, covering pit benches, road ramps and waste piles. The timeseries analysis was performed using the 31 interferometric pairs, which were selected based on the highest mean coherence of a stack of 107 interferograms, presenting less phase unwrapping errors. The time-series deformation was retrieved by the Least-Squares (LS) solution using an extension of the Singular Value Decomposition (SVD), with a set of additional weighted constrain on the acceleration deformation. The atmospheric phase artifacts were filtered in the space-time domain and the DEM height errors were estimated based on the normal baseline diversity. The DInSAR time-series investigation showed good results for monitoring surface displacement in the N5W mine located in a tropical rainforest environment, providing very useful information about the ground movement for alarm, planning and risk assessment.

Expanding the live kidney donor pool: ethical considerations regarding altruistic donors, paired and pooled programs.

PubMed

Patel, Shaneel Rajendra; Chadha, Priyanka; Papalois, Vassilios

2011-06-01

In renal transplant, there is a well-known deficiency in organ supply relative to demand. Live donation provides superior results when compared with deceased donation including a better rate of graft success and fewer immunologic complications. This deficiency in organs leads to significant morbidity and mortality rates. Alternative avenues have been extensively explored that may expand the live donor pool. They include altruistic donation as well as paired and pooled exchange programs. Altruistic donation is a truly selfless act from a donor unknown to the recipient. Kidney paired donation involves 2 incompatible donor-recipient pairs swapping donors to produce compatibility. Pooled donation involves at least 2 pairs, and can take the form of domino chains in which altruistic input sets up a chain of transplants, in which each recipient's incompatible donor makes a donation for the next recipient. Despite application of these various methods, there lie extensive ethical issues surrounding them. Misconceptions frequently occur; for instance, the perceived benefit that donating an organ to a loved one is greater for a related donor than for an altruistic one. Additionally, it is frequently believed that immunologic incompatibility offers coerced donors liberation from surgery, and that overcoming these barriers by introducing exchange programs provides vulnerable donors less protection. This article explores these and other complex ethical issues surrounding the various methods of expanding the donor pool. The authors offer opinions that challenge the ethical issues and attempt to overcome those views that hinder progress in the field.

Mid-infrared coincidence measurements based on intracavity frequency conversion

NASA Astrophysics Data System (ADS)

Piccione, S.; Mancinelli, M.; Trenti, A.; Fontana, G.; Dam, J.; Tidemand-Lichtenberg, P.; Pedersen, C.; Pavesi, L.

2018-02-01

In the last years, the Mid Infrared (MIR) spectral region has attracted the attention of many areas of science and technology, opening the way to important applications, such as molecular imaging, remote sensing, free- space communication and environmental monitoring. However, the development of new sources of light, such as quantum cascade laser, was not followed by an adequate improvement in the MIR detection system, able to exceed the current challenges. Here we demonstrate the single-photon counting capability of a new detection system, based on efficient up-converter modules, by proving the correlated nature of twin photons pairs at about 3.1μm, opening the way to the extension of quantum optics experiments in the MIR.

pp interaction at very high energies in cosmic ray experiments

NASA Astrophysics Data System (ADS)

Kendi Kohara, A.; Ferreira, Erasmo; Kodama, Takeshi

2014-11-01

An analysis of p-air cross section data from extensive air shower measurements is presented, based on an analytical representation of the pp scattering amplitudes that describes with high precision all available accelerator data at ISR, SPS and LHC energies. The theoretical basis of the representation, together with the very smooth energy dependence of parameters controlled by unitarity and dispersion relations, permits reliable extrapolation to high energy cosmic ray (CR) and asymptotic energy ranges. Calculations of σ p-airprod based on Glauber formalism are made using the input values of the quantities σ , ρ , BI and BR at high energies, with attention given to the independence of the slope parameters, with {{B}R}\

The limits of the nuclear landscape explored by the relativistic continuum Hartree-Bogoliubov theory

NASA Astrophysics Data System (ADS)

Xia, X. W.; Lim, Y.; Zhao, P. W.; Liang, H. Z.; Qu, X. Y.; Chen, Y.; Liu, H.; Zhang, L. F.; Zhang, S. Q.; Kim, Y.; Meng, J.

2018-05-01

The ground-state properties of nuclei with 8 ⩽ Z ⩽ 120 from the proton drip line to the neutron drip line have been investigated using the spherical relativistic continuum Hartree-Bogoliubov (RCHB) theory with the relativistic density functional PC-PK1. With the effects of the continuum included, there are totally 9035 nuclei predicted to be bound, which largely extends the existing nuclear landscapes predicted with other methods. The calculated binding energies, separation energies, neutron and proton Fermi surfaces, root-mean-square (rms) radii of neutron, proton, matter, and charge distributions, ground-state spins and parities are tabulated. The extension of the nuclear landscape obtained with RCHB is discussed in detail, in particular for the neutron-rich side, in comparison with the relativistic mean field calculations without pairing correlations and also other predicted landscapes. It is found that the coupling between the bound states and the continuum due to the pairing correlations plays an essential role in extending the nuclear landscape. The systematics of the separation energies, radii, densities, potentials and pairing energies of the RCHB calculations are also discussed. In addition, the α-decay energies and proton emitters based on the RCHB calculations are investigated.

Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots.

PubMed

Hajdin, Christine E; Bellaousov, Stanislav; Huggins, Wayne; Leonard, Christopher W; Mathews, David H; Weeks, Kevin M

2013-04-02

A pseudoknot forms in an RNA when nucleotides in a loop pair with a region outside the helices that close the loop. Pseudoknots occur relatively rarely in RNA but are highly overrepresented in functionally critical motifs in large catalytic RNAs, in riboswitches, and in regulatory elements of viruses. Pseudoknots are usually excluded from RNA structure prediction algorithms. When included, these pairings are difficult to model accurately, especially in large RNAs, because allowing this structure dramatically increases the number of possible incorrect folds and because it is difficult to search the fold space for an optimal structure. We have developed a concise secondary structure modeling approach that combines SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) experimental chemical probing information and a simple, but robust, energy model for the entropic cost of single pseudoknot formation. Structures are predicted with iterative refinement, using a dynamic programming algorithm. This melded experimental and thermodynamic energy function predicted the secondary structures and the pseudoknots for a set of 21 challenging RNAs of known structure ranging in size from 34 to 530 nt. On average, 93% of known base pairs were predicted, and all pseudoknots in well-folded RNAs were identified.

Search for long distance correlations between extensive air showers detected by the EEE network

NASA Astrophysics Data System (ADS)

Abbrescia, M.; Baldini, L.; Baldini Ferroli, R.; Batignani, G.; Battaglieri, M.; Boi, S.; Bossini, E.; Carnesecchi, F.; Chiavassa, A.; Cicalo, C.; Cifarelli, L.; Coccetti, F.; Coccia, E.; De Gruttola, D.; De Pasquale, S.; Fabbri, F. L.; Frolov, V.; Galeotti, P.; Garbini, M.; Gemme, G.; Gnesi, I.; Grazzi, S.; Gustavino, C.; Hatzifotiadou, D.; La Rocca, P.; Mandaglio, G.; Maragoto Rodriguez, O.; Maron, G.; Mazziotta, M. N.; Miozzi, S.; Nania, R.; Noferini, F.; Nozzoli, F.; Palmonari, F.; Panareo, M.; Panetta, M. P.; Paoletti, R.; Park, W.; Perasso, L.; Pilo, F.; Piragino, G.; Pisano, S.; Riggi, F.; Righini, G. C.; Ripoli, C.; Sartorelli, G.; Scapparone, E.; Schioppa, M.; Scribano, A.; Selvi, M.; Serci, S.; Squarcia, S.; Taiuti, M.; Terreni, G.; Trifirò, A.; Trimarchi, M.; Vistoli, M. C.; Votano, L.; Williams, M. C. S.; Zheng, L.; Zichichi, A.; Zuyeuski, R.

2018-02-01

A search for long distance correlations between individual Extensive Air Showers (EAS) detected by pairs of MRPC telescopes of the Extreme Energy Events (EEE) network was carried out. The search for an anomaly in these events is the purpose of our work. A dataset obtained by all the possible 45 pairs between 10 EEE cluster sites (hosting at least two telescopes), located at relative distances between 86 and 1200km, was analyzed, corresponding to an overall period of 3968 days time exposure. To estimate the possible event excess with respect to the spurious rate, the number of coincidence events was extracted as a function of the time difference between the arrival of the showers in the two sites, from ± 10 s to the smallest time interval where events are still observed. The analysis was done taking into account both the time and orientation correlation between the showers detected by the telescope pairs. A few candidate events with unusually small time difference and angular distance were observed, with a p-value sensibly smaller than a confidence level of 0.05.

Activation Energies for Dissociation of Double Strand Oligonucleotide Anions: Evidence for Watson–Crick Base Pairing in Vacuo

PubMed Central

Schnier, Paul D.; Klassen, John S.; Strittmatter, Eric F.; Williams*, Evan R.

2005-01-01

The dissociation kinetics of a series of complementary and noncomplementary DNA duplexes, (TGCA)23−, (CCGG)23−, (AATTAAT)23−, (CCGGCCG)23−, A7·T73−, A7·A73−, T7·T73−, and A7·C73− were investigated using blackbody infrared radiative dissociation in a Fourier transform mass spectrometer. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained. Activation energies range from 1.2 to 1.7 eV, and preexponential factors range from 1013 to 1019 s−1. Dissociation of the duplexes results in cleavage of the noncovalent bonds and/or cleavage of covalent bonds leading to loss of a neutral nucleobase followed by backbone cleavage producing sequence-specific (a – base) and w ions. Four pieces of evidence are presented which indicate that Watson–Crick (WC) base pairing is preserved in complementary DNA duplexes in the gas phase: i. the activation energy for dissociation of the complementary dimer, A7·T73−, to the single strands is significantly higher than that for the related noncomplementary A7·A73− and T7·T73− dimers, indicating a stronger interaction between strands with a specific base sequence, ii. extensive loss of neutral adenine occurs for A7·A73− and A7·C73− but not for A7·T73− consistent with this process being shut down by WC hydrogen bonding, iii. a correlation is observed between the measured activation energy for dissociation to single strands and the dimerization enthalpy (−ΔHd) in solution, and iv. molecular dynamics carried out at 300 and 400 K indicate that WC base pairing is preserved for A7·T73− duplex, although the helical structure is essentially lost. In combination, these results provide strong evidence that WC base pairing can exist in the complete absence of solvent. PMID:16498487

Efficient and accurate local single reference correlation methods for high-spin open-shell molecules using pair natural orbitals

NASA Astrophysics Data System (ADS)

Hansen, Andreas; Liakos, Dimitrios G.; Neese, Frank

2011-12-01

A production level implementation of the high-spin open-shell (spin unrestricted) single reference coupled pair, quadratic configuration interaction and coupled cluster methods with up to doubly excited determinants in the framework of the local pair natural orbital (LPNO) concept is reported. This work is an extension of the closed-shell LPNO methods developed earlier [F. Neese, F. Wennmohs, and A. Hansen, J. Chem. Phys. 130, 114108 (2009), 10.1063/1.3086717; F. Neese, A. Hansen, and D. G. Liakos, J. Chem. Phys. 131, 064103 (2009), 10.1063/1.3173827]. The internal space is spanned by localized orbitals, while the external space for each electron pair is represented by a truncated PNO expansion. The laborious integral transformation associated with the large number of PNOs becomes feasible through the extensive use of density fitting (resolution of the identity (RI)) techniques. Technical complications arising for the open-shell case and the use of quasi-restricted orbitals for the construction of the reference determinant are discussed in detail. As in the closed-shell case, only three cutoff parameters control the average number of PNOs per electron pair, the size of the significant pair list, and the number of contributing auxiliary basis functions per PNO. The chosen threshold default values ensure robustness and the results of the parent canonical methods are reproduced to high accuracy. Comprehensive numerical tests on absolute and relative energies as well as timings consistently show that the outstanding performance of the LPNO methods carries over to the open-shell case with minor modifications. Finally, hyperfine couplings calculated with the variational LPNO-CEPA/1 method, for which a well-defined expectation value type density exists, indicate the great potential of the LPNO approach for the efficient calculation of molecular properties.

Matrix Concentration Inequalities via the Method of Exchangeable Pairs

DTIC Science & Technology

2012-01-27

viewed as an exchangeable pairs version of the Burkholder –Davis–Gundy (BDG) inequality from classical martingale theory [Bur73]. Matrix extensions of...non-commutative probability. Math. Ann., 319:1–16, 2001. [Bur73] D. L. Burkholder . Distribution function inequalities for martingales. Ann. Probab., 1...Statist. Assoc., 58(301):13–30, 1963. [JX03] M. Junge and Q. Xu. Noncommutative Burkholder /Rosenthal inequalities. Ann. Probab., 31(2):948–995, 2003

Nucleotide sequence and proposed secondary structure of Columnea latent viroid: a natural mosaic of viroid sequences.

PubMed Central

Hammond, R; Smith, D R; Diener, T O

1989-01-01

The Columnea latent viroid (CLV) occurs latently in certain Columnea erythrophae plants grown commercially. In potato and tomato, CLV causes potato spindle tuber viroid (PSTV)-like symptoms. Its nucleotide sequence and proposed secondary structure reveal that CLV consists of a single-stranded circular RNA of 370 nucleotides which can assume a rod-like structure with extensive base-pairing characteristic of all known viroids. The electrophoretic mobility of circular CLV under nondenaturing conditions suggests a potential tertiary structure. CLV contains extensive sequence homologies to the PSTV group of viroids but contains a central conserved region identical to that of hop stunt viroid (HSV). CLV also shares some biological properties with each of the two types of viroids. Most probably, CLV is the result of intracellular RNA recombination between an HSV-type and one or more PSTV-type viroids replicating in the same plant. Images PMID:2602114

Orthographic effects in spoken word recognition: Evidence from Chinese.

PubMed

Qu, Qingqing; Damian, Markus F

2017-06-01

Extensive evidence from alphabetic languages demonstrates a role of orthography in the processing of spoken words. Because alphabetic systems explicitly code speech sounds, such effects are perhaps not surprising. However, it is less clear whether orthographic codes are involuntarily accessed from spoken words in languages with non-alphabetic systems, in which the sound-spelling correspondence is largely arbitrary. We investigated the role of orthography via a semantic relatedness judgment task: native Mandarin speakers judged whether or not spoken word pairs were related in meaning. Word pairs were either semantically related, orthographically related, or unrelated. Results showed that relatedness judgments were made faster for word pairs that were semantically related than for unrelated word pairs. Critically, orthographic overlap on semantically unrelated word pairs induced a significant increase in response latencies. These findings indicate that orthographic information is involuntarily accessed in spoken-word recognition, even in a non-alphabetic language such as Chinese.

Genetic Homologies Among Streptomyces violaceoruber Strains

PubMed Central

Monson, A. M.; Bradley, S. G.; Enquist, L. W.; Cruces, Griselda

1969-01-01

Most of the genetic studies on streptomycetes have been done with cultures erroneously designated as Streptomyces coelicolor. To determine whether these cultures are genetically homologous with the S. violaceoruber nominifer, their deoxyribonucleic acids (DNA) were analyzed, and selected pairs of mutants were crossed. The four cultures used in genetic studies, and called S. coelicolor in the literature, were found to constitute a genospecies, based upon DNA hybridization and recombination tests. In addition, DNA from Actinopycnidium caeruleum formed extensive duplexes with S. violaceoruber DNA. S. violaceoruber cultures and A. caeruleum were distinctly different from the S. coelicolor nominifer. PMID:5370275

APPLIED MECHANICS REVIEWS, WADEX WORD AND AUTHOR INDEX, VOLUME XVI, 1963,

DTIC Science & Technology

Author inDEX ) an IBM 1401 prepared mechanical index, extension of KWIC. WADEX usable for browsing and searching. This second WADEX is based on 8,000 titles of APPLIED MECHANICS REVIEWS (AMR), Vol. 16, 1963, an international critical review magazine. In WADEX, titles printed fully with author names, and as many lines used as necessary (60 characters per line). WADEX entry: word in title (except forbidden word) or author’s name. Alphabetically sequenced entries printed out of context. Words are single words or hypenated word pairs or ’Tagged Words’ (TW).

Microfluidic cell trap array for controlled positioning of single cells on adhesive micropatterns.

PubMed

Lin, Laiyi; Chu, Yeh-Shiu; Thiery, Jean Paul; Lim, Chwee Teck; Rodriguez, Isabel

2013-02-21

Adhesive micropattern arrays permit the continuous monitoring and systematic study of the behavior of spatially confined cells of well-defined shape and size in ordered configurations. This technique has contributed to defining mechanisms that control cell polarity and cell functions, including proliferation, apoptosis, differentiation and migration in two-dimensional cell culture systems. These micropattern studies often involve isolating a single cell on one adhesive protein micropattern using random seeding methods. Random seeding has been successful for isolated and, to a lesser degree, paired patterns, where two patterns are placed in close proximity. Using this method, we found that the probability of obtaining one cell per pattern decreases significantly as the number of micropatterns in a cluster increases, from 16% for paired micropatterns to 0.3% for clusters of 6 micropatterns. This work presents a simple yet effective platform based on a microfludic sieve-like trap array to exert precise control over the positioning of single cells on micropatterns. We observed a 4-fold improvement over random seeding in the efficiency of placing a pair of single cells on paired micropattern and a 40-fold improvement for 6-pattern clusters. The controlled nature of this platform can also allow the juxtaposition of two different cell populations through a simple modification in the trap arrangement. With excellent control of the identity, number and position of neighbouring cells, this cell-positioning platform provides a unique opportunity for the extension of two-dimensional micropattern studies beyond paired micropatterns to organizations containing many cells or different cell types.

Pairing Among the EET87503 Group of Howardites and Polymict Eucrites

NASA Technical Reports Server (NTRS)

Buchanan, P. C.; Lindstrom, D. J.; Mittlefehldt, D. W.

2000-01-01

The ten HED polymict breccias EET82600, EET87503, EET87509, EET87510, EET87512, EET87513, EET87518, EET87528, EET87531, and EET92022 were found over a broad area in the Elephant Moraine collecting region of Antarctica. Locations are scattered among the Main (Elephant Moraine), Meteorite City, and Texas Bowl icefields and the Northern Ice Patch. It was previously suggested that these polymict breccias are paired. However, degree of terrestrial alteration among these meteorites varies from relatively pristine (type A) to extensively altered (type B/C) and there are textural, mineralogical, and compositional differences. This study is a reevaluation of the pairing of these meteorites.

Pairing Among the EET87503 Group of Howardites and Polymict Eucrites

NASA Technical Reports Server (NTRS)

Buchanan, Paul C.; Lindstrom, D. J.; Mittlefehldt, D. W.

1999-01-01

The ten HED polymict breccias EET82600, EET87503, EET87509, EET87510, EET87512, EET87513, EET87518, EET87528, EET87531, and EET92022 were found over a broad area in the Elephant Moraine collecting region of Antarctica. Locations are scattered among the Main (Elephant Moraine), Meteorite City, and Texas Bowl icefields and the Northern Ice Patch. It was previously suggested that these polymict breccias are paired. However, degree of terrestrial alteration among these meteorites varies from relatively pristine (type A) to extensively altered (type B/C) and there are textural, mineralogical, and compositional differences. This study is a reevaluation of the pairing of these meteorites.

Report on Pairing-based Cryptography.

PubMed

Moody, Dustin; Peralta, Rene; Perlner, Ray; Regenscheid, Andrew; Roginsky, Allen; Chen, Lily

2015-01-01

This report summarizes study results on pairing-based cryptography. The main purpose of the study is to form NIST's position on standardizing and recommending pairing-based cryptography schemes currently published in research literature and standardized in other standard bodies. The report reviews the mathematical background of pairings. This includes topics such as pairing-friendly elliptic curves and how to compute various pairings. It includes a brief introduction to existing identity-based encryption (IBE) schemes and other cryptographic schemes using pairing technology. The report provides a complete study of the current status of standard activities on pairing-based cryptographic schemes. It explores different application scenarios for pairing-based cryptography schemes. As an important aspect of adopting pairing-based schemes, the report also considers the challenges inherent in validation testing of cryptographic algorithms and modules. Based on the study, the report suggests an approach for including pairing-based cryptography schemes in the NIST cryptographic toolkit. The report also outlines several questions that will require further study if this approach is followed.

Report on Pairing-based Cryptography

PubMed Central

Moody, Dustin; Peralta, Rene; Perlner, Ray; Regenscheid, Andrew; Roginsky, Allen; Chen, Lily

2015-01-01

This report summarizes study results on pairing-based cryptography. The main purpose of the study is to form NIST’s position on standardizing and recommending pairing-based cryptography schemes currently published in research literature and standardized in other standard bodies. The report reviews the mathematical background of pairings. This includes topics such as pairing-friendly elliptic curves and how to compute various pairings. It includes a brief introduction to existing identity-based encryption (IBE) schemes and other cryptographic schemes using pairing technology. The report provides a complete study of the current status of standard activities on pairing-based cryptographic schemes. It explores different application scenarios for pairing-based cryptography schemes. As an important aspect of adopting pairing-based schemes, the report also considers the challenges inherent in validation testing of cryptographic algorithms and modules. Based on the study, the report suggests an approach for including pairing-based cryptography schemes in the NIST cryptographic toolkit. The report also outlines several questions that will require further study if this approach is followed. PMID:26958435

Evolving a polymerase for hydrophobic base analogues.

PubMed

Loakes, David; Gallego, José; Pinheiro, Vitor B; Kool, Eric T; Holliger, Philipp

2009-10-21

Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene: varphi (abasic site), d5NI: varphi, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity.

Modeling DNA bubble formation at the atomic scale

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

Beleva, V; Rasmussen, K. O.; Garcia, A. E.

We describe the fluctuations of double stranded DNA molecules using a minimalist Go model over a wide range of temperatures. Minimalist models allow us to describe, at the atomic level, the opening and formation of bubbles in DNA double helices. This model includes all the geometrical constraints in helix melting imposed by the 3D structure of the molecule. The DNA forms melted bubbles within double helices. These bubbles form and break as a function of time. The equilibrium average number of broken base pairs shows a sharp change as a function of T. We observe a temperature profile of sequencemore » dependent bubble formation similar to those measured by Zeng et al. Long nuclei acid molecules melt partially through the formations of bubbles. It is known that CG rich sequences melt at higher temperatures than AT rich sequences. The melting temperature, however, is not solely determined by the CG content, but by the sequence through base stacking and solvent interactions. Recently, models that incorporate the sequence and nonlinear dynamics of DNA double strands have shown that DNA exhibits a very rich dynamics. Recent extensions of the Bishop-Peyrard model show that fluctuations in the DNA structure lead to opening in localized regions, and that these regions in the DNA are associated with transcription initiation sites. 1D and 2D models of DNA may contain enough information about stacking and base pairing interactions, but lack the coupling between twisting, bending and base pair opening imposed by the double helical structure of DNA that all atom models easily describe. However, the complexity of the energy function used in all atom simulations (including solvent, ions, etc) does not allow for the description of DNA folding/unfolding events that occur in the microsecond time scale.« less

Pair-bonding, female aggression and the evolution of lemur societies.

PubMed

Jolly, A

1998-01-01

Lemur societies have been described as convergent with those of anthropoids, including Papio-like female-bonded multi-male groups. Recent research, however, shows at least 5 pair-bonded species among the Lemuridae and Indriidae. Three more, Eulemur mongoz, Eulemur fulvus and Varecia variegata, have societies combining aspects of pairing with aspects of troop life. The best-known female-bonded societies, those of Lemur catta, Propithecus diadema edwardsi and Propithecus verreauxi, may be assemblages of mother-daughter dyads, capable of high aggression towards other females, but derived from more solitary female ancestors, perhaps also living as pairs. The internal structure of such lemur groups differs from the more extensive kin groups of catarrhines. This in turn may relate to the lemurs' level of social intelligence and to lemur female dominance over males.

Synchronization of low- and high-threshold motor units.

PubMed

Defreitas, Jason M; Beck, Travis W; Ye, Xin; Stock, Matt S

2014-04-01

We examined the degree of synchronization for both low- and high-threshold motor unit (MU) pairs at high force levels. MU spike trains were recorded from the quadriceps during high-force isometric leg extensions. Short-term synchronization (between -6 and 6 ms) was calculated for every unique MU pair for each contraction. At high force levels, earlier recruited motor unit pairs (low-threshold) demonstrated relatively low levels of short-term synchronization (approximately 7.3% extra firings than would have been expected by chance). However, the magnitude of synchronization increased significantly and linearly with mean recruitment threshold (reaching 22.1% extra firings for motor unit pairs recruited above 70% MVC). Three potential mechanisms that could explain the observed differences in synchronization across motor unit types are proposed and discussed. Copyright © 2013 Wiley Periodicals, Inc.

Widespread Transient Hoogsteen Base-Pairs in Canonical Duplex DNA with Variable Energetics

PubMed Central

Alvey, Heidi S.; Gottardo, Federico L.; Nikolova, Evgenia N.; Al-Hashimi, Hashim M.

2015-01-01

Hoogsteen base-pairing involves a 180 degree rotation of the purine base relative to Watson-Crick base-pairing within DNA duplexes, creating alternative DNA conformations that can play roles in recognition, damage induction, and replication. Here, using Nuclear Magnetic Resonance R1ρ relaxation dispersion, we show that transient Hoogsteen base-pairs occur across more diverse sequence and positional contexts than previously anticipated. We observe sequence-specific variations in Hoogsteen base-pair energetic stabilities that are comparable to variations in Watson-Crick base-pair stability, with Hoogsteen base-pairs being more abundant for energetically less favorable Watson-Crick base-pairs. Our results suggest that the variations in Hoogsteen stabilities and rates of formation are dominated by variations in Watson-Crick base pair stability, suggesting a late transition state for the Watson-Crick to Hoogsteen conformational switch. The occurrence of sequence and position-dependent Hoogsteen base-pairs provide a new potential mechanism for achieving sequence-dependent DNA transactions. PMID:25185517

Comparing two methods to record maximal voluntary contractions and different electrode positions in recordings of forearm extensor muscle activity: Refining risk assessments for work-related wrist disorders.

PubMed

Dahlqvist, Camilla; Nordander, Catarina; Granqvist, Lothy; Forsman, Mikael; Hansson, Gert-Åke

2018-01-01

Wrist disorders are common in force demanding industrial repetitive work. Visual assessment of force demands have a low reliability, instead surface electromyography (EMG) may be used as part of a risk assessment for work-related wrist disorders. For normalization of EMG recordings, a power grip (hand grip) is often used as maximal voluntary contraction (MVC) of the forearm extensor muscles. However, the test-retest reproducibility is poor and EMG amplitudes exceeding 100% have occasionally been recorded during work. An alternative MVC is resisted wrist extension, which may be more reliable. To compare hand grip and resisted wrist extension MVCs, in terms of amplitude and reproducibility, and to examine the effect of electrode positioning. Twelve subjects participated. EMG from right forearm extensors, from four electrode pairs, was recorded during MVCs, on three separate occasions. The group mean EMG amplitudes for resisted wrist extension were 1.2-1.7 times greater than those for hand grip. Resisted wrist extension showed better reproducibility than hand grip. The results indicate that the use of resisted wrist extension is a more accurate measurement of maximal effort of wrist extensor contractions than using hand grip and should increase the precision in EMG recordings from forearm extensor muscles, which in turn will increase the quality of risk assessments that are based on these.

Event-related potential N270 correlates of brand extension.

PubMed

Ma, Qingguo; Wang, Xiaoyi; Dai, Shenyi; Shu, Liangchao

2007-07-02

The aim of this study is to investigate the neural mechanism of extending a brand in a specific product category to other product categories. Facing two sequential stimuli in pairs consisting of beverage brand names (stimulus 1) and product names (stimulus 2) in other categories, 16 participants were asked to indicate the suitability of extending the brand in stimulus 1 to the product category in stimulus 2. These stimulus pairs were divided into four conditions depending on the product category in stimulus 2: beverage, snack, clothing, and household appliance. A negative component, N270, was recorded for each condition on the participants' scalps,whereas the maximum amplitude was observed at the frontal area. Greater N270 amplitude was observed when participants were presented with stronger conflict between the brand product category (stimulus 1) and the extension category (stimulus 2). It suggests that N270 can be evoked not only by a conflict of physical attributes (different shapes of words of brand and product names) but also by that of lexical content. From the marketing perspective, N270 can be potentially used as a reference measure in brand-extension attempts.

Age-Related Brain Activation Changes during Rule Repetition in Word-Matching.

PubMed

Methqal, Ikram; Pinsard, Basile; Amiri, Mahnoush; Wilson, Maximiliano A; Monchi, Oury; Provost, Jean-Sebastien; Joanette, Yves

2017-01-01

Objective: The purpose of this study was to explore the age-related brain activation changes during a word-matching semantic-category-based task, which required either repeating or changing a semantic rule to be applied. In order to do so, a word-semantic rule-based task was adapted from the Wisconsin Sorting Card Test, involving the repeated feedback-driven selection of given pairs of words based on semantic category-based criteria. Method: Forty healthy adults (20 younger and 20 older) performed a word-matching task while undergoing a fMRI scan in which they were required to pair a target word with another word from a group of three words. The required pairing is based on three word-pair semantic rules which correspond to different levels of semantic control demands: functional relatedness, moderately typical-relatedness (which were considered as low control demands), and atypical-relatedness (high control demands). The sorting period consisted of a continuous execution of the same sorting rule and an inferred trial-by-trial feedback was given. Results: Behavioral performance revealed increases in response times and decreases of correct responses according to the level of semantic control demands (functional vs. typical vs. atypical) for both age groups (younger and older) reflecting graded differences in the repetition of the application of a given semantic rule. Neuroimaging findings of significant brain activation showed two main results: (1) Greater task-related activation changes for the repetition of the application of atypical rules relative to typical and functional rules, and (2) Changes (older > younger) in the inferior prefrontal regions for functional rules and more extensive and bilateral activations for typical and atypical rules. Regarding the inter-semantic rules comparison, only task-related activation differences were observed for functional > typical (e.g., inferior parietal and temporal regions bilaterally) and atypical > typical (e.g., prefrontal, inferior parietal, posterior temporal, and subcortical regions). Conclusion: These results suggest that healthy cognitive aging relies on the adaptive changes of inferior prefrontal resources involved in the repetitive execution of semantic rules, thus reflecting graded differences in support of task demands.

Ghost imaging with paired x-ray photons

NASA Astrophysics Data System (ADS)

Schori, A.; Borodin, D.; Tamasaku, K.; Shwartz, S.

2018-06-01

We report the experimental observation of ghost imaging with paired x-ray photons, which are generated by parametric downconversion. We use the one-to-one relation between the photon energies and the emission angles and the anticorrelation between the k -vectors of the signal and the idler photons to reconstruct the images of slits with nominally zero background levels. Further extension of our procedure can be used for the observation of various quantum phenomena at x-ray wavelengths.

Initiation and strain compatibility of connected extension twins in AZ31 magnesium alloy at high temperature

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

Liu, Xiao, E-mail: liuxiao0105@163.com

2016-12-15

Uniaxial compression tests were carried out at 350 °C and a strain rate of 0.3 s{sup −1} on as-extruded AZ31 magnesium alloy samples. At a true strain of − 0.1, extension twin pairs in a grain and twin chains across adjacent grains were detected. The orientation of selected twins and their host grains were determined by electron backscattered diffraction (EBSD) techniques. The Schmid factors (SFs), accommodation strains and geometric compatibility factors (m{sup ′}) were calculated. Analysis of the data indicated that the formation of twin pair and twin chain was related to the SF and m{sup ′}. Regarding to twinmore » chain across adjacent grains, accommodation strain was also involved. The selection of twin variants in twin chain was generally determined by m{sup ′}. When the twins required the operation of pyramidal slip or twinning in adjacent grain, the corresponding connected twins with a relative high m{sup ′} were selected in this adjacent grain. - Highlights: •The formation of paired twins is studied during high temperature deformation. •The initiation of twinning in twin pair and twin chain obeys the Schmid law. •The twin variants' selection in twin chain is related to the geometric compatibility factor. •The accommodation strain plays an important role on the formation of twin chain.« less

Nucleic acid duplexes incorporating a dissociable covalent base pair

NASA Technical Reports Server (NTRS)

Gao, K.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

1999-01-01

We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure.

A challenging dissociation in masked identity priming with the lexical decision task.

PubMed

Perea, Manuel; Jiménez, María; Gómez, Pablo

2014-05-01

The masked priming technique has been used extensively to explore the early stages of visual-word recognition. One key phenomenon in masked priming lexical decision is that identity priming is robust for words, whereas it is small/unreliable for nonwords. This dissociation has usually been explained on the basis that masked priming effects are lexical in nature, and hence there should not be an identity prime facilitation for nonwords. We present two experiments whose results are at odds with the assumption made by models that postulate that identity priming is purely lexical, and also challenge the assumption that word and nonword responses are based on the same information. Our experiments revealed that for nonwords, but not for words, matched-case identity PRIME-TARGET pairs were responded to faster than mismatched-case identity prime-TARGET pairs, and this phenomenon was not modulated by the lowercase/uppercase feature similarity of the stimuli. Copyright © 2014 Elsevier B.V. All rights reserved.

An automated method for the analysis of phenolic acids in plasma based on ion-pairing micro-extraction coupled on-line to gas chromatography/mass spectrometry with in-liner derivatisation.

PubMed

Peters, Sonja; Kaal, Erwin; Horsting, Iwan; Janssen, Hans-Gerd

2012-02-24

A new method is presented for the analysis of phenolic acids in plasma based on ion-pairing 'Micro-extraction in packed sorbent' (MEPS) coupled on-line to in-liner derivatisation-gas chromatography-mass spectrometry (GC-MS). The ion-pairing reagent served a dual purpose. It was used both to improve extraction yields of the more polar analytes and as the methyl donor in the automated in-liner derivatisation method. In this way, a fully automated procedure for the extraction, derivatisation and injection of a wide range of phenolic acids in plasma samples has been obtained. An extensive optimisation of the extraction and derivatisation procedure has been performed. The entire method showed excellent repeatabilities of under 10% and linearities of 0.99 or better for all phenolic acids. The limits of detection of the optimised method for the majority of phenolic acids were 10ng/mL or lower with three phenolic acids having less-favourable detection limits of around 100 ng/mL. Finally, the newly developed method has been applied in a human intervention trial in which the bioavailability of polyphenols from wine and tea was studied. Forty plasma samples could be analysed within 24h in a fully automated method including sample extraction, derivatisation and gas chromatographic analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

Distance-dependent duplex DNA destabilization proximal to G-quadruplex/i-motif sequences

PubMed Central

König, Sebastian L. B.; Huppert, Julian L.; Sigel, Roland K. O.; Evans, Amanda C.

2013-01-01

G-quadruplexes and i-motifs are complementary examples of non-canonical nucleic acid substructure conformations. G-quadruplex thermodynamic stability has been extensively studied for a variety of base sequences, but the degree of duplex destabilization that adjacent quadruplex structure formation can cause has yet to be fully addressed. Stable in vivo formation of these alternative nucleic acid structures is likely to be highly dependent on whether sufficient spacing exists between neighbouring duplex- and quadruplex-/i-motif-forming regions to accommodate quadruplexes or i-motifs without disrupting duplex stability. Prediction of putative G-quadruplex-forming regions is likely to be assisted by further understanding of what distance (number of base pairs) is required for duplexes to remain stable as quadruplexes or i-motifs form. Using oligonucleotide constructs derived from precedented G-quadruplexes and i-motif-forming bcl-2 P1 promoter region, initial biophysical stability studies indicate that the formation of G-quadruplex and i-motif conformations do destabilize proximal duplex regions. The undermining effect that quadruplex formation can have on duplex stability is mitigated with increased distance from the duplex region: a spacing of five base pairs or more is sufficient to maintain duplex stability proximal to predicted quadruplex/i-motif-forming regions. PMID:23771141

Raman spectroscopy of DNA-metal complexes. I. Interactions and conformational effects of the divalent cations: Mg, Ca, Sr, Ba, Mn, Co, Ni, Cu, Pd, and Cd.

PubMed

Duguid, J; Bloomfield, V A; Benevides, J; Thomas, G J

1993-11-01

Interactions of divalent metal cations (Mg2+, Ca2+, Ba2+, Sr2+, Mn2+, Co2+, Ni2+, Cu2+, Pd2+, and Cd2+) with DNA have been investigated by laser Raman spectroscopy. Both genomic calf-thymus DNA (> 23 kilobase pairs) and mononucleosomal fragments (160 base pairs) were employed as targets of metal interaction in solutions containing 5 weight-% DNA and metal:phosphate molar ratios of 0.6:1. Raman difference spectra reveal that transition metal cations (Mn2+, Co2+, Ni2+, Cu2+, Pd2+, and Cd2+) induce the greatest structural changes in B-DNA. The Raman (vibrational) band differences are extensive and indicate partial disordering of the B-form backbone, reduction in base stacking, reduction in base pairing, and specific metal interaction with acceptor sites on the purine (N7) and pyrimidine (N3) rings. Many of the observed spectral changes parallel those accompanying thermal denaturation of B-DNA and suggest that the metals link the bases of denatured DNA. While exocyclic carbonyls of dT, dG, and dC may stabilize metal ligation, correlation plots show that perturbations of the carbonyls are mainly a consequence of metal-induced denaturation of the double helix. Transition metal interactions with the DNA phosphates are weak in comparison to interactions with the bases, except in the case of Cu2+, which strongly perturbs both base and phosphate group vibrations. On the other hand, the Raman signature of B-DNA is largely unperturbed by Mg2+, Ca2+, Sr2+, and Ba2+, suggesting much weaker interactions of the alkaline earth metals with both base and phosphate sites. A notable exception is a moderate perturbation by alkaline earths of purine N7 sites in 160-base pair DNA, with Ca2+ causing the greatest effect. Correlation plots demonstrate a strong interrelationship between perturbations of Raman bands assigned to ring vibrations of the bases and those of bands assigned to exocyclic carbonyls and backbone phosphodiester groups. However, strong correlations do not occur between the Raman phosphodioxy band (centered near 1092 cm-1) and other Raman bands, suggesting that the former is not highly sensitive to the structural changes induced by divalent metal cations. The structural perturbations induced by divalent cations are much greater for > 23-kilobase pair DNA than for 160-base pair DNA, as evidenced by both the Raman difference spectra and the tendency toward the formation of insoluble aggregates. In the presence of transition metals, aggregation of high-molecular-weight DNA is evident at temperatures as low as 11 degrees C. A relationship between DNA melting and aggregation is proposed in which initial metal binding at major groove sites locally destabilizes the B-DNA double helix, causing displacement of the bases away from one another and exposing additional metal binding sites. Metal cation linkage of two displaced bases would allow separate DNA strands to crosslink. Aggregation is proposed to result from the formation of an extended network of these crosslinks.

Microphysics of mass-transport in coupled droplet-pairs at low Reynolds number and the role of convective dynamics

NASA Astrophysics Data System (ADS)

Dong, Qingming; Sau, Amalendu

2016-06-01

Interfacial mass-transport and redistribution in the micro-scale liquid droplets are important in diverse fields of research interest. The role of the "inflow" and the "outflow" type convective eddy-pairs in the entrainment of outer solute and internal relocation are examined for different homogeneous and heterogeneous water droplet pairs appearing in a tandem arrangement. Two micro-droplets of pure (rain) water interact with an oncoming outer air stream (Re ≤ 100) contaminated by uniformly distributed SO2. By virtue of separation/attachment induced non-uniform interfacial shear-stress gradient, the well-defined inflow/outflow type pairs of recirculating eddy-based convective motion quickly develops, and the eddies effectively attract/repel the accumulated outer solute and control the physical process of mass-transport in the droplet-pair. The non-uniformly shear-driven flow interaction and bifurcation of the circulatory internal flow lead to growth of important micro-scale "secondary" eddies which suitably regroup with the adjacent "primary" one to create the sustained inflow/outflow type convective dynamics. The presently derived flow characteristics and in-depth analysis help to significantly improve our understanding of the micro-droplet based transport phenomena in a wider context. By tuning "Re" (defined in terms of the droplet diameter and the average oncoming velocity of the outer air) and gap-ratio "α," the internal convective forcing and the solute entrainment efficiency could be considerably enhanced. The quantitative estimates for mass entrainment, convective strength, and saturation characteristics for different coupled micro-droplet pairs are extensively examined here for 0.2 ≤ α ≤ 2.0 and 30 ≤ Re ≤ 100. Interestingly, for the compound droplets, with suitably tuned radius-ratio "B" (of upstream droplet with respect to downstream one) the generated "inflow" type coherent convective dynamics helped to significantly augment the centre-line mass flow, which in turn facilitate faster saturation of the upstream droplet. However, for heterogeneous droplet-pairs containing solid nucleus, while increased solid-fraction "S" (the ratio between the radius of the solid nucleus and that of the droplet) through 0.25 ≤ S ≤ 0.45 caused gradual reductions of convective strength and mass absorption rate (RSO2) for the upstream droplet, beyond a critical value S ≥ 0.45 the RSO2 therein continued to rise again owing to the reduced film thickness.

New approach to analyzing soil-building systems

USGS Publications Warehouse

Safak, E.

1998-01-01

A new method of analyzing seismic response of soil-building systems is introduced. The method is based on the discrete-time formulation of wave propagation in layered media for vertically propagating plane shear waves. Buildings are modeled as an extension of the layered soil media by assuming that each story in the building is another layer. The seismic response is expressed in terms of wave travel times between the layers, and the wave reflection and transmission coefficients at layer interfaces. The calculation of the response is reduced to a pair of simple finite-difference equations for each layer, which are solved recursively starting from the bedrock. Compared with commonly used vibration formulation, the wave propagation formulation provides several advantages, including the ability to incorporate soil layers, simplicity of the calculations, improved accuracy in modeling the mass and damping, and better tools for system identification and damage detection.A new method of analyzing seismic response of soil-building systems is introduced. The method is based on the discrete-time formulation of wave propagation in layered media for vertically propagating plane shear waves. Buildings are modeled as an extension of the layered soil media by assuming that each story in the building is another layer. The seismic response is expressed in terms of wave travel times between the layers, and the wave reflection and transmission coefficients at layer interfaces. The calculation of the response is reduced to a pair of simple finite-difference equations for each layer, which are solved recursively starting from the bedrock. Compared with commonly used vibration formulation, the wave propagation formulation provides several advantages, including the ability to incorporate soil layers, simplicity of the calculations, improved accuracy in modeling the mass and damping, and better tools for system identification and damage detection.

Longitudinal assessment of childhood optic gliomas: relationship between flicker visual evoked potentials and magnetic resonance imaging findings.

PubMed

Falsini, Benedetto; Ziccardi, Lucia; Lazzareschi, Ilaria; Ruggiero, Antonio; Placentino, Luca; Dickmann, Anna; Liotti, Lucia; Piccardi, Marco; Balestrazzi, Emilio; Colosimo, Cesare; Di Rocco, Concezio; Riccardi, Riccardo

2008-05-01

The aim of this study was to evaluate longitudinally functional and neuro-radiologic findings in childhood optic gliomas (OG), by comparing flicker visual evoked potentials (F-VEPs) with brain magnetic resonance imaging (MRI) changes. Fourteen children (age range: 1-13 years) with OGs underwent serial F-VEP, MRI and neuro-ophthalmic examinations over a 38 month (median, range: 6-76) follow-up. F-VEPs were elicited by 8 Hz sine-wave flicker stimuli presented in a mini-Ganzfeld. Contrast-enhanced MRI examinations were performed. Results of both tests were blindly assessed by independent evaluators. F-VEPs were judged to be improved, stable or worsened if changes in the amplitude and/or phase angle of the response exceeded the limits of test-retest variability (+/-90th percentile) established for the same patients. MRI results were judged to show regression, stabilization or progression of OG based on its changes in size (+/-20%) or extension. Two to seven pairs of F-VEP/MRI examinations per patient (median: 4) were collected. Based on a total of 38 pairs of F-VEP/MRI examinations, both tests agreed in showing worsening (progression), stabilization and improvement (regression) in 5, 15 and 10 cases, respectively. In 3 cases, F-VEPs showed a worsening and MRI a stabilization, while in 5 cases F-VEPs showed an improvement and MRI a stabilization. Agreement between F-VEP and MRI changes was 78.9% (95% CI: +/- 37%, K statistics = 0.67, P < 0.001). The results indicate that longitudinal F-VEP changes can predict changes in MRI-assessed OG size and extension, providing a non-invasive functional assay, complementary to neuro-imaging, for OG follow-up.

The nearest neighbor and next nearest neighbor effects on the thermodynamic and kinetic properties of RNA base pair

NASA Astrophysics Data System (ADS)

Wang, Yujie; Wang, Zhen; Wang, Yanli; Liu, Taigang; Zhang, Wenbing

2018-01-01

The thermodynamic and kinetic parameters of an RNA base pair with different nearest and next nearest neighbors were obtained through long-time molecular dynamics simulation of the opening-closing switch process of the base pair near its melting temperature. The results indicate that thermodynamic parameters of GC base pair are dependent on the nearest neighbor base pair, and the next nearest neighbor base pair has little effect, which validated the nearest-neighbor model. The closing and opening rates of the GC base pair also showed nearest neighbor dependences. At certain temperature, the closing and opening rates of the GC pair with nearest neighbor AU is larger than that with the nearest neighbor GC, and the next nearest neighbor plays little role. The free energy landscape of the GC base pair with the nearest neighbor GC is rougher than that with nearest neighbor AU.

[Structural and Dipole Structure Peculiarities of Hoogsteen Base Pairs Formed in Complementary Nucleobases according to ab initio Quantum Mechanics Studies].

PubMed

Petrenko, Y M

2015-01-01

Ab initio quantum mechanics studies for the detection of structure and dipole structure peculiarities of Hoogsteen base pairs relative to Watson-Crick base pairs, were performed during our work. These base pairs are formed as a result of complementary interactions. It was revealed, that adenine-thymine Hoogsteen base pair and adenine-thymine Watson-Crick base pairs can be formed depending on initial configuration. Cytosine-guanine Hoogsteen pairs are formed only when cytosine was originally protonated. Both types of Hoogsteen pairs have noticeable difference in the bond distances and angles. These differences appeared in purine as well as in pyrimidine parts of the pairs. Hoogsteen pairs have mostly shorter hydrogen bond lengths and significantly larger angles of hydrogen bonds and larger angles between the hydrogen bonds than Watson-Crick base pairs. Notable differences are also observed with respect to charge distribution and dipole moment. Quantitative data on these differences are shown in our work. It is also reported that the values of local parameters (according to Cambridge classification of the parameters which determine DNA properties) in Hoogsteen base pairs, are greatly different from Watson-Crick ones.

Nucleic acid duplexes incorporating a dissociable covalent base pair

PubMed Central

Gao, Kui; Orgel, Leslie E.

1999-01-01

We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure. PMID:10611299

Effect of the SOS response on the mean fitness of unicellular populations: a quasispecies approach.

PubMed

Kama, Amit; Tannenbaum, Emmanuel

2010-11-30

The goal of this paper is to develop a mathematical model that analyzes the selective advantage of the SOS response in unicellular organisms. To this end, this paper develops a quasispecies model that incorporates the SOS response. We consider a unicellular, asexually replicating population of organisms, whose genomes consist of a single, double-stranded DNA molecule, i.e. one chromosome. We assume that repair of post-replication mismatched base-pairs occurs with probability , and that the SOS response is triggered when the total number of mismatched base-pairs is at least . We further assume that the per-mismatch SOS elimination rate is characterized by a first-order rate constant . For a single fitness peak landscape where the master genome can sustain up to mismatches and remain viable, this model is analytically solvable in the limit of infinite sequence length. The results, which are confirmed by stochastic simulations, indicate that the SOS response does indeed confer a fitness advantage to a population, provided that it is only activated when DNA damage is so extensive that a cell will die if it does not attempt to repair its DNA.

Probabilistic model for quick detection of dissimilar binary images

NASA Astrophysics Data System (ADS)

Mustafa, Adnan A. Y.

2015-09-01

We present a quick method to detect dissimilar binary images. The method is based on a "probabilistic matching model" for image matching. The matching model is used to predict the probability of occurrence of distinct-dissimilar image pairs (completely different images) when matching one image to another. Based on this model, distinct-dissimilar images can be detected by matching only a few points between two images with high confidence, namely 11 points for a 99.9% successful detection rate. For image pairs that are dissimilar but not distinct-dissimilar, more points need to be mapped. The number of points required to attain a certain successful detection rate or confidence depends on the amount of similarity between the compared images. As this similarity increases, more points are required. For example, images that differ by 1% can be detected by mapping fewer than 70 points on average. More importantly, the model is image size invariant; so, images of any sizes will produce high confidence levels with a limited number of matched points. As a result, this method does not suffer from the image size handicap that impedes current methods. We report on extensive tests conducted on real images of different sizes.

Homology between DNA polymerases of poxviruses, herpesviruses, and adenoviruses: nucleotide sequence of the vaccinia virus DNA polymerase gene.

PubMed Central

Earl, P L; Jones, E V; Moss, B

1986-01-01

A 5400-base-pair segment of the vaccinia virus genome was sequenced and an open reading frame of 938 codons was found precisely where the DNA polymerase had been mapped by transfer of a phosphonoacetate-resistance marker. A single nucleotide substitution changing glycine at position 347 to aspartic acid accounts for the drug resistance of the mutant vaccinia virus. The 5' end of the DNA polymerase mRNA was located 80 base pairs before the methionine codon initiating the open reading frame. Correspondence between the predicted Mr 108,577 polypeptide and the 110,000 purified enzyme indicates that little or no proteolytic processing occurs. Extensive homology, extending over 435 amino acids, was found upon comparing the DNA polymerase of vaccinia virus and DNA polymerase of Epstein-Barr virus. A highly conserved sequence of 14 amino acids in the carboxyl-terminal regions of the above DNA polymerases is also present at a similar location in adenovirus DNA polymerase. This structure, which is predicted to form a turn flanked by beta-pleated sheets, may form part of an essential binding or catalytic site that accounts for its presence in DNA polymerases of poxviruses, herpesviruses, and adenoviruses. Images PMID:3012524

Structural determinants of an internal ribosome entry site that direct translational reading frame selection

PubMed Central

Ren, Qian; Au, Hilda H.T.; Wang, Qing S.; Lee, Seonghoon; Jan, Eric

2014-01-01

The dicistrovirus intergenic internal ribosome entry site (IGR IRES) directly recruits the ribosome and initiates translation using a non-AUG codon. A subset of IGR IRESs initiates translation in either of two overlapping open reading frames (ORFs), resulting in expression of the 0 frame viral structural polyprotein and an overlapping +1 frame ORFx. A U–G base pair adjacent to the anticodon-like pseudoknot of the IRES directs +1 frame translation. Here, we show that the U-G base pair is not absolutely required for +1 frame translation. Extensive mutagenesis demonstrates that 0 and +1 frame translation can be uncoupled. Ribonucleic acid (RNA) structural probing analyses reveal that the mutant IRESs adopt distinct conformations. Toeprinting analysis suggests that the reading frame is selected at a step downstream of ribosome assembly. We propose a model whereby the IRES adopts conformations to occlude the 0 frame aminoacyl-tRNA thereby allowing delivery of the +1 frame aminoacyl-tRNA to the A site to initiate translation of ORFx. This study provides a new paradigm for programmed recoding mechanisms that increase the coding capacity of a viral genome. PMID:25038250

Generalized derivation extensions of 3-Lie algebras and corresponding Nambu-Poisson structures

NASA Astrophysics Data System (ADS)

Song, Lina; Jiang, Jun

2018-01-01

In this paper, we introduce the notion of a generalized derivation on a 3-Lie algebra. We construct a new 3-Lie algebra using a generalized derivation and call it the generalized derivation extension. We show that the corresponding Leibniz algebra on the space of fundamental objects is the double of a matched pair of Leibniz algebras. We also determine the corresponding Nambu-Poisson structures under some conditions.

Whole exome sequencing to estimate alloreactivity potential between donors and recipients in stem cell transplantation

PubMed Central

Sampson, Juliana K.; Sheth, Nihar U.; Koparde, Vishal N.; Scalora, Allison F.; Serrano, Myrna G.; Lee, Vladimir; Roberts, Catherine H.; Jameson-Lee, Max; Ferreira-Gonzalez, Andrea; Manjili, Masoud H.; Buck, Gregory A.; Neale, Michael C.; Toor, Amir A.

2016-01-01

Summary Whole exome sequencing (WES) was performed on stem cell transplant donor-recipient (D-R) pairs to determine the extent of potential antigenic variation at a molecular level. In a small cohort of D-R pairs, a high frequency of sequence variation was observed between the donor and recipient exomes independent of human leucocyte antigen (HLA) matching. Nonsynonymous, nonconservative single nucleotide polymorphisms were approximately twice as frequent in HLA-matched unrelated, compared with related D-R pairs. When mapped to individual chromosomes, these polymorphic nucleotides were uniformly distributed across the entire exome. In conclusion, WES reveals extensive nucleotide sequence variation in the exomes of HLA-matched donors and recipients. PMID:24749631

Fuel cell stack with internal manifolds for reactant gases

DOEpatents

Schnacke, Arthur W.

1985-01-01

A fuel cell stack includes a plurality of plate-like fuel cells arranged along an axis generally parallel to cell thickness with electrically conductive separator plates between each pair of cells. A plurality of axial manifolds are provided at opposite sides of the stack in outer marginal portions beyond the edges of electrodes and electrolyte tiles. Sealing rings prevent cross-leakage of oxidant fuel gases through use of pairs of outwardly extending lips from opposite tile surfaces bonded to first and second electrode frames respectively. The frames provide transition between electrode edges and manifold perimeters. The pairs of extension lips are sealingly bonded together through an electrically insulative sealing ring with wedge shaped fastening members.

Fuel cell stack with internal manifolds for reactant gases

DOEpatents

Schnacke, A.W.

1983-10-12

A fuel cell stack includes a plurality of plate-like fuel cells arranged along an axis generally parallel to cell thickness with electrically conductive separator plates between each pair of cells. A plurality of axial manifolds are provided at opposite sides of the stack in outer marginal portions beyond the edges of electrodes and electrolyte tiles. Sealing rings prevent cross-leakage of oxidant fuel gases through use of pairs of outwardly extending lips from opposite tile surfaces bonded to first and second electrode frames respectively. The frames provide transition between electrode edges and manifold perimeters. The pairs of extension lips are sealingly bonded together through an electrically insulative sealing ring with wedge shaped fastening members.

Strategy for an Association Study of the Intestinal Microbiome and Brain Metabolome Across the Lifespan of Rats.

PubMed

Chen, Tianlu; You, Yijun; Xie, Guoxiang; Zheng, Xiaojiao; Zhao, Aihua; Liu, Jiajian; Zhao, Qing; Wang, Shouli; Huang, Fengjie; Rajani, Cynthia; Wang, Congcong; Chen, Shaoqiu; Ni, Yan; Yu, Herbert; Deng, Youping; Wang, Xiaoyan; Jia, Wei

2018-02-20

There is increased appreciation for the diverse roles of the microbiome-gut-brain axis on mammalian growth and health throughout the lifespan. Numerous studies have demonstrated that the gut microbiome and their metabolites are extensively involved in the communication between brain and gut. Association study of brain metabolome and gut microbiome is an active field offering large amounts of information on the interaction of microbiome, brain and gut but data size and complicated hierarchical relationships were found to be major obstacles to the formation of significant, reproducible conclusions. This study addressed a two-level strategy of brain metabolome and gut microbiome association analysis of male Wistar rats in the process of growth, employing several analytical platforms and various bioinformatics methods. Trajectory analysis showed that the age-related brain metabolome and gut microbiome had similarity in overall alteration patterns. Four high taxonomical level correlated pairs of "metabolite type-bacterial phylum", including "lipids-Spirochaetes", "free fatty acids (FFAs)-Firmicutes", "bile acids (BAs)-Firmicutes", and "Neurotransmitters-Bacteroidetes", were screened out based on unit- and multivariant correlation analysis and function analysis. Four groups of specific "metabolite-bacterium" association pairs from within the above high level key pairs were further identified. The key correlation pairs were validated by an independent animal study. This two-level strategy is effective in identifying principal correlations in big data sets obtained from the systematic multiomics study, furthering our understanding on the lifelong connection between brain and gut.

Molecular recognition of DNA base pairs by the formamido/pyrrole and formamido/imidazole pairings in stacked polyamides.

PubMed

Buchmueller, Karen L; Staples, Andrew M; Uthe, Peter B; Howard, Cameron M; Pacheco, Kimberly A O; Cox, Kari K; Henry, James A; Bailey, Suzanna L; Horick, Sarah M; Nguyen, Binh; Wilson, W David; Lee, Moses

2005-01-01

Polyamides containing an N-terminal formamido (f) group bind to the minor groove of DNA as staggered, antiparallel dimers in a sequence-specific manner. The formamido group increases the affinity and binding site size, and it promotes the molecules to stack in a staggered fashion thereby pairing itself with either a pyrrole (Py) or an imidazole (Im). There has not been a systematic study on the DNA recognition properties of the f/Py and f/Im terminal pairings. These pairings were analyzed here in the context of f-ImPyPy, f-ImPyIm, f-PyPyPy and f-PyPyIm, which contain the central pairing modes, -ImPy- and -PyPy-. The specificity of these triamides towards symmetrical recognition sites allowed for the f/Py and f/Im terminal pairings to be directly compared by SPR, CD and DeltaT (M) experiments. The f/Py pairing, when placed next to the -ImPy- or -PyPy- central pairings, prefers A/T and T/A base pairs to G/C base pairs, suggesting that f/Py has similar DNA recognition specificity to Py/Py. With -ImPy- central pairings, f/Im prefers C/G base pairs (>10 times) to the other Watson-Crick base pairs; therefore, f/Im behaves like the Py/Im pair. However, the f/Im pairing is not selective for the C/G base pair when placed next to the -PyPy- central pairings.

Water-separated ion pairs cause the slow dielectric mode of magnesium sulfate solutions

NASA Astrophysics Data System (ADS)

Mamatkulov, Shavkat I.; Rinne, Klaus F.; Buchner, Richard; Netz, Roland R.; Bonthuis, Douwe Jan

2018-06-01

We compare the dielectric spectra of aqueous MgSO4 and Na2SO4 solutions calculated from classical molecular dynamics simulations with experimental data, using an optimized thermodynamically consistent sulfate force field. Both the concentration-dependent shift of the static dielectric constant and the spectral shape match the experimental results very well for Na2SO4 solutions. For MgSO4 solutions, the simulations qualitatively reproduce the experimental observation of a slow mode, the origin of which we trace back to the ion-pair relaxation contribution via spectral decomposition. The radial distribution functions show that Mg2+ and SO42 - ions form extensive water-separated—and thus strongly dipolar—ion pairs, the orientational relaxation of which provides a simple physical explanation for the prominent slow dielectric mode in MgSO4 solutions. Remarkably, the Mg2+-SO42 - ion-pair relaxation extends all the way into the THz range, which we rationalize by the vibrational relaxation of tightly bound water-separated ion pairs. Thus, the relaxation of divalent ion pairs can give rise to widely separated orientational and vibrational spectroscopic features.

Direct visualization reveals kinetics of meiotic chromosome synapsis

DOE PAGES

Rog, Ofer; Dernburg, Abby  F.

2015-03-17

The synaptonemal complex (SC) is a conserved protein complex that stabilizes interactions along homologous chromosomes (homologs) during meiosis. The SC regulates genetic exchanges between homologs, thereby enabling reductional division and the production of haploid gametes. Here, we directly observe SC assembly (synapsis) by optimizing methods for long-term fluorescence recording in C. elegans. We report that synapsis initiates independently on each chromosome pair at or near pairing centers—specialized regions required for homolog associations. Once initiated, the SC extends rapidly and mostly irreversibly to chromosome ends. Quantitation of SC initiation frequencies and extension rates reveals that initiation is a rate-limiting step inmore » homolog interactions. Eliminating the dynein-driven chromosome movements that accompany synapsis severely retards SC extension, revealing a new role for these conserved motions. This work provides the first opportunity to directly observe and quantify key aspects of meiotic chromosome interactions and will enable future in vivo analysis of germline processes.« less

The limits of the nuclear landscape explored by the relativistic continuum Hartree–Bogoliubov theory

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

Xia, X. W.; Lim, Y.; Zhao, P. W.

The ground-state properties of nuclei with 8more » $$\\leqslant$$ Z $$\\leqslant$$ 120 from the proton drip line to the neutron drip line have been investigated using the relativistic continuum Hartree-Bogoliubov (RCHB) theory with the relativistic density functional PC-PK1. With the effects of the continuum included, there are totally 9035 nuclei predicted to be bound, which largely extends the existing nuclear landscapes predicted with other methods. The calculated binding energies, separation energies, neutron and proton Fermi surfaces, root-mean-square (rms) radii of neutron, proton, matter, and charge distributions, ground-state spins and parities are tabulated. The extension of the nuclear landscape obtained with RCHB is discussed in detail, in particular for the neutron-rich side, in comparison with the relativistic mean field calculations without pairing correlations and also other predicted landscapes. Here, it is found that the coupling between the bound states and the continuum due to the pairing correlations plays an essential role in extending the nuclear landscape. The systematics of the separation energies, radii, densities, potentials and pairing energies of the RCHB calculations are also discussed. In addition, the α-decay energies and proton emitters based on the RCHB calculations are investigated.« less

What is the minimum number of water molecules required to dissolve a potassium chloride molecule?

PubMed

Sen, Anik; Ganguly, Bishwajit

2010-12-01

This work answers an unsolved question that consists of determining the least number of water molecules necessary to separate a potassium chloride molecule. The answer based on accurate quantum chemical calculations suggests that tetramers are the smallest clusters necessary to dissociate KCl molecules. The study was made with Møller-Plesset second-order perturbation theory modified with the cluster theory having single, double, and perturbative triple excitations. With this extensive study, the dissociation of KCl molecule in different water clusters was evaluated. The calculated results show that four water molecules stabilize a solvent separated K(+)/Cl(-) ion-pair in prismatic structure and with six water molecules further dissociation was observed. Attenuated total reflection infrared spectroscopy of KCl dissolved in water establishes that clusters are made of closely bound ions with a mean of five water molecules per ion-pair [K(+)(H(2)O)(5)Cl(-)]. (Max and Chapados, Appl Spectrosc 1999, 53, 1601; Max and Chapados, J Chem Phys 2001, 115, 2664.) The calculated results tend to support that five water molecules leads toward the formation of contact ion-pair. The structures, energies, and infrared spectra of KCl molecules in different water clusters are also discussed. © 2010 Wiley Periodicals, Inc.

The Pavlovian analysis of instrumental conditioning.

PubMed

Gormezano, I; Tait, R W

1976-01-01

An account was given of the development within the Russian literature of a uniprocess formulation of classical and instrumental conditioning, known as the bidirectional conditioning hypothesis. The hypothesis purports to offer a single set of Pavlovian principles to account for both paradigms, based upon a neural model which assumes that bidirectional (forward and backward) connections are formed in both calssical and instrumental conditioning situations. In instrumental conditioning, the bidirectional connections are hypothesized to be simply more complex than those in classical conditioning, and any differences in empirical functions are presumed to lie not in difference in mechanism, but in the strength of the forward and backward connections. Although bidirectional connections are assumed to develop in instrumental conditioning, the experimental investigation of the bidirectional conditioning hypothesis has been essentially restricted to the classical conditioning operations of pairing two CSs (sensory preconditioning training), a US followed by a CS (backward conditioning training) and two USs. However, the paradigm involving the pairing of two USs, because of theoretical and analytical considerations, is the one most commonly employed by Russian investigators. The results of an initial experiment involving the pairing of two USs, and reference to the results of a more extensive investigation, leads us to tentatively question the validity of the bidirectional conditioning account of instrumental conditioning.

The limits of the nuclear landscape explored by the relativistic continuum Hartree–Bogoliubov theory

DOE PAGES

Xia, X. W.; Lim, Y.; Zhao, P. W.; ...

2017-11-01

The ground-state properties of nuclei with 8more » $$\\leqslant$$ Z $$\\leqslant$$ 120 from the proton drip line to the neutron drip line have been investigated using the relativistic continuum Hartree-Bogoliubov (RCHB) theory with the relativistic density functional PC-PK1. With the effects of the continuum included, there are totally 9035 nuclei predicted to be bound, which largely extends the existing nuclear landscapes predicted with other methods. The calculated binding energies, separation energies, neutron and proton Fermi surfaces, root-mean-square (rms) radii of neutron, proton, matter, and charge distributions, ground-state spins and parities are tabulated. The extension of the nuclear landscape obtained with RCHB is discussed in detail, in particular for the neutron-rich side, in comparison with the relativistic mean field calculations without pairing correlations and also other predicted landscapes. Here, it is found that the coupling between the bound states and the continuum due to the pairing correlations plays an essential role in extending the nuclear landscape. The systematics of the separation energies, radii, densities, potentials and pairing energies of the RCHB calculations are also discussed. In addition, the α-decay energies and proton emitters based on the RCHB calculations are investigated.« less

Unique Thermal Stability of Unnatural Hydrophobic Ds Bases in Double-Stranded DNAs.

PubMed

Kimoto, Michiko; Hirao, Ichiro

2017-10-20

Genetic alphabet expansion technology, the introduction of unnatural bases or base pairs into replicable DNA, has rapidly advanced as a new synthetic biology area. A hydrophobic unnatural base pair between 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds) and 2-nitro-4-propynylpyrrole (Px) exhibited high fidelity as a third base pair in PCR. SELEX methods using the Ds-Px pair enabled high-affinity DNA aptamer generation, and introducing a few Ds bases into DNA aptamers extremely augmented their affinities and selectivities to target proteins. Here, to further scrutinize the functions of this highly hydrophobic Ds base, the thermal stabilities of double-stranded DNAs (dsDNA) containing a noncognate Ds-Ds or G-Ds pair were examined. The thermal stability of the Ds-Ds self-pair was as high as that of the natural G-C pair, and apart from the generally higher stability of the G-C pair than that of the A-T pair, most of the 5'-pyrimidine-Ds-purine-3' sequences, such as CDsA and TDsA, exhibited higher stability than the 5'-purine-Ds-pyrimidine-3' sequences, such as GDsC and ADsC, in dsDNAs. This trait enabled the GC-content-independent control of the thermal stability of the designed dsDNA fragments. The melting temperatures of dsDNA fragments containing the Ds-Ds pair can be predicted from the nearest-neighbor parameters including the Ds base. In addition, the noncognate G-Ds pair can efficiently distinguish its neighboring cognate natural base pairs from noncognate pairs. We demonstrated that real-time PCR using primers containing Ds accurately detected a single-nucleotide mismatch in target DNAs. These unique properties of the Ds base that affect the stabilities of the neighboring base pairs could impart new functions to DNA molecules and technologies.

Extensions of the picture superiority effect in associative recognition.

PubMed

Hockley, William E; Bancroft, Tyler

2011-12-01

Previous research has shown that the picture superiority effect (PSE) is seen in tests of associative recognition for random pairs of line drawings compared to pairs of concrete words (Hockley, 2008). In the present study we demonstrated that the PSE for associative recognition is still observed when subjects have correctly identified the individual items of each pair as old (Experiment 1), and that this effect is not due to rehearsal borrowing (Experiment 2). The PSE for associative recognition also is shown to be present but attenuated for mixed picture-word pairs (Experiment 3), and similar in magnitude for pairs of simple black and white line drawings and coloured photographs of detailed objects (Experiment 4). The results are consistent with the view that the semantic meaning of nameable pictures is activated faster than that of words thereby affording subjects more time to generate and elaborate meaningful associations between items depicted in picture form. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Exploring the Roles of Nucleobase Desolvation and Shape Complementarity during the Misreplication of O6-Methylguanine

PubMed Central

Chavarria, Delia; Ramos-Serrano, Andrea; Hirao, Ichiro; Berdis, Anthony J.

2011-01-01

O6-methylguanine is a miscoding DNA lesion arising from the alkylation of guanine. This report uses the bacteriophage T4 DNA polymerase as a model to probe the roles hydrogen-bonding interactions, shape/size, and nucleobase desolvation during the replication of this miscoding lesion. This was accomplished by using transient kinetic techniques to monitor the kinetic parameters for incorporating and extending natural and non-natural nucleotides. In general, the efficiency of nucleotide incorporation does not depend on the hydrogen-bonding potential of the incoming nucleotide. Instead, nucleobase hydrophobicity and shape complementarity appear to be the preeminent factors controlling nucleotide incorporation. In addition, shape complementarity plays a large role in controlling the extension of various mispairs containing O6-methylguanine. This is evident as the rate constants for extension correlate with proper interglycosyl distances and symmetry between the base angles of the formed mispair. Base pairs not conforming to an acceptable geometry within the polymerase’s active site are refractory to elongation and are processed via exonuclease proofreading. The collective data set encompassing nucleotide incorporation, extension, and excision is used to generate a model accounting for the mutagenic potential of O6-methylguanine observed in vivo. In addition, kinetic studies monitoring the incorporation and extension of non-natural nucleotides identified an analog that displays high selectivity for incorporation opposite O6-methylguanine compared to unmodified purines. The unusual selectivity of this analog for replicating damaged DNA provides a novel biochemical tool to study translesion DNA synthesis. PMID:21819995

RDNAnalyzer: A tool for DNA secondary structure prediction and sequence analysis.

PubMed

Afzal, Muhammad; Shahid, Ahmad Ali; Shehzadi, Abida; Nadeem, Shahid; Husnain, Tayyab

2012-01-01

RDNAnalyzer is an innovative computer based tool designed for DNA secondary structure prediction and sequence analysis. It can randomly generate the DNA sequence or user can upload the sequences of their own interest in RAW format. It uses and extends the Nussinov dynamic programming algorithm and has various application for the sequence analysis. It predicts the DNA secondary structure and base pairings. It also provides the tools for routinely performed sequence analysis by the biological scientists such as DNA replication, reverse compliment generation, transcription, translation, sequence specific information as total number of nucleotide bases, ATGC base contents along with their respective percentages and sequence cleaner. RDNAnalyzer is a unique tool developed in Microsoft Visual Studio 2008 using Microsoft Visual C# and Windows Presentation Foundation and provides user friendly environment for sequence analysis. It is freely available. http://www.cemb.edu.pk/sw.html RDNAnalyzer - Random DNA Analyser, GUI - Graphical user interface, XAML - Extensible Application Markup Language.

GAAP: Genome-organization-framework-Assisted Assembly Pipeline for prokaryotic genomes.

PubMed

Yuan, Lina; Yu, Yang; Zhu, Yanmin; Li, Yulai; Li, Changqing; Li, Rujiao; Ma, Qin; Siu, Gilman Kit-Hang; Yu, Jun; Jiang, Taijiao; Xiao, Jingfa; Kang, Yu

2017-01-25

Next-generation sequencing (NGS) technologies have greatly promoted the genomic study of prokaryotes. However, highly fragmented assemblies due to short reads from NGS are still a limiting factor in gaining insights into the genome biology. Reference-assisted tools are promising in genome assembly, but tend to result in false assembly when the assigned reference has extensive rearrangements. Herein, we present GAAP, a genome assembly pipeline for scaffolding based on core-gene-defined Genome Organizational Framework (cGOF) described in our previous study. Instead of assigning references, we use the multiple-reference-derived cGOFs as indexes to assist in order and orientation of the scaffolds and build a skeleton structure, and then use read pairs to extend scaffolds, called local scaffolding, and distinguish between true and chimeric adjacencies in the scaffolds. In our performance tests using both empirical and simulated data of 15 genomes in six species with diverse genome size, complexity, and all three categories of cGOFs, GAAP outcompetes or achieves comparable results when compared to three other reference-assisted programs, AlignGraph, Ragout and MeDuSa. GAAP uses both cGOF and pair-end reads to create assemblies in genomic scale, and performs better than the currently available reference-assisted assembly tools as it recovers more assemblies and makes fewer false locations, especially for species with extensive rearranged genomes. Our method is a promising solution for reconstruction of genome sequence from short reads of NGS.

The influence of addition of ion-pairing acid and organic modifier of the mobile phase on retention and migration of peptides in pressurized planar electrochromatography system with octadecyl silica-based adsorbent.

PubMed

Gwarda, Radosław Ł; Dzido, Tadeusz H

2018-07-13

In our previous papers we have investigated the influence of the mobile phase composition on mechanism of retention, selectivity and efficiency of peptide separation in various high-performance thin-layer chromatography (HPTLC) systems with commercially available silica-based adsorbents. We have also investigated the influence of pH of the mobile phase buffer on migration and separation of peptides in pressurized planar electrochromatography (PPEC). Here we investigate the influence of concentration of ion-pairing additive, and concentration and type of organic modifier of the mobile phase on migration of peptides in PPEC system with octadecyl silica-based adsorbent, and with the same set of the solutes as before. We compare our current results with the results obtained before for similar HPTLC and PPEC systems, and discuss the influence of particular variables on retention, electrophoretic mobility of solutes and electroosmotic flow of the mobile phase. We show, that the final selectivity of peptide separation results from co-influence of all the three factors mentioned. Concentration of organic modifier of the mobile phase, as well as concentration of ion-pairing additive, affect the retention, the electrophoretic mobility, and the electroosmotic flow simultaneously. This makes independent optimization of these factors rather difficult. Anyway PPEC offers much faster separation of peptides with quite different selectivity, in comparison to HPTLC, with similar adsorbents and similar mobile phase composition. However, we also present and discuss the issue of extensive tailing of peptide zones in the PPEC in comparison to similar HPTLC systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Defects Induced Enhancement of Eu3+ Emission in Yttria ( Y2O3:Eu3+)

NASA Astrophysics Data System (ADS)

Jagannathan, R.; Kutty, T.; Kottaisamy, M.; Jeyagopal, P.

1994-11-01

Bixbyite type Y2O3:Eu3+ apart from being the efficient red phosphor extensively used in trichromatic fluorescent lamps, it is a typical system one can apply Jørgensen's refined electron spin pairing theory. This can be used to explain the enhancement in Eu3+ emission intensity observed with the aliovalent substitution in the yttria host matrix. Results based on these are explained qualitatively by considering a simple configurational coordinate model. Futhermore, an insight into the different types of defects induced with the aliovalent substitution in the yttria lattice has become possible with EPR probe.

Molecular recognition of DNA base pairs by the formamido/pyrrole and formamido/imidazole pairings in stacked polyamides

PubMed Central

Buchmueller, Karen L.; Staples, Andrew M.; Uthe, Peter B.; Howard, Cameron M.; Pacheco, Kimberly A. O.; Cox, Kari K.; Henry, James A.; Bailey, Suzanna L.; Horick, Sarah M.; Nguyen, Binh; Wilson, W. David; Lee, Moses

2005-01-01

Polyamides containing an N-terminal formamido (f) group bind to the minor groove of DNA as staggered, antiparallel dimers in a sequence-specific manner. The formamido group increases the affinity and binding site size, and it promotes the molecules to stack in a staggered fashion thereby pairing itself with either a pyrrole (Py) or an imidazole (Im). There has not been a systematic study on the DNA recognition properties of the f/Py and f/Im terminal pairings. These pairings were analyzed here in the context of f-ImPyPy, f-ImPyIm, f-PyPyPy and f-PyPyIm, which contain the central pairing modes, –ImPy– and –PyPy–. The specificity of these triamides towards symmetrical recognition sites allowed for the f/Py and f/Im terminal pairings to be directly compared by SPR, CD and ΔTM experiments. The f/Py pairing, when placed next to the –ImPy– or –PyPy– central pairings, prefers A/T and T/A base pairs to G/C base pairs, suggesting that f/Py has similar DNA recognition specificity to Py/Py. With –ImPy– central pairings, f/Im prefers C/G base pairs (>10 times) to the other Watson–Crick base pairs; therefore, f/Im behaves like the Py/Im pair. However, the f/Im pairing is not selective for the C/G base pair when placed next to the –PyPy– central pairings. PMID:15703305

Biomechanical Evaluation of Standard Versus Extended Proximal Fixation Olecranon Plates for Fixation of Olecranon Fractures.

PubMed

Boden, Allison L; Daly, Charles A; Dalwadi, Poonam P; Boden, Stephanie A; Hutton, William C; Muppavarapu, Raghuveer C; Gottschalk, Michael B

2018-01-01

Small olecranon fractures present a significant challenge for fixation, which has resulted in development of plates with proximal extension. Olecranon-specific plates with proximal extensions are widely thought to offer superior fixation of small proximal fragments but have distinct disadvantages: larger dissection, increased hardware prominence, and the increased possibility of impingement. Previous biomechanical studies of olecranon fracture fixation have compared methods of fracture fixation, but to date there have been no studies defining olecranon plate fixation strength for standard versus extended olecranon plates. The purpose of this study is to evaluate the biomechanical utility of the extended plate for treatment of olecranon fractures. Sixteen matched pairs of fresh-frozen human cadaveric elbows were used. Of the 16, 8 matched pairs received a transverse osteotomy including 25% and 8 including 50% of the articular surface on the proximal fragment. One elbow from each pair was randomly assigned to a standard-length plate, and the other elbow in the pair received the extended-length plate, for fixation of the fracture. The ulnae were cyclically loaded and subsequently loaded to failure, with ultimate load, number of cycles, and gap formation recorded. There was no statistically significant difference between the standard and extended fixation plates in simple transverse fractures at either 25% or 50% from the proximal most portion of the articular surface of the olecranon. Standard fixation plates are sufficient for the fixation of small transverse fractures, but caution should be utilized particularly with comminution and nontransverse fracture patterns.

Base-Pairing Energies of Protonated Nucleoside Base Pairs of dCyd and m5dCyd: Implications for the Stability of DNA i-Motif Conformations

NASA Astrophysics Data System (ADS)

Yang, Bo; Rodgers, M. T.

2015-08-01

Hypermethylation of cytosine in expanded (CCG)n•(CGG)n trinucleotide repeats results in Fragile X syndrome, the most common cause of inherited mental retardation. The (CCG)n•(CGG)n repeats adopt i-motif conformations that are preferentially stabilized by base-pairing interactions of protonated base pairs of cytosine. Here we investigate the effects of 5-methylation and the sugar moiety on the base-pairing energies (BPEs) of protonated cytosine base pairs by examining protonated nucleoside base pairs of 2'-deoxycytidine (dCyd) and 5-methyl-2'-deoxycytidine (m5dCyd) using threshold collision-induced dissociation techniques. 5-Methylation of a single or both cytosine residues leads to very small change in the BPE. However, the accumulated effect may be dramatic in diseased state trinucleotide repeats where many methylated base pairs may be present. The BPEs of the protonated nucleoside base pairs examined here significantly exceed those of Watson-Crick dGuo•dCyd and neutral dCyd•dCyd base pairs, such that these base-pairing interactions provide the major forces responsible for stabilization of DNA i-motif conformations. Compared with isolated protonated nucleobase pairs of cytosine and 1-methylcytosine, the 2'-deoxyribose sugar produces an effect similar to the 1-methyl substituent, and leads to a slight decrease in the BPE. These results suggest that the base-pairing interactions may be slightly weaker in nucleic acids, but that the extended backbone is likely to exert a relatively small effect on the total BPE. The proton affinity (PA) of m5dCyd is also determined by competitive analysis of the primary dissociation pathways that occur in parallel for the protonated (m5dCyd)H+(dCyd) nucleoside base pair and the absolute PA of dCyd previously reported.

Metal-mediated DNA base pairing: alternatives to hydrogen-bonded Watson-Crick base pairs.

PubMed

Takezawa, Yusuke; Shionoya, Mitsuhiko

2012-12-18

With its capacity to store and transfer the genetic information within a sequence of monomers, DNA forms its central role in chemical evolution through replication and amplification. This elegant behavior is largely based on highly specific molecular recognition between nucleobases through the specific hydrogen bonds in the Watson-Crick base pairing system. While the native base pairs have been amazingly sophisticated through the long history of evolution, synthetic chemists have devoted considerable efforts to create alternative base pairing systems in recent decades. Most of these new systems were designed based on the shape complementarity of the pairs or the rearrangement of hydrogen-bonding patterns. We wondered whether metal coordination could serve as an alternative driving force for DNA base pairing and why hydrogen bonding was selected on Earth in the course of molecular evolution. Therefore, we envisioned an alternative design strategy: we replaced hydrogen bonding with another important scheme in biological systems, metal-coordination bonding. In this Account, we provide an overview of the chemistry of metal-mediated base pairing including basic concepts, molecular design, characteristic structures and properties, and possible applications of DNA-based molecular systems. We describe several examples of artificial metal-mediated base pairs, such as Cu(2+)-mediated hydroxypyridone base pair, H-Cu(2+)-H (where H denotes a hydroxypyridone-bearing nucleoside), developed by us and other researchers. To design the metallo-base pairs we carefully chose appropriate combinations of ligand-bearing nucleosides and metal ions. As expected from their stronger bonding through metal coordination, DNA duplexes possessing metallo-base pairs exhibited higher thermal stability than natural hydrogen-bonded DNAs. Furthermore, we could also use metal-mediated base pairs to construct or induce other high-order structures. These features could lead to metal-responsive functional DNA molecules such as artificial DNAzymes and DNA machines. In addition, the metallo-base pairing system is a powerful tool for the construction of homogeneous and heterogeneous metal arrays, which can lead to DNA-based nanomaterials such as electronic wires and magnetic devices. Recently researchers have investigated these systems as enzyme replacements, which may offer an additional contribution to chemical biology and synthetic biology through the expansion of the genetic alphabet.

Theoretical determination of one-electron redox potentials for DNA bases, base pairs, and stacks.

PubMed

Paukku, Y; Hill, G

2011-05-12

Electron affinities, ionization potentials, and redox potentials for DNA bases, base pairs, and N-methylated derivatives are computed at the DFT/M06-2X/6-31++G(d,p) level of theory. Redox properties of a guanine-guanine stack model are explored as well. Reduction and oxidation potentials are in good agreement with the experimental ones. Electron affinities of base pairs were found to be negative. Methylation of canonical bases affects the ionization potentials the most. Base pair formation and base stacking lower ionization potentials by 0.3 eV. Pairing of guanine with the 5-methylcytosine does not seem to influence the redox properties of this base pair much.

Pulsar Pair Cascades in Magnetic Fields with Offset Polar Caps

NASA Technical Reports Server (NTRS)

Harding, Alice K.; Muslimov, Alex G.

2012-01-01

Neutron star magnetic fields may have polar caps (PC) that are offset from the dipole axis, through field-line sweepback near the light cylinder or non-symmetric currents within the star. The effects of such offsets on electron-positron pair cascades are investigated, using simple models of dipole magnetic fields with small distortions that shift the PCs by different amounts or directions. Using a Monte Carlo pair cascade simulation, we explore the changes in the pair spectrum, multiplicity and energy flux across the PC, as well as the trends in pair flux and pair energy flux with spin-down luminosity, L(sub sd). We also give an estimate of the distribution of heating flux from returning positrons on the PC for different offsets. We find that even modest offsets can produce significant increases in pair multiplicity, especially for pulsars that are near or beyond the pair death lines for centered PCs, primarily because of higher accelerating fields. Pair spectra cover several decades in energy, with the spectral range of millisecond pulsars (MSPs) two orders of magnitude higher than for normal pulsars, and PC offsets allow significant extension of all spectra to lower pair energies. We find that the total PC pair luminosity L(sub pair) is proportional to L(sub sd), with L(sub pair) approximates 10(exp -3) L(sub sd) for normal pulsars and L(sub pair) approximates 10(exp -2) L(sub sd) for MSPs. Remarkably, the total PC heating luminosity for even large offsets increases by less than a factor of two, even though the PC area increases by much larger factors, because most of the heating occurs near the magnetic axis.

Base pairing and base mis-pairing in nucleic acids

NASA Technical Reports Server (NTRS)

Wang, A. H. J.; Rich, A.

1986-01-01

In recent years we have learned that DNA is conformationally active. It can exist in a number of different stable conformations including both right-handed and left-handed forms. Using single crystal X-ray diffraction analysis we are able to discover not only additional conformations of the nucleic acids but also different types of hydrogen bonded base-base interactions. Although Watson-Crick base pairings are the predominant type of interaction in double helical DNA, they are not the only types. Recently, we have been able to examine mismatching of guanine-thymine base pairs in left-handed Z-DNA at atomic resolution (1A). A minimum amount of distortion of the sugar phosphate backbone is found in the G x T pairing in which the bases are held together by two hydrogen bonds in the wobble pairing interaction. Because of the high resolution of the analysis we can visualize water molecules which fill in to accommodate the other hydrogen bonding positions in the bases which are not used in the base-base interactions. Studies on other DNA oligomers have revealed that other types of non-Watson-Crick hydrogen bonding interactions can occur. In the structure of a DNA octamer with the sequence d(GCGTACGC) complexed to an antibiotic triostin A, it was found that the two central AT base pairs are held together by Hoogsteen rather than Watson-Crick base pairs. Similarly, the G x C base pairs at the ends are also Hoogsteen rather than Watson-Crick pairing. Hoogsteen base pairs make a modified helix which is distinct from the Watson-Crick double helix.

Do cervical collars and cervicothoracic orthoses effectively stabilize the injured cervical spine? A biomechanical investigation.

PubMed

Ivancic, Paul C

2013-06-01

In vitro biomechanical study. Our objective was to determine the effectiveness of cervical collars and cervicothoracic orthoses for stabilizing clinically relevant, experimentally produced cervical spine injuries. Most previous in vitro studies of cervical orthoses used a simplified injury model with all ligaments transected at a single spinal level, which differs from real-life neck injuries. Human volunteer studies are limited to measuring only sagittal motions or 3-dimensional motions only of the head or 1 or 2 spinal levels. Three-plane flexibility tests were performed to evaluate 2 cervical collars (Vista Collar and Vista Multipost Collar) and 2 cervicothoracic orthoses (Vista TS and Vista TS4) using a skull-neck-thorax model with 8 injured cervical spine specimens (manufacturer of orthoses: Aspen Medical Products Inc, Irvine, CA). The injuries consisted of flexion-compression at the lower cervical spine and extension-compression at superior spinal levels. Pair-wise repeated measures analysis of variance (P < 0.05) and Bonferroni post hoc tests determined significant differences in average range of motions of the head relative to the base, C7 or T1, among experimental conditions. RESULTS.: All orthoses significantly reduced unrestricted head/base flexion and extension. The orthoses allowed between 8.4% and 25.8% of unrestricted head/base motion in flexion/extension, 57.8% to 75.5% in axial rotation, and 53.8% to 73.7% in lateral bending. The average percentages of unrestricted motion allowed by the Vista Collar, Vista Multipost Collar, Vista TS, and Vista TS4 were: 14.0, 9.7, 6.1, and 4.7, respectively, for middle cervical spine extension and 13.2, 11.8, 3.3, and 0.4, respectively, for lower cervical spine flexion. Successive increases in immobilization were observed from Vista Collar to Vista Multipost Collar, Vista TS, and Vista TS4 in extension at the injured middle cervical spine and in flexion at the injured lower cervical spine. Our results may assist clinicians in selecting the most appropriate orthosis based upon patient-specific cervical spine injuries.

Hidden in Plain Sight: Subtle Effects of the 8-Oxoguanine Lesion on the Structure, Dynamics, and Thermodynamics of a 15-Base-Pair Oligodeoxynucleotide Duplex†

PubMed Central

Crenshaw, Charisse M.; Wade, Jacqueline E.; Arthanari, Haribabu; Frueh, Dominique; Lane, Benjamin F.; Núñez, Megan E.

2011-01-01

The base lesion 8-oxoguanine is formed readily by oxidation of DNA, potentially leading to G→T transversion mutations. Despite the apparent similarity of 8-oxoguanine-cytosine base pairs to normal guanine-cytosine base pairs, cellular base excision repair systems effectively recognize the lesion base. Here we apply several techniques to examine a single 8-oxoguanine lesion at the center of a nonpalindromic 15-mer duplex oligonucleotide in an effort to determine what, if anything, distinguishes an 8-oxoguanine-cytosine base pair from a normal base pair. The lesion duplex is globally almost indistinguishable from the unmodified parent duplex using CD spectroscopy and UV melting thermodynamics. The DNA mismatch-detecting photocleavage agent Rh(bpy)2chrysi3+ cleaves only weakly and nonspecifically, revealing that the 8oxoG-C pair is locally stable at the level of the individual base pairs. NMR spectra are also consistent with a well-conserved B-form duplex structure. In the 2D NOESY spectra, base-sugar and imino-imino crosspeaks are strikingly similar between parent and lesion duplexes. Changes in chemical shift due to the 8oxoG lesion are localized to its complementary cytosine and to the 2–3 base pairs immediately flanking the lesion on the lesion strand. Residues further removed from the lesion are shown to be unperturbed by its presence. Notably, imino exchange experiments indicate that the 8-oxoguanine-cytosine pair is strong and stable, with an apparent equilibrium constant for opening equal to that of other internal guanine-cytosine base pairs, on the order of 10−6. This collection of experiments shows that the 8-oxoguanine-cytosine base pair is incredibly stable and similar to the native pair. PMID:21902242

Fermion Cooper pairing with unequal masses: Standard field theory approach

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

He Lianyi; Jin Meng; Zhuang Pengfei

Fermion Cooper pairing with unequal masses is investigated in a standard field theory approach. We derived the superfluid density and Meissner mass squared of the U(1) gauge field in a general two-species model and found that the often used proportional relation between the two quantities is broken when the fermion masses are unequal. In the weak-coupling region, the superfluid density is always negative but the Meissner mass squared becomes mostly positive when the mass ratio between the pairing fermions is large enough. We established a proper momentum configuration of the LOFF pairing with unequal masses and showed that the LOFFmore » state is energetically favored due to the negative superfluid density. The single-plane-wave LOFF state is physically equivalent to an anisotropic state with a spontaneously generated superflow. The extension to a finite-range interaction is briefly discussed.« less

Assessment of DNA Contamination in RNA Samples Based on Ribosomal DNA

PubMed Central

Hashemipetroudi, Seyyed Hamidreza; Nematzadeh, Ghorbanali; Ahmadian, Gholamreza; Yamchi, Ahad; Kuhlmann, Markus

2018-01-01

One method extensively used for the quantification of gene expression changes and transcript abundances is reverse-transcription quantitative real-time PCR (RT-qPCR). It provides accurate, sensitive, reliable, and reproducible results. Several factors can affect the sensitivity and specificity of RT-qPCR. Residual genomic DNA (gDNA) contaminating RNA samples is one of them. In gene expression analysis, non-specific amplification due to gDNA contamination will overestimate the abundance of transcript levels and can affect the RT-qPCR results. Generally, gDNA is detected by qRT-PCR using primer pairs annealing to intergenic regions or an intron of the gene of interest. Unfortunately, intron/exon annotations are not yet known for all genes from vertebrate, bacteria, protist, fungi, plant, and invertebrate metazoan species. Here we present a protocol for detection of gDNA contamination in RNA samples by using ribosomal DNA (rDNA)-based primers. The method is based on the unique features of rDNA: their multigene nature, highly conserved sequences, and high frequency in the genome. Also as a case study, a unique set of primers were designed based on the conserved region of ribosomal DNA (rDNA) in the Poaceae family. The universality of these primer pairs was tested by melt curve analysis and agarose gel electrophoresis. Although our method explains how rDNA-based primers can be applied for the gDNA contamination assay in the Poaceae family, it could be easily used to other prokaryote and eukaryote species PMID:29443017

Geminga: A cooling superfluid neutron star

NASA Technical Reports Server (NTRS)

Page, Dany

1994-01-01

We compare the recent temperature estimate for Geminga with neutron star cooling models. Because of its age (approximately 3.4 x 10(exp 5) yr), Geminga is in the photon cooling era. We show that its surface temperature (approximately 5.2 x 10(exp 5) K) can be understood by both types of neutrino cooling scenarios, i.e., slow neutrino cooling by the modified Urca process or fast neutrino cooling by the direct Urca process or by some exotic matter, and thus does not allow us to discriminate between these two competing schemes. However, for both types of scenarios, agreement with the observed temperature can only be obtained if baryon pairing is present in most, if not all, of the core of the star. Within the slow neutrino cooling scenario, early neutrino cooling is not sufficient to explain the observed low temperature, and extensive pairing in the core is necessary to reduce the specific heat and increase the cooling rate in the present photon cooling era. Within all the fast neutrino cooling scenarios, pairing is necessary throughout the whole core to control the enormous early neutrino emission which, without pairing suppression, would result in a surface temperature at the present time much lower than observed. We also comment on the recent temperature estimates for PSR 0656+14 and PSR 1055-52, which pertain to the same photon cooling era. If one assumes that all neutron stars undergo fast neutrino cooling, then these two objects also provide evidence for extensive baryon pairing in their core; but observational uncertainties also permit a more conservative interpretation, with slow neutrino emission and no pairing at all. We argue though that observational evidence for the slow neutrino cooling model (the 'standard' model) is in fact very dim and that the interpretation of the surface temperature of all neutron stars could be done with a reasonable theoretical a priori within the fast neutrino cooling scenarios only. In this case, Geminga, PSR 0656+14, and PSR 1055-52 all show evidence of baryon pairing down to their very centers.

Structural landscape of base pairs containing post-transcriptional modifications in RNA

PubMed Central

Seelam, Preethi P.; Sharma, Purshotam

2017-01-01

Base pairs involving post-transcriptionally modified nucleobases are believed to play important roles in a wide variety of functional RNAs. Here we present our attempts toward understanding the structural and functional role of naturally occurring modified base pairs using a combination of X-ray crystal structure database analysis, sequence analysis, and advanced quantum chemical methods. Our bioinformatics analysis reveals that despite their presence in all major secondary structural elements, modified base pairs are most prevalent in tRNA crystal structures and most commonly involve guanine or uridine modifications. Further, analysis of tRNA sequences reveals additional examples of modified base pairs at structurally conserved tRNA regions and highlights the conservation patterns of these base pairs in three domains of life. Comparison of structures and binding energies of modified base pairs with their unmodified counterparts, using quantum chemical methods, allowed us to classify the base modifications in terms of the nature of their electronic structure effects on base-pairing. Analysis of specific structural contexts of modified base pairs in RNA crystal structures revealed several interesting scenarios, including those at the tRNA:rRNA interface, antibiotic-binding sites on the ribosome, and the three-way junctions within tRNA. These scenarios, when analyzed in the context of available experimental data, allowed us to correlate the occurrence and strength of modified base pairs with their specific functional roles. Overall, our study highlights the structural importance of modified base pairs in RNA and points toward the need for greater appreciation of the role of modified bases and their interactions, in the context of many biological processes involving RNA. PMID:28341704

Stability of non-Watson-Crick G-A/A-G base pair in synthetic DNA and RNA oligonucleotides.

PubMed

Ito, Yuko; Sone, Yumiko; Mizutani, Takaharu

2004-03-01

A non-Watson-Crick G-A/A-G base pair is found in SECIS (selenocysteine-insertion sequence) element in the 3'-untranslated region of Se-protein mRNAs and in the functional site of the hammerhead ribozyme. We studied the stability of G-A/A-G base pair (bold) in 17mer GT(U)GACGGAAACCGGAAC synthetic DNA and RNA oligonucleotides by thermal melting experiments and gel electrophoresis. The measured Tm value of DNA oligonucleotide having G-A/A-G pair showed an intermediate value (58 degrees C) between that of Watson-Crick G-C/C-G base pair (75 degrees C) and that of G-G/A-A of non-base-pair (40 degrees C). Similar thermal melting patterns were obtained with RNA oligonucleotides. This result indicates that the secondary structure of oligonucleotide having G-A/A-G base pair is looser than that of the G-C type Watson-Crick base pair. In the comparison between RNA and DNA having G-A/A-G base pair, the Tm value of the RNA oligonucleotide was 11 degrees C lower than that of DNA, indicating that DNA has a more rigid structure than RNA. The stained pattern of oligonucleotide on polyacrylamide gel clarified that the mobility of the DNA oligonucleotide G-A/A-G base pair changed according to the urea concentration from the rigid state (near the mobility of G-C/C-G oligonucleotide) in the absence of urea to the random state (near the mobility of G-G/A-A oligonucleotide) in 7 M urea. However, the RNA oligonucleotide with G-A/A-G pair moved at an intermediate mobility between that of oligonucleotide with G-C/C-G and of the oligonucleotide with G-G/A-A, and the mobility pattern did not depend on urea concentration. Thus, DNA and RNA oligonucleotides with the G-A/A-G base pair showed a pattern indicating an intermediate structure between the rigid Watson-Crick base pair and the random structure of non-base pair. RNA with G-A/A-G base pair has the intermediate structure not influenced by urea concentration. Finally, this study indicated that the intermediate rigidity imparted by Non-Watson-Crick base pair in SECIS element plays an important role in the selenocysteine expression by UGA codon.

Atomistic model of the spider silk nanostructure

NASA Astrophysics Data System (ADS)

Keten, Sinan; Buehler, Markus J.

2010-04-01

Spider silk is an ultrastrong and extensible self-assembling biopolymer that outperforms the mechanical characteristics of many synthetic materials including steel. Here we report atomic-level structures that represent aggregates of MaSp1 proteins from the N. Clavipes silk sequence based on a bottom-up computational approach using replica exchange molecular dynamics. We discover that poly-alanine regions predominantly form distinct and orderly beta-sheet crystal domains while disorderly structures are formed by poly-glycine repeats, resembling 31-helices. These could be the molecular source of the large semicrystalline fraction observed in silks, and also form the basis of the so-called "prestretched" molecular configuration. Our structures are validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots, alpha-carbon atomic distances, as well as secondary structure content.

Genotoxicity of Tri- and Hexavalent Chromium Compounds In Vivo and Their Modes of Action on DNA Damage In Vitro

PubMed Central

Fang, Zhijia; Zhao, Min; Zhen, Hong; Chen, Lifeng; Shi, Ping; Huang, Zhiwei

2014-01-01

Chromium occurs mostly in tri- and hexavalent states in the environment. Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements. In the present work, we report that they both induce genetic mutations in yeast cells. They both also cause DNA damage in both yeast and Jurkat cells and the effect of Cr(III) is greater than that of Cr(VI). We further show that Cr(III) and Cr(VI) cause DNA damage through different mechanisms. Cr(VI) intercalates DNA and Cr(III) interferes base pair stacking. Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo. PMID:25111056

Coprimeness-preserving non-integrable extension to the two-dimensional discrete Toda lattice equation

NASA Astrophysics Data System (ADS)

Kamiya, Ryo; Kanki, Masataka; Mase, Takafumi; Tokihiro, Tetsuji

2017-01-01

We introduce a so-called coprimeness-preserving non-integrable extension to the two-dimensional Toda lattice equation. We believe that this equation is the first example of such discrete equations defined over a three-dimensional lattice. We prove that all the iterates of the equation are irreducible Laurent polynomials of the initial data and that every pair of two iterates is co-prime, which indicate confined singularities of the equation. By reducing the equation to two- or one-dimensional lattices, we obtain coprimeness-preserving non-integrable extensions to the one-dimensional Toda lattice equation and the Somos-4 recurrence.

Whole exome sequencing to estimate alloreactivity potential between donors and recipients in stem cell transplantation.

PubMed

Sampson, Juliana K; Sheth, Nihar U; Koparde, Vishal N; Scalora, Allison F; Serrano, Myrna G; Lee, Vladimir; Roberts, Catherine H; Jameson-Lee, Max; Ferreira-Gonzalez, Andrea; Manjili, Masoud H; Buck, Gregory A; Neale, Michael C; Toor, Amir A

2014-08-01

Whole exome sequencing (WES) was performed on stem cell transplant donor-recipient (D-R) pairs to determine the extent of potential antigenic variation at a molecular level. In a small cohort of D-R pairs, a high frequency of sequence variation was observed between the donor and recipient exomes independent of human leucocyte antigen (HLA) matching. Nonsynonymous, nonconservative single nucleotide polymorphisms were approximately twice as frequent in HLA-matched unrelated, compared with related D-R pairs. When mapped to individual chromosomes, these polymorphic nucleotides were uniformly distributed across the entire exome. In conclusion, WES reveals extensive nucleotide sequence variation in the exomes of HLA-matched donors and recipients. © 2014 John Wiley & Sons Ltd.

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

Cable, J.W.

The diffuse scattering of neutrons from magnetic materials provides unique and important information regarding the spatial correlations of the atoms and the spins. Such measurements have been extensively applied to magnetically ordered systems, such as the ferromagnetic binary alloys, for which the observed correlations describe the magnetic moment fluctuations associated with local environment effects. With the advent of polarization analysis, these techniques are increasingly being applied to study disordered paramagnetic systems such as the spin-glasses and the diluted magnetic semiconductors. The spin-pair correlations obtained are essential in understanding the exchange interactions of such systems. In this paper, we describe recentmore » neutron diffuse scattering results on the atom-pair and spin-pair correlations in some of these disordered magnetic systems. 56 refs.« less

Precise location of San Andreas Fault tremors near Cholame, California using seismometer clusters: Slip on the deep extension of the fault?

USGS Publications Warehouse

Shelly, D.R.; Ellsworth, W.L.; Ryberg, T.; Haberland, C.; Fuis, G.S.; Murphy, J.; Nadeau, R.M.; Burgmann, R.

2009-01-01

We examine a 24-hour period of active San Andreas Fault (SAF) tremor and show that this tremor is largely composed of repeated similar events. Utilizing this similarity, we locate the subset of the tremor with waveforms similar to an identified low frequency earthquake (LFE) "master template," located using P and S wave arrivals to be ???26 km deep. To compensate for low signal-to-noise, we estimate event-pair differential times at "clusters" of nearby stations rather than at single stations. We find that the locations form a near-linear structure in map view, striking parallel to the SAF and near the surface trace. Therefore, we suggest that at least a portion of the tremor occurs on the deep extension of the fault, likely reflecting shear slip, similar to subduction zone tremor. If so, the SAF may extend to the base of the crust, ???10 km below the deepest regular earthquakes on the fault. ?? 2009 by the American Geophysical Union.

Enhancing graphical literacy skills in the high school science classroom via authentic, intensive data collection and graphical representation exposure

NASA Astrophysics Data System (ADS)

Palmeri, Anthony

This research project was developed to provide extensive practice and exposure to data collection and data representation in a high school science classroom. The student population engaged in this study included 40 high school sophomores enrolled in two microbiology classes. Laboratory investigations and activities were deliberately designed to include quantitative data collection that necessitated organization and graphical representation. These activities were embedded into the curriculum and conducted in conjunction with the normal and expected course content, rather than as a separate entity. It was expected that routine practice with graph construction and interpretation would result in improved competency when graphing data and proficiency in analyzing graphs. To objectively test the effectiveness in achieving this goal, a pre-test and post-test that included graph construction, interpretation, interpolation, extrapolation, and analysis was administered. Based on the results of a paired T-Test, graphical literacy was significantly enhanced by extensive practice and exposure to data representation.

pKa shifting in double-stranded RNA is highly dependent upon nearest neighbors and bulge positioning.

PubMed

Wilcox, Jennifer L; Bevilacqua, Philip C

2013-10-22

Shifting of pKa's in RNA is important for many biological processes; however, the driving forces responsible for shifting are not well understood. Herein, we determine how structural environments surrounding protonated bases affect pKa shifting in double-stranded RNA (dsRNA). Using (31)P NMR, we determined the pKa of the adenine in an A(+)·C base pair in various sequence and structural environments. We found a significant dependence of pKa on the base pairing strength of nearest neighbors and the location of a nearby bulge. Increasing nearest neighbor base pairing strength shifted the pKa of the adenine in an A(+)·C base pair higher by an additional 1.6 pKa units, from 6.5 to 8.1, which is well above neutrality. The addition of a bulge two base pairs away from a protonated A(+)·C base pair shifted the pKa by only ~0.5 units less than a perfectly base paired hairpin; however, positioning the bulge just one base pair away from the A(+)·C base pair prohibited formation of the protonated base pair as well as several flanking base pairs. Comparison of data collected at 25 °C and 100 mM KCl to biological temperature and Mg(2+) concentration revealed only slight pKa changes, suggesting that similar sequence contexts in biological systems have the potential to be protonated at biological pH. We present a general model to aid in the determination of the roles protonated bases may play in various dsRNA-mediated processes including ADAR editing, miRNA processing, programmed ribosomal frameshifting, and general acid-base catalysis in ribozymes.

An asymmetric pair of vortices adjacent to a spinning cylinder

NASA Astrophysics Data System (ADS)

Iosilevskii, G.; Seginer, A.

The two-dimensional flow field over a spinning circular cylinder is analyzed using an extension of the Foeppl method. Equilibrium equations for two asymmetric point vortices in the wake of the cylinder are solved for a case when both vortices are equidistant from the cylinder. The two Foeppl solutions for the cylinder are presented. It is observed that the spin does not affect the angle between the two vortices; however, it displaces the vortex pair in the spin direction and the sinus of the displacement angle is proportional to the spin rate.

Database of non-canonical base pairs found in known RNA structures

NASA Technical Reports Server (NTRS)

Nagaswamy, U.; Voss, N.; Zhang, Z.; Fox, G. E.

2000-01-01

Atomic resolution RNA structures are being published at an increasing rate. It is common to find a modest number of non-canonical base pairs in these structures in addition to the usual Watson-Crick pairs. This database summarizes the occurrence of these rare base pairs in accordance with standard nomenclature. The database, http://prion.bchs.uh.edu/, contains information such as sequence context, sugar pucker conformation, anti / syn base conformations, chemical shift, p K (a)values, melting temperature and free energy. Of the 29 anticipated pairs with two or more hydrogen bonds, 20 have been encountered to date. In addition, four unexpected pairs with two hydrogen bonds have been reported bringing the total to 24. Single hydrogen bond versions of five of the expected geometries have been encountered among the single hydrogen bond interactions. In addition, 18 different types of base triplets have been encountered, each of which involves three to six hydrogen bonds. The vast majority of the rare base pairs are antiparallel with the bases in the anti configuration relative to the ribose. The most common are the GU wobble, the Sheared GA pair, the Reverse Hoogsteen pair and the GA imino pair.

Astronaut Rhea Seddon works on flyswatter-like snagging device

NASA Technical Reports Server (NTRS)

1985-01-01

Astronaut Rhea Seddon begins works on flyswatter-like snagging device to be used as an extension to the remote manipulator system (RMS) arm on Discovery for an attempt to trip a lever on the troubled Syncom-IV satellite. She is seated on the floor of the aft flight deck with a pair of scissors in her mouth. She is using an exacto knife to cut the extension out of plastic. Her jacket is floating in the bottom right edge of the frame.

Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs

PubMed Central

2017-01-01

Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package. PMID:29107980

Determination of the Point-Spread Function for the FERMI Large Area Telescope from On-Orbit Data and Limits on Pair Halos of Active Galactic Nuclei

DOE PAGES

Ackermann, M.; Ajello, M.; Allafort, A.; ...

2013-02-15

We present the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope is a pair-conversion telescope designed to detect photons with energies from ≈20 MeV to >300 GeV. The pre-launch response functions of the LAT were determined through extensive Monte Carlo simulations and beam tests. The point-spread function (PSF) characterizing the angular distribution of reconstructed photons as a function of energy and geometry in the detector is determined here from two years of on-orbit data by examining the distributions of γ rays from pulsars and active galactic nuclei (AGNs). Above 3 GeV, the PSF is found to be broadermore » than the pre-launch PSF. We checked for dependence of the PSF on the class of γ-ray source and observation epoch and found none. We also investigated several possible spatial models for pair-halo emission around BL Lac AGNs. Finally, we found no evidence for a component with spatial extension larger than the PSF and set upper limits on the amplitude of halo emission in stacked images of low- and high-redshift BL Lac AGNs and the TeV blazars 1ES0229+200 and 1ES0347–121.« less

Pairing broadband noise with cortical stimulation induces extensive suppression of ascending sensory activity

NASA Astrophysics Data System (ADS)

Markovitz, Craig D.; Hogan, Patrick S.; Wesen, Kyle A.; Lim, Hubert H.

2015-04-01

Objective. The corticofugal system can alter coding along the ascending sensory pathway. Within the auditory system, electrical stimulation of the auditory cortex (AC) paired with a pure tone can cause egocentric shifts in the tuning of auditory neurons, making them more sensitive to the pure tone frequency. Since tinnitus has been linked with hyperactivity across auditory neurons, we sought to develop a new neuromodulation approach that could suppress a wide range of neurons rather than enhance specific frequency-tuned neurons. Approach. We performed experiments in the guinea pig to assess the effects of cortical stimulation paired with broadband noise (PN-Stim) on ascending auditory activity within the central nucleus of the inferior colliculus (CNIC), a widely studied region for AC stimulation paradigms. Main results. All eight stimulated AC subregions induced extensive suppression of activity across the CNIC that was not possible with noise stimulation alone. This suppression built up over time and remained after the PN-Stim paradigm. Significance. We propose that the corticofugal system is designed to decrease the brain’s input gain to irrelevant stimuli and PN-Stim is able to artificially amplify this effect to suppress neural firing across the auditory system. The PN-Stim concept may have potential for treating tinnitus and other neurological disorders.

Fidelity study of the superconducting phase diagram in the two-dimensional single-band Hubbard model

NASA Astrophysics Data System (ADS)

Jia, C. J.; Moritz, B.; Chen, C.-C.; Shastry, B. Sriram; Devereaux, T. P.

2011-09-01

Extensive numerical studies have demonstrated that the two-dimensional single-band Hubbard model contains much of the key physics in cuprate high-temperature superconductors. However, there is no definitive proof that the Hubbard model truly possesses a superconducting ground state or, if it does, of how it depends on model parameters. To answer these longstanding questions, we study an extension of the Hubbard model including an infinite-range d-wave pair field term, which precipitates a superconducting state in the d-wave channel. Using exact diagonalization on 16-site square clusters, we study the evolution of the ground state as a function of the strength of the pairing term. This is achieved by monitoring the fidelity metric of the ground state, as well as determining the ratio between the two largest eigenvalues of the d-wave pair/spin/charge-density matrices. The calculations show a d-wave superconducting ground state in doped clusters bracketed by a strong antiferromagnetic state at half filling controlled by the Coulomb repulsion U and a weak short-range checkerboard charge ordered state at larger hole doping controlled by the next-nearest-neighbor hopping t'. We also demonstrate that negative t' plays an important role in facilitating d-wave superconductivity.

Droplet Array-Based 3D Coculture System for High-Throughput Tumor Angiogenesis Assay.

PubMed

Du, Xiaohui; Li, Wanming; Du, Guansheng; Cho, Hansang; Yu, Min; Fang, Qun; Lee, Luke P; Fang, Jin

2018-03-06

Angiogenesis is critical for tumor progression and metastasis, and it progresses through orchestral multicellular interactions. Thus, there is urgent demand for high-throughput tumor angiogenesis assays for concurrent examination of multiple factors. For investigating tumor angiogenesis, we developed a microfluidic droplet array-based cell-coculture system comprising a two-layer polydimethylsiloxane chip featuring 6 × 9 paired-well arrays and an automated droplet-manipulation device. In each droplet-pair unit, tumor cells were cultured in 3D in one droplet by mixing cell suspensions with Matrigel, and in the other droplet, human umbilical vein endothelial cells (HUVECs) were cultured in 2D. Droplets were fused by a newly developed fusion method, and tumor angiogenesis was assayed by coculturing tumor cells and HUVECs in the fused droplet units. The 3D-cultured tumor cells formed aggregates harboring a hypoxic center-as observed in vivo-and secreted more vascular endothelial growth factor (VEGF) and more strongly induced HUVEC tubule formation than did 2D-cultured tumor cells. Our single array supported 54 assays in parallel. The angiogenic potentials of distinct tumor cells and their differential responses to antiangiogenesis agent, Fingolimod, could be investigated without mutual interference in a single array. Our droplet-based assay is convenient to evaluate multicellular interaction in high throughput in the context of tumor sprouting angiogenesis, and we envision that the assay can be extensively implementable for studying other cell-cell interactions.

Personalized Age Progression with Bi-Level Aging Dictionary Learning.

PubMed

Shu, Xiangbo; Tang, Jinhui; Li, Zechao; Lai, Hanjiang; Zhang, Liyan; Yan, Shuicheng

2018-04-01

Age progression is defined as aesthetically re-rendering the aging face at any future age for an individual face. In this work, we aim to automatically render aging faces in a personalized way. Basically, for each age group, we learn an aging dictionary to reveal its aging characteristics (e.g., wrinkles), where the dictionary bases corresponding to the same index yet from two neighboring aging dictionaries form a particular aging pattern cross these two age groups, and a linear combination of all these patterns expresses a particular personalized aging process. Moreover, two factors are taken into consideration in the dictionary learning process. First, beyond the aging dictionaries, each person may have extra personalized facial characteristics, e.g., mole, which are invariant in the aging process. Second, it is challenging or even impossible to collect faces of all age groups for a particular person, yet much easier and more practical to get face pairs from neighboring age groups. To this end, we propose a novel Bi-level Dictionary Learning based Personalized Age Progression (BDL-PAP) method. Here, bi-level dictionary learning is formulated to learn the aging dictionaries based on face pairs from neighboring age groups. Extensive experiments well demonstrate the advantages of the proposed BDL-PAP over other state-of-the-arts in term of personalized age progression, as well as the performance gain for cross-age face verification by synthesizing aging faces.

DNA base dimers are stabilized by hydrogen-bonding interactions including non-Watson-Crick pairing near graphite surfaces.

PubMed

Shankar, Akshaya; Jagota, Anand; Mittal, Jeetain

2012-10-11

Single- and double-stranded DNA are increasingly being paired with surfaces and nanoparticles for numerous applications, such as sensing, imaging, and drug delivery. Unlike the majority of DNA structures in bulk that are stabilized by canonical Watson-Crick pairing between Ade-Thy and Gua-Cyt, those adsorbed on surfaces are often stabilized by noncanonical base pairing, quartet formation, and base-surface stacking. Not much is known about these kinds of interactions. To build an understanding of the role of non-Watson-Crick pairing on DNA behavior near surfaces, one requires basic information on DNA base pair stacking and hydrogen-bonding interactions. All-atom molecular simulations of DNA bases in two cases--in bulk water and strongly adsorbed on a graphite surface--are conducted to study the relative strengths of stacking and hydrogen bond interactions for each of the 10 possible combinations of base pairs. The key information obtained from these simulations is the free energy as a function of distance between two bases in a pair. We find that stacking interactions exert the dominant influence on the stability of DNA base pairs in bulk water as expected. The strength of stability for these stacking interactions is found to decrease in the order Gua-Gua > Ade-Gua > Ade-Ade > Gua-Thy > Gua-Cyt > Ade-Thy > Ade-Cyt > Thy-Thy > Cyt-Thy > Cyt-Cyt. On the other hand, mutual interactions of surface-adsorbed base pairs are stabilized mostly by hydrogen-bonding interactions in the order Gua-Cyt > Ade-Gua > Ade-Thy > Ade-Ade > Cyt-Thy > Gua-Gua > Cyt-Cyt > Ade-Cyt > Thy-Thy > Gua-Thy. Interestingly, several non-Watson-Crick base pairings, which are commonly ignored, have similar stabilization free energies due to interbase hydrogen bonding as Watson-Crick pairs. This clearly highlights the importance of non-Watson-Crick base pairing in the development of secondary structures of oligonucleotides near surfaces.

Standing chromosomal variation in Lake Whitefish species pairs: the role of historical contingency and relevance for speciation.

PubMed

Dion-Côté, Anne-Marie; Symonová, Radka; Lamaze, Fabien C; Pelikánová, Šárka; Ráb, Petr; Bernatchez, Louis

2017-01-01

The role of chromosome changes in speciation remains a debated topic, although demographic conditions associated with divergence should promote their appearance. We tested a potential relationship between chromosome changes and speciation by studying two Lake Whitefish (Coregonus clupeaformis) lineages that recently colonized postglacial lakes following allopatry. A dwarf limnetic species evolved repeatedly from the normal benthic species, becoming reproductively isolated. Lake Whitefish hybrids experience mitotic and meiotic instability, which may result from structurally divergent chromosomes. Motivated by this observation, we test the hypothesis that chromosome organization differs between Lake Whitefish species pairs using cytogenetics. While chromosome and fundamental numbers are conserved between the species (2n = 80, NF = 98), we observe extensive polymorphism of subtle karyotype traits. We describe intrachromosomal differences associated with heterochromatin and repetitive DNA, and test for parallelism among three sympatric species pairs. Multivariate analyses support the hypothesis that differentiation at the level of subchromosomal markers mostly appeared during allopatry. Yet we find no evidence for parallelism between species pairs among lakes, consistent with colonization effect or postcolonization differentiation. The reported intrachromosomal polymorphisms do not appear to play a central role in driving adaptive divergence between normal and dwarf Lake Whitefish. We discuss how chromosomal differentiation in the Lake Whitefish system may contribute to the destabilization of mitotic and meiotic chromosome segregation in hybrids, as documented previously. The chromosome structures detected here are still difficult to sequence and assemble, demonstrating the value of cytogenetics as a complementary approach to understand the genomic bases of speciation. © 2016 John Wiley & Sons Ltd.

The MUSE Hubble Ultra Deep Field Survey. IX. Evolution of galaxy merger fraction since z ≈ 6

NASA Astrophysics Data System (ADS)

Ventou, E.; Contini, T.; Bouché, N.; Epinat, B.; Brinchmann, J.; Bacon, R.; Inami, H.; Lam, D.; Drake, A.; Garel, T.; Michel-Dansac, L.; Pello, R.; Steinmetz, M.; Weilbacher, P. M.; Wisotzki, L.; Carollo, M.

2017-11-01

We provide, for the first time, robust observational constraints on the galaxy major merger fraction up to z ≈ 6 using spectroscopic close pair counts. Deep Multi Unit Spectroscopic Explorer (MUSE) observations in the Hubble Ultra Deep Field (HUDF) and Hubble Deep Field South (HDF-S) are used to identify 113 secure close pairs of galaxies among a parent sample of 1801 galaxies spread over a large redshift range (0.2 < z < 6) and stellar masses (107-1011 M⊙), thus probing about 12 Gyr of galaxy evolution. Stellar masses are estimated from spectral energy distribution (SED) fitting over the extensive UV-to-NIR HST photometry available in these deep Hubble fields, adding Spitzer IRAC bands to better constrain masses for high-redshift (z ⩾ 3) galaxies. These stellar masses are used to isolate a sample of 54 major close pairs with a galaxy mass ratio limit of 1:6. Among this sample, 23 pairs are identified at high redshift (z ⩾ 3) through their Lyα emission. The sample of major close pairs is divided into five redshift intervals in order to probe the evolution of the merger fraction with cosmic time. Our estimates are in very good agreement with previous close pair counts with a constant increase of the merger fraction up to z ≈ 3 where it reaches a maximum of 20%. At higher redshift, we show that the fraction slowly decreases down to about 10% at z ≈ 6. The sample is further divided into two ranges of stellar masses using either a constant separation limit of 109.5 M⊙ or the median value of stellar mass computed in each redshift bin. Overall, the major close pair fraction for low-mass and massive galaxies follows the same trend. These new, homogeneous, and robust estimates of the major merger fraction since z ≈ 6 are in good agreement with recent predictions of cosmological numerical simulations. Based on observations made with ESO telescopes at the La Silla-Paranal Observatory under programmes 094.A-0289(B), 095.A-0010(A), 096.A-0045(A) and 096.A-0045(B).

Towards a quantitative description of tunneling conductance of superconductors: Application to LiFeAs

DOE PAGES

Kreisel, A.; Nelson, R.; Berlijn, T.; ...

2016-12-27

Since the discovery of iron-based superconductors, a number of theories have been put forward to explain the qualitative origin of pairing, but there have been few attempts to make quantitative, material-specific comparisons to experimental results. The spin-fluctuation theory of electronic pairing, based on first-principles electronic structure calculations, makes predictions for the superconducting gap. Within the same framework, the surface wave functions may also be calculated, allowing, e.g., for detailed comparisons between theoretical results and measured scanning tunneling topographs and spectra. We present such a comparison between theory and experiment on the Fe-based superconductor LiFeAs. Our results for the homogeneous surfacemore » as well as impurity states are presented as a benchmark test of the theory. For the homogeneous system, we argue that the maxima of topographic image intensity may be located at positions above either the As or Li atoms, depending on tip height and the setpoint current of the measurement. We further report the experimental observation of transitions between As- and Li-registered lattices as functions of both tip height and setpoint bias, in agreement with this prediction. Next, we give a detailed comparison between the simulated scanning tunneling microscopy images of transition-metal defects with experiment. Finally, we discuss possible extensions of the current framework to obtain a theory with true predictive power for scanning tunneling microscopy in Fe-based systems.« less

Towards a quantitative description of tunneling conductance of superconductors: Application to LiFeAs

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

Kreisel, A.; Nelson, R.; Berlijn, T.

Since the discovery of iron-based superconductors, a number of theories have been put forward to explain the qualitative origin of pairing, but there have been few attempts to make quantitative, material-specific comparisons to experimental results. The spin-fluctuation theory of electronic pairing, based on first-principles electronic structure calculations, makes predictions for the superconducting gap. Within the same framework, the surface wave functions may also be calculated, allowing, e.g., for detailed comparisons between theoretical results and measured scanning tunneling topographs and spectra. We present such a comparison between theory and experiment on the Fe-based superconductor LiFeAs. Our results for the homogeneous surfacemore » as well as impurity states are presented as a benchmark test of the theory. For the homogeneous system, we argue that the maxima of topographic image intensity may be located at positions above either the As or Li atoms, depending on tip height and the setpoint current of the measurement. We further report the experimental observation of transitions between As- and Li-registered lattices as functions of both tip height and setpoint bias, in agreement with this prediction. Next, we give a detailed comparison between the simulated scanning tunneling microscopy images of transition-metal defects with experiment. Finally, we discuss possible extensions of the current framework to obtain a theory with true predictive power for scanning tunneling microscopy in Fe-based systems.« less

Meraculous: De Novo Genome Assembly with Short Paired-End Reads

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

Chapman, Jarrod A.; Ho, Isaac; Sunkara, Sirisha

2011-08-18

We describe a new algorithm, meraculous, for whole genome assembly of deep paired-end short reads, and apply it to the assembly of a dataset of paired 75-bp Illumina reads derived from the 15.4 megabase genome of the haploid yeast Pichia stipitis. More than 95% of the genome is recovered, with no errors; half the assembled sequence is in contigs longer than 101 kilobases and in scaffolds longer than 269 kilobases. Incorporating fosmid ends recovers entire chromosomes. Meraculous relies on an efficient and conservative traversal of the subgraph of the k-mer (deBruijn) graph of oligonucleotides with unique high quality extensions inmore » the dataset, avoiding an explicit error correction step as used in other short-read assemblers. A novel memory-efficient hashing scheme is introduced. The resulting contigs are ordered and oriented using paired reads separated by ~280 bp or ~3.2 kbp, and many gaps between contigs can be closed using paired-end placements. Practical issues with the dataset are described, and prospects for assembling larger genomes are discussed.« less

Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications.

PubMed

Zhu, Guizhi; Hu, Rong; Zhao, Zilong; Chen, Zhuo; Zhang, Xiaobing; Tan, Weihong

2013-11-06

DNA nanotechnology has been extensively explored to assemble various functional nanostructures for versatile applications. Mediated by Watson-Crick base-pairing, these DNA nanostructures have been conventionally assembled through hybridization of many short DNA building blocks. Here we report the noncanonical self-assembly of multifunctional DNA nanostructures, termed as nanoflowers (NFs), and the versatile biomedical applications. These NFs were assembled from long DNA building blocks generated via rolling circle replication (RCR) of a designer template. NF assembly was driven by liquid crystallization and dense packaging of building blocks, without relying on Watson-Crick base-pairing between DNA strands, thereby avoiding the otherwise conventional complicated DNA sequence design. NF sizes were readily tunable in a wide range, by simply adjusting such parameters as assembly time and template sequences. NFs were exceptionally resistant to nuclease degradation, denaturation, or dissociation at extremely low concentration, presumably resulting from the dense DNA packaging in NFs. The exceptional biostability is critical for biomedical applications. By rational design, NFs can be readily incorporated with myriad functional moieties. All these properties make NFs promising for versatile applications. As a proof-of-principle demonstration, in this study, NFs were integrated with aptamers, bioimaging agents, and drug loading sites, and the resultant multifunctional NFs were demonstrated for selective cancer cell recognition, bioimaging, and targeted anticancer drug delivery.

Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications

PubMed Central

Zhu, Guizhi; Hu, Rong; Zhao, Zilong; Chen, Zhuo; Zhang, Xiaobing; Tan, Weihong

2013-01-01

DNA nanotechnology has been extensively explored to assemble various functional nanostructures for versatile applications. Mediated by Watson-Crick base-pairing, these DNA nanostructures have been conventionally assembled through hybridization of many short DNA building blocks. Here we report the noncanonical self-assembly of multifunctional DNA nanostructures, termed as nanoflowers (NFs), and the versatile biomedical applications. These NFs were assembled from long DNA building blocks generated via Rolling Circle Replication (RCR) of a designer template. NF assembly was driven by liquid crystallization and dense packaging of building blocks, without relying on Watson-Crick base-pairing between DNA strands, thereby avoiding the otherwise conventional complicated DNA sequence design. NF sizes were readily tunable in a wide range, by simply adjusting such parameters as assembly time and template sequences. NFs were exceptionally resistant to nuclease degradation, denaturation, or dissociation at extremely low concentration, presumably resulting from the dense DNA packaging in NFs. The exceptional biostability is critical for biomedical applications. By rational design, NFs can be readily incorporated with myriad functional moieties. All these properties make NFs promising for versatile applications. As a proof-of-principle demonstration, in this study, NFs were integrated with aptamers, bioimaging agents, and drug loading sites, and the resultant multifunctional NFs were demonstrated for selective cancer cell recognition, bioimaging, and targeted anticancer drug delivery. PMID:24164620

Time to Go Beyond Triple-Gauge-Boson-Coupling Interpretation of W Pair Production.

PubMed

Zhang, Zhengkang

2017-01-06

W boson pair production processes at e^{+}e^{-} and pp colliders have been conventionally interpreted as measurements of WWZ and WWγ triple gauge couplings (TGCs). Such an interpretation is based on the assumption that new physics effects other than anomalous TGCs are negligible. While this "TGC dominance assumption" was well motivated and useful at LEP2 thanks to precision electroweak constraints, it is already challenged by recent LHC data. In fact, contributions from anomalous Z boson couplings that are allowed by electroweak precision data but neglected in LHC analyses, which are enhanced at high energy, can even dominate over those from the anomalous TGCs considered. This limits the generality of the anomalous TGC constraints derived in current analyses and necessitates extension of the analysis framework and a change of physics interpretation. The issue will persist as we continue to explore the high-energy frontier. We clarify and analyze the situation in the effective field theory framework, which provides a useful organizing principle for understanding standard model deviations in the high-energy regime.

Dual responsive supramolecular hydrogel with electrochemical activity.

PubMed

Du, Ping; Liu, Jianghua; Chen, Guosong; Jiang, Ming

2011-08-02

Supramolecular materials with reversible responsiveness to environmental changes are of particular research interest in recent years. Inclusion complexation between cyclodextrin (CD) and ferrocene (Fc) is well-known and extensively studied because of its reversible association-dissociation controlled by the redox state of Fc. Although there are quite a few reported nanoscale materials incorporating this host-guest pair, polymeric hydrogels with electrochemical activity based on this interactive pair are still rare. Taking advantage of our previous reported hybrid inclusion complex (HIC) hydrogel structure, a new Fc-HIC was designed and obtained with β-CD-modified quantum dots as the core and Fc-ended diblock co-polymer p(DMA-b-NIPAM) as the shell, to achieve an electrochemically active hydrogel at elevated temperatures. Considering the two independent cross-linking strategies in the network structure, i.e., the interchain aggregation of pNIPAM and inclusion complexation between CD and Fc on the surface of the quantum dots, the hydrogel was fully thermo-reversible and its gel-sol transition was achieved after the addition of either an oxidizing agent or a competitive guest to Fc.

Three superconducting phases with different categories of pairing in hole- and electron-doped LaFeAs1 -xPxO

NASA Astrophysics Data System (ADS)

Miyasaka, S.; Uekubo, M.; Tsuji, H.; Nakajima, M.; Tajima, S.; Shiota, T.; Mukuda, H.; Sagayama, H.; Nakao, H.; Kumai, R.; Murakami, Y.

2017-06-01

The phase diagram of the LaFeAs1 -xPxO system has been extensively studied through hole and electron doping as well as As/P substitution. It has been revealed that there are three different superconducting phases with different Fermi surface (FS) topologies and thus with possibly different pairing glues. One of them is well understood as spin fluctuation-mediated superconductivity within a FS nesting scenario. Another one with the FSs in a bad nesting condition must be explained in a different context such as orbital or spin fluctuation in a strongly correlated electronic system. In both phases, T -linear resistivity was commonly observed when the superconducting transition temperature Tc becomes the highest value, indicating that the strength of bosonic fluctuation determines Tc. In the last superconducting phase, the nesting condition of FSs and the related bosonic fluctuation are moderate. Variety of phase diagram characterizes the multiple orbital nature of the iron-based superconductors which are just near the boundary between weak and strong correlation regimes.

Visual Associative Learning in Restrained Honey Bees with Intact Antennae

PubMed Central

Dobrin, Scott E.; Fahrbach, Susan E.

2012-01-01

A restrained honey bee can be trained to extend its proboscis in response to the pairing of an odor with a sucrose reward, a form of olfactory associative learning referred to as the proboscis extension response (PER). Although the ability of flying honey bees to respond to visual cues is well-established, associative visual learning in restrained honey bees has been challenging to demonstrate. Those few groups that have documented vision-based PER have reported that removing the antennae prior to training is a prerequisite for learning. Here we report, for a simple visual learning task, the first successful performance by restrained honey bees with intact antennae. Honey bee foragers were trained on a differential visual association task by pairing the presentation of a blue light with a sucrose reward and leaving the presentation of a green light unrewarded. A negative correlation was found between age of foragers and their performance in the visual PER task. Using the adaptations to the traditional PER task outlined here, future studies can exploit pharmacological and physiological techniques to explore the neural circuit basis of visual learning in the honey bee. PMID:22701575

Rotational-translational fourier imaging system

NASA Technical Reports Server (NTRS)

Campbell, Jonathan W. (Inventor)

2004-01-01

This invention has the ability to create Fourier-based images with only two grid pairs. The two grid pairs are manipulated in a manner that allows (1) a first grid pair to provide multiple real components of the Fourier-based image and (2) a second grid pair to provide multiple imaginary components of the Fourier-based image. The novelty of this invention resides in the use of only two grid pairs to provide the same imaging information that has been traditionally collected with multiple grid pairs.

Thermodynamic stability of Hoogsteen and Watson-Crick base pairs in the presence of histone H3-mimicking peptide.

PubMed

Pramanik, Smritimoy; Nakamura, Kaori; Usui, Kenji; Nakano, Shu-ichi; Saxena, Sarika; Matsui, Jun; Miyoshi, Daisuke; Sugimoto, Naoki

2011-03-14

We found that Hoogsteen base pairs were stabilized by molecular crowding and a histone H3-mimicking peptide, which was not observed for Watson-Crick base pairs. Our findings demonstrate that the type of DNA base pair is critical for the interaction between DNA and histones.

The USC Adult Twin Cohorts: International Twin Study and California Twin Program.

PubMed

Cozen, Wendy; Hwang, Amie E; Cockburn, Myles G; Hamilton, Ann S; Zadnick, John; Mack, Thomas M

2013-02-01

The study of twin subjects permits the documentation of crude heritability and may promote the identification of specific causal alleles. We believe that at the current time, the chief research advantage of twins as subjects, especially monozygotic twins, is that the commonality of their genetic and cultural identity simplifies the interpretation of biological associations. In order to study genetic and environmental determinants of cancer and chronic diseases, we developed two twin registries, maintained at the University of Southern California: The International Twin Study (ITS) and the California Twin Program (CTP). The ITS is a volunteer registry of twins with cancer and chronic disease consisting of 17,245 twin pairs affected by cancer and chronic disease, respectively, ascertained by advertising in periodicals from 1980-1991. The CTP is a population-based registry of California-born twin pairs ascertained by linking the California birth records to the State Department of Motor Vehicles. Over 51,000 individual California twins representing 36,965 pairs completed and returned 16-page questionnaires. Cancer diagnoses in the California twins are updated by regular linkage to the California Cancer Registry. Over 5,000 cancer patients are represented in the CTP. Twins from both registries have participated extensively in studies of breast cancer, melanoma, lymphoma, multiple sclerosis, systemic lupus erythematosus, diabetes mellitus type 1, mammographic density, smoking, and other traits and conditions.

Making the Connection.

ERIC Educational Resources Information Center

Renyi, Judith

1997-01-01

Designed by the National Foundation for the Improvement of education, Bill Gates's The Road Ahead Program features extensive Internet access for all students and teacher opportunities to work with networks and multimedia technologies. Each school in the 22 participating communities is paired with a community organization. Staff development should…

Practical Algorithms for the Longest Common Extension Problem

NASA Astrophysics Data System (ADS)

Ilie, Lucian; Tinta, Liviu

The Longest Common Extension problem considers a string s and computes, for each of a number of pairs (i,j), the longest substring of s that starts at both i and j. It appears as a subproblem in many fundamental string problems and can be solved by linear-time preprocessing of the string that allows (worst-case) constant-time computation for each pair. The two known approaches use powerful algorithms: either constant-time computation of the Lowest Common Ancestor in trees or constant-time computation of Range Minimum Queries (RMQ) in arrays. We show here that, from practical point of view, such complicated approaches are not needed. We give two very simple algorithms for this problem that require no preprocessing. The first needs only the string and is significantly faster than all previous algorithms on the average. The second combines the first with a direct RMQ computation on the Longest Common Prefix array. It takes advantage of the superior speed of the cache memory and is the fastest on virtually all inputs.

Search for neutral minimal supersymmetric standard model Higgs bosons decaying to tau pairs produced in association with b quarks in pp collisions at √s = 1.96 TeV.

PubMed

Abazov, V M; Abbott, B; Acharya, B S; Adams, M; Adams, T; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Aoki, M; Arov, M; Askew, A; Åsman, B; Atramentov, O; Avila, C; BackusMayes, J; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barberis, E; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bazterra, V; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Blazey, G; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brandt, O; Brock, R; Brooijmans, G; Bross, A; Brown, D; Brown, J; Bu, X B; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burnett, T H; Buszello, C P; Calpas, B; Camacho-Pérez, E; Carrasco-Lizarraga, M A; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Chen, G; Chevalier-Théry, S; Cho, D K; Cho, S W; Choi, S; Choudhary, B; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Croc, A; Cutts, D; Das, A; Davies, G; De, K; de Jong, S J; De La Cruz-Burelo, E; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Deterre, C; DeVaughan, K; Diehl, H T; Diesburg, M; Ding, P F; Dominguez, A; Dorland, T; Dubey, A; Dudko, L V; Duggan, D; Duperrin, A; Dutt, S; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Evans, H; Evdokimov, A; Evdokimov, V N; Facini, G; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fuess, S; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geng, W; Gerbaudo, D; Gerber, C E; Gershtein, Y; Ginther, G; Golovanov, G; Goussiou, A; Grannis, P D; Greder, S; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guillemin, T; Guo, F; Gutierrez, G; Gutierrez, P; Haas, A; Hagopian, S; Haley, J; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Head, T; Hebbeker, T; Hedin, D; Hegab, H; Heinson, A P; Heintz, U; Hensel, C; Heredia-De La Cruz, I; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hohlfeld, M; Hubacek, Z; Huske, N; Hynek, V; Iashvili, I; Ilchenko, Y; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jamin, D; Jayasinghe, A; Jesik, R; Johns, K; Johnson, M; Johnston, D; Jonckheere, A; Jonsson, P; Joshi, J; Jung, A W; Juste, A; Kaadze, K; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Kirby, M H; Kohli, J M; Kozelov, A V; Kraus, J; Kulikov, S; Kumar, A; Kupco, A; Kurča, T; Kuzmin, V A; Kvita, J; Lammers, S; Landsberg, G; Lebrun, P; Lee, H S; Lee, S W; Lee, W M; Lellouch, J; Li, L; Li, Q Z; Lietti, S M; Lim, J K; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Lopes de Sa, R; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Mackin, D; Madar, R; Magaña-Villalba, R; Malik, S; Malyshev, V L; Maravin, Y; Martínez-Ortega, J; McCarthy, R; McGivern, C L; Meijer, M M; Melnitchouk, A; Menezes, D; Mercadante, P G; Merkin, M; Meyer, A; Meyer, J; Miconi, F; Mondal, N K; Muanza, G S; Mulhearn, M; Nagy, E; Naimuddin, M; Narain, M; Nayyar, R; Neal, H A; Negret, J P; Neustroev, P; Novaes, S F; Nunnemann, T; Obrant, G; Orduna, J; Osman, N; Osta, J; Otero y Garzón, G J; Padilla, M; Pal, A; Parashar, N; Parihar, V; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Penning, B; Perfilov, M; Peters, K; Peters, Y; Petridis, K; Petrillo, G; Pétroff, P; Piegaia, R; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Polozov, P; Popov, A V; Prewitt, M; Price, D; Prokopenko, N; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rangel, M S; Ranjan, K; Ratoff, P N; Razumov, I; Renkel, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Rominsky, M; Ross, A; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Salcido, P; Sánchez-Hernández, A; Sanders, M P; Sanghi, B; Santos, A S; Savage, G; Sawyer, L; Scanlon, T; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schlobohm, S; Schwanenberger, C; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shary, V; Shchukin, A A; Shivpuri, R K; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Smith, K J; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Soustruznik, K; Stark, J; Stolin, V; Stoyanova, D A; Strauss, M; Strom, D; Stutte, L; Suter, L; Svoisky, P; Takahashi, M; Tanasijczuk, A; Taylor, W; Titov, M; Tokmenin, V V; Tsai, Y-T; Tschann-Grimm, K; Tsybychev, D; Tuchming, B; Tully, C; Uvarov, L; Uvarov, S; Uzunyan, S; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Vertogradov, L S; Verzocchi, M; Vesterinen, M; Vilanova, D; Vokac, P; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, M; Welty-Rieger, L; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Xu, C; Yacoob, S; Yamada, R; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Ye, Z; Yin, H; Yip, K; Youn, S W; Yu, J; Zelitch, S; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L

2011-09-16

We report results from a search for neutral Higgs bosons produced in association with b quarks using data recorded by the D0 experiment at the Fermilab Tevatron Collider and corresponding to an integrated luminosity of 7.3 fb(-1). This production mode can be enhanced in several extensions of the standard model (SM) such as in its minimal supersymmetric extension (MSSM) at high tanβ. We search for Higgs bosons decaying to tau pairs with one tau decaying to a muon and neutrinos and the other to hadrons. The data are found to be consistent with SM expectations, and we set upper limits on the cross section times branching ratio in the Higgs boson mass range from 90 to 320 GeV/c(2). We interpret our result in the MSSM parameter space, excluding tanβ values down to 25 for Higgs boson masses below 170 GeV/c(2).

Efficient Implementation of the Pairing on Mobilephones Using BREW

NASA Astrophysics Data System (ADS)

Yoshitomi, Motoi; Takagi, Tsuyoshi; Kiyomoto, Shinsaku; Tanaka, Toshiaki

Pairing based cryptosystems can accomplish novel security applications such as ID-based cryptosystems, which have not been constructed efficiently without the pairing. The processing speed of the pairing based cryptosystems is relatively slow compared with the other conventional public key cryptosystems. However, several efficient algorithms for computing the pairing have been proposed, namely Duursma-Lee algorithm and its variant ηT pairing. In this paper, we present an efficient implementation of the pairing over some mobilephones. Moreover, we compare the processing speed of the pairing with that of the other standard public key cryptosystems, i. e. RSA cryptosystem and elliptic curve cryptosystem. Indeed the processing speed of our implementation in ARM9 processors on BREW achieves under 100 milliseconds using the supersingular curve over F397. In addition, the pairing is more efficient than the other public key cryptosystems, and the pairing can be achieved enough also on BREW mobilephones. It has become efficient enough to implement security applications, such as short signature, ID-based cryptosystems or broadcast encryption, using the pairing on BREW mobilephones.

Duct attachment and extension for an air conditioning unit

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

Lang, R.D.; Frenia, F.J.

1986-12-16

An apparatus is described for attaching a fixed duct extension to the discharge opening of an air conditioning unit, the unit slidably inserted in and removed from a fixed through-the-wall sleeve, for supplying conditioned air to the space containing the unit and an adjacent space comprising: a discharge plenum assembly adapted to be connected to the unit encase the discharge opening. The discharge plenum assembly defines an air flow path for the conditioned air discharged from the unit and includes a first housing member having a forward wall, a rear wall, and a pair of opposed side walls joining themore » front wall to the rear wall, and a second housing member having a top wall connected to a front wall. The top wall and the front wall are fixedly attached to the rear wall and the forward wall respectively of the first housing member and forming a duct outlet in one of the side walls. The top wall and the front wall of the second housing member and one of the pair of opposed side walls of the lower housing member having longitudinal flanges extending therefrom forming a C-like flange; a bracket removably secured to the through the wall sleeve having an outwardly extending flange member at the top of the bracket; and a duct extension means secured to the outwardly extending flange of the bracket near one end and to the wall of the adjacent space at the opposite end. The duct extension means has a collar at one end configured to engage with the C-like flange whereby the unit with the discharge plenum assembly attached thereto slidably engages with and disengages from the through-the-wall sleeve while the duct extension is secured to the bracket.« less

Genome differentiation in a species pair of coregonine fishes: an extremely rapid speciation driven by stress-activated retrotransposons mediating extensive ribosomal DNA multiplications

PubMed Central

2013-01-01

Background Sympatric species pairs are particularly common in freshwater fishes associated with postglacial lakes in northern temperate environments. The nature of divergences between co-occurring sympatric species, factors contributing to reproductive isolation and modes of genome evolution is a much debated topic in evolutionary biology addressed by various experimental tools. To the best of our knowledge, nobody approached this field using molecular cytogenetics. We examined chromosomes and genomes of one postglacial species pair, sympatric European winter-spawning Coregonus albula and the local endemic dwarf-sized spring-spawning C. fontanae, both originating in Lake Stechlin. We have employed molecular cytogenetic tools to identify the genomic differences between the two species of the sympatric pair on the sub-chromosomal level of resolution. Results Fluorescence in situ hybridization (FISH) experiments consistently revealed a distinct variation in the copy number of loci of the major ribosomal DNA (the 45S unit) between C. albula and C. fontanae genomes. In C. fontanae, up to 40 chromosomes were identified to bear a part of the major ribosomal DNA, while in C. albula only 8–10 chromosomes possessed these genes. To determine mechanisms how such extensive genome alternation might have arisen, a PCR screening for retrotransposons from genomic DNA of both species was performed. The amplified retrotransposon Rex1 was used as a probe for FISH mapping onto chromosomes of both species. These experiments showed a clear co-localization of the ribosomal DNA and the retrotransposon Rex1 in a pericentromeric region of one or two acrocentric chromosomes in both species. Conclusion We demonstrated genomic consequences of a rapid ecological speciation on the level undetectable by neither sequence nor karyotype analysis. We provide indirect evidence that ribosomal DNA probably utilized the spreading mechanism of retrotransposons subsequently affecting recombination rates in both genomes, thus, leading to a rapid genome divergence. We attribute these extensive genome re-arrangements associated with speciation event to stress-induced retrotransposons (re)activation. Such causal interplay between genome differentiation, retrotransposons (re)activation and environmental conditions may become a topic to be explored in a broader genomic context in future evolutionary studies. PMID:23410024

Envisaging quantum transport phenomenon in a muddled base pair of DNA

NASA Astrophysics Data System (ADS)

Vohra, Rajan; Sawhney, Ravinder Singh

2018-05-01

The effect of muddled base pair on electron transfer through a deoxyribonucleic acid (DNA) molecule connected to the gold electrodes has been elucidated using tight binding model. The effect of hydrogen and nitrogen bonds on the resistance of the base pair has been minutely observed. Using the semiempirical extended Huckel approach within NEGF regime, we have determined the current and conductance vs. bias voltage for disordered base pairs of DNA made of thymine (T) and adenine (A). The asymmetrical behaviour amid five times depreciation in the current characteristics has been observed for deviated Au-AT base pair-Au devices. An interesting revelation is that the conductance of the intrinsic AT base pair configuration attains dramatically high values with the symmetrical zig-zag pattern of current, which clearly indicates the transformation of the bond length within the strands of base pair when compared with other samples. A thorough investigation of the transmission coefficients T( E) and HOMO-LUMO gap reveals the misalignment of the strands in base pairs of DNA. The observed results present an insight to extend this work to build biosensing devices to predict the abnormality with the DNA.

Higher order structural effects stabilizing the reverse Watson–Crick Guanine-Cytosine base pair in functional RNAs

PubMed Central

Chawla, Mohit; Abdel-Azeim, Safwat; Oliva, Romina; Cavallo, Luigi

2014-01-01

The G:C reverse Watson–Crick (W:W trans) base pair, also known as Levitt base pair in the context of tRNAs, is a structurally and functionally important base pair that contributes to tertiary interactions joining distant domains in functional RNA molecules and also participates in metabolite binding in riboswitches. We previously indicated that the isolated G:C W:W trans base pair is a rather unstable geometry, and that dicationic metal binding to the Guanine base or posttranscriptional modification of the Guanine can increase its stability. Herein, we extend our survey and report on other H-bonding interactions that can increase the stability of this base pair. To this aim, we performed a bioinformatics search of the PDB to locate all the occurencies of G:C trans base pairs. Interestingly, 66% of the G:C trans base pairs in the PDB are engaged in additional H-bonding interactions with other bases, the RNA backbone or structured water molecules. High level quantum mechanical calculations on a data set of representative crystal structures were performed to shed light on the structural stability and energetics of the various crystallographic motifs. This analysis was extended to the binding of the preQ1 metabolite to a preQ1-II riboswitch. PMID:24121683

Joint multifractal analysis based on wavelet leaders

NASA Astrophysics Data System (ADS)

Jiang, Zhi-Qiang; Yang, Yan-Hong; Wang, Gang-Jin; Zhou, Wei-Xing

2017-12-01

Mutually interacting components form complex systems and these components usually have long-range cross-correlated outputs. Using wavelet leaders, we propose a method for characterizing the joint multifractal nature of these long-range cross correlations; we call this method joint multifractal analysis based on wavelet leaders (MF-X-WL). We test the validity of the MF-X-WL method by performing extensive numerical experiments on dual binomial measures with multifractal cross correlations and bivariate fractional Brownian motions (bFBMs) with monofractal cross correlations. Both experiments indicate that MF-X-WL is capable of detecting cross correlations in synthetic data with acceptable estimating errors. We also apply the MF-X-WL method to pairs of series from financial markets (returns and volatilities) and online worlds (online numbers of different genders and different societies) and determine intriguing joint multifractal behavior.

Automated Monitoring and Analysis of Social Behavior in Drosophila

PubMed Central

Dankert, Heiko; Wang, Liming; Hoopfer, Eric D.; Anderson, David J.; Perona, Pietro

2009-01-01

We introduce a method based on machine vision for automatically measuring aggression and courtship in Drosophila melanogaster. The genetic and neural circuit bases of these innate social behaviors are poorly understood. High-throughput behavioral screening in this genetically tractable model organism is a potentially powerful approach, but it is currently very laborious. Our system monitors interacting pairs of flies, and computes their location, orientation and wing posture. These features are used for detecting behaviors exhibited during aggression and courtship. Among these, wing threat, lunging and tussling are specific to aggression; circling, wing extension (courtship “song”) and copulation are specific to courtship; locomotion and chasing are common to both. Ethograms may be constructed automatically from these measurements, saving considerable time and effort. This technology should enable large-scale screens for genes and neural circuits controlling courtship and aggression. PMID:19270697

Bifacial Base-Pairing Behaviors of 5-Hydroxyuracil DNA Bases through Hydrogen Bonding and Metal Coordination.

PubMed

Takezawa, Yusuke; Nishiyama, Kotaro; Mashima, Tsukasa; Katahira, Masato; Shionoya, Mitsuhiko

2015-10-12

A novel bifacial ligand-bearing nucleobase, 5-hydroxyuracil (U(OH) ), which forms both a hydrogen-bonded base pair (U(OH) -A) and a metal-mediated base pair (U(OH) -M-U(OH) ) has been developed. The U(OH) -M-U(OH) base pairs were quantitatively formed in the presence of lanthanide ions such as Gd(III) when U(OH) -U(OH) pairs were consecutively incorporated into DNA duplexes. This result established metal-assisted duplex stabilization as well as DNA-templated assembly of lanthanide ions. Notably, a duplex possessing U(OH) -A base pairs was destabilized by addition of Gd(III) ions. This observation suggests that the hybridization behaviors of the U(OH) -containing DNA strands are altered by metal complexation. Thus, the U(OH) nucleobase with a bifacial base-pairing property holds great promise as a component for metal-responsive DNA materials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular switching behavior in isosteric DNA base pairs.

PubMed

Jissy, A K; Konar, Sukanya; Datta, Ayan

2013-04-15

The structures and proton-coupled behavior of adenine-thymine (A-T) and a modified base pair containing a thymine isostere, adenine-difluorotoluene (A-F), are studied in different solvents by dispersion-corrected density functional theory. The stability of the canonical Watson-Crick base pair and the mismatched pair in various solvents with low and high dielectric constants is analyzed. It is demonstrated that A-F base pairing is favored in solvents with low dielectric constant. The stabilization and conformational changes induced by protonation are also analyzed for the natural as well as the mismatched base pair. DNA sequences capable of changing their sequence conformation on protonation are used in the construction of pH-based molecular switches. An acidic medium has a profound influence in stabilizing the isostere base pair. Such a large gain in stability on protonation leads to an interesting pH-controlled molecular switch, which can be incorporated in a natural DNA tract. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quality Matters: Extension of Clusters of Residues with Good Hydrophobic Contacts Stabilize (Hyper)Thermophilic Proteins

PubMed Central

2015-01-01

Identifying determinant(s) of protein thermostability is key for rational and data-driven protein engineering. By analyzing more than 130 pairs of mesophilic/(hyper)thermophilic proteins, we identified the quality (residue-wise energy) of hydrophobic interactions as a key factor for protein thermostability. This distinguishes our study from previous ones that investigated predominantly structural determinants. Considering this key factor, we successfully discriminated between pairs of mesophilic/(hyper)thermophilic proteins (discrimination accuracy: ∼80%) and searched for structural weak spots in E. coli dihydrofolate reductase (classification accuracy: 70%). PMID:24437522

Ionic liquid-induced aggregate formation and their applications.

PubMed

Dutta, Rupam; Kundu, Sangita; Sarkar, Nilmoni

2018-06-01

In the last two decades, researchers have extensively studied highly stable and ordered supramolecular assembly formation using oppositely charged surfactants. Thereafter, surface-active ionic liquids (SAILs), a special class of room temperature ionic liquids (RTILs), replace the surfactants to form various supramolecular aggregates. Therefore, in the last decade, the building blocks of the supramolecular aggregates (micelle, mixed micelle, and vesicular assemblies) have changed from oppositely charged surfactant/surfactant pair to surfactant/SAIL and SAIL/SAIL pair. It is also found that various biomolecules can also interact with SAILs to construct biologically important supramolecular assemblies. The very latest addition to this combination of ion pairs is the dye molecules having a long hydrophobic chain part along with a hydrophilic ionic head group. Thus, dye/surfactant or dye/SAIL pair also produces different assemblies through electrostatic, hydrophobic, and π-π stacking interactions. Vesicles are one of the important self-assemblies which mimic cellular membranes, and thus have biological application as a drug carrier. Moreover, vesicles can act as a suitable microreactor for nanoparticle synthesis.

Kappa statistic for clustered matched-pair data.

PubMed

Yang, Zhao; Zhou, Ming

2014-07-10

Kappa statistic is widely used to assess the agreement between two procedures in the independent matched-pair data. For matched-pair data collected in clusters, on the basis of the delta method and sampling techniques, we propose a nonparametric variance estimator for the kappa statistic without within-cluster correlation structure or distributional assumptions. The results of an extensive Monte Carlo simulation study demonstrate that the proposed kappa statistic provides consistent estimation and the proposed variance estimator behaves reasonably well for at least a moderately large number of clusters (e.g., K ≥50). Compared with the variance estimator ignoring dependence within a cluster, the proposed variance estimator performs better in maintaining the nominal coverage probability when the intra-cluster correlation is fair (ρ ≥0.3), with more pronounced improvement when ρ is further increased. To illustrate the practical application of the proposed estimator, we analyze two real data examples of clustered matched-pair data. Copyright © 2014 John Wiley & Sons, Ltd.

Electron-pair-production cross section in the tip region of the positron spectrum

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

Sud, K.K.; Sharma, D.K.

1984-11-01

The radial integrals for electron-pair production in a point Coulomb potential have been expressed by Sud, Sharma, and Sud in terms of the matrix generalization of the GAMMA function. Two new partial differential equations in photon energy satisfied by the matrix GAMMA function are obtained. We have obtained, on integrating the partial differential equations, accurate radial integrals as a function of photon energy for the pair production by intermediate-energy photons. The cross section in the tip region of the spectrum are calculated for photons of energy 5.0 to 10.0 MeV for /sup 92/U. The new technique results in extensive savingmore » in computer time as the basic radial integrals in terms of the hypergeometric function F/sub 2/ are computed at one photon energy for each pair of partial waves. The results of our calculations are compared with plane-wave Born-approximation results and with the calculations of Dugne and of Deck, Moroi, and Alling.« less

1,8-Naphthyridine-2,7-diamine: a potential universal reader of Watson-Crick base pairs for DNA sequencing by electron tunneling.

PubMed

Liang, Feng; Lindsay, Stuart; Zhang, Peiming

2012-11-21

With the aid of Density Functional Theory (DFT), we designed 1,8-naphthyridine-2,7-diamine as a recognition molecule to read DNA base pairs for genomic sequencing by electron tunneling. NMR studies show that it can form stable triplets with both A : T and G : C base pairs through hydrogen bonding. Our results suggest that the naphthyridine molecule should be able to function as a universal base pair reader in a tunneling gap, generating distinguishable signatures under electrical bias for each of DNA base pairs.

1,8-Naphthyridine-2,7-diamine: A Potential Universal Reader of the Watson-Crick Base Pairs for DNA Sequencing by Electron Tunneling

PubMed Central

Liang, Feng; Lindsay, Stuart; Zhang, Peiming

2013-01-01

With the aid of Density Functional Theory (DFT), we designed 1,8-naphthyridine-2,7-diamine as a recognition molecule to read the DNA base pairs for genomic sequencing by electron tunneling. NMR studies show that it can form stable triplets with both A:T and G:C base pairs through hydrogen bonding. Our results suggest that the naphthyridine molecule should be able to function as a universal base pair reader in a tunneling gap, generating distinguishable signatures under electrical bias for each of DNA base pairs. PMID:23038027

76 FR 34668 - Notice of Proposed Information Collection Requests

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-14

... Education and Rehabilitative Services Type of Review: Extension. Title of Collection: Protection and... the Protection and Advocacy of Individual Rights (PAIR) grantees to submit an application to the... required to be part of the protection and advocacy system in each State established under the Developmental...

Differential effects of context on psychomotor sensitization to ethanol and cocaine.

PubMed

Didone, Vincent; Quoilin, Caroline; Dieupart, Julie; Tirelli, Ezio; Quertemont, Etienne

2016-04-01

Repeated drug injections lead to sensitization of their stimulant effects in mice, a phenomenon sometimes referred to as drug psychomotor sensitization. Previous studies showed that sensitization to cocaine is context dependent as its expression is reduced in an environment that was not paired with cocaine administration. In contrast, the effects of the test context on ethanol sensitization remain unclear. In the present study, female OF1 mice were repeatedly injected with 1.5 g/kg ethanol to test for both the effects of context novelty/familiarity and association on ethanol sensitization. A first group of mice was extensively pre-exposed to the test context before ethanol sensitization and ethanol injections were paired with the test context (familiar and paired group). A second group was not pre-exposed to the test context, but ethanol injections were paired with the test context (nonfamiliar and paired group). Finally, a third group of mice was not pre-exposed to the test context and ethanol was repeatedly injected in the home cage (unpaired group). Control groups were similarly exposed to the test context, but were injected with saline. In a second experiment, cocaine was used as a positive control. The same behavioral procedure was used, except that mice were injected with 10 mg/kg cocaine instead of ethanol. The results show a differential involvement of the test context in the sensitization to ethanol and cocaine. Cocaine sensitization is strongly context dependent and is not expressed in the unpaired group. In contrast, the expression of ethanol sensitization is independent of the context in which it was administered, but is strongly affected by the relative novelty/familiarity of the environment. Extensive pre-exposure to the test context prevented the expression of ethanol sensitization. One possible explanation is that expression of ethanol sensitization requires an arousing environment.

Gene-Based Testing of Interactions in Association Studies of Quantitative Traits

PubMed Central

Ma, Li; Clark, Andrew G.; Keinan, Alon

2013-01-01

Various methods have been developed for identifying gene–gene interactions in genome-wide association studies (GWAS). However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene–gene interaction (GGG) tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein–protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies. PMID:23468652

Direct and Inverse Kinematics of a Novel Tip-Tilt-Piston Parallel Manipulator

NASA Technical Reports Server (NTRS)

Tahmasebi, Farhad

2004-01-01

Closed-form direct and inverse kinematics of a new three degree-of-freedom (DOF) parallel manipulator with inextensible limbs and base-mounted actuators are presented. The manipulator has higher resolution and precision than the existing three DOF mechanisms with extensible limbs. Since all of the manipulator actuators are base-mounted; higher payload capacity, smaller actuator sizes, and lower power dissipation can be obtained. The manipulator is suitable for alignment applications where only tip, tilt, and piston motions are significant. The direct kinematics of the manipulator is reduced to solving an eighth-degree polynomial in the square of tangent of half-angle between one of the limbs and the base plane. Hence, there are at most 16 assembly configurations for the manipulator. In addition, it is shown that the 16 solutions are eight pairs of reflected configurations with respect to the base plane. Numerical examples for the direct and inverse kinematics of the manipulator are also presented.

RDNAnalyzer: A tool for DNA secondary structure prediction and sequence analysis

PubMed Central

Afzal, Muhammad; Shahid, Ahmad Ali; Shehzadi, Abida; Nadeem, Shahid; Husnain, Tayyab

2012-01-01

RDNAnalyzer is an innovative computer based tool designed for DNA secondary structure prediction and sequence analysis. It can randomly generate the DNA sequence or user can upload the sequences of their own interest in RAW format. It uses and extends the Nussinov dynamic programming algorithm and has various application for the sequence analysis. It predicts the DNA secondary structure and base pairings. It also provides the tools for routinely performed sequence analysis by the biological scientists such as DNA replication, reverse compliment generation, transcription, translation, sequence specific information as total number of nucleotide bases, ATGC base contents along with their respective percentages and sequence cleaner. RDNAnalyzer is a unique tool developed in Microsoft Visual Studio 2008 using Microsoft Visual C# and Windows Presentation Foundation and provides user friendly environment for sequence analysis. It is freely available. Availability http://www.cemb.edu.pk/sw.html Abbreviations RDNAnalyzer - Random DNA Analyser, GUI - Graphical user interface, XAML - Extensible Application Markup Language. PMID:23055611

Kinematics of a New High Precision Three Degree-of-Freedom Parallel Manipulator

NASA Technical Reports Server (NTRS)

Tahmasebi, Farhad

2005-01-01

Closed-form direct and inverse kinematics of a new three degree-of-freedom (DOF) parallel manipulator with inextensible limbs and base-mounted actuators are presented. The manipulator has higher resolution and precision than the existing three DOF mechanisms with extensible limbs. Since all of the manipulator actuators are base-mounted; higher payload capacity, smaller actuator sizes, and lower power dissipation can be obtained. The manipulator is suitable for alignment applications where only tip, tilt, and piston motions are significant. The direct kinematics of the manipulator is reduced to solving an eighth-degree polynomial in the square of tangent of half-angle between one of the limbs and the base plane. Hence, there are at most sixteen assembly configurations for the manipulator. In addition, it is shown that the sixteen solutions are eight pairs of reflected configurations with respect to the base plane. Numerical examples for the direct and inverse kinematics of the manipulator are also presented.

Propagation based phase retrieval of simulated intensity measurements using artificial neural networks

NASA Astrophysics Data System (ADS)

Kemp, Z. D. C.

2018-04-01

Determining the phase of a wave from intensity measurements has many applications in fields such as electron microscopy, visible light optics, and medical imaging. Propagation based phase retrieval, where the phase is obtained from defocused images, has shown significant promise. There are, however, limitations in the accuracy of the retrieved phase arising from such methods. Sources of error include shot noise, image misalignment, and diffraction artifacts. We explore the use of artificial neural networks (ANNs) to improve the accuracy of propagation based phase retrieval algorithms applied to simulated intensity measurements. We employ a phase retrieval algorithm based on the transport-of-intensity equation to obtain the phase from simulated micrographs of procedurally generated specimens. We then train an ANN with pairs of retrieved and exact phases, and use the trained ANN to process a test set of retrieved phase maps. The total error in the phase is significantly reduced using this method. We also discuss a variety of potential extensions to this work.

Hot carrier multiplication on graphene/TiO2 Schottky nanodiodes

PubMed Central

Lee, Young Keun; Choi, Hongkyw; Lee, Hyunsoo; Lee, Changhwan; Choi, Jin Sik; Choi, Choon-Gi; Hwang, Euyheon; Park, Jeong Young

2016-01-01

Carrier multiplication (i.e. generation of multiple electron–hole pairs from a single high-energy electron, CM) in graphene has been extensively studied both theoretically and experimentally, but direct application of hot carrier multiplication in graphene has not been reported. Here, taking advantage of efficient CM in graphene, we fabricated graphene/TiO2 Schottky nanodiodes and found CM-driven enhancement of quantum efficiency. The unusual photocurrent behavior was observed and directly compared with Fowler’s law for photoemission on metals. The Fowler’s law exponent for the graphene-based nanodiode is almost twice that of a thin gold film based diode; the graphene-based nanodiode also has a weak dependence on light intensity—both are significant evidence for CM in graphene. Furthermore, doping in graphene significantly modifies the quantum efficiency by changing the Schottky barrier. The CM phenomenon observed on the graphene/TiO2 nanodiodes can lead to intriguing applications of viable graphene-based light harvesting. PMID:27271245

Blind Predictions of DNA and RNA Tweezers Experiments with Force and Torque

PubMed Central

Chou, Fang-Chieh; Lipfert, Jan; Das, Rhiju

2014-01-01

Single-molecule tweezers measurements of double-stranded nucleic acids (dsDNA and dsRNA) provide unprecedented opportunities to dissect how these fundamental molecules respond to forces and torques analogous to those applied by topoisomerases, viral capsids, and other biological partners. However, tweezers data are still most commonly interpreted post facto in the framework of simple analytical models. Testing falsifiable predictions of state-of-the-art nucleic acid models would be more illuminating but has not been performed. Here we describe a blind challenge in which numerical predictions of nucleic acid mechanical properties were compared to experimental data obtained recently for dsRNA under applied force and torque. The predictions were enabled by the HelixMC package, first presented in this paper. HelixMC advances crystallography-derived base-pair level models (BPLMs) to simulate kilobase-length dsDNAs and dsRNAs under external forces and torques, including their global linking numbers. These calculations recovered the experimental bending persistence length of dsRNA within the error of the simulations and accurately predicted that dsRNA's “spring-like” conformation would give a two-fold decrease of stretch modulus relative to dsDNA. Further blind predictions of helix torsional properties, however, exposed inaccuracies in current BPLM theory, including three-fold discrepancies in torsional persistence length at the high force limit and the incorrect sign of dsRNA link-extension (twist-stretch) coupling. Beyond these experiments, HelixMC predicted that ‘nucleosome-excluding’ poly(A)/poly(T) is at least two-fold stiffer than random-sequence dsDNA in bending, stretching, and torsional behaviors; Z-DNA to be at least three-fold stiffer than random-sequence dsDNA, with a near-zero link-extension coupling; and non-negligible effects from base pair step correlations. We propose that experimentally testing these predictions should be powerful next steps for understanding the flexibility of dsDNA and dsRNA in sequence contexts and under mechanical stresses relevant to their biology. PMID:25102226

Marcus Theory of Ion-Pairing

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

Roy, Santanu; Baer, Marcel D.; Mundy, Christopher J.

We present a theory for ion pair dissociation and association, motivated by the concepts of the Marcus theory of electron transfer. Despite the extensive research on ion-pairing in many chemical and biological processes, much can be learned from the exploration of collective reaction coordinates. To this end, we explore two reaction coordinates, ion pair distance and coordination number. The study of the correlation between these reaction coordinates provides a new insight into the mechanism and kinetics of ion pair dissociation and association in water. The potential of mean force on these 2D-surfaces computed from molecular dynamics simulations of different monovalentmore » ion pairs reveal a Marcus-like mechanism for ion-pairing: Water molecules rearrange forming an activated coordination state prior to ion pair dissociation or association, followed by relaxation of the coordination state due to further water rearrangement. Like Marcus theory, we find the existence of an inverted region where the transition rates are slower with increasing exergonicity. This study provides a new perspective for the future investigations of ion-pairing and transport. SR, CJM, and GKS were supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. MDB was supported by MS3 (Materials Synthesis and Simulation Across Scales) Initiative, a Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory (PNNL). The research was performed using PNNL Institutional Computing. PNNL is a multi-program national laboratory operated by Battelle for the U.S. Department of Energy.« less

Parametric analysis for matched pair survival data.

PubMed

Manatunga, A K; Oakes, D

1999-12-01

Hougaard's (1986) bivariate Weibull distribution with positive stable frailties is applied to matched pairs survival data when either or both components of the pair may be censored and covariate vectors may be of arbitrary fixed length. When there is no censoring, we quantify the corresponding gain in Fisher information over a fixed-effects analysis. With the appropriate parameterization, the results take a simple algebraic form. An alternative marginal ("independence working model") approach to estimation is also considered. This method ignores the correlation between the two survival times in the derivation of the estimator, but provides a valid estimate of standard error. It is shown that when both the correlation between the two survival times is high, and the ratio of the within-pair variability to the between-pair variability of the covariates is high, the fixed-effects analysis captures most of the information about the regression coefficient but the independence working model does badly. When the correlation is low, and/or most of the variability of the covariates occurs between pairs, the reverse is true. The random effects model is applied to data on skin grafts, and on loss of visual acuity among diabetics. In conclusion some extensions of the methods are indicated and they are placed in a wider context of Generalized Estimation Equation methodology.

Comparison of clinical knowledge bases for summarization of electronic health records.

PubMed

McCoy, Allison B; Sittig, Dean F; Wright, Adam

2013-01-01

Automated summarization tools that create condition-specific displays may improve clinician efficiency. These tools require new kinds of knowledge that is difficult to obtain. We compared five problem-medication pair knowledge bases generated using four previously described knowledge base development approaches. The number of pairs in the resulting mapped knowledge bases varied widely due to differing mapping techniques from the source terminologies, ranging from 2,873 to 63,977,738 pairs. The number of overlapping pairs across knowledge bases was low, with one knowledge base having half of the pairs overlapping with another knowledge base, and most having less than a third overlapping. Further research is necessary to better evaluate the knowledge bases independently in additional settings, and to identify methods to integrate the knowledge bases.

Sliding over the Blocks in Enzyme-Free RNA Copying – One-Pot Primer Extension in Ice

PubMed Central

Löffler, Philipp M. G.; Groen, Joost; Dörr, Mark; Monnard, Pierre-Alain

2013-01-01

Template-directed polymerization of RNA in the absence of enzymes is the basis for an information transfer in the ‘RNA-world’ hypothesis and in novel nucleic acid based technology. Previous investigations established that only cytidine rich strands are efficient templates in bulk aqueous solutions while a few specific sequences completely block the extension of hybridized primers. We show that a eutectic water/ice system can support Pb2+/Mg2+-ion catalyzed extension of a primer across such sequences, i.e. AA, AU and AG, in a one-pot synthesis. Using mixtures of imidazole activated nucleotide 5′-monophosphates, the two first “blocking” residues could be passed during template-directed polymerization, i.e., formation of triply extended products containing a high fraction of faithful copies was demonstrated. Across the AG sequence, a mismatch sequence was formed in similar amounts to the correct product due to U·G wobble pairing. Thus, the template-directed extension occurs both across pyrimidine and purine rich sequences and insertions of pyrimidines did not inhibit the subsequent insertions. Products were mainly formed with 2′-5′-phosphodiester linkages, however, the abundance of 3′–5′-linkages was higher than previously reported for pyrimidine insertions. When enzyme-free, template-directed RNA polymerization is performed in a eutectic water ice environment, various intrinsic reaction limitations observed in bulk solution can then be overcome. PMID:24058695

Moral Appraisals Affect Doing/Allowing Judgments

ERIC Educational Resources Information Center

Cushman, Fiery; Knobe, Joshua; Sinnott-Armstrong, Walter

2008-01-01

An extensive body of research suggests that the distinction between doing and allowing plays a critical role in shaping moral appraisals. Here, we report evidence from a pair of experiments suggesting that the converse is also true: moral appraisals affect doing/allowing judgments. Specifically, morally bad behavior is more likely to be construed…

First-Principle Construction of U(1) Symmetric Matrix Product States

NASA Astrophysics Data System (ADS)

Rakov, Mykhailo V.

2018-07-01

The algorithm to calculate the sets of symmetry sectors for virtual indices of U(1) symmetric matrix product states (MPS) is described. The principal differences between open (OBC) and periodic (PBC) boundary conditions are stressed, and the extension of PBC MPS algorithm to projected entangled pair states is outlined.

Preference Assessment Training via Self-Instruction: A Replication and Extension

ERIC Educational Resources Information Center

Shapiro, Marnie; Kazemi, Ellie; Pogosjana, Meline; Rios, Denice; Mendoza, Melissa

2016-01-01

We examined the effects of a self-instructional and feedback package on participants' implementation of a paired-stimulus preference assessment. Specifically, in Experiment 1, we used a multiple baseline design across participants to replicate and extend the results of Graff and Karsten (2012) by evaluating the effectiveness of their…

Early Verb Learning: How Do Children Learn How to Compare Events?

ERIC Educational Resources Information Center

Childers, Jane B.; Parrish, Rebecca; Olson, Christina V.; Burch, Clare; Fung, Gavin; McIntyre, Kevin P.

2016-01-01

An important problem verb learners must solve is how to extend verbs. Children could use cross-situational information to guide their extensions; however, comparing events is difficult. In 2 studies, researchers tested whether children benefit from initially seeing a pair of similar events ("progressive alignment") while learning new…

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

Okutsu, N.; Shimamura, K.; Shimizu, E.

To elucidate the effect of radicals on DNA base pairs, we investigated the attacking mechanism of OH and H radicals to the G-C and A-T base pairs, using the density functional theory (DFT) calculations in water approximated by the continuum solvation model. The DFT calculations revealed that the OH radical abstracts the hydrogen atom of a NH{sub 2} group of G or A base and induces a tautomeric reaction for an A-T base pair more significantly than for a G-C base pair. On the other hand, the H radical prefers to bind to the Cytosine NH{sub 2} group of G-Cmore » base pair and induce a tautomeric reaction from G-C to G*-C*, whose activation free energy is considerably small (−0.1 kcal/mol) in comparison with that (42.9 kcal/mol) for the reaction of an A-T base pair. Accordingly, our DFT calculations elucidated that OH and H radicals have a significant effect on A-T and G-C base pairs, respectively. This finding will be useful for predicting the effect of radiation on the genetic information recorded in the base sequences of DNA duplexes.« less

Extensive Karyotype Reorganization in the Fish Gymnotus arapaima (Gymnotiformes, Gymnotidae) Highlighted by Zoo-FISH Analysis.

PubMed

Machado, Milla de Andrade; Pieczarka, Julio C; Silva, Fernando H R; O'Brien, Patricia C M; Ferguson-Smith, Malcolm A; Nagamachi, Cleusa Y

2018-01-01

The genus Gymnotus (Gymnotiformes) contains over 40 species of freshwater electric fishes exhibiting a wide distribution throughout Central and South America, and being particularly prevalent in the Amazon basin. Cytogenetics has been an important tool in the cytotaxonomy and elucidation of evolutionary processes in this genus, including the unraveling the variety of diploid chromosome number (2 n = from 34 to 54), the high karyotype diversity among species with a shared diploid number, different sex chromosome systems, and variation in the distribution of several Repetitive DNAs and colocation and association between those sequences. Recently whole chromosome painting (WCP) has been used for tracking the chromosomal evolution of the genus, showing highly reorganized karyotypes and the conserved synteny of the NOR bearing par within the clade G. carapo . In this study, painting probes derived from the chromosomes of G. carapo (GCA, 2 n = 42, 30 m/sm + 12 st/a) were hybridized to the mitotic metaphases of G. arapaima (GAR, 2 n = 44, 24 m/sm + 20 st/a). Our results uncovered chromosomal rearrangements and a high number of repetitive DNA regions. From the 12 chromosome pairs of G. carapo that can be individually differentiated (GCA1-3, 6, 7, 9, 14, 16, and 18-21), six pairs (GCA 1, 9, 14, 18, 20, 21) show conserved homology with GAR, five pairs (GCA 1, 9, 14, 20, 21) are also shared with cryptic species G. carapo 2 n = 40 (34 m/sm + 6 st/a) and only the NOR bearing pair (GCA 20) is shared with G. capanema (GCP 2 n = 34, 20 m/sm + 14 st/a). The remaining chromosomes are reorganized in the karyotype of GAR. Despite the close phylogenetic relationships of these species, our chromosome painting studies demonstrate an extensive reorganization of their karyotypes.

A Three-Dimensional View of Titan's Surface Features from Cassini RADAR Stereogrammetry

NASA Astrophysics Data System (ADS)

Kirk, R. L.; Howington-Kraus, E.; Redding, B. L.; Becker, T. L.; Lee, E. M.; Stiles, B. W.; Hensley, S.; Hayes, A.; Lopes, R. M.; Lorenz, R. D.; Mitchell, K. L.; Radebaugh, J.; Paganelli, F.; Soderblom, L. A.; Stofan, E. R.; Wood, C. A.; Wall, S. D.; Cassini RADAR Team

2008-12-01

As of the end of its four-year Prime Mission, Cassini has obtained 300-1500 m resolution synthetic aperture radar images of the surface of Titan during 19 flybys. The elongated image swaths overlap extensively, and ~2% of the surface has now been imaged two or more times. The majority of image pairs have different viewing directions, and thus contain stereo parallax that encodes information about Titan's surface relief over distances of ~1 km and greater. As we have previously reported, the first step toward extracting quantitative topographic information was the development of rigorous "sensor models" that allowed the stereo systems previously used at the USGS and JPL to map Venus with Magellan images to be used for Titan mapping. The second major step toward extensive topomapping of Titan has been the reprocessing of the RADAR images based on an improved model of the satellite's rotation. Whereas the original images (except for a few pairs obtained at similar orbital phase, some of which we have mapped previously) were offset by as much as 30 km, the new versions align much better. The remaining misalignments, typically <1 km, can be removed by a least-squares adjustment of the spacecraft trajectories before mapping, which also ensures that the stereo digital topographic models (DTMs) are made consistent with altimetry and SAR topography profiles. The useful stereo coverage now available includes a much larger portion of Titan's north polar lake country than we previously presented, a continuous traverse of high resolution data from the lakes to mid-southern latitudes, and widely distributed smaller areas. A remaining challenge is that many pairs of images are illuminated from opposite sides or from near-perpendicular directions, which can make image matching more difficult. We find that the high-contrast polarizing display of the stereo workstation at USGS provides a much clearer view of these unfavorably illuminated pairs than (for example) anaglyphs, and lets us supplement automatic image matching with interactive measurements where the former fails. We are collecting DTMs of all usable image pairs and will present the most interesting results. Examples of geologic questions that may be addressed are: What is the relation between Ganesa and surrounding features? Is it a dome or shield? Can the height of Titan's dunes be measured, and what is the relief of the bright "islands" that appear to divert the dunes? How high are the mountains of Xanadu and what gradients drive the channels between them? What are the relative and absolute height relations between seas and lakes of different types, and what does this tell us about the "hydro(carbono)logic" cycle of precipitation, evaporation, and surface and subsurface fluid flow?

Recognition of Watson-Crick base pairs: constraints and limits due to geometric selection and tautomerism

PubMed Central

Yusupov, Marat; Yusupova, Gulnara

2014-01-01

The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential. However, base pairs observed in recent crystal structures of polymerases and ribosomes are best explained by an alternative base tautomer, leading to the formation of base pairs with Watson-Crick-like geometries. These observations set limits to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes. PMID:24765524

Structure, Stiffness and Substates of the Dickerson-Drew Dodecamer

PubMed Central

Dršata, Tomáš; Pérez, Alberto; Orozco, Modesto; Morozov, Alexandre V.; Šponer, Jiřĺ; Lankaš, Filip

2013-01-01

The Dickerson–Drew dodecamer (DD) d-[CGCGAATTCGCG]2 is a prototypic B-DNA molecule whose sequence-specific structure and dynamics have been investigated by many experimental and computational studies. Here, we present an analysis of DD properties based on extensive atomistic molecular dynamics (MD) simulations using different ionic conditions and water models. The 0.6–2.4-µs-long MD trajectories are compared to modern crystallographic and NMR data. In the simulations, the duplex ends can adopt an alternative base-pairing, which influences the oligomer structure. A clear relationship between the BI/BII backbone substates and the basepair step conformation has been identified, extending previous findings and exposing an interesting structural polymorphism in the helix. For a given end pairing, distributions of the basepair step coordinates can be decomposed into Gaussian-like components associated with the BI/BII backbone states. The nonlocal stiffness matrices for a rigid-base mechanical model of DD are reported for the first time, suggesting salient stiffness features of the central A-tract. The Riemann distance and Kullback–Leibler divergence are used for stiffness matrix comparison. The basic structural parameters converge very well within 300 ns, convergence of the BI/BII populations and stiffness matrices is less sharp. Our work presents new findings about the DD structural dynamics, mechanical properties, and the coupling between basepair and backbone configurations, including their statistical reliability. The results may also be useful for optimizing future force fields for DNA. PMID:23976886

Dependence of the rate of LiF ion pairing on the description of molecular interaction

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

Pluharova, Eva; Baer, Marcel D.; Schenter, Gregory K.

2016-03-03

We present an analysis of the dynamics of ion-pairing of Lithium Fluoride (LiF) in aqueous solvent using both detailed molecular simulation as well as reduced models within a Gener- alized Langevin Equation (GLE) framework. We explored the sensitivity of the ion-pairing phenomena to the details of descriptions of molecular interaction, comparing two empirical potentials to explicit quantum based density functional theory. We find quantitative differences in the potentials of mean force for ion-pairing as well as time dependent frictions that lead to variations in the rate constant and reactive flux correlation functions. These details reflect differences in solvent response tomore » ion-pairing between different representations of molecular interaction and influence anharmonicity of the dynamic response. We find that the short time anharmonic response is recovered with a GLE parameterization. Recovery of the details of long time response may require extensions to the reduced model. We show that the utility of using a reduced model leads to a straight forward application of variational transition state the- ory concepts to the condensed phase system. The significance of this is reflected in the analysis of committor distributions and the variation of planar hypersurfaces, leading to an improved understanding of factors that determine the rate of LiF ion-pairing. CJM and GKS are supported by the U.S. Department of Energy‘s (DOE) Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences. Pacific Northwest Na- tional Laboratory (PNNL) is operated for the Department of Energy by Battelle. MDB is grateful for the support of Laboratory Directed Research and Development funding under the auspices of PNNL’s Laboratory Initiative Materials Synthesis and Simulation across Scales (MS3). Additional computing resources were generously allocated by PNNL’s Institutional Computing program. EP acknowledges support from PNNL’s Alternate Sponsored Fellowship program and IMPRS Dres- den.Support to P.J. from the Czech Science Foundation (grant P208/12/G016) and the Academy of Sciences (Praemium Academie award) is gratefully acknowledged.« less

RNAstructure: software for RNA secondary structure prediction and analysis.

PubMed

Reuter, Jessica S; Mathews, David H

2010-03-15

To understand an RNA sequence's mechanism of action, the structure must be known. Furthermore, target RNA structure is an important consideration in the design of small interfering RNAs and antisense DNA oligonucleotides. RNA secondary structure prediction, using thermodynamics, can be used to develop hypotheses about the structure of an RNA sequence. RNAstructure is a software package for RNA secondary structure prediction and analysis. It uses thermodynamics and utilizes the most recent set of nearest neighbor parameters from the Turner group. It includes methods for secondary structure prediction (using several algorithms), prediction of base pair probabilities, bimolecular structure prediction, and prediction of a structure common to two sequences. This contribution describes new extensions to the package, including a library of C++ classes for incorporation into other programs, a user-friendly graphical user interface written in JAVA, and new Unix-style text interfaces. The original graphical user interface for Microsoft Windows is still maintained. The extensions to RNAstructure serve to make RNA secondary structure prediction user-friendly. The package is available for download from the Mathews lab homepage at http://rna.urmc.rochester.edu/RNAstructure.html.

Search extension transforms Wiki into a relational system: a case for flavonoid metabolite database.

PubMed

Arita, Masanori; Suwa, Kazuhiro

2008-09-17

In computer science, database systems are based on the relational model founded by Edgar Codd in 1970. On the other hand, in the area of biology the word 'database' often refers to loosely formatted, very large text files. Although such bio-databases may describe conflicts or ambiguities (e.g. a protein pair do and do not interact, or unknown parameters) in a positive sense, the flexibility of the data format sacrifices a systematic query mechanism equivalent to the widely used SQL. To overcome this disadvantage, we propose embeddable string-search commands on a Wiki-based system and designed a half-formatted database. As proof of principle, a database of flavonoid with 6902 molecular structures from over 1687 plant species was implemented on MediaWiki, the background system of Wikipedia. Registered users can describe any information in an arbitrary format. Structured part is subject to text-string searches to realize relational operations. The system was written in PHP language as the extension of MediaWiki. All modifications are open-source and publicly available. This scheme benefits from both the free-formatted Wiki style and the concise and structured relational-database style. MediaWiki supports multi-user environments for document management, and the cost for database maintenance is alleviated.

Search extension transforms Wiki into a relational system: A case for flavonoid metabolite database

PubMed Central

Arita, Masanori; Suwa, Kazuhiro

2008-01-01

Background In computer science, database systems are based on the relational model founded by Edgar Codd in 1970. On the other hand, in the area of biology the word 'database' often refers to loosely formatted, very large text files. Although such bio-databases may describe conflicts or ambiguities (e.g. a protein pair do and do not interact, or unknown parameters) in a positive sense, the flexibility of the data format sacrifices a systematic query mechanism equivalent to the widely used SQL. Results To overcome this disadvantage, we propose embeddable string-search commands on a Wiki-based system and designed a half-formatted database. As proof of principle, a database of flavonoid with 6902 molecular structures from over 1687 plant species was implemented on MediaWiki, the background system of Wikipedia. Registered users can describe any information in an arbitrary format. Structured part is subject to text-string searches to realize relational operations. The system was written in PHP language as the extension of MediaWiki. All modifications are open-source and publicly available. Conclusion This scheme benefits from both the free-formatted Wiki style and the concise and structured relational-database style. MediaWiki supports multi-user environments for document management, and the cost for database maintenance is alleviated. PMID:18822113

Solubility modeling of refrigerant/lubricant mixtures

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

Michels, H.H.; Sienel, T.H.

1996-12-31

A general model for predicting the solubility properties of refrigerant/lubricant mixtures has been developed based on applicable theory for the excess Gibbs energy of non-ideal solutions. In our approach, flexible thermodynamic forms are chosen to describe the properties of both the gas and liquid phases of refrigerant/lubricant mixtures. After an extensive study of models for describing non-ideal liquid effects, the Wohl-suffix equations, which have been extensively utilized in the analysis of hydrocarbon mixtures, have been developed into a general form applicable to mixtures where one component is a POE lubricant. In the present study we have analyzed several POEs wheremore » structural and thermophysical property data were available. Data were also collected from several sources on the solubility of refrigerant/lubricant binary pairs. We have developed a computer code (NISC), based on the Wohl model, that predicts dew point or bubble point conditions over a wide range of composition and temperature. Our present analysis covers mixtures containing up to three refrigerant molecules and one lubricant. The present code can be used to analyze the properties of R-410a and R-407c in mixtures with a POE lubricant. Comparisons with other models, such as the Wilson or modified Wilson equations, indicate that the Wohl-suffix equations yield more reliable predictions for HFC/POE mixtures.« less

Structure based alignment and clustering of proteins (STRALCP)

DOEpatents

Zemla, Adam T.; Zhou, Carol E.; Smith, Jason R.; Lam, Marisa W.

2013-06-18

Disclosed are computational methods of clustering a set of protein structures based on local and pair-wise global similarity values. Pair-wise local and global similarity values are generated based on pair-wise structural alignments for each protein in the set of protein structures. Initially, the protein structures are clustered based on pair-wise local similarity values. The protein structures are then clustered based on pair-wise global similarity values. For each given cluster both a representative structure and spans of conserved residues are identified. The representative protein structure is used to assign newly-solved protein structures to a group. The spans are used to characterize conservation and assign a "structural footprint" to the cluster.

Sequence Requirements of the 5-Enolpyruvylshikimate-3-phosphate Synthase 5[prime]-Upstream Region for Tissue-Specific Expression in Flowers and Seedlings.

PubMed Central

Benfey, PN; Takatsuji, H; Ren, L; Shah, DM; Chua, NH

1990-01-01

We have analyzed expression from deletion derivatives of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) 5[prime]-upstream region in transgenic petunia flowers and seedlings. In seedlings, expression was strongest in root cortex cells and in trichomes. High-level expression in petals and in seedling roots was conferred by large (>500 base-pair) stretches of sequence, but was lost when smaller fragments were analyzed individually. This apparent requirement for extensive sequence suggests that combinations of cis-elements that are widely separated control tissue-specific expression from the EPSPS promoter. We have also used the high-level, petal-specific expression of the EPSPS promoter to change petal color in two mutant petunia lines. PMID:12354968

“Ultra-high resolution optical trap with single fluorophore sensitivity”

PubMed Central

Comstock, Matthew J; Ha, Taekjip; Chemla, Yann R

2013-01-01

We present a single-molecule instrument that combines a timeshared ultra-high resolution dual optical trap interlaced with a confocal fluorescence microscope. In a demonstration experiment, individual single-fluorophore labeled DNA oligonucleotides were observed to bind and unbind to complementary DNA suspended between two trapped beads. Simultaneous with the single-fluorophore detection, coincident angstrom-scale changes in tether extension could be clearly observed. Fluorescence readout allowed us to determine the duplex melting rate as a function of force. The new instrument will enable the simultaneous measurement of angstrom-scale mechanical motion of individual DNA-binding proteins (e.g., single base pair stepping of DNA translocases) along with the detection of fluorescently labeled protein properties (e.g., internal configuration). PMID:21336286

One- and two-dimensional divalent copper coordination polymers based on kinked organodiimine and long flexible aliphatic dicarboxylate ligands

NASA Astrophysics Data System (ADS)

Mallika Krishnan, Subhashree; Supkowski, Ronald M.; LaDuca, Robert L.

2008-11-01

Hydrothermal synthesis under acidic conditions has afforded a pair of divalent copper coordination polymers containing the kinked dipodal tethering organodiimine 4,4'-dipyridylamine (dpa) and flexible long-chain aliphatic dicarboxylate ligands. The new materials were characterized by single crystal X-ray structure determination, infrared spectroscopy, and thermogravimetric analysis. [CuCl(suberate) 0.5(dpa)] ( 1) manifests 1-D ladder-like motifs aggregated into 3-D through hydrogen bonding and copper-mediated supramolecular interactions. Extension of the aliphatic chain within the dicarboxylate ligand by one methylene unit resulted in {[Cu(azelate)(dpa)(H 2O)] · 3H 2O} ( 2), a (4,4) rhomboid grid 2-D coordination polymer encapsulating acyclic water molecule trimers.

Nonenzymatic oligomerization reactions on templates containing inosinic acid or diaminopurine nucleotide residues

NASA Technical Reports Server (NTRS)

Kozlov, I. A.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

1999-01-01

The template-directed oligomerization of nucleoside-5'-phosphoro-2-methyl imidazolides on standard oligonucleotide templates has been studied extensively. Here, we describe experiments with templates in which inosinic acid (I) is substituted for guanylic acid, or 2,6-diaminopurine nucleotide (D) for adenylic acid. We find that the substitution of I for G in a template is strongly inhibitory and prevents any incorporation of C into internal positions in the oligomeric products of the reaction. The substitution of D for A, on the contrary, leads to increased incorporation of U into the products. We found no evidence for the template-directed facilitation of oligomerization of A or I through A-I base pairing. The significance of these results for prebiotic chemistry is discussed.

Correction of amplitude-phase distortion for polarimetric active radar calibrator

NASA Astrophysics Data System (ADS)

Lin, Jianzhi; Li, Weixing; Zhang, Yue; Chen, Zengping

2015-01-01

The polarimetric active radar calibrator (PARC) is extensively used as an external test target for system distortion compensation and polarimetric calibration for the high-resolution polarimetric radar. However, the signal undergoes distortion in the PARC, affecting the effectiveness of the compensation and the calibration. The system distortion compensation resulting from the distortion of the amplitude and phase in the PARC was analyzed based on the "method of paired echoes." Then the correction method was proposed, which separated the ideal signals from the distorted signals. Experiments were carried on real radar data, and the experimental results were in good agreement with the theoretical analysis. After the correction, the PARC can be better used as an external test target for the system distortion compensation.

DBS-LC-MS/MS assay for caffeine: validation and neonatal application.

PubMed

Bruschettini, Matteo; Barco, Sebastiano; Romantsik, Olga; Risso, Francesco; Gennai, Iulian; Chinea, Benito; Ramenghi, Luca A; Tripodi, Gino; Cangemi, Giuliana

2016-09-01

DBS might be an appropriate microsampling technique for therapeutic drug monitoring of caffeine in infants. Nevertheless, its application presents several issues that still limit its use. This paper describes a validated DBS-LC-MS/MS method for caffeine. The results of the method validation showed an hematocrit dependence. In the analysis of 96 paired plasma and DBS clinical samples, caffeine levels measured in DBS were statistically significantly lower than in plasma but the observed differences were independent from hematocrit. These results clearly showed the need for extensive validation with real-life samples for DBS-based methods. DBS-LC-MS/MS can be considered to be a good alternative to traditional methods for therapeutic drug monitoring or PK studies in preterm infants.

QRPA plus phonon coupling model and the photoabsorption cross section for 18,20,22O

NASA Astrophysics Data System (ADS)

Colò, G.; Bortignon, P. F.

2001-12-01

We have calculated the electric dipole strength distributions in the unstable neutron-rich oxygen isotopes 18,20,22O, in a model which include up to four quasiparticle-type configurations. The model is the extension, to include the effect of the pairing correlations, of a previous model very successful around closed shell nuclei, and it is based on the quasiparticle-phonon coupling. Low-lying dipole strength is found, which exhausts between 5 and 10% of the Thomas-Reiche-Kuhn (TRK) energy-weighted sum rule (EWSR) below 15 MeV excitation energy, in rather good agreement with recent experimental data. The role of the phonon coupling is shown to be crucial in order to obtain this result.

Probing the exchange statistics of one-dimensional anyon models

NASA Astrophysics Data System (ADS)

Greschner, Sebastian; Cardarelli, Lorenzo; Santos, Luis

2018-05-01

We propose feasible scenarios for revealing the modified exchange statistics in one-dimensional anyon models in optical lattices based on an extension of the multicolor lattice-depth modulation scheme introduced in [Phys. Rev. A 94, 023615 (2016), 10.1103/PhysRevA.94.023615]. We show that the fast modulation of a two-component fermionic lattice gas in the presence a magnetic field gradient, in combination with additional resonant microwave fields, allows for the quantum simulation of hardcore anyon models with periodic boundary conditions. Such a semisynthetic ring setup allows for realizing an interferometric arrangement sensitive to the anyonic statistics. Moreover, we show as well that simple expansion experiments may reveal the formation of anomalously bound pairs resulting from the anyonic exchange.

Theoretical study on the binding mechanism between N6-methyladenine and natural DNA bases.

PubMed

Song, Qi-Xia; Ding, Zhen-Dong; Liu, Jian-Hua; Li, Yan; Wang, Hai-Jun

2013-03-01

N6-methyladenine (m(6)A) is a rare base naturally occurring in DNA. It is different from the base adenine due to its N-CH(3). Therefore, the base not only pairs with thymine, but also with other DNA bases (cytosine, adenine and guanine). In this work, Møller-Plesset second-order (MP2) method has been used to investigate the binding mechanism between m(6)A and natural DNA bases in gas phase and in aqueous solution. The results show that N-CH(3) changed the way of N6-methyladenine binding to natural DNA bases. The binding style significantly influences the stability of base pairs. The trans-m(6)A:G and trans-m(6)A:C conformers are the most stable among all the base pairs. The existence of solvent can remarkably reduce the stability of the base pairs, and the DNA bases prefer pairing with trans-m(6)A to cis-m(6)A. Besides, the properties of these hydrogen bonds have been analyzed by atom in molecules (AIM) theory, natural bond orbital (NBO) analysis and Wiberg bond indexes (WBI). In addition, pairing with m(6)A decreases the binding energies compared to the normal Watson-Crick base pairs, it may explain the instability of the N6 site methylated DNA in theory.

Validation of a Crowdsourcing Methodology for Developing a Knowledge Base of Related Problem-Medication Pairs.

PubMed

McCoy, A B; Wright, A; Krousel-Wood, M; Thomas, E J; McCoy, J A; Sittig, D F

2015-01-01

Clinical knowledge bases of problem-medication pairs are necessary for many informatics solutions that improve patient safety, such as clinical summarization. However, developing these knowledge bases can be challenging. We sought to validate a previously developed crowdsourcing approach for generating a knowledge base of problem-medication pairs in a large, non-university health care system with a widely used, commercially available electronic health record. We first retrieved medications and problems entered in the electronic health record by clinicians during routine care during a six month study period. Following the previously published approach, we calculated the link frequency and link ratio for each pair then identified a threshold cutoff for estimated problem-medication pair appropriateness through clinician review; problem-medication pairs meeting the threshold were included in the resulting knowledge base. We selected 50 medications and their gold standard indications to compare the resulting knowledge base to the pilot knowledge base developed previously and determine its recall and precision. The resulting knowledge base contained 26,912 pairs, had a recall of 62.3% and a precision of 87.5%, and outperformed the pilot knowledge base containing 11,167 pairs from the previous study, which had a recall of 46.9% and a precision of 83.3%. We validated the crowdsourcing approach for generating a knowledge base of problem-medication pairs in a large non-university health care system with a widely used, commercially available electronic health record, indicating that the approach may be generalizable across healthcare settings and clinical systems. Further research is necessary to better evaluate the knowledge, to compare crowdsourcing with other approaches, and to evaluate if incorporating the knowledge into electronic health records improves patient outcomes.

Validation of a Crowdsourcing Methodology for Developing a Knowledge Base of Related Problem-Medication Pairs

PubMed Central

Wright, A.; Krousel-Wood, M.; Thomas, E. J.; McCoy, J. A.; Sittig, D. F.

2015-01-01

Summary Background Clinical knowledge bases of problem-medication pairs are necessary for many informatics solutions that improve patient safety, such as clinical summarization. However, developing these knowledge bases can be challenging. Objective We sought to validate a previously developed crowdsourcing approach for generating a knowledge base of problem-medication pairs in a large, non-university health care system with a widely used, commercially available electronic health record. Methods We first retrieved medications and problems entered in the electronic health record by clinicians during routine care during a six month study period. Following the previously published approach, we calculated the link frequency and link ratio for each pair then identified a threshold cutoff for estimated problem-medication pair appropriateness through clinician review; problem-medication pairs meeting the threshold were included in the resulting knowledge base. We selected 50 medications and their gold standard indications to compare the resulting knowledge base to the pilot knowledge base developed previously and determine its recall and precision. Results The resulting knowledge base contained 26,912 pairs, had a recall of 62.3% and a precision of 87.5%, and outperformed the pilot knowledge base containing 11,167 pairs from the previous study, which had a recall of 46.9% and a precision of 83.3%. Conclusions We validated the crowdsourcing approach for generating a knowledge base of problem-medication pairs in a large non-university health care system with a widely used, commercially available electronic health record, indicating that the approach may be generalizable across healthcare settings and clinical systems. Further research is necessary to better evaluate the knowledge, to compare crowdsourcing with other approaches, and to evaluate if incorporating the knowledge into electronic health records improves patient outcomes. PMID:26171079

KAPAO first light: the design, construction and operation of a low-cost natural guide star adaptive optics system

NASA Astrophysics Data System (ADS)

Severson, Scott A.; Choi, Philip I.; Badham, Katherine E.; Bolger, Dalton; Contreras, Daniel S.; Gilbreth, Blaine N.; Guerrero, Christian; Littleton, Erik; Long, Joseph; McGonigle, Lorcan P.; Morrison, William A.; Ortega, Fernando; Rudy, Alex R.; Wong, Jonathan R.; Spjut, Erik; Baranec, Christoph; Riddle, Reed

2014-07-01

We present the instrument design and first light observations of KAPAO, a natural guide star adaptive optics (AO) system for the Pomona College Table Mountain Observatory (TMO) 1-meter telescope. The KAPAO system has dual science channels with visible and near-infrared cameras, a Shack-Hartmann wavefront sensor, and a commercially available 140-actuator MEMS deformable mirror. The pupil relays are two pairs of custom off-axis parabolas and the control system is based on a version of the Robo-AO control software. The AO system and telescope are remotely operable, and KAPAO is designed to share the Cassegrain focus with the existing TMO polarimeter. We discuss the extensive integration of undergraduate students in the program including the multiple senior theses/capstones and summer assistantships amongst our partner institutions. This material is based upon work supported by the National Science Foundation under Grant No. 0960343.

Bridge helix bending promotes RNA polymerase II backtracking through a critical and conserved threonine residue

NASA Astrophysics Data System (ADS)

da, Lin-Tai; Pardo-Avila, Fátima; Xu, Liang; Silva, Daniel-Adriano; Zhang, Lu; Gao, Xin; Wang, Dong; Huang, Xuhui

2016-04-01

The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH residue T831 as a sensing probe for the 3'-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3'-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation.

Identification of a new Apscaviroid from Japanese persimmon.

PubMed

Nakaune, Ryoji; Nakano, Masaaki

2008-01-01

Three viroid-like sequences were detected from Japanese persimmon (Diospyrus kaki Thunb.) by RT-PCR using primers specific for members of the genus Apscaviroid. Based on the sequences, we determined the complete genomic sequences. Two had 92.1-94.3% sequence identity with citrus viroid OS (CVd-OS) and 91.4-96.3% identity with apple fruit crinkle viroid (AFCVd), respectively. Another one, tentatively named persimmon viroid (PVd), had 396 nucleotides and less than 70% sequence identity with known viroids. The secondary structure of PVd is proposed to be rod-like with extensive base pairing and contains the terminal conserved region and the central conserved region characteristic of the genus Apscaviroid. Moreover, we confirmed that the viroids, including PVd, are graft transmissible from persimmon to persimmon and that persimmon is a natural host of these viroids. According to its molecular and biological properties, PVd should be considered a member of a new species in the genus Apscaviroid.

Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide-protein complexes.

PubMed

Kondo, Jiro; Westhof, Eric

2011-10-01

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide-protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson-Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson-Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues.

Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide–protein complexes

PubMed Central

Kondo, Jiro; Westhof, Eric

2011-01-01

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide–protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson–Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson–Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues. PMID:21737431

Integrable equations of the infinite nonlinear Schrödinger equation hierarchy with time variable coefficients.

PubMed

Kedziora, D J; Ankiewicz, A; Chowdury, A; Akhmediev, N

2015-10-01

We present an infinite nonlinear Schrödinger equation hierarchy of integrable equations, together with the recurrence relations defining it. To demonstrate integrability, we present the Lax pairs for the whole hierarchy, specify its Darboux transformations and provide several examples of solutions. These resulting wavefunctions are given in exact analytical form. We then show that the Lax pair and Darboux transformation formalisms still apply in this scheme when the coefficients in the hierarchy depend on the propagation variable (e.g., time). This extension thus allows for the construction of complicated solutions within a greatly diversified domain of generalised nonlinear systems.

Defect pair formation in fluorine and nitrogen codoped TiO2

NASA Astrophysics Data System (ADS)

Kordatos, A.; Kelaidis, N.; Chroneos, A.

2018-04-01

Titanium oxide is extensively investigated because of its high chemical stability and its photocatalytic properties; nevertheless, the large band gap limits its activity to a small portion of the solar spectrum. Nitrogen and fluorine codoping is an efficient defect engineering strategy to increase the photocatalytic activity of titanium oxide. In the present study, we apply density functional theory to investigate the interaction of nitrogen with fluorine and the formation of defect pairs. We show that in fluorine and nitrogen codoped titanium oxide, the FiNi, FONi, and FiNTi defects can form. Their impact on the electronic structure of titanium oxide is discussed.

Enhancing genome assemblies by integrating non-sequence based data

PubMed Central

2011-01-01

Introduction Many genome projects were underway before the advent of high-throughput sequencing and have thus been supported by a wealth of genome information from other technologies. Such information frequently takes the form of linkage and physical maps, both of which can provide a substantial amount of data useful in de novo sequencing projects. Furthermore, the recent abundance of genome resources enables the use of conserved synteny maps identified in related species to further enhance genome assemblies. Methods The tammar wallaby (Macropus eugenii) is a model marsupial mammal with a low coverage genome. However, we have access to extensive comparative maps containing over 14,000 markers constructed through the physical mapping of conserved loci, chromosome painting and comprehensive linkage maps. Using a custom Bioperl pipeline, information from the maps was aligned to assembled tammar wallaby contigs using BLAT. This data was used to construct pseudo paired-end libraries with intervals ranging from 5-10 MB. We then used Bambus (a program designed to scaffold eukaryotic genomes by ordering and orienting contigs through the use of paired-end data) to scaffold our libraries. To determine how map data compares to sequence based approaches to enhance assemblies, we repeated the experiment using a 0.5× coverage of unique reads from 4 KB and 8 KB Illumina paired-end libraries. Finally, we combined both the sequence and non-sequence-based data to determine how a combined approach could further enhance the quality of the low coverage de novo reconstruction of the tammar wallaby genome. Results Using the map data alone, we were able order 2.2% of the initial contigs into scaffolds, and increase the N50 scaffold size to 39 KB (36 KB in the original assembly). Using only the 0.5× paired-end sequence based data, 53% of the initial contigs were assigned to scaffolds. Combining both data sets resulted in a further 2% increase in the number of initial contigs integrated into a scaffold (55% total) but a 35% increase in N50 scaffold size over the use of sequence-based data alone. Conclusions We provide a relatively simple pipeline utilizing existing bioinformatics tools to integrate map data into a genome assembly which is available at http://www.mcb.uconn.edu/fac.php?name=paska. While the map data only contributed minimally to assigning the initial contigs to scaffolds in the new assembly, it greatly increased the N50 size. This process added structure to our low coverage assembly, greatly increasing its utility in further analyses. PMID:21554765

Enhancing genome assemblies by integrating non-sequence based data.

PubMed

Heider, Thomas N; Lindsay, James; Wang, Chenwei; O'Neill, Rachel J; Pask, Andrew J

2011-05-28

Many genome projects were underway before the advent of high-throughput sequencing and have thus been supported by a wealth of genome information from other technologies. Such information frequently takes the form of linkage and physical maps, both of which can provide a substantial amount of data useful in de novo sequencing projects. Furthermore, the recent abundance of genome resources enables the use of conserved synteny maps identified in related species to further enhance genome assemblies. The tammar wallaby (Macropus eugenii) is a model marsupial mammal with a low coverage genome. However, we have access to extensive comparative maps containing over 14,000 markers constructed through the physical mapping of conserved loci, chromosome painting and comprehensive linkage maps. Using a custom Bioperl pipeline, information from the maps was aligned to assembled tammar wallaby contigs using BLAT. This data was used to construct pseudo paired-end libraries with intervals ranging from 5-10 MB. We then used Bambus (a program designed to scaffold eukaryotic genomes by ordering and orienting contigs through the use of paired-end data) to scaffold our libraries. To determine how map data compares to sequence based approaches to enhance assemblies, we repeated the experiment using a 0.5× coverage of unique reads from 4 KB and 8 KB Illumina paired-end libraries. Finally, we combined both the sequence and non-sequence-based data to determine how a combined approach could further enhance the quality of the low coverage de novo reconstruction of the tammar wallaby genome. Using the map data alone, we were able order 2.2% of the initial contigs into scaffolds, and increase the N50 scaffold size to 39 KB (36 KB in the original assembly). Using only the 0.5× paired-end sequence based data, 53% of the initial contigs were assigned to scaffolds. Combining both data sets resulted in a further 2% increase in the number of initial contigs integrated into a scaffold (55% total) but a 35% increase in N50 scaffold size over the use of sequence-based data alone. We provide a relatively simple pipeline utilizing existing bioinformatics tools to integrate map data into a genome assembly which is available at http://www.mcb.uconn.edu/fac.php?name=paska. While the map data only contributed minimally to assigning the initial contigs to scaffolds in the new assembly, it greatly increased the N50 size. This process added structure to our low coverage assembly, greatly increasing its utility in further analyses.

Closing loop base pairs in RNA loop-loop complexes: structural behavior, interaction energy and solvation analysis through molecular dynamics simulations.

PubMed

Golebiowski, Jérôme; Antonczak, Serge; Fernandez-Carmona, Juan; Condom, Roger; Cabrol-Bass, Daniel

2004-12-01

Nanosecond molecular dynamics using the Ewald summation method have been performed to elucidate the structural and energetic role of the closing base pair in loop-loop RNA duplexes neutralized by Mg2+ counterions in aqueous phases. Mismatches GA, CU and Watson-Crick GC base pairs have been considered for closing the loop of an RNA in complementary interaction with HIV-1 TAR. The simulations reveal that the mismatch GA base, mediated by a water molecule, leads to a complex that presents the best compromise between flexibility and energetic contributions. The mismatch CU base pair, in spite of the presence of an inserted water molecule, is too short to achieve a tight interaction at the closing-loop junction and seems to force TAR to reorganize upon binding. An energetic analysis has allowed us to quantify the strength of the interactions of the closing and the loop-loop pairs throughout the simulations. Although the water-mediated GA closing base pair presents an interaction energy similar to that found on fully geometry-optimized structure, the water-mediated CU closing base pair energy interaction reaches less than half the optimal value.

Molecular mechanisms of ribosomal protein gene coregulation

PubMed Central

Reja, Rohit; Vinayachandran, Vinesh; Ghosh, Sujana; Pugh, B. Franklin

2015-01-01

The 137 ribosomal protein genes (RPGs) of Saccharomyces provide a model for gene coregulation. We examined the positional and functional organization of their regulators (Rap1 [repressor activator protein 1], Fhl1, Ifh1, Sfp1, and Hmo1), the transcription machinery (TFIIB, TFIID, and RNA polymerase II), and chromatin at near-base-pair resolution using ChIP-exo, as RPGs are coordinately reprogrammed. Where Hmo1 is enriched, Fhl1, Ifh1, Sfp1, and Hmo1 cross-linked broadly to promoter DNA in an RPG-specific manner and demarcated by general minor groove widening. Importantly, Hmo1 extended 20–50 base pairs (bp) downstream from Fhl1. Upon RPG repression, Fhl1 remained in place. Hmo1 dissociated, which was coupled to an upstream shift of the +1 nucleosome, as reflected by the Hmo1 extension and core promoter region. Fhl1 and Hmo1 may create two regulatable and positionally distinct barriers, against which chromatin remodelers position the +1 nucleosome into either an activating or a repressive state. Consistent with in vitro studies, we found that specific TFIID subunits, in addition to cross-linking at the core promoter, made precise cross-links at Rap1 sites, which we interpret to reflect native Rap1–TFIID interactions. Our findings suggest how sequence-specific DNA binding regulates nucleosome positioning and transcription complex assembly >300 bp away and how coregulation coevolved with coding sequences. PMID:26385964

Characterization of DNA condensates induced by poly(ethylene oxide) and polylysine.

PubMed Central

Laemmli, U K

1975-01-01

High-molecular-weight DNA is known to collapse into very compact particles in a salt solution containing polymers like poly(ethylene oxide) [(EO)n] or polyacrylate. The biological relevance of this phenomenon is suggested by our recent finding that high concentrations of the highly acidic internal peptides found in the mature T4 bacteriophage head, as well as poly(glutamic acid) and poly(aspartic acid), can collapse DNA in a similar manner. The structure of DNAs collapsed by various methods has been studied with electron microscope. We find (EO)n collapses T4 or T7 bacteriophage DNA into compact particles only slightly larger than the size of the T4 and T7 head, respectively. In contrast, polylysine collapses DNA into different types of structures. Double-stranded DNA collapsed with (EO)n is cut by the single-strand specific Neurospora crassa endonuclease (EC 3.1.4.21) into small fragments. Extensive digestion only occurs above the critical concentration of polymer required for DNA collapse, demonstrating the (EO)n-collapsed DNA contains enzyme-vulnerable regions (probably at each fold), which are preferentially attacked. The size of the DNA fragments produced by limit-digestion with the nuclease ranges between 200 and 400 base pairs when DNA is collapsed by (EO)n. Only fragments of DNA which are larger than 600 base pairs are cut by the endonuclease in (EO)n-containing solution. Images PMID:1060108

Software dependability in the Tandem GUARDIAN system

NASA Technical Reports Server (NTRS)

Lee, Inhwan; Iyer, Ravishankar K.

1995-01-01

Based on extensive field failure data for Tandem's GUARDIAN operating system this paper discusses evaluation of the dependability of operational software. Software faults considered are major defects that result in processor failures and invoke backup processes to take over. The paper categorizes the underlying causes of software failures and evaluates the effectiveness of the process pair technique in tolerating software faults. A model to describe the impact of software faults on the reliability of an overall system is proposed. The model is used to evaluate the significance of key factors that determine software dependability and to identify areas for improvement. An analysis of the data shows that about 77% of processor failures that are initially considered due to software are confirmed as software problems. The analysis shows that the use of process pairs to provide checkpointing and restart (originally intended for tolerating hardware faults) allows the system to tolerate about 75% of reported software faults that result in processor failures. The loose coupling between processors, which results in the backup execution (the processor state and the sequence of events) being different from the original execution, is a major reason for the measured software fault tolerance. Over two-thirds (72%) of measured software failures are recurrences of previously reported faults. Modeling, based on the data, shows that, in addition to reducing the number of software faults, software dependability can be enhanced by reducing the recurrence rate.

Structural studies demonstrating a bacteriophage-like replication cycle of the eukaryote-infecting Paramecium bursaria chlorella virus-1

PubMed Central

Shimoni, Eyal; Dadosh, Tali; Rechav, Katya; Unger, Tamar

2017-01-01

A fundamental stage in viral infection is the internalization of viral genomes in host cells. Although extensively studied, the mechanisms and factors responsible for the genome internalization process remain poorly understood. Here we report our observations, derived from diverse imaging methods on genome internalization of the large dsDNA Paramecium bursaria chlorella virus-1 (PBCV-1). Our studies reveal that early infection stages of this eukaryotic-infecting virus occurs by a bacteriophage-like pathway, whereby PBCV-1 generates a hole in the host cell wall and ejects its dsDNA genome in a linear, base-pair-by-base-pair process, through a membrane tunnel generated by the fusion of the virus internal membrane with the host membrane. Furthermore, our results imply that PBCV-1 DNA condensation that occurs shortly after infection probably plays a role in genome internalization, as hypothesized for the infection of some bacteriophages. The subsequent perforation of the host photosynthetic membranes presumably enables trafficking of viral genomes towards host nuclei. Previous studies established that at late infection stages PBCV-1 generates cytoplasmic organelles, termed viral factories, where viral assembly takes place, a feature characteristic of many large dsDNA viruses that infect eukaryotic organisms. PBCV-1 thus appears to combine a bacteriophage-like mechanism during early infection stages with a eukaryotic-like infection pathway in its late replication cycle. PMID:28850602

Sub-Network Kernels for Measuring Similarity of Brain Connectivity Networks in Disease Diagnosis.

PubMed

Jie, Biao; Liu, Mingxia; Zhang, Daoqiang; Shen, Dinggang

2018-05-01

As a simple representation of interactions among distributed brain regions, brain networks have been widely applied to automated diagnosis of brain diseases, such as Alzheimer's disease (AD) and its early stage, i.e., mild cognitive impairment (MCI). In brain network analysis, a challenging task is how to measure the similarity between a pair of networks. Although many graph kernels (i.e., kernels defined on graphs) have been proposed for measuring the topological similarity of a pair of brain networks, most of them are defined using general graphs, thus ignoring the uniqueness of each node in brain networks. That is, each node in a brain network denotes a particular brain region, which is a specific characteristics of brain networks. Accordingly, in this paper, we construct a novel sub-network kernel for measuring the similarity between a pair of brain networks and then apply it to brain disease classification. Different from current graph kernels, our proposed sub-network kernel not only takes into account the inherent characteristic of brain networks, but also captures multi-level (from local to global) topological properties of nodes in brain networks, which are essential for defining the similarity measure of brain networks. To validate the efficacy of our method, we perform extensive experiments on subjects with baseline functional magnetic resonance imaging data obtained from the Alzheimer's disease neuroimaging initiative database. Experimental results demonstrate that the proposed method outperforms several state-of-the-art graph-based methods in MCI classification.

Population Level Purifying Selection and Gene Expression Shape Subgenome Evolution in Maize.

PubMed

Pophaly, Saurabh D; Tellier, Aurélien

2015-12-01

The maize ancestor experienced a recent whole-genome duplication (WGD) followed by gene erosion which generated two subgenomes, the dominant subgenome (maize1) experiencing fewer deletions than maize2. We take advantage of available extensive polymorphism and gene expression data in maize to study purifying selection and gene expression divergence between WGD retained paralog pairs. We first report a strong correlation in nucleotide diversity between duplicate pairs, except for upstream regions. We then show that maize1 genes are under stronger purifying selection than maize2. WGD retained genes have higher gene dosage and biased Gene Ontologies consistent with previous studies. The relative gene expression of paralogs across tissues demonstrates that 98% of duplicate pairs have either subfunctionalized in a tissuewise manner or have diverged consistently in their expression thereby preventing functional complementation. Tissuewise subfunctionalization seems to be a hallmark of transcription factors, whereas consistent repression occurs for macromolecular complexes. We show that dominant gene expression is a strong determinant of the strength of purifying selection, explaining the inferred stronger negative selection on maize1 genes. We propose a novel expression-based classification of duplicates which is more robust to explain observed polymorphism patterns than the subgenome location. Finally, upstream regions of repressed genes exhibit an enrichment in transposable elements which indicates a possible mechanism for expression divergence. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Under what conditions does G.C Watson-Crick DNA base pair acquire all four configurations characteristic for A.T Watson-Crick DNA base pair?].

PubMed

Brovarets', O O

2013-01-01

At the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory it was established for the first time, that the Löwdin's G*.C* DNA base pair formed by the mutagenic tautomers can acquire, as the A-T Watson-Crick DNA base pair, four biologically important configurations, namely: Watson-Crick, reverse Watson-Crick, Hoogsteen and reverse Hoogsteen. This fact demonstrates rather unexpected role of the tautomerisation of the one of the Watson-Crick DNA base pairs, in particular, via double proton transfer: exactly the G.C-->G*.C* tautomerisation allows to overcome steric hindrances for the implementation of the above mentioned configurations. Geometric, electron-topological and energetic properties of the H-bonds that stabilise the studied pairs, as well as the energetic characteristics of the latters are presented.

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

Leszczynski, Jerzy; Sponer, Judit; Sponer, Jiri

Recent experimental studies on the Watson Crick type base pairing of triazine and aminopyrimidine derivatives suggest that acid/base properties of the constituent bases might be related to the duplex stabilities measured in solution. Herein we use high-level quantum chemical calculations and molecular dynamics simulations to evaluate the base pairing and stacking interactions of seven selected base pairs, which are common in that they are stabilized by two NH O hydrogen bonds separated by one NH N hydrogen bond. We show that neither the base pairing nor the base stacking interaction energies correlate with the reported pKa data of the basesmore » and the melting points of the duplexes. This suggests that the experimentally observed correlation between the melting point data of the duplexes and the pKa values of the constituent bases is not rooted in the intrinsic base pairing and stacking properties. The physical chemistry origin of the observed experimental correlation thus remains unexplained and requires further investigations. In addition, since our calculations are carried out with extrapolation to the complete basis set of atomic orbitals and with inclusion of higher electron correlation effects, they provide reference data for stacking and base pairing energies of non-natural bases.« less

SiC/Si diode trigger circuit provides automatic range switching for log amplifier

NASA Technical Reports Server (NTRS)

1967-01-01

SiC/Si diode pair provides automatic range change to extend the operating range of a logarithmic amplifier-conversion circuit and assures stability at or near the range switch-over point. the diode provides hysteresis for a trigger circuit that actuates a relay at the desired range extension point.

Does H → γγ taste like vanilla new physics?

NASA Astrophysics Data System (ADS)

Almeida, L. G.; Bertuzzo, E.; Machado, P. A. N.; Funchal, R. Zukanovich

2012-11-01

We analyse the interplay between the Higgs to diphoton rate and electroweak precision measurements constraints in extensions of the Standard Model with new uncolored charged fermions that do not mix with the ordinary ones. We also compute the pair production cross sections for the lightest fermion and compare them with current bounds.

Nuclear Cartography: Patterns in Binding Energies and Subatomic Structure

ERIC Educational Resources Information Center

Simpson, E. C.; Shelley, M.

2017-01-01

Nuclear masses and binding energies are some of the first nuclear properties met in high school physics, and can be used to introduce radioactive decays, fusion, and fission. With relatively little extension, they can also illustrate fundamental concepts in nuclear physics, such as shell structure and pairing, and to discuss how the elements…

The Maximum Likelihood Estimation of Signature Transformation /MLEST/ algorithm. [for affine transformation of crop inventory data

NASA Technical Reports Server (NTRS)

Thadani, S. G.

1977-01-01

The Maximum Likelihood Estimation of Signature Transformation (MLEST) algorithm is used to obtain maximum likelihood estimates (MLE) of affine transformation. The algorithm has been evaluated for three sets of data: simulated (training and recognition segment pairs), consecutive-day (data gathered from Landsat images), and geographical-extension (large-area crop inventory experiment) data sets. For each set, MLEST signature extension runs were made to determine MLE values and the affine-transformed training segment signatures were used to classify the recognition segments. The classification results were used to estimate wheat proportions at 0 and 1% threshold values.

Thermal transport in topological-insulator-based superconducting hybrid structures with mixed singlet and triplet pairing states.

PubMed

Li, Hai; Zhao, Yuan Yuan

2017-11-22

In the framework of the Bogoliubov-de Gennes equation, we investigate the thermal transport properties in topological-insulator-based superconducting hybrid structures with mixed spin-singlet and spin-triplet pairing states, and emphasize the different manifestations of the spin-singlet and spin-triplet pairing states in the thermal transport signatures. It is revealed that the temperature-dependent differential thermal conductance strongly depends on the components of the pairing state, and the negative differential thermal conductance only occurs in the spin-singlet pairing state dominated regime. It is also found that the thermal conductance is profoundly sensitive to the components of the pairing state. In the spin-singlet pairing state controlled regime, the thermal conductance obviously oscillates with the phase difference and junction length. With increasing the proportion of the spin-triplet pairing state, the oscillating characteristic of the thermal conductance fades out distinctly. These results suggest an alternative route for distinguishing the components of pairing states in topological-insulator-based superconducting hybrid structures.

Analysis of global gene expression in Brachypodium distachyon reveals extensive network plasticity in response to abiotic stress.

PubMed

Priest, Henry D; Fox, Samuel E; Rowley, Erik R; Murray, Jessica R; Michael, Todd P; Mockler, Todd C

2014-01-01

Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium.

Formulating face verification with semidefinite programming.

PubMed

Yan, Shuicheng; Liu, Jianzhuang; Tang, Xiaoou; Huang, Thomas S

2007-11-01

This paper presents a unified solution to three unsolved problems existing in face verification with subspace learning techniques: selection of verification threshold, automatic determination of subspace dimension, and deducing feature fusing weights. In contrast to previous algorithms which search for the projection matrix directly, our new algorithm investigates a similarity metric matrix (SMM). With a certain verification threshold, this matrix is learned by a semidefinite programming approach, along with the constraints of the kindred pairs with similarity larger than the threshold, and inhomogeneous pairs with similarity smaller than the threshold. Then, the subspace dimension and the feature fusing weights are simultaneously inferred from the singular value decomposition of the derived SMM. In addition, the weighted and tensor extensions are proposed to further improve the algorithmic effectiveness and efficiency, respectively. Essentially, the verification is conducted within an affine subspace in this new algorithm and is, hence, called the affine subspace for verification (ASV). Extensive experiments show that the ASV can achieve encouraging face verification accuracy in comparison to other subspace algorithms, even without the need to explore any parameters.

Genetic and DNA sequence analysis of the kanamycin resistance transposon Tn903.

PubMed Central

Grindley, N D; Joyce, C M

1980-01-01

The kanamycin resistance transposon Tn903 consists of a unique region of about 1000 base pairs bounded by a pair of 1050-base-pair inverted repeat sequences. Each repeat contains two Pvu II endonuclease cleavage sites separated by 520 base pairs. We have constructed derivatives of Tn903 in which this 520-base-pair fragment is deleted from one or both repeats. Those derivatives that lack both 520-base-pair fragments cannot transpose, whereas those that lack just one remain transposition proficient. One such transposable derivative, Tn903 delta I, has been selected for further study. We have determined the sequence of the intact inverted repeat. The 18 base pairs at each end are identical and inverted relative to one another, a structure characteristic of insertion sequences. Additional experiments indicate that a single inverted repeat from Tn903 can, in fact, transpose; we propose that this element be called IS903. To correlate the DNA sequence with genetic activities, we have created mutations by inserting a 10-base-pair DNA fragment at several sites within the intact repeat of Tn903 delta 1, and we have examined the effect of such insertions on transposability. The results suggest that IS903 encodes a 307-amino-acid polypeptide (a "transposase") that is absolutely required for transposition of IS903 or Tn903. Images PMID:6261245

Models and methods to characterize site amplification from a pair of records

USGS Publications Warehouse

Safak, E.

1997-01-01

The paper presents a tutorial review of the models and methods that are used to characterize site amplification from the pairs of rock- and soil-site records, and introduces some new techniques with better theoretical foundations. The models and methods discussed include spectral and cross-spectral ratios, spectral ratios for downhole records, response spectral ratios, constant amplification factors, parametric models, physical models, and time-varying filters. An extensive analytical and numerical error analysis of spectral and cross-spectral ratios shows that probabilistically cross-spectral ratios give more reliable estimates of site amplification. Spectral ratios should not be used to determine site amplification from downhole-surface recording pairs because of the feedback in the downhole sensor. Response spectral ratios are appropriate for low frequencies, but overestimate the amplification at high frequencies. The best method to be used depends on how much precision is required in the estimates.

Bipropellant propulsion with reciprocating pumps

NASA Astrophysics Data System (ADS)

Whitehead, John C.

1993-06-01

A pressure regulated gas generator rocket cycle with alternately pressurized pairs of reciprocating pumps offers thrust-on-demand operation with significantly lower inert mass than conventional spacecraft liquid propulsion systems. The operation of bipropellant feed systems with reciprocating pumps is explained, with consideration for both short and long term missions. There are several methods for startup and shutdown of this self-starting pump-fed system, with preference determined by thrust duty cycle and mission duration. Progress to date includes extensive development testing of components unique to this type of system, and several live tests with monopropellant hydrazine. Pneumatic pump control valves which render pistons and bellows automatically responsive to downstream liquid demand are significantly simpler than those described previously. A compact pumpset mounted to central liquid manifolds has a pair of oxidizer pumps pneumatically slaved to a pair of fuel pumps to reduce vibration. A warm gas pressure reducer for tank expulsion can eliminate any remaining need for inert gas storage.

R-matrix-valued Lax pairs and long-range spin chains

NASA Astrophysics Data System (ADS)

Sechin, I.; Zotov, A.

2018-06-01

In this paper we discuss R-matrix-valued Lax pairs for slN Calogero-Moser model and their relation to integrable quantum long-range spin chains of the Haldane-Shastry-Inozemtsev type. First, we construct the R-matrix-valued Lax pairs for the third flow of the classical Calogero-Moser model. Then we notice that the scalar parts (in the auxiliary space) of the M-matrices corresponding to the second and third flows have form of special spin exchange operators. The freezing trick restricts them to quantum Hamiltonians of long-range spin chains. We show that for a special choice of the R-matrix these Hamiltonians reproduce those for the Inozemtsev chain. In the general case related to the Baxter's elliptic R-matrix we obtain a natural anisotropic extension of the Inozemtsev chain. Commutativity of the Hamiltonians is verified numerically. Trigonometric limits lead to the Haldane-Shastry chains and their anisotropic generalizations.

Silver(I)-Mediated Base Pairs in DNA Sequences Containing 7-Deazaguanine/Cytosine: towards DNA with Entirely Metallated Watson-Crick Base Pairs.

PubMed

Méndez-Arriaga, José M; Maldonado, Carmen R; Dobado, José A; Galindo, Miguel A

2018-03-26

DNA sequences comprising noncanonical 7-deazaguanine ( 7C G) and canonical cytosine (C) are capable of forming Watson-Crick base pairs via hydrogen bonds as well as silver(I)-mediated base pairs by coordination to central silver(I) ions. Duplexes I and II containing 7C G and C have been synthesized and characterized. The incorporation of silver(I) ions into these duplexes has been studied by means of temperature-dependent UV spectroscopy, circular dichroism, and DFT calculations. The results suggest the formation of DNA molecules comprising contiguous metallated 7C G-Ag I -C Watson-Crick base pairs that preserve the original B-type conformation. Furthermore, additional studies performed on duplex III indicated that, in the presence of Ag I ions, 7C G-C and 7C A-T Watson-Crick base pairs ( 7C A, 7-deazadenine; T, thymine) can be converted to metallated 7C G-Ag I -C and 7C A-Ag I -T base pairs inside the same DNA molecule whilst maintaining its initial double helix conformation. These findings are very important for the development of customized silver-DNA nanostructures based on a Watson-Crick complementarity pattern. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine

USGS Publications Warehouse

Guerreiro, Isabel; Nunes, Andreia; Woltering, Joost M.; Casaca, Ana; Nóvoa, Ana; Vinagre, Tânia; Hunter, Margaret E.; Duboule, Denis; Mallo, Moisés

2013-01-01

Patterning of the vertebrate skeleton requires the coordinated activity of Hox genes. In particular, Hox10 proteins are essential to set the transition from thoracic to lumbar vertebrae because of their rib-repressing activity. In snakes, however, the thoracic region extends well into Hox10-expressing areas of the embryo, suggesting that these proteins are unable to block rib formation. Here, we show that this is not a result of the loss of rib-repressing properties by the snake proteins, but rather to a single base pair change in a Hox/Paired box (Pax)-responsive enhancer, which prevents the binding of Hox proteins. This polymorphism is also found in Paenungulata, such as elephants and manatees, which have extended rib cages. In vivo, this modified enhancer failed to respond to Hox10 activity, supporting its role in the extension of rib cages. In contrast, the enhancer could still interact with Hoxb6 and Pax3 to promote rib formation. These results suggest that a polymorphism in the Hox/Pax-responsive enhancer may have played a role in the evolution of the vertebrate spine by differently modulating its response to rib-suppressing and rib-promoting Hox proteins.

Three-dimensional reconstruction of vessels with stenoses and aneurysms from dual biplane angiograms

NASA Astrophysics Data System (ADS)

Fessler, Jeffrey A.; Macovski, Albert

1989-05-01

Parametric model-based approaches to 3-D reconstruction of vessels overcome the inherent problem of underdeterminancy in reconstruction from limited views by incorporating a priori knowledge about the structure of vessels and about the measurement statistics. In this paper, we describe two extensions to the parametric approach. First, we consider the problem of reconstruction from a pair of bi-plane angiograms that are acquired at different projection angles. Since bi-plane angiography systems are widely available, this is a practical measurement geometry. The patient may move between acquisitions, so we have extended our model to allow for object translation between the first and second pair of projections. Second, we describe how to accurately estimate the dimensions of a aneurysm from the dual-biplane angiogram. We applied the new algorithm to four synthetic angiograms (projection angles 0°, 20°, 90°, and 110°) of a vessel with a small aneurysm and an eccentric stenosis. The angiograms were corrupted by additive noise and background structure. Except near the top and bottom of the aneurysm, the estimated cross sections of the aneurysm and stenosis agree very well with the true cross sections.

The use of the ph1b mutant to induce recombination between the chromosomes of wheat and barley

PubMed Central

Rey, María-Dolores; Calderón, María C.; Prieto, Pilar

2015-01-01

Intensive breeding has led to a narrowing in the genetic base of our major crops. In wheat, access to the extensive gene pool residing in its many and varied relatives (some cultivated, others wild) is hampered by the block on recombination imposed by the Ph1 (Pairing homoeologous 1) gene. Here, the ph1b mutant has been exploited to induced allosyndesis between wheat chromosomes and those of both Hordeum vulgare (cultivated barley) and H. chilense (a wild barley). A number of single chromosome Hordeum sp. substitution and addition lines in wheat were crossed and backcrossed to the ph1b mutant to produce plants in which pairing between the wheat and the non-wheat chromosomes was not suppressed by the presence of Ph1. Genomic in situ hybridization was applied to almost 500 BC1F2 progeny as a screen for allosyndetic recombinants. Chromosome rearrangements were detected affecting H. chilense chromosomes 4Hch, 5Hch, 6Hch, and 7Hch and H. vulgare chromosomes 4Hv, 6Hv, and 7Hv. Two of these were clearly the product of a recombination event involving chromosome 4Hch and a wheat chromosome. PMID:25852713

A radon-thoron isotope pair as a reliable earthquake precursor

PubMed Central

Hwa Oh, Yong; Kim, Guebuem

2015-01-01

Abnormal increases in radon (222Rn, half-life = 3.82 days) activity have occasionally been observed in underground environments before major earthquakes. However, 222Rn alone could not be used to forecast earthquakes since it can also be increased due to diffusive inputs over its lifetime. Here, we show that a very short-lived isotope, thoron (220Rn, half-life = 55.6 s; mean life = 80 s), in a cave can record earthquake signals without interference from other environmental effects. We monitored 220Rn together with 222Rn in air of a limestone-cave in Korea for one year. Unusually large 220Rn peaks were observed only in February 2011, preceding the 2011 M9.0 Tohoku-Oki Earthquake, Japan, while large 222Rn peaks were observed in both February 2011 and the summer. Based on our analyses, we suggest that the anomalous peaks of 222Rn and 220Rn activities observed in February were precursory signals related to the Tohoku-Oki Earthquake. Thus, the 220Rn-222Rn combined isotope pair method can present new opportunities for earthquake forecasting if the technique is extensively employed in earthquake monitoring networks around the world. PMID:26269105

Non-perturbative RPA-method implemented in the Coulomb gauge QCD Hamiltonian: From quarks and gluons to baryons and mesons

NASA Astrophysics Data System (ADS)

Yepez-Martinez, Tochtli; Civitarese, Osvaldo; Hess, Peter O.

2018-02-01

Starting from an algebraic model based on the QCD-Hamiltonian and previously applied to study meson states, we have developed an extension of it in order to explore the structure of baryon states. In developing our approach we have adapted concepts taken from group theory and non-perturbative many-body methods to describe states built from effective quarks and anti-quarks degrees of freedom. As a Hamiltonian we have used the QCD Hamiltonian written in the Coulomb Gauge, and expressed it in terms of effective quark-antiquark, di-quarks and di-antiquark excitations. To gain some insights about the relevant interactions of quarks in hadronic states, the Hamiltonian was approximately diagonalized by mapping quark-antiquark pairs and di-quarks (di-antiquarks) onto phonon states. In dealing with the structure of the vacuum of the theory, color-scalar and color-vector states are introduced to account for ground-state correlations. While the use of a purely color-scalar ground state is an obvious choice, so that colorless hadrons contain at least three quarks, the presence of coupled color-vector pairs in the ground state allows for colorless excitations resulting from the action of color objects upon it.

Iapetus: Tectonic structure and geologic history

NASA Technical Reports Server (NTRS)

Croft, Steven K.

1991-01-01

Many papers have been written about the surface of Iapetus, but most of these have discussed either the nature of the strongly contrasting light and dark materials or the cratering record. Little has been said about other geologic features on Iapetus, such as tectonic structures, which would provide constraints on Iapetus' thermal history. Most references have suggested that there is no conclusive evidence for any tectonic activity, even when thermal history studies indicate that there should be. However, a new study of Iapetus' surface involving the use of stereo pairs, an extensive tectonic network has been recognized. A few new observations concerning the craters and dark material were also made. Thus the geology and geologic history of Iapetus can be more fully outlined than before. The tectonic network is shown along with prominent craters and part of the dark material in the geologic/tectonic sketch map. The topology of crater rims and scarps are quite apparent and recognizable in the different image pairs. The heights and slopes of various features given are based on comparison with the depths of craters 50 to 100 km in diameter, which are assumed to have the same depths as craters of similar diameter on Rhea and Titania.

Comparable stability of Hoogsteen and Watson-Crick base pairs in ionic liquid choline dihydrogen phosphate.

PubMed

Tateishi-Karimata, Hisae; Nakano, Miki; Sugimoto, Naoki

2014-01-08

The instability of Hoogsteen base pairs relative to Watson-Crick base pairs has limited biological applications of triplex-forming oligonucleotides. Hydrated ionic liquids (ILs) provide favourable environments for a wide range of chemical reactions and are known to impact the stabilities of Watson-Crick base pairs. We found that DNA triplex formation was significantly stabilized in hydrated choline dihydrogen phosphate as compared with an aqueous buffer at neutral pH. Interestingly, the stability of Hoogsteen base pairs was found to be comparable with that of Watson-Crick base pairs in the hydrated IL. Molecular dynamics simulations of a DNA triplex in the presence of choline ions revealed that the DNA triplex was stabilized because of the binding of choline ion around the third strand in the grooves. Our finding will facilitate the development of new DNA materials. Our data also indicate that triplex formation may be stabilized inside cells where choline ions and their derivatives are abundant in vivo.

Comparable Stability of Hoogsteen and Watson–Crick Base Pairs in Ionic Liquid Choline Dihydrogen Phosphate

PubMed Central

Tateishi-Karimata, Hisae; Nakano, Miki; Sugimoto, Naoki

2014-01-01

The instability of Hoogsteen base pairs relative to Watson–Crick base pairs has limited biological applications of triplex-forming oligonucleotides. Hydrated ionic liquids (ILs) provide favourable environments for a wide range of chemical reactions and are known to impact the stabilities of Watson–Crick base pairs. We found that DNA triplex formation was significantly stabilized in hydrated choline dihydrogen phosphate as compared with an aqueous buffer at neutral pH. Interestingly, the stability of Hoogsteen base pairs was found to be comparable with that of Watson–Crick base pairs in the hydrated IL. Molecular dynamics simulations of a DNA triplex in the presence of choline ions revealed that the DNA triplex was stabilized because of the binding of choline ion around the third strand in the grooves. Our finding will facilitate the development of new DNA materials. Our data also indicate that triplex formation may be stabilized inside cells where choline ions and their derivatives are abundant in vivo. PMID:24399194

m1A and m1G Potently Disrupt A-RNA Structure Due to the Intrinsic Instability of Hoogsteen Base Pairs

PubMed Central

Zhou, Huiqing; Kimsey, Isaac J.; Nikolova, Evgenia N.; Sathyamoorthy, Bharathwaj; Grazioli, Gianmarc; McSally, James; Bai, Tianyu; Wunderlich, Christoph H.; Kreutz, Christoph; Andricioaei, Ioan; Al-Hashimi, Hashim M.

2016-01-01

The B-DNA double helix can dynamically accommodate G–C and A–T base pairs in either Watson-Crick or Hoogsteen configurations. Here, we show that G–C+ and A–U Hoogsteen base pairs are strongly disfavored in A-RNA. As a result, N1-methyl adenosine and N1-methyl guanosine, which occur in DNA as a form of alkylation damage, and in RNA as a posttranscriptional modification, have dramatically different consequences. They create G–C+ and A–U Hoogsteen base pairs in duplex DNA that maintain the structural integrity of the double helix, but block base pairing all together and induce local duplex melting in RNA, providing a mechanism for potently disrupting RNA structure through posttranscriptional modifications. The markedly different propensities to form Hoogsteen base pairs in B-DNA and A-RNA may help meet the opposing requirements of maintaining genome stability on one hand, and dynamically modulating the structure of the epitranscriptome on the other. PMID:27478929

Efficient anomalous reflection through near-field interactions in metasurfaces

NASA Astrophysics Data System (ADS)

Chalabi, H.; Ra'di, Y.; Sounas, D. L.; Alù, A.

2017-08-01

Gradient metasurfaces have been extensively used in the past few years for advanced wave manipulation over a thin surface. These metasurfaces have been mostly designed based on the generalized laws of reflection and refraction. However, it was recently revealed that metasurfaces based on this approach tend to suffer from inefficiencies and complex design requirements. We have recently proposed a different approach to the problem of efficient beam steering using a surface, based on bianisotropic particles in a periodic array. Here, we show highly efficient reflective metasurfaces formed by pairs of isotropic dielectric rods, which can offer asymmetrical scattering of normally incident beams with unitary efficiency. Our theory shows that moderately broadband anomalous reflection can be achieved with suitably designed periodic arrays of isotropic nanoparticles. We also demonstrate practical designs using TiO2 cylindrical nanorods to deflect normally incident light toward a desired direction. The proposed structures may pave the way to a broader range of light management opportunities, with applications in energy harvesting, signaling, and communications.

Structural Basis of Ligand Binding by a C-di-GMP Riboswitch

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

Smith, K.; Lipchock, S; Ames, T

2009-01-01

The second messenger signaling molecule bis-(3{prime}-5{prime})-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 {angstrom} resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structuralmore » data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling.« less

Generalized Detectability for Discrete Event Systems

PubMed Central

Shu, Shaolong; Lin, Feng

2011-01-01

In our previous work, we investigated detectability of discrete event systems, which is defined as the ability to determine the current and subsequent states of a system based on observation. For different applications, we defined four types of detectabilities: (weak) detectability, strong detectability, (weak) periodic detectability, and strong periodic detectability. In this paper, we extend our results in three aspects. (1) We extend detectability from deterministic systems to nondeterministic systems. Such a generalization is necessary because there are many systems that need to be modeled as nondeterministic discrete event systems. (2) We develop polynomial algorithms to check strong detectability. The previous algorithms are based on observer whose construction is of exponential complexity, while the new algorithms are based on a new automaton called detector. (3) We extend detectability to D-detectability. While detectability requires determining the exact state of a system, D-detectability relaxes this requirement by asking only to distinguish certain pairs of states. With these extensions, the theory on detectability of discrete event systems becomes more applicable in solving many practical problems. PMID:21691432

Skeleton-based tracing of curved fibers from 3D X-ray microtomographic imaging

NASA Astrophysics Data System (ADS)

Huang, Xiang; Wen, Donghui; Zhao, Yanwei; Wang, Qinghui; Zhou, Wei; Deng, Daxiang

A skeleton-based fiber tracing algorithm is described and applied on a specific fibrous material, porous metal fiber sintered sheet (PMFSS), featuring high porosity and curved fibers. The skeleton segments are firstly categorized according to the connectivity of the skeleton paths. Spurious segments like fiber bonds are detected making extensive use of the distance transform (DT) values. Single fibers are then traced and reconstructed by consecutively choosing the connecting skeleton segment pairs that show the most similar orientations and radius. Moreover, to reduce the misconnection due to the tracing orders, a multilevel tracing strategy is proposed. The fibrous network is finally reconstructed by dilating single fibers according to the DT values. Based on the traced single fibers, various morphology information regarding fiber length, radius, orientation, and tortuosity are quantitatively analyzed and compared with our previous results (Wang et al., 2013). Moreover, the number of bonds per fibers are firstly accessed. The methodology described in this paper can be expanded to other fibrous materials with adapted parameters.

BARTERING FOR A COMPATIBLE KIDNEY USING YOUR INCOMPATIBLE, LIVE KIDNEY DONOR: LEGAL AND ETHICAL ISSUES RELATED TO KIDNEY CHAINS.

PubMed

Tenenbaum, Evelyn M

2016-01-01

Kidney chains are a recent and novel method of increasing the number of available kidneys for transplantation and have the potential to save thousands of lives. However, because they are novel, kidney chains do not fit neatly within existing legal and ethicalframeworks, raising potential barriers to their full implementation. Kidney chains are an extension of paired kidney donation, which began in the United States in 2000. Paired kidney donations allow kidney patients with willing, but incompatible, donors to swap donors to increase the number of donor/recipient pairs and consequently, the number of transplants. More recently, transplant centers have been using non-simultaneous, extended, altruistic donor ("NEAD") kidney chains--which consist of a sequence of donations by incompatible donors--to further expand the number of donations. This Article fully explains paired kidney donation and kidney chains and focuses on whether NEAD chains are more coercive than traditional kidney donation to a family member or close friend and whether NEAD chains violate the National Organ Transplant Act's prohibition on the transfer of organs for valuable consideration.

Self-consistent description of the SHFB equations for 112Sn

NASA Astrophysics Data System (ADS)

Ghafouri, M.; Sadeghi, H.; Torkiha, M.

2018-03-01

The Hartree-Fock (HF) method is an excellent approximation of the closed shell magic nuclei. Pair correlation is essential for the description of open shell nuclei and has been derived for even-even, odd-odd and even-odd nuclei. These effects are reported by Hartree-Fock with BCS (HFBCS) or Hartree-Fock-Bogolyubov (HFB). These issues have been investigated, especially in the nuclear charts, and such studies have been compared with the observed information. We compute observations such as total binding energy, charge radius, densities, separation energies, pairing gaps and potential energy surfaces for neutrons and protons, and compare them with experimental data and the result of the spherical codes. In spherical even-even neutron-rich nuclei are considered in the Skyrme-Hartree-Fock-Bogolyubov (SHFB) method with density-dependent pairing interaction. Zero-range density-dependent interactions is used in the pairing channel. We solve SHF or SHFB equations in the spatial coordinates with spherical symmetry for tin isotopes such as 112Sn. The numerical accuracy of solving equations in the coordinate space is much greater than the fundamental extensions, which yields almost precise results.

Central region component1, a novel synaptonemal complex component, is essential for meiotic recombination initiation in rice.

PubMed

Miao, Chunbo; Tang, Ding; Zhang, Honggen; Wang, Mo; Li, Yafei; Tang, Shuzhu; Yu, Hengxiu; Gu, Minghong; Cheng, Zhukuan

2013-08-01

In meiosis, homologous recombination entails programmed DNA double-strand break (DSB) formation and synaptonemal complex (SC) assembly coupled with the DSB repair. Although SCs display extensive structural conservation among species, their components identified are poorly conserved at the sequence level. Here, we identified a novel SC component, designated central region component1 (CRC1), in rice (Oryza sativa). CRC1 colocalizes with ZEP1, the rice SC transverse filament protein, to the central region of SCs in a mutually dependent fashion. Consistent with this colocalization, CRC1 interacts with ZEP1 in yeast two-hybrid assays. CRC1 is orthologous to Saccharomyces cerevisiae pachytene checkpoint2 (Pch2) and Mus musculus THYROID receptor-interacting protein13 (TRIP13) and may be a conserved SC component. Additionally, we provide evidence that CRC1 is essential for meiotic DSB formation. CRC1 interacts with homologous pairing aberration in rice meiosis1 (PAIR1) in vitro, suggesting that these proteins act as a complex to promote DSB formation. PAIR2, the rice ortholog of budding yeast homolog pairing1, is required for homologous chromosome pairing. We found that CRC1 is also essential for the recruitment of PAIR2 onto meiotic chromosomes. The roles of CRC1 identified here have not been reported for Pch2 or TRIP13.

CENTRAL REGION COMPONENT1, a Novel Synaptonemal Complex Component, Is Essential for Meiotic Recombination Initiation in Rice[C][W

PubMed Central

Miao, Chunbo; Tang, Ding; Zhang, Honggen; Wang, Mo; Li, Yafei; Tang, Shuzhu; Yu, Hengxiu; Gu, Minghong; Cheng, Zhukuan

2013-01-01

In meiosis, homologous recombination entails programmed DNA double-strand break (DSB) formation and synaptonemal complex (SC) assembly coupled with the DSB repair. Although SCs display extensive structural conservation among species, their components identified are poorly conserved at the sequence level. Here, we identified a novel SC component, designated CENTRAL REGION COMPONENT1 (CRC1), in rice (Oryza sativa). CRC1 colocalizes with ZEP1, the rice SC transverse filament protein, to the central region of SCs in a mutually dependent fashion. Consistent with this colocalization, CRC1 interacts with ZEP1 in yeast two-hybrid assays. CRC1 is orthologous to Saccharomyces cerevisiae pachytene checkpoint2 (Pch2) and Mus musculus THYROID RECEPTOR-INTERACTING PROTEIN13 (TRIP13) and may be a conserved SC component. Additionally, we provide evidence that CRC1 is essential for meiotic DSB formation. CRC1 interacts with HOMOLOGOUS PAIRING ABERRATION IN RICE MEIOSIS1 (PAIR1) in vitro, suggesting that these proteins act as a complex to promote DSB formation. PAIR2, the rice ortholog of budding yeast homolog pairing1, is required for homologous chromosome pairing. We found that CRC1 is also essential for the recruitment of PAIR2 onto meiotic chromosomes. The roles of CRC1 identified here have not been reported for Pch2 or TRIP13. PMID:23943860

Noninvasive analysis of human neck muscle function

NASA Technical Reports Server (NTRS)

Conley, M. S.; Meyer, R. A.; Bloomberg, J. J.; Feeback, D. L.; Dudley, G. A.

1995-01-01

STUDY DESIGN. Muscle use evoked by exercise was determined by quantifying shifts in signal relaxation times of T2-weighted magnetic resonance images. Images were collected at rest and after exercise at each of two intensities (moderate and intense) for each of four head movements: 1) extension, 2) flexion, 3) rotation, and 4) lateral flexion. OBJECTIVE. This study examined the intensity and pattern of neck muscle use evoked by various movements of the head. The results will help elucidate the pathophysiology, and thus methods for treating disorders of the cervical musculoskeletal system. SUMMARY OF BACKGROUND DATA. Exercise-induced contrast shifts in T2 has been shown to indicate muscle use during the activity. The noninvasive nature of magnetic resonance imaging appears to make it an ideal approach for studying the function of the complex neuromuscular system of the neck. METHODS. The extent of T2 increase was examined to gauge how intensely nine different neck muscles or muscle pairs were used in seven subjects. The absolute and relative cross-sectional area of muscle showing a shift in signal relaxation was assessed to infer the pattern of use among and within individual neck muscles or muscle pairs. RESULTS. Signal relaxation increased with exercise intensity for each head movement. The absolute and relative cross-sectional area of muscle showing a shift in signal relaxation also increased with exercise load. Neck muscles or muscle pairs extensively used to perform each head movement were: extension--semispinalis capitis and cervicis and splenius capitis; flexion--sternocleidomastoid and longus capitis and colli; rotation--splenius capitis, levator scapulae, scalenus, semispinalis capitis ipsilateral to the rotation, and sternocleidomastoid contralateral; and lateral flexion--sternocleidomastoid CONCLUSION. The results of this study, in part, agree with the purported functions of neck muscles derived from anatomic location. This also was true for the few selected muscles that have been examined in human electromyographic studies. Neck muscle function and morphology can be studied at a detailed level using exercise-induced shifts in magnetic resonance images.

Base Pair Opening in a Deoxynucleotide Duplex Containing a cis-syn Thymine Cyclobutane Dimer Lesion

PubMed Central

Wenke, Belinda B.; Huiting, Leah N.; Frankel, Elisa B.; Lane, Benjamin F.; Núñez, Megan E.

2014-01-01

The cis-syn thymine cyclobutane dimer is a DNA photoproduct implicated in skin cancer. We compared the stability of individual base pairs in thymine dimer-containing duplexes to undamaged parent 10-mer duplexes. UV melting thermodynamic measurements, CD spectroscopy, and 2D NOESY NMR spectroscopy confirm that the thymine dimer lesion is locally and moderately destabilizing within an overall B-form duplex conformation. We measured the rates of exchange of individual imino protons by NMR using magnetization transfer from water and determined the equilibrium constant for the opening of each base pair Kop. In the normal duplex Kop decreases from the frayed ends of the duplex toward the center, such that the central TA pair is the most stable with a Kop of 8×10−7. In contrast, base pair opening at the 5’T of the thymine dimer is facile. The 5’T of the dimer has the largest equilibrium constant (Kop =3×10−4) in its duplex, considerably larger than even the frayed penultimate base pairs. Notably, base pairing by the 3’T of the dimer is much more stable than by the 5’T, indicating that the predominant opening mechanism for the thymine dimer lesion is not likely to be flipping out into solution as a single unit. The dimer asymmetrically affects the stability of the duplex in its vicinity, destabilizing base pairing on its 5’ side more than on the 3’ side. The striking differences in base pair opening between parent and dimer duplexes occur independently of the duplex-single strand melting transitions. PMID:24328089

Imidazopyridine/Pyrrole and hydroxybenzimidazole/pyrrole pairs for DNA minor groove recognition.

PubMed

Renneberg, Dorte; Dervan, Peter B

2003-05-14

The DNA binding properties of fused heterocycles imidazo[4,5-b]pyridine (Ip) and hydroxybenzimidazole (Hz) paired with pyrrole (Py) in eight-ring hairpin polyamides are reported. The recognition profile of Ip/Py and Hz/Py pairs were compared to the five-membered ring pairs Im/Py and Hp/Py on a DNA restriction fragment at four 6-base pair recognition sites which vary at a single position 5'-TGTNTA-3', where N = G, C, T, A. The Ip/Py pair distinguishes G.C from C.G, T.A, and A.T, and the Hz/Py pair distinguishes T.A from A.T, G.C, and C.G, affording a new set of heterocycle pairs to target the four Watson-Crick base pairs in the minor groove of DNA.

Sparse maps—A systematic infrastructure for reduced-scaling electronic structure methods. I. An efficient and simple linear scaling local MP2 method that uses an intermediate basis of pair natural orbitals

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

Pinski, Peter; Riplinger, Christoph; Neese, Frank, E-mail: evaleev@vt.edu, E-mail: frank.neese@cec.mpg.de

2015-07-21

In this work, a systematic infrastructure is described that formalizes concepts implicit in previous work and greatly simplifies computer implementation of reduced-scaling electronic structure methods. The key concept is sparse representation of tensors using chains of sparse maps between two index sets. Sparse map representation can be viewed as a generalization of compressed sparse row, a common representation of a sparse matrix, to tensor data. By combining few elementary operations on sparse maps (inversion, chaining, intersection, etc.), complex algorithms can be developed, illustrated here by a linear-scaling transformation of three-center Coulomb integrals based on our compact code library that implementsmore » sparse maps and operations on them. The sparsity of the three-center integrals arises from spatial locality of the basis functions and domain density fitting approximation. A novel feature of our approach is the use of differential overlap integrals computed in linear-scaling fashion for screening products of basis functions. Finally, a robust linear scaling domain based local pair natural orbital second-order Möller-Plesset (DLPNO-MP2) method is described based on the sparse map infrastructure that only depends on a minimal number of cutoff parameters that can be systematically tightened to approach 100% of the canonical MP2 correlation energy. With default truncation thresholds, DLPNO-MP2 recovers more than 99.9% of the canonical resolution of the identity MP2 (RI-MP2) energy while still showing a very early crossover with respect to the computational effort. Based on extensive benchmark calculations, relative energies are reproduced with an error of typically <0.2 kcal/mol. The efficiency of the local MP2 (LMP2) method can be drastically improved by carrying out the LMP2 iterations in a basis of pair natural orbitals. While the present work focuses on local electron correlation, it is of much broader applicability to computation with sparse tensors in quantum chemistry and beyond.« less

Frnakenstein: multiple target inverse RNA folding.

PubMed

Lyngsø, Rune B; Anderson, James W J; Sizikova, Elena; Badugu, Amarendra; Hyland, Tomas; Hein, Jotun

2012-10-09

RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures when the target structures are real structures, while no deterioration was observed for predicted structures. Design for two structure targets is considerably more difficult, but far from impossible, demonstrating the feasibility of automated design of artificial riboswitches. The Python implementation is available at http://www.stats.ox.ac.uk/research/genome/software/frnakenstein.

Frnakenstein: multiple target inverse RNA folding

PubMed Central

2012-01-01

Background RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. Results In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. Conclusions Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures when the target structures are real structures, while no deterioration was observed for predicted structures. Design for two structure targets is considerably more difficult, but far from impossible, demonstrating the feasibility of automated design of artificial riboswitches. The Python implementation is available at http://www.stats.ox.ac.uk/research/genome/software/frnakenstein. PMID:23043260

Sparse maps—A systematic infrastructure for reduced-scaling electronic structure methods. I. An efficient and simple linear scaling local MP2 method that uses an intermediate basis of pair natural orbitals.

PubMed

Pinski, Peter; Riplinger, Christoph; Valeev, Edward F; Neese, Frank

2015-07-21

In this work, a systematic infrastructure is described that formalizes concepts implicit in previous work and greatly simplifies computer implementation of reduced-scaling electronic structure methods. The key concept is sparse representation of tensors using chains of sparse maps between two index sets. Sparse map representation can be viewed as a generalization of compressed sparse row, a common representation of a sparse matrix, to tensor data. By combining few elementary operations on sparse maps (inversion, chaining, intersection, etc.), complex algorithms can be developed, illustrated here by a linear-scaling transformation of three-center Coulomb integrals based on our compact code library that implements sparse maps and operations on them. The sparsity of the three-center integrals arises from spatial locality of the basis functions and domain density fitting approximation. A novel feature of our approach is the use of differential overlap integrals computed in linear-scaling fashion for screening products of basis functions. Finally, a robust linear scaling domain based local pair natural orbital second-order Möller-Plesset (DLPNO-MP2) method is described based on the sparse map infrastructure that only depends on a minimal number of cutoff parameters that can be systematically tightened to approach 100% of the canonical MP2 correlation energy. With default truncation thresholds, DLPNO-MP2 recovers more than 99.9% of the canonical resolution of the identity MP2 (RI-MP2) energy while still showing a very early crossover with respect to the computational effort. Based on extensive benchmark calculations, relative energies are reproduced with an error of typically <0.2 kcal/mol. The efficiency of the local MP2 (LMP2) method can be drastically improved by carrying out the LMP2 iterations in a basis of pair natural orbitals. While the present work focuses on local electron correlation, it is of much broader applicability to computation with sparse tensors in quantum chemistry and beyond.

Isometric shoulder strength in young swimmers.

PubMed

McLaine, Sally J; Ginn, Karen A; Fell, James W; Bird, Marie-Louise

2018-01-01

The prevalence of shoulder pain in young swimmers is high. Shoulder rotation strength and the ratio of internal to external rotation strength have been reported as potential modifiable risk factors associated with shoulder pain. However, relative strength measures in elevated positions, which include flexion and extension, have not been established for the young swimmer. The aim of this study was to establish clinically useful, normative shoulder strength measures and ratios for swimmers (14-20 years) without shoulder pain. Cross-sectional, observational study. Swimmers (N=85) without a recent history of shoulder pain underwent strength testing of shoulder flexion and extension (in 140° abduction); and internal and external rotation (in 90° abduction). Strength tests were performed in supine using a hand-held dynamometer and values normalised to body weight. Descriptive statistics were calculated for strength and strength ratios (flexion:extension and internal:external rotation). Differences between groups (based on gender, history of pain, test and arm dominance) were explored using independent and paired t tests. Normative shoulder strength values and ratios were established for young swimmers. There was a significant difference (p<0.002) in relative strength between males and females for all tests with no differences in strength ratios. Relative strength of the dominant and non-dominant shoulders (except for extension); and for swimmers with and without a history of shoulder pain was not significantly different. A normal shoulder strength profile for the young swimmer has been established which provides a valuable reference for the clinician assessing shoulder strength in this population. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Influence of snow shovel shaft configuration on lumbosacral biomechanics during a load-lifting task.

PubMed

Lewinson, Ryan T; Rouhi, Gholamreza; Robertson, D Gordon E

2014-03-01

Lower-back injury from snow shovelling may be related to excessive joint loading. Bent-shaft snow shovels are commonly available for purchase; however, their influence on lower back-joint loading is currently not known. Therefore, the purpose of this study was to compare L5/S1 extension angular impulses between a bent-shaft and a standard straight-shaft snow shovel. Eight healthy subjects participated in this study. Each completed a simulated snow-lifting task in a biomechanics laboratory with each shovel design. A standard motion analysis procedure was used to determine L5/S1 angular impulses during each trial, as well as peak L5/S1 extension moments and peak upper body flexion angle. Paired-samples t-tests (α = 0.05) were used to compare variables between shovel designs. Correlation was used to determine the relationship between peak flexion and peak moments. Results of this study show that the bent-shaft snow shovel reduced L5/S1 extension angular impulses by 16.5% (p = 0.022), decreased peak moments by 11.8% (p = 0.044), and peak flexion by 13.0% (p = 0.002) compared to the straight-shaft shovel. Peak L5/S1 extension moment magnitude was correlated with peak upper body flexion angle (r = 0.70). Based on these results, it is concluded that the bent-shaft snow shovel can likely reduce lower-back joint loading during snow shovelling, and thus may have a role in snow shovelling injury prevention. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Purification and Characterization of Four β-Expansins (Zea m 1 Isoforms) from Maize Pollen1[w

PubMed Central

Li, Lian-Chao; Bedinger, Patricia A.; Volk, Carol; Jones, A. Daniel; Cosgrove, Daniel J.

2003-01-01

Four proteins with wall extension activity on grass cell walls were purified from maize (Zea mays) pollen by conventional column chromatography and high-performance liquid chromatography. Each is a basic glycoprotein (isoelectric point = 9.1–9.5) of approximately 28 kD and was identified by immunoblot analysis as an isoform of Zea m 1, the major group 1 allergen of maize pollen and member of the β-expansin family. Four distinctive cDNAs for Zea m 1 were identified by cDNA library screening and by GenBank analysis. One pair (GenBank accession nos. AY104999 and AY104125) was much closer in sequence to well-characterized allergens such as Lol p 1 and Phl p 1 from ryegrass (Lolium perenne) and Phleum pretense, whereas a second pair was much more divergent. The N-terminal sequence and mass spectrometry fingerprint of the most abundant isoform (Zea m 1d) matched that predicted for AY197353, whereas N-terminal sequences of the other isoforms matched or nearly matched AY104999 and AY104125. Highly purified Zea m 1d induced extension of a variety of grass walls but not dicot walls. Wall extension activity of Zea m 1d was biphasic with respect to protein concentration, had a broad pH optimum between 5 and 6, required more than 50 μg mL-1 for high activity, and led to cell wall breakage after only approximately 10% extension. These characteristics differ from those of α-expansins. Some of the distinctive properties of Zea m 1 may not be typical of β-expansins as a class but may relate to the specialized function of this β-expansin in pollen function. PMID:12913162

Development and evaluation of a crowdsourcing methodology for knowledge base construction: identifying relationships between clinical problems and medications

PubMed Central

Wright, Adam; Laxmisan, Archana; Ottosen, Madelene J; McCoy, Jacob A; Butten, David; Sittig, Dean F

2012-01-01

Objective We describe a novel, crowdsourcing method for generating a knowledge base of problem–medication pairs that takes advantage of manually asserted links between medications and problems. Methods Through iterative review, we developed metrics to estimate the appropriateness of manually entered problem–medication links for inclusion in a knowledge base that can be used to infer previously unasserted links between problems and medications. Results Clinicians manually linked 231 223 medications (55.30% of prescribed medications) to problems within the electronic health record, generating 41 203 distinct problem–medication pairs, although not all were accurate. We developed methods to evaluate the accuracy of the pairs, and after limiting the pairs to those meeting an estimated 95% appropriateness threshold, 11 166 pairs remained. The pairs in the knowledge base accounted for 183 127 total links asserted (76.47% of all links). Retrospective application of the knowledge base linked 68 316 medications not previously linked by a clinician to an indicated problem (36.53% of unlinked medications). Expert review of the combined knowledge base, including inferred and manually linked problem–medication pairs, found a sensitivity of 65.8% and a specificity of 97.9%. Conclusion Crowdsourcing is an effective, inexpensive method for generating a knowledge base of problem–medication pairs that is automatically mapped to local terminologies, up-to-date, and reflective of local prescribing practices and trends. PMID:22582202

Oxidation of DNA bases, deoxyribonucleosides and homopolymers by peroxyl radicals.

PubMed Central

Simandan, T; Sun, J; Dix, T A

1998-01-01

DNA base oxidation is considered to be a key event associated with disease initiation and progression in humans. Peroxyl radicals (ROO. ) are important oxidants found in cells whose ability to react with the DNA bases has not been characterized extensively. In this paper, the products resulting from ROO. oxidation of the DNA bases are determined by gas chromatography/MS in comparison with authentic standards. ROO. radicals oxidize adenine and guanine to their 8-hydroxy derivatives, which are considered biomarkers of hydroxyl radical (HO.) oxidations in cells. ROO. radicals also oxidize adenine to its hydroxylamine, a previously unidentified product. ROO. radicals oxidize cytosine and thymine to the monohydroxy and dihydroxy derivatives that are formed by oxidative damage in cells. Identical ROO. oxidation profiles are observed for each base when exposed as deoxyribonucleosides, monohomopolymers and base-paired dihomopolymers. These results have significance for the development, utilization and interpretation of DNA base-derived biomarkers of oxidative damage associated with disease initiation and propagation, and support the idea that the mutagenic potential of N-oxidized bases, when generated in cellular DNA, will require careful evaluation. Adenine hydroxylamine is proposed as a specific molecular probe for the activity of ROO. in cellular systems. PMID:9761719

Acuity of a Cryptochrome and Vision-Based Magnetoreception System in Birds

PubMed Central

Solov'yov, Ilia A.; Mouritsen, Henrik; Schulten, Klaus

2010-01-01

Abstract The magnetic compass of birds is embedded in the visual system and it has been hypothesized that the primary sensory mechanism is based on a radical pair reaction. Previous models of magnetoreception have assumed that the radical pair-forming molecules are rigidly fixed in space, and this assumption has been a major objection to the suggested hypothesis. In this article, we investigate theoretically how much disorder is permitted for the radical pair-forming, protein-based magnetic compass in the eye to remain functional. Our study shows that only one rotational degree of freedom of the radical pair-forming protein needs to be partially constrained, while the other two rotational degrees of freedom do not impact the magnetoreceptive properties of the protein. The result implies that any membrane-associated protein is sufficiently restricted in its motion to function as a radical pair-based magnetoreceptor. We relate our theoretical findings to the cryptochromes, currently considered the likeliest candidate to furnish radical pair-based magnetoreception. PMID:20655831

A structural determinant in the uracil DNA glycosylase superfamily for the removal of uracil from adenine/uracil base pairs

PubMed Central

Lee, Dong-Hoon; Liu, Yinling; Lee, Hyun-Wook; Xia, Bo; Brice, Allyn R.; Park, Sung-Hyun; Balduf, Hunter; Dominy, Brian N.; Cao, Weiguo

2015-01-01

The uracil DNA glycosylase superfamily consists of several distinct families. Family 2 mismatch-specific uracil DNA glycosylase (MUG) from Escherichia coli is known to exhibit glycosylase activity on three mismatched base pairs, T/U, G/U and C/U. Family 1 uracil N-glycosylase (UNG) from E. coli is an extremely efficient enzyme that can remove uracil from any uracil-containing base pairs including the A/U base pair. Here, we report the identification of an important structural determinant that underlies the functional difference between MUG and UNG. Substitution of a Lys residue at position 68 with Asn in MUG not only accelerates the removal of uracil from mismatched base pairs but also enables the enzyme to gain catalytic activity on A/U base pairs. Binding and kinetic analysis demonstrate that the MUG-K68N substitution results in enhanced ground state binding and transition state interactions. Molecular modeling reveals that MUG-K68N, UNG-N123 and family 5 Thermus thermophiles UDGb-A111N can form bidentate hydrogen bonds with the N3 and O4 moieties of the uracil base. Genetic analysis indicates the gain of function for A/U base pairs allows the MUG-K68N mutant to remove uracil incorporated into the genome during DNA replication. The implications of this study in the origin of life are discussed. PMID:25550433

Structural features of the DNA hairpin d(ATCCTA-GTTA-TAGGAT): formation of a G-A base pair in the loop.

PubMed Central

van Dongen, M J; Mooren, M M; Willems, E F; van der Marel, G A; van Boom, J H; Wijmenga, S S; Hilbers, C W

1997-01-01

The three-dimensional structure of the hairpin formed by d(ATCCTA-GTTA-TAGGAT) has been determined by means of two-dimensional NMR studies, distance geometry and molecular dynamics calculations. The first and the last residues of the tetraloop of this hairpin form a sheared G-A base pair on top of the six Watson-Crick base pairs in the stem. The glycosidic torsion angles of the guanine and adenine residues in the G-A base pair reside in the anti and high- anti domain ( approximately -60 degrees ) respectively. Several dihedral angles in the loop adopt non-standard values to accommodate this base pair. The first and second residue in the loop are stacked in a more or less normal helical fashion; the fourth loop residue also stacks upon the stem, while the third residue is directed away from the loop region. The loop structure can be classified as a so-called type-I loop, in which the bases at the 5'-end of the loop stack in a continuous fashion. In this situation, loop stability is unlikely to depend heavily on the nature of the unpaired bases in the loop. Moreover, the present study indicates that the influence of the polarity of a closing A.T pair is much less significant than that of a closing C.G base pair. PMID:9092659

S-adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the SMK box translational riboswitch RNA

PubMed Central

Fuchs, Ryan T.; Grundy, Frank J.; Henkin, Tina M.

2007-01-01

The SMK box is a conserved riboswitch motif found in the 5′ untranslated region of metK genes [encoding S-adenosylmethionine (SAM) synthetase] in lactic acid bacteria, including Enterococcus, Streptococcus, and Lactococcus sp. Previous studies showed that this RNA element binds SAM in vitro, and SAM binding causes a structural rearrangement that sequesters the Shine–Dalgarno (SD) sequence by pairing with an anti-SD (ASD) element. A model was proposed in which SAM binding inhibits metK translation by preventing binding of the ribosome to the SD region of the mRNA. In the current work, the addition of SAM was shown to inhibit binding of 30S ribosomal subunits to SMK box RNA; in contrast, the addition of S-adenosylhomocysteine (SAH) had no effect. A mutant RNA, which has a disrupted SD-ASD pairing, was defective in SAM binding and showed no reduction of ribosome binding in the presence of SAM, whereas a compensatory mutation that restored SD-ASD pairing restored the response to SAM. Primer extension inhibition assays provided further evidence for SD-ASD pairing in the presence of SAM. These results strongly support the model that SMK box translational repression operates through occlusion of the ribosome binding site and that SAM binding requires the SD-ASD pairing. PMID:17360376

Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain

PubMed Central

Agúndez, José A. G.; Abad-Santos, Francisco; Aldea, Ana; Alonso-Navarro, Hortensia; Bernal, María L.; Borobia, Alberto M.; Borrás, Emma; Carballo, Miguel; Carvajal, Alfonso; García-Muñiz, José D.; Gervasini, Guillermo; Jiménez-Jiménez, Félix J.; Lucena, María I.; Martínez, Carmen; Sacristán, José A.; Salado, Inés; Sinués, Blanca; Vicente, Jorge; García-Martín, Elena

2012-01-01

The development of clinical practice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance with regard to adverse drug reactions. The potential of pharmacogenomic biomarkers has been extensively investigated in recent years. However, several barriers to implementing the use of pharmacogenomics testing exist. We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of major gene/drug pairs. Of 11 potential barriers, the highest importance was attributed to lack of institutional support for pharmacogenomics testing, and to the issues related to the lack of guidelines. Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen. In this perspective article, we compare the relative importance of 29 gene/drug pairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology and Therapeutics study, and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testing. PMID:23233861

[CuCl(n)](2-n) ion-pair species in 1-ethyl-3-methylimidazolium chloride ionic liquid-water mixtures: ultraviolet-visible, X-ray absorption fine structure, and density functional theory characterization.

PubMed

Li, Guosheng; Camaioni, Donald M; Amonette, James E; Zhang, Z Conrad; Johnson, Timothy J; Fulton, John L

2010-10-07

We studied the coordination environment about Cu(II) in a pure ionic liquid, 1-ethyl-3-methylimidazolium chloride ([EMIM]Cl), and in binary mixtures of this compound with water across the entire range of compositions, using a combination of X-ray absorption fine structure (XAFS), ultraviolet-visible (UV-vis) spectroscopy, and electronic structure calculations. Our results show a series of stages in the ion pairing of the divalent cation, Cu(II), including the contact ion pairing of Cu(2+) with multiple Cl(-) ligands to form various CuCl(n)((2-n)) polyanions, as well as the subsequent solvation and ion pairing of the polychlorometallate anion with the EMIM(+) cation. Ion-pair formation is strongly promoted in [EMIM]Cl by the low dielectric constant and by the extensive breakdown of the water hydrogen-bond network in [EMIM]Cl-water mixtures. The CuCl(4)(2-) species dominates in the [EMIM]Cl solvent, and calculations along with spectroscopy show that its geometry distorts to C(2) symmetry compared to D(2d) in the gas phase. These results are important in understanding catalysis and separation processes involving transition metals in ionic liquid systems.

Hydration of Watson-Crick base pairs and dehydration of Hoogsteen base pairs inducing structural polymorphism under molecular crowding conditions.

PubMed

Miyoshi, Daisuke; Nakamura, Kaori; Tateishi-Karimata, Hisae; Ohmichi, Tatsuo; Sugimoto, Naoki

2009-03-18

It has been revealed recently that molecular crowding, which is one of the largest differences between in vivo and in vitro conditions, is a critical factor determining the structure, stability, and function of nucleic acids. However, the effects of molecular crowding on Watson-Crick and Hoogsteen base pairs remain unclear. In order to investigate directly and quantitatively the molecular crowding effects on base pair types in nucleic acids, we designed intramolecular parallel- and antiparallel-stranded DNA duplexes consisting of Hoogsteen and Watson-Crick base pairs, respectively, as well as an intramolecular parallel-stranded triplex containing both types of base pairs. Thermodynamic analyses demonstrated that the values of free energy change at 25 degrees C for Hoogsteen base-pair formations decreased from +1.45 +/- 0.15 to +1.09 +/- 0.13 kcal mol(-1), and from -1.89 +/- 0.13 to -2.71 +/- 0.11 kcal mol(-1) in the intramolecular duplex and triplex, respectively, when the concentration of PEG 200 (polyethylene glycol with average molecular weight 200) increased from 0 to 20 wt %. However, corresponding values for Watson-Crick formation in the duplex and triplex increased from -10.2 +/- 0.2 to -8.7 +/- 0.1 kcal mol(-1), and from -10.8 +/- 0.2 to -9.2 +/- 0.2 kcal mol(-1), respectively. Furthermore, it was revealed that the opposing effects of molecular crowding on the Hoogsteen and Watson-Crick base pairs were due to different behaviors of water molecules binding to the DNA strands.

Design and fabrication of a brassboard optical bench structure for space interferometry mission

NASA Technical Reports Server (NTRS)

Buck, Stephanie

2006-01-01

The Space Interferometry Mission (SIM), consisting of an orbiting pair of telescopes, will be used for characterization of extrasolar planetary systems and for associated astrophysics research. To maximize the capabilities of this instrument, extensive technology development has been performed, much of it to understand and verify the performance of precision structures.

Ultrastructure and development of the new stylets inside pre-molting first instar nymphs of the Asian citrus psyllid Diaphorina citri (Hemiptera: Liviidae)

USDA-ARS?s Scientific Manuscript database

The ultrastructure and development of new stylets was studied in pre-molting first instar nymph of Diaphorina citri. Two oval-shaped masses of cuboidal hypodermal cells, located in the cephalic region, had long extensions that ended with developing pairs of mandibular and maxillary stylets, apparent...

James C. McGroddy Prize Lecutre: Iron-Based Superconductors: Discovery and Progress

NASA Astrophysics Data System (ADS)

Hosono, Hideo

2015-03-01

The largest breakthrough in the history is the discovery of high Tc Cuprates by G.Bednorz and A.Muller in 1986 and the maximum Tc exceeded 77K, boiling temperature of liquid nitrogen in 1987. However, no new superconductors with high Tc had been reported since then except MgB2 (Tc =39K) discovered by J.Akimitsu in 2001.We found LaFePO superconductor with Tc =3K in 2006 and LaFeAsO1-xFx with Tc =26K (42K at under high pressure of 5GPa) in early 2008. The latter discovery rekindled the extensive superconductivity research globally, and more than 10,000 papers have been published to now. This excitement originates from disprovement of a widely accepted belief that iron with a large magnetic moment is harmful for emergence of superconductivity and relatively high Tc. Extensive research on iron-based superconductors pushed up the maximal Tc to 56K, which is next to high Tc cuprates and has led to the discovery of more than 50 new iron-based superconducting materials to date. Seen are so many advances in elucidation of superconducting properties and pairing mechanism. In this talk, I introduce a tale to the discovery and show the current status by reviewing progresses in materials, properties, mechanism and the application covering the recent hot topics. Emphases are placed on the unique characteristics arising from multi-orbital nature which totally differs from high Tc cuprates.

Theory of nodal s ±-wave pairing symmetry in the Pu-based 115 superconductor family

DOE PAGES

Das, Tanmoy; Zhu, Jian -Xin; Graf, Matthias J.

2015-02-27

The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-T c superconductors and predict the presence of a nodal s⁺⁻ wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface “hot-spots” in the inter-band scatteringmore » channel, which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s⁺⁻ wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry.« less

Growth properties associated with A-U replacement of specific G-C base pairs in 16S rRNA from Escherichia coli.

PubMed Central

Triman, K L

1995-01-01

Mutations that disrupt each of seven specific G-C base pairs in 16S rRNA from Escherichia coli confer loss of expression of a plasmid-encoded 16S rRNA selectable marker (spectinomycin resistance). However, A-U replacement of G-C base pairs at nucleotides 359/52 or 1292/1245 in 16S rRNA permits normal expression of the marker. By contrast, A-U replacements at 146/176, 153/168, 350/339, or 1293/1244 are associated with loss of expression of the marker. These genetic studies are designed to determine the importance of specific base pairs by assessment of the structural and functional impairments of 16S rRNA molecules resulting from expression of base pair substitutions at these positions. PMID:7543481

Automated next-to-leading order predictions for new physics at the LHC: The case of colored scalar pair production

DOE PAGES

Degrande, Céline; Fuks, Benjamin; Hirschi, Valentin; ...

2015-05-05

We present for the first time the full automation of collider predictions matched with parton showers at the next-to-leading accuracy in QCD within nontrivial extensions of the standard model. The sole inputs required from the user are the model Lagrangian and the process of interest. As an application of the above, we explore scenarios beyond the standard model where new colored scalar particles can be pair produced in hadron collisions. Using simplified models to describe the new field interactions with the standard model, we present precision predictions for the LHC within the MadGraph5_aMC@NLO framework.

Three-dimensional axisymmetric sources for Majumdar-Papapetrou type spacetimes

NASA Astrophysics Data System (ADS)

García-Reyes, Gonzalo; Hernández-Gómez, Kevin A.

From Newtonian potential-density pairs, we construct three-dimensional axisymmetric relativistic sources for a Majumdar-Papapetrou type conformastatic spacetime. As simple examples, we build two families of relativistic thick disks from the first two Miyamoto-Nagai potential-density pairs used in Newtonian gravity to model flat galaxies, and a three-component relativistic model of galaxy (bulge, disk and dark matter halo). We study the equatorial circular motion of test particles around such structures. Also the stability of the orbits is analyzed for radial perturbation using an extension of the Rayleigh criterion. In all examples, the relativistic effects are analyzed and compared with the Newtonian approximation. The models are considered satisfying all the energy conditions.

Two pairs of farnesyl phenolic enantiomers as natural nitric oxide inhibitors from Ganoderma sinense.

PubMed

Wang, Meng; Wang, Fei; Xu, Feng; Ding, Li-Qin; Zhang, Qian; Li, Hui-Xiang; Zhao, Feng; Wang, Li-Qing; Zhu, Li-Han; Chen, Li-Xia; Qiu, Feng

2016-07-15

Four new farnesyl phenolic compounds, ganosinensols A-D (1-4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Two pairs of enantiomers, 1/2, and 3/4 were isolated by HPLC using a Daicel Chiralpak IE column. Their structures were elucidated from extensive spectroscopic analyses and comparison with literature data. The absolute configurations of 1-4 were assigned by ECD spectra. All of these isolated compounds showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values from 1.15 to 2.26μM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Generation of Single Photons and Entangled Photon Pairs from a Quantum Dot

NASA Astrophysics Data System (ADS)

Yamamoto, Y.; Pelton, M.; Santori, C.; Solomon, G. S.

2002-10-01

Current quantum cryptography systems are limited by the Poissonian photon statistics of a standard light source: a security loophole is opened up by the possibility of multiple-photon pulses. By replacing the source with a single-photon emitter, transmission rates of secure information can be improved. A single photon source is also essential to implement a linear optics quantum computer. We have investigated the use of single self-assembled InAs/GaAs quantum dots as such single-photon sources, and have seen a hundred-fold reduction in the multi-photon probability as compared to Poissonian pulses. An extension of our experiment should also allow for the generation of triggered, polarizationentangled photon pairs.

Upon Generating Discrete Expanding Integrable Models of the Toda Lattice Systems and Infinite Conservation Laws

NASA Astrophysics Data System (ADS)

Zhang, Yufeng; Zhang, Xiangzhi; Wang, Yan; Liu, Jiangen

2017-01-01

With the help of R-matrix approach, we present the Toda lattice systems that have extensive applications in statistical physics and quantum physics. By constructing a new discrete integrable formula by R-matrix, the discrete expanding integrable models of the Toda lattice systems and their Lax pairs are generated, respectively. By following the constructing formula again, we obtain the corresponding (2+1)-dimensional Toda lattice systems and their Lax pairs, as well as their (2+1)-dimensional discrete expanding integrable models. Finally, some conservation laws of a (1+1)-dimensional generalised Toda lattice system and a new (2+1)-dimensional lattice system are generated, respectively.

Vibrational quasi-degenerate perturbation theory with optimized coordinates: applications to ethylene and trans-1,3-butadiene.

PubMed

Yagi, Kiyoshi; Otaki, Hiroki

2014-02-28

A perturbative extension to optimized coordinate vibrational self-consistent field (oc-VSCF) is proposed based on the quasi-degenerate perturbation theory (QDPT). A scheme to construct the degenerate space (P space) is developed, which incorporates degenerate configurations and alleviates the divergence of perturbative expansion due to localized coordinates in oc-VSCF (e.g., local O-H stretching modes of water). An efficient configuration selection scheme is also implemented, which screens out the Hamiltonian matrix element between the P space configuration (p) and the complementary Q space configuration (q) based on a difference in their quantum numbers (λpq = ∑s|ps - qs|). It is demonstrated that the second-order vibrational QDPT based on optimized coordinates (oc-VQDPT2) smoothly converges with respect to the order of the mode coupling, and outperforms the conventional one based on normal coordinates. Furthermore, an improved, fast algorithm is developed for optimizing the coordinates. First, the minimization of the VSCF energy is conducted in a restricted parameter space, in which only a portion of pairs of coordinates is selectively transformed. A rational index is devised for this purpose, which identifies the important coordinate pairs to mix from others that may remain unchanged based on the magnitude of harmonic coupling induced by the transformation. Second, a cubic force field (CFF) is employed in place of a quartic force field, which bypasses intensive procedures that arise due to the presence of the fourth-order force constants. It is found that oc-VSCF based on CFF together with the pair selection scheme yields the coordinates similar in character to the conventional ones such that the final vibrational energy is affected very little while gaining an order of magnitude acceleration. The proposed method is applied to ethylene and trans-1,3-butadiene. An accurate, multi-resolution potential, which combines the MP2 and coupled-cluster with singles, doubles, and perturbative triples level of electronic structure theory, is generated and employed in the oc-VQDPT2 calculation to obtain the fundamental tones as well as selected overtones/combination tones coupled to the fundamentals through the Fermi resonance. The calculated frequencies of ethylene and trans-1,3-butadiene are found to be in excellent agreement with the experimental values with a mean absolute error of 8 and 9 cm(-1), respectively.

Let's stay together? Intrinsic and extrinsic factors involved in pair bond dissolution in a recolonizing wolf population.

PubMed

Milleret, Cyril; Wabakken, Petter; Liberg, Olof; Åkesson, Mikael; Flagstad, Øystein; Andreassen, Harry Peter; Sand, Håkan

2017-01-01

For socially monogamous species, breeder bond dissolution has important consequences for population dynamics, but the extent to which extrinsic or intrinsic population factors causes pair dissolution remain poorly understood, especially among carnivores. Using an extensive life-history data set, a survival analysis and competing risks framework, we examined the fate of 153 different wolf (Canis lupus) pairs in the recolonizing Scandinavian wolf population, during 14 winters of snow tracking and DNA monitoring. Wolf pair dissolution was generally linked to a mortality event and was strongly affected by extrinsic (i.e. anthropogenic) causes. No divorce was observed, and among the pair dissolution where causes have been identified, death of one or both wolves was always involved. Median time from pair formation to pair dissolution was three consecutive winters (i.e. approximately 2 years). Pair dissolution was mostly human-related, primarily caused by legal control actions (36·7%), verified poaching (9·2%) and traffic-related causes (2·1%). Intrinsic factors, such as disease and age, accounted for only 7·7% of pair dissolutions. The remaining 44·3% of dissolution events were from unknown causes, but we argue that a large portion could be explained by an additional source of human-caused mortality, cryptic poaching. Extrinsic population factors, such as variables describing the geographical location of the pair, had a stronger effect on risk of pair dissolution compared to anthropogenic landscape characteristics. Population intrinsic factors, such as the inbreeding coefficient of the male pair member, had a negative effect on pair bond duration. The mechanism behind this result remains unknown, but might be explained by lower survival of inbred males or more complex inbreeding effects mediated by behaviour. Our study provides quantitative estimates of breeder bond duration in a social carnivore and highlights the effect of extrinsic (i.e. anthropogenic) and intrinsic factors (i.e. inbreeding) involved in wolf pair bond duration. Unlike the effects of intrinsic and extrinsic factors that are commonly reported on individual survival or population growth, here we provide quantitative estimates of their potential effect on the social unit of the population, the wolf pair. © 2016 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.

Experimental demonstration of wavelength domain rogue-free ONU based on wavelength-pairing for TDM/WDM optical access networks.

PubMed

Lee, Jie Hyun; Park, Heuk; Kang, Sae-Kyoung; Lee, Joon Ki; Chung, Hwan Seok

2015-11-30

In this study, we propose and experimentally demonstrate a wavelength domain rogue-free ONU based on wavelength-pairing of downstream and upstream signals for time/wavelength division-multiplexed optical access networks. The wavelength-pairing tunable filter is aligned to the upstream wavelength channel by aligning it to one of the downstream wavelength channels. Wavelength-pairing is implemented with a compact and cyclic Si-AWG integrated with a Ge-PD. The pairing filter covered four 100 GHz-spaced wavelength channels. The feasibility of the wavelength domain rogue-free operation is investigated by emulating malfunction of the misaligned laser. The wavelength-pairing tunable filter based on the Si-AWG blocks the upstream signal in the non-assigned wavelength channel before data collision with other ONUs.

Orbital selective pairing and gap structures of iron-based superconductors

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

Kreisel, Andreas; Andersen, Brian M.; Sprau, P. O.

We discuss the in uence on spin-fluctuation pairing theory of orbital selective strong correlation effects in Fe-based superconductors, particularly Fe chalcogenide systems. We propose that a key ingredient for an improved itinerant pairing theory is orbital selectivity, i.e., incorporating the reduced coherence of quasiparticles occupying specific orbital states. This modifies the usual spin-fluctuation via suppression of pair scattering processes involving those less coherent states and results in orbital selective Cooper pairing of electrons in the remaining states. We show that this paradigm yields remarkably good agreement with the experimentally observed anisotropic gap structures in both bulk and monolayer FeSe, asmore » well as LiFeAs, indicating that orbital selective Cooper pairing plays a key role in the more strongly correlated iron-based superconductors.« less

Orbital selective pairing and gap structures of iron-based superconductors

DOE PAGES

Kreisel, Andreas; Andersen, Brian M.; Sprau, P. O.; ...

2017-05-08

We discuss the in uence on spin-fluctuation pairing theory of orbital selective strong correlation effects in Fe-based superconductors, particularly Fe chalcogenide systems. We propose that a key ingredient for an improved itinerant pairing theory is orbital selectivity, i.e., incorporating the reduced coherence of quasiparticles occupying specific orbital states. This modifies the usual spin-fluctuation via suppression of pair scattering processes involving those less coherent states and results in orbital selective Cooper pairing of electrons in the remaining states. We show that this paradigm yields remarkably good agreement with the experimentally observed anisotropic gap structures in both bulk and monolayer FeSe, asmore » well as LiFeAs, indicating that orbital selective Cooper pairing plays a key role in the more strongly correlated iron-based superconductors.« less

Acid-induced exchange of the imino proton in G.C pairs.

PubMed Central

Nonin, S; Leroy, J L; Gueron, M

1996-01-01

Acid-induced catalysis of imino proton exchange in G.C pairs of DNA duplexes is surprisingly fast, being nearly as fast as for the isolated nucleoside, despite base-pair dissociation constants in the range of 10(-5) at neutral or basic pH. It is also observed in terminal G.C pairs of duplexes and in base pairs of drug-DNA complexes. We have measured imino proton exchange in deoxyguanosine and in the duplex (ATATAGATCTATAT) as a function of pH. We show that acid-induced exchange can be assigned to proton transfer from N7-protonated guanosine to cytidine in the open state of the pair. This is faster than transfer from neutral guanosine (the process of intrinsic catalysis previously characterized at neutral ph) due to the lower imino proton pK of the protonated form, 7.2 instead of 9.4. Other interpretations are excluded by a study of exchange catalysis by formiate and cytidine as exchange catalysts. The cross-over pH between the regimes of pH-independent and acid-induced exchange rates is more basic in the case of base pairs than in the mononucleoside, suggestive of an increase by one to two decades in the dissociation constant of the base pair upon N7 protonation of G. Acid-induced catalysis is much weaker in A.T base pairs, as expected in view of the low pK for protonation of thymidine. PMID:8604298

Acid-induced exchange of the imino proton in G.C pairs.

PubMed

Nonin, S; Leroy, J L; Gueron, M

1996-02-15

Acid-induced catalysis of imino proton exchange in G.C pairs of DNA duplexes is surprisingly fast, being nearly as fast as for the isolated nucleoside, despite base-pair dissociation constants in the range of 10(-5) at neutral or basic pH. It is also observed in terminal G.C pairs of duplexes and in base pairs of drug-DNA complexes. We have measured imino proton exchange in deoxyguanosine and in the duplex (ATATAGATCTATAT) as a function of pH. We show that acid-induced exchange can be assigned to proton transfer from N7-protonated guanosine to cytidine in the open state of the pair. This is faster than transfer from neutral guanosine (the process of intrinsic catalysis previously characterized at neutral ph) due to the lower imino proton pK of the protonated form, 7.2 instead of 9.4. Other interpretations are excluded by a study of exchange catalysis by formiate and cytidine as exchange catalysts. The cross-over pH between the regimes of pH-independent and acid-induced exchange rates is more basic in the case of base pairs than in the mononucleoside, suggestive of an increase by one to two decades in the dissociation constant of the base pair upon N7 protonation of G. Acid-induced catalysis is much weaker in A.T base pairs, as expected in view of the low pK for protonation of thymidine.

Binding to the DNA Minor Groove by Heterocyclic Dications: From AT Specific Monomers to GC Recognition with Dimers

PubMed Central

Nanjunda, Rupesh; Wilson, W. David

2012-01-01

Compounds that bind in the DNA minor groove have provided critical information on DNA molecular recognition, they have found extensive uses in biotechnology and they are providing clinically useful drugs against diseases as diverse as cancer and sleeping sickness. This review focuses on the development of clinically useful heterocyclic diamidine minor groove binders. These compounds have shown us that the classical model for minor groove binding in AT DNA sequences must be expanded in several ways: compounds with nonstandard shapes can bind strongly to the groove, water can be directly incorporated into the minor groove complex in an interfacial interaction, and the compounds can form cooperative stacked dimers to recognize GC and mixed AT/GC base pair sequences. PMID:23255206

Parallel seed-based approach to multiple protein structure similarities detection

DOE PAGES

Chapuis, Guillaume; Le Boudic-Jamin, Mathilde; Andonov, Rumen; ...

2015-01-01

Finding similarities between protein structures is a crucial task in molecular biology. Most of the existing tools require proteins to be aligned in order-preserving way and only find single alignments even when multiple similar regions exist. We propose a new seed-based approach that discovers multiple pairs of similar regions. Its computational complexity is polynomial and it comes with a quality guarantee—the returned alignments have both root mean squared deviations (coordinate-based as well as internal-distances based) lower than a given threshold, if such exist. We do not require the alignments to be order preserving (i.e., we consider nonsequential alignments), which makesmore » our algorithm suitable for detecting similar domains when comparing multidomain proteins as well as to detect structural repetitions within a single protein. Because the search space for nonsequential alignments is much larger than for sequential ones, the computational burden is addressed by extensive use of parallel computing techniques: a coarse-grain level parallelism making use of available CPU cores for computation and a fine-grain level parallelism exploiting bit-level concurrency as well as vector instructions.« less

Predicting links based on knowledge dissemination in complex network

NASA Astrophysics Data System (ADS)

Zhou, Wen; Jia, Yifan

2017-04-01

Link prediction is the task of mining the missing links in networks or predicting the next vertex pair to be connected by a link. A lot of link prediction methods were inspired by evolutionary processes of networks. In this paper, a new mechanism for the formation of complex networks called knowledge dissemination (KD) is proposed with the assumption of knowledge disseminating through the paths of a network. Accordingly, a new link prediction method-knowledge dissemination based link prediction (KDLP)-is proposed to test KD. KDLP characterizes vertex similarity based on knowledge quantity (KQ) which measures the importance of a vertex through H-index. Extensive numerical simulations on six real-world networks demonstrate that KDLP is a strong link prediction method which performs at a higher prediction accuracy than four well-known similarity measures including common neighbors, local path index, average commute time and matrix forest index. Furthermore, based on the common conclusion that an excellent link prediction method reveals a good evolving mechanism, the experiment results suggest that KD is a considerable network evolving mechanism for the formation of complex networks.

Diffuse skull base/cervical fusion syndromes in two siblings with spondylocostal dysostosis syndrome: analysis via three dimensional computed tomography scanning.

PubMed

Al Kaissi, Ali; Ben Chehida, Farid; Ben Ghachem, Maher; Klaushofer, Klaus; Grill, Franz

2008-06-01

A study on a pair of male sibs to reach for the etiological understanding of unusual skull base/spine maldevelopment. Previously, radiographs alone were used to formulate this diagnosis. Here, three-dimensional computed tomography (3D CT) studies further clarified the typical diagnostic findings associated with spondylocostal dysostosis (SCD). Interestingly, patients with SCD are at increased risk for diffuse skull base/cervical fusion syndromes and can result in severe neurologic deficits associated with any degree of trauma. Classically SCD is defined as a skeletal dysplasia with clinical and radiologic manifestations, consisting of short neck and trunk, nonprogressive scoliosis and abnormalities of vertebral segmentation and of the ribs. Radiograms have been adopted as the only modality for the classification and prognostication of patients with SCD. Detailed clinical and radiographic examinations were undertaken with emphasis on the significance of the 3D CT scanning. We observed extensive fusion of the clivus with the cervical/entire spine, resulting in a remarkable solid, immobile, and fixed bony ankylosis of extremely serious outcome. Patients with spondylcostal dysostosis are predisposed to develop extensive skull-base-cervical spine fusion. The latter might lead to the development of a solid, immobile, and fixed bony ankylosis. In children/adults trivial injuries and/or high-energy trauma can lead to serious intracranial and spinal cord injury. Comprehensive orthopedic and neurosurgeons management must follow the recognition of these anomalies. To the best of our knowledge, no previous CT studies of the spine have been published in patients with SCD.

MITIE: Simultaneous RNA-Seq-based transcript identification and quantification in multiple samples.

PubMed

Behr, Jonas; Kahles, André; Zhong, Yi; Sreedharan, Vipin T; Drewe, Philipp; Rätsch, Gunnar

2013-10-15

High-throughput sequencing of mRNA (RNA-Seq) has led to tremendous improvements in the detection of expressed genes and reconstruction of RNA transcripts. However, the extensive dynamic range of gene expression, technical limitations and biases, as well as the observed complexity of the transcriptional landscape, pose profound computational challenges for transcriptome reconstruction. We present the novel framework MITIE (Mixed Integer Transcript IdEntification) for simultaneous transcript reconstruction and quantification. We define a likelihood function based on the negative binomial distribution, use a regularization approach to select a few transcripts collectively explaining the observed read data and show how to find the optimal solution using Mixed Integer Programming. MITIE can (i) take advantage of known transcripts, (ii) reconstruct and quantify transcripts simultaneously in multiple samples, and (iii) resolve the location of multi-mapping reads. It is designed for genome- and assembly-based transcriptome reconstruction. We present an extensive study based on realistic simulated RNA-Seq data. When compared with state-of-the-art approaches, MITIE proves to be significantly more sensitive and overall more accurate. Moreover, MITIE yields substantial performance gains when used with multiple samples. We applied our system to 38 Drosophila melanogaster modENCODE RNA-Seq libraries and estimated the sensitivity of reconstructing omitted transcript annotations and the specificity with respect to annotated transcripts. Our results corroborate that a well-motivated objective paired with appropriate optimization techniques lead to significant improvements over the state-of-the-art in transcriptome reconstruction. MITIE is implemented in C++ and is available from http://bioweb.me/mitie under the GPL license.

Developing Topological Insulator Fiber Based Photon Pairs Source for Ultrafast Optoelectronic Applications

DTIC Science & Technology

2016-04-01

DEVELOPING TOPOLOGICAL INSULATOR FIBER BASED PHOTON PAIRS SOURCE FOR ULTRAFAST OPTOELECTRONIC APPLICATIONS NORTHWESTERN UNIVERSITY...REPORT TYPE FINAL TECHNICAL REPORT 3. DATES COVERED (From - To) APRIL 2015 – DEC 2015 4. TITLE AND SUBTITLE DEVELOPING TOPOLOGICAL INSULATOR FIBER BASED...in developing a new source for the production of correlated/entangled photon pairs based on the unique nanolayer properties of topological insulator

BioWires: Conductive DNA Nanowires in a Computationally-Optimized, Synthetic Biological Platform for Nanoelectronic Fabrication

NASA Technical Reports Server (NTRS)

Vecchioni, Simon; Toomey, Emily; Capece, Mark C.; Rothschild, Lynn; Wind, Shalom

2017-01-01

DNA is an ideal template for a biological nanowire-it has a linear structure several atoms thick; it possesses addressable nucleobase geometry that can be precisely defined; and it is massively scalable into branched networks. Until now, the drawback of DNA as a conducting nanowire been, simply put, its low conductance. To address this deficiency, we extensively characterize a chemical variant of canonical DNA that exploits the affinity of natural cytosine bases for silver ions. We successfully construct chains of single silver ions inside double-stranded DNA, confirm the basic dC-Ag+-dC bond geometry and kinetics, and show length-tunability dependent on mismatch distribution, ion availability and enzyme activity. An analysis of the absorbance spectra of natural DNA and silver-binding, poly-cytosine DNA demonstrates the heightened thermostability of the ion chain and its resistance to aqueous stresses such as precipitation, dialysis and forced reduction. These chemically critical traits lend themselves to an increase in electrical conductivity of over an order of magnitude for 11-base silver-paired duplexes over natural strands when assayed by STM break junction. We further construct and implement a genetic pathway in the E. coli bacterium for the biosynthesis of highly ionizable DNA sequences. Toward future circuits, we construct a model of transcription network architectures to determine the most efficient and robust connectivity for cell-based fabrication, and we perform sequence optimization with a genetic algorithm to identify oligonucleotides robust to changes in the base-pairing energy landscape. We propose that this system will serve as a synthetic biological fabrication platform for more complex DNA nanotechnology and nanoelectronics with applications to deep space and low resource environments.

Base pairing among three cis-acting sequences contributes to template switching during hepadnavirus reverse transcription.

PubMed

Liu, Ning; Tian, Ru; Loeb, Daniel D

2003-02-18

Synthesis of the relaxed-circular (RC) DNA genome of hepadnaviruses requires two template switches during plus-strand DNA synthesis: primer translocation and circularization. Although primer translocation and circularization use different donor and acceptor sequences, and are distinct temporally, they share the common theme of switching from one end of the minus-strand template to the other end. Studies of duck hepatitis B virus have indicated that, in addition to the donor and acceptor sequences, three other cis-acting sequences, named 3E, M, and 5E, are required for the synthesis of RC DNA by contributing to primer translocation and circularization. The mechanism by which 3E, M, and 5E act was not known. We present evidence that these sequences function by base pairing with each other within the minus-strand template. 3E base-pairs with one portion of M (M3) and 5E base-pairs with an adjacent portion of M (M5). We found that disrupting base pairing between 3E and M3 and between 5E and M5 inhibited primer translocation and circularization. More importantly, restoring base pairing with mutant sequences restored the production of RC DNA. These results are consistent with the model that, within duck hepatitis B virus capsids, the ends of the minus-strand template are juxtaposed via base pairing to facilitate the two template switches during plus-strand DNA synthesis.

Loss of G-A base pairs is insufficient for achieving a large opening of U4 snRNA K-turn motif.

PubMed

Cojocaru, Vlad; Klement, Reinhard; Jovin, Thomas M

2005-01-01

Upon binding to the 15.5K protein, two tandem-sheared G-A base pairs are formed in the internal loop of the kink-turn motif of U4 snRNA (Kt-U4). We have reported that the folding of Kt-U4 is assisted by protein binding. Unstable interactions that contribute to a large opening of the free RNA ('k-e motion') were identified using locally enhanced sampling molecular dynamics simulations, results that agree with experiments. A detailed analysis of the simulations reveals that the k-e motion in Kt-U4 is triggered both by loss of G-A base pairs in the internal loop and backbone flexibility in the stems. Essential dynamics show that the loss of G-A base pairs is correlated along the first mode but anti-correlated along the third mode with the k-e motion. Moreover, when enhanced sampling was confined to the internal loop, the RNA adopted an alternative conformation characterized by a sharper kink, opening of G-A base pairs and modified stacking interactions. Thus, loss of G-A base pairs is insufficient for achieving a large opening of the free RNA. These findings, supported by previously published RNA structure probing experiments, suggest that G-A base pair formation occurs upon protein binding, thereby stabilizing a selective orientation of the stems.

Discrimination among individual Watson–Crick base pairs at the termini of single DNA hairpin molecules

PubMed Central

Vercoutere, Wenonah A.; Winters-Hilt, Stephen; DeGuzman, Veronica S.; Deamer, David; Ridino, Sam E.; Rodgers, Joseph T.; Olsen, Hugh E.; Marziali, Andre; Akeson, Mark

2003-01-01

Nanoscale α-hemolysin pores can be used to analyze individual DNA or RNA molecules. Serial examination of hundreds to thousands of molecules per minute is possible using ionic current impedance as the measured property. In a recent report, we showed that a nanopore device coupled with machine learning algorithms could automatically discriminate among the four combinations of Watson–Crick base pairs and their orientations at the ends of individual DNA hairpin molecules. Here we use kinetic analysis to demonstrate that ionic current signatures caused by these hairpin molecules depend on the number of hydrogen bonds within the terminal base pair, stacking between the terminal base pair and its nearest neighbor, and 5′ versus 3′ orientation of the terminal bases independent of their nearest neighbors. This report constitutes evidence that single Watson–Crick base pairs can be identified within individual unmodified DNA hairpin molecules based on their dynamic behavior in a nanoscale pore. PMID:12582251

[Mass spectrometric and quantum chemical study of dimeric associates of nucleosides].

PubMed

Sukhodub, L F; Aksenov, S A; Boldeskul, A I

1995-01-01

Deoxyribonucleosides H-bonded pairs were investigated using fast atom bombardment mass spectrometry and MNDO/H quantum chemistry method. It was shown that "rare" (enol or imin) forms of the nitrogen bases could form pairs with energy comparable with "canonical" base pair energy. It was shown that pair stability rows, which are measured using different experimental techniques, were in conformity each with other.

Twin hydroxymethyluracil-A base pair steps define the binding site for the DNA-binding protein TF1.

PubMed

Grove, A; Figueiredo, M L; Galeone, A; Mayol, L; Geiduschek, E P

1997-05-16

The DNA-bending protein TF1 is the Bacillus subtilis bacteriophage SPO1-encoded homolog of the bacterial HU proteins and the Escherichia coli integration host factor. We recently proposed that TF1, which binds with high affinity (Kd was approximately 3 nM) to preferred sites within the hydroxymethyluracil (hmU)-containing phage genome, identifies its binding sites based on sequence-dependent DNA flexibility. Here, we show that two hmU-A base pair steps coinciding with two previously proposed sites of DNA distortion are critical for complex formation. The affinity of TF1 is reduced 10-fold when both of these hmU-A base pair steps are replaced with A-hmU, G-C, or C-G steps; only modest changes in affinity result when substitutions are made at other base pairs of the TF1 binding site. Replacement of all hmU residues with thymine decreases the affinity of TF1 greatly; remarkably, the high affinity is restored when the two hmU-A base pair steps corresponding to previously suggested sites of distortion are reintroduced into otherwise T-containing DNA. T-DNA constructs with 3-base bulges spaced apart by 9 base pairs of duplex also generate nM affinity of TF1. We suggest that twin hmU-A base pair steps located at the proposed sites of distortion are key to target site selection by TF1 and that recognition is based largely, if not entirely, on sequence-dependent DNA flexibility.

Understanding the kinetic mechanism of RNA single base pair formation

PubMed Central

Xu, Xiaojun; Yu, Tao; Chen, Shi-Jie

2016-01-01

RNA functions are intrinsically tied to folding kinetics. The most elementary step in RNA folding is the closing and opening of a base pair. Understanding this elementary rate process is the basis for RNA folding kinetics studies. Previous studies mostly focused on the unfolding of base pairs. Here, based on a hybrid approach, we investigate the folding process at level of single base pairing/stacking. The study, which integrates molecular dynamics simulation, kinetic Monte Carlo simulation, and master equation methods, uncovers two alternative dominant pathways: Starting from the unfolded state, the nucleotide backbone first folds to the native conformation, followed by subsequent adjustment of the base conformation. During the base conformational rearrangement, the backbone either retains the native conformation or switches to nonnative conformations in order to lower the kinetic barrier for base rearrangement. The method enables quantification of kinetic partitioning among the different pathways. Moreover, the simulation reveals several intriguing ion binding/dissociation signatures for the conformational changes. Our approach may be useful for developing a base pair opening/closing rate model. PMID:26699466

Design of hair-like appendages and comparative analysis on their coordination toward steady and efficient swimming.

PubMed

Kwak, Bokeon; Bae, Joonbum

2017-05-22

The locomotion of water beetles has been widely studied in biology owing to their remarkable swimming skills. Inspired by the oar-like legs of water beetles, designing a robot that swims under the principle of drag-powered propulsion can lead to highly agile mobility. But its motion can easily be discontinuous and jerky due to backward motions (i.e. retraction) of the legs. Here we proposed novel hair-like appendages and consider their coordination to achieve steady and efficient swimming on the water surface. First of all, we propose several design schemes and fabrication methods of the hair-like appendages, which can passively adjust their projected area while obtaining enough thrust. The coordination between the two pairs of legs, as with water beetles in nature, were also investigated to achieve steady swimming without backward movement by varying the beating frequency and phase of the legs. To verify the functionality of the hair-like appendages and their coordinations, six different types of appendages were fabricated, and two robots (one with a single pair of legs and the other with two pairs of legs) were built. Locomotion of the robots was extensively compared through experiments, and it was found that steady swimming was achieved by properly coordinating the two pairs of legs without sacrificing their speed. Also, owing to the lower velocity fluctuation during swimming, it was shown that using two pairs of legs was more energy efficient than the robot with single pair of legs.

Imino proton exchange and base-pair kinetics in the AMP-RNA aptamer complex.

PubMed

Nonin, S; Jiang, F; Patel, D J

1997-05-02

We report on the dynamics of base-pair opening in the ATP-binding asymmetric internal loop and flanking base-pairs of the AMP-RNA aptamer complex by monitoring the exchange characteristics of the extremely well resolved imino protons in the NMR spectrum of the complex. The kinetics of imino proton exchange as a function of basic pH or added ammonia catalyst are used to measure the apparent base-pair dissociation constants and lifetimes of Watson-Crick and mismatched base-pairs, as well as the solvent accessibility of the unpaired imino protons in the complex. The exchange characteristics of the imino protons identify the existence of four additional hydrogen bonds stabilizing the conformation of the asymmetric ATP-binding internal loop that were not detected by NOEs and coupling constants alone, but are readily accommodated in the previously reported solution structure of the AMP-RNA aptamer complex published from our laboratory. The hydrogen exchange kinetics of the non-Watson-Crick pairs in the asymmetric internal loop of the AMP-RNA aptamer complex have been characterized and yield apparent dissociation constants (alphaKd) that range from 10(-2) to 10(-7). Surprisingly, three of these alphaKd values are amongst the lowest measured for all base-pairs in the AMP-RNA aptamer complex. Comparative studies of hydrogen exchange of the imino protons in the free RNA aptamer and the AMP-RNA aptamer complex establish that complexation stabilizes not only the bases within the ATP-binding asymmetric internal loop, but also the flanking stem base-pairs (two pairs on either side) of the binding site. We also outline some preliminary results related to the exchange properties of a sugar 2'-hydroxyl proton of a guanosine residue involved in a novel hydrogen bond that has been shown to contribute to the immobilization of the bound AMP by the RNA aptamer, and whose resonance is narrow and downfield shifted in the spectrum.

The 5S rRNA loop E: chemical probing and phylogenetic data versus crystal structure.

PubMed

Leontis, N B; Westhof, E

1998-09-01

A significant fraction of the bases in a folded, structured RNA molecule participate in noncanonical base pairing interactions, often in the context of internal loops or multi-helix junction loops. The appearance of each new high-resolution RNA structure provides welcome data to guide efforts to understand and predict RNA 3D structure, especially when the RNA in question is a functionally conserved molecule. The recent publication of the crystal structure of the "Loop E" region of bacterial 5S ribosomal RNA is such an event [Correll CC, Freeborn B, Moore PB, Steitz TA, 1997, Cell 91:705-712]. In addition to providing more examples of already established noncanonical base pairs, such as purine-purine sheared pairings, trans-Hoogsteen UA, and GU wobble pairs, the structure provides the first high-resolution views of two new purine-purine pairings and a new GU pairing. The goal of the present analysis is to expand the capabilities of both chemical probing and phylogenetic analysis to predict with greater accuracy the structures of RNA molecules. First, in light of existing chemical probing data, we investigate what lessons could be learned regarding the interpretation of this widely used method of RNA structure probing. Then we analyze the 3D structure with reference to molecular phylogeny data (assuming conservation of function) to discover what alternative base pairings are geometrically compatible with the structure. The comparisons between previous modeling efforts and crystal structures show that the intricate involvements of ions and water molecules in the maintenance of non-Watson-Crick pairs render the process of correctly identifying the interacting sites in such pairs treacherous, except in cases of trans-Hoogsteen A/U or sheared A/G pairs for the adenine N1 site. The phylogenetic analysis identifies A/A, A/C, A/U and C/A, C/C, and C/U pairings isosteric with sheared A/G, as well as A/A and A/C pairings isosteric with both G/U and G/G bifurcated pairings. Thus, each non-Watson-Crick pair could be characterized by a phylogenetic signature of variations between isosteric-like pairings. In addition to the conservative changes, which form a dictionary of pairings isosterically compatible with those observed in the crystal structure, concerted changes involving several base pairs also occur. The latter covariations may indicate transitions between related but distinctive motifs within the loop E of 5S ribosomal RNA.

The electrostatic characteristics of G·U wobble base pairs

PubMed Central

Xu, Darui; Landon, Theresa; Greenbaum, Nancy L.; Fenley, Marcia O.

2007-01-01

G·U wobble base pairs are the most common and highly conserved non-Watson–Crick base pairs in RNA. Previous surface maps imply uniformly negative electrostatic potential at the major groove of G·U wobble base pairs embedded in RNA helices, suitable for entrapment of cationic ligands. In this work, we have used a Poisson–Boltzmann approach to gain a more detailed and accurate characterization of the electrostatic profile. We found that the major groove edge of an isolated G·U wobble displays distinctly enhanced negativity compared with standard GC or AU base pairs; however, in the context of different helical motifs, the electrostatic pattern varies. G·U wobbles with distinct widening have similar major groove electrostatic potentials to their canonical counterparts, whereas those with minimal widening exhibit significantly enhanced electronegativity, ranging from 0.8 to 2.5 kT/e, depending upon structural features. We propose that the negativity at the major groove of G·U wobble base pairs is determined by the combined effect of the base atoms and the sugar-phosphate backbone, which is impacted by stacking pattern and groove width as a result of base sequence. These findings are significant in that they provide predictive power with respect to which G·U sites in RNA are most likely to bind cationic ligands. PMID:17526525

Learning in the Africanized honey bee: Apis mellifera L.

PubMed

Abramson, C I; Aquino, I S; Silva, M C; Price, J M

1997-09-01

Several series of experiments are reported that investigate learning in the Africanized honey bee. In the first series, classical conditioning of proboscis extension was studied by confining bees to small metal tubes where they received pairings of an odor with a 3-s feeding of sucrose. After a number of odor-sucrose pairings, the bees began to extend their proboscis to the odor. Controls include Unpaired, Discrimination, and Pseudoconditioning Groups. This technique was used to look at conditioning to a light CS, and to the odors of beeswax, geraniol, citral, and hexanal. The results indicate that acquisition was best when sucrose was paired with the odor of beeswax. Conditioning to the remaining odors was roughly similar, but acquisition did not occur using a light. In a second series of experiments, odors were no longer followed by sucrose feedings and the conditioned response slowly disappeared. With the exception of geraniol as a CS, this extinction effect did not occur if the animals continued to be fed on an unpaired schedule. In a third series of experiments, conditioned inhibition was demonstrated when geraniol was used as conditioned stimuli, but no effect was found when the odors of hexanal, citral and wax were used. In a fourth series of experiments, unrestrained bees flew back and forth from the laboratory to the hive, where they were taught to distinguish targets based on color and odor. With this technique, color and odor discrimination in the Africanized bees was demonstrated. In addition, it was found that more intruder bees visited the experimental station when the stimuli used were olfactory rather than visual.

Extracting biomedical events from pairs of text entities

PubMed Central

2015-01-01

Background Huge amounts of electronic biomedical documents, such as molecular biology reports or genomic papers are generated daily. Nowadays, these documents are mainly available in the form of unstructured free texts, which require heavy processing for their registration into organized databases. This organization is instrumental for information retrieval, enabling to answer the advanced queries of researchers and practitioners in biology, medicine, and related fields. Hence, the massive data flow calls for efficient automatic methods of text-mining that extract high-level information, such as biomedical events, from biomedical text. The usual computational tools of Natural Language Processing cannot be readily applied to extract these biomedical events, due to the peculiarities of the domain. Indeed, biomedical documents contain highly domain-specific jargon and syntax. These documents also describe distinctive dependencies, making text-mining in molecular biology a specific discipline. Results We address biomedical event extraction as the classification of pairs of text entities into the classes corresponding to event types. The candidate pairs of text entities are recursively provided to a multiclass classifier relying on Support Vector Machines. This recursive process extracts events involving other events as arguments. Compared to joint models based on Markov Random Fields, our model simplifies inference and hence requires shorter training and prediction times along with lower memory capacity. Compared to usual pipeline approaches, our model passes over a complex intermediate problem, while making a more extensive usage of sophisticated joint features between text entities. Our method focuses on the core event extraction of the Genia task of BioNLP challenges yielding the best result reported so far on the 2013 edition. PMID:26201478

Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations.

PubMed Central

Cotton, R G; Rodrigues, N R; Campbell, R D

1988-01-01

The chemical reactivity of thymine (T), when mismatched with the bases cytosine, guanine, and thymine, and of cytosine (C), when mismatched with thymine, adenine, and cytosine, has been examined. Heteroduplex DNAs containing such mismatched base pairs were first incubated with osmium tetroxide (for T and C mismatches) or hydroxylamine (for C mismatches) and then incubated with piperidine to cleave the DNA at the modified mismatched base. This cleavage was studied with an internally labeled strand containing the mismatched T or C, such that DNA cleavage and thus reactivity could be detected by gel electrophoresis. Cleavage at a total of 13 T and 21 C mismatches isolated (by at least three properly paired bases on both sides) single-base-pair mismatches was identified. All T or C mismatches studied were cleaved. By using end-labeled DNA probes containing T or C single-base-pair mismatches and conditions for limited cleavage, we were able to show that cleavage was at the base predicted by sequence analysis and that mismatches in a length of DNA could be readily detected by such an approach. This procedure may enable detection of all single-base-pair mismatches by use of sense and antisense probes and thus may be used to identify the mutated base and its position in a heteroduplex. Images PMID:3260032

Electrostatics Explains the Position-Dependent Effect of G⋅U Wobble Base Pairs on the Affinity of RNA Kissing Complexes.

PubMed

Abi-Ghanem, Josephine; Rabin, Clémence; Porrini, Massimiliano; Dausse, Eric; Toulmé, Jean-Jacques; Gabelica, Valérie

2017-10-06

In the RNA realm, non-Watson-Crick base pairs are abundant and can affect both the RNA 3D structure and its function. Here, we investigated the formation of RNA kissing complexes in which the loop-loop interaction is modulated by non-Watson-Crick pairs. Mass spectrometry, surface plasmon resonance, and UV-melting experiments show that the G⋅U wobble base pair favors kissing complex formation only when placed at specific positions. We tried to rationalize this effect by molecular modeling, including molecular mechanics Poisson-Boltzmann surface area (MMPBSA) thermodynamics calculations and PBSA calculations of the electrostatic potential surfaces. Modeling reveals that the G⋅U stabilization is due to a specific electrostatic environment defined by the base pairs of the entire loop-loop region. The loop is not symmetric, and therefore the identity and position of each base pair matters. Predicting and visualizing the electrostatic environment created by a given sequence can help to design specific kissing complexes with high affinity, for potential therapeutic, nanotechnology or analytical applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Extensive Karyotype Reorganization in the Fish Gymnotus arapaima (Gymnotiformes, Gymnotidae) Highlighted by Zoo-FISH Analysis

PubMed Central

Machado, Milla de Andrade; Pieczarka, Julio C.; Silva, Fernando H. R.; O'Brien, Patricia C. M.; Ferguson-Smith, Malcolm A.; Nagamachi, Cleusa Y.

2018-01-01

The genus Gymnotus (Gymnotiformes) contains over 40 species of freshwater electric fishes exhibiting a wide distribution throughout Central and South America, and being particularly prevalent in the Amazon basin. Cytogenetics has been an important tool in the cytotaxonomy and elucidation of evolutionary processes in this genus, including the unraveling the variety of diploid chromosome number (2n = from 34 to 54), the high karyotype diversity among species with a shared diploid number, different sex chromosome systems, and variation in the distribution of several Repetitive DNAs and colocation and association between those sequences. Recently whole chromosome painting (WCP) has been used for tracking the chromosomal evolution of the genus, showing highly reorganized karyotypes and the conserved synteny of the NOR bearing par within the clade G. carapo. In this study, painting probes derived from the chromosomes of G. carapo (GCA, 2n = 42, 30 m/sm + 12 st/a) were hybridized to the mitotic metaphases of G. arapaima (GAR, 2n = 44, 24 m/sm + 20 st/a). Our results uncovered chromosomal rearrangements and a high number of repetitive DNA regions. From the 12 chromosome pairs of G. carapo that can be individually differentiated (GCA1–3, 6, 7, 9, 14, 16, and 18–21), six pairs (GCA 1, 9, 14, 18, 20, 21) show conserved homology with GAR, five pairs (GCA 1, 9, 14, 20, 21) are also shared with cryptic species G. carapo 2n = 40 (34 m/sm + 6 st/a) and only the NOR bearing pair (GCA 20) is shared with G. capanema (GCP 2n = 34, 20 m/sm + 14 st/a). The remaining chromosomes are reorganized in the karyotype of GAR. Despite the close phylogenetic relationships of these species, our chromosome painting studies demonstrate an extensive reorganization of their karyotypes. PMID:29434621

Preservation affinity in consensus modules among stages of HIV-1 progression.

PubMed

Mosaddek Hossain, Sk Md; Ray, Sumanta; Mukhopadhyay, Anirban

2017-03-20

Analysis of gene expression data provides valuable insights into disease mechanism. Investigating relationship among co-expression modules of different stages is a meaningful tool to understand the way in which a disease progresses. Identifying topological preservation of modular structure also contributes to that understanding. HIV-1 disease provides a well-documented progression pattern through three stages of infection: acute, chronic and non-progressor. In this article, we have developed a novel framework to describe the relationship among the consensus (or shared) co-expression modules for each pair of HIV-1 infection stages. The consensus modules are identified to assess the preservation of network properties. We have investigated the preservation patterns of co-expression networks during HIV-1 disease progression through an eigengene-based approach. We discovered that the expression patterns of consensus modules have a strong preservation during the transitions of three infection stages. In particular, it is noticed that between acute and non-progressor stages the preservation is slightly more than the other pair of stages. Moreover, we have constructed eigengene networks for the identified consensus modules and observed the preservation structure among them. Some consensus modules are marked as preserved in two pairs of stages and are analyzed further to form a higher order meta-network consisting of a group of preserved modules. Additionally, we observed that module membership (MM) values of genes within a module are consistent with the preservation characteristics. The MM values of genes within a pair of preserved modules show strong correlation patterns across two infection stages. We have performed an extensive analysis to discover preservation pattern of co-expression network constructed from microarray gene expression data of three different HIV-1 progression stages. The preservation pattern is investigated through identification of consensus modules in each pair of infection stages. It is observed that the preservation of the expression pattern of consensus modules remains more prominent during the transition of infection from acute stage to non-progressor stage. Additionally, we observed that the module membership values of genes are coherent with preserved modules across the HIV-1 progression stages.

Interval-valued intuitionistic fuzzy matrix games based on Archimedean t-conorm and t-norm

NASA Astrophysics Data System (ADS)

Xia, Meimei

2018-04-01

Fuzzy game theory has been applied in many decision-making problems. The matrix game with interval-valued intuitionistic fuzzy numbers (IVIFNs) is investigated based on Archimedean t-conorm and t-norm. The existing matrix games with IVIFNs are all based on Algebraic t-conorm and t-norm, which are special cases of Archimedean t-conorm and t-norm. In this paper, the intuitionistic fuzzy aggregation operators based on Archimedean t-conorm and t-norm are employed to aggregate the payoffs of players. To derive the solution of the matrix game with IVIFNs, several mathematical programming models are developed based on Archimedean t-conorm and t-norm. The proposed models can be transformed into a pair of primal-dual linear programming models, based on which, the solution of the matrix game with IVIFNs is obtained. It is proved that the theorems being valid in the exiting matrix game with IVIFNs are still true when the general aggregation operator is used in the proposed matrix game with IVIFNs. The proposed method is an extension of the existing ones and can provide more choices for players. An example is given to illustrate the validity and the applicability of the proposed method.

The Rare-Variant Generalized Disequilibrium Test for Association Analysis of Nuclear and Extended Pedigrees with Application to Alzheimer Disease WGS Data.

PubMed

He, Zongxiao; Zhang, Di; Renton, Alan E; Li, Biao; Zhao, Linhai; Wang, Gao T; Goate, Alison M; Mayeux, Richard; Leal, Suzanne M

2017-02-02

Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger effect sizes than those found in sporadic cases, so family-based designs can be a more powerful approach than population-based designs. Moreover, some family-based designs are robust to confounding due to population admixture or substructure. We developed a RV extension of the generalized disequilibrium test (GDT) to analyze sequence data obtained from nuclear and extended families. The GDT utilizes genotype differences of all discordant relative pairs to assess associations within a family, and the RV extension combines the single-variant GDT statistic over a genomic region of interest. The RV-GDT has increased power by efficiently incorporating information beyond first-degree relatives and allows for the inclusion of covariates. Using simulated genetic data, we demonstrated that the RV-GDT method has well-controlled type I error rates, even when applied to admixed populations and populations with substructure. It is more powerful than existing family-based RV association methods, particularly for the analysis of extended pedigrees and pedigrees with missing data. We analyzed whole-genome sequence data from families affected by Alzheimer disease to illustrate the application of the RV-GDT. Given the capability of the RV-GDT to adequately control for population admixture or substructure and analyze pedigrees with missing genotype data and its superior power over other family-based methods, it is an effective tool for elucidating the involvement of RVs in the etiology of complex traits. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Test of CPT and Lorentz symmetry in entangled neutral kaons with the KLOE experiment

NASA Astrophysics Data System (ADS)

Babusci, D.; Balwierz-Pytko, I.; Bencivenni, G.; Bloise, C.; Bossi, F.; Branchini, P.; Budano, A.; Caldeira Balkeståhl, L.; Capon, G.; Ceradini, F.; Ciambrone, P.; Curciarello, F.; Czerwiński, E.; Danè, E.; De Leo, V.; De Lucia, E.; De Robertis, G.; De Santis, A.; De Simone, P.; Di Cicco, A.; Di Domenico, A.; Di Donato, C.; Di Salvo, R.; Domenici, D.; Erriquez, O.; Fanizzi, G.; Fantini, A.; Felici, G.; Fiore, S.; Franzini, P.; Gajos, A.; Gauzzi, P.; Giardina, G.; Giovannella, S.; Graziani, E.; Happacher, F.; Heijkenskjöld, L.; Höistad, B.; Jacewicz, M.; Johansson, T.; Kacprzak, K.; Kamińska, D.; Kupsc, A.; Lee-Franzini, J.; Loddo, F.; Loffredo, S.; Mandaglio, G.; Martemianov, M.; Martini, M.; Mascolo, M.; Messi, R.; Miscetti, S.; Morello, G.; Moricciani, D.; Moskal, P.; Nguyen, F.; Palladino, A.; Passeri, A.; Patera, V.; Prado Longhi, I.; Ranieri, A.; Santangelo, P.; Sarra, I.; Schioppa, M.; Sciascia, B.; Silarski, M.; Taccini, C.; Tortora, L.; Venanzoni, G.; Wiślicki, W.; Wolke, M.; Zdebik, J.

2014-03-01

Neutral kaon pairs produced in ϕ decays in anti-symmetric entangled state can be exploited to search for violation of CPT symmetry and Lorentz invariance. We present an analysis of the CP-violating process ϕ→KSKL→π+π-π+π- based on 1.7 fb of data collected by the KLOE experiment at the Frascati ϕ-factory DAΦNE. The data are used to perform a measurement of the CPT-violating parameters Δaμ for neutral kaons in the context of the Standard Model Extension framework. The parameters measured in the reference frame of the fixed stars are: Δa0=(-6.0±7.7stat±3.1syst)×10-18 GeV, ΔaX=(0.9±1.5stat±0.6syst)×10-18 GeV, ΔaY=(-2.0±1.5stat±0.5syst)×10-18 GeV, ΔaZ=(3.1±1.7stat±0.5syst)×10-18 GeV. These are presently the most precise measurements in the quark sector of the Standard Model Extension.

The origin of infrasonic ionosphere oscillations over tropospheric thunderstorms

NASA Astrophysics Data System (ADS)

Shao, Xuan-Min; Lay, Erin H.

2016-07-01

Thunderstorms have been observed to introduce infrasonic oscillations in the ionosphere, but it is not clear what processes or which parts of the thunderstorm generate the oscillations. In this paper, we present a new technique that uses an array of ground-based GPS total electron content (TEC) measurements to locate the source of the infrasonic oscillations and compare the source locations with thunderstorm features to understand the possible source mechanisms. The location technique utilizes instantaneous phase differences between pairs of GPS-TEC measurements and an algorithm to best fit the measured and the expected phase differences for assumed source positions and other related parameters. In this preliminary study, the infrasound waves are assumed to propagate along simple geometric raypaths from the source to the measurement locations to avoid extensive computations. The located sources are compared in time and space with thunderstorm development and lightning activity. Sources are often found near the main storm cells, but they are more likely related to the downdraft process than to the updraft process. The sources are also commonly found in the convectively quiet stratiform regions behind active cells and are in good coincidence with extensive lightning discharges and inferred high-altitude sprites discharges.

Image Restoration Using Functional and Anatomical Information Fusion with Application to SPECT-MRI Images

PubMed Central

Benameur, S.; Mignotte, M.; Meunier, J.; Soucy, J. -P.

2009-01-01

Image restoration is usually viewed as an ill-posed problem in image processing, since there is no unique solution associated with it. The quality of restored image closely depends on the constraints imposed of the characteristics of the solution. In this paper, we propose an original extension of the NAS-RIF restoration technique by using information fusion as prior information with application in SPECT medical imaging. That extension allows the restoration process to be constrained by efficiently incorporating, within the NAS-RIF method, a regularization term which stabilizes the inverse solution. Our restoration method is constrained by anatomical information extracted from a high resolution anatomical procedure such as magnetic resonance imaging (MRI). This structural anatomy-based regularization term uses the result of an unsupervised Markovian segmentation obtained after a preliminary registration step between the MRI and SPECT data volumes from each patient. This method was successfully tested on 30 pairs of brain MRI and SPECT acquisitions from different subjects and on Hoffman and Jaszczak SPECT phantoms. The experiments demonstrated that the method performs better, in terms of signal-to-noise ratio, than a classical supervised restoration approach using a Metz filter. PMID:19812704

The Impact of a Peer-Learning Agent Based on Pair Programming in a Programming Course

ERIC Educational Resources Information Center

Han, Keun-Woo; Lee, EunKyoung; Lee, YoungJun

2010-01-01

This paper analyzes the educational effects of a peer-learning agent based on pair programming in programming courses. A peer-learning agent system was developed to facilitate the learning of a programming language through the use of pair programming strategies. This system is based on the role of a peer-learning agent from pedagogical and…

Weak nanoscale chaos and anomalous relaxation in DNA

NASA Astrophysics Data System (ADS)

Mazur, Alexey K.

2017-06-01

Anomalous nonexponential relaxation in hydrated biomolecules is commonly attributed to the complexity of the free-energy landscapes, similarly to polymers and glasses. It was found recently that the hydrogen-bond breathing of terminal DNA base pairs exhibits a slow power-law relaxation attributable to weak Hamiltonian chaos, with parameters similar to experimental data. Here, the relationship is studied between this motion and spectroscopic signals measured in DNA with a small molecular photoprobe inserted into the base-pair stack. To this end, the earlier computational approach in combination with an analytical theory is applied to the experimental DNA fragment. It is found that the intensity of breathing dynamics is strongly increased in the internal base pairs that flank the photoprobe, with anomalous relaxation quantitatively close to that in terminal base pairs. A physical mechanism is proposed to explain the coupling between the relaxation of base-pair breathing and the experimental response signal. It is concluded that the algebraic relaxation observed experimentally is very likely a manifestation of weakly chaotic dynamics of hydrogen-bond breathing in the base pairs stacked to the photoprobe and that the weak nanoscale chaos can represent an ubiquitous hidden source of nonexponential relaxation in ultrafast spectroscopy.

Distribution of Base Pair Alternations in a Periodic DNA Chain: Application of Pólya Counting to a Physical System

NASA Astrophysics Data System (ADS)

Hillebrand, Malcolm; Paterson-Jones, Guy; Kalosakas, George; Skokos, Charalampos

2018-03-01

In modeling DNA chains, the number of alternations between Adenine-Thymine (AT) and Guanine-Cytosine (GC) base pairs can be considered as a measure of the heterogeneity of the chain, which in turn could affect its dynamics. A probability distribution function of the number of these alternations is derived for circular or periodic DNA. Since there are several symmetries to account for in the periodic chain, necklace counting methods are used. In particular, Polya's Enumeration Theorem is extended for the case of a group action that preserves partitioned necklaces. This, along with the treatment of generating functions as formal power series, allows for the direct calculation of the number of possible necklaces with a given number of AT base pairs, GC base pairs and alternations. The theoretically obtained probability distribution functions of the number of alternations are accurately reproduced by Monte Carlo simulations and fitted by Gaussians. The effect of the number of base pairs on the characteristics of these distributions is also discussed, as well as the effect of the ratios of the numbers of AT and GC base pairs.

Weak nanoscale chaos and anomalous relaxation in DNA.

PubMed

Mazur, Alexey K

2017-06-01

Anomalous nonexponential relaxation in hydrated biomolecules is commonly attributed to the complexity of the free-energy landscapes, similarly to polymers and glasses. It was found recently that the hydrogen-bond breathing of terminal DNA base pairs exhibits a slow power-law relaxation attributable to weak Hamiltonian chaos, with parameters similar to experimental data. Here, the relationship is studied between this motion and spectroscopic signals measured in DNA with a small molecular photoprobe inserted into the base-pair stack. To this end, the earlier computational approach in combination with an analytical theory is applied to the experimental DNA fragment. It is found that the intensity of breathing dynamics is strongly increased in the internal base pairs that flank the photoprobe, with anomalous relaxation quantitatively close to that in terminal base pairs. A physical mechanism is proposed to explain the coupling between the relaxation of base-pair breathing and the experimental response signal. It is concluded that the algebraic relaxation observed experimentally is very likely a manifestation of weakly chaotic dynamics of hydrogen-bond breathing in the base pairs stacked to the photoprobe and that the weak nanoscale chaos can represent an ubiquitous hidden source of nonexponential relaxation in ultrafast spectroscopy.

Molecular mechanisms of ribosomal protein gene coregulation.

PubMed

Reja, Rohit; Vinayachandran, Vinesh; Ghosh, Sujana; Pugh, B Franklin

2015-09-15

The 137 ribosomal protein genes (RPGs) of Saccharomyces provide a model for gene coregulation. We examined the positional and functional organization of their regulators (Rap1 [repressor activator protein 1], Fhl1, Ifh1, Sfp1, and Hmo1), the transcription machinery (TFIIB, TFIID, and RNA polymerase II), and chromatin at near-base-pair resolution using ChIP-exo, as RPGs are coordinately reprogrammed. Where Hmo1 is enriched, Fhl1, Ifh1, Sfp1, and Hmo1 cross-linked broadly to promoter DNA in an RPG-specific manner and demarcated by general minor groove widening. Importantly, Hmo1 extended 20-50 base pairs (bp) downstream from Fhl1. Upon RPG repression, Fhl1 remained in place. Hmo1 dissociated, which was coupled to an upstream shift of the +1 nucleosome, as reflected by the Hmo1 extension and core promoter region. Fhl1 and Hmo1 may create two regulatable and positionally distinct barriers, against which chromatin remodelers position the +1 nucleosome into either an activating or a repressive state. Consistent with in vitro studies, we found that specific TFIID subunits, in addition to cross-linking at the core promoter, made precise cross-links at Rap1 sites, which we interpret to reflect native Rap1-TFIID interactions. Our findings suggest how sequence-specific DNA binding regulates nucleosome positioning and transcription complex assembly >300 bp away and how coregulation coevolved with coding sequences. © 2015 Reja et al.; Published by Cold Spring Harbor Laboratory Press.

The 5΄ UTR of the type I toxin ZorO can both inhibit and enhance translation

PubMed Central

Wen, Jia; Harp, John R.

2017-01-01

Abstract Many bacterial type I toxin mRNAs possess a long 5΄ untranslated region (UTR) that serves as the target site of the corresponding antitoxin sRNA. This is the case for the zorO-orzO type I system where the OrzO antitoxin base pairs to the 174-nucleotide zorO 5΄ UTR. Here, we demonstrate that the full-length 5΄ UTR of the zorO type I toxin hinders its own translation independent of the sRNA whereas a processed 5΄ UTR (zorO Δ28) promotes translation. The full-length zorO 5΄ UTR folds into an extensive secondary structure sequestering the ribosome binding site (RBS). Processing of the 5΄ UTR does not alter the RBS structure, but opens a large region (EAP region) located upstream of the RBS. Truncation of this EAP region impairs zorO translation, but this defect can be rescued upon exposing the RBS. Additionally, the region spanning +35 to +50 of the zorO mRNA is needed for optimal translation of zorO. Importantly, the positive and negative effects on translation imparted by the 5΄ UTR can be transferred onto a reporter gene, indicative that the 5΄ UTR can solely drive regulation. Moreover, we show that the OrzO sRNA can inhibit zorO translation via base pairing to the of the EAP region. PMID:27903909

Brachial artery stiffness estimation using ARTSENS.

PubMed

Kiran, V Raj; Nabeel, P M; Joseph, Jayaraj; Sivaprakasam, Mohanasankar

2017-07-01

Central and peripheral arteries stiffening prominently affect hemodynamics thus increasing the risk of coronary heart disease, chronic kidney disease and end stage renal disease. There are several commercially available non-invasive measurement technologies for the evaluation of stiffness that are expensive, demand dedicated expertise and fall short for mass screening. Considering this, we have developed ARTSENS ® , a highly compact and portable image-free ultrasound device for evaluation of arterial stiffness. The capability of the device to perform accurate measurements of carotid artery stiffness has been validated through extensive in-vivo studies. In this paper we demonstrate the feasibility of using ARTSENS ® for measuring brachial artery stiffness. An inter-operator repeatability study was done based on in-vivo experiments on 9 young healthy subjects. The study included measurement of distension, end diastolic lumen diameter, arterial compliance and stiffness index performed both on carotid artery and brachial artery by two operators successively. The degree of agreement between the measurements made by operators has been investigated based on Bland-Altman plots and paired t-test. The measurements were populated within the limits of agreement. No statistically significant difference (p-values from paired t-test for end-diastolic diameter, distension, stiffness index, arterial compliance were 0.36, 0.24, 0.47 and 0.11 respectively) was seen for the brachial artery measurements performed by the two operators. The correlation between the measurement made by the operators was highly significant (r=0.86, p-value=0.003).

Combining Accuracy and Efficiency: An Incremental Focal-Point Method Based on Pair Natural Orbitals.

PubMed

Fiedler, Benjamin; Schmitz, Gunnar; Hättig, Christof; Friedrich, Joachim

2017-12-12

In this work, we present a new pair natural orbitals (PNO)-based incremental scheme to calculate CCSD(T) and CCSD(T0) reaction, interaction, and binding energies. We perform an extensive analysis, which shows small incremental errors similar to previous non-PNO calculations. Furthermore, slight PNO errors are obtained by using T PNO = T TNO with appropriate values of 10 -7 to 10 -8 for reactions and 10 -8 for interaction or binding energies. The combination with the efficient MP2 focal-point approach yields chemical accuracy relative to the complete basis-set (CBS) limit. In this method, small basis sets (cc-pVDZ, def2-TZVP) for the CCSD(T) part are sufficient in case of reactions or interactions, while some larger ones (e.g., (aug)-cc-pVTZ) are necessary for molecular clusters. For these larger basis sets, we show the very high efficiency of our scheme. We obtain not only tremendous decreases of the wall times (i.e., factors >10 2 ) due to the parallelization of the increment calculations as well as of the total times due to the application of PNOs (i.e., compared to the normal incremental scheme) but also smaller total times with respect to the standard PNO method. That way, our new method features a perfect applicability by combining an excellent accuracy with a very high efficiency as well as the accessibility to larger systems due to the separation of the full computation into several small increments.

Differential stabilities and sequence-dependent base pair opening dynamics of Watson-Crick base pairs with 5-hydroxymethylcytosine, 5-formylcytosine, or 5-carboxylcytosine.

PubMed

Szulik, Marta W; Pallan, Pradeep S; Nocek, Boguslaw; Voehler, Markus; Banerjee, Surajit; Brooks, Sonja; Joachimiak, Andrzej; Egli, Martin; Eichman, Brandt F; Stone, Michael P

2015-02-10

5-Hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) form during active demethylation of 5-methylcytosine (5mC) and are implicated in epigenetic regulation of the genome. They are differentially processed by thymine DNA glycosylase (TDG), an enzyme involved in active demethylation of 5mC. Three modified Dickerson-Drew dodecamer (DDD) sequences, amenable to crystallographic and spectroscopic analyses and containing the 5'-CG-3' sequence associated with genomic cytosine methylation, containing 5hmC, 5fC, or 5caC placed site-specifically into the 5'-T(8)X(9)G(10)-3' sequence of the DDD, were compared. The presence of 5caC at the X(9) base increased the stability of the DDD, whereas 5hmC or 5fC did not. Both 5hmC and 5fC increased imino proton exchange rates and calculated rate constants for base pair opening at the neighboring base pair A(5):T(8), whereas 5caC did not. At the oxidized base pair G(4):X(9), 5fC exhibited an increase in the imino proton exchange rate and the calculated kop. In all cases, minimal effects to imino proton exchange rates occurred at the neighboring base pair C(3):G(10). No evidence was observed for imino tautomerization, accompanied by wobble base pairing, for 5hmC, 5fC, or 5caC when positioned at base pair G(4):X(9); each favored Watson-Crick base pairing. However, both 5fC and 5caC exhibited intranucleobase hydrogen bonding between their formyl or carboxyl oxygens, respectively, and the adjacent cytosine N(4) exocyclic amines. The lesion-specific differences observed in the DDD may be implicated in recognition of 5hmC, 5fC, or 5caC in DNA by TDG. However, they do not correlate with differential excision of 5hmC, 5fC, or 5caC by TDG, which may be mediated by differences in transition states of the enzyme-bound complexes.

Differential stabilities and sequence-dependent base pair opening dynamics of Watson–Crick base pairs with 5-hydroxymethylcytosine, 5-formylcytosine, or 5-carboxylcytosine

DOE PAGES

Szulik, Marta W.; Pallan, Pradeep S.; Nocek, Boguslaw; ...

2015-01-29

5-Hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) form during active demethylation of 5-methylcytosine (5mC) and are implicated in epigenetic regulation of the genome. They are differentially processed by thymine DNA glycosylase (TDG), an enzyme involved in active demethylation of 5mC. Three modified Dickerson–Drew dodecamer (DDD) sequences, amenable to crystallographic and spectroscopic analyses and containing the 5'-CG-3' sequence associated with genomic cytosine methylation, containing 5hmC, 5fC, or 5caC placed site-specifically into the 5'-T 8X 9G 10-3' sequence of the DDD, were compared. The presence of 5caC at the X9 base increased the stability of the DDD, whereas 5hmC or 5fC didmore » not. Both 5hmC and 5fC increased imino proton exchange rates and calculated rate constants for base pair opening at the neighboring base pair A 5:T 8, whereas 5caC did not. At the oxidized base pair G 4:X 9, 5fC exhibited an increase in the imino proton exchange rate and the calculated k op. In all cases, minimal effects to imino proton exchange rates occurred at the neighboring base pair C 3:G 10. No evidence was observed for imino tautomerization, accompanied by wobble base pairing, for 5hmC, 5fC, or 5caC when positioned at base pair G 4:X 9; each favored Watson–Crick base pairing. However, both 5fC and 5caC exhibited intranucleobase hydrogen bonding between their formyl or carboxyl oxygens, respectively, and the adjacent cytosine N 4 exocyclic amines. The lesion-specific differences observed in the DDD may be implicated in recognition of 5hmC, 5fC, or 5caC in DNA by TDG. Furthermore, they do not correlate with differential excision of 5hmC, 5fC, or 5caC by TDG, which may be mediated by differences in transition states of the enzyme-bound complexes.« less

Differential Stabilities and Sequence-Dependent Base Pair Opening Dynamics of Watson–Crick Base Pairs with 5-Hydroxymethylcytosine, 5-Formylcytosine, or 5-Carboxylcytosine

PubMed Central

2016-01-01

5-Hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) form during active demethylation of 5-methylcytosine (5mC) and are implicated in epigenetic regulation of the genome. They are differentially processed by thymine DNA glycosylase (TDG), an enzyme involved in active demethylation of 5mC. Three modified Dickerson–Drew dodecamer (DDD) sequences, amenable to crystallographic and spectroscopic analyses and containing the 5′-CG-3′ sequence associated with genomic cytosine methylation, containing 5hmC, 5fC, or 5caC placed site-specifically into the 5′-T8X9G10-3′ sequence of the DDD, were compared. The presence of 5caC at the X9 base increased the stability of the DDD, whereas 5hmC or 5fC did not. Both 5hmC and 5fC increased imino proton exchange rates and calculated rate constants for base pair opening at the neighboring base pair A5:T8, whereas 5caC did not. At the oxidized base pair G4:X9, 5fC exhibited an increase in the imino proton exchange rate and the calculated kop. In all cases, minimal effects to imino proton exchange rates occurred at the neighboring base pair C3:G10. No evidence was observed for imino tautomerization, accompanied by wobble base pairing, for 5hmC, 5fC, or 5caC when positioned at base pair G4:X9; each favored Watson–Crick base pairing. However, both 5fC and 5caC exhibited intranucleobase hydrogen bonding between their formyl or carboxyl oxygens, respectively, and the adjacent cytosine N4 exocyclic amines. The lesion-specific differences observed in the DDD may be implicated in recognition of 5hmC, 5fC, or 5caC in DNA by TDG. However, they do not correlate with differential excision of 5hmC, 5fC, or 5caC by TDG, which may be mediated by differences in transition states of the enzyme-bound complexes. PMID:25632825

Peer Tutoring in Reading: The Effects of Role and Organization on Two Dimensions of Self-Esteem

ERIC Educational Resources Information Center

Miller, David; Topping, Keith; Thurston, Allen

2010-01-01

Background: Paired reading (PR) is an application of peer tutoring. It has been extensively researched, and its efficacy across a range of outcomes has been established. Benefits include improvements in key reading skills, and also in affective aspects of learning. Several studies have shown gains in self-esteem, although measurement methods have…

Validating the Technology Acceptance Model in the Context of the Laboratory Information System-Electronic Health Record Interface System

ERIC Educational Resources Information Center

Aquino, Cesar A.

2014-01-01

This study represents a research validating the efficacy of Davis' Technology Acceptance Model (TAM) by pairing it with the Organizational Change Readiness Theory (OCRT) to develop another extension to the TAM, using the medical Laboratory Information Systems (LIS)--Electronic Health Records (EHR) interface as the medium. The TAM posits that it is…

Understanding the effectiveness of vegetated streamside management zones for protecting water quality (Chapter 5)

Treesearch

Philip Smethurst; Kevin Petrone; Daniel Neary

2012-01-01

We set out to improve understanding of the effectiveness of streamside management zones (SMZs) for protecting water quality in landscapes dominated by agriculture. We conducted a paired-catchment experiment that included water quality monitoring before and after the establishment of a forest plantation as an SMZ on cleared farmland that was used for extensive grazing....

Layer-Based Approach for Image Pair Fusion.

PubMed

Son, Chang-Hwan; Zhang, Xiao-Ping

2016-04-20

Recently, image pairs, such as noisy and blurred images or infrared and noisy images, have been considered as a solution to provide high-quality photographs under low lighting conditions. In this paper, a new method for decomposing the image pairs into two layers, i.e., the base layer and the detail layer, is proposed for image pair fusion. In the case of infrared and noisy images, simple naive fusion leads to unsatisfactory results due to the discrepancies in brightness and image structures between the image pair. To address this problem, a local contrast-preserving conversion method is first proposed to create a new base layer of the infrared image, which can have visual appearance similar to another base layer such as the denoised noisy image. Then, a new way of designing three types of detail layers from the given noisy and infrared images is presented. To estimate the noise-free and unknown detail layer from the three designed detail layers, the optimization framework is modeled with residual-based sparsity and patch redundancy priors. To better suppress the noise, an iterative approach that updates the detail layer of the noisy image is adopted via a feedback loop. This proposed layer-based method can also be applied to fuse another noisy and blurred image pair. The experimental results show that the proposed method is effective for solving the image pair fusion problem.

A Stem-Loop Structure in Potato Leafroll Virus Open Reading Frame 5 (ORF5) Is Essential for Readthrough Translation of the Coat Protein ORF Stop Codon 700 Bases Upstream.

PubMed

Xu, Yi; Ju, Ho-Jong; DeBlasio, Stacy; Carino, Elizabeth J; Johnson, Richard; MacCoss, Michael J; Heck, Michelle; Miller, W Allen; Gray, Stewart M

2018-06-01

Translational readthrough of the stop codon of the capsid protein (CP) open reading frame (ORF) is used by members of the Luteoviridae to produce their minor capsid protein as a readthrough protein (RTP). The elements regulating RTP expression are not well understood, but they involve long-distance interactions between RNA domains. Using high-resolution mass spectrometry, glutamine and tyrosine were identified as the primary amino acids inserted at the stop codon of Potato leafroll virus (PLRV) CP ORF. We characterized the contributions of a cytidine-rich domain immediately downstream and a branched stem-loop structure 600 to 700 nucleotides downstream of the CP stop codon. Mutations predicted to disrupt and restore the base of the distal stem-loop structure prevented and restored stop codon readthrough. Motifs in the downstream readthrough element (DRTE) are predicted to base pair to a site within 27 nucleotides (nt) of the CP ORF stop codon. Consistent with a requirement for this base pairing, the DRTE of Cereal yellow dwarf virus was not compatible with the stop codon-proximal element of PLRV in facilitating readthrough. Moreover, deletion of the complementary tract of bases from the stop codon-proximal region or the DRTE of PLRV prevented readthrough. In contrast, the distance and sequence composition between the two domains was flexible. Mutants deficient in RTP translation moved long distances in plants, but fewer infection foci developed in systemically infected leaves. Selective 2'-hydroxyl acylation and primer extension (SHAPE) probing to determine the secondary structure of the mutant DRTEs revealed that the functional mutants were more likely to have bases accessible for long-distance base pairing than the nonfunctional mutants. This study reveals a heretofore unknown combination of RNA structure and sequence that reduces stop codon efficiency, allowing translation of a key viral protein. IMPORTANCE Programmed stop codon readthrough is used by many animal and plant viruses to produce key viral proteins. Moreover, such "leaky" stop codons are used in host mRNAs or can arise from mutations that cause genetic disease. Thus, it is important to understand the mechanism(s) of stop codon readthrough. Here, we shed light on the mechanism of readthrough of the stop codon of the coat protein ORFs of viruses in the Luteoviridae by identifying the amino acids inserted at the stop codon and RNA structures that facilitate this "leakiness" of the stop codon. Members of the Luteoviridae encode a C-terminal extension to the capsid protein known as the readthrough protein (RTP). We characterized two RNA domains in Potato leafroll virus (PLRV), located 600 to 700 nucleotides apart, that are essential for efficient RTP translation. We further determined that the PLRV readthrough process involves both local structures and long-range RNA-RNA interactions. Genetic manipulation of the RNA structure altered the ability of PLRV to translate RTP and systemically infect the plant. This demonstrates that plant virus RNA contains multiple layers of information beyond the primary sequence and extends our understanding of stop codon readthrough. Strategic targets that can be exploited to disrupt the virus life cycle and reduce its ability to move within and between plant hosts were revealed. Copyright © 2018 American Society for Microbiology.

Cumulative approaches to track formation under swift heavy ion (SHI) irradiation: Phenomenological correlation with formation energies of Frenkel pairs

NASA Astrophysics Data System (ADS)

Crespillo, M. L.; Agulló-López, F.; Zucchiatti, A.

2017-03-01

An extensive survey for the formation energies of Frenkel pairs, as representative candidates for radiation-induced point defects, is presented and discussed in relation to the cumulative mechanisms (CM) of track formation in dielectric materials under swift heavy ion (SHI) irradiation. These mechanisms rely on the generation and accumulation of point defects during irradiation followed by collapse of the lattice once a threshold defect concentration is reached. The physical basis of those approaches has been discussed by Fecht as a defect-assisted transition to an amorphous phase. Although a first quantitative analysis of the CM model was previously performed for LiNbO3 crystals, we have, here, adopted a broader phenomenological approach. It explores the correlation between track formation thresholds and the energies for Frenkel pair formation for a broad range of materials. It is concluded that the threshold stopping powers can be roughly scaled with the energies required to generate a critical Frenkel pair concentration in the order of a few percent of the total atomic content. Finally, a comparison with the predictions of the thermal spike model is discussed within the analytical Szenes approximation.

Collider tests of the Renormalizable Coloron Model

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

Bai, Yang; Dobrescu, Bogdan A.

The coloron, a massive version of the gluon present in gauge extensions of QCD, has been searched for at the LHC as a dijet or top quark pair resonance. We point out that in the Renormalizable Coloron Model (ReCoM) with a minimal field content to break the gauge symmetry, a color-octet scalar and a singlet scalar are naturally lighter than the coloron because they are pseudo Nambu-Goldstone bosons. Consequently, the coloron may predominantly decay into scalar pairs, leading to novel signatures at the LHC. When the color-octet scalar is lighter than the singlet, or when the singlet mass is above roughly 1 TeV, the signatures consist of multi-jet resonances of multiplicity up to 12, including topologies with multi-prong jet substructure, slightly displaced vertices, and sometimes a top quark pair. When the singlet is the lightest ReCoM boson and lighter than about 1 TeV, its main decays (more » $W^+W^-$, $$\\gamma Z$$, $ZZ$) arise at three loops. The LHC signatures then involve two or four boosted electroweak bosons, often originating from highly displaced vertices, plus one or two pairs of prompt jets or top quarks.« less

Optical storage networking

NASA Astrophysics Data System (ADS)

Mohr, Ulrich

2001-11-01

For efficient business continuance and backup of mission- critical data an inter-site storage network is required. Where traditional telecommunications costs are prohibitive for all but the largest organizations, there is an opportunity for regional carries to deliver an innovative storage service. This session reveals how a combination of optical networking and protocol-aware SAN gateways can provide an extended storage networking platform with the lowest cost of ownership and the highest possible degree of reliability, security and availability. Companies of every size, with mainframe and open-systems environments, can afford to use this integrated service. Three mayor applications are explained; channel extension, Network Attached Storage (NAS), Storage Area Networks (SAN) and how optical networks address the specific requirements. One advantage of DWDM is the ability for protocols such as ESCON, Fibre Channel, ATM and Gigabit Ethernet, to be transported natively and simultaneously across a single fiber pair, and the ability to multiplex many individual fiber pairs over a single pair, thereby reducing fiber cost and recovering fiber pairs already in use. An optical storage network enables a new class of service providers, Storage Service Providers (SSP) aiming to deliver value to the enterprise by managing storage, backup, replication and restoration as an outsourced service.

Optimal packaging of FIV genomic RNA depends upon a conserved long-range interaction and a palindromic sequence within gag.

PubMed

Rizvi, Tahir A; Kenyon, Julia C; Ali, Jahabar; Aktar, Suriya J; Phillip, Pretty S; Ghazawi, Akela; Mustafa, Farah; Lever, Andrew M L

2010-10-15

The feline immunodeficiency virus (FIV) is a lentivirus that is related to human immunodeficiency virus (HIV), causing a similar pathology in cats. It is a potential small animal model for AIDS and the FIV-based vectors are also being pursued for human gene therapy. Previous studies have mapped the FIV packaging signal (ψ) to two or more discontinuous regions within the 5' 511 nt of the genomic RNA and structural analyses have determined its secondary structure. The 5' and 3' sequences within ψ region interact through extensive long-range interactions (LRIs), including a conserved heptanucleotide interaction between R/U5 and gag. Other secondary structural elements identified include a conserved 150 nt stem-loop (SL2) and a small palindromic stem-loop within gag open reading frame that might act as a viral dimerization initiation site. We have performed extensive mutational analysis of these sequences and structures and ascertained their importance in FIV packaging using a trans-complementation assay. Disrupting the conserved heptanucleotide LRI to prevent base pairing between R/U5 and gag reduced packaging by 2.8-5.5 fold. Restoration of pairing using an alternative, non-wild type (wt) LRI sequence restored RNA packaging and propagation to wt levels, suggesting that it is the structure of the LRI, rather than its sequence, that is important for FIV packaging. Disrupting the palindrome within gag reduced packaging by 1.5-3-fold, but substitution with a different palindromic sequence did not restore packaging completely, suggesting that the sequence of this region as well as its palindromic nature is important. Mutation of individual regions of SL2 did not have a pronounced effect on FIV packaging, suggesting that either it is the structure of SL2 as a whole that is necessary for optimal packaging, or that there is redundancy within this structure. The mutational analysis presented here has further validated the previously predicted RNA secondary structure of FIV ψ. Copyright © 2010 Elsevier Ltd. All rights reserved.

On the assimilation-discrimination relationship in American English adults’ French vowel learning1

PubMed Central

Levy, Erika S.

2009-01-01

A quantitative “cross-language assimilation overlap” method for testing predictions of the Perceptual Assimilation Model (PAM) was implemented to compare results of a discrimination experiment with the listeners’ previously reported assimilation data. The experiment examined discrimination of Parisian French (PF) front rounded vowels ∕y∕ and ∕œ∕. Three groups of American English listeners differing in their French experience (no experience [NoExp], formal experience [ModExp], and extensive formal-plus-immersion experience [HiExp]) performed discrimination of PF ∕y-u∕, ∕y-o∕, ∕œ-o∕, ∕œ-u∕, ∕y-i∕, ∕y-ɛ∕, ∕œ-ɛ∕, ∕œ-i∕, ∕y-œ∕, ∕u-i∕, and ∕a-ɛ∕. Vowels were in bilabial ∕rabVp∕ and alveolar ∕radVt∕ contexts. More errors were found for PF front vs back rounded vowel pairs (16%) than for PF front unrounded vs rounded pairs (2%). Overall, ModExp listeners did not perform more accurately (11% errors) than NoExp listeners (13% errors). Extensive immersion experience, however, was associated with fewer errors (3%) than formal experience alone, although discrimination of PF ∕y-u∕ remained relatively poor (12% errors) for HiExp listeners. More errors occurred on pairs involving front vs back rounded vowels in alveolar context (20% errors) than in bilabial (11% errors). Significant correlations were revealed between listeners’ assimilation overlap scores and their discrimination errors, suggesting that the PAM may be extended to second-language (L2) vowel learning. PMID:19894844

Base pairing among three cis-acting sequences contributes to template switching during hepadnavirus reverse transcription

PubMed Central

Liu, Ning; Tian, Ru; Loeb, Daniel D.

2003-01-01

Synthesis of the relaxed-circular (RC) DNA genome of hepadnaviruses requires two template switches during plus-strand DNA synthesis: primer translocation and circularization. Although primer translocation and circularization use different donor and acceptor sequences, and are distinct temporally, they share the common theme of switching from one end of the minus-strand template to the other end. Studies of duck hepatitis B virus have indicated that, in addition to the donor and acceptor sequences, three other cis-acting sequences, named 3E, M, and 5E, are required for the synthesis of RC DNA by contributing to primer translocation and circularization. The mechanism by which 3E, M, and 5E act was not known. We present evidence that these sequences function by base pairing with each other within the minus-strand template. 3E base-pairs with one portion of M (M3) and 5E base-pairs with an adjacent portion of M (M5). We found that disrupting base pairing between 3E and M3 and between 5E and M5 inhibited primer translocation and circularization. More importantly, restoring base pairing with mutant sequences restored the production of RC DNA. These results are consistent with the model that, within duck hepatitis B virus capsids, the ends of the minus-strand template are juxtaposed via base pairing to facilitate the two template switches during plus-strand DNA synthesis. PMID:12578983

DNA polymerase catalysis in the absence of Watson-Crick hydrogen bonds

PubMed Central

Potapova, Olga; Chan, Chikio; DeLucia, Angela M.; Helquist, Sandra A.; Kool, Eric T.; Grindley, Nigel D. F.; Joyce, Catherine M.

2008-01-01

We report the first pre-steady-state kinetic studies of DNA replication in the absence of hydrogen bonds. We have used nonpolar nucleotide analogues that mimic the shape of a Watson-Crick base pair in order to investigate the kinetic consequences of a lack of hydrogen bonds in the polymerase reaction catalyzed by the Klenow fragment of DNA Polymerase I from Escherichia coli. With a thymine isostere lacking hydrogen bonding ability in the nascent pair, the efficiency (kpol/Kd) of the polymerase reaction is decreased by 30-fold, affecting ground state (Kd) and transition state (kpol) approximately equally. When both thymine and adenine analogues in the nascent pair lack hydrogen bonding ability, the efficiency of the polymerase reaction is decreased by about 1000-fold, with most the decrease attributable to the transition state. Reactions using nonpolar analogues at the primer terminal base pair demonstrated the requirement for a hydrogen bond between the polymerase and the minor groove of the primer-terminal base. The R668A mutation of Klenow fragment abolished this requirement, identifying R668 as the probable hydrogen bond donor. Detailed examination of the kinetic data suggested that Klenow fragment has an extremely low tolerance of even minor deviations of the analogue base pairs from ideal Watson-Crick geometry. Consistent with this idea, some analogue pairings were better tolerated by Klenow fragment mutants having more spacious active sites. By contrast, the Y-family polymerase Dbh was much less sensitive to changes in base pair dimensions, and more dependent on hydrogen bonding between base-paired partners. PMID:16411765

Comparative morphology and ultrastructure of the prosomal salivary glands in the unfed larvae Leptotrombidium orientale (Acariformes, Trombiculidae), a possible vector of tsutsugamushi disease agent.

PubMed

Shatrov, Andrew B

2015-07-01

The prosomal salivary glands of the unfed larvae Leptotrombidium orientale (Schluger) were investigated using transmission electron microscopy. In total, four pairs of the prosomal glands were identified--three pairs, the lateral, the medial and the anterior, belong to the podocephalic system, and one pair, the posterior, is separate having an own excretory duct. All glands are simple alveolar/acinous with prismatic cells arranged around a relatively small intra-alveolar lumen with the duct base. The cells of all glands besides the lateral ones contain practically mature electron-dense secretory granules ready to be discharged from the cells. The secretory granules in the lateral glands undergo formation and maturation due to the Golgi body activity. The cells of all gland types contain a large basally located nucleus and variously expressed rough endoplasmic reticulum. Specialized duct-forming cells filled with numerous freely scattered microtubules are situated in the middle zone of each gland's acinus and form the intra-alveolar lumen and the duct base. Both the acinar (secretory) and the duct-forming cells contact each other via gap junctions and septate desmosomes. Axons of nerve cells come close to the basal extensions of the duct-forming cells where they form the bulb-shaped synaptic terminations. The process of secretion is under the control of the nerve system that provides contraction of the duct-forming cells and discharge of secretion from the secretory cells into the intra-alveolar lumen and further to the exterior. Unfed larvae of L. orientale, the potential vector of tsutsugamushi disease agents, contain the most simply organized salivary secretory granules among known trombiculid larvae, and this secretion, besides the lateral glands, does not undergo significant additional maturation. Thus, the larvae are apparently ready to feed on the appropriate host just nearly after hatching.

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

DOE PAGES

Khachatryan, Vardan

2014-10-28

Our search for neutral Higgs bosons in the minimal supersymmetric extension of the standard model (MSSM) decaying to tau-lepton pairs in pp collisions is performed, using events recorded by the CMS experiment at the LHC. The dataset corresponds to an integrated luminosity of 24.6 fb -1, with 4.9 fb -1 at 7 TeV and 19.7 fb -1 at 8 TeV. To enhance the sensitivity to neutral MSSM Higgs bosons, the search includes the case where the Higgs boson is produced in association with a b-quark jet. No excess is observed in the tau-lepton-pair invariant mass spectrum. Exclusion limits are presentedmore » in the MSSM parameter space for different benchmark scenarios, m h max , m h mod + , m h mod - , light-stop, light-stau, τ-phobic, and low- m H. Lastly, upper limits on the cross section times branching fraction for gluon fusion and b-quark associated Higgs boson production are also given.« less

Discovery prospects of a light Higgs boson at the LHC in type-I 2HDM

NASA Astrophysics Data System (ADS)

Bhatia, Disha; Maitra, Ushoshi; Niyogi, Saurabh

2018-03-01

We present a comprehensive analysis of observing a light Higgs boson in the mass range 70-110 GeV at the 13 /14 TeV LHC, in the context of the type-I two-Higgs-doublet model. The decay of the light Higgs to a pair of bottom quarks is dominant in most parts of the parameter space, except in the fermiophobic limit. Here its decay to bosons (mainly a pair of photons) becomes important. We perform an extensive collider analysis for the b b ¯ and γ γ final states. The light scalar is tagged in the highly boosted regimes for the b b ¯ mode to reduce the enormous QCD background. This decay can be observed with a few thousand fb-1 of integrated luminosity at the LHC. Near the fermiophobic limit, the decay of the light Higgs to a pair of photons can even be probed with a few hundred fb-1 of integrated luminosity at the LHC.

Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

PubMed Central

Hodson, Charlotte; Purkiss, Andrew; Miles, Jennifer Anne; Walden, Helen

2014-01-01

Summary The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ∼40 E2s and ∼600 E3s giving rise to a possible ∼24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL. PMID:24389026

Drop-in compatible entanglement for optical-fiber networks.

PubMed

Hall, Matthew A; Altepeter, Joseph B; Kumar, Prem

2009-08-17

A growing number of quantum communication protocols require entanglement distribution among remote parties, which is best accomplished by exploiting the mature technology and extensive infrastructure of low-loss optical fiber. For this reason, a practical source of entangled photons must be drop-in compatible with optical fiber networks. Here we demonstrate such a source for the first time, in which the nonlinearity of standard single-mode fiber is utilized to yield entangled photon pairs in the 1310-nm O-band. Using an ultra-stable design, we produce polarization entanglement with 98.0% +/- 0.5% fidelity to a maximally entangled state as characterized via coincidence-basis tomography. To demonstrate the source's drop-in capability, we transmit one photon from each entangled pair through a telecommunications-grade optical amplifier set to boost classical 1550-nm (C-band) communication signals. We verify that the photon pairs experience no measurable decoherence upon passing through the active amplifier (the output state's fidelity with a maximally entangled state is 98.4% +/- 1.4%). (c) 2009 Optical Society of America

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

NASA Astrophysics Data System (ADS)

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Taurok, A.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Bansal, M.; Bansal, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Luyckx, S.; Ochesanu, S.; Rougny, R.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Daci, N.; Heracleous, N.; Keaveney, J.; Lowette, S.; Maes, M.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Dobur, D.; Favart, L.; Gay, A. P. R.; Grebenyuk, A.; Léonard, A.; Mohammadi, A.; Perniè, L.; Reis, T.; Seva, T.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wang, J.; Zenoni, F.; Adler, V.; Beernaert, K.; Benucci, L.; Cimmino, A.; Costantini, S.; Crucy, S.; Dildick, S.; Fagot, A.; Garcia, G.; Mccartin, J.; Ocampo Rios, A. A.; Ryckbosch, D.; Salva Diblen, S.; Sigamani, M.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bruno, G.; Castello, R.; Caudron, A.; Ceard, L.; Da Silveira, G. G.; Delaere, C.; du Pree, T.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Jafari, A.; Jez, P.; Komm, M.; Lemaitre, V.; Nuttens, C.; Pagano, D.; Perrini, L.; Pin, A.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Aldá, W. L.; Alves, G. A.; Brito, L.; Correa Martins, M.; Dos Reis Martins, T.; Mora Herrera, C.; Pol, M. E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santaolalla, J.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Bernardes, C. A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Aleksandrov, A.; Genchev, V.; Iaydjiev, P.; Marinov, A.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Du, R.; Jiang, C. H.; Plestina, R.; Tao, J.; Wang, Z.; Asawatangtrakuldee, C.; Ban, Y.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Zou, W.; Avila, C.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Mekterovic, D.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Bodlak, M.; Finger, M.; Finger, M.; Assran, Y.; Ellithi Kamel, A.; Mahmoud, M. A.; Radi, A.; Kadastik, M.; Murumaa, M.; Raidal, M.; Tiko, A.; Eerola, P.; Fedi, G.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Baffioni, S.; Beaudette, F.; Busson, P.; Charlot, C.; Dahms, T.; Dalchenko, M.; Dobrzynski, L.; Filipovic, N.; Florent, A.; Granier de Cassagnac, R.; Mastrolorenzo, L.; Miné, P.; Mironov, C.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Paganini, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Veelken, C.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Chabert, E. C.; Collard, C.; Conte, E.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Beaupere, N.; Boudoul, G.; Bouvier, E.; Brochet, S.; Carrillo Montoya, C. A.; Chasserat, J.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Kurca, T.; Lethuillier, M.; Mirabito, L.; Perries, S.; Ruiz Alvarez, J. D.; Sabes, D.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Xiao, H.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Bontenackels, M.; Edelhoff, M.; Feld, L.; Hindrichs, O.; Klein, K.; Ostapchuk, A.; Perieanu, A.; Raupach, F.; Sammet, J.; Schael, S.; Weber, H.; Wittmer, B.; Zhukov, V.; Ata, M.; Brodski, M.; Dietz-Laursonn, E.; Duchardt, D.; Erdmann, M.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Klingebiel, D.; Knutzen, S.; Kreuzer, P.; Merschmeyer, M.; Meyer, A.; Millet, P.; Olschewski, M.; Padeken, K.; Papacz, P.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Weber, M.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Haj Ahmad, W.; Heister, A.; Hoehle, F.; Kargoll, B.; Kress, T.; Kuessel, Y.; Künsken, A.; Lingemann, J.; Nowack, A.; Nugent, I. M.; Perchalla, L.; Pooth, O.; Stahl, A.; Asin, I.; Bartosik, N.; Behr, J.; Behrenhoff, W.; Behrens, U.; Bell, A. J.; Bergholz, M.; Bethani, A.; Borras, K.; Burgmeier, A.; Cakir, A.; Calligaris, L.; Campbell, A.; Choudhury, S.; Costanza, F.; Diez Pardos, C.; Dooling, S.; Dorland, T.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Flucke, G.; Garay Garcia, J.; Geiser, A.; Gunnellini, P.; Hauk, J.; Hellwig, G.; Hempel, M.; Horton, D.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Katsas, P.; Kieseler, J.; Kleinwort, C.; Krücker, D.; Lange, W.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Lutz, B.; Mankel, R.; Marfin, I.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Nayak, A.; Novgorodova, O.; Ntomari, E.; Perrey, H.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Ribeiro Cipriano, P. M.; Roland, B.; Ron, E.; Sahin, M. Ö.; Salfeld-Nebgen, J.; Saxena, P.; Schmidt, R.; Schoerner-Sadenius, T.; Schröder, M.; Seitz, C.; Spannagel, S.; Vargas Trevino, A. D. R.; Walsh, R.; Wissing, C.; Aldaya Martin, M.; Blobel, V.; Centis Vignali, M.; Draeger, A. r.; Erfle, J.; Garutti, E.; Goebel, K.; Görner, M.; Haller, J.; Hoffmann, M.; Höing, R. S.; Kirschenmann, H.; Klanner, R.; Kogler, R.; Lange, J.; Lapsien, T.; Lenz, T.; Marchesini, I.; Ott, J.; Peiffer, T.; Pietsch, N.; Poehlsen, J.; Poehlsen, T.; Rathjens, D.; Sander, C.; Schettler, H.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Seidel, M.; Sola, V.; Stadie, H.; Steinbrück, G.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Butz, E.; Chwalek, T.; De Boer, W.; Descroix, A.; Dierlamm, A.; Feindt, M.; Frensch, F.; Giffels, M.; Hartmann, F.; Hauth, T.; Husemann, U.; Katkov, I.; Kornmayer, A.; Kuznetsova, E.; Lobelle Pardo, P.; Mozer, M. U.; Müller, Th.; Nürnberg, A.; Quast, G.; Rabbertz, K.; Ratnikov, F.; Röcker, S.; Simonis, H. J.; Stober, F. M.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weiler, T.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Markou, A.; Markou, C.; Psallidas, A.; Topsis-Giotis, I.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Stiliaris, E.; Aslanoglou, X.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Bencze, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Molnar, J.; Palinkas, J.; Szillasi, Z.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Swain, S. K.; Beri, S. B.; Bhatnagar, V.; Gupta, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, M.; Kumar, R.; Mittal, M.; Nishu, N.; Singh, J. B.; Kumar, Ashok; Kumar, Arun; Ahuja, S.; Bhardwaj, A.; Choudhary, B. C.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, V.; Banerjee, S.; Bhattacharya, S.; Chatterjee, K.; Dutta, S.; Gomber, B.; Jain, Sa.; Jain, Sh.; Khurana, R.; Modak, A.; Mukherjee, S.; Roy, D.; Sarkar, S.; Sharan, M.; Abdulsalam, A.; Dutta, D.; Kailas, S.; Kumar, V.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Banerjee, S.; Bhowmik, S.; Chatterjee, R. M.; Dewanjee, R. K.; Dugad, S.; Ganguly, S.; Ghosh, S.; Guchait, M.; Gurtu, A.; Kole, G.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Mohanty, G. B.; Parida, B.; Sudhakar, K.; Wickramage, N.; Bakhshiansohi, H.; Behnamian, H.; Etesami, S. M.; Fahim, A.; Goldouzian, R.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Barbone, L.; Calabria, C.; Chhibra, S. S.; Colaleo, A.; Creanza, D.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Selvaggi, G.; Silvestris, L.; Singh, G.; Venditti, R.; Zito, G.; Abbiendi, G.; Benvenuti, A. C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Primavera, F.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Travaglini, R.; Albergo, S.; Cappello, G.; Chiorboli, M.; Costa, S.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Gallo, E.; Gonzi, S.; Gori, V.; Lenzi, P.; Meschini, M.; Paoletti, S.; Sguazzoni, G.; Tropiano, A.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Ferretti, R.; Ferro, F.; Lo Vetere, M.; Robutti, E.; Tosi, S.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Gerosa, R.; Ghezzi, A.; Govoni, P.; Lucchini, M. T.; Malvezzi, S.; Manzoni, R. A.; Martelli, A.; Marzocchi, B.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Ragazzi, S.; Redaelli, N.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Fabozzi, F.; Iorio, A. O. 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V.; Vinogradov, A.; Belyaev, A.; Boos, E.; Bunichev, V.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Ekmedzic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Battilana, C.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Domínguez Vázquez, D.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Navarro De Martino, E.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Albajar, C.; de Trocóniz, J. 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I.; Vlimant, J. R.; Wardle, N.; Wöhri, H. K.; Wollny, H.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Renker, D.; Rohe, T.; Bachmair, F.; Bäni, L.; Bianchini, L.; Buchmann, M. A.; Casal, B.; Chanon, N.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dünser, M.; Eller, P.; Grab, C.; Hits, D.; Hoss, J.; Lustermann, W.; Mangano, B.; Marini, A. C.; Martinez Ruiz del Arbol, P.; Masciovecchio, M.; Meister, D.; Mohr, N.; Nägeli, C.; Nessi-Tedaldi, F.; Pandolfi, F.; Pauss, F.; Peruzzi, M.; Quittnat, M.; Rebane, L.; Rossini, M.; Starodumov, A.; Takahashi, M.; Theofilatos, K.; Wallny, R.; Weber, H. A.; Amsler, C.; Canelli, M. F.; Chiochia, V.; De Cosa, A.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Lange, C.; Millan Mejias, B.; Ngadiuba, J.; Robmann, P.; Ronga, F. J.; Taroni, S.; Verzetti, M.; Yang, Y.; Cardaci, M.; Chen, K. H.; Ferro, C.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Volpe, R.; Yu, S. S.; Chang, P.; Chang, Y. 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R.; Dominguez, A.; Gonzalez Suarez, R.; Keller, J.; Knowlton, D.; Kravchenko, I.; Lazo-Flores, J.; Malik, S.; Meier, F.; Snow, G. R.; Zvada, M.; Dolen, J.; Godshalk, A.; Iashvili, I.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Haley, J.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Trocino, D.; Wang, R.-J.; Wood, D.; Zhang, J.; Hahn, K. A.; Kubik, A.; Mucia, N.; Odell, N.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Sung, K.; Velasco, M.; Won, S.; Brinkerhoff, A.; Chan, K. M.; Drozdetskiy, A.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Pearson, T.; Planer, M.; Ruchti, R.; Valls, N.; Wayne, M.; Wolf, M.; Woodard, A.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Hill, C.; Hughes, R.; Kotov, K.; Ling, T. Y.; Puigh, D.; Rodenburg, M.; Smith, G.; Winer, B. L.; Wolfe, H.; Wulsin, H. W.; Driga, O.; Elmer, P.; Hebda, P.; Hunt, A.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zuranski, A.; Brownson, E.; Mendez, H.; Ramirez Vargas, J. E.; Barnes, V. E.; Benedetti, D.; Bortoletto, D.; De Mattia, M.; Gutay, L.; Hu, Z.; Jha, M. K.; Jones, M.; Jung, K.; Kress, M.; Leonardo, N.; Lopes Pegna, D.; Maroussov, V.; Miller, D. H.; Neumeister, N.; Radburn-Smith, B. C.; Shi, X.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Ecklund, K. M.; Geurts, F. J. M.; Li, W.; Michlin, B.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; Covarelli, R.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Garcia-Bellido, A.; Goldenzweig, P.; Han, J.; Harel, A.; Khukhunaishvili, A.; Petrillo, G.; Vishnevskiy, D.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Lungu, G.; Mesropian, C.; Arora, S.; Barker, A.; Chou, J. P.; Contreras-Campana, C.; Contreras-Campana, E.; Duggan, D.; Ferencek, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Kaplan, S.; Lath, A.; Panwalkar, S.; Park, M.; Patel, R.; Salur, S.; Schnetzer, S.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Rose, K.; Spanier, S.; York, A.; Bouhali, O.; Castaneda Hernandez, A.; Eusebi, R.; Flanagan, W.; Gilmore, J.; Kamon, T.; Khotilovich, V.; Krutelyov, V.; Montalvo, R.; Osipenkov, I.; Pakhotin, Y.; Perloff, A.; Roe, J.; Rose, A.; Safonov, A.; Sakuma, T.; Suarez, I.; Tatarinov, A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kovitanggoon, K.; Kunori, S.; Lee, S. W.; Libeiro, T.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Sharma, M.; Sheldon, P.; Snook, B.; Tuo, S.; Velkovska, J.; Arenton, M. W.; Boutle, S.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Lin, C.; Neu, C.; Wood, J.; Clarke, C.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Dodd, L.; Duric, S.; Friis, E.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Lazaridis, C.; Levine, A.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ross, I.; Sarangi, T.; Savin, A.; Smith, W. H.; Taylor, D.; Verwilligen, P.; Vuosalo, C.; Woods, N.

2014-10-01

A search for neutral Higgs bosons in the minimal supersymmetric extension of the standard model (MSSM) decaying to tau-lepton pairs in pp collisions is performed, using events recorded by the CMS experiment at the LHC. The dataset corresponds to an integrated luminosity of 24.6 fb-1, with 4.9 fb-1 at 7 TeV and 19.7 fb-1 at 8 TeV. To enhance the sensitivity to neutral MSSM Higgs bosons, the search includes the case where the Higgs boson is produced in association with a b-quark jet. No excess is observed in the tau-lepton-pair invariant mass spectrum. Exclusion limits are presented in the MSSM parameter space for different benchmark scenarios, m {h/max}, m {h/mod +}, m {h/mod -}, light-stop, light-stau, τ-phobic, and low- m H. Upper limits on the cross section times branching fraction for gluon fusion and b-quark associated Higgs boson production are also given. [Figure not available: see fulltext.

Nonlocal Intuition: Replication and Paired-subjects Enhancement Effects

PubMed Central

Mirzaei, Maryam; Zali, Mohammad Reza

2014-01-01

This article reports the results of a study of repeat entrepreneurs in Tehran, Iran, in which nonlocal intuition was investigated in a replication and extension of experiment using measures of heart rate variability (HRV). Nonlocal intuition is the perception of information about a distant or future event by the body's psychophysiological systems, which is not based on reason or memories of prior experience. This study follows up on the McCraty, Radin, and Bradley studies, which found evidence of nonlocal intuition. We used Radin's experimental protocol, with the addition of HRV measures as in the McCraty studies involving computer administration of a random sequence of calm and emotional pictures as the stimulus, and conducted two experiments on mutually exclusive samples—the first on a group of single participants (N=15) and the second on a group of co-participant pairs (N=30)—to investigate the question of the “amplification” of intuition effects by social connection. Each experiment was conducted over 45 trials while heart rate rhythm activity was recorded continuously. Results, using random permutation analysis, a statistically conservative procedure, show significant pre-stimulus results—that is, for the period before the computer had randomly selected the picture stimulus—for both experiments. Moreover, while significant separation between the emotional and calm HRV curves was observed in the single-participant experiment, an even larger separation was apparent for the experiment on co-participant pairs; the difference between the two groups was also significant. Overall, the results of the single-participant experiment confirm previous finding: that electrophysiological measures, especially changes in the heart rhythm, can detect intuitive foreknowledge. This result is notable because it constitutes cross-cultural corroboration in a non-Western context—namely, Iran. In addition, the results for co-participant pairs offer new evidence on the amplification of the nonlocal intuition signal. PMID:24808977

Base drive circuit

DOEpatents

Lange, A.C.

1995-04-04

An improved base drive circuit having a level shifter for providing bistable input signals to a pair of non-linear delays. The non-linear delays provide gate control to a corresponding pair of field effect transistors through a corresponding pair of buffer components. The non-linear delays provide delayed turn-on for each of the field effect transistors while an associated pair of transistors shunt the non-linear delays during turn-off of the associated field effect transistor. 2 figures.

An Intelligent Model for Pairs Trading Using Genetic Algorithms.

PubMed

Huang, Chien-Feng; Hsu, Chi-Jen; Chen, Chi-Chung; Chang, Bao Rong; Li, Chen-An

2015-01-01

Pairs trading is an important and challenging research area in computational finance, in which pairs of stocks are bought and sold in pair combinations for arbitrage opportunities. Traditional methods that solve this set of problems mostly rely on statistical methods such as regression. In contrast to the statistical approaches, recent advances in computational intelligence (CI) are leading to promising opportunities for solving problems in the financial applications more effectively. In this paper, we present a novel methodology for pairs trading using genetic algorithms (GA). Our results showed that the GA-based models are able to significantly outperform the benchmark and our proposed method is capable of generating robust models to tackle the dynamic characteristics in the financial application studied. Based upon the promising results obtained, we expect this GA-based method to advance the research in computational intelligence for finance and provide an effective solution to pairs trading for investment in practice.

An Intelligent Model for Pairs Trading Using Genetic Algorithms

PubMed Central

Hsu, Chi-Jen; Chen, Chi-Chung; Li, Chen-An

2015-01-01

Pairs trading is an important and challenging research area in computational finance, in which pairs of stocks are bought and sold in pair combinations for arbitrage opportunities. Traditional methods that solve this set of problems mostly rely on statistical methods such as regression. In contrast to the statistical approaches, recent advances in computational intelligence (CI) are leading to promising opportunities for solving problems in the financial applications more effectively. In this paper, we present a novel methodology for pairs trading using genetic algorithms (GA). Our results showed that the GA-based models are able to significantly outperform the benchmark and our proposed method is capable of generating robust models to tackle the dynamic characteristics in the financial application studied. Based upon the promising results obtained, we expect this GA-based method to advance the research in computational intelligence for finance and provide an effective solution to pairs trading for investment in practice. PMID:26339236

The fidelity of replication of the three-base-pair set adenine/thymine, hypoxanthine/cytosine and 6-thiopurine/5-methyl-2-pyrimidinone with T7 DNA polymerase

PubMed Central

2004-01-01

With the goal of constructing a genetic alphabet consisting of a set of three base pairs, the fidelity of replication of the three base pairs TH (5-methyl-2-pyrimidinone)/HS (6-thiopurine; thiohypoxanthine), C/H (hypoxanthine) and T/A was evaluated using T7 DNA polymerase, a polymerase with a strong 3′→5′ exonuclease activity. An evaluation of the suitability of a new base pair for replication should include both the contribution of the fidelity of a polymerase activity and the contribution of proofreading by a 3′→5′ exonuclease activity. Using a steady-state kinetics method that included the contribution of the 3′→5′ exonuclease activity, the fidelity of replication was determined. The method determined the ratio of the apparent rate constant for the addition of a deoxynucleotide to the primer across from a template base by the polymerase activity and the rate constant for removal of the added deoxynucleotide from the primer by the 3′→5′ exonuclease activity. This ratio was designated the eni (efficiency of net incorporation). The eni of the base pair C/H was equal to or greater than the eni of T/A. The eni of the base pair TH/HS was 0.1 times that of A/T for TH in the template and 0.01 times that of A/T for HS in the template. The ratio of the eni of a mismatched deoxynucleotide to the eni of a matched deoxynucleotide was a measure of the error frequency. The error frequencies were as follows: thymine or TH opposite a template hypoxanthine, 2×10−6; HS opposite a template cytosine, <3×10−4. The remaining 24 mismatched combinations of bases gave no detectable net incorporation. Two mismatches, hypoxanthine opposite a template thymine or a template TH, showed trace incorporation in the presence of a standard dNTP complementary to the next template base. T7 DNA polymerase extended the primer beyond each of the matched base pairs of the set. The level of fidelity of replication of the three base pairs with T7 DNA polymerase suggests that they are adequate for a three-base-pair alphabet for DNA replication. PMID:15078225

Embryonic Development of the Light Organ of the Sepiolid Squid Euprymna scolopes Berry.

PubMed

Montgomery, M K; McFall-Ngai, M

1993-06-01

The sepiolid squid Euprymna scolopes maintains luminous bacterial symbionts of the species Vibrio fischeri in a bilobed light organ partially embedded in the ventral surface of the ink sac. Anatomical and ultrastructural observations of the light organ during embryogenesis indicate that the organ begins development as a paired proliferation of the mesoderm of the hindgut-ink sac complex. Three-dimensional reconstruction of the incipient light organ of a newly hatched juvenile revealed the presence of three pairs of sacculate crypts, each crypt joined to a pore on the surface of the light organ by a ciliated duct. The crypts, which become populated with bacterial symbionts within hours after the juvenile hatches, appear to result from sequential paired invaginations of the surface epithelium of the hindgut-ink sac complex during embryogenesis. A pair of anterior and a pair of posterior ciliated epithelial appendages, which may facilitate infection of the incipient light organ with symbiotic bacteria, develop by extension and growth of the surface epithelium. The ink sac and reflector develop dorsal to the crypts and together function to direct luminescence ventrally. These two accessory tissues are present at the time of hatching, although changes in their overall structure accompany growth and maturation of the light organ. A third accessory tissue, the muscle-derived lens, appears during post-hatch maturation of the light organ.

Can honey bees discriminate between floral-fragrance isomers?

PubMed

Aguiar, João Marcelo Robazzi Bignelli Valente; Roselino, Ana Carolina; Sazima, Marlies; Giurfa, Martin

2018-05-24

Many flowering plants present variable complex fragrances, which usually include different isomers of the same molecule. As fragrance is an essential cue for flower recognition by pollinators, we ask if honey bees discriminate between floral-fragrance isomers in an appetitive context. We used the olfactory conditioning of the proboscis extension response (PER), which allows training a restrained bee to an odor paired with sucrose solution. Bees were trained under an absolute (a single odorant rewarded) or a differential conditioning regime (a rewarded vs. a non-rewarded odorant) using four different pairs of isomers. One hour after training, discrimination and generalization between pairs of isomers were tested. Bees trained under absolute conditioning exhibited high generalization between isomers and discriminated only one out of four isomer pairs; after differential conditioning, they learned to differentiate between two out of four pairs of isomers but in all cases generalization responses to the non-rewarding isomer remained high. Adding an aversive taste to the non-rewarded isomer facilitated discrimination of isomers that otherwise seemed non-discriminable, but generalization remained high. Although honey bees discriminated isomers under certain conditions, they achieved the task with difficulty and tended to generalize between them, thus showing that these molecules were perceptually similar to them. We conclude that the presence of isomers within floral fragrances might not necessarily contribute to a dramatic extent to floral odor diversity. © 2018. Published by The Company of Biologists Ltd.

Pairing States of Spin-3/2 Fermions: Symmetry-Enforced Topological Gap Functions

NASA Astrophysics Data System (ADS)

Venderbos, Jörn W. F.; Savary, Lucile; Ruhman, Jonathan; Lee, Patrick A.; Fu, Liang

2018-01-01

We study the topological properties of superconductors with paired j =3/2 quasiparticles. Higher spin Fermi surfaces can arise, for instance, in strongly spin-orbit coupled band-inverted semimetals. Examples include the Bi-based half-Heusler materials, which have recently been established as low-temperature and low-carrier density superconductors. Motivated by this experimental observation, we obtain a comprehensive symmetry-based classification of topological pairing states in systems with higher angular momentum Cooper pairing. Our study consists of two main parts. First, we develop the phenomenological theory of multicomponent (i.e., higher angular momentum) pairing by classifying the stationary points of the free energy within a Ginzburg-Landau framework. Based on the symmetry classification of stationary pairing states, we then derive the symmetry-imposed constraints on their gap structures. We find that, depending on the symmetry quantum numbers of the Cooper pairs, different types of topological pairing states can occur: fully gapped topological superconductors in class DIII, Dirac superconductors, and superconductors hosting Majorana fermions. Notably, we find a series of nematic fully gapped topological superconductors, as well as double- and triple-Dirac superconductors, with quadratic and cubic dispersion, respectively. Our approach, applied here to the case of j =3/2 Cooper pairing, is rooted in the symmetry properties of pairing states, and can therefore also be applied to other systems with higher angular momentum and high-spin pairing. We conclude by relating our results to experimentally accessible signatures in thermodynamic and dynamic probes.

The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition.

PubMed

Sullivan, Lucy C; Clements, Craig S; Beddoe, Travis; Johnson, Darryl; Hoare, Hilary L; Lin, Jie; Huyton, Trevor; Hopkins, Emma J; Reid, Hugh H; Wilce, Matthew C J; Kabat, Juraj; Borrego, Francisco; Coligan, John E; Rossjohn, Jamie; Brooks, Andrew G

2007-12-01

The CD94-NKG2 receptor family that regulates NK and T cells is unique among the lectin-like receptors encoded within the natural killer cell complex. The function of the CD94-NKG2 receptors is dictated by the pairing of the invariant CD94 polypeptide with specific NKG2 isoforms to form a family of functionally distinct heterodimeric receptors. However, the structural basis for this selective pairing and how they interact with their ligand, HLA-E, is unknown. We describe the 2.5 A resolution crystal structure of CD94-NKG2A in which the mode of dimerization contrasts with that of other homodimeric NK receptors. Despite structural homology between the CD94 and NKG2A subunits, the dimer interface is asymmetric, thereby providing a structural basis for the preferred heterodimeric assembly. Structure-based sequence comparisons of other CD94-NKG2 family members, combined with extensive mutagenesis studies on HLA-E and CD94-NKG2A, allows a model of the interaction between CD94-NKG2A and HLA-E to be established, in which the invariant CD94 chain plays a more dominant role in interacting with HLA-E in comparison to the variable NKG2 chain.

pgRNAFinder: a web-based tool to design distance independent paired-gRNA.

PubMed

Xiong, Yuanyan; Xie, Xiaowei; Wang, Yanzhi; Ma, Wenbing; Liang, Puping; Songyang, Zhou; Dai, Zhiming

2017-11-15

The CRISPR/Cas System has been shown to be an efficient and accurate genome-editing technique. There exist a number of tools to design the guide RNA sequences and predict potential off-target sites. However, most of the existing computational tools on gRNA design are restricted to small deletions. To address this issue, we present pgRNAFinder, with an easy-to-use web interface, which enables researchers to design single or distance-free paired-gRNA sequences. The web interface of pgRNAFinder contains both gRNA search and scoring system. After users input query sequences, it searches gRNA by 3' protospacer-adjacent motif (PAM), and possible off-targets, and scores the conservation of the deleted sequences rapidly. Filters can be applied to identify high-quality CRISPR sites. PgRNAFinder offers gRNA design functionality for 8 vertebrate genomes. Furthermore, to keep pgRNAFinder open, extensible to any organism, we provide the source package for local use. The pgRNAFinder is freely available at http://songyanglab.sysu.edu.cn/wangwebs/pgRNAFinder/, and the source code and user manual can be obtained from https://github.com/xiexiaowei/pgRNAFinder. songyang@bcm.edu or daizhim@mail.sysu.edu.cn. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Representability of algebraic topology for biomolecules in machine learning based scoring and virtual screening

PubMed Central

Mu, Lin

2018-01-01

This work introduces a number of algebraic topology approaches, including multi-component persistent homology, multi-level persistent homology, and electrostatic persistence for the representation, characterization, and description of small molecules and biomolecular complexes. In contrast to the conventional persistent homology, multi-component persistent homology retains critical chemical and biological information during the topological simplification of biomolecular geometric complexity. Multi-level persistent homology enables a tailored topological description of inter- and/or intra-molecular interactions of interest. Electrostatic persistence incorporates partial charge information into topological invariants. These topological methods are paired with Wasserstein distance to characterize similarities between molecules and are further integrated with a variety of machine learning algorithms, including k-nearest neighbors, ensemble of trees, and deep convolutional neural networks, to manifest their descriptive and predictive powers for protein-ligand binding analysis and virtual screening of small molecules. Extensive numerical experiments involving 4,414 protein-ligand complexes from the PDBBind database and 128,374 ligand-target and decoy-target pairs in the DUD database are performed to test respectively the scoring power and the discriminatory power of the proposed topological learning strategies. It is demonstrated that the present topological learning outperforms other existing methods in protein-ligand binding affinity prediction and ligand-decoy discrimination. PMID:29309403

The gene for PAX7, a member of the paired-box-containing genes, is localized on human chromosome arm 1p36.

PubMed

Shapiro, D N; Sublett, J E; Li, B; Valentine, M B; Morris, S W; Noll, M

1993-09-01

The murine Pax-7 gene and the cognate human gene, formerly designated HuP1, are members of the multigene paired-box-containing class of developmental regulatory genes first identified in Drosophila. By analysis of somatic cell hybrids segregating human chromosomes, the gene encoding PAX7 was localized to human chromosome 1. Fluorescence in situ hybridization confirmed this assignment and allowed mapping of the gene to the terminal region of the short arm (1p36) of the chromosome. Additionally, these results confirm the extensive homology between human chromosome 1p and the distal segment of mouse chromosome 4, extending from bands C5 through E2.

Ionic association of lithium salts in propylene carbonate/ 1,2-dimethoxyethane mixed systems for lithium batteries

NASA Astrophysics Data System (ADS)

Ishikawa, Masashi; Wen, Shi-Qui; Matsuda, Yoshiharu

1993-06-01

The ionic association constants of lithium perchlorate, lithium trifluoremethylsulfate, lithium hexafluorophosphate, and lithium tetrafluoroborate have been determined experimentally (by Shedlovsky's method) in various mixtures of propylene carbonate and 1,2-dimethoxyethane as typical electrolyte systems for rechargeable lithium batteries. The association constants vary extensively for different mixing ratios of propylene to 1,2-dimethoxyethane and for different species of salts. These values are compared with the theoretical values as predicted by the Fuoss and Bjerrum equations. On the basis of this comparison and some physical properties of the solution, the variation in the ionic association constants may be ascribed to the charge of ionic association species, i.e., a contact ion-pair and a solvent-separated ion-pair.

Structure of 2,4-Diaminopyrimidine - Theobromine Alternate Base Pairs

NASA Technical Reports Server (NTRS)

Gengeliczki, Zsolt; Callahan, Michael P.; Kabelac, Martin; Rijs, Anouk M.; deVries, Mattanjah S.

2011-01-01

We report the structure of clusters of 2,4-diaminopyrimidine with 3,7-dimethylxanthine (theobromine) in the gas phase determined by IR-UV double resonance spectroscopy in both the near-IR and mid-IR regions in combination with ab initio computations. These clusters represent potential alternate nucleobase pairs, geometrically equivalent to guanine-cytosine. We have found the four lowest energy structures, which include the Watson-Crick base pairing motif. This Watson-Crick structure has not been observed by resonant two-photon ionization (R2PI) in the gas phase for the canonical DNA base pairs.

N-H Stretching Excitations in Adenosine-Thymidine Base Pairs in Solution: Base Pair Geometries, Infrared Line Shapes and Ultrafast Vibrational Dynamics

PubMed Central

Greve, Christian; Preketes, Nicholas K.; Fidder, Henk; Costard, Rene; Koeppe, Benjamin; Heisler, Ismael A.; Mukamel, Shaul; Temps, Friedrich; Nibbering, Erik T. J.; Elsaesser, Thomas

2013-01-01

We explore the N-H stretching vibrations of adenosine-thymidine base pairs in chloroform solution with linear and nonlinear infrared spectroscopy. Based on estimates from NMR measurements and ab initio calculations, we conclude that adenosine and thymidine form hydrogen bonded base pairs in Watson-Crick, reverse Watson-Crick, Hoogsteen and reverse Hoogsteen configurations with similar probability. Steady-state concentration- and temperature dependent linear FT-IR studies, including H/D exchange experiments, reveal that these hydrogen-bonded base pairs have complex N-H/N-D stretching spectra with a multitude of spectral components. Nonlinear 2D-IR spectroscopic results, together with IR-pump-IR-probe measurements, as also corroborated by ab initio calculations, reveal that the number of N-H stretching transitions is larger than the total number of N-H stretching modes. This is explained by couplings to other modes, such as an underdamped low-frequency hydrogen-bond mode, and a Fermi resonance with NH2 bending overtone levels of the adenosine amino-group. Our results demonstrate that modeling based on local N-H stretching vibrations only is not sufficient and call for further refinement of the description of the N-H stretching manifolds of nucleic acid base pairs of adenosine and thymidine, incorporating a multitude of couplings with fingerprint and low-frequency modes. PMID:23234439

Structural Basis for the Lesion-scanning Mechanism of the MutY DNA Glycosylase

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

Wang, Lan; Chakravarthy, Srinivas; Verdine, Gregory L.

The highly mutagenic A:8-oxoguanine (oxoG) base pair is generated mainly by misreplication of the C:oxoG base pair, the oxidation product of the C:G base pair. The A:oxoG base pair is particularly insidious because neither base in it carries faithful information to direct the repair of the other. The bacterial MutY (MUTYH in humans) adenine DNA glycosylase is able to initiate the repair of A:oxoG by selectively cleaving the A base from the A:oxoG base pair. The difference between faithful repair and wreaking mutagenic havoc on the genome lies in the accurate discrimination between two structurally similar base pairs: A:oxoG andmore » A:T. Here we present two crystal structures of the MutY N-terminal domain in complex with either undamaged DNA or DNA containing an intrahelical lesion. These structures have captured for the first time a DNA glycosylase scanning the genome for a damaged base in the very first stage of lesion recognition and the base extrusion pathway. The mode of interaction observed here has suggested a common lesion-scanning mechanism across the entire helix-hairpin-helix superfamily to which MutY belongs. In addition, small angle X-ray scattering studies together with accompanying biochemical assays have suggested a possible role played by the C-terminal oxoG-recognition domain of MutY in lesion scanning.« less

Identification of novel Theileria genotypes from Grant's gazelle

PubMed Central

Hooge, Janis; Howe, Laryssa; Ezenwa, Vanessa O.

2015-01-01

Blood samples collected from Grant's gazelles (Nanger granti) in Kenya were screened for hemoparasites using a combination of microscopic and molecular techniques. All 69 blood smears examined by microscopy were positive for hemoparasites. In addition, Theileria/Babesia DNA was detected in all 65 samples screened by PCR for a ~450-base pair fragment of the V4 hypervariable region of the 18S rRNA gene. Sequencing and BLAST analysis of a subset of PCR amplicons revealed widespread co-infection (25/39) and the existence of two distinct Grant's gazelle Theileria subgroups. One group of 11 isolates clustered as a subgroup with previously identified Theileria ovis isolates from small ruminants from Europe, Asia and Africa; another group of 3 isolates clustered with previously identified Theileria spp. isolates from other African antelope. Based on extensive levels of sequence divergence (1.2–2%) from previously reported Theileria species within Kenya and worldwide, the Theileria isolates detected in Grant's gazelles appear to represent at least two novel Theileria genotypes. PMID:25973394

Identification of novel Theileria genotypes from Grant's gazelle.

PubMed

Hooge, Janis; Howe, Laryssa; Ezenwa, Vanessa O

2015-08-01

Blood samples collected from Grant's gazelles (Nanger granti) in Kenya were screened for hemoparasites using a combination of microscopic and molecular techniques. All 69 blood smears examined by microscopy were positive for hemoparasites. In addition, Theileria/Babesia DNA was detected in all 65 samples screened by PCR for a ~450-base pair fragment of the V4 hypervariable region of the 18S rRNA gene. Sequencing and BLAST analysis of a subset of PCR amplicons revealed widespread co-infection (25/39) and the existence of two distinct Grant's gazelle Theileria subgroups. One group of 11 isolates clustered as a subgroup with previously identified Theileria ovis isolates from small ruminants from Europe, Asia and Africa; another group of 3 isolates clustered with previously identified Theileria spp. isolates from other African antelope. Based on extensive levels of sequence divergence (1.2-2%) from previously reported Theileria species within Kenya and worldwide, the Theileria isolates detected in Grant's gazelles appear to represent at least two novel Theileria genotypes.

Ontology aided modeling of organic reaction mechanisms with flexible and fragment based XML markup procedures.

PubMed

Sankar, Punnaivanam; Aghila, Gnanasekaran

2007-01-01

The mechanism models for primary organic reactions encoding the structural fragments undergoing substitution, addition, elimination, and rearrangements are developed. In the proposed models, each and every structural component of mechanistic pathways is represented with flexible and fragment based markup technique in XML syntax. A significant feature of the system is the encoding of the electron movements along with the other components like charges, partial charges, half bonded species, lone pair electrons, free radicals, reaction arrows, etc. needed for a complete representation of reaction mechanism. The rendering of reaction schemes described with the proposed methodology is achieved with a concise XML extension language interoperating with the structure markup. The reaction scheme is visualized as 2D graphics in a browser by converting them into SVG documents enabling the desired layouts normally perceived by the chemists conventionally. An automatic representation of the complex patterns of the reaction mechanism is achieved by reusing the knowledge in chemical ontologies and developing artificial intelligence components in terms of axioms.

Analysis of short tandem repeat polymorphisms using infrared fluorescence with M18 tailed primers

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

Oetting, W.S.; Wiesner, G.; Laken, S.

The use of short tandem repeat polymorphisms (STRPs) are becoming increasingly important as markers for linkage analysis due to their large numbers of the human genome and their high degree of polymorphism. Fluorescence based detection of the STRP pattern using the LI-COR model 4000S automated DNA sequencer eliminates the need for radioactivity and produces a digitized image that can be used for the analysis of the polymorphisms. In an effort to reduce the cost of STRP analysis, we have synthesized primers with a 19 bp extension complementary to the sequence of the M13 primer on the 5{prime} end of onemore » of the two primers used in the amplification of the STRP instead of using primers with direct conjugation of the infrared fluorescent dye. Up to 5 primer pairs can be multiplexed together with the M13 primer-dye conjugate as the sole primer conjugated to the fluorescent dye. Comparisons between primers that have been directly conjugated to the fluor with those having the M13 sequence extension show no difference in the ability to determine the STRP pattern. At present, the entire Weber 4A set of STRP markers is available with the M13 5{prime} extension. We are currently using this technique for linkage analysis of familial breast cancer and asthma. The combination of STRP analysis using fluorescence detection will allow this technique to be fully automated for allele scoring and linkage analysis.« less

A novel knowledge-based potential for RNA 3D structure evaluation

NASA Astrophysics Data System (ADS)

Yang, Yi; Gu, Qi; Zhang, Ben-Gong; Shi, Ya-Zhou; Shao, Zhi-Gang

2018-03-01

Ribonucleic acids (RNAs) play a vital role in biology, and knowledge of their three-dimensional (3D) structure is required to understand their biological functions. Recently structural prediction methods have been developed to address this issue, but a series of RNA 3D structures are generally predicted by most existing methods. Therefore, the evaluation of the predicted structures is generally indispensable. Although several methods have been proposed to assess RNA 3D structures, the existing methods are not precise enough. In this work, a new all-atom knowledge-based potential is developed for more accurately evaluating RNA 3D structures. The potential not only includes local and nonlocal interactions but also fully considers the specificity of each RNA by introducing a retraining mechanism. Based on extensive test sets generated from independent methods, the proposed potential correctly distinguished the native state and ranked near-native conformations to effectively select the best. Furthermore, the proposed potential precisely captured RNA structural features such as base-stacking and base-pairing. Comparisons with existing potential methods show that the proposed potential is very reliable and accurate in RNA 3D structure evaluation. Project supported by the National Science Foundation of China (Grants Nos. 11605125, 11105054, 11274124, and 11401448).

Enzyme-Free Replication with Two or Four Bases.

PubMed

Richert, Clemens; Hänle, Elena

2018-05-20

All known forms of life encode their genetic information in a sequence of bases of a genetic polymer and produce copies of their genes via semiconservative replication. How this process started before polymerase enzymes had been evolved is unclear. Enzyme-free copying of short stretches of DNA or RNA sequence has been demonstrated, using activated nucleotides, but not replication. We have developed a methodology for replication. It involves extension with reversible termination, enzyme-free ligation, and strand capture and allowed us to monitor nucleotide incorporation for an entire helical turn of DNA, both during a first and a second round of copying. When tracking replication mass spectrometrically, we found that with all four bases (A/C/G/T) an 'error catastrophe' occurs, with the correct sequence being 'overwhelmed' by incorrect ones. When only C and G were used, approx. half of all daughter strands had the mass of the correct sequence after 20 nonenzymatic copying steps. We conclude that enzyme-free replication is more likely to be successful with the two strongly pairing bases, rather than all four bases of the genetic alphabet. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KlenTaq polymerase replicates unnatural base pairs by inducing a Watson-Crick geometry.

PubMed

Betz, Karin; Malyshev, Denis A; Lavergne, Thomas; Welte, Wolfram; Diederichs, Kay; Dwyer, Tammy J; Ordoukhanian, Phillip; Romesberg, Floyd E; Marx, Andreas

2012-07-01

Many candidate unnatural DNA base pairs have been developed, but some of the best-replicated pairs adopt intercalated structures in free DNA that are difficult to reconcile with known mechanisms of polymerase recognition. Here we present crystal structures of KlenTaq DNA polymerase at different stages of replication for one such pair, dNaM-d5SICS, and show that efficient replication results from the polymerase itself, inducing the required natural-like structure.

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

Egli, Martin; Pallan, Pradeep S.; Pattanayek, Rekha

An experimental rationalization of the structure type encountered in DNA and RNA by systematically investigating the chemical and physical properties of alternative nucleic acids has identified systems with a variety of sugar-phosphate backbones that are capable of Watson-Crick base pairing and in some cases cross-pairing with the natural nucleic acids. The earliest among the model systems tested to date, (4{prime} {yields} 6{prime})-linked oligo(2{prime},3{prime}-dideoxy-{beta}-d-glucopyranosyl)nucleotides or homo-DNA, shows stable self-pairing, but the pairing rules for the four natural bases are not the same as those in DNA. However, a complete interpretation and understanding of the properties of the hexapyranosyl (4{prime} {yields} 6{prime})more » family of nucleic acids has been impeded until now by the lack of detailed 3D-structural data. We have determined the crystal structure of a homo-DNA octamer. It reveals a weakly twisted right-handed duplex with a strong inclination between the hexose-phosphate backbones and base-pair axes, and highly irregular values for helical rise and twist at individual base steps. The structure allows a rationalization of the inability of allo-, altro-, and glucopyranosyl-based oligonucleotides to form stable pairing systems.« less

Sequence-dependent base pair stepping dynamics in XPD helicase unwinding

PubMed Central

Qi, Zhi; Pugh, Robert A; Spies, Maria; Chemla, Yann R

2013-01-01

Helicases couple the chemical energy of ATP hydrolysis to directional translocation along nucleic acids and transient duplex separation. Understanding helicase mechanism requires that the basic physicochemical process of base pair separation be understood. This necessitates monitoring helicase activity directly, at high spatio-temporal resolution. Using optical tweezers with single base pair (bp) resolution, we analyzed DNA unwinding by XPD helicase, a Superfamily 2 (SF2) DNA helicase involved in DNA repair and transcription initiation. We show that monomeric XPD unwinds duplex DNA in 1-bp steps, yet exhibits frequent backsteps and undergoes conformational transitions manifested in 5-bp backward and forward steps. Quantifying the sequence dependence of XPD stepping dynamics with near base pair resolution, we provide the strongest and most direct evidence thus far that forward, single-base pair stepping of a helicase utilizes the spontaneous opening of the duplex. The proposed unwinding mechanism may be a universal feature of DNA helicases that move along DNA phosphodiester backbones. DOI: http://dx.doi.org/10.7554/eLife.00334.001 PMID:23741615

Efficient Acceleration of the Pair-HMMs Forward Algorithm for GATK HaplotypeCaller on Graphics Processing Units.

PubMed

Ren, Shanshan; Bertels, Koen; Al-Ars, Zaid

2018-01-01

GATK HaplotypeCaller (HC) is a popular variant caller, which is widely used to identify variants in complex genomes. However, due to its high variants detection accuracy, it suffers from long execution time. In GATK HC, the pair-HMMs forward algorithm accounts for a large percentage of the total execution time. This article proposes to accelerate the pair-HMMs forward algorithm on graphics processing units (GPUs) to improve the performance of GATK HC. This article presents several GPU-based implementations of the pair-HMMs forward algorithm. It also analyzes the performance bottlenecks of the implementations on an NVIDIA Tesla K40 card with various data sets. Based on these results and the characteristics of GATK HC, we are able to identify the GPU-based implementations with the highest performance for the various analyzed data sets. Experimental results show that the GPU-based implementations of the pair-HMMs forward algorithm achieve a speedup of up to 5.47× over existing GPU-based implementations.

DNA bases ring-expanded with a cyclopentadiene free radical: a theoretical investigation of building blocks with diradical character.

PubMed

Zhao, Peiwen; Bu, Yuxiang

2016-01-14

In this work, we computationally design radical nucleobases which possess improved electronic properties, especially diradical properties through introducing a cyclopentadiene radical. We predict that the detailed electromagnetic features of base assemblies are based on the orientation of the extra five-membered cyclopentadiene ring. Broken symmetry DFT calculations take into account the relevant structures and properties. Our results reveal that both the radicalized DNA bases and the base pairs formed when they combine with their counterparts remain stable and display larger spin delocalization. The mode of embedding the cyclopentadiene free radical in the structures has some influence on the degree of π-conjugation, which results in various diradical characteristics. Single-layered radical base pairs all have an open-shell singlet ground state, but the energy difference between singlet and triplet is not significant. For two-layered radical base pairs, the situation is more complex. All of them have an open-shell state as their ground state, including an open-shell singlet state and an open-shell triplet state. That is, the majority of radical base pairs possess anti-ferromagnetic or ferromagnetic characteristics. We present here a more in-depth discussion and analyses to study the magnetic characteristics of radical bases and base pairs. As an important factor, two-layered radical base pairs also have been carefully analyzed. We hope that all the measurements and results presented here will stimulate further detailed insights into the related mechanisms in modified DNA bases and the design of better ring-expanded DNA magnetic materials.

sEMG-based joint force control for an upper-limb power-assist exoskeleton robot.

PubMed

Li, Zhijun; Wang, Baocheng; Sun, Fuchun; Yang, Chenguang; Xie, Qing; Zhang, Weidong

2014-05-01

This paper investigates two surface electromyogram (sEMG)-based control strategies developed for a power-assist exoskeleton arm. Different from most of the existing position control approaches, this paper develops force control methods to make the exoskeleton robot behave like humans in order to provide better assistance. The exoskeleton robot is directly attached to a user's body and activated by the sEMG signals of the user's muscles, which reflect the user's motion intention. In the first proposed control method, the forces of agonist and antagonist muscles pair are estimated, and their difference is used to produce the torque of the corresponding joints. In the second method, linear discriminant analysis-based classifiers are introduced as the indicator of the motion type of the joints. Then, the classifier's outputs together with the estimated force of corresponding active muscle determine the torque control signals. Different from the conventional approaches, one classifier is assigned to each joint, which decreases the training time and largely simplifies the recognition process. Finally, the extensive experiments are conducted to illustrate the effectiveness of the proposed approaches.

F2Dock: Fast Fourier Protein-Protein Docking

PubMed Central

Bajaj, Chandrajit; Chowdhury, Rezaul; Siddavanahalli, Vinay

2009-01-01

The functions of proteins is often realized through their mutual interactions. Determining a relative transformation for a pair of proteins and their conformations which form a stable complex, reproducible in nature, is known as docking. It is an important step in drug design, structure determination and understanding function and structure relationships. In this paper we extend our non-uniform fast Fourier transform docking algorithm to include an adaptive search phase (both translational and rotational) and thereby speed up its execution. We have also implemented a multithreaded version of the adaptive docking algorithm for even faster execution on multicore machines. We call this protein-protein docking code F2Dock (F2 = Fast Fourier). We have calibrated F2Dock based on an extensive experimental study on a list of benchmark complexes and conclude that F2Dock works very well in practice. Though all docking results reported in this paper use shape complementarity and Coulombic potential based scores only, F2Dock is structured to incorporate Lennard-Jones potential and re-ranking docking solutions based on desolvation energy. PMID:21071796

Thermodynamic heuristics with case-based reasoning: combined insights for RNA pseudoknot secondary structure.

PubMed

Al-Khatib, Ra'ed M; Rashid, Nur'Aini Abdul; Abdullah, Rosni

2011-08-01

The secondary structure of RNA pseudoknots has been extensively inferred and scrutinized by computational approaches. Experimental methods for determining RNA structure are time consuming and tedious; therefore, predictive computational approaches are required. Predicting the most accurate and energy-stable pseudoknot RNA secondary structure has been proven to be an NP-hard problem. In this paper, a new RNA folding approach, termed MSeeker, is presented; it includes KnotSeeker (a heuristic method) and Mfold (a thermodynamic algorithm). The global optimization of this thermodynamic heuristic approach was further enhanced by using a case-based reasoning technique as a local optimization method. MSeeker is a proposed algorithm for predicting RNA pseudoknot structure from individual sequences, especially long ones. This research demonstrates that MSeeker improves the sensitivity and specificity of existing RNA pseudoknot structure predictions. The performance and structural results from this proposed method were evaluated against seven other state-of-the-art pseudoknot prediction methods. The MSeeker method had better sensitivity than the DotKnot, FlexStem, HotKnots, pknotsRG, ILM, NUPACK and pknotsRE methods, with 79% of the predicted pseudoknot base-pairs being correct.

Centrifugal Microfluidic System for Nucleic Acid Amplification and Detection.

PubMed

Miao, Baogang; Peng, Niancai; Li, Lei; Li, Zheng; Hu, Fei; Zhang, Zengming; Wang, Chaohui

2015-11-04

We report here the development of a rapid PCR microfluidic system comprising a double-shaft turntable and centrifugal-based disc that rapidly drives the PCR mixture between chambers set at different temperatures, and the bidirectional flow improved the space utilization of the disc. Three heating resistors and thermistors maintained uniform, specific temperatures for the denaturation, annealing, and extension steps of the PCR. Infrared imaging showed that there was little thermal interference between reaction chambers; the system enabled the cycle number and reaction time of each step to be independently adjusted. To validate the function and efficiency of the centrifugal microfluidic system, a 350-base pair target gene from the hepatitis B virus was amplified and quantitated by fluorescence detection. By optimizing the cycling parameters, the reaction time was reduced to 32 min as compared to 120 min for a commercial PCR machine. DNA samples with concentrations ranging from 10 to 10⁶ copies/mL could be quantitatively analyzed using this system. This centrifugal-based microfluidic platform is a useful system and possesses industrialization potential that can be used for portable diagnostics.

Centrifugal Microfluidic System for Nucleic Acid Amplification and Detection

PubMed Central

Miao, Baogang; Peng, Niancai; Li, Lei; Li, Zheng; Hu, Fei; Zhang, Zengming; Wang, Chaohui

2015-01-01

We report here the development of a rapid PCR microfluidic system comprising a double-shaft turntable and centrifugal-based disc that rapidly drives the PCR mixture between chambers set at different temperatures, and the bidirectional flow improved the space utilization of the disc. Three heating resistors and thermistors maintained uniform, specific temperatures for the denaturation, annealing, and extension steps of the PCR. Infrared imaging showed that there was little thermal interference between reaction chambers; the system enabled the cycle number and reaction time of each step to be independently adjusted. To validate the function and efficiency of the centrifugal microfluidic system, a 350-base pair target gene from the hepatitis B virus was amplified and quantitated by fluorescence detection. By optimizing the cycling parameters, the reaction time was reduced to 32 min as compared to 120 min for a commercial PCR machine. DNA samples with concentrations ranging from 10 to 106 copies/mL could be quantitatively analyzed using this system. This centrifugal-based microfluidic platform is a useful system and possesses industrialization potential that can be used for portable diagnostics. PMID:26556354

Molecular dynamics study of some non-hydrogen-bonding base pair DNA strands

NASA Astrophysics Data System (ADS)

Tiwari, Rakesh K.; Ojha, Rajendra P.; Tiwari, Gargi; Pandey, Vishnudatt; Mall, Vijaysree

2018-05-01

In order to elucidate the structural activity of hydrophobic modified DNA, the DMMO2-D5SICS, base pair is introduced as a constituent in different set of 12-mer and 14-mer DNA sequences for the molecular dynamics (MD) simulation in explicit water solvent. AMBER 14 force field was employed for each set of duplex during the 200ns production-dynamics simulation in orthogonal-box-water solvent by the Particle-Mesh-Ewald (PME) method in infinite periodic boundary conditions (PBC) to determine conformational parameters of the complex. The force-field parameters of modified base-pair were calculated by Gaussian-code using Hartree-Fock /ab-initio methodology. RMSD Results reveal that the conformation of the duplex is sequence dependent and the binding energy of the complex depends on the position of the modified base-pair in the nucleic acid strand. We found that non-bonding energy had a significant contribution to stabilising such type of duplex in comparison to electrostatic energy. The distortion produced within strands by such type of base-pair was local and destabilised the duplex integrity near to substitution, moreover the binding energy of duplex depends on the position of substitution of hydrophobic base-pair and the DNA sequence and strongly supports the corresponding experimental study.

2-Methoxypyridine as a Thymidine Mimic in Watson-Crick Base Pairs of DNA and PNA: Synthesis, Thermal Stability, and NMR Structural Studies.

PubMed

Novosjolova, Irina; Kennedy, Scott D; Rozners, Eriks

2017-11-02

The development of nucleic acid base-pair analogues that use new modes of molecular recognition is important both for fundamental research and practical applications. The goal of this study was to evaluate 2-methoxypyridine as a cationic thymidine mimic in the A-T base pair. The hypothesis was that including protonation in the Watson-Crick base pairing scheme would enhance the thermal stability of the DNA double helix without compromising the sequence selectivity. DNA and peptide nucleic acid (PNA) sequences containing the new 2-methoxypyridine nucleobase (P) were synthesized and studied by using UV thermal melting and NMR spectroscopy. Introduction of P nucleobase caused a loss of thermal stability of ≈10 °C in DNA-DNA duplexes and ≈20 °C in PNA-DNA duplexes over a range of mildly acidic to neutral pH. Despite the decrease in thermal stability, the NMR structural studies showed that P-A formed the expected protonated base pair at pH 4.3. Our study demonstrates the feasibility of cationic unnatural base pairs; however, future optimization of such analogues will be required. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radical-pair based avian magnetoreception

NASA Astrophysics Data System (ADS)

Procopio, Maria; Ritz, Thorsten

2014-03-01

Behavioural experiments suggest that migratory birds possess a magnetic compass sensor able to detect the direction of the geomagnetic. One hypothesis for the basis of this remarkable sensory ability is that the coherent quantum spin dynamics of photoinduced radical pair reactions transduces directional magnetic information from the geomagnetic field into changes of reaction yields, possibly involving the photoreceptor cryptochrome in the birds retina. The suggested radical-pair based avian magnetoreception has attracted attention in the field of quantum biology as an example of a biological sensor which might exploit quantum coherences for its biological function. Investigations on such a spin-based sensor have focussed on uncovering the design features for the design of a biomimetic magnetic field sensor. We study the effects of slow fluctuations in the nuclear spin environment on the directional signal. We quantitatively evaluate the robustness of signals under fluctuations on a timescale longer than the lifetime of a radical pair, utilizing two models of radical pairs. Our results suggest design principles for building a radical-pair based compass sensor that is both robust and highly directional sensitive.

Comparison of the conformation of an oligonucleotide containing a central G-T base pair with the non-mismatch sequence by proton NMR.

PubMed Central

Quignard, E; Fazakerley, G V; van der Marel, G; van Boom, J H; Guschlbauer, W

1987-01-01

We have recorded NOESY spectra of two non-selfcomplementary undecanucleotide duplexes. From the observed NOEs we do not detect any significant distortion of the helix when a G-C pair is replaced by a G-T pair and the normal interresidue connectivities can be followed through the mismatch site. We conclude that the 2D spectra of the non-exchangeable protons do not allow differentiation between a wobble or rare tautomer form for the mismatch. NOE measurements in H2O, however, clearly show that the mismatch adopts a wobble structure and give information on the hydration in the minor groove for the G-T base pair which is embedded between two A-T base pairs in the sequence. PMID:3033602

RNA therapeutics: Beyond RNA interference and antisense oligonucleotides

PubMed Central

Kole, Ryszard; Krainer, Adrian R.; Altman, Sidney

2016-01-01

Here we discuss three RNA therapeutic technologies exploiting various oligonucleotides that bind RNA by base-pairing in a sequence-specific manner yet have different mechanisms of action and effects. RNA interference and antisense oligonucleotides downregulate gene expression by enzyme-dependent degradation of targeted mRNA. Steric blocking oligonucleotides block access of cellular machinery to pre-mRNA and mRNA without degrading the RNA. Through this mechanism, blocking oligonucleotides can redirect alternative splicing, repair defective RNA, restore protein production or also downregulate gene expression. Moreover, they can be extensively chemically modified, resulting in more drug-like properties. The ability of RNA blocking oligonucleotides to restore gene function makes them suited for treatment of genetic disorders. Positive results from clinical trials for the treatment of Duchenne muscular dystrophy show that this technology is close to realizing its clinical potential. PMID:22262036

Nutritional epigenomics: a portal to disease prevention.

PubMed

Choi, Sang-Woon; Claycombe, Kate J; Martinez, J Alfredo; Friso, Simonetta; Schalinske, Kevin L

2013-09-01

Epigenetics can be defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence. Epigenomics is the study of genome-wide epigenetic modifications. Because gene expression changes are critical in both normal development and disease progression, epigenetics is widely applicable to many aspects of biological research. The influences of nutrients and bioactive food components on epigenetic phenomena such as DNA methylation and various types of histone modifications have been extensively investigated. Because an individual's epigenetic patterns are established during early gestation and are changed and personalized by environmental factors during our lifetime, epigenetic mechanisms are quite important in the development of transgenerational and adult obesity as well as in the development of diabetes mellitus. Aging and cancer demonstrate profound genome-wide DNA methylation changes, suggesting that nutrition may affect the aging process and cancer development through epigenetic mechanisms.

sl(1|2) Super-Toda Fields

NASA Astrophysics Data System (ADS)

Yang, Zhan-Ying; Xue, Pan-Pan; Zhao, Liu; Shi, Kang-Jie

2008-11-01

Explicit exact solution of supersymmetric Toda fields associated with the Lie superalgebra sl(2|1) is constructed. The approach used is a super extension of Leznov Saveliev algebraic analysis, which is based on a pair of chiral and antichiral Drienfeld Sokolov systems. Though such approach is well understood for Toda field theories associated with ordinary Lie algebras, its super analogue was only successful in the super Liouville case with the underlying Lie superalgebra osp(1|2). The problem lies in that a key step in the construction makes use of the tensor product decomposition of the highest weight representations of the underlying Lie superalgebra, which is not clear until recently. So our construction made in this paper presents a first explicit example of Leznov Saveliev analysis for super Toda systems associated with underlying Lie superalgebras of the rank higher than 1.

Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position.

PubMed

Liu, Wei; Shin, Dongwon; Ng, Martin; Sanbonmatsu, Karissa Y; Tor, Yitzhak; Cooperman, Barry S

2017-08-29

Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5'- and 3'-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix.

Characterization of the Trans Watson-Crick GU Base Pair Located in the Catalytic Core of the Antigenomic HDV Ribozyme

PubMed Central

Lévesque, Dominique; Reymond, Cédric; Perreault, Jean-Pierre

2012-01-01

The HDV ribozyme’s folding pathway is, by far, the most complex folding pathway elucidated to date for a small ribozyme. It includes 6 different steps that have been shown to occur before the chemical cleavage. It is likely that other steps remain to be discovered. One of the most critical of these unknown steps is the formation of the trans Watson-Crick GU base pair within loop III. The U23 and G28 nucleotides that form this base pair are perfectly conserved in all natural variants of the HDV ribozyme, and therefore are considered as being part of the signature of HDV-like ribozymes. Both the formation and the transformation of this base pair have been studied mainly by crystal structure and by molecular dynamic simulations. In order to obtain physical support for the formation of this base pair in solution, a set of experiments, including direct mutagenesis, the site-specific substitution of chemical groups, kinetic studies, chemical probing and magnesium-induced cleavage, were performed with the specific goal of characterizing this trans Watson-Crick GU base pair in an antigenomic HDV ribozyme. Both U23 and G28 can be substituted for nucleotides that likely preserve some of the H-bond interactions present before and after the cleavage step. The formation of the more stable trans Watson-Crick base pair is shown to be a post-cleavage event, while a possibly weaker trans Watson-Crick/Hoogsteen interaction seems to form before the cleavage step. The formation of this unusually stable post-cleavage base pair may act as a driving force on the chemical cleavage by favouring the formation of a more stable ground state of the product-ribozyme complex. To our knowledge, this represents the first demonstration of a potential stabilising role of a post-cleavage conformational switch event in a ribozyme-catalyzed reaction. PMID:22768274

Building a knowledge base of severe adverse drug events based on AERS reporting data using semantic web technologies.

PubMed

Jiang, Guoqian; Wang, Liwei; Liu, Hongfang; Solbrig, Harold R; Chute, Christopher G

2013-01-01

A semantically coded knowledge base of adverse drug events (ADEs) with severity information is critical for clinical decision support systems and translational research applications. However it remains challenging to measure and identify the severity information of ADEs. The objective of the study is to develop and evaluate a semantic web based approach for building a knowledge base of severe ADEs based on the FDA Adverse Event Reporting System (AERS) reporting data. We utilized a normalized AERS reporting dataset and extracted putative drug-ADE pairs and their associated outcome codes in the domain of cardiac disorders. We validated the drug-ADE associations using ADE datasets from SIDe Effect Resource (SIDER) and the UMLS. We leveraged the Common Terminology Criteria for Adverse Event (CTCAE) grading system and classified the ADEs into the CTCAE in the Web Ontology Language (OWL). We identified and validated 2,444 unique Drug-ADE pairs in the domain of cardiac disorders, of which 760 pairs are in Grade 5, 775 pairs in Grade 4 and 2,196 pairs in Grade 3.

Ion pair particles at the air–water interface

NASA Astrophysics Data System (ADS)

Kumar, Manoj; Francisco, Joseph S.

2017-11-01

Although the role of methanesulfonic acid (HMSA) in particle formation in the gas phase has been extensively studied, the details of the HMSA-induced ion pair particle formation at the air–water interface are yet to be examined. In this work, we have performed Born–Oppenheimer molecular dynamics simulations and density functional theory calculations to investigate the ion pair particle formation from HMSA and (R1)(R2)NH (for NH3, R1 = R2 = H; for CH3NH2, R1 = H and R2 = CH3; and for CH3NH2, R1 = R2 = CH3) at the air–water interface. The results show that, at the air–water interface, HMSA deprotonates within a few picoseconds and results in the formation of methanesulfonate ion (MSA‑)ṡṡH3O+ ion pair. However, this ion pair decomposes immediately, explaining why HMSA and water alone are not sufficient for forming stable particles in atmosphere. Interestingly, the particle formation from the gas-phase hydrogen-bonded complexes of HMSA with (R1)(R2)NH on the water droplet is observed with a few femtoseconds, suggesting a mechanism for the gas to particle conversion in aqueous environments. The reaction involves a direct proton transfer between HMSA and (R1)(R2)NH, and the resulting MSA‑ṡṡ(R1)(R2)NH2+ complex is bound by one to four interfacial water molecules. The mechanistic insights gained from this study may serve as useful leads for understanding about the ion pair particle formation from other precursors in forested and polluted urban environments.

Early Verb Learning: How Do Children Learn How to Compare Events?

PubMed Central

Childers, Jane B.; Parrish, Rebecca; Olson, Christina V.; Burch, Clare; Fung, Gavin; McIntyre, Kevin

2015-01-01

An important problem verb learners must solve is how to extend verbs. Children could use cross-situational information to guide their extensions, however comparing events is difficult. Two studies test whether children benefit from initially seeing a pair of similar events (‘progressive alignment’) while learning new verbs, and whether this influence changes with age. In Study 1, 2 ½- and 3 ½-year-old children participated in an interactive task. Children who saw a pair of similar events and then varied events were able to extend verbs at test, differing from a control group; children who saw two pairs of varied events did not differ from the control group. In Study 2, events were presented on a monitor. Following the initial pair of events that varied by condition, a Tobii x120 eye tracker recorded 2 ½-, 3 ½- and 4 ½-year-olds’ fixations to specific elements of events (AOIs) during the second pair of events, which were the same across conditions. After seeing the pair of events that were highly similar, 2 ½-year-olds showed significantly longer fixation durations to agents and to affected objects as compared to the all varied condition. At test, 3 ½-year-olds were able to extend the verb, but only in the progressive alignment condition. These results are important because they show children’s visual attention to relevant elements in dynamic events is influenced by their prior comparison experience, and they show that young children benefit from seeing similar events as they learn to compare events to each other. PMID:27092030

Continuous separation of multiple size microparticles using alternating current dielectrophoresis in microfluidic device with acupuncture needle electrodes

NASA Astrophysics Data System (ADS)

Tao, Ye; Ren, Yukun; Yan, Hui; Jiang, Hongyuan

2016-03-01

The need to continuously separate multiple microparticles is required for the recent development of lab-on-chip technology. Dielectrophoresis(DEP)-based separation device is extensively used in kinds of microfluidic applications. However, such conventional DEP-based device is relatively complicated and difficult for fabrication. A concise microfluidic device is presented for effective continuous separation of multiple size particle mixtures. A pair of acupuncture needle electrodes are creatively employed and embedded in a PDMS(poly-dimethylsiloxane) hurdle for generating non-uniform electric field thereby achieving a continuous DEP separation. The separation mechanism is that the incoming particle samples with different sizes experience different negative DEP(nDEP) forces and then they can be transported into different downstream outlets. The DEP characterizations of particles are calculated, and their trajectories are numerically predicted by considering the combined action of the incoming laminar flow and the nDEP force field for guiding the separation experiments. The device performance is verified by successfully separating a three-sized particle mixture, including polystyrene microspheres with diameters of 3 μm, 10 μm and 25 μm. The separation purity is below 70% when the flow rate ratio is less than 3.5 or more than 5.1, while the separation purity can be up to more than 90% when the flow rate ratio is between 3.5 and 5.1 and meanwhile ensure the voltage output falls in between 120 V and 150 V. Such simple DEP-based separation device has extensive applications in future microfluidic systems.

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

Ghosh, Tarini Shankar; Chaitanya, S. Krishna; Sankararamakrishnan, Ramasubbu, E-mail: rsankar@iitk.ac.in

New classes of helix–helix interactions in protein structures are reported in which interactions only occur at the terminal regions or between the terminal region of one helix and the middle region of another helix. Helix–helix interactions are important for the structure, stability and function of α-helical proteins. Helices that either cross in the middle or show extensive contacts between each other, such as coiled coils, have been investigated in previous studies. Interactions between two helices can also occur only at the terminal regions or between the terminal region of one helix and the middle region of another helix. Examples ofmore » such helix pairs are found in aquaporin, H{sup +}/Cl{sup −} transporter and Bcl-2 proteins. The frequency of the occurrence of such ‘end-to-end’ (EE) and ‘end-to-middle’ (EM) helix pairs in protein structures is not known. Questions regarding the residue preferences in the interface and the mode of interhelical interactions in such helix pairs also remain unanswered. In this study, high-resolution structures of all-α proteins from the PDB have been systematically analyzed and the helix pairs that interact only in EE or EM fashion have been extracted. EE and EM helix pairs have been categorized into five classes (N–N, N–C, C–C, N–MID and C–MID) depending on the region of interaction. Nearly 13% of 5725 helix pairs belonged to one of the five classes. Analysis of single-residue propensities indicated that hydrophobic and polar residues prefer to occur in the C-terminal and N-terminal regions, respectively. Hydrophobic C-terminal interacting residues and polar N-terminal interacting residues are also highly conserved. A strong correlation exists between some of the residue properties (surface area/volume and length of side chains) and their preferences for occurring in the interface of EE and EM helix pairs. In contrast to interacting non-EE/EM helix pairs, helices in EE and EM pairs are farther apart. In these helix pairs, residues with large surface area/volume and longer side chains are preferred in the interfacial region.« less

Terminal base pairs of oligodeoxynucleotides: imino proton exchange and fraying.

PubMed

Nonin, S; Leroy, J L; Guéron, M

1995-08-22

We have estimated the dissociation constant of the terminal base pairs of the B-DNA duplexes formed by 5'-d(CGCGATCGCG) and 5'-d(TAGCGCTA) by two methods, one based on the change in imino proton chemical shift with temperature and the other on the apparent pK shift of the imino proton, as monitored by the change in chemical shift of aromatic protons. These methods do not rely on imino proton exchange, whose rate was also measured. (1) The effect of ammonia on the imino proton exchange rate of the terminal pair of the 5'-d(CGCGATCGCG) duplex is 67 times less than on the isolated nucleoside. This provides an upper limit on the exchange rate from the closed pair. In fact, the effect is just as predicted from the dissociation constant, assuming that there is no exchange at all from the closed pair and that, as has been argued previously, external catalysts act on the open state as they do on the isolated nucleoside. The inhibition of catalyzed proton exchange in the closed pair, despite exposure of one face of the pair to solvent, is a new feature of the exchange process. It will allow determination of the dissociation constant of terminal pairs from the exchange rate. (2) Intrinsic catalysis of proton exchange is less efficient for the terminal pair than for an internal one. A possible explanation is that proton transfer across the water bridge responsible for intrinsic catalysis is slower, as expected if the open-state separation of the bases is larger in a terminal pair. This observation may lead to a direct method for the study of fraying. (3) At 0 degrees C, the dissociation constant of the second pair of the 5'-d(CGCGATCGCG) duplex is close to the square of the constant for the terminal pair, as predicted from a simple model of fraying. The enthalpy and entropy of opening of the terminal pairs may be compared with those of nearest neighbor interactions derived from calorimetry [Breslauer, K. J., et al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 3746-3750].

Structural and functional analyses reveal the contributions of the C- and N-lobes of Argonaute protein to selectivity of RNA target cleavage.

PubMed

Dayeh, Daniel M; Kruithoff, Bradley C; Nakanishi, Kotaro

2018-04-27

Some gene transcripts have cellular functions as regulatory noncoding RNAs. For example, ∼23-nucleotide (nt)-long siRNAs are loaded into Argonaute proteins. The resultant ribonucleoprotein assembly, the RNA-induced silencing complex (RISC), cleaves RNAs that are extensively base-paired with the loaded siRNA. To date, base complementarity is recognized as the major determinant of specific target cleavage (or slicing), but little is known about how Argonaute inspects base pairing before cleavage. A hallmark of Argonaute proteins is their bilobal structure, but despite the significance of this structure for curtailing slicing activity against mismatched targets, the molecular mechanism remains elusive. Here, our structural and functional studies of a bilobed yeast Argonaute protein and its isolated catalytic C-terminal lobe (C-lobe) revealed that the C-lobe alone retains almost all properties of bilobed Argonaute: siRNA-duplex loading, passenger cleavage/ejection, and siRNA-dependent RNA cleavage. A 2.1 Å-resolution crystal structure revealed that the catalytic C-lobe mirrors the bilobed Argonaute in terms of guide-RNA recognition and that all requirements for transitioning to the catalytically active conformation reside in the C-lobe. Nevertheless, we found that in the absence of the N-terminal lobe (N-lobe), target RNAs are scanned for complementarity only at positions 5-14 on a 23-nt guide RNA before endonucleolytic cleavage, thereby allowing for some off-target cleavage. Of note, acquisition of an N-lobe expanded the range of the guide RNA strand used for inspecting target complementarity to positions 2-23. These findings offer clues to the evolution of the bilobal structure of catalytically active Argonaute proteins. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Theoretical rate constants of super-exchange hole transfer and thermally induced hopping in DNA.

PubMed

Shimazaki, Tomomi; Asai, Yoshihiro; Yamashita, Koichi

2005-01-27

Recently, the electronic properties of DNA have been extensively studied, because its conductivity is important not only to the study of fundamental biological problems, but also in the development of molecular-sized electronics and biosensors. We have studied theoretically the reorganization energies, the activation energies, the electronic coupling matrix elements, and the rate constants of hole transfer in B-form double-helix DNA in water. To accommodate the effects of DNA nuclear motions, a subset of reaction coordinates for hole transfer was extracted from classical molecular dynamics (MD) trajectories of DNA in water and then used for ab initio quantum chemical calculations of electron coupling constants based on the generalized Mulliken-Hush model. A molecular mechanics (MM) method was used to determine the nuclear Franck-Condon factor. The rate constants for two types of mechanisms of hole transfer-the thermally induced hopping (TIH) and the super-exchange mechanisms-were determined based on Marcus theory. We found that the calculated matrix elements are strongly dependent on the conformations of the nucleobase pairs of hole-transferable DNA and extend over a wide range of values for the "rise" base-step parameter but cluster around a particular value for the "twist" parameter. The calculated activation energies are in good agreement with experimental results. Whereas the rate constant for the TIH mechanism is not dependent on the number of A-T nucleobase pairs that act as a bridge, the rate constant for the super-exchange process rapidly decreases when the length of the bridge increases. These characteristic trends in the calculated rate constants effectively reproduce those in the experimental data of Giese et al. [Nature 2001, 412, 318]. The calculated rate constants were also compared with the experimental results of Lewis et al. [Nature 2000, 406, 51].

Hybrid-denovo: a de novo OTU-picking pipeline integrating single-end and paired-end 16S sequence tags.

PubMed

Chen, Xianfeng; Johnson, Stephen; Jeraldo, Patricio; Wang, Junwen; Chia, Nicholas; Kocher, Jean-Pierre A; Chen, Jun

2018-03-01

Illumina paired-end sequencing has been increasingly popular for 16S rRNA gene-based microbiota profiling. It provides higher phylogenetic resolution than single-end reads due to a longer read length. However, the reverse read (R2) often has significant low base quality, and a large proportion of R2s will be discarded after quality control, resulting in a mixture of paired-end and single-end reads. A typical 16S analysis pipeline usually processes either paired-end or single-end reads but not a mixture. Thus, the quantification accuracy and statistical power will be reduced due to the loss of a large amount of reads. As a result, rare taxa may not be detectable with the paired-end approach, or low taxonomic resolution will result in a single-end approach. To have both the higher phylogenetic resolution provided by paired-end reads and the higher sequence coverage by single-end reads, we propose a novel OTU-picking pipeline, hybrid-denovo, that can process a hybrid of single-end and paired-end reads. Using high-quality paired-end reads as a gold standard, we show that hybrid-denovo achieved the highest correlation with the gold standard and performed better than the approaches based on paired-end or single-end reads in terms of quantifying the microbial diversity and taxonomic abundances. By applying our method to a rheumatoid arthritis (RA) data set, we demonstrated that hybrid-denovo captured more microbial diversity and identified more RA-associated taxa than a paired-end or single-end approach. Hybrid-denovo utilizes both paired-end and single-end 16S sequencing reads and is recommended for 16S rRNA gene targeted paired-end sequencing data.

Relativistic coupled cluster theory based on the no-pair Dirac-Coulomb-Breit Hamiltonian: Relativistic pair correlation energies of the Xe atom

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

Eliav, E.; Kaldor, U.; Ishikawa, Y.

1994-12-31

Relativistic pair correlation energies of Xe were computed by employing a recently developed relativistic coupled cluster theory based on the no-pair Dirac-Coulomb-Breit Hamiltonian. The matrix Dirac-Fock-Breit SCF and relativistic coupled cluster calculations were performed by means of expansion in basis sets of well-tempered Gaussian spinors. A detailed study of the pair correlation energies in Xe is performed, in order to investigate the effects of the low-frequency Breit interaction on the correlation energies of Xe. Nonadditivity of correlation and relativistic (particularly Breit) effects is discussed.

On twelve types of covering-based rough sets.

PubMed

Safari, Samira; Hooshmandasl, Mohammad Reza

2016-01-01

Covering approximation spaces are a generalization of equivalence-based rough set theories. In this paper, we will consider twelve types of covering based approximation operators by combining four types of covering lower approximation operators and three types of covering upper approximation operators. Then, we will study the properties of these new pairs and show they have most of the common properties among existing covering approximation pairs. Finally, the relation between these new pairs is studied.

Evidence for Watson-Crick and not Hoogsteen or wobble base pairing in the selection of nucleotides for insertion opposite pyrimidines and a thymine dimer by yeast DNA pol eta.

PubMed

Hwang, Hanshin; Taylor, John-Stephen

2005-03-29

We have recently reported that pyrene nucleotide is preferentially inserted opposite an abasic site, the 3'-T of a thymine dimer, and most undamaged bases by yeast DNA polymerase eta (pol eta). Because pyrene is a nonpolar molecule with no H-bonding ability, the unusually high efficiencies of dPMP insertion are ascribed to its superior base stacking ability, and underscore the importance of base stacking in the selection of nucleotides by pol eta. To investigate the role of H-bonding and base pair geometry in the selection of nucleotides by pol eta, we determined the insertion efficiencies of the base-modified nucleotides 2,6-diaminopurine, 2-aminopurine, 6-chloropurine, and inosine which would make a different number of H-bonds with the template base depending on base pair geometry. Watson-Crick base pairing appears to play an important role in the selection of nucleotide analogues for insertion opposite C and T as evidenced by the decrease in the relative insertion efficiencies with a decrease in the number of Watson-Crick H-bonds and an increase in the number of donor-donor and acceptor-acceptor interactions. The selectivity of nucleotide insertion is greater opposite the 5'-T than the 3'-T of the thymine dimer, in accord with previous work suggesting that the 5'-T is held more rigidly than the 3'-T. Furthermore, insertion of A opposite both Ts of the dimer appears to be mediated by Watson-Crick base pairing and not by Hoogsteen base pairing based on the almost identical insertion efficiencies of A and 7-deaza-A, the latter of which lacks H-bonding capability at N7. The relative efficiencies for insertion of nucleotides that can form Watson-Crick base pairs parallel those for the Klenow fragment, whereas the Klenow fragment more strongly discriminates against mismatches, in accord with its greater shape selectivity. These results underscore the importance of H-bonding and Watson-Crick base pair geometry in the selection of nucleotides by both pol eta and the Klenow fragment, and the lesser role of shape selection in insertion by pol eta due to its more open and less constrained active site.

Energy barriers and rates of tautomeric transitions in DNA bases: ab initio quantum chemical study.

PubMed

Basu, Soumalee; Majumdar, Rabi; Das, Gourab K; Bhattacharyya, Dhananjay

2005-12-01

Tautomeric transitions of DNA bases are proton transfer reactions, which are important in biology. These reactions are involved in spontaneous point mutations of the genetic material. In the present study, intrinsic reaction coordinates (IRC) analyses through ab initio quantum chemical calculations have been carried out for the individual DNA bases A, T, G, C and also A:T and G:C base pairs to estimate the kinetic and thermodynamic barriers using MP2/6-31G** method for tautomeric transitions. Relatively higher values of kinetic barriers (about 50-60 kcal/mol) have been observed for the single bases, indicating that tautomeric alterations of isolated single bases are quite unlikely. On the other hand, relatively lower values of the kinetic barriers (about 20-25 kcal/mol) for the DNA base pairs A:T and G:C clearly suggest that the tautomeric shifts are much more favorable in DNA base pairs than in isolated single bases. The unusual base pairing A':C, T':G, C':A or G':T in the daughter DNA molecule, resulting from a parent DNA molecule with tautomeric shifts, is found to be stable enough to result in a mutation. The transition rate constants for the single DNA bases in addition to the base pairs are also calculated by computing the free energy differences between the transition states and the reactants.

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

Wang, Yujie; Gong, Sha; Wang, Zhen

The thermodynamic and kinetic parameters of an RNA base pair were obtained through a long-time molecular dynamics simulation of the opening-closing switch process of the base pair near its melting temperature. The thermodynamic parameters were in good agreement with the nearest-neighbor model. The opening rates showed strong temperature dependence, however, the closing rates showed only weak temperature dependence. The transition path time was weakly temperature dependent and was insensitive to the energy barrier. The diffusion constant exhibited super-Arrhenius behavior. The free energy barrier of breaking a single base stack results from the enthalpy increase, ΔH, caused by the disruption ofmore » hydrogen bonding and base-stacking interactions. The free energy barrier of base pair closing comes from the unfavorable entropy loss, ΔS, caused by the restriction of torsional angles. These results suggest that a one-dimensional free energy surface is sufficient to accurately describe the dynamics of base pair opening and closing, and the dynamics are Brownian.« less

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

Gao, X.; Patel, D.J.

The authors report on two-dimensional proton NMR studies of echinomycin complexes with the self-complementary d(A1-C2-G3-Tr) and d(T1-C2-G3-A4) duplexes in aqueous solution. The exchangeable and nonexchangeable antibiotic and nucleic acid protons in the 1 echinomycin per tetranucleotide duplex complexes have been assigned from analyses of scalar coupling and distance connectivities in two-dimensional data sets records in H/sub 2/O and D/sub 2/O solution. An analysis of the intermolecular NOE patterns for both complexes combined with large upfield imino proton and large downfield phosphorus complexation chemical shift changes demonstrates that the two quinoxaline chromophores of echinomycin bisintercalate into the minor groove surrounding themore » dC-dG step of each tetranucleotide duplex. Further, the quinoxaline rings selectively stack between A1 and C2 bases in the d(ACGT) complex and between T1 and C2 bases in the d(TCGA) complex. The intermolecular NOE patterns and the base and sugar proton chemical shifts for residues C2 and G3 are virtually identical for the d(ACGT) and d(TCGA) complexes. A large set of intermolecular contacts established from nuclear Overhauser effects (NOEs) between antibiotic and nucleic acid protons in the echinomycin-tetranucleotide complexes in solution are consistent with corresponding contacts reported for echinomycin-oligonucleotide complexes in the crystalline state. The authors demonstrate that the G x G base pairs adopt Watson-Crick pairing in both d(ACGT) and d(TCGA) complexes in solution. By contrast, the A1 x T4 base pairs adopt Hoogsteen pairing for the echinomycin-d(A1-C2-G3-Tr) complex while the T1 x A4 base pairs adopt Watson-Crick pairing for the echinomycin-d(T1-C2-G3-A4) complex in aqueous solution. These results emphasize the role of sequence in discriminating between Watson-Crick and Hoogsteen pairs at base pairs flanking the echinomycin bisintercalation site in solution.« less