Sequence-dependent response of DNA to torsional stress: a potential biological regulation mechanism

PubMed Central

Reymer, Anna; Zakrzewska, Krystyna; Lavery, Richard

2018-01-01

Abstract Torsional restraints on DNA change in time and space during the life of the cell and are an integral part of processes such as gene expression, DNA repair and packaging. The mechanical behavior of DNA under torsional stress has been studied on a mesoscopic scale, but little is known concerning its response at the level of individual base pairs and the effects of base pair composition. To answer this question, we have developed a geometrical restraint that can accurately control the total twist of a DNA segment during all-atom molecular dynamics simulations. By applying this restraint to four different DNA oligomers, we are able to show that DNA responds to both under- and overtwisting in a very heterogeneous manner. Certain base pair steps, in specific sequence environments, are able to absorb most of the torsional stress, leaving other steps close to their relaxed conformation. This heterogeneity also affects the local torsional modulus of DNA. These findings suggest that modifying torsional stress on DNA could act as a modulator for protein binding via the heterogeneous changes in local DNA structure. PMID:29267977

Solar array stepping to minimize array excitation

NASA Technical Reports Server (NTRS)

Bhat, Mahabaleshwar K. P. (Inventor); Liu, Tung Y. (Inventor); Plescia, Carl T. (Inventor)

1989-01-01

Mechanical oscillations of a mechanism containing a stepper motor, such as a solar-array powered spacecraft, are reduced and minimized by the execution of step movements in pairs of steps, the period between steps being equal to one-half of the period of torsional oscillation of the mechanism. Each pair of steps is repeated at needed intervals to maintain desired continuous movement of the portion of elements to be moved, such as the solar array of a spacecraft. In order to account for uncertainty as well as slow change in the period of torsional oscillation, a command unit may be provided for varying the interval between steps in a pair.

Functional base-pairing interaction between highly conserved elements of U3 small nucleolar RNA and the small ribosomal subunit RNA.

PubMed

Hughes, J M

1996-06-21

The U3 nucleolar RNA has a remarkably wide phyletic distribution extending from the Eukarya to the Archaea. It functions in maturation of the small subunit (SSU) rRNA through a mechanism which is as yet unknown but which involves base-pairing with pre-rRNA. The most conserved part of U3 is within 30 nucleotides of the 5' end, but as yet no function for this domain has been proposed. Elements within this domain are complementary to highly conserved sequences in the SSU rRNA which, in the mature form, fold into a universally conserved pseudoknot. The nature of the complementarity suggests a novel mechanism for U3 function whereby U3 facilitates correct folding of the pseudoknot. Wide phylogenetic comparison provides compelling evidence in support of the interaction in that significant complementary changes have taken place, particularly in the archaeon Sulfolobus, which maintain the base-pairing. Base-substitution mutations in yeast U3 designed to disrupt the base-pairing indicate that the interaction is probably essential. These include cold-sensitivity mutations which exhibit phenotypes similar to U3-depletion, but without impairment of the AO processing step, which occurs within the 5' ETS. These phenotypes are consistent with the destabilization of SSU precursors and partial impairment of the processing steps A1, at the 5' ETS/18 S boundary, and A2, within the ITS1.

MSP-HTPrimer: a high-throughput primer design tool to improve assay design for DNA methylation analysis in epigenetics.

PubMed

Pandey, Ram Vinay; Pulverer, Walter; Kallmeyer, Rainer; Beikircher, Gabriel; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas

2016-01-01

Bisulfite (BS) conversion-based and methylation-sensitive restriction enzyme (MSRE)-based PCR methods have been the most commonly used techniques for locus-specific DNA methylation analysis. However, both methods have advantages and limitations. Thus, an integrated approach would be extremely useful to quantify the DNA methylation status successfully with great sensitivity and specificity. Designing specific and optimized primers for target regions is the most critical and challenging step in obtaining the adequate DNA methylation results using PCR-based methods. Currently, no integrated, optimized, and high-throughput methylation-specific primer design software methods are available for both BS- and MSRE-based methods. Therefore an integrated, powerful, and easy-to-use methylation-specific primer design pipeline with great accuracy and success rate will be very useful. We have developed a new web-based pipeline, called MSP-HTPrimer, to design primers pairs for MSP, BSP, pyrosequencing, COBRA, and MSRE assays on both genomic strands. First, our pipeline converts all target sequences into bisulfite-treated templates for both forward and reverse strand and designs all possible primer pairs, followed by filtering for single nucleotide polymorphisms (SNPs) and known repeat regions. Next, each primer pairs are annotated with the upstream and downstream RefSeq genes, CpG island, and cut sites (for COBRA and MSRE). Finally, MSP-HTPrimer selects specific primers from both strands based on custom and user-defined hierarchical selection criteria. MSP-HTPrimer produces a primer pair summary output table in TXT and HTML format for display and UCSC custom tracks for resulting primer pairs in GTF format. MSP-HTPrimer is an integrated, web-based, and high-throughput pipeline and has no limitation on the number and size of target sequences and designs MSP, BSP, pyrosequencing, COBRA, and MSRE assays. It is the only pipeline, which automatically designs primers on both genomic strands to increase the success rate. It is a standalone web-based pipeline, which is fully configured within a virtual machine and thus can be readily used without any configuration. We have experimentally validated primer pairs designed by our pipeline and shown a very high success rate of primer pairs: out of 66 BSP primer pairs, 63 were successfully validated without any further optimization step and using the same qPCR conditions. The MSP-HTPrimer pipeline is freely available from http://sourceforge.net/p/msp-htprimer.

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

Effects of student pairing and public review on physical activity during school recess.

PubMed

Zerger, Heather M; Miller, Bryon G; Valbuena, Diego; Miltenberger, Raymond G

2017-07-01

The purpose of this study was to evaluate the effects of student pairing and feedback during recess on children's step counts. During baseline, participants wore a sealed pedometer during recess. During intervention, we paired participants with higher step counts with participants with lower step counts. We encouraged teams to compete for the highest step count each day and provided feedback on their performance during each recess session. Results showed a large mean increase in step count from baseline to intervention. These results suggest that children's steps during recess can be increased with a simple and cost-effective intervention. © 2017 Society for the Experimental Analysis of Behavior.

Sequence-dependent DNA deformability studied using molecular dynamics simulations.

PubMed

Fujii, Satoshi; Kono, Hidetoshi; Takenaka, Shigeori; Go, Nobuhiro; Sarai, Akinori

2007-01-01

Proteins recognize specific DNA sequences not only through direct contact between amino acids and bases, but also indirectly based on the sequence-dependent conformation and deformability of the DNA (indirect readout). We used molecular dynamics simulations to analyze the sequence-dependent DNA conformations of all 136 possible tetrameric sequences sandwiched between CGCG sequences. The deformability of dimeric steps obtained by the simulations is consistent with that by the crystal structures. The simulation results further showed that the conformation and deformability of the tetramers can highly depend on the flanking base pairs. The conformations of xATx tetramers show the most rigidity and are not affected by the flanking base pairs and the xYRx show by contrast the greatest flexibility and change their conformations depending on the base pairs at both ends, suggesting tetramers with the same central dimer can show different deformabilities. These results suggest that analysis of dimeric steps alone may overlook some conformational features of DNA and provide insight into the mechanism of indirect readout during protein-DNA recognition. Moreover, the sequence dependence of DNA conformation and deformability may be used to estimate the contribution of indirect readout to the specificity of protein-DNA recognition as well as nucleosome positioning and large-scale behavior of nucleic acids.

Dynamic investigation of DNA bending and wrapping by type II topoisomerases

NASA Astrophysics Data System (ADS)

Shao, Qing; Finzi, Laura; Dunlap, David

2009-11-01

Type II topoisomerases catalyze DNA decatenation and unwinding which is crucial for cell division, and therefore type II topoisomerases are some of the main targets of anti-cancer drugs. A recent crystal structure shows that, during the catalytic cycle, a yeast type II topoimerase can bend a 10 base pair DNA segment by up to 150 degrees. Bacterial gyrase, another type II topoisomerase, can wrap DNA into a tight 180 degree turn. Bending a stiff polymer like DNA requires considerable energy and could represent the rate limiting step in the catalytic (topological) cycle. Using modified deoxyribonucleotides in PCR reactions, stiffer DNA fragments have been produced and used as substrates for topoisomerase II-mediated relaxation of plectonemes introduced in single molecules using magnetic tweezers. The wrapping ability of gyrase decreases for diamino-purine-substituted DNA in which every base pair has three hydrogen-bonds. The overall rate of relaxation of plectonemes by recombinant human topoisomerase II alpha also decreases. These results reveal the dynamic properties of DNA bending and wrapping by type II topisomerases and suggest that A:T base pair melting is a rate determining step for bending and wrapping.

Electrical Conductivity through a Single Atomic Step Measured with the Proximity-Induced Superconducting Pair Correlation

DOE PAGES

Kim, Howon; Lin, Shi -Zeng; Graf, Matthias J.; ...

2016-09-08

Local disordered nanostructures in an atomically thick metallic layer on a semiconducting substrate play significant and decisive roles in transport properties of two-dimensional (2D) conductive systems. We measured the electrical conductivity through a step of monoatomic height in a truly microscopic manner by using as a signal the superconducting pair correlation induced by the proximity effect. The transport property across a step of a one-monolayer Pb surface metallic phase, formed on a Si(111) substrate, was evaluated by inducing the pair correlation around the local defect and measuring its response, i.e., the reduced density of states at the Fermi energy usingmore » scanning tunneling microscopy. We found that the step resistance has a significant contribution to the total resistance on a nominally flat surface. Our study also revealed that steps in the 2D metallic layer terminate the propagation of the pair correlation. Furthermore, superconductivity is enhanced between the first surface step and the superconductor–normal-metal interface by reflectionless tunneling when the step is located within a coherence length.« less

Electrical Conductivity through a Single Atomic Step Measured with the Proximity-Induced Superconducting Pair Correlation.

PubMed

Kim, Howon; Lin, Shi-Zeng; Graf, Matthias J; Miyata, Yoshinori; Nagai, Yuki; Kato, Takeo; Hasegawa, Yukio

2016-09-09

Local disordered nanostructures in an atomically thick metallic layer on a semiconducting substrate play significant and decisive roles in transport properties of two-dimensional (2D) conductive systems. We measured the electrical conductivity through a step of monoatomic height in a truly microscopic manner by using as a signal the superconducting pair correlation induced by the proximity effect. The transport property across a step of a one-monolayer Pb surface metallic phase, formed on a Si(111) substrate, was evaluated by inducing the pair correlation around the local defect and measuring its response, i.e., the reduced density of states at the Fermi energy using scanning tunneling microscopy. We found that the step resistance has a significant contribution to the total resistance on a nominally flat surface. Our study also revealed that steps in the 2D metallic layer terminate the propagation of the pair correlation. Superconductivity is enhanced between the first surface step and the superconductor-normal-metal interface by reflectionless tunneling when the step is located within a coherence length.

Design and implementation of magnetically maneuverable capsule endoscope system with direction reference for image navigation.

PubMed

Sun, Zhen-Jun; Ye, Bo; Sun, Yi; Zhang, Hong-Hai; Liu, Sheng

2014-07-01

This article describes a novel magnetically maneuverable capsule endoscope system with direction reference for image navigation. This direction reference was employed by utilizing a specific magnet configuration between a pair of external permanent magnets and a magnetic shell coated on the external capsule endoscope surface. A pair of customized Cartesian robots, each with only 4 degrees of freedom, was built to hold the external permanent magnets as their end-effectors. These robots, together with their external permanent magnets, were placed on two opposite sides of a "patient bed." Because of the optimized configuration based on magnetic analysis between the external permanent magnets and the magnetic shell, a simplified control strategy was proposed, and only two parameters, yaw step angle and moving step, were necessary for the employed robotic system. Step-by-step experiments demonstrated that the proposed system is capable of magnetically maneuvering the capsule endoscope while providing direction reference for image navigation. © IMechE 2014.

Tri-Texts: A Potential Next Step for Paired Texts

ERIC Educational Resources Information Center

Ciecierski, Lisa M.; Bintz, William P.

2018-01-01

This article presents the concept of tri-texts as a potential next step from paired texts following a collaborative inquiry with fifth-grade students. Paired texts are two texts intertextually connected, whereas tri-texts are three texts connected this way. The authors begin the article with a short literature review highlighting some of the…

Intrinsic flexibility of B-DNA: the experimental TRX scale.

PubMed

Heddi, Brahim; Oguey, Christophe; Lavelle, Christophe; Foloppe, Nicolas; Hartmann, Brigitte

2010-01-01

B-DNA flexibility, crucial for DNA-protein recognition, is sequence dependent. Free DNA in solution would in principle be the best reference state to uncover the relation between base sequences and their intrinsic flexibility; however, this has long been hampered by a lack of suitable experimental data. We investigated this relationship by compiling and analyzing a large dataset of NMR (31)P chemical shifts in solution. These measurements reflect the BI <--> BII equilibrium in DNA, intimately correlated to helicoidal descriptors of the curvature, winding and groove dimensions. Comparing the ten complementary DNA dinucleotide steps indicates that some steps are much more flexible than others. This malleability is primarily controlled at the dinucleotide level, modulated by the tetranucleotide environment. Our analyses provide an experimental scale called TRX that quantifies the intrinsic flexibility of the ten dinucleotide steps in terms of Twist, Roll, and X-disp (base pair displacement). Applying the TRX scale to DNA sequences optimized for nucleosome formation reveals a 10 base-pair periodic alternation of stiff and flexible regions. Thus, DNA flexibility captured by the TRX scale is relevant to nucleosome formation, suggesting that this scale may be of general interest to better understand protein-DNA recognition.

Light-dependent magnetoreception in birds: the crucial step occurs in the dark.

PubMed

Wiltschko, Roswitha; Ahmad, Margaret; Nießner, Christine; Gehring, Dennis; Wiltschko, Wolfgang

2016-05-01

The Radical Pair Model proposes that the avian magnetic compass is based on spin-chemical processes: since the ratio between the two spin states singlet and triplet of radical pairs depends on their alignment in the magnetic field, it can provide information on magnetic directions. Cryptochromes, blue light-absorbing flavoproteins, with flavin adenine dinucleotide as chromophore, are suggested as molecules forming the radical pairs underlying magnetoreception. When activated by light, cryptochromes undergo a redox cycle, in the course of which radical pairs are generated during photo-reduction as well as during light-independent re-oxidation. This raised the question as to which radical pair is crucial for mediating magnetic directions. Here, we present the results from behavioural experiments with intermittent light and magnetic field pulses that clearly show that magnetoreception is possible in the dark interval, pointing to the radical pair formed during flavin re-oxidation. This differs from the mechanism considered for cryptochrome signalling the presence of light and rules out most current models of an avian magnetic compass based on the radical pair generated during photo-reduction. Using the radical pair formed during re-oxidation may represent a specific adaptation of the avian magnetic compass. © 2016 The Authors.

Enhanced sampling simulations of DNA step parameters.

PubMed

Karolak, Aleksandra; van der Vaart, Arjan

2014-12-15

A novel approach for the selection of step parameters as reaction coordinates in enhanced sampling simulations of DNA is presented. The method uses three atoms per base and does not require coordinate overlays or idealized base pairs. This allowed for a highly efficient implementation of the calculation of all step parameters and their Cartesian derivatives in molecular dynamics simulations. Good correlation between the calculated and actual twist, roll, tilt, shift, and slide parameters is obtained, while the correlation with rise is modest. The method is illustrated by its application to the methylated and unmethylated 5'-CATGTGACGTCACATG-3' double stranded DNA sequence. One-dimensional umbrella simulations indicate that the flexibility of the central CG step is only marginally affected by methylation. © 2014 Wiley Periodicals, Inc.

Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations

PubMed Central

Tan, Cheng; Takada, Shoji

2017-01-01

While nucleosome positioning on eukaryotic genome play important roles for genetic regulation, molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood. Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-grained molecular simulation method that incorporates both long-range electrostatic and short-range hydrogen-bond interactions between histone octamer and DNA. The simulations revealed two distinct sliding modes depending on the nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one base pair step in a rotation-coupled manner, akin to screw-like motions. On the contrary, a strong positioning sequence, the so-called 601 sequence, exhibits rare, abrupt transitions of five and ten base pair steps without rotation. Moreover, we evaluated the importance of hydrogen bond interactions on the sliding mode, finding that strong and weak bonds favor respectively the rotation-coupled and -uncoupled sliding movements. PMID:29194442

Identification in a pseudoknot of a U.G motif essential for the regulation of the expression of ribosomal protein S15.

PubMed

Bénard, L; Mathy, N; Grunberg-Manago, M; Ehresmann, B; Ehresmann, C; Portier, C

1998-03-03

The ribosomal protein S15 from Escherichia coli binds to a pseudoknot in its own messenger. This interaction is an essential step in the mechanism of S15 translational autoregulation. In a previous study, a recognition determinant for S15 autoregulation, involving a U.G wobble pair, was located in the center of stem I of the pseudoknot. In this study, an extensive mutagenesis analysis has been conducted in and around this U.G pair by comparing the effects of these mutations on the expression level of S15. The results show that the U.G wobble pair cannot be substituted by A.G, C.A, A.C, G.U, or C.G without loss of the autocontrol. In addition, the base pair C.G, adjacent to the 5' side of U, cannot be flipped or changed to another complementary base pair without also inducing derepression of translation. A unique motif, made of only two adjacent base pairs, U.G/C.G, is essential for S15 autoregulation and is presumably involved in direct recognition by the S15 protein.

Identification in a pseudoknot of a U⋅G motif essential for the regulation of the expression of ribosomal protein S15

PubMed Central

Bénard, Lionel; Mathy, Nathalie; Grunberg-Manago, Marianne; Ehresmann, Bernard; Ehresmann, Chantal; Portier, Claude

1998-01-01

The ribosomal protein S15 from Escherichia coli binds to a pseudoknot in its own messenger. This interaction is an essential step in the mechanism of S15 translational autoregulation. In a previous study, a recognition determinant for S15 autoregulation, involving a U⋅G wobble pair, was located in the center of stem I of the pseudoknot. In this study, an extensive mutagenesis analysis has been conducted in and around this U⋅G pair by comparing the effects of these mutations on the expression level of S15. The results show that the U⋅G wobble pair cannot be substituted by A⋅G, C⋅A, A⋅C, G⋅U, or C⋅G without loss of the autocontrol. In addition, the base pair C⋅G, adjacent to the 5′ side of U, cannot be flipped or changed to another complementary base pair without also inducing derepression of translation. A unique motif, made of only two adjacent base pairs, U⋅G/C⋅G, is essential for S15 autoregulation and is presumably involved in direct recognition by the S15 protein. PMID:9482926

RNAHelix: computational modeling of nucleic acid structures with Watson-Crick and non-canonical base pairs.

PubMed

Bhattacharyya, Dhananjay; Halder, Sukanya; Basu, Sankar; Mukherjee, Debasish; Kumar, Prasun; Bansal, Manju

2017-02-01

Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-canonical, is seriously needed. Here we describe a program RNAHelix, which is an updated version of our widely used software, NUCGEN. The program can regenerate duplexes using the dinucleotide step and base pair orientation parameters for a given double helical DNA or RNA sequence with defined Watson-Crick or non-Watson-Crick base pairs. The original structure and the corresponding regenerated structure of double helices were found to be very close, as indicated by the small RMSD values between positions of the corresponding atoms. Structures of several usual and unusual double helices have been regenerated and compared with their original structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes.

A multilevel-skin neighbor list algorithm for molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Zhang, Chenglong; Zhao, Mingcan; Hou, Chaofeng; Ge, Wei

2018-01-01

Searching of the interaction pairs and organization of the interaction processes are important steps in molecular dynamics (MD) algorithms and are critical to the overall efficiency of the simulation. Neighbor lists are widely used for these steps, where thicker skin can reduce the frequency of list updating but is discounted by more computation in distance check for the particle pairs. In this paper, we propose a new neighbor-list-based algorithm with a precisely designed multilevel skin which can reduce unnecessary computation on inter-particle distances. The performance advantages over traditional methods are then analyzed against the main simulation parameters on Intel CPUs and MICs (many integrated cores), and are clearly demonstrated. The algorithm can be generalized for various discrete simulations using neighbor lists.

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

Relative Motion of the WDS 05110+3203 STF 648 System, With a Protocol for Calculating Relative Motion

NASA Astrophysics Data System (ADS)

Wiley, E. O.

2010-07-01

Relative motion studies of visual double stars can be investigated using least squares regression techniques and readily accessible programs such as Microsoft Excel and a calculator. Optical pairs differ from physical pairs under most geometries in both their simple scatter plots and their regression models. A step-by-step protocol for estimating the rectilinear elements of an optical pair is presented. The characteristics of physical pairs using these techniques are discussed.

Amplification of the Gp41 gene for detection of mutations conferring resistance to HIV-1 fusion inhibitors on genotypic assay

NASA Astrophysics Data System (ADS)

Tanumihardja, J.; Bela, B.

2017-08-01

Fusion inhibitors have potential for future use in HIV control programs in Indonesia, so the capacity to test resistance to such drugs needs to be developed. Resistance-detection with a genotypic assay began with amplification of the target gene, gp41. Based on the sequence of the two most common HIV subtypes in Indonesia, AE and B, a primer pair was designed. Plasma samples containing both subtypes were extracted to obtain HIV RNA. Using PCR, the primer pair was used to produce the amplification product, the identity of which was checked based on length under electrophoresis. Eleven plasma samples were included in this study. One-step PCR using the primer pair was able to amplify gp41 from 54.5% of the samples, and an unspecific amplification product was seen in 1.1% of the samples. Amplification failed in 36.4% of the samples, which may be due to an inappropriate primer sequence. It was also found that the optimal annealing temperature for producing the single expected band was 57.2 °C. With one-step PCR, the designed primer pair amplified the HIV-1 gp41 gene from subtypes AE and B. However, further research should be done to determine the conditions that will increase the sensitivity and specificity of the amplification process.

Assessment of replicate bias in 454 pyrosequencing and a multi-purpose read-filtering tool.

PubMed

Jérôme, Mariette; Noirot, Céline; Klopp, Christophe

2011-05-26

Roche 454 pyrosequencing platform is often considered the most versatile of the Next Generation Sequencing technology platforms, permitting the sequencing of large genomes, the analysis of variations or the study of transcriptomes. A recent reported bias leads to the production of multiple reads for a unique DNA fragment in a random manner within a run. This bias has a direct impact on the quality of the measurement of the representation of the fragments using the reads. Other cleaning steps are usually performed on the reads before assembly or alignment. PyroCleaner is a software module intended to clean 454 pyrosequencing reads in order to ease the assembly process. This program is a free software and is distributed under the terms of the GNU General Public License as published by the Free Software Foundation. It implements several filters using criteria such as read duplication, length, complexity, base-pair quality and number of undetermined bases. It also permits to clean flowgram files (.sff) of paired-end sequences generating on one hand validated paired-ends file and the other hand single read file. Read cleaning has always been an important step in sequence analysis. The pyrocleaner python module is a Swiss knife dedicated to 454 reads cleaning. It includes commonly used filters as well as specialised ones such as duplicated read removal and paired-end read verification.

Recursive Directional Ligation Approach for Cloning Recombinant Spider Silks.

PubMed

Dinjaski, Nina; Huang, Wenwen; Kaplan, David L

2018-01-01

Recent advances in genetic engineering have provided a route to produce various types of recombinant spider silks. Different cloning strategies have been applied to achieve this goal (e.g., concatemerization, step-by-step ligation, recursive directional ligation). Here we describe recursive directional ligation as an approach that allows for facile modularity and control over the size of the genetic cassettes. This approach is based on sequential ligation of genetic cassettes (monomers) where the junctions between them are formed without interrupting key gene sequences with additional base pairs.

An illustration of new methods in machine condition monitoring, Part I: stochastic resonance

NASA Astrophysics Data System (ADS)

Worden, K.; Antoniadou, I.; Marchesiello, S.; Mba, C.; Garibaldi, L.

2017-05-01

There have been many recent developments in the application of data-based methods to machine condition monitoring. A powerful methodology based on machine learning has emerged, where diagnostics are based on a two-step procedure: extraction of damage-sensitive features, followed by unsupervised learning (novelty detection) or supervised learning (classification). The objective of the current pair of papers is simply to illustrate one state-of-the-art procedure for each step, using synthetic data representative of reality in terms of size and complexity. The first paper in the pair will deal with feature extraction. Although some papers have appeared in the recent past considering stochastic resonance as a means of amplifying damage information in signals, they have largely relied on ad hoc specifications of the resonator used. In contrast, the current paper will adopt a principled optimisation-based approach to the resonator design. The paper will also show that a discrete dynamical system can provide all the benefits of a continuous system, but also provide a considerable speed-up in terms of simulation time in order to facilitate the optimisation approach.

Speech Privacy Problems

DTIC Science & Technology

1945-08-18

were interconnected, how? ever,, it was found that one of the oscillators had an intermit - tent, defect-. This trouble was cleared by removing the...switches> i.e., two pairsL are included in.the unit," one of ä pair of selectors {the " fast selector") steps .each time the latch operates, the other (the...34slow seleotor") steps oiice eaoh time the fast seleotor completes 25 steps. Thus, a total of 625 steps, or changes in permutation, is involved be

Building dynamic population graph for accurate correspondence detection.

PubMed

Du, Shaoyi; Guo, Yanrong; Sanroma, Gerard; Ni, Dong; Wu, Guorong; Shen, Dinggang

2015-12-01

In medical imaging studies, there is an increasing trend for discovering the intrinsic anatomical difference across individual subjects in a dataset, such as hand images for skeletal bone age estimation. Pair-wise matching is often used to detect correspondences between each individual subject and a pre-selected model image with manually-placed landmarks. However, the large anatomical variability across individual subjects can easily compromise such pair-wise matching step. In this paper, we present a new framework to simultaneously detect correspondences among a population of individual subjects, by propagating all manually-placed landmarks from a small set of model images through a dynamically constructed image graph. Specifically, we first establish graph links between models and individual subjects according to pair-wise shape similarity (called as forward step). Next, we detect correspondences for the individual subjects with direct links to any of model images, which is achieved by a new multi-model correspondence detection approach based on our recently-published sparse point matching method. To correct those inaccurate correspondences, we further apply an error detection mechanism to automatically detect wrong correspondences and then update the image graph accordingly (called as backward step). After that, all subject images with detected correspondences are included into the set of model images, and the above two steps of graph expansion and error correction are repeated until accurate correspondences for all subject images are established. Evaluations on real hand X-ray images demonstrate that our proposed method using a dynamic graph construction approach can achieve much higher accuracy and robustness, when compared with the state-of-the-art pair-wise correspondence detection methods as well as a similar method but using static population graph. Copyright © 2015 Elsevier B.V. All rights reserved.

Indirect photometric detection of boron cluster anions electrophoretically separated in methanol.

PubMed

Vítová, Lada; Fojt, Lukáš; Vespalec, Radim

2014-04-18

3,5-Dinitrobenzoate and picrate are light absorbing anions pertinent to indirect photometric detection of boron cluster anions in buffered methanolic background electrolytes (BGEs). Tris(hydroxymethyl)aminomethane and morpholine have been used as buffering bases, which eliminated baseline steps, and minimized the baseline noise. In methanolic BGEs, mobilities of boron cluster anions depend on both ionic constituents of the BGE buffer. This dependence can be explained by ion pair interaction of detected anions with BGE cations, which are not bonded into ion pairs with the BGE anions. The former ion pair interaction decreases sensitivity of the indirect photometric detection. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical Isotope Labeling LC-MS for High Coverage and Quantitative Profiling of the Hydroxyl Submetabolome in Metabolomics.

PubMed

Zhao, Shuang; Luo, Xian; Li, Liang

2016-11-01

A key step in metabolomics is to perform accurate relative quantification of the metabolomes in comparative samples with high coverage. Hydroxyl-containing metabolites are an important class of the metabolome with diverse structures and physical/chemical properties; however, many of them are difficult to detect with high sensitivity. We present a high-performance chemical isotope labeling liquid chromatography mass spectrometry (LC-MS) technique for in-depth profiling of the hydroxyl submetabolome, which involves the use of acidic liquid-liquid extraction to enrich hydroxyl metabolites into ethyl acetate from an aqueous sample. After drying and then redissolving in acetonitrile, the metabolite extract is labeled using a base-activated 12 C- or 13 C-dansylation reaction. A fast step-gradient LC-UV method is used to determine the total concentration of labeled metabolites. On the basis of the concentration information, a 12 C-labeled individual sample is mixed with an equal mole amount of a 13 C-labeled pool or control for relative metabolite quantification. The 12 C-/ 13 C-labeled mixtures are individually analyzed by LC-MS, and the resultant peak pairs of labeled metabolites in MS are measured for relative quantification and metabolite identification. A standard library of 85 hydroxyl compounds containing MS, retention time, and MS/MS information was constructed for positive metabolite identification based on matches of two or all three of these parameters with those of an unknown. Using human urine as an example, we analyzed samples of 1:1 12 C-/ 13 C-labeled urine in triplicate with triplicate runs per sample and detected an average of 3759 ± 45 peak pairs or metabolites per run and 3538 ± 71 pairs per sample with 3093 pairs in common (n = 9). Out of the 3093 peak pairs, 2304 pairs (75%) could be positively or putatively identified based on metabolome database searches, including 20 pairs positively identified using the dansylated hydroxyl standards library. The majority of detected metabolites were those containing hydroxyl groups. This technique opens a new avenue for the detailed characterization of the hydroxyl submetabolome in metabolomics research.

MOCAT: A Metagenomics Assembly and Gene Prediction Toolkit

PubMed Central

Li, Junhua; Chen, Weineng; Chen, Hua; Mende, Daniel R.; Arumugam, Manimozhiyan; Pan, Qi; Liu, Binghang; Qin, Junjie; Wang, Jun; Bork, Peer

2012-01-01

MOCAT is a highly configurable, modular pipeline for fast, standardized processing of single or paired-end sequencing data generated by the Illumina platform. The pipeline uses state-of-the-art programs to quality control, map, and assemble reads from metagenomic samples sequenced at a depth of several billion base pairs, and predict protein-coding genes on assembled metagenomes. Mapping against reference databases allows for read extraction or removal, as well as abundance calculations. Relevant statistics for each processing step can be summarized into multi-sheet Excel documents and queryable SQL databases. MOCAT runs on UNIX machines and integrates seamlessly with the SGE and PBS queuing systems, commonly used to process large datasets. The open source code and modular architecture allow users to modify or exchange the programs that are utilized in the various processing steps. Individual processing steps and parameters were benchmarked and tested on artificial, real, and simulated metagenomes resulting in an improvement of selected quality metrics. MOCAT can be freely downloaded at http://www.bork.embl.de/mocat/. PMID:23082188

Helicase Stepping Investigated with One-Nucleotide Resolution Fluorescence Resonance Energy Transfer

NASA Astrophysics Data System (ADS)

Lin, Wenxia; Ma, Jianbing; Nong, Daguan; Xu, Chunhua; Zhang, Bo; Li, Jinghua; Jia, Qi; Dou, Shuoxing; Ye, Fangfu; Xi, Xuguang; Lu, Ying; Li, Ming

2017-09-01

Single-molecule Förster resonance energy transfer is widely applied to study helicases by detecting distance changes between a pair of dyes anchored to overhangs of a forked DNA. However, it has been lacking single-base pair (1-bp) resolution required for revealing stepping kinetics of helicases. We designed a nanotensioner in which a short DNA is bent to exert force on the overhangs, just as in optical or magnetic tweezers. The strategy improved the resolution of Förster resonance energy transfer to 0.5 bp, high enough to uncover differences in DNA unwinding by yeast Pif1 and E. coli RecQ whose unwinding behaviors cannot be differentiated by currently practiced methods. We found that Pif1 exhibits 1-bp-stepping kinetics, while RecQ breaks 1 bp at a time but sequesters the nascent nucleotides and releases them randomly. The high-resolution data allowed us to propose a three-parameter model to quantitatively interpret the apparently different unwinding behaviors of the two helicases which belong to two superfamilies.

MOCAT: a metagenomics assembly and gene prediction toolkit.

PubMed

Kultima, Jens Roat; Sunagawa, Shinichi; Li, Junhua; Chen, Weineng; Chen, Hua; Mende, Daniel R; Arumugam, Manimozhiyan; Pan, Qi; Liu, Binghang; Qin, Junjie; Wang, Jun; Bork, Peer

2012-01-01

MOCAT is a highly configurable, modular pipeline for fast, standardized processing of single or paired-end sequencing data generated by the Illumina platform. The pipeline uses state-of-the-art programs to quality control, map, and assemble reads from metagenomic samples sequenced at a depth of several billion base pairs, and predict protein-coding genes on assembled metagenomes. Mapping against reference databases allows for read extraction or removal, as well as abundance calculations. Relevant statistics for each processing step can be summarized into multi-sheet Excel documents and queryable SQL databases. MOCAT runs on UNIX machines and integrates seamlessly with the SGE and PBS queuing systems, commonly used to process large datasets. The open source code and modular architecture allow users to modify or exchange the programs that are utilized in the various processing steps. Individual processing steps and parameters were benchmarked and tested on artificial, real, and simulated metagenomes resulting in an improvement of selected quality metrics. MOCAT can be freely downloaded at http://www.bork.embl.de/mocat/.

Ultrasonic guided wave propagation across waveguide transitions: energy transfer and mode conversion.

PubMed

Puthillath, Padmakumar; Galan, Jose M; Ren, Baiyang; Lissenden, Cliff J; Rose, Joseph L

2013-05-01

Ultrasonic guided wave inspection of structures containing adhesively bonded joints requires an understanding of the interaction of guided waves with geometric and material discontinuities or transitions in the waveguide. Such interactions result in mode conversion with energy being partitioned among the reflected and transmitted modes. The step transition between an aluminum layer and an aluminum-adhesive-aluminum multi-layer waveguide is analyzed as a model structure. Dispersion analysis enables assessment of (i) synchronism through dispersion curve overlap and (ii) wavestructure correlation. Mode-pairs in the multi-layer waveguide are defined relative to a prescribed mode in a single layer as being synchronized and having nearly perfect wavestructure matching. Only a limited number of mode-pairs exist, and each has a unique frequency range. A hybrid model based on semi-analytical finite elements and the normal mode expansion is implemented to assess mode conversion at a step transition in a waveguide. The model results indicate that synchronism and wavestructure matching is associated with energy transfer through the step transition, and that the energy of an incident wave mode in a single layer is transmitted almost entirely to the associated mode-pair, where one exists. This analysis guides the selection of incident modes that convert into transmitted modes and improve adhesive joint inspection with ultrasonic guided waves.

Ab initio O(N) elongation-counterpoise method for BSSE-corrected interaction energy analyses in biosystems

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

Orimoto, Yuuichi; Xie, Peng; Liu, Kai

2015-03-14

An Elongation-counterpoise (ELG-CP) method was developed for performing accurate and efficient interaction energy analysis and correcting the basis set superposition error (BSSE) in biosystems. The method was achieved by combining our developed ab initio O(N) elongation method with the conventional counterpoise method proposed for solving the BSSE problem. As a test, the ELG-CP method was applied to the analysis of the DNAs’ inter-strands interaction energies with respect to the alkylation-induced base pair mismatch phenomenon that causes a transition from G⋯C to A⋯T. It was found that the ELG-CP method showed high efficiency (nearly linear-scaling) and high accuracy with a negligiblymore » small energy error in the total energy calculations (in the order of 10{sup −7}–10{sup −8} hartree/atom) as compared with the conventional method during the counterpoise treatment. Furthermore, the magnitude of the BSSE was found to be ca. −290 kcal/mol for the calculation of a DNA model with 21 base pairs. This emphasizes the importance of BSSE correction when a limited size basis set is used to study the DNA models and compare small energy differences between them. In this work, we quantitatively estimated the inter-strands interaction energy for each possible step in the transition process from G⋯C to A⋯T by the ELG-CP method. It was found that the base pair replacement in the process only affects the interaction energy for a limited area around the mismatch position with a few adjacent base pairs. From the interaction energy point of view, our results showed that a base pair sliding mechanism possibly occurs after the alkylation of guanine to gain the maximum possible number of hydrogen bonds between the bases. In addition, the steps leading to the A⋯T replacement accompanied with replications were found to be unfavorable processes corresponding to ca. 10 kcal/mol loss in stabilization energy. The present study indicated that the ELG-CP method is promising for performing effective interaction energy analyses in biosystems.« less

Quantum-mechanical analysis of the energetic contributions to π stacking in nucleic acids versus rise, twist, and slide.

PubMed

Parker, Trent M; Hohenstein, Edward G; Parrish, Robert M; Hud, Nicholas V; Sherrill, C David

2013-01-30

Symmetry-adapted perturbation theory (SAPT) is applied to pairs of hydrogen-bonded nucleobases to obtain the energetic components of base stacking (electrostatic, exchange-repulsion, induction/polarization, and London dispersion interactions) and how they vary as a function of the helical parameters Rise, Twist, and Slide. Computed average values of Rise and Twist agree well with experimental data for B-form DNA from the Nucleic Acids Database, even though the model computations omitted the backbone atoms (suggesting that the backbone in B-form DNA is compatible with having the bases adopt their ideal stacking geometries). London dispersion forces are the most important attractive component in base stacking, followed by electrostatic interactions. At values of Rise typical of those in DNA (3.36 Å), the electrostatic contribution is nearly always attractive, providing further evidence for the importance of charge-penetration effects in π-π interactions (a term neglected in classical force fields). Comparison of the computed stacking energies with those from model complexes made of the "parent" nucleobases purine and 2-pyrimidone indicates that chemical substituents in DNA and RNA account for 20-40% of the base-stacking energy. A lack of correspondence between the SAPT results and experiment for Slide in RNA base-pair steps suggests that the backbone plays a larger role in determining stacking geometries in RNA than in B-form DNA. In comparisons of base-pair steps with thymine versus uracil, the thymine methyl group tends to enhance the strength of the stacking interaction through a combination of dispersion and electrosatic interactions.

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

Two-Way Gene Interaction From Microarray Data Based on Correlation Methods.

PubMed

Alavi Majd, Hamid; Talebi, Atefeh; Gilany, Kambiz; Khayyer, Nasibeh

2016-06-01

Gene networks have generated a massive explosion in the development of high-throughput techniques for monitoring various aspects of gene activity. Networks offer a natural way to model interactions between genes, and extracting gene network information from high-throughput genomic data is an important and difficult task. The purpose of this study is to construct a two-way gene network based on parametric and nonparametric correlation coefficients. The first step in constructing a Gene Co-expression Network is to score all pairs of gene vectors. The second step is to select a score threshold and connect all gene pairs whose scores exceed this value. In the foundation-application study, we constructed two-way gene networks using nonparametric methods, such as Spearman's rank correlation coefficient and Blomqvist's measure, and compared them with Pearson's correlation coefficient. We surveyed six genes of venous thrombosis disease, made a matrix entry representing the score for the corresponding gene pair, and obtained two-way interactions using Pearson's correlation, Spearman's rank correlation, and Blomqvist's coefficient. Finally, these methods were compared with Cytoscape, based on BIND, and Gene Ontology, based on molecular function visual methods; R software version 3.2 and Bioconductor were used to perform these methods. Based on the Pearson and Spearman correlations, the results were the same and were confirmed by Cytoscape and GO visual methods; however, Blomqvist's coefficient was not confirmed by visual methods. Some results of the correlation coefficients are not the same with visualization. The reason may be due to the small number of data.

A Bulky Rhodium Complex Bound to an Adenosine-Adenosine DNA Mismatch: General Architecture of the Metalloinsertion Binding Mode†

PubMed Central

Zeglis, Brian M.; Pierre, Valérie C.; Kaiser, Jens T.; Barton, Jacqueline K.

2009-01-01

Two crystal structures are determined for Δ-Rh(bpy)2(chrysi)3+ (chrysi = 5,6-chrysenequinone diimine) bound to the oligonucleotide duplex 5′-CGGAAATTACCG-3′ containing two adenosine-adenosine mismatches (italics) through metalloinsertion. Diffraction quality crystals with two different space groups (P3221 and P43212) were obtained under very similar crystallization conditions. In both structures, the bulky rhodium complex inserts into the two mismatched sites from the minor groove side, ejecting the mismatched bases into the major groove. The conformational changes are localized to the mismatched site; the metal complex replaces the mismatched base pair without an increase in base pair rise. The expansive metal complex is accommodated in the duplex by a slight opening in the phosphodiester backbone; all sugars retain a C2′-endo puckering, and flanking base pairs neither stretch nor shear. The structures differ, however, in that in one of the structures, an additional metal complex is bound by intercalation from the major groove at the central 5′-AT-3′ step. We conclude that this additional metal complex is intercalated into this central step because of crystal packing forces. The structures described here of Δ-Rh(bpy)2(chrysi)3+ bound to thermodynamically destabilized AA mismatches share critical features with binding by metalloinsertion in two other oligonucleotides containing different single base mismatches. These results underscore the generality of the metalloinsertion as a new mode of non-covalent binding by small molecules with a DNA duplex. PMID:19374348

The semantic distance task: Quantifying semantic distance with semantic network path length.

PubMed

Kenett, Yoed N; Levi, Effi; Anaki, David; Faust, Miriam

2017-09-01

Semantic distance is a determining factor in cognitive processes, such as semantic priming, operating upon semantic memory. The main computational approach to compute semantic distance is through latent semantic analysis (LSA). However, objections have been raised against this approach, mainly in its failure at predicting semantic priming. We propose a novel approach to computing semantic distance, based on network science methodology. Path length in a semantic network represents the amount of steps needed to traverse from 1 word in the network to the other. We examine whether path length can be used as a measure of semantic distance, by investigating how path length affect performance in a semantic relatedness judgment task and recall from memory. Our results show a differential effect on performance: Up to 4 steps separating between word-pairs, participants exhibit an increase in reaction time (RT) and decrease in the percentage of word-pairs judged as related. From 4 steps onward, participants exhibit a significant decrease in RT and the word-pairs are dominantly judged as unrelated. Furthermore, we show that as path length between word-pairs increases, success in free- and cued-recall decreases. Finally, we demonstrate how our measure outperforms computational methods measuring semantic distance (LSA and positive pointwise mutual information) in predicting participants RT and subjective judgments of semantic strength. Thus, we provide a computational alternative to computing semantic distance. Furthermore, this approach addresses key issues in cognitive theory, namely the breadth of the spreading activation process and the effect of semantic distance on memory retrieval. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Correlative feature analysis on FFDM

PubMed Central

Yuan, Yading; Giger, Maryellen L.; Li, Hui; Sennett, Charlene

2008-01-01

Identifying the corresponding images of a lesion in different views is an essential step in improving the diagnostic ability of both radiologists and computer-aided diagnosis (CAD) systems. Because of the nonrigidity of the breasts and the 2D projective property of mammograms, this task is not trivial. In this pilot study, we present a computerized framework that differentiates between corresponding images of the same lesion in different views and noncorresponding images, i.e., images of different lesions. A dual-stage segmentation method, which employs an initial radial gradient index (RGI) based segmentation and an active contour model, is applied to extract mass lesions from the surrounding parenchyma. Then various lesion features are automatically extracted from each of the two views of each lesion to quantify the characteristics of density, size, texture and the neighborhood of the lesion, as well as its distance to the nipple. A two-step scheme is employed to estimate the probability that the two lesion images from different mammographic views are of the same physical lesion. In the first step, a correspondence metric for each pairwise feature is estimated by a Bayesian artificial neural network (BANN). Then, these pairwise correspondence metrics are combined using another BANN to yield an overall probability of correspondence. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the individual features and the selected feature subset in the task of distinguishing corresponding pairs from noncorresponding pairs. Using a FFDM database with 123 corresponding image pairs and 82 noncorresponding pairs, the distance feature yielded an area under the ROC curve (AUC) of 0.81±0.02 with leave-one-out (by physical lesion) evaluation, and the feature metric subset, which included distance, gradient texture, and ROI-based correlation, yielded an AUC of 0.87±0.02. The improvement by using multiple feature metrics was statistically significant compared to single feature performance. PMID:19175108

Airborne Lidar Measurements of Atmospheric Pressure Made Using the Oxygen A-Band

NASA Technical Reports Server (NTRS)

Riris, Haris; Rodriquez, Michael; Allan, Graham R.; Hasselbrack, William E.; Stephen, Mark A.; Abshire, James B.

2011-01-01

We report on airborne measurements of atmospheric pressure using a fiber-laser based lidar operating in the oxygen A-band near 765 nm and the integrated path differential absorption measurement technique. Our lidar uses fiber optic technology and non-linear optics to generate tunable laser radiation at 765 nm, which overlaps an absorption line pair in the Oxygen A-band. We use a pulsed time resolved technique, which rapidly steps the laser wavelength across the absorption line pair, a 20 cm telescope and photon counting detector to measure Oxygen concentrations.

Using a Fluorescent Cytosine Analogue tC[superscript o] To Probe the Effect of the Y567 to Ala Substitution on the Preinsertion Steps of dNMP Incorporation by RB69 DNA Polymerase

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

Xia, Shuangluo; Beckman, Jeff; Wang, Jimin

2012-10-10

Residues in the nascent base pair binding pocket (NBP) of bacteriophage RB69 DNA polymerase (RB69pol) are responsible for base discrimination. Replacing Tyr567 with Ala leads to greater flexibility in the NBP, increasing the probability of misincorporation. We used the fluorescent cytosine analogue, 1,3-diaza-2-oxophenoxazine (tC{sup o}), to identify preinsertion step(s) altered by NBP flexibility. When tC{sup o} is the templating base in a wild-type (wt) RB69pol ternary complex, its fluorescence is quenched only in the presence of dGTP. However, with the RB69pol Y567A mutant, the fluorescence of tC{sup o} is also quenched in the presence of dATP. We determined the crystalmore » structure of the dATP/tC{sup o}-containing ternary complex of the RB69pol Y567A mutant at 1.9 {angstrom} resolution and found that the incoming dATP formed two hydrogen bonds with an imino-tautomerized form of tC{sup o}. Stabilization of the dATP/tC{sup o} base pair involved movement of the tC{sup o} backbone sugar into the DNA minor groove and required tilting of the tC{sup o} tricyclic ring to prevent a steric clash with L561. This structure, together with the pre-steady-state kinetic parameters and dNTP binding affinity, estimated from equilibrium fluorescence titrations, suggested that the flexibility of the NBP, provided by the Y567 to Ala substitution, led to a more favorable forward isomerization step resulting in an increase in dNTP binding affinity.« less

Small Molecule Activation by Intermolecular Zr(IV)-Phosphine Frustrated Lewis Pairs.

PubMed

Metters, Owen J; Forrest, Sebastian J K; Sparkes, Hazel A; Manners, Ian; Wass, Duncan F

2016-02-17

We report intermolecular transition metal frustrated Lewis pairs (FLPs) based on zirconocene aryloxide and phosphine moieties that exhibit a broad range of small molecule activation chemistry that has previously been the preserve of only intramolecular pairs. Reactions with D2, CO2, THF, and PhCCH are reported. By contrast with previous intramolecular examples, these systems allow facile access to a variety of steric and electronic characteristics at the Lewis acidic and Lewis basic components, with the three-step syntheses of 10 new intermolecular transition metal FLPs being reported. Systematic variation to the phosphine Lewis base is used to unravel steric considerations, with the surprising conclusion that phosphines with relatively small Tolman steric parameters not only give highly reactive FLPs but are often seen to have the highest selectivity for the desired product. DOSY NMR spectroscopic studies on these systems reveal for the first time the nature of the Lewis acid/Lewis base interactions in transition metal FLPs of this type.

The Satellite Test of the Equivalence Principle (STEP)

NASA Technical Reports Server (NTRS)

2004-01-01

STEP will carry concentric test masses to Earth orbit to test a fundamental assumption underlying Einstein's theory of general relativity: that gravitational mass is equivalent to inertial mass. STEP is a 21st-century version of the test that Galileo is said to have performed by dropping a carnon ball and a musket ball simultaneously from the top of the Leaning Tower of Pisa to compare their accelerations. During the STEP experiment, four pairs of test masses will be falling around the Earth, and their accelerations will be measured by superconducting quantum interference devices (SQUIDS). The extended time sensitivity of the instruments will allow the measurements to be a million times more accurate than those made in modern ground-based tests.

Statistical deprojection of galaxy pairs

NASA Astrophysics Data System (ADS)

Nottale, Laurent; Chamaraux, Pierre

2018-06-01

Aims: The purpose of the present paper is to provide methods of statistical analysis of the physical properties of galaxy pairs. We perform this study to apply it later to catalogs of isolated pairs of galaxies, especially two new catalogs we recently constructed that contain ≈1000 and ≈13 000 pairs, respectively. We are particularly interested by the dynamics of those pairs, including the determination of their masses. Methods: We could not compute the dynamical parameters directly since the necessary data are incomplete. Indeed, we only have at our disposal one component of the intervelocity between the members, namely along the line of sight, and two components of their interdistance, i.e., the projection on the sky-plane. Moreover, we know only one point of each galaxy orbit. Hence we need statistical methods to find the probability distribution of 3D interdistances and 3D intervelocities from their projections; we designed those methods under the term deprojection. Results: We proceed in two steps to determine and use the deprojection methods. First we derive the probability distributions expected for the various relevant projected quantities, namely intervelocity vz, interdistance rp, their ratio, and the product rp v_z^2, which is involved in mass determination. In a second step, we propose various methods of deprojection of those parameters based on the previous analysis. We start from a histogram of the projected data and we apply inversion formulae to obtain the deprojected distributions; lastly, we test the methods by numerical simulations, which also allow us to determine the uncertainties involved.

Highly efficient hyperentanglement concentration with two steps assisted by quantum swap gates.

PubMed

Ren, Bao-Cang; Long, Gui Lu

2015-11-10

We present a two-step hyperentanglement concentration protocol (hyper-ECP) for polarization-spatial hyperentangled Bell states based on the high-capacity character of hyperentanglement resorting to the swap gates, which is used to obtain maximally hyperentangled states from partially hyperentangled pure states in long-distance quantum communication. The swap gate, which is constructed with the giant optical circular birefringence (GOCB) of a diamond nitrogen-vacancy (NV) center embedded in a photonic crystal cavity, can be used to transfer the information in one degree of freedom (DOF) between photon systems. By transferring the useful information between hyperentangled photon pairs, more photon pairs in maximally hyperentangled state can be obtained in our hyper-ECP, and the success probability of the hyper-ECP is greatly improved. Moreover, we show that the high-fidelity quantum gate operations can be achieved by mapping the infidelities to heralded losses even in the weak coupling regime.

Highly efficient hyperentanglement concentration with two steps assisted by quantum swap gates

PubMed Central

Ren, Bao-Cang; Long, Gui Lu

2015-01-01

We present a two-step hyperentanglement concentration protocol (hyper-ECP) for polarization-spatial hyperentangled Bell states based on the high-capacity character of hyperentanglement resorting to the swap gates, which is used to obtain maximally hyperentangled states from partially hyperentangled pure states in long-distance quantum communication. The swap gate, which is constructed with the giant optical circular birefringence (GOCB) of a diamond nitrogen-vacancy (NV) center embedded in a photonic crystal cavity, can be used to transfer the information in one degree of freedom (DOF) between photon systems. By transferring the useful information between hyperentangled photon pairs, more photon pairs in maximally hyperentangled state can be obtained in our hyper-ECP, and the success probability of the hyper-ECP is greatly improved. Moreover, we show that the high-fidelity quantum gate operations can be achieved by mapping the infidelities to heralded losses even in the weak coupling regime. PMID:26552898

Interobserver Agreement in Clinical Grading of Vitreous Haze Using Alternative Grading Scales

PubMed Central

Hornbeak, Dana M; Payal, Abhishek; Pistilli, Maxwell; Biswas, Jyotirmay; Ganesh, Sudha K; Gupta, Vishali; Rathinam, Sivakumar R; Davis, Janet L; Kempen, John H

2014-01-01

Purpose To evaluate the reliability of clinical grading of vitreous haze using a new 9-step ordinal scale vs. the existing 6-step ordinal scale. Design Evaluation of Diagnostic Test (interobserver agreement study). Participants 119 consecutive patients (204 uveitic eyes) presenting for uveitis subspecialty care on the study day at one of three large uveitis centers. Methods Five pairs of uveitis specialists clinically graded vitreous haze in the same eyes, one after the other using the same equipment, using the 6- and 9-step scales. Main Outcome Measures Agreement in vitreous haze grade between each pair of specialists was evaluated by the κ statistic (exact agreement and agreement within one or two grades). Results The scales correlated well (Spearman’s ρ=0.84). Exact agreement was modest using both the 6-step and 9-step scales: average κ=0.46 (range 0.28–0.81) and κ=0.40 (range 0.15–0.63), respectively. Within-1-grade agreement was slightly more favorable for the scale with fewer steps, but values were excellent for both scales: κ=0.75 (range 0.66–0.96) and κ=0.62 (range 0.38–0.87), respectively. Within-2-grade agreement for the 9-step scale also was excellent [κ=0.85 (range 0.79–0.92)]. Two-fold more cases were potentially clinical trial eligible based on the 9- than the 6-step scale (p<0.001). Conclusions Both scales are sufficiently reproducible using clinical grading for clinical and research use with the appropriate threshold (a ≥2 and ≥3 step differences for the 6-step and 9-step scales respectively). The results suggest that more eyes are likely to meet eligibility criteria for trials using the 9-step scale. The 9-step scale appears to have higher reproducibility with Reading Center grading than clinical grading, suggesting Reading Center grading may be preferable for clinical trials. PMID:24697913

Generating photon pairs from a silicon microring resonator using an electronic step recovery diode for pump pulse generation

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

Savanier, Marc, E-mail: msavanier@eng.ucsd.edu; Mookherjea, Shayan, E-mail: smookherjea@eng.ucsd.edu

Generation of photon pairs from compact, manufacturable, and inexpensive silicon (Si) photonic devices at room temperature may help develop practical applications of quantum photonics. An important characteristic of photon-pair generation is the two-photon joint spectral intensity, which describes the frequency correlations of the photon pair. Recent attempts to generate a factorizable photon-pair state suitable for heralding have used short optical pump pulses from mode-locked lasers, which are much more expensive and bigger table-top or rack-sized instruments compared with the Si microchip used for generating photon pairs, and thus dominate the cost and inhibit the miniaturization of the source. Here, wemore » generate photon pairs from an Si microring resonator by using an electronic step-recovery diode to drive an electro-optic modulator which carves the pump light from a continuous-wave laser diode into pulses of the appropriate width, thus potentially eliminating the need for optical mode-locked lasers.« less

Generating photon pairs from a silicon microring resonator using an electronic step recovery diode for pump pulse generation

NASA Astrophysics Data System (ADS)

Savanier, Marc; Mookherjea, Shayan

2016-06-01

Generation of photon pairs from compact, manufacturable, and inexpensive silicon (Si) photonic devices at room temperature may help develop practical applications of quantum photonics. An important characteristic of photon-pair generation is the two-photon joint spectral intensity, which describes the frequency correlations of the photon pair. Recent attempts to generate a factorizable photon-pair state suitable for heralding have used short optical pump pulses from mode-locked lasers, which are much more expensive and bigger table-top or rack-sized instruments compared with the Si microchip used for generating photon pairs, and thus dominate the cost and inhibit the miniaturization of the source. Here, we generate photon pairs from an Si microring resonator by using an electronic step-recovery diode to drive an electro-optic modulator which carves the pump light from a continuous-wave laser diode into pulses of the appropriate width, thus potentially eliminating the need for optical mode-locked lasers.

Transition from Sign-Reversed to Sign-Preserved Cooper-Pairing Symmetry in Sulfur-Doped Iron Selenide Superconductors.

PubMed

Wang, Qisi; Park, J T; Feng, Yu; Shen, Yao; Hao, Yiqing; Pan, Bingying; Lynn, J W; Ivanov, A; Chi, Songxue; Matsuda, M; Cao, Huibo; Birgeneau, R J; Efremov, D V; Zhao, Jun

2016-05-13

An essential step toward elucidating the mechanism of superconductivity is to determine the sign or phase of the superconducting order parameter, as it is closely related to the pairing interaction. In conventional superconductors, the electron-phonon interaction induces attraction between electrons near the Fermi energy and results in a sign-preserved s-wave pairing. For high-temperature superconductors, including cuprates and iron-based superconductors, prevalent weak coupling theories suggest that the electron pairing is mediated by spin fluctuations which lead to repulsive interactions, and therefore that a sign-reversed pairing with an s_{±} or d-wave symmetry is favored. Here, by using magnetic neutron scattering, a phase sensitive probe of the superconducting gap, we report the observation of a transition from the sign-reversed to sign-preserved Cooper-pairing symmetry with insignificant changes in T_{c} in the S-doped iron selenide superconductors K_{x}Fe_{2-y}(Se_{1-z}S_{z})_{2}. We show that a rather sharp magnetic resonant mode well below the superconducting gap (2Δ) in the undoped sample (z=0) is replaced by a broad hump structure above 2Δ under 50% S doping. These results cannot be readily explained by simple spin fluctuation-exchange pairing theories and, therefore, multiple pairing channels are required to describe superconductivity in this system. Our findings may also yield a simple explanation for the sometimes contradictory data on the sign of the superconducting order parameter in iron-based materials.

Compromised Structures: Verbal Descriptions of Mechanism Diagrams

ERIC Educational Resources Information Center

Bhattacharyya, Gautam; Harris, Michael S.

2018-01-01

We report our research of seven pairs of students enrolled in the second semester of sophomore-level organic chemistry as they attempted to describe (in their own words) and draw, respectively, three electron-pushing diagrams of three-step reaction mechanisms. The tasks' objective was to accurately reproduce the diagrams based solely on the…

Two-Way Gene Interaction From Microarray Data Based on Correlation Methods

PubMed Central

Alavi Majd, Hamid; Talebi, Atefeh; Gilany, Kambiz; Khayyer, Nasibeh

2016-01-01

Background Gene networks have generated a massive explosion in the development of high-throughput techniques for monitoring various aspects of gene activity. Networks offer a natural way to model interactions between genes, and extracting gene network information from high-throughput genomic data is an important and difficult task. Objectives The purpose of this study is to construct a two-way gene network based on parametric and nonparametric correlation coefficients. The first step in constructing a Gene Co-expression Network is to score all pairs of gene vectors. The second step is to select a score threshold and connect all gene pairs whose scores exceed this value. Materials and Methods In the foundation-application study, we constructed two-way gene networks using nonparametric methods, such as Spearman’s rank correlation coefficient and Blomqvist’s measure, and compared them with Pearson’s correlation coefficient. We surveyed six genes of venous thrombosis disease, made a matrix entry representing the score for the corresponding gene pair, and obtained two-way interactions using Pearson’s correlation, Spearman’s rank correlation, and Blomqvist’s coefficient. Finally, these methods were compared with Cytoscape, based on BIND, and Gene Ontology, based on molecular function visual methods; R software version 3.2 and Bioconductor were used to perform these methods. Results Based on the Pearson and Spearman correlations, the results were the same and were confirmed by Cytoscape and GO visual methods; however, Blomqvist’s coefficient was not confirmed by visual methods. Conclusions Some results of the correlation coefficients are not the same with visualization. The reason may be due to the small number of data. PMID:27621916

Using stepped anvils to make even insulation layers in laser-heated diamond-anvil cell samples

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

Du, Zhixue; Gu, Tingting; Dobrosavljevic, Vasilije

Here, we describe a method to make even insulation layers for high-pressure laser-heated diamond-anvil cell samples using stepped anvils. Moreover, the method works for both single-sided and double-sided laser heating using solid or fluid insulation. The stepped anvils are used as matched pairs or paired with a flat culet anvil to make gasket insulation layers and not actually used at high pressures; thus, their longevity is ensured. We also compare the radial temperature gradients and Soret diffusion of iron between self-insulating samples and samples produced with stepped anvils and find that less pronounced Soret diffusion occurs in samples with evenmore » insulation layers produced by stepped anvils.« less

Using stepped anvils to make even insulation layers in laser-heated diamond-anvil cell samples

DOE PAGES

Du, Zhixue; Gu, Tingting; Dobrosavljevic, Vasilije; ...

2015-09-01

Here, we describe a method to make even insulation layers for high-pressure laser-heated diamond-anvil cell samples using stepped anvils. Moreover, the method works for both single-sided and double-sided laser heating using solid or fluid insulation. The stepped anvils are used as matched pairs or paired with a flat culet anvil to make gasket insulation layers and not actually used at high pressures; thus, their longevity is ensured. We also compare the radial temperature gradients and Soret diffusion of iron between self-insulating samples and samples produced with stepped anvils and find that less pronounced Soret diffusion occurs in samples with evenmore » insulation layers produced by stepped anvils.« less

Sparse maps—A systematic infrastructure for reduced-scaling electronic structure methods. II. Linear scaling domain based pair natural orbital coupled cluster theory

NASA Astrophysics Data System (ADS)

Riplinger, Christoph; Pinski, Peter; Becker, Ute; Valeev, Edward F.; Neese, Frank

2016-01-01

Domain based local pair natural orbital coupled cluster theory with single-, double-, and perturbative triple excitations (DLPNO-CCSD(T)) is a highly efficient local correlation method. It is known to be accurate and robust and can be used in a black box fashion in order to obtain coupled cluster quality total energies for large molecules with several hundred atoms. While previous implementations showed near linear scaling up to a few hundred atoms, several nonlinear scaling steps limited the applicability of the method for very large systems. In this work, these limitations are overcome and a linear scaling DLPNO-CCSD(T) method for closed shell systems is reported. The new implementation is based on the concept of sparse maps that was introduced in Part I of this series [P. Pinski, C. Riplinger, E. F. Valeev, and F. Neese, J. Chem. Phys. 143, 034108 (2015)]. Using the sparse map infrastructure, all essential computational steps (integral transformation and storage, initial guess, pair natural orbital construction, amplitude iterations, triples correction) are achieved in a linear scaling fashion. In addition, a number of additional algorithmic improvements are reported that lead to significant speedups of the method. The new, linear-scaling DLPNO-CCSD(T) implementation typically is 7 times faster than the previous implementation and consumes 4 times less disk space for large three-dimensional systems. For linear systems, the performance gains and memory savings are substantially larger. Calculations with more than 20 000 basis functions and 1000 atoms are reported in this work. In all cases, the time required for the coupled cluster step is comparable to or lower than for the preceding Hartree-Fock calculation, even if this is carried out with the efficient resolution-of-the-identity and chain-of-spheres approximations. The new implementation even reduces the error in absolute correlation energies by about a factor of two, compared to the already accurate previous implementation.

Microgravity

NASA Image and Video Library

2004-04-15

STEP will carry concentric test masses to Earth orbit to test a fundamental assumption underlying Einstein's theory of general relativity: that gravitational mass is equivalent to inertial mass. STEP is a 21st-century version of the test that Galileo is said to have performed by dropping a carnon ball and a musket ball simultaneously from the top of the Leaning Tower of Pisa to compare their accelerations. During the STEP experiment, four pairs of test masses will be falling around the Earth, and their accelerations will be measured by superconducting quantum interference devices (SQUIDS). The extended time sensitivity of the instruments will allow the measurements to be a million times more accurate than those made in modern ground-based tests.

Learning the moon's phases through CL

NASA Astrophysics Data System (ADS)

Barbera, Maria

2013-04-01

This work is a CLIL experience for a class of 14-year-old students, a first grade of a Secondary school, level B1/B2. It is presented an Astronomy lesson whose topic is about the Moon's phases, a quite difficult phenomenon to visualize. Students' attention is attracted by presenting them songs and a short documentary; comprehension is made easier using both Internet-based materials and a card game using Cooperative Learning strategies through Johnsons' ' Learning Together'. The lesson consists of three steps for a total length of three hours. The teacher assigns a time limit for each activity. During the pre-task step, students' interest for present-day music is used to catch their attention and make them aware of the importance of the Moon as an inspiring subject for artistic expression such as popular or rock music. Then the students are requested to brainstorm some simple ideas of ther own about the moon. In the task step, a clear short BBC video is shown in order to stimulate students' listening and comprehension skills and an animation is proposed to help them view the moon cycle. In the post-task step, students are engaged in a card game through Johnsons' 'Learning Together'.Learners are divided into pairs and they have to cooperate to rebuild the moon's cicle as fast as they can. Then the two pairs join together to form groups of four and check their answers. The Assessor shares the group's keys with the whole class. The teacher gives feedback. The groups celebrate their success by clapping their hands and saying what they appreciated regarding their way of working together as pairs and groups.

Refined BCF-type boundary conditions for mesoscale surface step dynamics

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

Zhao, Renjie; Ackerman, David M.; Evans, James W.

Deposition on a vicinal surface with alternating rough and smooth steps is described by a solid-on-solid model with anisotropic interactions. Kinetic Monte Carlo (KMC) simulations of the model reveal step pairing in the absence of any additional step attachment barriers. We explore the description of this behavior within an analytic Burton-Cabrera-Frank (BCF)-type step dynamics treatment. Without attachment barriers, conventional kinetic coefficients for the rough and smooth steps are identical, as are the predicted step velocities for a vicinal surface with equal terrace widths. However, we determine refined kinetic coefficients from a two-dimensional discrete deposition-diffusion equation formalism which accounts for stepmore » structure. These coefficients are generally higher for rough steps than for smooth steps, reflecting a higher propensity for capture of diffusing terrace adatoms due to a higher kink density. Such refined coefficients also depend on the local environment of the step and can even become negative (corresponding to net detachment despite an excess adatom density) for a smooth step in close proximity to a rough step. Incorporation of these refined kinetic coefficients into a BCF-type step dynamics treatment recovers quantitatively the mesoscale step-pairing behavior observed in the KMC simulations.« less

Refined BCF-type boundary conditions for mesoscale surface step dynamics

DOE PAGES

Zhao, Renjie; Ackerman, David M.; Evans, James W.

2015-06-24

Deposition on a vicinal surface with alternating rough and smooth steps is described by a solid-on-solid model with anisotropic interactions. Kinetic Monte Carlo (KMC) simulations of the model reveal step pairing in the absence of any additional step attachment barriers. We explore the description of this behavior within an analytic Burton-Cabrera-Frank (BCF)-type step dynamics treatment. Without attachment barriers, conventional kinetic coefficients for the rough and smooth steps are identical, as are the predicted step velocities for a vicinal surface with equal terrace widths. However, we determine refined kinetic coefficients from a two-dimensional discrete deposition-diffusion equation formalism which accounts for stepmore » structure. These coefficients are generally higher for rough steps than for smooth steps, reflecting a higher propensity for capture of diffusing terrace adatoms due to a higher kink density. Such refined coefficients also depend on the local environment of the step and can even become negative (corresponding to net detachment despite an excess adatom density) for a smooth step in close proximity to a rough step. Incorporation of these refined kinetic coefficients into a BCF-type step dynamics treatment recovers quantitatively the mesoscale step-pairing behavior observed in the KMC simulations.« less

The formation of catalytically competent enzyme-substrate complex is not a bottleneck in lesion excision by human alkyladenine DNA glycosylase.

PubMed

Kuznetsov, N A; Kiryutin, A S; Kuznetsova, A A; Panov, M S; Barsukova, M O; Yurkovskaya, A V; Fedorova, O S

2017-04-01

Human alkyladenine DNA glycosylase (AAG) protects DNA from alkylated and deaminated purine lesions. AAG flips out the damaged nucleotide from the double helix of DNA and catalyzes the hydrolysis of the N-glycosidic bond to release the damaged base. To understand better, how the step of nucleotide eversion influences the overall catalytic process, we performed a pre-steady-state kinetic analysis of AAG interaction with specific DNA-substrates, 13-base pair duplexes containing in the 7th position 1-N6-ethenoadenine (εA), hypoxanthine (Hx), and the stable product analogue tetrahydrofuran (F). The combination of the fluorescence of tryptophan, 2-aminopurine, and 1-N6-ethenoadenine was used to record conformational changes of the enzyme and DNA during the processes of DNA lesion recognition, damaged base eversion, excision of the N-glycosidic bond, and product release. The thermal stability of the duplexes characterized by the temperature of melting, T m , and the rates of spontaneous opening of individual nucleotide base pairs were determined by NMR spectroscopy. The data show that the relative thermal stability of duplexes containing a particular base pair in position 7, (T m (F/T) < T m (εA/T) < T m (Hx/T) < T m (A/T)) correlates with the rate of reversible spontaneous opening of the base pair. However, in contrast to that, the catalytic lesion excision rate is two orders of magnitude higher for Hx-containing substrates than for substrates containing εA, proving that catalytic activity is not correlated with the stability of the damaged base pair. Our study reveals that the formation of the catalytically competent enzyme-substrate complex is not the bottleneck controlling the catalytic activity of AAG.

Analyzing ion distributions around DNA: sequence-dependence of potassium ion distributions from microsecond molecular dynamics

PubMed Central

Pasi, Marco; Maddocks, John H.; Lavery, Richard

2015-01-01

Microsecond molecular dynamics simulations of B-DNA oligomers carried out in an aqueous environment with a physiological salt concentration enable us to perform a detailed analysis of how potassium ions interact with the double helix. The oligomers studied contain all 136 distinct tetranucleotides and we are thus able to make a comprehensive analysis of base sequence effects. Using a recently developed curvilinear helicoidal coordinate method we are able to analyze the details of ion populations and densities within the major and minor grooves and in the space surrounding DNA. The results show higher ion populations than have typically been observed in earlier studies and sequence effects that go beyond the nature of individual base pairs or base pair steps. We also show that, in some special cases, ion distributions converge very slowly and, on a microsecond timescale, do not reflect the symmetry of the corresponding base sequence. PMID:25662221

Reversed-phase ion-pair liquid chromatography method for purification of duplex DNA with single base pair resolution

PubMed Central

Wysoczynski, Christina L.; Roemer, Sarah C.; Dostal, Vishantie; Barkley, Robert M.; Churchill, Mair E. A.; Malarkey, Christopher S.

2013-01-01

Obtaining quantities of highly pure duplex DNA is a bottleneck in the biophysical analysis of protein–DNA complexes. In traditional DNA purification methods, the individual cognate DNA strands are purified separately before annealing to form DNA duplexes. This approach works well for palindromic sequences, in which top and bottom strands are identical and duplex formation is typically complete. However, in cases where the DNA is non-palindromic, excess of single-stranded DNA must be removed through additional purification steps to prevent it from interfering in further experiments. Here we describe and apply a novel reversed-phase ion-pair liquid chromatography purification method for double-stranded DNA ranging in lengths from 17 to 51 bp. Both palindromic and non-palindromic DNA can be readily purified. This method has the unique ability to separate blunt double-stranded DNA from pre-attenuated (n-1, n-2, etc) synthesis products, and from DNA duplexes with single base pair overhangs. Additionally, palindromic DNA sequences with only minor differences in the central spacer sequence of the DNA can be separated, and the purified DNA is suitable for co-crystallization of protein–DNA complexes. Thus, double-stranded ion-pair liquid chromatography is a useful approach for duplex DNA purification for many applications. PMID:24013567

Evaluation of new collision-pair selection models in DSMC

NASA Astrophysics Data System (ADS)

Akhlaghi, Hassan; Roohi, Ehsan

2017-10-01

The current paper investigates new collision-pair selection procedures in a direct simulation Monte Carlo (DSMC) method. Collision partner selection based on the random procedure from nearest neighbor particles and deterministic selection of nearest neighbor particles have already been introduced as schemes that provide accurate results in a wide range of problems. In the current research, new collision-pair selections based on the time spacing and direction of the relative movement of particles are introduced and evaluated. Comparisons between the new and existing algorithms are made considering appropriate test cases including fluctuations in homogeneous gas, 2D equilibrium flow, and Fourier flow problem. Distribution functions for number of particles and collisions in cell, velocity components, and collisional parameters (collision separation, time spacing, relative velocity, and the angle between relative movements of particles) are investigated and compared with existing analytical relations for each model. The capability of each model in the prediction of the heat flux in the Fourier problem at different cell numbers, numbers of particles, and time steps is examined. For new and existing collision-pair selection schemes, the effect of an alternative formula for the number of collision-pair selections and avoiding repetitive collisions are investigated via the prediction of the Fourier heat flux. The simulation results demonstrate the advantages and weaknesses of each model in different test cases.

An atomistic mechanism study of GaN step-flow growth in vicinal m-plane orientations

DOE PAGES

Liu, Zhun; Wang, Ru-Zhi; Zapol, Peter

2016-10-12

We present elucidation of homoepitaxial growth mechanisms on vicinal non-polar surfaces of GaN that is highly important for gaining an understanding of and control thin film surface morphology and properties. Using first-principles calculations, we study the step-flow growth in m-plane GaN based on atomic row nucleation and kink propagation kinetics. Ga–N dimer adsorption onto the m-plane is energetically more favorable than that of Ga and N isolated adatoms. Therefore, we have treated the dimers as the dominant growth species attached to the step edges. By calculating the free energies of sequentially attached Ga–N dimers, we have elucidated that the a-stepmore » edge kink growth proceeds by parallel attachment rather than by across the step edge approach. We found a series of favorable configurations of kink propagation and calculated the free energy and nucleation barriers for kink evolution on five types of step edges (a, +c, -c, +a + c, and -a - c). By changing the chemical potential μGa and the excess chemical potential Δμ, the growth velocities at the five types of edges are controlled by the corresponding kink pair nucleation barrier E* in their free energy profiles. To explore the kink-flow growth instability observed at different Ga/N flux ratios, calculations of kink pairs on the incompact -c and +c-step edges are further performed to study their formation energies. Variations of these step edge morphologies with a tuned chemical environment are consistent with previous experimental observations, including stable diagonal ±a ± c-direction steps. In conclusion, our work provides a first-principles approach to explore step growth and surface morphology of the vicinal m-plane GaN, which is applicable to analyze and control the step-flow growth of other binary thin films.« less

DNA sequence alignment by microhomology sampling during homologous recombination

PubMed Central

Qi, Zhi; Redding, Sy; Lee, Ja Yil; Gibb, Bryan; Kwon, YoungHo; Niu, Hengyao; Gaines, William A.; Sung, Patrick

2015-01-01

Summary Homologous recombination (HR) mediates the exchange of genetic information between sister or homologous chromatids. During HR, members of the RecA/Rad51 family of recombinases must somehow search through vast quantities of DNA sequence to align and pair ssDNA with a homologous dsDNA template. Here we use single-molecule imaging to visualize Rad51 as it aligns and pairs homologous DNA sequences in real-time. We show that Rad51 uses a length-based recognition mechanism while interrogating dsDNA, enabling robust kinetic selection of 8-nucleotide (nt) tracts of microhomology, which kinetically confines the search to sites with a high probability of being a homologous target. Successful pairing with a 9th nucleotide coincides with an additional reduction in binding free energy and subsequent strand exchange occurs in precise 3-nt steps, reflecting the base triplet organization of the presynaptic complex. These findings provide crucial new insights into the physical and evolutionary underpinnings of DNA recombination. PMID:25684365

Inhibiting Polysulfide Shuttle in Lithium-Sulfur Batteries through Low-Ion-Pairing Salts and a Triflamide Solvent.

PubMed

Shyamsunder, Abhinandan; Beichel, Witali; Klose, Petra; Pang, Quan; Scherer, Harald; Hoffmann, Anke; Murphy, Graham K; Krossing, Ingo; Nazar, Linda F

2017-05-22

The step-change in gravimetric energy density needed for electrochemical energy storage devices to power unmanned autonomous vehicles, electric vehicles, and enable low-cost clean grid storage is unlikely to be provided by conventional lithium ion batteries. Lithium-sulfur batteries comprising lightweight elements provide a promising alternative, but the associated polysulfide shuttle in typical ether-based electrolytes generates loss in capacity and low coulombic efficiency. The first new electrolyte based on a unique combination of a relatively hydrophobic sulfonamide solvent and a low ion-pairing salt, which inhibits the polysulfide shuttle, is presented. This system behaves as a sparingly solvating electrolyte at slightly elevated temperatures, where it sustains reversible capacities as high as 1200-1500 mAh g -1 over a wide range of current density (2C-C/5, respectively) when paired with a lithium metal anode, with a coulombic efficiency of >99.7 % in the absence of LiNO 3 additive. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Featured-Based Strategy for Stereovision Matching in Sensors with Fish-Eye Lenses for Forest Environments

PubMed Central

Herrera, Pedro Javier; Pajares, Gonzalo; Guijarro, Maria; Ruz, José J.; Cruz, Jesús M.; Montes, Fernando

2009-01-01

This paper describes a novel feature-based stereovision matching process based on a pair of omnidirectional images in forest stands acquired with a stereovision sensor equipped with fish-eye lenses. The stereo analysis problem consists of the following steps: image acquisition, camera modelling, feature extraction, image matching and depth determination. Once the depths of significant points on the trees are obtained, the growing stock volume can be estimated by considering the geometrical camera modelling, which is the final goal. The key steps are feature extraction and image matching. This paper is devoted solely to these two steps. At a first stage a segmentation process extracts the trunks, which are the regions used as features, where each feature is identified through a set of attributes of properties useful for matching. In the second step the features are matched based on the application of the following four well known matching constraints, epipolar, similarity, ordering and uniqueness. The combination of the segmentation and matching processes for this specific kind of sensors make the main contribution of the paper. The method is tested with satisfactory results and compared against the human expert criterion. PMID:22303134

Classified one-step high-radix signed-digit arithmetic units

NASA Astrophysics Data System (ADS)

Cherri, Abdallah K.

1998-08-01

High-radix number systems enable higher information storage density, less complexity, fewer system components, and fewer cascaded gates and operations. A simple one-step fully parallel high-radix signed-digit arithmetic is proposed for parallel optical computing based on new joint spatial encodings. This reduces hardware requirements and improves throughput by reducing the space-bandwidth produce needed. The high-radix signed-digit arithmetic operations are based on classifying the neighboring input digit pairs into various groups to reduce the computation rules. A new joint spatial encoding technique is developed to present both the operands and the computation rules. This technique increases the spatial bandwidth product of the spatial light modulators of the system. An optical implementation of the proposed high-radix signed-digit arithmetic operations is also presented. It is shown that our one-step trinary signed-digit and quaternary signed-digit arithmetic units are much simpler and better than all previously reported high-radix signed-digit techniques.

A robust fingerprint matching algorithm based on compatibility of star structures

NASA Astrophysics Data System (ADS)

Cao, Jia; Feng, Jufu

2009-10-01

In fingerprint verification or identification systems, most minutiae-based matching algorithms suffered from the problems of non-linear distortion and missing or faking minutiae. Local structures such as triangle or k-nearest structure are widely used to reduce the impact of non-linear distortion, but are suffered from missing and faking minutiae. In our proposed method, star structure is used to present local structure. A star structure contains various number of minutiae, thus, it is more robust with missing and faking minutiae. Our method consists of four steps: 1) Constructing star structures at minutia level; 2) Computing similarity score for each structure pair, and eliminating impostor matched pairs which have the low scores. As it is generally assumed that there is only linear distortion in local area, the similarity is defined by rotation and shifting. 3) Voting for remained matched pairs according to the compatibility between them, and eliminating impostor matched pairs which gain few votes. The concept of compatibility is first introduced by Yansong Feng [4], the original definition is only based on triangles. We define the compatibility for star structures to adjust to our proposed algorithm. 4) Computing the matching score, based on the number of matched structures and their voting scores. The score also reflects the fact that, it should get higher score if minutiae match in more intensive areas. Experiments evaluated on FVC 2004 show both effectiveness and efficiency of our methods.

Synthesis and triplex forming properties of pyrimidine derivative containing extended functionality.

PubMed

Gianolio, D A; McLaughlin, L W

1999-08-01

Two pyrimidine nucleosides have been synthesized containing extended hydrogen bonding functionality. In one case the side chain is based upon semicarbazide and in the second monoacetylated carbohydrazide was employed. DNA sequences could be prepared using both analogue nucleosides in a reverse coupling protocol, and provided that the normal capping step was eliminated and that the iodine-based oxidizing solution was replaced with one based upon 10-camphorsulfonyl oxaziridine. Both derivatives exhibited moderate effects in targeting selectively C-G base pairs embedded within a polypurine target sequence.

Antimatter Production at a Potential Boundary

NASA Technical Reports Server (NTRS)

LaPointe, Michael R.; Reddy, Dhanireddy (Technical Monitor)

2001-01-01

Current antiproton production techniques rely on high-energy collisions between beam particles and target nuclei to produce particle and antiparticle pairs, but inherently low production and capture efficiencies render these techniques impractical for the cost-effective production of antimatter for space propulsion and other commercial applications. Based on Dirac's theory of the vacuum field, a new antimatter production concept is proposed in which particle-antiparticle pairs are created at the boundary of a steep potential step formed by the suppression of the local vacuum fields. Current antimatter production techniques are reviewed, followed by a description of Dirac's relativistic quantum theory of the vacuum state and corresponding solutions for particle tunneling and reflection from a potential barrier. The use of the Casimir effect to suppress local vacuum fields is presented as a possible technique for generating the sharp potential gradients required for particle-antiparticle pair creation.

Interobserver concordance of assessments of dysplasia and blast counts for the diagnosis of patients with cytopenia: From the Japanese central review study.

PubMed

Matsuda, Akira; Kawabata, Hiroshi; Tohyama, Kaoru; Maeda, Tomoya; Araseki, Kayano; Hata, Tomoko; Suzuki, Takahiro; Kayano, Hidekazu; Shimbo, Kei; Usuki, Kensuke; Chiba, Shigeru; Ishikawa, Takayuki; Arima, Nobuyoshi; Nohgawa, Masaharu; Ohta, Akiko; Miyazaki, Yasushi; Nakao, Sinnji; Ozawa, Keiya; Arai, Shunya; Kurokawa, Mineo; Mitani, Kinuko; Takaori-Kondo, Akifumi

2018-06-07

The diagnosis of myelodysplastic syndromes (MDS) is based on morphology and cytogenetics. However, limited information is currently available on the interobserver concordance of the assessment of dysplastic lineages (<10% or ≥10% in bone marrow (BM)). The revised International Prognostic Scoring System (IPSS-R) described a new threshold (2%) for BM blasts. However, the interobserver concordance of the categories (0-≤2% and >2-<5%) has limited data. The purpose of the present study was to investigate the assessment of dysplastic lineages and IPSS-R reproducibility. Our study was divided into two Steps. In each Step, the microscopic examinations were performed separately by two morphologists. Regarding the category of BM blasts ≤2% and >2-<5%, interobserver agreement was more than 'moderate' in all pairs (kappa test: 0.43-0.90). Regarding dysgranulopoiesis (dysG) and dyserythropoiesis (dysE) in BM, interobserver agreement was more than 'moderate' in all pairs (kappa test, dysG: 0.45-0.96, dysE: 0.45-0.81). Regarding the category of dysmegakaryopoiesis (dysMgk) in BM, interobserver agreement was more than moderate in 4 out of 5 pairs (kappa test: 0.58-1.00), and was fair for one pair (kappa test: 0.37). We consider that high interobserver concordance may be possible for the BM blast cell count (≤2% or >2-<5%) and dysplasia (<10% or ≥10%) of each lineage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Titi Monkeys as a Novel Non-Human Primate Model for the Neurobiology of Pair Bonding


PubMed Central

Bales, Karen L.; Arias del Razo, Rocío; Conklin, Quinn A.; Hartman, Sarah; Mayer, Heather S.; Rogers, Forrest D.; Simmons, Trenton C.; Smith, Leigh K.; Williams, Alexia; Williams, Donald R.; Witczak, Lynea R.; Wright, Emily C.

2017-01-01

It is now widely recognized that social bonds are critical to human health and well-being. One of the most important social bonds is the attachment relationship between two adults, known as the pair bond. The pair bond involves many characteristics that are inextricably linked to quality of health, including providing a secure psychological base and acting as a social buffer against stress. The majority of our knowledge about the neurobiology of pair bonding comes from studies of a socially monogamous rodent, the prairie vole (Microtus ochrogaster), and from human imaging studies, which inherently lack control. Here, we first review what is known of the neurobiology of pair bonding from humans and prairie voles. We then present a summary of the studies we have conducted in titi monkeys (Callicebus cupreus)—a species of socially monogamous New World primates. Finally, we construct a neural model based on the location of neuropeptide receptors in the titi monkey brain, as well as the location of neural changes in our imaging studies, with some basic assumptions based on the prairie vole model. In this model, we emphasize the role of visual mating stimuli as well as contributions of the dopaminergic reward system and a strong role for the lateral septum. This model represents an important step in understanding the neurobiology of social bonds in non-human primates, which will in turn facilitate a better understanding of these mechanisms in humans. PMID:28955178

Chemoselective Polymerization of Polar Divinyl Monomers with Rare-Earth/Phosphine Lewis Pairs.

PubMed

Xu, Pengfei; Wu, Lei; Dong, Liqiu; Xu, Xin

2018-02-08

This work reports the chemoselective polymerization of polar divinyl monomers, including allyl methacrylate (AMA), vinyl methacrylate (VMA), and 4-vinylbenzyl methacrylate (VBMA), by using simple Lewis pairs comprised of homoleptic rare-earth (RE) aryloxide complexes RE(OAr)₃ (RE = Sc ( 1 ), Y ( 2 ), Sm ( 3 ), La ( 4 ), Ar = 2,6- t Bu₂C₆H₃) and phosphines PR₃ (R = Ph, Cy, Et, Me). Catalytic activities of polymerizations relied heavily upon the cooperation of Lewis acid and Lewis base components. The produced polymers were soluble in common organic solvents and often had a narrow molecular weight distribution. A highly syndiotactic poly(allyl methacrylate) (PAMA) with rr ~88% could be obtained by the scandium complex 1 /PEt₃ pair at -30 °C. In the case of poly(4-vinylbenzyl methacrylate) (PVBMA), it could be post-functionalized with PhCH₂SH. Mechanistic study, including the isolation of the zwitterionic active species and the end-group analysis, revealed that the frustrated Lewis pair (FLP)-type addition was the initiating step in the polymerization.

3D road marking reconstruction from street-level calibrated stereo pairs

NASA Astrophysics Data System (ADS)

Soheilian, Bahman; Paparoditis, Nicolas; Boldo, Didier

This paper presents an automatic approach to road marking reconstruction using stereo pairs acquired by a mobile mapping system in a dense urban area. Two types of road markings were studied: zebra crossings (crosswalks) and dashed lines. These two types of road markings consist of strips having known shape and size. These geometric specifications are used to constrain the recognition of strips. In both cases (i.e. zebra crossings and dashed lines), the reconstruction method consists of three main steps. The first step extracts edge points from the left and right images of a stereo pair and computes 3D linked edges using a matching process. The second step comprises a filtering process that uses the known geometric specifications of road marking objects. The goal is to preserve linked edges that can plausibly belong to road markings and to filter others out. The final step uses the remaining linked edges to fit a theoretical model to the data. The method developed has been used for processing a large number of images. Road markings are successfully and precisely reconstructed in dense urban areas under real traffic conditions.

Specific effects of background electrolytes on the kinetics of step propagation during calcite growth

NASA Astrophysics Data System (ADS)

Ruiz-Agudo, Encarnación; Putnis, Christine V.; Wang, Lijun; Putnis, Andrew

2011-07-01

The mechanisms by which background electrolytes modify the kinetics of non-equivalent step propagation during calcite growth were investigated using Atomic Force Microscopy (AFM), at constant driving force and solution stoichiometry. Our results suggest that the acute step spreading rate is controlled by kink-site nucleation and, ultimately, by the dehydration of surface sites, while the velocity of obtuse step advancement is mainly determined by hydration of calcium ions in solution. According to our results, kink nucleation at acute steps could be promoted by carbonate-assisted calcium attachment. The different sensitivity of obtuse and acute step propagation kinetics to cation and surface hydration could be the origin of the reversed geometries of calcite growth hillocks (i.e., rate of obtuse step spreading < rate of acute step spreading) observed in concentrated (ionic strength, IS = 0.1) KCl and CsCl solutions. At low IS (0.02), ion-specific effects seem to be mainly associated with changes in the solvation environment of calcium ions in solution. With increasing electrolyte concentration, the stabilization of surface water by weakly paired salts appears to become increasingly important in determining step spreading rate. At high ionic strength (IS = 0.1), overall calcite growth rates increased with increasing hydration of calcium in solution (i.e., decreasing ion pairing of background electrolytes for sodium-bearing salts) and with decreasing hydration of the carbonate surface site (i.e., increasing ion pairing for chloride-bearing salts). Changes in growth hillock morphology were observed in the presence of Li +, F - and SO42-, and can be interpreted as the result of the stabilization of polar surfaces due to increased ion hydration. These results increase our ability to predict crystal reactivity in natural fluids which contain significant amounts of solutes.

Labeling proteins on live mammalian cells using click chemistry.

PubMed

Nikić, Ivana; Kang, Jun Hee; Girona, Gemma Estrada; Aramburu, Iker Valle; Lemke, Edward A

2015-05-01

We describe a protocol for the rapid labeling of cell-surface proteins in living mammalian cells using click chemistry. The labeling method is based on strain-promoted alkyne-azide cycloaddition (SPAAC) and strain-promoted inverse-electron-demand Diels-Alder cycloaddition (SPIEDAC) reactions, in which noncanonical amino acids (ncAAs) bearing ring-strained alkynes or alkenes react, respectively, with dyes containing azide or tetrazine groups. To introduce ncAAs site specifically into a protein of interest (POI), we use genetic code expansion technology. The protocol can be described as comprising two steps. In the first step, an Amber stop codon is introduced--by site-directed mutagenesis--at the desired site on the gene encoding the POI. This plasmid is then transfected into mammalian cells, along with another plasmid that encodes an aminoacyl-tRNA synthetase/tRNA (RS/tRNA) pair that is orthogonal to the host's translational machinery. In the presence of the ncAA, the orthogonal RS/tRNA pair specifically suppresses the Amber codon by incorporating the ncAA into the polypeptide chain of the POI. In the second step, the expressed POI is labeled with a suitably reactive dye derivative that is directly supplied to the growth medium. We provide a detailed protocol for using commercially available ncAAs and dyes for labeling the insulin receptor, and we discuss the optimal surface-labeling conditions and the limitations of labeling living mammalian cells. The protocol involves an initial cloning step that can take 4-7 d, followed by the described transfections and labeling reaction steps, which can take 3-4 d.

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.

Evaluative Priming in the Pronunciation Task.

PubMed

Klauer, Karl Christoph; Becker, Manuel; Spruyt, Adriaan

2016-01-01

We replicated and extended a study by Spruyt and Hermans (2008) in which picture primes engendered an evaluative-priming effect on the pronunciation of target words. As preliminary steps, we assessed data reproducibility of the original study, conducted Pilot Study I to identify highly semantically related prime-target pairs, reanalyzed the original data excluding such pairs, conducted Pilot Study II to demonstrate that we can replicate traditional associative priming effects in the pronunciation task, and conducted Pilot Study III to generate relatively unrelated sets of prime pictures and target words. The main study comprised three between-participants conditions: (1) a close replication of the original study, (2) the same condition excluding highly related prime-target pairs, and (3) a condition based on the relatively unrelated sets of prime pictures and target words developed in Pilot Study III. There was little evidence for an evaluative priming effect independent of semantic relatedness.

Evaluation of Several Two-Step Scoring Functions Based on Linear Interaction Energy, Effective Ligand Size, and Empirical Pair Potentials for Prediction of Protein-Ligand Binding Geometry and Free Energy

PubMed Central

Rahaman, Obaidur; Estrada, Trilce P.; Doren, Douglas J.; Taufer, Michela; Brooks, Charles L.; Armen, Roger S.

2011-01-01

The performance of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for “step 2 discrimination” were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only “interacting” ligand atoms as the “effective size” of the ligand, and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and five-fold cross validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new dataset (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ dataset where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of predicted ligand efficiencies is most relevant to real-world drug design efforts. PMID:21644546

Evaluation of several two-step scoring functions based on linear interaction energy, effective ligand size, and empirical pair potentials for prediction of protein-ligand binding geometry and free energy.

PubMed

Rahaman, Obaidur; Estrada, Trilce P; Doren, Douglas J; Taufer, Michela; Brooks, Charles L; Armen, Roger S

2011-09-26

The performances of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for "step 2 discrimination" were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only "interacting" ligand atoms as the "effective size" of the ligand and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and 5-fold cross-validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new data set (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ data set where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of predicted ligand efficiencies is most relevant to real-world drug design efforts.

Multilayer checkpoints for microRNA authenticity during RISC assembly.

PubMed

Kawamata, Tomoko; Yoda, Mayuko; Tomari, Yukihide

2011-09-01

MicroRNAs (miRNAs) function through the RNA-induced silencing complex (RISC), which contains an Argonaute (Ago) protein at the core. RISC assembly follows a two-step pathway: miRNA/miRNA* duplex loading into Ago, and separation of the two strands within Ago. Here we show that the 5' phosphate of the miRNA strand is essential for duplex loading into Ago, whereas the preferred 5' nucleotide of the miRNA strand and the base-pairing status in the seed region and the middle of the 3' region function as additive anchors to Ago. Consequently, the miRNA authenticity is inspected at multiple steps during RISC assembly.

A Method to Predict the Structure and Stability of RNA/RNA Complexes.

PubMed

Xu, Xiaojun; Chen, Shi-Jie

2016-01-01

RNA/RNA interactions are essential for genomic RNA dimerization and regulation of gene expression. Intermolecular loop-loop base pairing is a widespread and functionally important tertiary structure motif in RNA machinery. However, computational prediction of intermolecular loop-loop base pairing is challenged by the entropy and free energy calculation due to the conformational constraint and the intermolecular interactions. In this chapter, we describe a recently developed statistical mechanics-based method for the prediction of RNA/RNA complex structures and stabilities. The method is based on the virtual bond RNA folding model (Vfold). The main emphasis in the method is placed on the evaluation of the entropy and free energy for the loops, especially tertiary kissing loops. The method also uses recursive partition function calculations and two-step screening algorithm for large, complicated structures of RNA/RNA complexes. As case studies, we use the HIV-1 Mal dimer and the siRNA/HIV-1 mutant (T4) to illustrate the method.

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.

Kinetic mechanism and fidelity of nick sealing by Escherichia coli NAD+-dependent DNA ligase (LigA)

PubMed Central

Chauleau, Mathieu; Shuman, Stewart

2016-01-01

Escherichia coli DNA ligase (EcoLigA) repairs 3′-OH/5′-PO4 nicks in duplex DNA via reaction of LigA with NAD+ to form a covalent LigA-(lysyl-Nζ)–AMP intermediate (step 1); transfer of AMP to the nick 5′-PO4 to form an AppDNA intermediate (step 2); and attack of the nick 3′-OH on AppDNA to form a 3′-5′ phosphodiester (step 3). A distinctive feature of EcoLigA is its stimulation by ammonium ion. Here we used rapid mix-quench methods to analyze the kinetic mechanism of single-turnover nick sealing by EcoLigA–AMP. For substrates with correctly base-paired 3′-OH/5′-PO4 nicks, kstep2 was fast (6.8–27 s−1) and similar to kstep3 (8.3–42 s−1). Absent ammonium, kstep2 and kstep3 were 48-fold and 16-fold slower, respectively. EcoLigA was exquisitely sensitive to 3′-OH base mispairs and 3′ N:abasic lesions, which elicited 1000- to >20000-fold decrements in kstep2. The exception was the non-canonical 3′ A:oxoG configuration, which EcoLigA accepted as correctly paired for rapid sealing. These results underscore: (i) how EcoLigA requires proper positioning of the nick 3′ nucleoside for catalysis of 5′ adenylylation; and (ii) EcoLigA's potential to embed mutations during the repair of oxidative damage. EcoLigA was relatively tolerant of 5′-phosphate base mispairs and 5′ N:abasic lesions. PMID:26857547

Unnatural substrates reveal the importance of 8-oxoguanine for in vivo mismatch repair by MutY

PubMed Central

Livingston, Alison L.; O’Shea, Valerie L.; Kim, Taewoo; Kool, Eric T.; David, Sheila S.

2009-01-01

Escherchia coli MutY plays an important role in preventing mutations associated with the oxidative lesion 7,8-dihydro-8-oxo-2′-deoxyguanosine (OG) in DNA by excising adenines from OG:A mismatches as the first step of base excision repair. To determine the importance of specific steps in the base pair recognition and base removal process of MutY, we have evaluated the effects of modifications of the OG:A substrate on the kinetics of base removal, mismatch affinity and repair to G:C in an Escherchia coli-based assay. Surprisingly, adenine modification was tolerated in the cellular assay, while modification of OG results in minimal cellular repair. High affinity for the mismatch and efficient base removal require the presence of OG. Taken together, these results suggest that the presence of OG is a critical feature for MutY to locate OG:A mismatches and select the appropriate adenines for excision to initiate repair in vivo prior to replication. PMID:18026095

DNA dynamics in aqueous solution: opening the double helix

NASA Technical Reports Server (NTRS)

Pohorille, A.; Ross, W. S.; Tinoco, I. Jr; MacElroy, R. D. (Principal Investigator)

1990-01-01

The opening of a DNA base pair is a simple reaction that is a prerequisite for replication, transcription, and other vital biological functions. Understanding the molecular mechanisms of biological reactions is crucial for predicting and, ultimately, controlling them. Realistic computer simulations of the reactions can provide the needed understanding. To model even the simplest reaction in aqueous solution requires hundreds of hours of supercomputing time. We have used molecular dynamics techniques to simulate fraying of the ends of a six base pair double strand of DNA, [TCGCGA]2, where the four bases of DNA are denoted by T (thymine), C (cytosine), G (guanine), and A (adenine), and to estimate the free energy barrier to this process. The calculations, in which the DNA was surrounded by 2,594 water molecules, required 50 hours of CRAY-2 CPU time for every simulated 100 picoseconds. A free energy barrier to fraying, which is mainly characterized by the movement of adenine away from thymine into aqueous environment, was estimated to be 4 kcal/mol. Another fraying pathway, which leads to stacking between terminal adenine and thymine, was also observed. These detailed pictures of the motions and energetics of DNA base pair opening in water are a first step toward understanding how DNA will interact with any molecule.

Locating pairs of comparable study areas...new system developed

Treesearch

Raymond D. Ratliff; Jack N. Reppert

1966-01-01

A new system developed for locating pairs of comparable areas consists of three steps: (a) characterizing each of two areas according to 18 site factors and soil properties, (b) rating each pair of characteristics for comparability, and (c) rating the two areas for comparability by using the individual ratings as the basis. Two areas scoring 85 or more points out of a...

An efficient and near linear scaling pair natural orbital based local coupled cluster method.

PubMed

Riplinger, Christoph; Neese, Frank

2013-01-21

In previous publications, it was shown that an efficient local coupled cluster method with single- and double excitations can be based on the concept of pair natural orbitals (PNOs) [F. Neese, A. Hansen, and D. G. Liakos, J. Chem. Phys. 131, 064103 (2009)]. The resulting local pair natural orbital-coupled-cluster single double (LPNO-CCSD) method has since been proven to be highly reliable and efficient. For large molecules, the number of amplitudes to be determined is reduced by a factor of 10(5)-10(6) relative to a canonical CCSD calculation on the same system with the same basis set. In the original method, the PNOs were expanded in the set of canonical virtual orbitals and single excitations were not truncated. This led to a number of fifth order scaling steps that eventually rendered the method computationally expensive for large molecules (e.g., >100 atoms). In the present work, these limitations are overcome by a complete redesign of the LPNO-CCSD method. The new method is based on the combination of the concepts of PNOs and projected atomic orbitals (PAOs). Thus, each PNO is expanded in a set of PAOs that in turn belong to a given electron pair specific domain. In this way, it is possible to fully exploit locality while maintaining the extremely high compactness of the original LPNO-CCSD wavefunction. No terms are dropped from the CCSD equations and domains are chosen conservatively. The correlation energy loss due to the domains remains below <0.05%, which implies typically 15-20 but occasionally up to 30 atoms per domain on average. The new method has been given the acronym DLPNO-CCSD ("domain based LPNO-CCSD"). The method is nearly linear scaling with respect to system size. The original LPNO-CCSD method had three adjustable truncation thresholds that were chosen conservatively and do not need to be changed for actual applications. In the present treatment, no additional truncation parameters have been introduced. Any additional truncation is performed on the basis of the three original thresholds. There are no real-space cutoffs. Single excitations are truncated using singles-specific natural orbitals. Pairs are prescreened according to a multipole expansion of a pair correlation energy estimate based on local orbital specific virtual orbitals (LOSVs). Like its LPNO-CCSD predecessor, the method is completely of black box character and does not require any user adjustments. It is shown here that DLPNO-CCSD is as accurate as LPNO-CCSD while leading to computational savings exceeding one order of magnitude for larger systems. The largest calculations reported here featured >8800 basis functions and >450 atoms. In all larger test calculations done so far, the LPNO-CCSD step took less time than the preceding Hartree-Fock calculation, provided no approximations have been introduced in the latter. Thus, based on the present development reliable CCSD calculations on large molecules with unprecedented efficiency and accuracy are realized.

The causes of parent-offspring transmission of drug abuse: a Swedish population-based study.

PubMed

Kendler, K S; Ohlsson, H; Sundquist, K; Sundquist, J

2015-01-01

While drug abuse (DA) is strongly familial, we still have limited knowledge about the causes of its cross-generational transmission. We examined DA ascertained from national registers in offspring of three family types from the Swedish population [intact (n = 2,111,074), 'not-lived-with' (n = 165,315, where biological parents never lived with their offspring) and 'step' (n = 124,800 offspring)], which reflected, respectively, the effects of genes + rearing, genes only and rearing only. We replicated these results in three high-risk co-relative designs. Combined across mothers and fathers, the hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact, 2.73 in 'not-lived-with' and 1.79 in stepfamilies. In 968 biological full or half-sibling pairs one of whom was reared by and the other never lived with their parent with DA, the HR for DA was greater in the reared than 'not-lived-with' child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was greater in a reared biological v. step-parented non-biological child (HR 3.33). In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with biological child and the second a step-parented non-biological child, the HR for DA was greater in the biological v. stepchild (HR 1.80). Both genetic and environmental factors contribute substantially to parent-offspring resemblance for DA. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.

On the biophysics and kinetics of toehold-mediated DNA strand displacement

PubMed Central

Srinivas, Niranjan; Ouldridge, Thomas E.; Šulc, Petr; Schaeffer, Joseph M.; Yurke, Bernard; Louis, Ard A.; Doye, Jonathan P. K.; Winfree, Erik

2013-01-01

Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems. PMID:24019238

On the biophysics and kinetics of toehold-mediated DNA strand displacement.

PubMed

Srinivas, Niranjan; Ouldridge, Thomas E; Sulc, Petr; Schaeffer, Joseph M; Yurke, Bernard; Louis, Ard A; Doye, Jonathan P K; Winfree, Erik

2013-12-01

Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.

Multiple reaction monitoring-ion pair finder: a systematic approach to transform nontargeted mode to pseudotargeted mode for metabolomics study based on liquid chromatography-mass spectrometry.

PubMed

Luo, Ping; Dai, Weidong; Yin, Peiyuan; Zeng, Zhongda; Kong, Hongwei; Zhou, Lina; Wang, Xiaolin; Chen, Shili; Lu, Xin; Xu, Guowang

2015-01-01

Pseudotargeted metabolic profiling is a novel strategy combining the advantages of both targeted and untargeted methods. The strategy obtains metabolites and their product ions from quadrupole time-of-flight (Q-TOF) MS by information-dependent acquisition (IDA) and then picks targeted ion pairs and measures them on a triple-quadrupole MS by multiple reaction monitoring (MRM). The picking of ion pairs from thousands of candidates is the most time-consuming step of the pseudotargeted strategy. Herein, a systematic and automated approach and software (MRM-Ion Pair Finder) were developed to acquire characteristic MRM ion pairs by precursor ions alignment, MS(2) spectrum extraction and reduction, characteristic product ion selection, and ion fusion. To test the reliability of the approach, a mixture of 15 metabolite standards was first analyzed; the representative ion pairs were correctly picked out. Then, pooled serum samples were further studied, and the results were confirmed by the manual selection. Finally, a comparison with a commercial peak alignment software was performed, and a good characteristic ion coverage of metabolites was obtained. As a proof of concept, the proposed approach was applied to a metabolomics study of liver cancer; 854 metabolite ion pairs were defined in the positive ion mode from serum. Our approach provides a high throughput method which is reliable to acquire MRM ion pairs for pseudotargeted metabolomics with improved metabolite coverage and facilitate more reliable biomarkers discoveries.

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.

SGM-based seamline determination for urban orthophoto mosaicking

NASA Astrophysics Data System (ADS)

Pang, Shiyan; Sun, Mingwei; Hu, Xiangyun; Zhang, Zuxun

2016-02-01

Mosaicking is a key step in the production of digital orthophoto maps (DOMs), especially for large-scale urban orthophotos. During this step, manual intervention is commonly involved to avoid the case where the seamline crosses obvious objects (e.g., buildings), which causes geometric discontinuities on the DOMs. How to guide the seamline to avoid crossing obvious objects has become a popular topic in the field of photogrammetry and remote sensing. Thus, a new semi-global matching (SGM)-based method to guide seamline determination is proposed for urban orthophoto mosaicking in this study, which can greatly eliminate geometric discontinuities. The approximate epipolar geometry of the orthophoto pairs is first derived and proven, and the approximate epipolar image pair is then generated by rotating the two orthorectified images according to the parallax direction. A SGM algorithm is applied to their overlaps to obtain the corresponding pixel-wise disparity. According to a predefined disparity threshold, the overlap area is identified as the obstacle and non-obstacle areas. For the non-obstacle regions, Hilditch thinning algorithm is used to obtain the skeleton line, followed by Dijkstra's algorithm to search for the optimal path on the skeleton network as the seamline between two orthophotos. A whole seamline network is constructed based on the strip information recorded in flight. In the experimental section, the approximate epipolar geometric theory of the orthophoto is first analyzed and verified, and the effectiveness of the proposed method is then validated by comparing its results with the results of the geometry-based, OrthoVista, and orthoimage elevation synchronous model (OESM)-based methods.

A Parallel Spectroscopic Method for Examining Dynamic Phenomena on the Millisecond Time Scale

PubMed Central

Snively, Christopher M.; Chase, D. Bruce; Rabolt, John F.

2009-01-01

An infrared spectroscopic technique based on planar array infrared (PAIR) spectroscopy has been developed that allows the acquisition of spectra from multiple samples simultaneously. Using this technique, it is possible to acquire spectra over a spectral range of 950–1900cm−1 with a temporal resolution of 2.2ms. The performance of this system was demonstrated by determining the shear-induced orientational response of several low molecular weight liquid crystals. Five different liquid crystals were examined in combination with five different alignment layers, and both primary and secondary screens were demonstrated. Implementation of this high throughput PAIR technique resulted in a reduction in acquisition time as compared to both step-scan and ultra-rapid-scanning FTIR spectroscopy. PMID:19239197

Pair-Wise, Deformable Mirror, Image Plane-Based Diversity Electric Field Estimation for High Contrast Coronagraphy

NASA Technical Reports Server (NTRS)

Give'on, Amir; Kern, Brian D.; Shaklan, Stuart

2011-01-01

In this paper we describe the complex electric field reconstruction from image plane intensity measurements for high contrast coronagraphic imaging. A deformable mirror (DM) surface is modied with pairs of complementary shapes to create diversity in the image plane of the science camera where the intensity of the light is measured. Along with the Electric Field Conjugation correction algorithm, this estimation method has been used in various high contrast imaging testbeds to achieve the best contrasts to date both in narrow and in broad band light. We present the basic methodology of estimation in easy to follow list of steps, present results from HCIT and raise several open quations we are confronted with using this method.

Detection of canine distemper virus (CDV) through one step RT-PCR combined with nested PCR.

PubMed

Kim, Y H; Cho, K W; Youn, H Y; Yoo, H S; Han, H R

2001-04-01

A one step reverse transcription PCR (RT-PCR) combined nested PCR was set up to increase efficiency in the diagnosis of canine distemper virus (CDV) infection after developement of nested PCR. Two PCR primer sets were designed based on the sequence of nucleocapsid gene of CDV Onderstepoort strain. One-step RT-PCR with the outer primer pair was revealed to detect 10(2) PFU/ml. The sensitivity was increased hundredfold using the one-step RT-PCR combined with the nested PCR. Specificity of the PCR was also confirmed using other related canine virus and peripheral blood mononuclear cells (PBMC) and body secretes of healthy dogs. Of the 51 blood samples from dogs clinically suspected of CD, 45 samples were revealed as positive by one-step RT-PCR combined with nested PCR. However, only 15 samples were identified as positive with a single one step RT-PCR. Therefore approximately 60% increase in the efficiency of the diagnosis was observed by the combined method. These results suggested that one step RT-PCR combined with nested PCR could be a sensitive, specific, and practical method for diagnosis of CDV infection.

Isoguanine and 5-Methyl-Isocytosine Bases, In Vitro and In Vivo

PubMed Central

Bande, Omprakash; Abu El Asrar, Rania; Braddick, Darren; Dumbre, Shrinivas; Pezo, Valérie; Schepers, Guy; Pinheiro, Vitor B; Lescrinier, Eveline; Holliger, Philipp; Marlière, Philippe; Herdewijn, Piet

2015-01-01

The synthesis, base-pairing properties and in vitro and in vivo characteristics of 5-methyl-isocytosine (isoCMe) and isoguanine (isoG) nucleosides, incorporated in an HNA(h) (hexitol nucleic acid)–DNA(d) mosaic backbone, are described. The required h-isoG phosphoramidite was prepared by a selective deamination as a key step. As demonstrated by Tm measurements the hexitol sugar showed slightly better mismatch discrimination against dT. The d-isoG base mispairing follows the order T>G>C while the h-isoG base mispairing follows the order G>C>T. The h- and d-isoCMe bases mainly mispair with G. Enzymatic incorporation experiments show that the hexitol backbone has a variable effect on selectivity. In the enzymatic assays, isoG misincorporates mainly with T, and isoCMe misincorporates mainly with A. Further analysis in vivo confirmed the patterns of base-pair interpretation for the deoxyribose and hexitol isoCMe/isoG bases in a cellular context, through incorporation of the bases into plasmidic DNA. Results in vivo demonstrated that mispairing and misincorporation was dependent on the backbone scaffold of the base, which indicates rational advances towards orthogonality. PMID:25684598

Multilayer checkpoints for microRNA authenticity during RISC assembly

PubMed Central

Kawamata, Tomoko; Yoda, Mayuko; Tomari, Yukihide

2011-01-01

MicroRNAs (miRNAs) function through the RNA-induced silencing complex (RISC), which contains an Argonaute (Ago) protein at the core. RISC assembly follows a two-step pathway: miRNA/miRNA* duplex loading into Ago, and separation of the two strands within Ago. Here we show that the 5′ phosphate of the miRNA strand is essential for duplex loading into Ago, whereas the preferred 5′ nucleotide of the miRNA strand and the base-pairing status in the seed region and the middle of the 3′ region function as additive anchors to Ago. Consequently, the miRNA authenticity is inspected at multiple steps during RISC assembly. PMID:21738221

Student goal orientation in learning inquiry skills with modifiable software advisors

NASA Astrophysics Data System (ADS)

Shimoda, Todd A.; White, Barbara Y.; Frederiksen, John R.

2002-03-01

A computer support environment (SCI-WISE) for learning and doing science inquiry projects was designed. SCI-WISE incorporates software advisors that give general advice about a skill such as hypothesizing. By giving general advice (rather than step-by-step procedures), the system is intended to help students conduct experiments that are more epistemologically authentic. Also, students using SCI-WISE can select the type of advice the advisors give and when they give advice, as well as modify the advisors' knowledge bases. The system is based partly on a theoretical framework of levels of agency and goal orientation. This framework assumes that giving students higher levels of agency facilitates higher-level goal orientations (such as mastery or knowledge building as opposed to task completion) that in turn produce higher levels of competence. A study of sixth grade science students was conducted. Students took a pretest questionnaire that measured their goal orientations for science projects and their inquiry skills. The students worked in pairs on an open-ended inquiry project that requires complex reasoning about human memory. The students used one of two versions of SCI-WISE - one that was modifiable and one that was not. After finishing the project, the students took a posttest questionnaire similar to the pretest, and evaluated the version of the system they used. The main results showed that (a) there was no correlation of goal orientation with grade point average, (b) knowledge-oriented students using the modifiable version tended to rate SCI-WISE more helpful than task-oriented students, and (c) knowledge-oriented pairs using the nonmodifiable version tended to have higher posttest inquiry skills scores than other pair types.

Correlative feature analysis of FFDM images

NASA Astrophysics Data System (ADS)

Yuan, Yading; Giger, Maryellen L.; Li, Hui; Sennett, Charlene

2008-03-01

Identifying the corresponding image pair of a lesion is an essential step for combining information from different views of the lesion to improve the diagnostic ability of both radiologists and CAD systems. Because of the non-rigidity of the breasts and the 2D projective property of mammograms, this task is not trivial. In this study, we present a computerized framework that differentiates the corresponding images from different views of a lesion from non-corresponding ones. A dual-stage segmentation method, which employs an initial radial gradient index(RGI) based segmentation and an active contour model, was initially applied to extract mass lesions from the surrounding tissues. Then various lesion features were automatically extracted from each of the two views of each lesion to quantify the characteristics of margin, shape, size, texture and context of the lesion, as well as its distance to nipple. We employed a two-step method to select an effective subset of features, and combined it with a BANN to obtain a discriminant score, which yielded an estimate of the probability that the two images are of the same physical lesion. ROC analysis was used to evaluate the performance of the individual features and the selected feature subset in the task of distinguishing between corresponding and non-corresponding pairs. By using a FFDM database with 124 corresponding image pairs and 35 non-corresponding pairs, the distance feature yielded an AUC (area under the ROC curve) of 0.8 with leave-one-out evaluation by lesion, and the feature subset, which includes distance feature, lesion size and lesion contrast, yielded an AUC of 0.86. The improvement by using multiple features was statistically significant as compared to single feature performance. (p<0.001)

Combining automatic table classification and relationship extraction in extracting anticancer drug-side effect pairs from full-text articles.

PubMed

Xu, Rong; Wang, QuanQiu

2015-02-01

Anticancer drug-associated side effect knowledge often exists in multiple heterogeneous and complementary data sources. A comprehensive anticancer drug-side effect (drug-SE) relationship knowledge base is important for computation-based drug target discovery, drug toxicity predication and drug repositioning. In this study, we present a two-step approach by combining table classification and relationship extraction to extract drug-SE pairs from a large number of high-profile oncological full-text articles. The data consists of 31,255 tables downloaded from the Journal of Oncology (JCO). We first trained a statistical classifier to classify tables into SE-related and -unrelated categories. We then extracted drug-SE pairs from SE-related tables. We compared drug side effect knowledge extracted from JCO tables to that derived from FDA drug labels. Finally, we systematically analyzed relationships between anti-cancer drug-associated side effects and drug-associated gene targets, metabolism genes, and disease indications. The statistical table classifier is effective in classifying tables into SE-related and -unrelated (precision: 0.711; recall: 0.941; F1: 0.810). We extracted a total of 26,918 drug-SE pairs from SE-related tables with a precision of 0.605, a recall of 0.460, and a F1 of 0.520. Drug-SE pairs extracted from JCO tables is largely complementary to those derived from FDA drug labels; as many as 84.7% of the pairs extracted from JCO tables have not been included a side effect database constructed from FDA drug labels. Side effects associated with anticancer drugs positively correlate with drug target genes, drug metabolism genes, and disease indications. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Gloves Reprocessing: Does It Really Save Money?

PubMed

Arora, Pankaj; Kumari, Santosh; Sodhi, Jitender; Talati, Shweta; Gupta, Anil Kumar

2015-12-01

Gloves are reprocessed and reused in health-care facilities in resource-limited settings to reduce the cost of availability of gloves. The study was done with the aim to compute the cost of reprocessing of gloves so that an economically rationale decision can be taken. A retrospective record-based cross-sectional study was undertaken in a central sterile supply department where different steps during reprocessing of gloves were identified and the cost involved in reprocessing per pair of gloves was calculated. The cost of material and manpower was calculated to arrive at the cost of reprocessing per pair of gloves. The cost of a reprocessed pair of surgical gloves was calculated to be Indian Rupee (INR) 14.33 which was greater than the cost of a new pair of disposable surgical gloves (INR 9.90) as the cost of sterilization of one pair of gloves itself came out to  be INR 10.97. The current study showed that the purchase of sterile disposable single-use gloves is cheaper than the process of recycling. Reprocessing of gloves is not economical on tangible terms even in resource-limited settings, and from the perspective of better infection control as well as health-care worker safety, it further justifies the use of disposable gloves.

In trans paired nicking triggers seamless genome editing without double-stranded DNA cutting.

PubMed

Chen, Xiaoyu; Janssen, Josephine M; Liu, Jin; Maggio, Ignazio; 't Jong, Anke E J; Mikkers, Harald M M; Gonçalves, Manuel A F V

2017-09-22

Precise genome editing involves homologous recombination between donor DNA and chromosomal sequences subjected to double-stranded DNA breaks made by programmable nucleases. Ideally, genome editing should be efficient, specific, and accurate. However, besides constituting potential translocation-initiating lesions, double-stranded DNA breaks (targeted or otherwise) are mostly repaired through unpredictable and mutagenic non-homologous recombination processes. Here, we report that the coordinated formation of paired single-stranded DNA breaks, or nicks, at donor plasmids and chromosomal target sites by RNA-guided nucleases based on CRISPR-Cas9 components, triggers seamless homology-directed gene targeting of large genetic payloads in human cells, including pluripotent stem cells. Importantly, in addition to significantly reducing the mutagenicity of the genome modification procedure, this in trans paired nicking strategy achieves multiplexed, single-step, gene targeting, and yields higher frequencies of accurately edited cells when compared to the standard double-stranded DNA break-dependent approach.CRISPR-Cas9-based gene editing involves double-strand breaks at target sequences, which are often repaired by mutagenic non-homologous end-joining. Here the authors use Cas9 nickases to generate coordinated single-strand breaks in donor and target DNA for precise homology-directed gene editing.

Operator care and eco-concerned development of a fast, facile and economical assay for basic nitrogenous drugs based on simplified ion-pair mini-scale extraction using safer solvent combined with drop-based spectrophotometry.

PubMed

Plianwong, Samarwadee; Sripattanaporn, Areerut; Waewsa-nga, Kwanrutai; Buacheen, Parin; Opanasopit, Praneet; Ngawhirunpat, Tanasait; Rojanarata, Theerasak

2012-08-30

A fast, facile, and economical assay for basic nitrogenous drugs has been developed based on the mini-scale extraction of the drug-dye ion pair complex combined with the use of safe-for-analyst and eco-friendlier organic extractant and drop-based micro-spectrophotometry. Instead of using large volume devices, the extraction was simply carried out in typical 1.5 mL microcentrifuge tubes along with the use of micropipettes for accurate transfer of liquids, vortex mixer for efficient partitioning of solutes and benchtop centrifuge for rapid phase separation. In the last step, back-extraction was performed by using the microvolume of acidic solution in order to concentrate the colored species into a confined aqueous microdrop and to keep the analyst away from unwanted contact and inhalation of organic solvents during the quantitation step which was achieved by using cuvetteless UV-vis micro-spectrophotometry without any prior dilutions. Using chlorpheniramine maleate as a representative analyte and n-butyl acetate as a less toxic and non-ozone depleting extractant, the miniaturized method was less laborious and much faster. It was accurate, precise and insensitive to the interferences from common excipients. Notably, it gave the assay results of drug in tablets and oral solution comparable to the large-scale pharmacopeial method while the consumption of organic solvents and the release of wastes were lowered by 200-400 folds. Copyright © 2012 Elsevier B.V. All rights reserved.

The problem of extreme events in paired-watershed studies

Treesearch

James W. Hornbeck

1973-01-01

In paired-watershed studies, the occurrence of an extreme event during the after-treatment period presents a problem: the effects of treatment must be determined by using greatly extrapolated regression statistics. Several steps are presented to help insure careful handling of extreme events during analysis and reporting of research results.

Fingerprint Identification Using SIFT-Based Minutia Descriptors and Improved All Descriptor-Pair Matching

PubMed Central

Zhou, Ru; Zhong, Dexing; Han, Jiuqiang

2013-01-01

The performance of conventional minutiae-based fingerprint authentication algorithms degrades significantly when dealing with low quality fingerprints with lots of cuts or scratches. A similar degradation of the minutiae-based algorithms is observed when small overlapping areas appear because of the quite narrow width of the sensors. Based on the detection of minutiae, Scale Invariant Feature Transformation (SIFT) descriptors are employed to fulfill verification tasks in the above difficult scenarios. However, the original SIFT algorithm is not suitable for fingerprint because of: (1) the similar patterns of parallel ridges; and (2) high computational resource consumption. To enhance the efficiency and effectiveness of the algorithm for fingerprint verification, we propose a SIFT-based Minutia Descriptor (SMD) to improve the SIFT algorithm through image processing, descriptor extraction and matcher. A two-step fast matcher, named improved All Descriptor-Pair Matching (iADM), is also proposed to implement the 1:N verifications in real-time. Fingerprint Identification using SMD and iADM (FISiA) achieved a significant improvement with respect to accuracy in representative databases compared with the conventional minutiae-based method. The speed of FISiA also can meet real-time requirements. PMID:23467056

Sordaria, a model system to uncover links between meiotic pairing and recombination

PubMed Central

Zickler, Denise; Espagne, Eric

2017-01-01

The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) The identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination. PMID:26877138

In search of functional association from time-series microarray data based on the change trend and level of gene expression

PubMed Central

He, Feng; Zeng, An-Ping

2006-01-01

Background The increasing availability of time-series expression data opens up new possibilities to study functional linkages of genes. Present methods used to infer functional linkages between genes from expression data are mainly based on a point-to-point comparison. Change trends between consecutive time points in time-series data have been so far not well explored. Results In this work we present a new method based on extracting main features of the change trend and level of gene expression between consecutive time points. The method, termed as trend correlation (TC), includes two major steps: 1, calculating a maximal local alignment of change trend score by dynamic programming and a change trend correlation coefficient between the maximal matched change levels of each gene pair; 2, inferring relationships of gene pairs based on two statistical extraction procedures. The new method considers time shifts and inverted relationships in a similar way as the local clustering (LC) method but the latter is merely based on a point-to-point comparison. The TC method is demonstrated with data from yeast cell cycle and compared with the LC method and the widely used Pearson correlation coefficient (PCC) based clustering method. The biological significance of the gene pairs is examined with several large-scale yeast databases. Although the TC method predicts an overall lower number of gene pairs than the other two methods at a same p-value threshold, the additional number of gene pairs inferred by the TC method is considerable: e.g. 20.5% compared with the LC method and 49.6% with the PCC method for a p-value threshold of 2.7E-3. Moreover, the percentage of the inferred gene pairs consistent with databases by our method is generally higher than the LC method and similar to the PCC method. A significant number of the gene pairs only inferred by the TC method are process-identity or function-similarity pairs or have well-documented biological interactions, including 443 known protein interactions and some known cell cycle related regulatory interactions. It should be emphasized that the overlapping of gene pairs detected by the three methods is normally not very high, indicating a necessity of combining the different methods in search of functional association of genes from time-series data. For a p-value threshold of 1E-5 the percentage of process-identity and function-similarity gene pairs among the shared part of the three methods reaches 60.2% and 55.6% respectively, building a good basis for further experimental and functional study. Furthermore, the combined use of methods is important to infer more complete regulatory circuits and network as exemplified in this study. Conclusion The TC method can significantly augment the current major methods to infer functional linkages and biological network and is well suitable for exploring temporal relationships of gene expression in time-series data. PMID:16478547

Reduced-order aeroelastic model for limit-cycle oscillations in vortex-dominated unsteady airfoil flows

NASA Astrophysics Data System (ADS)

Suresh Babu, Arun Vishnu; Ramesh, Kiran; Gopalarathnam, Ashok

2017-11-01

In previous research, Ramesh et al. (JFM,2014) developed a low-order discrete vortex method for modeling unsteady airfoil flows with intermittent leading edge vortex (LEV) shedding using a leading edge suction parameter (LESP). LEV shedding is initiated using discrete vortices (DVs) whenever the Leading Edge Suction Parameter (LESP) exceeds a critical value. In subsequent research, the method was successfully employed by Ramesh et al. (JFS, 2015) to predict aeroelastic limit-cycle oscillations in airfoil flows dominated by intermittent LEV shedding. When applied to flows that require large number of time steps, the computational cost increases due to the increasing vortex count. In this research, we apply an amalgamation strategy to actively control the DV count, and thereby reduce simulation time. A pair each of LEVs and TEVs are amalgamated at every time step. The ideal pairs for amalgamation are identified based on the requirement that the flowfield in the vicinity of the airfoil is least affected (Spalart, 1988). Instead of placing the amalgamated vortex at the centroid, we place it at an optimal location to ensure that the leading-edge suction and the airfoil bound circulation are conserved. Results of the initial study are promising.

Efficient Green's Function Reaction Dynamics (GFRD) simulations for diffusion-limited, reversible reactions

NASA Astrophysics Data System (ADS)

Bashardanesh, Zahedeh; Lötstedt, Per

2018-03-01

In diffusion controlled reversible bimolecular reactions in three dimensions, a dissociation step is typically followed by multiple, rapid re-association steps slowing down the simulations of such systems. In order to improve the efficiency, we first derive an exact Green's function describing the rate at which an isolated pair of particles undergoing reversible bimolecular reactions and unimolecular decay separates beyond an arbitrarily chosen distance. Then the Green's function is used in an algorithm for particle-based stochastic reaction-diffusion simulations for prediction of the dynamics of biochemical networks. The accuracy and efficiency of the algorithm are evaluated using a reversible reaction and a push-pull chemical network. The computational work is independent of the rates of the re-associations.

Cryptosystem based on two-step phase-shifting interferometry and the RSA public-key encryption algorithm

NASA Astrophysics Data System (ADS)

Meng, X. F.; Peng, X.; Cai, L. Z.; Li, A. M.; Gao, Z.; Wang, Y. R.

2009-08-01

A hybrid cryptosystem is proposed, in which one image is encrypted to two interferograms with the aid of double random-phase encoding (DRPE) and two-step phase-shifting interferometry (2-PSI), then three pairs of public-private keys are utilized to encode and decode the session keys (geometrical parameters, the second random-phase mask) and interferograms. In the stage of decryption, the ciphered image can be decrypted by wavefront reconstruction, inverse Fresnel diffraction, and real amplitude normalization. This approach can successfully solve the problem of key management and dispatch, resulting in increased security strength. The feasibility of the proposed cryptosystem and its robustness against some types of attack are verified and analyzed by computer simulations.

Robust prediction of consensus secondary structures using averaged base pairing probability matrices.

PubMed

Kiryu, Hisanori; Kin, Taishin; Asai, Kiyoshi

2007-02-15

Recent transcriptomic studies have revealed the existence of a considerable number of non-protein-coding RNA transcripts in higher eukaryotic cells. To investigate the functional roles of these transcripts, it is of great interest to find conserved secondary structures from multiple alignments on a genomic scale. Since multiple alignments are often created using alignment programs that neglect the special conservation patterns of RNA secondary structures for computational efficiency, alignment failures can cause potential risks of overlooking conserved stem structures. We investigated the dependence of the accuracy of secondary structure prediction on the quality of alignments. We compared three algorithms that maximize the expected accuracy of secondary structures as well as other frequently used algorithms. We found that one of our algorithms, called McCaskill-MEA, was more robust against alignment failures than others. The McCaskill-MEA method first computes the base pairing probability matrices for all the sequences in the alignment and then obtains the base pairing probability matrix of the alignment by averaging over these matrices. The consensus secondary structure is predicted from this matrix such that the expected accuracy of the prediction is maximized. We show that the McCaskill-MEA method performs better than other methods, particularly when the alignment quality is low and when the alignment consists of many sequences. Our model has a parameter that controls the sensitivity and specificity of predictions. We discussed the uses of that parameter for multi-step screening procedures to search for conserved secondary structures and for assigning confidence values to the predicted base pairs. The C++ source code that implements the McCaskill-MEA algorithm and the test dataset used in this paper are available at http://www.ncrna.org/papers/McCaskillMEA/. Supplementary data are available at Bioinformatics online.

A two-dimensional 1H-NMR study of the dam methylase site: comparison between the hemimethylated GATC sequence, its unmethylated analogue and a hemimethylated CATG sequence. The sequence dependence of methylation upon base-pair lifetimes.

PubMed

Fazakerley, G V; Quignard, E; Teoule, R; Guy, A; Guschlbauer, W

1987-09-15

We report two-dimensional NOE (NOESY) spectra on the sequence d(GCGATCATGG).d(CCATGATCGC) which contains the unmethylated dam site. As expected the DNA adopts a B-form conformation but appears to be distorted at the TG step of the second strand. This distorsion, probably bending, is not seen on the opposite strand. When the first strand is methylated on adenine in the GATC or CATG sequence the NOESY spectra indicate little or no change in the conformation. However the single strand-duplex exchange is slowed down to the slow-exchange region on a proton NMR time scale. We have assigned the exchangeable imino and cytidine amino resonances of the three duplexes. From the imino linewidths as a function of temperature, we observe that the unmethylated and the hemimethylated Gm6ATC duplexes melt normally from the ends. However, this is not so for the hemimethylated Cm6ATG duplex which, apart from the terminal base pairs, melts cooperatively and at higher temperature. In spectra recorded in H2O a second duplex is observed, for the Gm6ATC sequence, which we have not been able to identify. It is however unlikely to be a hairpin structure. Ultraviolet-melting curves also indicate the presence of two transitions for this duplex. The effect of methylation upon base-pair lifetimes has been studied by comparing the above three duplexes. Little effect is observed upon methylation in the GATC sequence but a drastic increase in the lifetimes of all base pairs is observed upon methylation in the CATG sequence.

Ionic force field optimization based on single-ion and ion-pair solvation properties: Going beyond standard mixing rules

NASA Astrophysics Data System (ADS)

Fyta, Maria; Netz, Roland R.

2012-03-01

Using molecular dynamics (MD) simulations in conjunction with the SPC/E water model, we optimize ionic force-field parameters for seven different halide and alkali ions, considering a total of eight ion-pairs. Our strategy is based on simultaneous optimizing single-ion and ion-pair properties, i.e., we first fix ion-water parameters based on single-ion solvation free energies, and in a second step determine the cation-anion interaction parameters (traditionally given by mixing or combination rules) based on the Kirkwood-Buff theory without modification of the ion-water interaction parameters. In doing so, we have introduced scaling factors for the cation-anion Lennard-Jones (LJ) interaction that quantify deviations from the standard mixing rules. For the rather size-symmetric salt solutions involving bromide and chloride ions, the standard mixing rules work fine. On the other hand, for the iodide and fluoride solutions, corresponding to the largest and smallest anion considered in this work, a rescaling of the mixing rules was necessary. For iodide, the experimental activities suggest more tightly bound ion pairing than given by the standard mixing rules, which is achieved in simulations by reducing the scaling factor of the cation-anion LJ energy. For fluoride, the situation is different and the simulations show too large attraction between fluoride and cations when compared with experimental data. For NaF, the situation can be rectified by increasing the cation-anion LJ energy. For KF, it proves necessary to increase the effective cation-anion Lennard-Jones diameter. The optimization strategy outlined in this work can be easily adapted to different kinds of ions.

Normal-Mode Analysis of Circular DNA at the Base-Pair Level. 2. Large-Scale Configurational Transformation of a Naturally Curved Molecule.

PubMed

Matsumoto, Atsushi; Tobias, Irwin; Olson, Wilma K

2005-01-01

Fine structural and energetic details embedded in the DNA base sequence, such as intrinsic curvature, are important to the packaging and processing of the genetic material. Here we investigate the internal dynamics of a 200 bp closed circular molecule with natural curvature using a newly developed normal-mode treatment of DNA in terms of neighboring base-pair "step" parameters. The intrinsic curvature of the DNA is described by a 10 bp repeating pattern of bending distortions at successive base-pair steps. We vary the degree of intrinsic curvature and the superhelical stress on the molecule and consider the normal-mode fluctuations of both the circle and the stable figure-8 configuration under conditions where the energies of the two states are similar. To extract the properties due solely to curvature, we ignore other important features of the double helix, such as the extensibility of the chain, the anisotropy of local bending, and the coupling of step parameters. We compare the computed normal modes of the curved DNA model with the corresponding dynamical features of a covalently closed duplex of the same chain length constructed from naturally straight DNA and with the theoretically predicted dynamical properties of a naturally circular, inextensible elastic rod, i.e., an O-ring. The cyclic molecules with intrinsic curvature are found to be more deformable under superhelical stress than rings formed from naturally straight DNA. As superhelical stress is accumulated in the DNA, the frequency, i.e., energy, of the dominant bending mode decreases in value, and if the imposed stress is sufficiently large, a global configurational rearrangement of the circle to the figure-8 form takes place. We combine energy minimization with normal-mode calculations of the two states to decipher the configurational pathway between the two states. We also describe and make use of a general analytical treatment of the thermal fluctuations of an elastic rod to characterize the motions of the minicircle as a whole from knowledge of the full set of normal modes. The remarkable agreement between computed and theoretically predicted values of the average deviation and dispersion of the writhe of the circular configuration adds to the reliability in the computational approach. Application of the new formalism to the computed modes of the figure-8 provides insights into macromolecular motions which are beyond the scope of current theoretical treatments.

Pair Negotiation When Developing English Speaking Tasks

ERIC Educational Resources Information Center

Bohórquez Suárez, Ingrid Liliana; Gómez Sará, Mary Mily; Medina Mosquera, Sindy Lorena

2011-01-01

This study analyzes what characterizes the negotiations of seventh graders at a public school in Bogotá when working in pairs to develop speaking tasks in EFL classes. The inquiry is a descriptive case study that follows the qualitative paradigm. As a result of analyzing the data, we obtained four consecutive steps that characterize students'…

Chromosome togetherness at the onset of ESC differentiation

PubMed Central

Krivega, Ivan; Dean, Ann

2015-01-01

Pairing of homologous alleles is a phenomenon generally associated with imprinted and monoallelically expressed loci. In this issue, Hogan et al. (2015) examine the earliest steps between pluripotency and lineage commitment in ESCs and find a critical role for transient pairing of Oct4 alleles in exiting the pluripotent state. PMID:25748925

Selective photooxidation of hydrocarbons in zeolites by oxygen

DOEpatents

Frei, Heinz; Blatter, Fritz; Sun, Hai

1998-01-01

A selective photooxidation process for the conversion of hydrocarbon molecules to partially oxygenated derivatives, which comprises the steps of adsorbing a hydrocarbon and oxygen onto a dehydrated zeolite support matrix to form a hydrocarbon-oxygen contact pair, and subsequently exposing the hydrocarbon-oxygen contact pair to visible light, thereby forming a partially oxygenated derivative.

Development of a multiplex probe combination-based one-step real-time reverse transcription-PCR for NA subtype typing of avian influenza virus.

PubMed

Sun, Zhihao; Qin, Tao; Meng, Feifei; Chen, Sujuan; Peng, Daxin; Liu, Xiufan

2017-10-18

Nine influenza virus neuraminidase (NA) subtypes have been identified in poultry and wild birds. Few methods are available for rapid and simple NA subtyping. Here we developed a multiplex probe combination-based one-step real-time reverse transcriptase PCR (rRT-PCR) to detect nine avian influenza virus NA subtypes. Nine primer-probe pairs were assigned to three groups based on the different fluorescent dyes of the probes (FAM, HEX, or Texas Red). Each probe detected only one NA subtype, without cross reactivity. The detection limit was less than 100 EID 50 or 100 copies of cDNA per reaction. Data obtained using this method with allantoic fluid samples isolated from live bird markets and H9N2-infected chickens correlated well with data obtained using virus isolation and sequencing, but was more sensitive. This new method provides a specific and sensitive alternative to conventional NA-subtyping methods.

Quantum anharmonic oscillator plus delta-function potential: a molecular view of pairing formation and breaking in the coordinate space

NASA Astrophysics Data System (ADS)

Sumaryada, Tony; Maha Putra, Bima; Pramudito, Sidikrubadi

2017-05-01

We propose an alternative way to describe the pairing formation and breaking via a quantum anharmonic oscillator with a delta-function potential model. Unlike BCS theory, which describes the pairing formation in the momentum space, this model works in the coordinate space and is able to give a molecular view of pairing formation and breaking in the coordinate space. By exploring the dynamical interplay between the intrinsic factor (dissociation energy) and external factor (pairing strength) of this system additional information was gained, including the critical pairing strength and critical scattering length, which might relate to the BCS-BEC crossover phenomena and halo state formation. Although only the energetic aspect of pairing is described by this model, its simplicity and pedagogical steps might help undergraduate students to understand the pairing problem in a simple way.

Harnessing the landscape of microbial culture media to predict new organism–media pairings

PubMed Central

Oberhardt, Matthew A.; Zarecki, Raphy; Gronow, Sabine; Lang, Elke; Klenk, Hans-Peter; Gophna, Uri; Ruppin, Eytan

2015-01-01

Culturing microorganisms is a critical step in understanding and utilizing microbial life. Here we map the landscape of existing culture media by extracting natural-language media recipes into a Known Media Database (KOMODO), which includes >18,000 strain–media combinations, >3300 media variants and compound concentrations (the entire collection of the Leibniz Institute DSMZ repository). Using KOMODO, we show that although media are usually tuned for individual strains using biologically common salts, trace metals and vitamins/cofactors are the most differentiating components between defined media of strains within a genus. We leverage KOMODO to predict new organism–media pairings using a transitivity property (74% growth in new in vitro experiments) and a phylogeny-based collaborative filtering tool (83% growth in new in vitro experiments and stronger growth on predicted well-scored versus poorly scored media). These resources are integrated into a web-based platform that predicts media given an organism's 16S rDNA sequence, facilitating future cultivation efforts. PMID:26460590

Lemur behaviour informs the evolution of social monogamy.

PubMed

Kappeler, Peter M

2014-11-01

Recent comparative analyses reached contradictory conclusions about the evolutionary origins of social monogamy in primates and other mammals, but they ignored variation in social bond quality between pair-partners. Recent field studies of Malagasy primates (lemurs) with variable intersexual bonds indicate independent evolutionary transitions to pair-living from solitary and group-living ancestors, respectively, as well as four cumulative steps in evolutionary transitions from a solitary life style to pair-living that resolve some contradictory results of previous studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toward best practices for developing regional connectivity maps.

PubMed

Beier, Paul; Spencer, Wayne; Baldwin, Robert F; McRae, Brad H

2011-10-01

To conserve ecological connectivity (the ability to support animal movement, gene flow, range shifts, and other ecological and evolutionary processes that require large areas), conservation professionals need coarse-grained maps to serve as decision-support tools or vision statements and fine-grained maps to prescribe site-specific interventions. To date, research has focused primarily on fine-grained maps (linkage designs) covering small areas. In contrast, we devised 7 steps to coarsely map dozens to hundreds of linkages over a large area, such as a nation, province, or ecoregion. We provide recommendations on how to perform each step on the basis of our experiences with 6 projects: California Missing Linkages (2001), Arizona Wildlife Linkage Assessment (2006), California Essential Habitat Connectivity (2010), Two Countries, One Forest (northeastern United States and southeastern Canada) (2010), Washington State Connected Landscapes (2010), and the Bhutan Biological Corridor Complex (2010). The 2 most difficult steps are mapping natural landscape blocks (areas whose conservation value derives from the species and ecological processes within them) and determining which pairs of blocks can feasibly be connected in a way that promotes conservation. Decision rules for mapping natural landscape blocks and determining which pairs of blocks to connect must reflect not only technical criteria, but also the values and priorities of stakeholders. We recommend blocks be mapped on the basis of a combination of naturalness, protection status, linear barriers, and habitat quality for selected species. We describe manual and automated procedures to identify currently functioning or restorable linkages. Once pairs of blocks have been identified, linkage polygons can be mapped by least-cost modeling, other approaches from graph theory, or individual-based movement models. The approaches we outline make assumptions explicit, have outputs that can be improved as underlying data are improved, and help implementers focus strictly on ecological connectivity. ©2011 Society for Conservation Biology.

Structure-affinity relationships for the binding of actinomycin D to DNA

NASA Astrophysics Data System (ADS)

Gallego, José; Ortiz, Angel R.; de Pascual-Teresa, Beatriz; Gago, Federico

1997-03-01

Molecular models of the complexes between actinomycin D and 14 different DNA hexamers were built based on the X-ray crystal structure of the actinomycin-d(GAAGCTTC)2 complex. The DNA sequences included the canonical GpC binding step flanked by different base pairs, nonclassical binding sites such as GpG and GpT, and sites containing 2,6-diamino- purine. A good correlation was found between the intermolecular interaction energies calculated for the refined complexes and the relative preferences of actinomycin binding to standard and modified DNA. A detailed energy decomposition into van der Waals and electrostatic components for the interactions between the DNA base pairs and either the chromophore or the peptidic part of the antibiotic was performed for each complex. The resulting energy matrix was then subjected to principal component analysis, which showed that actinomycin D discriminates among different DNA sequences by an interplay of hydrogen bonding and stacking interactions. The structure-affinity relationships for this important antitumor drug are thus rationalized and may be used to advantage in the design of novel sequence-specific DNA-binding agents.

Parallel inferencing method and apparatus for rule-based expert systems

NASA Technical Reports Server (NTRS)

Schwuttke, Ursula M. (Inventor); Moldovan, Dan (Inventor); Kuo, Steve (Inventor)

1993-01-01

The invention analyzes areas of conditions with an expert knowledge base of rules using plural separate nodes which fire respective rules of said knowledge base, each of said rules upon being fired altering certain of said conditions predicated upon the existence of other said conditions. The invention operates by constructing a P representation of all pairs of said rules which are input dependent or output dependent; constructing a C representation of all pairs of said rules which are communication dependent or input dependent; determining which of the rules are ready to fire by matching the predicate conditions of each rule with the conditions of said set; enabling said node means to simultaneously fire those of the rules ready to fire which are defined by said P representation as being free of input and output dependencies; and communicating from each node enabled by said enabling step the alteration of conditions by the corresponding rule to other nodes whose rules are defined by said C matrix means as being input or communication dependent upon the rule of said enabled node.

GRIL-Seq, a method for identifying direct targets of bacterial small regulatory RNA by in vivo proximity ligation

PubMed Central

Han, Kook; Tjaden, Brian; Lory, Stephen

2017-01-01

The first step in the post-transcriptional regulatory function of most bacterial small non-coding RNAs (sRNAs) is base-pairing with partially complementary sequences of targeted transcripts. We present a simple method for identifying sRNA targets in vivo and defining processing sites of the regulated transcripts. The technique (referred to as GRIL-Seq) is based on preferential ligation of sRNAs to ends of base-paired targets in bacteria co-expressing T4 RNA ligase, followed by sequencing to identify the chimeras. In addition to the RNA chaperone Hfq, the GRIL-Seq method depends on the activity of the pyrophosphorylase RppH. Using PrrF1, an iron-regulated sRNA in Pseudomonas aeruginosa, we demonstrate that direct regulatory targets of this sRNA can be readily identified. Therefore, GRIL-Seq represents a powerful tool not only for identifying direct targets of sRNAs in a variety of environments, but can also result in uncovering novel roles for sRNAs and their targets in complex regulatory networks. PMID:28005055

GRIL-seq provides a method for identifying direct targets of bacterial small regulatory RNA by in vivo proximity ligation.

PubMed

Han, Kook; Tjaden, Brian; Lory, Stephen

2016-12-22

The first step in the post-transcriptional regulatory function of most bacterial small non-coding RNAs (sRNAs) is base pairing with partially complementary sequences of targeted transcripts. We present a simple method for identifying sRNA targets in vivo and defining processing sites of the regulated transcripts. The technique, referred to as global small non-coding RNA target identification by ligation and sequencing (GRIL-seq), is based on preferential ligation of sRNAs to the ends of base-paired targets in bacteria co-expressing T4 RNA ligase, followed by sequencing to identify the chimaeras. In addition to the RNA chaperone Hfq, the GRIL-seq method depends on the activity of the pyrophosphorylase RppH. Using PrrF1, an iron-regulated sRNA in Pseudomonas aeruginosa, we demonstrated that direct regulatory targets of this sRNA can readily be identified. Therefore, GRIL-seq represents a powerful tool not only for identifying direct targets of sRNAs in a variety of environments, but also for uncovering novel roles for sRNAs and their targets in complex regulatory networks.

Peer Coaching: Principals Learning from Principals. Pairing Novice and Experienced Principals Provides Both with Opportunities To Promote Reflective Thinking In Their Decision-Making

ERIC Educational Resources Information Center

Rich, Robert A.; Jackson, Sherion H.

2005-01-01

Unlike mentoring relationships, peer coaching is a voluntary partnership that uses reflections of past experiences to influence decision-making. The authors provide a step-by-step guide for establishing and maintaining peer-coaching partnerships.

SU-F-J-66: Anatomy Deformation Based Comparison Between One-Step and Two-Step Optimization for Online ART

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

Feng, Z; Yu, G; Qin, S

Purpose: This study investigated that how the quality of adapted plan was affected by inter-fractional anatomy deformation by using one-step and two-step optimization for on line adaptive radiotherapy (ART) procedure. Methods: 10 lung carcinoma patients were chosen randomly to produce IMRT plan by one-step and two-step algorithms respectively, and the prescribed dose was set as 60 Gy on the planning target volume (PTV) for all patients. To simulate inter-fractional target deformation, four specific cases were created by systematic anatomy variation; including target superior shift 0.5 cm, 0.3cm contraction, 0.3 cm expansion and 45-degree rotation. Based on these four anatomy deformation,more » adapted plan, regenerated plan and non-adapted plan were created to evaluate quality of adaptation. Adapted plans were generated automatically by using one-step and two-step algorithms respectively to optimize original plans, and regenerated plans were manually created by experience physicists. Non-adapted plans were produced by recalculating the dose distribution based on corresponding original plans. The deviations among these three plans were statistically analyzed by paired T-test. Results: In PTV superior shift case, adapted plans had significantly better PTV coverage by using two-step algorithm compared with one-step one, and meanwhile there was a significant difference of V95 by comparison with adapted and non-adapted plans (p=0.0025). In target contraction deformation, with almost same PTV coverage, the total lung received lower dose using one-step algorithm than two-step algorithm (p=0.0143,0.0126 for V20, Dmean respectively). In other two deformation cases, there were no significant differences observed by both two optimized algorithms. Conclusion: In geometry deformation such as target contraction, with comparable PTV coverage, one-step algorithm gave better OAR sparing than two-step algorithm. Reversely, the adaptation by using two-step algorithm had higher efficiency and accuracy as target occurred position displacement. We want to thank Dr. Lei Xing and Dr. Yong Yang in the Stanford University School of Medicine for this work. This work was jointly supported by NSFC (61471226), Natural Science Foundation for Distinguished Young Scholars of Shandong Province (JQ201516), and China Postdoctoral Science Foundation (2015T80739, 2014M551949).« less

Iterative non-sequential protein structural alignment.

PubMed

Salem, Saeed; Zaki, Mohammed J; Bystroff, Christopher

2009-06-01

Structural similarity between proteins gives us insights into their evolutionary relationships when there is low sequence similarity. In this paper, we present a novel approach called SNAP for non-sequential pair-wise structural alignment. Starting from an initial alignment, our approach iterates over a two-step process consisting of a superposition step and an alignment step, until convergence. We propose a novel greedy algorithm to construct both sequential and non-sequential alignments. The quality of SNAP alignments were assessed by comparing against the manually curated reference alignments in the challenging SISY and RIPC datasets. Moreover, when applied to a dataset of 4410 protein pairs selected from the CATH database, SNAP produced longer alignments with lower rmsd than several state-of-the-art alignment methods. Classification of folds using SNAP alignments was both highly sensitive and highly selective. The SNAP software along with the datasets are available online at http://www.cs.rpi.edu/~zaki/software/SNAP.

Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

PubMed Central

Williams, Charles H.; Hong, Charles C.

2011-01-01

In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design. PMID:21731440

Towards Scalable Entangled Photon Sources with Self-Assembled InAs /GaAs Quantum Dots

NASA Astrophysics Data System (ADS)

Wang, Jianping; Gong, Ming; Guo, G.-C.; He, Lixin

2015-08-01

The biexciton cascade process in self-assembled quantum dots (QDs) provides an ideal system for realizing deterministic entangled photon-pair sources, which are essential to quantum information science. The entangled photon pairs have recently been generated in experiments after eliminating the fine-structure splitting (FSS) of excitons using a number of different methods. Thus far, however, QD-based sources of entangled photons have not been scalable because the wavelengths of QDs differ from dot to dot. Here, we propose a wavelength-tunable entangled photon emitter mounted on a three-dimensional stressor, in which the FSS and exciton energy can be tuned independently, thereby enabling photon entanglement between dissimilar QDs. We confirm these results via atomistic pseudopotential calculations. This provides a first step towards future realization of scalable entangled photon generators for quantum information applications.

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.

Optical switch using Risley prisms

DOEpatents

Sweatt, William C.; Christenson, Todd R.

2003-04-15

An optical switch using Risley prisms and rotary microactuators to independently rotate the wedge prisms of each Risley prism pair is disclosed. The optical switch comprises an array of input Risley prism pairs that selectively redirect light beams from a plurality of input ports to an array of output Risley prism pairs that similarly direct the light beams to a plurality of output ports. Each wedge prism of each Risley prism pair can be independently rotated by a variable-reluctance stepping rotary microactuator that is fabricated by a multi-layer LIGA process. Each wedge prism can be formed integral to the annular rotor of the rotary microactuator by a DXRL process.

Optical Switch Using Risley Prisms

DOEpatents

Sweatt, William C.; Christenson, Todd R.

2005-02-22

An optical switch using Risley prisms and rotary microactuators to independently rotate the wedge prisms of each Risley prism pair is disclosed. The optical switch comprises an array of input Risley prism pairs that selectively redirect light beams from a plurality of input ports to an array of output Risley prism pairs that similarly direct the light beams to a plurality of output ports. Each wedge prism of each Risley prism pair can be independently rotated by a variable-reluctance stepping rotary microactuator that is fabricated by a multi-layer LIGA process. Each wedge prism can be formed integral to the annular rotor of the rotary microactuator by a DXRL process.

Methodological aspects of an adaptive multidirectional pattern search to optimize speech perception using three hearing-aid algorithms

NASA Astrophysics Data System (ADS)

Franck, Bas A. M.; Dreschler, Wouter A.; Lyzenga, Johannes

2004-12-01

In this study we investigated the reliability and convergence characteristics of an adaptive multidirectional pattern search procedure, relative to a nonadaptive multidirectional pattern search procedure. The procedure was designed to optimize three speech-processing strategies. These comprise noise reduction, spectral enhancement, and spectral lift. The search is based on a paired-comparison paradigm, in which subjects evaluated the listening comfort of speech-in-noise fragments. The procedural and nonprocedural factors that influence the reliability and convergence of the procedure are studied using various test conditions. The test conditions combine different tests, initial settings, background noise types, and step size configurations. Seven normal hearing subjects participated in this study. The results indicate that the reliability of the optimization strategy may benefit from the use of an adaptive step size. Decreasing the step size increases accuracy, while increasing the step size can be beneficial to create clear perceptual differences in the comparisons. The reliability also depends on starting point, stop criterion, step size constraints, background noise, algorithms used, as well as the presence of drifting cues and suboptimal settings. There appears to be a trade-off between reliability and convergence, i.e., when the step size is enlarged the reliability improves, but the convergence deteriorates. .

Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.

PubMed

Kutchukian, Peter S; Wassermann, Anne Mai; Lindvall, Mika K; Wright, S Kirk; Ottl, Johannes; Jacob, Jaison; Scheufler, Clemens; Marzinzik, Andreas; Brooijmans, Natasja; Glick, Meir

2015-06-01

A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits. © 2014 Society for Laboratory Automation and Screening.

DIALIGN P: fast pair-wise and multiple sequence alignment using parallel processors.

PubMed

Schmollinger, Martin; Nieselt, Kay; Kaufmann, Michael; Morgenstern, Burkhard

2004-09-09

Parallel computing is frequently used to speed up computationally expensive tasks in Bioinformatics. Herein, a parallel version of the multi-alignment program DIALIGN is introduced. We propose two ways of dividing the program into independent sub-routines that can be run on different processors: (a) pair-wise sequence alignments that are used as a first step to multiple alignment account for most of the CPU time in DIALIGN. Since alignments of different sequence pairs are completely independent of each other, they can be distributed to multiple processors without any effect on the resulting output alignments. (b) For alignments of large genomic sequences, we use a heuristics by splitting up sequences into sub-sequences based on a previously introduced anchored alignment procedure. For our test sequences, this combined approach reduces the program running time of DIALIGN by up to 97%. By distributing sub-routines to multiple processors, the running time of DIALIGN can be crucially improved. With these improvements, it is possible to apply the program in large-scale genomics and proteomics projects that were previously beyond its scope.

Controlling the orientation of spin-correlated radical pairs by covalent linkage to nanoporous anodic aluminum oxide membranes.

PubMed

Chen, Hsiao-Fan; Gardner, Daniel M; Carmieli, Raanan; Wasielewski, Michael R

2013-10-07

Ordered multi-spin assemblies are required for developing solid-state molecule-based spintronics. A linear donor-chromophore-acceptor (D-C-A) molecule was covalently attached inside the 150 nm diam. nanopores of an anodic aluminum oxide (AAO) membrane. Photoexcitation of D-C-A in a 343 mT magnetic field results in sub-nanosecond, two-step electron transfer to yield the spin-correlated radical ion pair (SCRP) (1)(D(+)˙-C-A(-)˙), which then undergoes radical pair intersystem crossing (RP-ISC) to yield (3)(D(+)˙-C-A(-)˙). RP-ISC results in S-T0 mixing to selectively populate the coherent superposition states |S'> and |T'>. Microwave-induced transitions between these states and the unpopulated |T(+1)> and |T(-1)> states result in spin-polarized time-resolved EPR (TREPR) spectra. The dependence of the electron spin polarization (ESP) phase of the TREPR spectra on the orientation of the AAO membrane pores relative to the externally applied magnetic field is used to determine the overall orientation of the SCRPs within the pores at room temperature.

Robotic Enrichment Processing of Roche 454 Titanium Emlusion PCR at the DOE Joint Genome Institute

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

Hamilton, Matthew; Wilson, Steven; Bauer, Diane

2010-05-28

Enrichment of emulsion PCR product is the most laborious and pipette-intensive step in the 454 Titanium process, posing the biggest obstacle for production-oriented scale up. The Joint Genome Institute has developed a pair of custom-made robots based on the Microlab Star liquid handling deck manufactured by Hamilton to mediate the complexity and ergonomic demands of the 454 enrichment process. The robot includes a custom built centrifuge, magnetic deck positions, as well as heating and cooling elements. At present processing eight emulsion cup samples in a single 2.5 hour run, these robots are capable of processing up to 24 emulsion cupmore » samples. Sample emulsions are broken using the standard 454 breaking process and transferred from a pair of 50ml conical tubes to a single 2ml tube and loaded on the robot. The robot performs the enrichment protocol and produces beads in 2ml tubes ready for counting. The robot follows the Roche 454 enrichment protocol with slight exceptions to the manner in which it resuspends beads via pipette mixing rather than vortexing and a set number of null bead removal washes. The robotic process is broken down in similar discrete steps: First Melt and Neutralization, Enrichment Primer Annealing, Enrichment Bead Incubation, Null Bead Removal, Second Melt and Neutralization and Sequencing Primer Annealing. Data indicating our improvements in enrichment efficiency and total number of bases per run will also be shown.« less

Development of Michelson interferometer based spatial phase-shift digital shearography

NASA Astrophysics Data System (ADS)

Xie, Xin

Digital shearography is a non-contact, full field, optical measurement method, which has the capability of directly measuring the gradient of deformation. For high measurement sensitivity, phase evaluation method has to be introduced into digital shearography by phase-shift technique. Catalog by phase-shift method, digital phase-shift shearography can be divided into Temporal Phase-Shift Digital Shearography (TPS-DS) and Spatial Phase-Shift Digital Shearography (SPS-DS). TPS-DS is the most widely used phase-shift shearography system, due to its simple algorithm, easy operation and good phase-map quality. However, the application of TPS-DS is only limited in static/step-by-step loading measurement situation, due to its multi-step shifting process. In order to measure the strain under dynamic/continuous loading situation, a SPS-DS system has to be developed. This dissertation aims to develop a series of Michelson Interferometer based SPS-DS measurement methods to achieve the strain measurement by using only a single pair of speckle pattern images. The Michelson Interferometer based SPS-DS systems utilize special designed optical setup to introduce extra carrier frequency into the laser wavefront. The phase information corresponds to the strain field can be separated on the Fourier domain using a Fourier Transform and can further be evaluated with a Windowed Inverse Fourier Transform. With different optical setups and carrier frequency arrangements, the Michelson Interferometer based SPS-DS method is capable to achieve a variety of measurement tasks using only single pair of speckle pattern images. Catalog by the aimed measurand, these capable measurement tasks can be divided into five categories: 1) measurement of out-of-plane strain field with small shearing amount; 2) measurement of relative out-of-plane deformation field with big shearing amount; 3) simultaneous measurement of relative out-of-plane deformation field and deformation gradient field by using multiple carrier frequencies; 4) simultaneous measurement of two directional strain field using dual measurement channels 5) measurement of pure in-plane strain and pure out-of-plane strain with multiple carrier frequencies. The basic theory, optical path analysis, preliminary studies, results analysis and research plan are shown in detail in this dissertation.

Desktop Parallax and Proper Motion: A Laboratory Exercise on Astrometry of Asteroids from Project CLEA

NASA Astrophysics Data System (ADS)

Marschall, L. A.; Snyder, G. A.; Good, R. F.; Hayden, M. B.; Cooper, P. R.

1998-12-01

Students in introductory and advanced astronomy classes can now experience the process of discovering asteroids, can measure proper motions, and can actually see the parallax of real astronomical objects on the screen, using a new set of computer-based exercises from Project CLEA. The heart of the exercise is a sophisticated astrometry program "Astrometry of Asteroids", which is a restricted version of CLEA's research software "Tools for Astrometry" described elsewhere at this meeting. The program, as used in the teaching lab, allows students to read and display digital images, co-align pairs of images using designated reference stars, blink and identify moving objects on the pairs, compare images with charts produced from the HST Guide Star Catalog (GSC), and fit equatorial coordinates to the images using designated reference stars from the GSC. Complete technical manuals for the exercise are provided for the use of the instructor, and a set of digital images, in FITS format, is included for the exercise. A student manual is provided for an exercise in which students go through the step-by-step process of determining the tangential velocity of an asteroid. Students first examine a series of images of a near-earth asteroid taken over several hours, blinking pairs to identify the moving object. They next measure the equatorial coordinates on a half-dozen images, and from this calculate an angular velocity of the object. Finally, using a pair of images of the asteroid taken simultaneously at the National Undergraduate Research Observatory (NURO) and at Colgate University, they measure the parallax of the asteroid, and thus its distance, which enables them to convert the angular velocity into a tangential velocity. An optional set of 10 pairs of images is provided, some of which contain asteroids, so that students can try to "find the asteroid" for themselves. The software is extremely flexible, and though materials are provided for a self-contained exercise, teachers can adapt the material to a wide variety of uses. The software and manuals are currently available on the Web. Project CLEA is supported by grants from Gettysburg College and the National Science Foundation.

A gp41-based heteroduplex mobility assay provides rapid and accurate assessment of intrasubtype epidemiological linkage in HIV type 1 heterosexual transmission Pairs.

PubMed

Manigart, Olivier; Boeras, Debrah I; Karita, Etienne; Hawkins, Paulina A; Vwalika, Cheswa; Makombe, Nathan; Mulenga, Joseph; Derdeyn, Cynthia A; Allen, Susan; Hunter, Eric

2012-12-01

A critical step in HIV-1 transmission studies is the rapid and accurate identification of epidemiologically linked transmission pairs. To date, this has been accomplished by comparison of polymerase chain reaction (PCR)-amplified nucleotide sequences from potential transmission pairs, which can be cost-prohibitive for use in resource-limited settings. Here we describe a rapid, cost-effective approach to determine transmission linkage based on the heteroduplex mobility assay (HMA), and validate this approach by comparison to nucleotide sequencing. A total of 102 HIV-1-infected Zambian and Rwandan couples, with known linkage, were analyzed by gp41-HMA. A 400-base pair fragment within the envelope gp41 region of the HIV proviral genome was PCR amplified and HMA was applied to both partners' amplicons separately (autologous) and as a mixture (heterologous). If the diversity between gp41 sequences was low (<5%), a homoduplex was observed upon gel electrophoresis and the transmission was characterized as having occurred between partners (linked). If a new heteroduplex formed, within the heterologous migration, the transmission was determined to be unlinked. Initial blind validation of gp-41 HMA demonstrated 90% concordance between HMA and sequencing with 100% concordance in the case of linked transmissions. Following validation, 25 newly infected partners in Kigali and 12 in Lusaka were evaluated prospectively using both HMA and nucleotide sequences. Concordant results were obtained in all but one case (97.3%). The gp41-HMA technique is a reliable and feasible tool to detect linked transmissions in the field. All identified unlinked results should be confirmed by sequence analyses.

Waist Circumference, Pedometer Placement, and Step-Counting Accuracy in Youth

ERIC Educational Resources Information Center

Abel, Mark G.; Hannon, James C.; Eisenman, Patricia A.; Ransdell, Lynda B.; Pett, Marjorie; Williams, Daniel P.

2009-01-01

This study examined whether differences in waist circumference (WC) and pedometer placement (anterior vs. midaxillary vs. posterior) affect the agreement between pedometer and observed steps during treadmill and self-paced walking. Participants included 19 pairs of youth (9-15 years old) who were matched for sex, race, and height and stratified by…

The clinical features of alcohol use disorders in biological and step-fathers that predict risk for alcohol use disorders in offspring.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Edwards, Alexis; Sundquist, Jan; Sundquist, Kristina

2017-12-01

Given that Alcohol Use Disorder (AUD) is clinically heterogeneous, can we, in a large epidemiological sample using public registries, identify clinical features of AUD cases in biological and step-fathers that index, respectively, genetic and familial-environmental risk for AUD in their offspring? From all father-offspring pairs where the father had AUD and the offspring was born 1960-1990, we identified not-lived-with (NLW) biological fathers (n = 38,376) and step-father pairs (n = 9,711). The relationship between clinical and historical features of the father's AUD and risk for AUD in offspring was assessed by linear hazard regression. Age at first registration for AUD and recurrence of AUD registration were significantly stronger predictors of risk for AUD in the offspring of NLW fathers than in step-fathers. By contrast, number of AUD registrations in NLW fathers and step-fathers were equally predictive of risk for AUD in offspring. However, while the number of step-father AUD registrations that occurred when he was living them with significantly predicted risk for AUD in his step-children, the number of registrations that occurred when not residing with his step-children was unassociated with their AUD risk. In an epidemiological sample, we could meaningfully differentiate between features of AUD in fathers that indexed genetic risk which was transmitted to biological offspring (early age at onset and recurrence) versus indexed environmental risk (registrations while rearing) which increased risk in step-children. © 2017 Wiley Periodicals, Inc.

Fission control system for nuclear reactor

DOEpatents

Conley, G.H.; Estes, G.P.

Control system for nuclear reactor comprises a first set of reactivity modifying rods fixed in a reactor core with their upper ends stepped in height across the core, and a second set of reactivity modifying rods movable vertically within the reactor core and having their lower ends stepped to correspond with the stepped arrangement of the first set of rods, pairs of the rods of the first and second sets being in coaxial alignment.

A solvent-based intelligence ink for oxygen.

PubMed

Mills, Andrew; Hazafy, David

2008-02-01

A solvent-based, irreversible oxygen indicator ink is described, comprising semiconductor photocatalyst nanoparticles, a solvent-soluble redox dye, mild reducing agent and polymer. Based on such an ink, a film -- made of titanium dioxide, a blue, solvent-soluble, coloured ion-paired methylene blue dye, glycerol and the polymer zein -- loses its colour rapidly (<30 s) upon exposure to UVA light and remains colourless in an oxygen-free atmosphere, returning to its original blue colour upon exposure to air. In the latter step the rate of colour recovery is proportional to the level of ambient oxygen and the same film can be UV-activated repeatedly. The mechanism of this novel, UV-activated, solvent-based, colorimetric oxygen indicator is discussed, along with its possible applications.

Chromosome togetherness at the onset of ESC differentiation.

PubMed

Krivega, Ivan; Dean, Ann

2015-03-05

Pairing of homologous alleles is a phenomenon generally associated with imprinted and mono-allelically expressed loci. In this issue, Hogan et al. (2015) examine the earliest steps between pluripotency and lineage commitment in ESCs and find a critical role for transient pairing of Oct4 alleles in exiting the pluripotent state. Copyright © 2015 Elsevier Inc. All rights reserved.

Stereoelectronic control in peptide bond formation. Ab initio calculations and speculations on the mechanism of action of serine proteases.

PubMed Central

Gorenstein, D G; Taira, K

1984-01-01

Ab initio molecular orbital calculations have been performed on the reaction profile for the addition/elimination reaction between ammonia and formic acid, proceeding via a tetrahedral intermediate: NH3 + HCO2H----H2NCH(OH)2----NH2CHO + H2O. Calculated transition state energies for the first addition step of the reaction revealed that a lone pair on the oxygen of the OH group, which is antiperiplanar to the attacking nitrogen, stabilized the transition state by 3.9 kcal/mol, thus supporting the hypothesis of stereoelectronic control for this reaction. In addition, a secondary, counterbalancing stereoelectronic effect stabilizes the second step, water elimination, transition state by 3.1 kcal/mol if the lone pair on the leaving water oxygen is not antiperiplanar to the C-N bond. The best conformation for the transition states was thus one with a lone pair antiperiplanar to the adjacent scissile bond and also one without a lone-pair orbital on the scissile bond oxygen or nitrogen antiperiplanar to the adjacent polar bond. The significance of these stereoelectronic effects for the mechanism of action of serine proteases is discussed. PMID:6394065

Sordaria, a model system to uncover links between meiotic pairing and recombination.

PubMed

Zickler, Denise; Espagne, Eric

2016-06-01

The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) the identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unraveling the sequence-dependent polymorphic behavior of d(CpG) steps in B-DNA.

PubMed

Dans, Pablo Daniel; Faustino, Ignacio; Battistini, Federica; Zakrzewska, Krystyna; Lavery, Richard; Orozco, Modesto

2014-10-01

We have made a detailed study of one of the most surprising sources of polymorphism in B-DNA: the high twist/low twist (HT/LT) conformational change in the d(CpG) base pair step. Using extensive computations, complemented with database analysis, we were able to characterize the twist polymorphism in the d(CpG) step in all the possible tetranucleotide environment. We found that twist polymorphism is coupled with BI/BII transitions, and, quite surprisingly, with slide polymorphism in the neighboring step. Unexpectedly, the penetration of cations into the minor groove of the d(CpG) step seems to be the key element in promoting twist transitions. The tetranucleotide environment also plays an important role in the sequence-dependent d(CpG) polymorphism. In this connection, we have detected a previously unexplored intramolecular C-H···O hydrogen bond interaction that stabilizes the low twist state when 3'-purines flank the d(CpG) step. This work explains a coupled mechanism involving several apparently uncorrelated conformational transitions that has only been partially inferred by earlier experimental or theoretical studies. Our results provide a complete description of twist polymorphism in d(CpG) steps and a detailed picture of the molecular choreography associated with this conformational change. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Investigating the role of ion-pair strategy in regulating nicotine release from patch: Mechanistic insights based on intermolecular interaction and mobility of pressure sensitive adhesive.

PubMed

Li, Qiaoyun; Wan, Xiaocao; Liu, Chao; Fang, Liang

2018-07-01

The aim of this study was to prepare a drug-in-adhesive patch of nicotine (NIC) and use ion-pair strategy to regulate drug delivery rate. Moreover, the mechanism of how ion-pair strategy regulated drug release was elucidated at molecular level. Formulation factors including pressure sensitive adhesives (PSAs), drug loading and counter ions (C 4 , C 6 , C 8 , C 10 , and C 12 ) were screened. In vitro release experiment and in vitro transdermal experiment were conducted to determine the rate-limiting step in drug delivery process. FT-IR and molecular modeling were used to characterize the interaction between drug and PSA. Thermal analysis and rheology study were conducted to investigate the mobility variation of PSA. The optimized patch prepared with NIC-C 8 had the transdermal profile fairly close to that of the commercial product (p > 0.05). The release rate constants (k) of NIC, NIC-C 4 and NIC-C 10 were 21.1, 14.4 and 32.4, respectively. Different release rates of NIC ion-pair complexes were attributed to the dual effect of ion-pair strategy on drug release. On one hand, ion-pair strategy enhanced the interaction between drug and PSA, which inhibited drug release. On the other hand, using ion-pair strategy improved the mobility of PSA, which facilitated drug release. Drug release behavior was determined by combined effect of two aspects above. These conclusions provided a new idea for us to regulate drug release behavior from patch. Copyright © 2018 Elsevier B.V. All rights reserved.

Plasma Heating and Alfvénic Turbulence Enhancement During Two Steps of Energy Conversion in Magnetic Reconnection Exhaust Region of Solar Wind

NASA Astrophysics Data System (ADS)

Jiansen, He; Xingyu, Zhu; Yajie, Chen; Chadi, Salem; Michael, Stevens; Hui, Li; Wenzhi, Ruan; Lei, Zhang; Chuanyi, Tu

2018-04-01

The magnetic reconnection exhaust is a pivotal region with enormous magnetic energy being continuously released and converted. The physical processes of energy conversion involved are so complicated that an all-round understanding based on in situ measurements is still lacking. We present the evidence of plasma heating by illustrating the broadening of proton and electron velocity distributions, which are extended mainly along the magnetic field, in an exhaust of interchange reconnection between two interplanetary magnetic flux tubes of the same polarity on the Sun. The exhaust is asymmetric across an interface, with both sides being bounded by a pair of compound discontinuities consisting of rotational discontinuity and slow shock. The energized plasmas are found to be firehose unstable, and responsible for the emanation of Alfvén waves during the second step of energy conversion. It is realized that the energy conversion in the exhaust can be a two-step process involving both plasma energization and wave emission.

Rapid Differentiation and In Situ Detection of 16 Sourdough Lactobacillus Species by Multiplex PCR

PubMed Central

Settanni, Luca; van Sinderen, Douwe; Rossi, Jone; Corsetti, Aldo

2005-01-01

A two-step multiplex PCR-based method was designed for the rapid detection of 16 species of lactobacilli known to be commonly present in sourdough. The first step of multiplex PCR was developed with a mixture of group-specific primers, while the second step included three multiplex PCR assays with a mixture of species-specific primers. Primers were derived from sequences that specify the 16S rRNA, the 16S-23S rRNA intergenic spacer region, and part of the 23S rRNA gene. The primer pairs designed were shown to exclusively amplify the targeted rrn operon fragment of the corresponding species. Due to the reliability of simultaneously identifying Lactobacillus plantarum, Lactobacillus pentosus, and Lactobacillus paraplantarum, a previously described multiplex PCR method employing recA gene-derived primers was included in the multiplex PCR system. The combination of a newly developed, quick bacterial DNA extraction method from sourdough and this multiplex PCR assay allows the rapid in situ detection of several sourdough-associated lactobacilli, including the recently described species Lactobacillus rossii, and thus represents a very useful alternative to culture-based methodologies. PMID:15933001

Statistical models for detecting differential chromatin interactions mediated by a protein.

PubMed

Niu, Liang; Li, Guoliang; Lin, Shili

2014-01-01

Chromatin interactions mediated by a protein of interest are of great scientific interest. Recent studies show that protein-mediated chromatin interactions can have different intensities in different types of cells or in different developmental stages of a cell. Such differences can be associated with a disease or with the development of a cell. Thus, it is of great importance to detect protein-mediated chromatin interactions with different intensities in different cells. A recent molecular technique, Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET), which uses formaldehyde cross-linking and paired-end sequencing, is able to detect genome-wide chromatin interactions mediated by a protein of interest. Here we proposed two models (One-Step Model and Two-Step Model) for two sample ChIA-PET count data (one biological replicate in each sample) to identify differential chromatin interactions mediated by a protein of interest. Both models incorporate the data dependency and the extent to which a fragment pair is related to a pair of DNA loci of interest to make accurate identifications. The One-Step Model makes use of the data more efficiently but is more computationally intensive. An extensive simulation study showed that the models can detect those differentially interacted chromatins and there is a good agreement between each classification result and the truth. Application of the method to a two-sample ChIA-PET data set illustrates its utility. The two models are implemented as an R package MDM (available at http://www.stat.osu.edu/~statgen/SOFTWARE/MDM).

Statistical Models for Detecting Differential Chromatin Interactions Mediated by a Protein

PubMed Central

Niu, Liang; Li, Guoliang; Lin, Shili

2014-01-01

Chromatin interactions mediated by a protein of interest are of great scientific interest. Recent studies show that protein-mediated chromatin interactions can have different intensities in different types of cells or in different developmental stages of a cell. Such differences can be associated with a disease or with the development of a cell. Thus, it is of great importance to detect protein-mediated chromatin interactions with different intensities in different cells. A recent molecular technique, Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET), which uses formaldehyde cross-linking and paired-end sequencing, is able to detect genome-wide chromatin interactions mediated by a protein of interest. Here we proposed two models (One-Step Model and Two-Step Model) for two sample ChIA-PET count data (one biological replicate in each sample) to identify differential chromatin interactions mediated by a protein of interest. Both models incorporate the data dependency and the extent to which a fragment pair is related to a pair of DNA loci of interest to make accurate identifications. The One-Step Model makes use of the data more efficiently but is more computationally intensive. An extensive simulation study showed that the models can detect those differentially interacted chromatins and there is a good agreement between each classification result and the truth. Application of the method to a two-sample ChIA-PET data set illustrates its utility. The two models are implemented as an R package MDM (available at http://www.stat.osu.edu/~statgen/SOFTWARE/MDM). PMID:24835279

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

PubMed

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

2014-01-01

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

A powerful nonparametric method for detecting differentially co-expressed genes: distance correlation screening and edge-count test.

PubMed

Zhang, Qingyang

2018-05-16

Differential co-expression analysis, as a complement of differential expression analysis, offers significant insights into the changes in molecular mechanism of different phenotypes. A prevailing approach to detecting differentially co-expressed genes is to compare Pearson's correlation coefficients in two phenotypes. However, due to the limitations of Pearson's correlation measure, this approach lacks the power to detect nonlinear changes in gene co-expression which is common in gene regulatory networks. In this work, a new nonparametric procedure is proposed to search differentially co-expressed gene pairs in different phenotypes from large-scale data. Our computational pipeline consisted of two main steps, a screening step and a testing step. The screening step is to reduce the search space by filtering out all the independent gene pairs using distance correlation measure. In the testing step, we compare the gene co-expression patterns in different phenotypes by a recently developed edge-count test. Both steps are distribution-free and targeting nonlinear relations. We illustrate the promise of the new approach by analyzing the Cancer Genome Atlas data and the METABRIC data for breast cancer subtypes. Compared with some existing methods, the new method is more powerful in detecting nonlinear type of differential co-expressions. The distance correlation screening can greatly improve computational efficiency, facilitating its application to large data sets.

WAKES: Wavelet Adaptive Kinetic Evolution Solvers

NASA Astrophysics Data System (ADS)

Mardirian, Marine; Afeyan, Bedros; Larson, David

2016-10-01

We are developing a general capability to adaptively solve phase space evolution equations mixing particle and continuum techniques in an adaptive manner. The multi-scale approach is achieved using wavelet decompositions which allow phase space density estimation to occur with scale dependent increased accuracy and variable time stepping. Possible improvements on the SFK method of Larson are discussed, including the use of multiresolution analysis based Richardson-Lucy Iteration, adaptive step size control in explicit vs implicit approaches. Examples will be shown with KEEN waves and KEEPN (Kinetic Electrostatic Electron Positron Nonlinear) waves, which are the pair plasma generalization of the former, and have a much richer span of dynamical behavior. WAKES techniques are well suited for the study of driven and released nonlinear, non-stationary, self-organized structures in phase space which have no fluid, limit nor a linear limit, and yet remain undamped and coherent well past the drive period. The work reported here is based on the Vlasov-Poisson model of plasma dynamics. Work supported by a Grant from the AFOSR.

A machine learning approach to computer-aided molecular design

NASA Astrophysics Data System (ADS)

Bolis, Giorgio; Di Pace, Luigi; Fabrocini, Filippo

1991-12-01

Preliminary results of a machine learning application concerning computer-aided molecular design applied to drug discovery are presented. The artificial intelligence techniques of machine learning use a sample of active and inactive compounds, which is viewed as a set of positive and negative examples, to allow the induction of a molecular model characterizing the interaction between the compounds and a target molecule. The algorithm is based on a twofold phase. In the first one — the specialization step — the program identifies a number of active/inactive pairs of compounds which appear to be the most useful in order to make the learning process as effective as possible and generates a dictionary of molecular fragments, deemed to be responsible for the activity of the compounds. In the second phase — the generalization step — the fragments thus generated are combined and generalized in order to select the most plausible hypothesis with respect to the sample of compounds. A knowledge base concerning physical and chemical properties is utilized during the inductive process.

Hi-C 2.0: An optimized Hi-C procedure for high-resolution genome-wide mapping of chromosome conformation.

PubMed

Belaghzal, Houda; Dekker, Job; Gibcus, Johan H

2017-07-01

Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (kb) resolution. It also includes steps to reduce random ligation and the generation of uninformative molecules, such as unligated ends, to improve the amount of valid intra-chromosomal read pairs. This protocol allows for obtaining information on conformational structures such as compartment and topologically associating domains, as well as high-resolution conformational features such as DNA loops. Copyright © 2017 Elsevier Inc. All rights reserved.

Unwanted signal leakage in excitation sculpting with single axis gradients.

PubMed

Jerschow, A

1999-03-01

Excitation sculpting (T-L. Hwang and A. J. Shaka, J. Magn. Reson. A 112, 275-279 (1995)) used for solvent suppression and selective excitation in NMR bases its success on the ability to remove baseline and phase errors created by the application of selective rf pulses. This is achieved by the application of two pulsed field gradient (PFG) echoes in sequence. It is essential that the two pairs of PFGs select the coherence transfer steps independently of each other, which is conveniently achieved if they are applied along orthogonal spatial axes. Here, the much more common case where both PFG pairs must be applied along a single axis is investigated. This is shown to lead to complications for certain ratios of PFG strengths. The original theory of excitation sculpting is restated in the spherical basis for convenience. Some of the effects can only be explained by invoking the dipolar demagnetizing field. Copyright 1999 Academic Press.

Design Considerations for a Dedicated Gravity Recovery Satellite Mission Consisting of Two Pairs of Satellites

NASA Technical Reports Server (NTRS)

Wiese, D. N.; Nerem, R. S.; Lemoine, F. G.

2011-01-01

Future satellite missions dedicated to measuring time-variable gravity will need to address the concern of temporal aliasing errors; i.e., errors due to high-frequency mass variations. These errors have been shown to be a limiting error source for future missions with improved sensors. One method of reducing them is to fly multiple satellite pairs, thus increasing the sampling frequency of the mission. While one could imagine a system architecture consisting of dozens of satellite pairs, this paper explores the more economically feasible option of optimizing the orbits of two pairs of satellites. While the search space for this problem is infinite by nature, steps have been made to reduce it via proper assumptions regarding some parameters and a large number of numerical simulations exploring appropriate ranges for other parameters. A search space originally consisting of 15 variables is reduced to two variables with the utmost impact on mission performance: the repeat period of both pairs of satellites (shown to be near-optimal when they are equal to each other), as well as the inclination of one of the satellite pairs (the other pair is assumed to be in a polar orbit). To arrive at this conclusion, we assume circular orbits, repeat groundtracks for both pairs of satellites, a 100-km inter-satellite separation distance, and a minimum allowable operational satellite altitude of 290 km based on a projected 10-year mission lifetime. Given the scientific objectives of determining time-variable hydrology, ice mass variations, and ocean bottom pressure signals with higher spatial resolution, we find that an optimal architecture consists of a polar pair of satellites coupled with a pair inclined at 72deg, both in 13-day repeating orbits. This architecture provides a 67% reduction in error over one pair of satellites, in addition to reducing the longitudinal striping to such a level that minimal post-processing is required, permitting a substantial increase in the spatial resolution of the gravity field products. It should be emphasized that given different sets of scientific objectives for the mission, or a different minimum allowable satellite altitude, different architectures might be selected.

Hidden Hydride Transfer as a Decisive Mechanistic Step in the Reactions of the Unligated Gold Carbide [AuC]+ with Methane under Ambient Conditions.

PubMed

Li, Jilai; Zhou, Shaodong; Schlangen, Maria; Weiske, Thomas; Schwarz, Helmut

2016-10-10

The reactivity of the cationic gold carbide [AuC] + (bearing an electrophilic carbon atom) towards methane has been studied using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The product pairs generated, that is, Au + /C 2 H 4 , [Au(C 2 H 2 )] + /H 2 , and [C 2 H 3 ] + /AuH, point to the breaking and making of C-H, C-C, and H-H bonds under single-collision conditions. The mechanisms of these rather efficient reactions have been elucidated by high-level quantum-chemical calculations. As a major result, based on molecular orbital and NBO-based charge analysis, an unprecedented hydride transfer from methane to the carbon atom of [AuC] + has been identified as a key step. Also, the origin of this novel mechanistic scenario has been addressed. The mechanistic insights derived from this study may provide guidance for the rational design of carbon-based catalysts. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

FRET-based glucose monitoring for bioprocessing

NASA Astrophysics Data System (ADS)

Bartolome, Amelita; Smalls-Mantey, Lauren; Lin, Debora; Rao, Govind; Tolosa, Leah

2006-02-01

The glucose-mediated conformational changes in the glucose binding protein (GBP) have been exploited in the development of fluorescence based glucose sensors. The fluorescence response is generated by a polarity sensitive dye attached to a specific site. Such fluorescent sensors respond to submicromolar glucose at diffusion-controlled rates mimicking the wild type. However, such sensors have been limited to in vitro glucose sensing because of the preliminary dye-labeling step. In the study described here, the dye-labeling step is omitted by genetically encoding the GBP with two green fluorescent mutants namely, the green fluorescent protein (GFP) and the yellow fluorescent protein (YFP) in the N- and C-terminal ends, respectively. These two GFP mutants comprise a fluorescence resonance energy transfer (FRET) donor and acceptor pair. Thus, when glucose binds with GBP, the conformational changes affect the FRET efficiency yielding a dose-dependent response. A potential application for this FRET-based glucose biosensor is online glucose sensing in bioprocessing and cell culture. This was demonstrated by the measurement of glucose consumption in yeast fermentation. Further development of this system should yield in vivo measurement of glucose in bioprocesses.

Support Vector Machine-based classification of protein folds using the structural properties of amino acid residues and amino acid residue pairs.

PubMed

Shamim, Mohammad Tabrez Anwar; Anwaruddin, Mohammad; Nagarajaram, H A

2007-12-15

Fold recognition is a key step in the protein structure discovery process, especially when traditional sequence comparison methods fail to yield convincing structural homologies. Although many methods have been developed for protein fold recognition, their accuracies remain low. This can be attributed to insufficient exploitation of fold discriminatory features. We have developed a new method for protein fold recognition using structural information of amino acid residues and amino acid residue pairs. Since protein fold recognition can be treated as a protein fold classification problem, we have developed a Support Vector Machine (SVM) based classifier approach that uses secondary structural state and solvent accessibility state frequencies of amino acids and amino acid pairs as feature vectors. Among the individual properties examined secondary structural state frequencies of amino acids gave an overall accuracy of 65.2% for fold discrimination, which is better than the accuracy by any method reported so far in the literature. Combination of secondary structural state frequencies with solvent accessibility state frequencies of amino acids and amino acid pairs further improved the fold discrimination accuracy to more than 70%, which is approximately 8% higher than the best available method. In this study we have also tested, for the first time, an all-together multi-class method known as Crammer and Singer method for protein fold classification. Our studies reveal that the three multi-class classification methods, namely one versus all, one versus one and Crammer and Singer method, yield similar predictions. Dataset and stand-alone program are available upon request.

Free-space quantum key distribution with a high generation rate potassium titanyl phosphate waveguide photon-pair source

NASA Astrophysics Data System (ADS)

Wilson, Jeffrey D.; Chaffee, Dalton W.; Wilson, Nathaniel C.; Lekki, John D.; Tokars, Roger P.; Pouch, John J.; Roberts, Tony D.; Battle, Philip R.; Floyd, Bertram; Lind, Alexander J.; Cavin, John D.; Helmick, Spencer R.

2016-09-01

A high generation rate photon-pair source using a dual element periodically-poled potassium titanyl phosphate (PP KTP) waveguide is described. The fully integrated photon-pair source consists of a 1064-nm pump diode laser, fiber-coupled to a dual element waveguide within which a pair of 1064-nm photons are up-converted to a single 532-nm photon in the first stage. In the second stage, the 532-nm photon is down-converted to an entangled photon-pair at 800 nm and 1600 nm which are fiber-coupled at the waveguide output. The photon-pair source features a high pair generation rate, a compact power-efficient package, and continuous wave (CW) or pulsed operation. This is a significant step towards the long term goal of developing sources for high-rate Quantum Key Distribution (QKD) to enable Earth-space secure communications. Characterization and test results are presented. Details and preliminary results of a laboratory free space QKD experiment with the B92 protocol are also presented.

Free-Space Quantum Key Distribution with a High Generation Rate Potassium Titanyl Phosphate Waveguide Photon-Pair Source

NASA Technical Reports Server (NTRS)

Wilson, Jeffrey D.; Chaffee, Dalton W.; Wilson, Nathaniel C.; Lekki, John D.; Tokars, Roger P.; Pouch, John J.; Roberts, Tony D.; Battle, Philip; Floyd, Bertram M.; Lind, Alexander J.;

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

Devadoss, C.; Fessenden, R.W.

The transient that is produced in the quenching of triplet benzophenone by 1,4-diazabicyclo(2.2.2)octane (DABCO) has been examined by use of nano- and picosecond laser photolysis. The initial step in all solvents, both polar and nonpolar, is electron transfer to form a triplet contact ion pair. In nonpolar solvents, the ion pair remains in this form until it decays. For polar solvents, the spectra change somewhat over the first 100 ps showing that the solvation changes and the ion pair becomes solvent separated. The lifetime of the ion pair varies greatly with the solvent. In saturated hydrocarbons it is about 80more » ps. Nonpolar solvents with either {pi} electrons or a lone pair of electrons stabilize the ion pair on the nanosecond to microsecond time scale. A small amount of alcohol in benzene also stabilizes the ion pair by hydrogen bonding. A shift in the peak position with time toward the blue accompanies the formation of hydrogen bonds in this case.« less

Lewis pair polymerization by classical and frustrated Lewis pairs: acid, base and monomer scope and polymerization mechanism.

PubMed

Zhang, Yuetao; Miyake, Garret M; John, Mallory G; Falivene, Laura; Caporaso, Lucia; Cavallo, Luigi; Chen, Eugene Y-X

2012-08-14

Classical and frustrated Lewis pairs (LPs) of the strong Lewis acid (LA) Al(C(6)F(5))(3) with several Lewis base (LB) classes have been found to exhibit exceptional activity in the Lewis pair polymerization (LPP) of conjugated polar alkenes such as methyl methacrylate (MMA) as well as renewable α-methylene-γ-butyrolactone (MBL) and γ-methyl-α-methylene-γ-butyrolactone (γ-MMBL), leading to high molecular weight polymers, often with narrow molecular weight distributions. This study has investigated a large number of LPs, consisting of 11 LAs as well as 10 achiral and 4 chiral LBs, for LPP of 12 monomers of several different types. Although some more common LAs can also be utilized for LPP, Al(C(6)F(5))(3)-based LPs are far more active and effective than other LA-based LPs. On the other hand, several classes of LBs, when paired with Al(C(6)F(5))(3), can render highly active and effective LPP of MMA and γ-MMBL; such LBs include phosphines (e.g., P(t)Bu(3)), chiral chelating diphosphines, N-heterocyclic carbenes (NHCs), and phosphazene superbases (e.g., P(4)-(t)Bu). The P(4)-(t)Bu/Al(C(6)F(5))(3) pair exhibits the highest activity of the LP series, with a remarkably high turn-over frequency of 9.6 × 10(4) h(-1) (0.125 mol% catalyst, 100% MMA conversion in 30 s, M(n) = 2.12 × 10(5) g mol(-1), PDI = 1.34). The polymers produced by LPs at RT are typically atactic (P(γ)MMBL with ∼47% mr) or syndio-rich (PMMA with ∼70-75% rr), but highly syndiotactic PMMA with rr ∼91% can be produced by chiral or achiral LPs at -78 °C. Mechanistic studies have identified and structurally characterized zwitterionic phosphonium and imidazolium enolaluminates as the active species of the current LPP system, which are formed by the reaction of the monomer·Al(C(6)F(5))(3) adduct with P(t)Bu(3) and NHC bases, respectively. Kinetic studies have revealed that the MMA polymerization by the (t)Bu(3)P/Al(C(6)F(5))(3) pair is zero-order in monomer concentration after an initial induction period, and the polymerization is significantly catalyzed by the LA, thus pointing to a bimetallic, activated monomer propagation mechanism. Computational study on the active species formation as well as the chain initiation and propagation events involved in the LPP of MMA with some of the most representative LPs has added our understanding of fundamental steps of LPP. The main difference between NHC and PR(3) bases is in the energetics of zwitterion formation, with the NHC-based zwitterions being remarkably more stable than the PR(3)-based zwitterions. Comparison of the monometallic and bimetallic mechanisms for MMA addition shows a clear preference for the bimetallic mechanism.

3DNALandscapes: a database for exploring the conformational features of DNA.

PubMed

Zheng, Guohui; Colasanti, Andrew V; Lu, Xiang-Jun; Olson, Wilma K

2010-01-01

3DNALandscapes, located at: http://3DNAscapes.rutgers.edu, is a new database for exploring the conformational features of DNA. In contrast to most structural databases, which archive the Cartesian coordinates and/or derived parameters and images for individual structures, 3DNALandscapes enables searches of conformational information across multiple structures. The database contains a wide variety of structural parameters and molecular images, computed with the 3DNA software package and known to be useful for characterizing and understanding the sequence-dependent spatial arrangements of the DNA sugar-phosphate backbone, sugar-base side groups, base pairs, base-pair steps, groove structure, etc. The data comprise all DNA-containing structures--both free and bound to proteins, drugs and other ligands--currently available in the Protein Data Bank. The web interface allows the user to link, report, plot and analyze this information from numerous perspectives and thereby gain insight into DNA conformation, deformability and interactions in different sequence and structural contexts. The data accumulated from known, well-resolved DNA structures can serve as useful benchmarks for the analysis and simulation of new structures. The collective data can also help to understand how DNA deforms in response to proteins and other molecules and undergoes conformational rearrangements.

Sulphur responsiveness of the Chlamydomonas reinhardtii LHCBM9 promoter.

PubMed

Sawyer, Anne L; Hankamer, Ben D; Ross, Ian L

2015-05-01

A 44-base-pair region in the Chlamydomonas reinhardtii LHCBM9 promoter is essential for sulphur responsiveness. The photosynthetic light-harvesting complex (LHC) proteins play essential roles both in light capture, the first step of photosynthesis, and in photoprotective mechanisms. In contrast to the other LHC proteins and the majority of photosynthesis proteins, the Chlamydomonas reinhardtii photosystem II-associated LHC protein, LHCBM9, was recently reported to be up-regulated under sulphur deprivation conditions, which also induce hydrogen production. Here, we examined the sulphur responsiveness of the LHCBM9 gene at the transcriptional level, through promoter deletion analysis. The LHCBM9 promoter was found to be responsive to sulphur deprivation, with a 44-base-pair region between nucleotide positions -136 and -180 relative to the translation start site identified as essential for this response. Anaerobiosis was found to enhance promoter activity under sulphur deprivation conditions, however, alone was unable to induce promoter activity. The study of LHCBM9 is of biological and biotechnological importance, as its expression is linked to photobiological hydrogen production, theoretically the most efficient process for biofuel production, while the simplicity of using an S-deprivation trigger enables the development of a novel C. reinhardtii-inducible promoter system based on LHCBM9.

Stopband-Extended and Size-Miniaturized Low-Pass Filter Based on Interdigital Capacitor Loaded Hairpin Resonator with Four Transmission Zeros

NASA Astrophysics Data System (ADS)

Wu, Jia-Jia; Li, Lin

2018-04-01

In this paper, a compact low-pass filter (LPF) with wide stopband is proposed based on interdigital capacitor loaded hairpin resonator. The structure composed of an upper high-impedance transmission line, a middle interdigital capacitor, and a pair of inter-coupled symmetrical stepped-impedance stubs. Detailed investigation into this structure based on even-odd mode approach reveals that up to four transmission zeros can be generated and reallocated by choosing the proper circuit parameters. And owing to the aid of transmission zeros, the fabricated quasi-elliptic LPFs experimentally demonstrate a wide 20dB stopband from 1.4fc to 5.1fc using a compact size of only 0.005 λg2.

CryoEM structure of the spliceosome immediately after branching

PubMed Central

Galej, Wojciech P.; Wilkinson, Max E.; Fica, Sebastian M.; Oubridge, Chris; Newman, Andrew J.; Nagai, Kiyoshi

2016-01-01

Pre-mRNA splicing proceeds by two consecutive trans-esterification reactions via a lariat-intron intermediate. We present the 3.8Å cryoEM structure of the spliceosome immediately after lariat formation. The 5’-splice site is cleaved but remains close to the catalytic Mg2+ site in the U2/U6 snRNA triplex, and the 5’-phosphate of the intron nucleotide G(+1) is linked to the branch adenosine 2’OH. The 5’-exon is held between the Prp8 N-terminal and Linker domains, and base-pairs with U5 snRNA loop 1. Non-Watson-Crick interactions between the branch helix and 5’-splice site dock the branch adenosine into the active site, while intron nucleotides +3 to +6 base-pair with the U6 snRNA ACAGAGA sequence. Isy1 and the step one factors Yju2 and Cwc25 stabilise docking of the branch helix. The intron downstream of the branch site emerges between the Prp8 RT and Linker domains and extends towards Prp16 helicase, suggesting a plausible mechanism of remodelling before exon ligation. PMID:27459055

The Importance of Electron Correlation on Stacking Interaction of Adenine-Thymine Base-Pair Step in B-DNA: A Quantum Monte Carlo Study.

PubMed

Hongo, Kenta; Cuong, Nguyen Thanh; Maezono, Ryo

2013-02-12

We report fixed-node diffusion Monte Carlo (DMC) calculations of stacking interaction energy between two adenine(A)-thymine(T) base pairs in B-DNA (AA:TT), for which reference data are available, obtained from a complete basis set estimate of CCSD(T) (coupled-cluster with singles, doubles, and perturbative triples). We consider four sets of nodal surfaces obtained from self-consistent field calculations and examine how the different nodal surfaces affect the DMC potential energy curves of the AA:TT molecule and the resulting stacking energies. We find that the DMC potential energy curves using the different nodes look similar to each other as a whole. We also benchmark the performance of various quantum chemistry methods, including Hartree-Fock (HF) theory, second-order Møller-Plesset perturbation theory (MP2), and density functional theory (DFT). The DMC and recently developed DFT results of the stacking energy reasonably agree with the reference, while the HF, MP2, and conventional DFT methods give unsatisfactory results.

Comparison of two novel in-syringe dispersive liquid-liquid microextraction techniques for the determination of iodide in water samples using spectrophotometry.

PubMed

Kaykhaii, Massoud; Sargazi, Mona

2014-01-01

Two new, rapid methodologies have been developed and applied successfully for the determination of trace levels of iodide in real water samples. Both techniques are based on a combination of in-syringe dispersive liquid-liquid microextraction (IS-DLLME) and micro-volume UV-Vis spectrophotometry. In the first technique, iodide is oxidized with nitrous acid to the colorless anion of ICl2(-) at high concentration of hydrochloric acid. Rhodamine B is added and by means of one step IS-DLLME, the ion-pair formed was extracted into toluene and measured spectrophotometrically. Acetone is used as dispersive solvent. The second method is based on the IS-DLLME microextraction of iodide as iodide/1, 10-phenanthroline-iron((II)) chelate cation ion-pair (colored) into nitrobenzene. Methanol was selected as dispersive solvent. Optimal conditions for iodide extraction were determined for both approaches. Methods are compared in terms of analytical parameters such as precision, accuracy, speed and limit of detection. Both methods were successfully applied to determining iodide in tap and river water samples. Copyright © 2013 Elsevier B.V. All rights reserved.

DNA denaturation bubbles: free-energy landscape and nucleation/closure rates.

PubMed

Sicard, François; Destainville, Nicolas; Manghi, Manoel

2015-01-21

The issue of the nucleation and slow closure mechanisms of non-superhelical stress-induced denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (respectively, closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of 22 kBT (respectively, 13 kBT) at room temperature T. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, those more than 4 base-pair bubbles are of biological relevance, for example, when a pre-existing state of denaturation is required by specific DNA-binding proteins.

Fast algorithms for computing phylogenetic divergence time.

PubMed

Crosby, Ralph W; Williams, Tiffani L

2017-12-06

The inference of species divergence time is a key step in most phylogenetic studies. Methods have been available for the last ten years to perform the inference, but the performance of the methods does not yet scale well to studies with hundreds of taxa and thousands of DNA base pairs. For example a study of 349 primate taxa was estimated to require over 9 months of processing time. In this work, we present a new algorithm, AncestralAge, that significantly improves the performance of the divergence time process. As part of AncestralAge, we demonstrate a new method for the computation of phylogenetic likelihood and our experiments show a 90% improvement in likelihood computation time on the aforementioned dataset of 349 primates taxa with over 60,000 DNA base pairs. Additionally, we show that our new method for the computation of the Bayesian prior on node ages reduces the running time for this computation on the 349 taxa dataset by 99%. Through the use of these new algorithms we open up the ability to perform divergence time inference on large phylogenetic studies.

Inductive Game Theory and the Dynamics of Animal Conflict

PubMed Central

DeDeo, Simon; Krakauer, David C.; Flack, Jessica C.

2010-01-01

Conflict destabilizes social interactions and impedes cooperation at multiple scales of biological organization. Of fundamental interest are the causes of turbulent periods of conflict. We analyze conflict dynamics in an monkey society model system. We develop a technique, Inductive Game Theory, to extract directly from time-series data the decision-making strategies used by individuals and groups. This technique uses Monte Carlo simulation to test alternative causal models of conflict dynamics. We find individuals base their decision to fight on memory of social factors, not on short timescale ecological resource competition. Furthermore, the social assessments on which these decisions are based are triadic (self in relation to another pair of individuals), not pairwise. We show that this triadic decision making causes long conflict cascades and that there is a high population cost of the large fights associated with these cascades. These results suggest that individual agency has been over-emphasized in the social evolution of complex aggregates, and that pair-wise formalisms are inadequate. An appreciation of the empirical foundations of the collective dynamics of conflict is a crucial step towards its effective management. PMID:20485557

Inductive game theory and the dynamics of animal conflict.

PubMed

DeDeo, Simon; Krakauer, David C; Flack, Jessica C

2010-05-13

Conflict destabilizes social interactions and impedes cooperation at multiple scales of biological organization. Of fundamental interest are the causes of turbulent periods of conflict. We analyze conflict dynamics in an monkey society model system. We develop a technique, Inductive Game Theory, to extract directly from time-series data the decision-making strategies used by individuals and groups. This technique uses Monte Carlo simulation to test alternative causal models of conflict dynamics. We find individuals base their decision to fight on memory of social factors, not on short timescale ecological resource competition. Furthermore, the social assessments on which these decisions are based are triadic (self in relation to another pair of individuals), not pairwise. We show that this triadic decision making causes long conflict cascades and that there is a high population cost of the large fights associated with these cascades. These results suggest that individual agency has been over-emphasized in the social evolution of complex aggregates, and that pair-wise formalisms are inadequate. An appreciation of the empirical foundations of the collective dynamics of conflict is a crucial step towards its effective management.

Example-based learning: comparing the effects of additionally providing three different integrative learning activities on physiotherapy intervention knowledge.

PubMed

Dyer, Joseph-Omer; Hudon, Anne; Montpetit-Tourangeau, Katherine; Charlin, Bernard; Mamede, Sílvia; van Gog, Tamara

2015-03-07

Example-based learning using worked examples can foster clinical reasoning. Worked examples are instructional tools that learners can use to study the steps needed to solve a problem. Studying worked examples paired with completion examples promotes acquisition of problem-solving skills more than studying worked examples alone. Completion examples are worked examples in which some of the solution steps remain unsolved for learners to complete. Providing learners engaged in example-based learning with self-explanation prompts has been shown to foster increased meaningful learning compared to providing no self-explanation prompts. Concept mapping and concept map study are other instructional activities known to promote meaningful learning. This study compares the effects of self-explaining, completing a concept map and studying a concept map on conceptual knowledge and problem-solving skills among novice learners engaged in example-based learning. Ninety-one physiotherapy students were randomized into three conditions. They performed a pre-test and a post-test to evaluate their gains in conceptual knowledge and problem-solving skills (transfer performance) in intervention selection. They studied three pairs of worked/completion examples in a digital learning environment. Worked examples consisted of a written reasoning process for selecting an optimal physiotherapy intervention for a patient. The completion examples were partially worked out, with the last few problem-solving steps left blank for students to complete. The students then had to engage in additional self-explanation, concept map completion or model concept map study in order to synthesize and deepen their knowledge of the key concepts and problem-solving steps. Pre-test performance did not differ among conditions. Post-test conceptual knowledge was higher (P < .001) in the concept map study condition (68.8 ± 21.8%) compared to the concept map completion (52.8 ± 17.0%) and self-explanation (52.2 ± 21.7%) conditions. Post-test problem-solving performance was higher (P < .05) in the self-explanation (63.2 ± 16.0%) condition compared to the concept map study (53.3 ± 16.4%) and concept map completion (51.0 ± 13.6%) conditions. Students in the self-explanation condition also invested less mental effort in the post-test. Studying model concept maps led to greater conceptual knowledge, whereas self-explanation led to higher transfer performance. Self-explanation and concept map study can be combined with worked example and completion example strategies to foster intervention selection.

Earth Exploration Toolbook Workshops: Helping Teachers and Students Analyze Web-based Scientific Data

NASA Astrophysics Data System (ADS)

McAuliffe, C.; Ledley, T.; Dahlman, L.; Haddad, N.

2007-12-01

One of the challenges faced by Earth science teachers, particularly in K-12 settings, is that of connecting scientific research to classroom experiences. Helping teachers and students analyze Web-based scientific data is one way to bring scientific research to the classroom. The Earth Exploration Toolbook (EET) was developed as an online resource to accomplish precisely that. The EET consists of chapters containing step-by-step instructions for accessing Web-based scientific data and for using a software analysis tool to explore issues or concepts in science, technology, and mathematics. For example, in one EET chapter, users download Earthquake data from the USGS and bring it into a geographic information system (GIS), analyzing factors affecting the distribution of earthquakes. The goal of the EET Workshops project is to provide professional development that enables teachers to incorporate Web-based scientific data and analysis tools in ways that meet their curricular needs. In the EET Workshops project, Earth science teachers participate in a pair of workshops that are conducted in a combined teleconference and Web-conference format. In the first workshop, the EET Data Analysis Workshop, participants are introduced to the National Science Digital Library (NSDL) and the Digital Library for Earth System Education (DLESE). They also walk through an Earth Exploration Toolbook (EET) chapter and discuss ways to use Earth science datasets and tools with their students. In a follow-up second workshop, the EET Implementation Workshop, teachers share how they used these materials in the classroom by describing the projects and activities that they carried out with students. The EET Workshops project offers unique and effective professional development. Participants work at their own Internet-connected computers, and dial into a toll-free group teleconference for step-by-step facilitation and interaction. They also receive support via Elluminate, a Web-conferencing software program. The software allows participants to see the facilitator's computer as the analysis techniques of an EET chapter are demonstrated. If needed, the facilitator can also view individual participant's computers, assisting with technical difficulties. In addition, it enables a large number of end users, often widely distributed, to engage in interactive, real-time instruction. In this presentation, we will describe the elements of an EET Workshop pair, highlighting the capabilities and use of Elluminate. We will share lessons learned through several years of conducting this type of professional development. We will also share findings from survey data gathered from teachers who have participated in our workshops.

The causes of parent–offspring transmission of drug abuse: a Swedish population-based study

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2014-01-01

Background While drug abuse (DA) is strongly familial, we still have limited knowledge about the causes of its cross-generational transmission. Method We examined DA ascertained from national registers in offspring of three family types from the Swedish population [intact (n=2111074), ‘not-lived-with’ (n = 165315, where biological parents never lived with their offspring) and ‘step’ (n = 124800 offspring)], which reflected, respectively, the effects of genes+rearing, genes only and rearing only. We replicated these results in three high-risk co-relative designs. Results Combined across mothers and fathers, the hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact, 2.73 in ‘not-lived-with’ and 1.79 in stepfamilies. In 968 biological full or half-sibling pairs one of whom was reared by and the other never lived with their parent with DA, the HR for DA was greater in the reared than ‘not-lived-with’ child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was greater in a reared biological v. step-parented non-biological child (HR 3.33). In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with biological child and the second a step-parented non-biological child, the HR for DA was greater in the biological v. stepchild (HR 1.80). Conclusions Both genetic and environmental factors contribute substantially to parent–offspring resemblance for DA. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent–offspring resemblance. PMID:25066684

Temperature Dependence of Quasiparticle Spectral Weight and Coherence in High Tc Superconductors

NASA Astrophysics Data System (ADS)

He, Yang; Zhang, Jessie; Hoffman, Jennifer; Hoffman Lab Team

2014-03-01

Superconductivity arises from the Cooper pairing of quasiparticles on the Fermi surface. Understanding the formation of Cooper pairs is an essential step towards unveiling the mechanism of high Tc superconductivity. We compare scanning tunneling microscope investigations of the temperature dependence of quasiparticle spectral weight and quasiparticle interference in several families of high Tc materials. We calculate the coherent spectral weight related to superconductivity, despite the coexistence of competing orders. The relation between pairing temperature and coherent spectral weight is discussed. We acknowledge support by the New York Community Trust-George Merck Fund.

Expanding the universe of categorical syllogisms: a challenge for reasoning researchers.

PubMed

Roberts, Maxwell J

2005-11-01

Syllogistic reasoning, in which people identify conclusions from quantified premise pairs, remains a benchmark task whose patterns of data must be accounted for by general theories of deductive reasoning. However, psychologists have confined themselves to administering only the 64 premise pairs historically identified by Aristotle. By utilizing all combinations of negations, the present article identifies an expanded set of 576 premise pairs and gives the valid conclusions that they support. Many of these have interesting properties, and the identification of predictions and their verification will be an important next step for all proponents of such theories.

Scattering Matrix Elements for the Nonadiabatic Collision

DTIC Science & Technology

2010-12-01

orthogonality relationship expressed in (77). This technique, known as the Channel Packet Method (CPM), is laid out by Weeks and Tannor [2...time and energy are Fourier transform pairs, and share the same relationship as the coordinate/momentum pairs: max min 2E t t π ∆ = − (99) As...elements, will exibit ringing. Selection of an inappropriatly large time step introduces an erroneous phase shift in the correlation funtion . This

Unlocking Short Read Sequencing for Metagenomics

DOE PAGES

Rodrigue, Sébastien; Materna, Arne C.; Timberlake, Sonia C.; ...

2010-07-28

We describe an experimental and computational pipeline yielding millions of reads that can exceed 200 bp with quality scores approaching that of traditional Sanger sequencing. The method combines an automatable gel-less library construction step with paired-end sequencing on a short-read instrument. With appropriately sized library inserts, mate-pair sequences can overlap, and we describe the SHERA software package that joins them to form a longer composite read.

Investigation of Item-Pair Presentation and Construct Validity of the Navy Computer Adaptive Personality Scales (NCAPS)

DTIC Science & Technology

2006-10-01

NCAPS ) Christina M. Underhill, Ph.D. Approved for public release; distribution is unlimited. NPRST-TN-06-9 October 2006...Investigation of Item-Pair Presentation and Construct Validity of the Navy Computer Adaptive Personality Scales ( NCAPS ) Christina M. Underhill, Ph.D...documents one of the steps in our development of the Navy Computer Adaptive Personality Scales ( NCAPS ). NCAPS is a computer adaptive personality measure

Real-time observation of formation and relaxation dynamics of NH4 in (CH3OH)m(NH3)n clusters.

PubMed

Yamada, Yuji; Nishino, Yoko; Fujihara, Akimasa; Ishikawa, Haruki; Fuke, Kiyokazu

2009-03-26

The formation and relaxation dynamics of NH4(CH3OH)m(NH3)n clusters produced by photolysis of ammonia-methanol mixed clusters has been observed by a time-resolved pump-probe method with femtosecond pulse lasers. From the detailed analysis of the time evolutions of the protonated cluster ions, NH4(+)(CH3OH)m(NH3)n, the kinetic model has been constructed, which consists of sequential three-step reaction: ultrafast hydrogen-atom transfer producing the radical pair (NH4-NH2)*, the relaxation process of radical-pair clusters, and dissociation of the solvated NH4 clusters. The initial hydrogen transfer hardly occurs between ammonia and methanol, implying the unfavorable formation of radical pair, (CH3OH2-NH2)*. The remarkable dependence of the time constants in each step on the number and composition of solvents has been explained by the following factors: hydrogen delocalization within the clusters, the internal conversion of the excited-state radical pair, and the stabilization of NH4 by solvation. The dependence of the time profiles on the probe wavelength is attributed to the different ionization efficiency of the NH4(CH3OH)m(NH3)n clusters.

Self-Regulated Strategy Development Instruction for Teaching Multi-Step Equations to Middle School Students Struggling in Math

ERIC Educational Resources Information Center

Cuenca-Carlino, Yojanna; Freeman-Green, Shaqwana; Stephenson, Grant W.; Hauth, Clara

2016-01-01

Six middle school students identified as having a specific learning disability or at risk for mathematical difficulties were taught how to solve multi-step equations by using the self-regulated strategy development (SRSD) model of instruction. A multiple-probe-across-pairs design was used to evaluate instructional effects. Instruction was provided…

Accuracy of the Yamax CW-701 Pedometer for measuring steps in controlled and free-living conditions

PubMed Central

Coffman, Maren J; Reeve, Charlie L; Butler, Shannon; Keeling, Maiya; Talbot, Laura A

2016-01-01

Objective The Yamax Digi-Walker CW-701 (Yamax CW-701) is a low-cost pedometer that includes a 7-day memory, a 2-week cumulative memory, and automatically resets to zero at midnight. To date, the accuracy of the Yamax CW-701 has not been determined. The purpose of this study was to assess the accuracy of steps recorded by the Yamax CW-701 pedometer compared with actual steps and two other devices. Methods The study was conducted in a campus-based lab and in free-living settings with 22 students, faculty, and staff at a mid-sized university in the Southeastern US. While wearing a Yamax CW-701, Yamax Digi-Walker SW-200, and an ActiGraph GTX3 accelerometer, participants engaged in activities at variable speeds and conditions. To assess accuracy of each device, steps recorded were compared with actual step counts. Statistical tests included paired sample t-tests, percent accuracy, intraclass correlation coefficient, and Bland–Altman plots. Results The Yamax CW-701 demonstrated reliability and concurrent validity during walking at a fast pace and walking on a track, and in free-living conditions. Decreased accuracy was noted walking at a slow pace. Conclusions These findings are consistent with prior research. With most pedometers and accelerometers, adequate force and intensity must be present for a step to register. The Yamax CW-701 is accurate in recording steps taken while walking at a fast pace and in free-living settings. PMID:29942555

Accuracy of the Yamax CW-701 Pedometer for measuring steps in controlled and free-living conditions.

PubMed

Coffman, Maren J; Reeve, Charlie L; Butler, Shannon; Keeling, Maiya; Talbot, Laura A

2016-01-01

The Yamax Digi-Walker CW-701 (Yamax CW-701) is a low-cost pedometer that includes a 7-day memory, a 2-week cumulative memory, and automatically resets to zero at midnight. To date, the accuracy of the Yamax CW-701 has not been determined. The purpose of this study was to assess the accuracy of steps recorded by the Yamax CW-701 pedometer compared with actual steps and two other devices. The study was conducted in a campus-based lab and in free-living settings with 22 students, faculty, and staff at a mid-sized university in the Southeastern US. While wearing a Yamax CW-701, Yamax Digi-Walker SW-200, and an ActiGraph GTX3 accelerometer, participants engaged in activities at variable speeds and conditions. To assess accuracy of each device, steps recorded were compared with actual step counts. Statistical tests included paired sample t -tests, percent accuracy, intraclass correlation coefficient, and Bland-Altman plots. The Yamax CW-701 demonstrated reliability and concurrent validity during walking at a fast pace and walking on a track, and in free-living conditions. Decreased accuracy was noted walking at a slow pace. These findings are consistent with prior research. With most pedometers and accelerometers, adequate force and intensity must be present for a step to register. The Yamax CW-701 is accurate in recording steps taken while walking at a fast pace and in free-living settings.

Ex situ investigation of the step bunching on crystal surfaces by atomic force microscopy

NASA Astrophysics Data System (ADS)

Krasinski, Mariusz J.

1997-07-01

We are describing ex situ observation of step bunching on the surfaces of solution grown potassium dihydrogen phosphate (KDP) and sodium chlorate monocrystals. The measurements have been done with the use of atomic force microscope. The use of this equipment allowed us to see directly the structure of macrosteps. Observation confirmed the existence of step pinning which is one of the proposed mechanisms of step bunching. Despite the very high resolution of AFM it was not possible to determine the nature of pinning point. The monatomic steps on KDP and sodium chlorate crystal surfaces are mainly one unit cell high what seems to be the result of the steps pairing. The origin of observed step pattern is discussed in frames of existing theories.

Enhanced aerobic exercise performance in women by a combination of three mineral Chelates plus two conditionally essential nutrients.

PubMed

DiSilvestro, Robert A; Hart, Staci; Marshall, Trisha; Joseph, Elizabeth; Reau, Alyssa; Swain, Carmen B; Diehl, Jason

2017-01-01

Certain essential and conditionally essential nutrients (CENs) perform functions involved in aerobic exercise performance. However, increased intake of such nutrient combinations has not actually been shown to improve such performance. For 1 mo, aerobically fit, young adult women took either a combination of 3 mineral glycinate complexes (daily dose: 36 mg iron, 15 mg zinc, and 2 mg copper) + 2 CENs (daily dose: 2 g carnitine and 400 mg phosphatidylserine), or the same combination with generic mineral complexes, or placebo ( n  = 14/group). In Trial 1, before and after 1 mo, subjects were tested for 3 mile run time (primary outcome), followed by distance covered in 25 min on a stationary bike (secondary outcome), followed by a 90 s step test (secondary outcome). To test reproducibility of the run results, and to examine a lower dose of carnitine, a second trial was done. New subjects took either mineral glycinates + CENs (1 g carnitine) or placebo ( n  = 17/group); subjects were tested for pre- and post-treatment 3 mile run time (primary outcome). In Trial 1, the mineral glycinates + CENs decreased 3 mile run time (25.6 ± 2.4 vs 26.5 ± 2.3 min, p  < 0.05, paired t-test) increased stationary bike distance after 25 min (6.5 ± 0.6 vs 6.0 ± 0.8 miles, p  < 0.05, paired t-test), and increased steps in the step test (43.8 ± 4.8 vs 40.3 ± 6.4 steps, p < 0.05, paired t-test). The placebo significantly affected only the biking distance, but it was less than for the glycinates-CENs treatment (0.2 ± 0.4. vs 0.5 ± 0.1 miles, p < 0.05, ANOVA + Tukey). The generic minerals + CENs only significantly affected the step test (44.1 ± 5.2 vs 41.0 ± 5.9 steps, p < 0.05, paired t-test) In Trial 2, 3 mile run time was decreased for the mineral glycinates + CENs (23.9 ± 3.1 vs 24.7 ± 2.5, p  < 0.005, paired t-test), but not by the placebo. All changes for Test Formula II or III were high compared to placebo (1.9 to 4.9, Cohen's D), and high for Test Formula II vs I for running and biking (3.2 & 3.5, Cohen's D). In summary, a combination of certain mineral complexes plus two CENs improved aerobic exercise performance in fit young adult women.

Double-Edge Molecular Measurement of Lidar Wind Profiles at 355 nm

NASA Technical Reports Server (NTRS)

Flesia, Cristina; Korb, C. Laurence; Hirt, Christian; Einaudi, Franco (Technical Monitor)

2000-01-01

We built a direct detection Doppler lidar based on the double-edge molecular technique and made the first molecular based wind measurements using the eyesafe 355 nm wavelength. Three etalon bandpasses are obtained with Step etalons on a single pair of etalon plates. Long-term frequency drift of the laser and the capacitively stabilized etalon is removed by locking the etalon to the laser frequency. We use a low angle design to avoid polarization effects. Wind measurements of 1 to 2 m/s accuracy are obtained to 10 km altitude with 5 mJ of laser energy, a 750s integration, and a 25 cm telescope. Good agreement is obtained between the lidar and rawinsonde measurements.

Towards Agile Ontology Maintenance

NASA Astrophysics Data System (ADS)

Luczak-Rösch, Markus

Ontologies are an appropriate means to represent knowledge on the Web. Research on ontology engineering reached practices for an integrative lifecycle support. However, a broader success of ontologies in Web-based information systems remains unreached while the more lightweight semantic approaches are rather successful. We assume, paired with the emerging trend of services and microservices on the Web, new dynamic scenarios gain momentum in which a shared knowledge base is made available to several dynamically changing services with disparate requirements. Our work envisions a step towards such a dynamic scenario in which an ontology adapts to the requirements of the accessing services and applications as well as the user's needs in an agile way and reduces the experts' involvement in ontology maintenance processes.

TACT: A Set of MSC/PATRAN- and MSC/NASTRAN- based Modal Correlation Tools

NASA Technical Reports Server (NTRS)

Marlowe, Jill M.; Dixon, Genevieve D.

1998-01-01

This paper describes the functionality and demonstrates the utility of the Test Analysis Correlation Tools (TACT), a suite of MSC/PATRAN Command Language (PCL) tools which automate the process of correlating finite element models to modal survey test data. The initial release of TACT provides a basic yet complete set of tools for performing correlation totally inside the PATRAN/NASTRAN environment. Features include a step-by-step menu structure, pre-test accelerometer set evaluation and selection, analysis and test result export/import in Universal File Format, calculation of frequency percent difference and cross-orthogonality correlation results using NASTRAN, creation and manipulation of mode pairs, and five different ways of viewing synchronized animations of analysis and test modal results. For the PATRAN-based analyst, TACT eliminates the repetitive, time-consuming and error-prone steps associated with transferring finite element data to a third-party modal correlation package, which allows the analyst to spend more time on the more challenging task of model updating. The usefulness of this software is presented using a case history, the correlation for a NASA Langley Research Center (LaRC) low aspect ratio research wind tunnel model. To demonstrate the improvements that TACT offers the MSC/PATRAN- and MSC/DIASTRAN- based structural analysis community, a comparison of the modal correlation process using TACT within PATRAN versus external third-party modal correlation packages is presented.

A Digital PCR-Based Method for Efficient and Highly Specific Screening of Genome Edited Cells

PubMed Central

Berman, Jennifer R.; Postovit, Lynne-Marie

2016-01-01

The rapid adoption of gene editing tools such as CRISPRs and TALENs for research and eventually therapeutics necessitates assays that can rapidly detect and quantitate the desired alterations. Currently, the most commonly used assay employs “mismatch nucleases” T7E1 or “Surveyor” that recognize and cleave heteroduplexed DNA amplicons containing mismatched base-pairs. However, this assay is prone to false positives due to cancer-associated mutations and/or SNPs and requires large amounts of starting material. Here we describe a powerful alternative wherein droplet digital PCR (ddPCR) can be used to decipher homozygous from heterozygous mutations with superior levels of both precision and sensitivity. We use this assay to detect knockout inducing alterations to stem cell associated proteins, NODAL and SFRP1, generated using either TALENs or an “all-in-one” CRISPR/Cas plasmid that we have modified for one-step cloning and blue/white screening of transformants. Moreover, we highlight how ddPCR can be used to assess the efficiency of varying TALEN-based strategies. Collectively, this work highlights how ddPCR-based screening can be paired with CRISPR and TALEN technologies to enable sensitive, specific, and streamlined approaches to gene editing and validation. PMID:27089539

COHeRE: Cross-Ontology Hierarchical Relation Examination for Ontology Quality Assurance.

PubMed

Cui, Licong

Biomedical ontologies play a vital role in healthcare information management, data integration, and decision support. Ontology quality assurance (OQA) is an indispensable part of the ontology engineering cycle. Most existing OQA methods are based on the knowledge provided within the targeted ontology. This paper proposes a novel cross-ontology analysis method, Cross-Ontology Hierarchical Relation Examination (COHeRE), to detect inconsistencies and possible errors in hierarchical relations across multiple ontologies. COHeRE leverages the Unified Medical Language System (UMLS) knowledge source and the MapReduce cloud computing technique for systematic, large-scale ontology quality assurance work. COHeRE consists of three main steps with the UMLS concepts and relations as the input. First, the relations claimed in source vocabularies are filtered and aggregated for each pair of concepts. Second, inconsistent relations are detected if a concept pair is related by different types of relations in different source vocabularies. Finally, the uncovered inconsistent relations are voted according to their number of occurrences across different source vocabularies. The voting result together with the inconsistent relations serve as the output of COHeRE for possible ontological change. The highest votes provide initial suggestion on how such inconsistencies might be fixed. In UMLS, 138,987 concept pairs were found to have inconsistent relationships across multiple source vocabularies. 40 inconsistent concept pairs involving hierarchical relationships were randomly selected and manually reviewed by a human expert. 95.8% of the inconsistent relations involved in these concept pairs indeed exist in their source vocabularies rather than being introduced by mistake in the UMLS integration process. 73.7% of the concept pairs with suggested relationship were agreed by the human expert. The effectiveness of COHeRE indicates that UMLS provides a promising environment to enhance qualities of biomedical ontologies by performing cross-ontology examination.

Difference magnitude is not measured by discrimination steps for order of point patterns.

PubMed

Protonotarios, Emmanouil D; Johnston, Alan; Griffin, Lewis D

2016-07-01

We have shown in previous work that the perception of order in point patterns is consistent with an interval scale structure (Protonotarios, Baum, Johnston, Hunter, & Griffin, 2014). The psychophysical scaling method used relies on the confusion between stimuli with similar levels of order, and the resulting discrimination scale is expressed in just-noticeable differences (jnds). As with other perceptual dimensions, an interesting question is whether suprathreshold (perceptual) differences are consistent with distances between stimuli on the discrimination scale. To test that, we collected discrimination data, and data based on comparison of perceptual differences. The stimuli were jittered square lattices of dots, covering the range from total disorder (Poisson) to perfect order (square lattice), roughly equally spaced on the discrimination scale. Observers picked the most ordered pattern from a pair, and the pair of patterns with the greatest difference in order from two pairs. Although the judgments of perceptual difference were found to be consistent with an interval scale, like the discrimination judgments, no common interval scale that could predict both sets of data was possible. In particular, the midpattern of the perceptual scale is 11 jnds away from the ordered end, and 5 jnds from the disordered end of the discrimination scale.

Mutual Mate Choice: When it Pays Both Sexes to Avoid Inbreeding

PubMed Central

Lihoreau, Mathieu; Zimmer, Cédric; Rivault, Colette

2008-01-01

Theoretical models of sexual selection predict that both males and females of many species should benefit by selecting their mating partners. However, empirical evidence testing and validating this prediction is scarce. In particular, whereas inbreeding avoidance is expected to induce sexual conflicts, in some cases both partners could benefit by acting in concert and exerting mutual mate choice for non-assortative pairings. We tested this prediction with the gregarious cockroach Blattella germanica (L.). We demonstrated that males and females base their mate choice on different criteria and that choice occurs at different steps during the mating sequence. Males assess their relatedness to females through antennal contacts before deciding to court preferentially non-siblings. Conversely, females biased their choice towards the most vigorously courting males that happened to be non-siblings. This study is the first to demonstrate mutual mate choice leading to close inbreeding avoidance. The fact that outbred pairs were more fertile than inbred pairs strongly supports the adaptive value of this mating system, which includes no “best phenotype” as the quality of two mating partners is primarily linked to their relatedness. We discuss the implications of our results in the light of inbreeding conflict models. PMID:18843373

Mutual mate choice: when it pays both sexes to avoid inbreeding.

PubMed

Lihoreau, Mathieu; Zimmer, Cédric; Rivault, Colette

2008-01-01

Theoretical models of sexual selection predict that both males and females of many species should benefit by selecting their mating partners. However, empirical evidence testing and validating this prediction is scarce. In particular, whereas inbreeding avoidance is expected to induce sexual conflicts, in some cases both partners could benefit by acting in concert and exerting mutual mate choice for non-assortative pairings. We tested this prediction with the gregarious cockroach Blattella germanica (L.). We demonstrated that males and females base their mate choice on different criteria and that choice occurs at different steps during the mating sequence. Males assess their relatedness to females through antennal contacts before deciding to court preferentially non-siblings. Conversely, females biased their choice towards the most vigorously courting males that happened to be non-siblings. This study is the first to demonstrate mutual mate choice leading to close inbreeding avoidance. The fact that outbred pairs were more fertile than inbred pairs strongly supports the adaptive value of this mating system, which includes no "best phenotype" as the quality of two mating partners is primarily linked to their relatedness. We discuss the implications of our results in the light of inbreeding conflict models.

Compensatory Evolution of Intrinsic Transcription Terminators in Bacillus Cereus

PubMed Central

Safina, Ksenia R.; Mironov, Andrey A.

2017-01-01

Many RNA molecules possess complicated secondary structure critical to their function. Mutations in double-helical regions of RNA may disrupt Watson–Crick (WC) interactions causing structure destabilization or even complete loss of function. Such disruption can be compensated by another mutation restoring base pairing, as has been shown for mRNA, rRNA and tRNA. Here, we investigate the evolution of intrinsic transcription terminators between closely related strains of Bacillus cereus. While the terminator structure is maintained by strong natural selection, as evidenced by the low frequency of disrupting mutations, we observe multiple instances of pairs of disrupting-compensating mutations in RNA structure stems. Such two-step switches between different WC pairs occur very fast, consistent with the low fitness conferred by the intermediate non-WC variant. Still, they are not instantaneous, and probably involve transient fixation of the intermediate variant. The GU wobble pair is the most frequent intermediate, and remains fixed longer than other intermediates, consistent with its less disruptive effect on the RNA structure. Double switches involving non-GU intermediates are more frequent at the ends of RNA stems, probably because they are associated with smaller fitness loss. Together, these results show that the fitness landscape of bacterial transcription terminators is rather rugged, but that the fitness valleys associated with unpaired stem nucleotides are rather shallow, facilitating evolution. PMID:28201729

The predictive power of Japanese candlestick charting in Chinese stock market

NASA Astrophysics Data System (ADS)

Chen, Shi; Bao, Si; Zhou, Yu

2016-09-01

This paper studies the predictive power of 4 popular pairs of two-day bullish and bearish Japanese candlestick patterns in Chinese stock market. Based on Morris' study, we give the quantitative details of definition of long candlestick, which is important in two-day candlestick pattern recognition but ignored by several previous researches, and we further give the quantitative definitions of these four pairs of two-day candlestick patterns. To test the predictive power of candlestick patterns on short-term price movement, we propose the definition of daily average return to alleviate the impact of correlation among stocks' overlap-time returns in statistical tests. To show the robustness of our result, two methods of trend definition are used for both the medium-market-value and large-market-value sample sets. We use Step-SPA test to correct for data snooping bias. Statistical results show that the predictive power differs from pattern to pattern, three of the eight patterns provide both short-term and relatively long-term prediction, another one pair only provide significant forecasting power within very short-term period, while the rest three patterns present contradictory results for different market value groups. For all the four pairs, the predictive power drops as predicting time increases, and forecasting power is stronger for stocks with medium market value than those with large market value.

Probing the unconventional superconducting state of LiFeAs by quasiparticle interference.

PubMed

Hänke, Torben; Sykora, Steffen; Schlegel, Ronny; Baumann, Danny; Harnagea, Luminita; Wurmehl, Sabine; Daghofer, Maria; Büchner, Bernd; van den Brink, Jeroen; Hess, Christian

2012-03-23

A crucial step in revealing the nature of unconventional superconductivity is to investigate the symmetry of the superconducting order parameter. Scanning tunneling spectroscopy has proven a powerful technique to probe this symmetry by measuring the quasiparticle interference (QPI) which sensitively depends on the superconducting pairing mechanism. A particularly well-suited material to apply this technique is the stoichiometric superconductor LiFeAs as it features clean, charge neutral cleaved surfaces without surface states and a relatively high T(c)∼18  K. Our data reveal that in LiFeAs the quasiparticle scattering is governed by a van Hove singularity at the center of the Brillouin zone which is in stark contrast to other pnictide superconductors where nesting is crucial for both scattering and s(±) superconductivity. Indeed, within a minimal model and using the most elementary order parameters, calculations of the QPI suggest a dominating role of the holelike bands for the quasiparticle scattering. Our theoretical findings do not support the elementary singlet pairing symmetries s(++), s(±), and d wave. This brings to mind that the superconducting pairing mechanism in LiFeAs is based on an unusual pairing symmetry such as an elementary p wave (which provides optimal agreement between the experimental data and QPI simulations) or a more complex order parameter (e.g., s+id wave symmetry).

Short communication: measures of weight distribution and frequency of steps as indicators of restless behavior.

PubMed

Chapinal, N; de Passillé, A M; Rushen, J; Tucker, C B

2011-02-01

Restless behavior, as measured by the steps taken or weight shifting between legs, may be a useful tool to assess the comfort of dairy cattle. These behaviors increase when cows stand on uncomfortable surfaces or are lame. The objective of this study was to compare 2 measures of restless behavior, stepping behavior and changes in weight distribution, on 2 standing surfaces: concrete and rubber. Twelve cows stood on a weighing platform with 1 scale/hoof for 1h. The platform was covered with either concrete or rubber, presented in a crossover design. Restlessness, as measured by both the frequency of steps and weight shifting (measured as the standard deviation of weight applied over time to the legs), increased over 1h of forced standing on either concrete or rubber. A positive relationship was found between the frequency of steps and the standard deviation of weight over 1h for both treatments and pairs of legs (r ≥ 0.66). No differences existed in the standard deviation of weight applied to the front (27.6 ± 1.6 kg) or rear legs (33.5 ± 1.4 kg) or the frequency of steps (10.2 ± 1.6 and 20.8 ± 3.2 steps/10 min for the front and rear pair, respectively) between rubber and concrete. Measures of restlessness are promising tools for assessing specific types of discomfort, such as those associated with lameness, but additional tools are needed to assess comfort of non-concrete standing surfaces. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Gene network interconnectedness and the generalized topological overlap measure

PubMed Central

Yip, Andy M; Horvath, Steve

2007-01-01

Background Network methods are increasingly used to represent the interactions of genes and/or proteins. Genes or proteins that are directly linked may have a similar biological function or may be part of the same biological pathway. Since the information on the connection (adjacency) between 2 nodes may be noisy or incomplete, it can be desirable to consider alternative measures of pairwise interconnectedness. Here we study a class of measures that are proportional to the number of neighbors that a pair of nodes share in common. For example, the topological overlap measure by Ravasz et al. [1] can be interpreted as a measure of agreement between the m = 1 step neighborhoods of 2 nodes. Several studies have shown that two proteins having a higher topological overlap are more likely to belong to the same functional class than proteins having a lower topological overlap. Here we address the question whether a measure of topological overlap based on higher-order neighborhoods could give rise to a more robust and sensitive measure of interconnectedness. Results We generalize the topological overlap measure from m = 1 step neighborhoods to m ≥ 2 step neighborhoods. This allows us to define the m-th order generalized topological overlap measure (GTOM) by (i) counting the number of m-step neighbors that a pair of nodes share and (ii) normalizing it to take a value between 0 and 1. Using theoretical arguments, a yeast co-expression network application, and a fly protein network application, we illustrate the usefulness of the proposed measure for module detection and gene neighborhood analysis. Conclusion Topological overlap can serve as an important filter to counter the effects of spurious or missing connections between network nodes. The m-th order topological overlap measure allows one to trade-off sensitivity versus specificity when it comes to defining pairwise interconnectedness and network modules. PMID:17250769

Clinical gait evaluation of patients with knee osteoarthritis.

PubMed

Sun, Jun; Liu, Yancheng; Yan, Songhua; Cao, Guanglei; Wang, Shasha; Lester, D Kevin; Zhang, Kuan

2017-10-01

Knee osteoarthritis (KOA) is the most common osteoarthritis in lower limbs, and gait measurement is important to evaluate walking function of KOA patients before and after treatment. The third generation Intelligent Device for Energy Expenditure and Activity (IDEEA3) is a portable gait analysis system to evaluate gaits. This study is to evaluate the accuracy and reliability of IDEEA3 for gait measurement of KOA patients. Meanwhile, gait differences between KOA patients and healthy subjects are examined. Twelve healthy volunteers were recruited for measurement comparison of gait cycle (GC), cadence, step length, velocity and step counts between a motion analysis system and a high-speed camera (GoPro Hero3). Twenty-three KOA patients were recruited for measurement comparison of former five parameters between GoPro Hero3 and IDEEA3. Paired t-test, Concordance Correlation Coefficient (CCC) and Intraclass Correlation Coefficient (ICC) were used for data analysis. All p-values of paired t-tests for GC, cadence, step length and velocity were greater than 0.05 while all CCC and ICC results were above 0.95. The measurements of GC, cadence, step length, velocity and step counts by motion analysis system are highly consistent with the measurements by GoPro Hero3. The measurements of former parameters by GoPro Hero3 are not statistically different from the measurements by IDEEA3. IDEEA3 can be effectively used for the measurement of GC, cadence, step length, velocity and step counts in KOA patients. The KOA patients walk with longer GC, lower cadence, shorter step length and slower speed compared with healthy subjects in natural speed with flat shoes. Copyright © 2017 Elsevier B.V. All rights reserved.

Technology Needs for Gamma Ray Astronomy

NASA Technical Reports Server (NTRS)

Gehrels, Neil

2011-01-01

Gamma ray astronomy is currently in an exciting period of multiple missions and a wealth of data. Results from INTEGRAL, Fermi, AGILE, Suzaku and Swift are making large contributions to our knowledge of high energy processes in the universe. The advances are due to new detector and imaging technologies. The steps to date have been from scintillators to solid state detectors for sensors and from light buckets to coded aperture masks and pair telescopes for imagers. A key direction for the future is toward focusing telescopes pushing into the hard X-ray regime and Compton telescopes and pair telescopes with fine spatial resolution for medium and high energy gamma rays. These technologies will provide finer imaging of gamma-ray sources. Importantly, they will also enable large steps forward in sensitivity by reducing background.

Extremely Efficient Multiple Electron-hole Pair Generation in Carbon Nanotube Photodiodes

NASA Astrophysics Data System (ADS)

Gabor, Nathaniel

2010-03-01

The efficient generation of multiple electron-hole (e-h) pairs from a single photon could improve the efficiency of photovoltaic solar cells beyond standard thermodynamic limits [1] and has been the focus of much recent work in semiconductor nanomaterials [2,3]. In single walled carbon nanotubes (SWNTs), the small Fermi velocity and low dielectric constant suggests that electron-electron interactions are very strong and that high-energy carriers should efficiently generate e-h pairs. Here, I will discuss observations of highly efficient generation of e-h pairs due to impact excitation in SWNT p-n junction photodiodes [4]. To investigate optoelectronic transport properties of individual SWNT photodiodes, we focus a laser beam over the device while monitoring the electronic characteristics. Optical excitation into the second electronic subband E22 ˜ 2 EGAP leads to striking photocurrent steps in the device I-VSD characteristics that occur at voltage intervals of the band gap energy EGAP/ e. Spatially and spectrally resolved photocurrent combined with temperature-dependent studies suggest that these steps result from efficient generation of multiple e-h pairs from a single hot E22 carrier. We conclude that in the SWNT photodiode, a single photon with energy greater than 2EGAP is converted into multiple e-h pairs, leading to enhanced photocurrent and increased photo-conversion efficiency. [1] W. Shockley, and H. J. Queisser, Journal of Applied Physics 32, 510 (1961). [2] R. D. Schaller, and V. I. Klimov, Physical Review Letters 92 (18), 186601 (2004). [3] R. J. Ellingson, et al, Nano Letters, 5 (5), 865-871 (2005). [4] Nathaniel M. Gabor, Zhaohui Zhong, Ken Bosnick, Jiwoong Park, and Paul McEuen, Science, 325, 1367 (2009).

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

Conjugate fracture pairs in the Molina Member of the Wasatch Formation, Piceance basin, Colorado: Implications for fracture origins and hydrocarbon production/exploration

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

Lorenz, J.C.

1997-05-01

The sandstones of the Molina Member of the Wasatch Formation in the Piceance basin of northwestern Colorado contain a suite of fractures that have a conjugate-pair geometry. The fractures are vertical and intersect at an acute angle of between 20 and 40 degrees. Although direct evidence of shear is rare, the fracture surfaces commonly display small steps. The fracture geometries suggest that the maximum compressive stress during fracturing was in the plane of the acute angle of the conjugate fractures: the steps are interpreted as broken-face manifestations of very low angle en echelon fractures, formed within exceptionally narrow zones ofmore » incipient shear. In contrast to the highly anisotropic permeability enhancement created by subparallel vertical extension fractures in the underlying Mesaverde Formation, the conjugate pairs in the Molina sandstones should create a well connected and relatively isotropic mesh of fracture conductivity. Increases in stress magnitudes and anisotropy during production drawdown of reservoir pressures should cause shear offsets along the fractures, initially enhancing permeability.« less

Efficient algorithm for multiconfiguration pair-density functional theory with application to the heterolytic dissociation energy of ferrocene

NASA Astrophysics Data System (ADS)

Sand, Andrew M.; Truhlar, Donald G.; Gagliardi, Laura

2017-01-01

The recently developed multiconfiguration pair-density functional theory (MC-PDFT) combines multiconfiguration wave function theory with a density functional that depends on the on-top pair density of an electronic system. In an MC-PDFT calculation, there are two steps: a conventional multiconfiguration self-consistent-field (MCSCF) calculation and a post-MCSCF evaluation of the energy with an on-top density functional. In this work, we present the details of the MC-PDFT algorithm that avoids steeply scaling steps that are present in other post-self-consistent-field multireference calculations of dynamic correlation energy. We demonstrate the favorable scaling by considering systems of H2 molecules with active spaces of several different sizes. We then apply the MC-PDFT method to calculate the heterolytic dissociation enthalpy of ferrocene. We find that MC-PDFT yields results that are at least as accurate as complete active space second-order perturbation theory and are more stable with respect to basis set, but at a fraction of the cost in both time and memory.

Efficient algorithm for multiconfiguration pair-density functional theory with application to the heterolytic dissociation energy of ferrocene.

PubMed

Sand, Andrew M; Truhlar, Donald G; Gagliardi, Laura

2017-01-21

The recently developed multiconfiguration pair-density functional theory (MC-PDFT) combines multiconfiguration wave function theory with a density functional that depends on the on-top pair density of an electronic system. In an MC-PDFT calculation, there are two steps: a conventional multiconfiguration self-consistent-field (MCSCF) calculation and a post-MCSCF evaluation of the energy with an on-top density functional. In this work, we present the details of the MC-PDFT algorithm that avoids steeply scaling steps that are present in other post-self-consistent-field multireference calculations of dynamic correlation energy. We demonstrate the favorable scaling by considering systems of H 2 molecules with active spaces of several different sizes. We then apply the MC-PDFT method to calculate the heterolytic dissociation enthalpy of ferrocene. We find that MC-PDFT yields results that are at least as accurate as complete active space second-order perturbation theory and are more stable with respect to basis set, but at a fraction of the cost in both time and memory.

Simulation of Unique Pressure Changing Steps and Situations in Psa Processes

NASA Technical Reports Server (NTRS)

Ebner, Armin D.; Mehrotra, Amal; Knox, James C.; LeVan, Douglas; Ritter, James A.

2007-01-01

A more rigorous cyclic adsorption process simulator is being developed for use in the development and understanding of new and existing PSA processes. Unique features of this new version of the simulator that Ritter and co-workers have been developing for the past decade or so include: multiple absorbent layers in each bed, pressure drop in the column, valves for entering and exiting flows and predicting real-time pressurization and depressurization rates, ability to account for choked flow conditions, ability to pressurize and depressurize simultaneously from both ends of the columns, ability to equalize between multiple pairs of columns, ability to equalize simultaneously from both ends of pairs of columns, and ability to handle very large pressure ratios and hence velocities associated with deep vacuum systems. These changes to the simulator now provide for unique opportunities to study the effects of novel pressure changing steps and extreme process conditions on the performance of virtually any commercial or developmental PSA process. This presentation will provide an overview of the cyclic adsorption process simulator equations and algorithms used in the new adaptation. It will focus primarily on the novel pressure changing steps and their effects on the performance of a PSA system that epitomizes the extremes of PSA process design and operation. This PSA process is a sorbent-based atmosphere revitalization (SBAR) system that NASA is developing for new manned exploration vehicles. This SBAR system consists of a 2-bed 3-step 3-layer system that operates between atmospheric pressure and the vacuum of space, evacuates from both ends of the column simultaneously, experiences choked flow conditions during pressure changing steps, and experiences a continuously changing feed composition, as it removes metabolic CO2 and H20 from a closed and fixed volume, i.e., the spacecraft cabin. Important process performance indicators of this SBAR system are size, and the corresponding CO2 and H20 removal efficiencies, and N2 and O2 loss rates. Results of the fundamental behavior of this PSA process during extreme operating conditions will be presented and discussed.

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

Tailoring plasmonic properties of metal nanoparticle-embedded dielectric thin films: the sandwich method of preparation

NASA Astrophysics Data System (ADS)

Laha, Ranjit; Malar, P.; Osipowicz, Thomas; Kasiviswanathan, S.

2017-09-01

Tailoring of plasmonic properties of metal nanoparticle-embedded dielectric thin films are very crucial for many thin film-based applications. We, herein, investigate the various ways of tuning the plasmonic positions of gold nanoparticles (AuNPs)-embedded indium oxide thin films (Au:IO) through a sequence-specific sandwich method. The sandwich method is a four-step process involving deposition of In2O3 film by magnetron sputtering in first and fourth steps, thermal evaporation of Au on to In2O3 film in second and annealing of Au/In2O3 film in the third step. The Au:IO films were characterized by x-ray diffraction, spectrophotometry and transmission electron microscopy. The size and shape of the embedded nanoparticles were found from Rutherford back-scattering spectrometry. Based on dynamic Maxwell Garnett theory, the observed plasmon resonance position was ascribed to the oblate shape of AuNPs formed in sandwich method. Finally, through experimental data, it was shown that the plasmon resonance position of Au:IO thin films can be tuned by 125 nm. The method shown here can be used to tune the plasmon resonance position over the entire range of visible region for the thin films made from other combinations of metal-dielectric pair.

MIDAS robust trend estimator for accurate GPS station velocities without step detection

PubMed Central

Kreemer, Corné; Hammond, William C.; Gazeaux, Julien

2016-01-01

Abstract Automatic estimation of velocities from GPS coordinate time series is becoming required to cope with the exponentially increasing flood of available data, but problems detectable to the human eye are often overlooked. This motivates us to find an automatic and accurate estimator of trend that is resistant to common problems such as step discontinuities, outliers, seasonality, skewness, and heteroscedasticity. Developed here, Median Interannual Difference Adjusted for Skewness (MIDAS) is a variant of the Theil‐Sen median trend estimator, for which the ordinary version is the median of slopes vij = (xj–xi)/(tj–ti) computed between all data pairs i > j. For normally distributed data, Theil‐Sen and least squares trend estimates are statistically identical, but unlike least squares, Theil‐Sen is resistant to undetected data problems. To mitigate both seasonality and step discontinuities, MIDAS selects data pairs separated by 1 year. This condition is relaxed for time series with gaps so that all data are used. Slopes from data pairs spanning a step function produce one‐sided outliers that can bias the median. To reduce bias, MIDAS removes outliers and recomputes the median. MIDAS also computes a robust and realistic estimate of trend uncertainty. Statistical tests using GPS data in the rigid North American plate interior show ±0.23 mm/yr root‐mean‐square (RMS) accuracy in horizontal velocity. In blind tests using synthetic data, MIDAS velocities have an RMS accuracy of ±0.33 mm/yr horizontal, ±1.1 mm/yr up, with a 5th percentile range smaller than all 20 automatic estimators tested. Considering its general nature, MIDAS has the potential for broader application in the geosciences. PMID:27668140

MIDAS robust trend estimator for accurate GPS station velocities without step detection.

PubMed

Blewitt, Geoffrey; Kreemer, Corné; Hammond, William C; Gazeaux, Julien

2016-03-01

Automatic estimation of velocities from GPS coordinate time series is becoming required to cope with the exponentially increasing flood of available data, but problems detectable to the human eye are often overlooked. This motivates us to find an automatic and accurate estimator of trend that is resistant to common problems such as step discontinuities, outliers, seasonality, skewness, and heteroscedasticity. Developed here, Median Interannual Difference Adjusted for Skewness (MIDAS) is a variant of the Theil-Sen median trend estimator, for which the ordinary version is the median of slopes v ij  = ( x j -x i )/( t j -t i ) computed between all data pairs i  >  j . For normally distributed data, Theil-Sen and least squares trend estimates are statistically identical, but unlike least squares, Theil-Sen is resistant to undetected data problems. To mitigate both seasonality and step discontinuities, MIDAS selects data pairs separated by 1 year. This condition is relaxed for time series with gaps so that all data are used. Slopes from data pairs spanning a step function produce one-sided outliers that can bias the median. To reduce bias, MIDAS removes outliers and recomputes the median. MIDAS also computes a robust and realistic estimate of trend uncertainty. Statistical tests using GPS data in the rigid North American plate interior show ±0.23 mm/yr root-mean-square (RMS) accuracy in horizontal velocity. In blind tests using synthetic data, MIDAS velocities have an RMS accuracy of ±0.33 mm/yr horizontal, ±1.1 mm/yr up, with a 5th percentile range smaller than all 20 automatic estimators tested. Considering its general nature, MIDAS has the potential for broader application in the geosciences.

MIDAS robust trend estimator for accurate GPS station velocities without step detection

NASA Astrophysics Data System (ADS)

Blewitt, Geoffrey; Kreemer, Corné; Hammond, William C.; Gazeaux, Julien

2016-03-01

Automatic estimation of velocities from GPS coordinate time series is becoming required to cope with the exponentially increasing flood of available data, but problems detectable to the human eye are often overlooked. This motivates us to find an automatic and accurate estimator of trend that is resistant to common problems such as step discontinuities, outliers, seasonality, skewness, and heteroscedasticity. Developed here, Median Interannual Difference Adjusted for Skewness (MIDAS) is a variant of the Theil-Sen median trend estimator, for which the ordinary version is the median of slopes vij = (xj-xi)/(tj-ti) computed between all data pairs i > j. For normally distributed data, Theil-Sen and least squares trend estimates are statistically identical, but unlike least squares, Theil-Sen is resistant to undetected data problems. To mitigate both seasonality and step discontinuities, MIDAS selects data pairs separated by 1 year. This condition is relaxed for time series with gaps so that all data are used. Slopes from data pairs spanning a step function produce one-sided outliers that can bias the median. To reduce bias, MIDAS removes outliers and recomputes the median. MIDAS also computes a robust and realistic estimate of trend uncertainty. Statistical tests using GPS data in the rigid North American plate interior show ±0.23 mm/yr root-mean-square (RMS) accuracy in horizontal velocity. In blind tests using synthetic data, MIDAS velocities have an RMS accuracy of ±0.33 mm/yr horizontal, ±1.1 mm/yr up, with a 5th percentile range smaller than all 20 automatic estimators tested. Considering its general nature, MIDAS has the potential for broader application in the geosciences.

Highly Efficient Perovskite-Quantum-Dot Light-Emitting Diodes by Surface Engineering.

PubMed

Pan, Jun; Quan, Li Na; Zhao, Yongbiao; Peng, Wei; Murali, Banavoth; Sarmah, Smritakshi P; Yuan, Mingjian; Sinatra, Lutfan; Alyami, Noktan M; Liu, Jiakai; Yassitepe, Emre; Yang, Zhenyu; Voznyy, Oleksandr; Comin, Riccardo; Hedhili, Mohamed N; Mohammed, Omar F; Lu, Zheng Hong; Kim, Dong Ha; Sargent, Edward H; Bakr, Osman M

2016-10-01

A two-step ligand-exchange strategy is developed, in which the long-carbon- chain ligands on all-inorganic perovskite (CsPbX 3 , X = Br, Cl) quantum dots (QDs) are replaced with halide-ion-pair ligands. Green and blue light-emitting diodes made from the halide-ion-pair-capped quantum dots exhibit high external quantum efficiencies compared with the untreated QDs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Meiotic Nuclear Oscillations Are Necessary to Avoid Excessive Chromosome Associations.

PubMed

Chacón, Mariola R; Delivani, Petrina; Tolić, Iva M

2016-11-01

Pairing of homologous chromosomes is a crucial step in meiosis, which in fission yeast depends on nuclear oscillations. However, how nuclear oscillations help pairing is unknown. Here, we show that homologous loci typically pair when the spindle pole body is at the cell pole and the nucleus is elongated, whereas they unpair when the spindle pole body is in the cell center and the nucleus is round. Inhibition of oscillations demonstrated that movement is required for initial pairing and that prolonged association of loci leads to mis-segregation. The double-strand break marker Rec25 accumulates in elongated nuclei, indicating that prolonged chromosome stretching triggers recombinatory pathways leading to mis-segregation. Mis-segregation is rescued by overexpression of the Holliday junction resolvase Mus81, suggesting that prolonged pairing results in irresolvable recombination intermediates. We conclude that nuclear oscillations exhibit a dual role, promoting initial pairing and restricting the time of chromosome associations to ensure proper segregation. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Properties of true quaternary fission of nuclei with allowance for its multistep and sequential character

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

Kadmensky, S. G., E-mail: kadmensky@phys.vsu.ru; Titova, L. V.; Bulychev, A. O.

An analysis of basicmechanisms of binary and ternary fission of nuclei led to the conclusion that true ternary and quaternary fission of nuclei has a sequential two-step (three-step) character, where, at the first step, a fissile nucleus emits a third light particle (third and fourth light particles) under shakeup effects associated with a nonadiabatic character of its collective deformation motion, whereupon the residual nucleus undergoes fission to two fission fragments. Owing to this, the formulas derived earlier for the widths with respect to sequential two- and three-step decays of nuclei in constructing the theory of two-step twoproton decays and multistepmore » decays in chains of genetically related nuclei could be used to describe the relative yields and angular and energy distributions of third and fourth light particles emitted in (α, α), (t, t), and (α, t) pairs upon the true quaternary spontaneous fission of {sup 252}Cf and thermal-neutron-induced fission of {sup 235}U and {sup 233}U target nuclei. Mechanisms that explain a sharp decrease in the yield of particles appearing second in time and entering into the composition of light-particle pairs that originate from true quaternary fission of nuclei in relation to the yields of analogous particles in true ternary fission of nuclei are proposed.« less

40 CFR 86.1310-90 - Exhaust gas sampling and analytical system; diesel engines.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the port entrance to the analyzer to within 90 percent of the step change. (B) 20 seconds from an instantaneous step change at the entrance to the sample probe or overflow span gas port to within 90 percent of... avoid moisture condensation. A filter pair loading of 1 mg is typically proportional to a 0.1 g/bhp-hr...

40 CFR 86.1310-90 - Exhaust gas sampling and analytical system; diesel engines.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the port entrance to the analyzer to within 90 percent of the step change. (B) 20 seconds from an instantaneous step change at the entrance to the sample probe or overflow span gas port to within 90 percent of... avoid moisture condensation. A filter pair loading of 1 mg is typically proportional to a 0.1 g/bhp-hr...

Molecular Dynamics Simulations of the 136 Unique Tetranucleotide Sequences of DNA Oligonucleotides. I. Research Design and Results on d(CpG) Steps

PubMed Central

Beveridge, David L.; Barreiro, Gabriela; Byun, K. Suzie; Case, David A.; Cheatham, Thomas E.; Dixit, Surjit B.; Giudice, Emmanuel; Lankas, Filip; Lavery, Richard; Maddocks, John H.; Osman, Roman; Seibert, Eleanore; Sklenar, Heinz; Stoll, Gautier; Thayer, Kelly M.; Varnai, Péter; Young, Matthew A.

2004-01-01

We describe herein a computationally intensive project aimed at carrying out molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide base sequences. This initiative was undertaken by an international collaborative effort involving nine research groups, the “Ascona B-DNA Consortium” (ABC). Calculations were carried out on the 136 cases imbedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs. All MD simulations were carried out using a well-defined protocol, the AMBER suite of programs, and the parm94 force field. Phase I of the ABC project involves a total of ∼0.6 μs of simulation for systems containing ∼24,000 atoms. The resulting trajectories involve 600,000 coordinate sets and represent ∼400 gigabytes of data. In this article, the research design, details of the simulation protocol, informatics issues, and the organization of the results into a web-accessible database are described. Preliminary results from 15-ns MD trajectories are presented for the d(CpG) step in its 10 unique sequence contexts, and issues of stability and convergence, the extent of quasiergodic problems, and the possibility of long-lived conformational substates are discussed. PMID:15326025

Stepping Stone Mechanism: Carrier-Free Long-Range Magnetism Mediated by Magnetized Cation States in Quintuple Layer

NASA Astrophysics Data System (ADS)

Chan, Chunkai; Zhang, Xiaodong; Zhang, Yiou; Tse, Kinfai; Deng, Bei; Zhang, Jingzhao; Zhu, Junyi

2018-01-01

The long-range magnetism observed in group-V tellurides quintuple layers is the only working example of carrier-free dilute magnetic semiconductors (DMS), whereas the physical mechanism is unclear, except the speculation on the band topology enhanced van Vleck paramagnetism. Based on DFT calculations, we find a stable long-range ferromagnetic order in a single quintuple layer of Cr-doped Bi2Te3 or Sb2Te3, with the dopant separation more than 9 Å. This configuration is the global energy minimum among all configurations. Different from the conventional super exchange theory, the magnetism is facilitated by the lone pair derived anti-bonding states near the cations. Such anti-bonding states work as stepping stones merged in the electron sea and conduct magnetism. Further, spin orbit coupling induced band inversion is found to be insignificant in the magnetism. Therefore, our findings directly dismiss the common misbelief that band topology is the only factor that enhances the magnetism. We further demonstrate that removal of the lone pair derived states destroys the long-range magnetism. This novel mechanism sheds light on the fundamental understanding of long-range magnetism and may lead to discoveries of new classes of DMS. Supported by Chinese University of Hong Kong (CUHK) under Grant No 4053084, University Grants Committee of Hong Kong under Grant No 24300814, and the Start-up Funding of CUHK.

Investigating the Effects of Side Airbag Deployment in Real-World Crashes Using Crash Comparison Techniques

PubMed Central

Loftis, Kathryn L.; Weaver, Ashley A.; Stitzel, Joel D.

2011-01-01

The objective of this study was to investigate side airbag (SAB) deployment in near side crashes and compare injuries and contact points between occupants with and without SAB deployment. Using NASS 2000–2008 and selecting for near side cases, with PDOF ± 20 degrees from 90 or 270, for non-pregnant adult belted occupants, there were 20,253 (weighted) SAB deployments. NASS showed that SABs have been increasing within the fleet, comprising 2% of airbags in 2000 and increasing to 33% of airbags in 2008. To investigate deployed SABs, we developed a three-step methology to pair CIREN cases to study the effects of deployment on occupant outcome. The first step involved extracting near side impacts from CIREN with adult, non-pregnant occupants seated in row 1 (drivers or right front passengers). In the second step, each case was quantitatively compared to FMVSS 214 barrier test standards using a 6 point similarity scoring system. Cases scoring at least 3 points were then qualitatively analyzed and 33 pairs of cases of the same vehicle make/model but opposite SAB status were chosen. Occupants with deployed SAB had reduced occurrences and severity of head and face, neck and cervical spine, and thoracic injuries and fewer injurious contacts to side components including the door, a-pillar, and window sill. SAB deployment was statistically significant for reducing occupant MAIS and ISS and thorax airbags were statistically significant for reducing thoracic and neck/cervical spine injury severity. The average ISS with SAB deployment was 21, while the average ISS of those without was 33. This study establishes methods for performing comparisons between CIREN cases based on regulatory conditions and shows injury reduction in key body regions with SAB deployment. PMID:22105386

Real-time fluorescence ligase chain reaction for sensitive detection of single nucleotide polymorphism based on fluorescence resonance energy transfer.

PubMed

Sun, Yueying; Lu, Xiaohui; Su, Fengxia; Wang, Limei; Liu, Chenghui; Duan, Xinrui; Li, Zhengping

2015-12-15

Most of practical methods for detection of single nucleotide polymorphism (SNP) need at least two steps: amplification (usually by PCR) and detection of SNP by using the amplification products. Ligase chain reaction (LCR) can integrate the amplification and allele discrimination in one step. However, the detection of LCR products still remains a great challenge for highly sensitive and quantitative SNP detection. Herein, a simple but robust strategy for real-time fluorescence LCR has been developed for highly sensitive and quantitative SNP detection. A pair of LCR probes are firstly labeled with a fluorophore and a quencher, respectively. When the pair of LCR probes are ligated in LCR, the fluorophore will be brought close to the quencher, and thus, the fluorescence will be specifically quenched by fluorescence resonance energy transfer (FRET). The decrease of fluorescence intensity resulted from FRET can be real-time monitored in the LCR process. With the proposed real-time fluorescence LCR assay, 10 aM DNA targets or 100 pg genomic DNA can be accurately determined and as low as 0.1% mutant DNA can be detected in the presence of a large excess of wild-type DNA, indicating the high sensitivity and specificity. The real-time measuring does not require the detection step after LCR and gives a wide dynamic range for detection of DNA targets (from 10 aM to 1 pM). As LCR has been widely used for detection of SNP, DNA methylation, mRNA and microRNA, the real-time fluorescence LCR assay shows great potential for various genetic analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Effectively identifying compound-protein interactions by learning from positive and unlabeled examples.

PubMed

Cheng, Zhanzhan; Zhou, Shuigeng; Wang, Yang; Liu, Hui; Guan, Jihong; Chen, Yi-Ping Phoebe

2016-05-18

Prediction of compound-protein interactions (CPIs) is to find new compound-protein pairs where a protein is targeted by at least a compound, which is a crucial step in new drug design. Currently, a number of machine learning based methods have been developed to predict new CPIs in the literature. However, as there is not yet any publicly available set of validated negative CPIs, most existing machine learning based approaches use the unknown interactions (not validated CPIs) selected randomly as the negative examples to train classifiers for predicting new CPIs. Obviously, this is not quite reasonable and unavoidably impacts the CPI prediction performance. In this paper, we simply take the unknown CPIs as unlabeled examples, and propose a new method called PUCPI (the abbreviation of PU learning for Compound-Protein Interaction identification) that employs biased-SVM (Support Vector Machine) to predict CPIs using only positive and unlabeled examples. PU learning is a class of learning methods that leans from positive and unlabeled (PU) samples. To the best of our knowledge, this is the first work that identifies CPIs using only positive and unlabeled examples. We first collect known CPIs as positive examples and then randomly select compound-protein pairs not in the positive set as unlabeled examples. For each CPI/compound-protein pair, we extract protein domains as protein features and compound substructures as chemical features, then take the tensor product of the corresponding compound features and protein features as the feature vector of the CPI/compound-protein pair. After that, biased-SVM is employed to train classifiers on different datasets of CPIs and compound-protein pairs. Experiments over various datasets show that our method outperforms six typical classifiers, including random forest, L1- and L2-regularized logistic regression, naive Bayes, SVM and k-nearest neighbor (kNN), and three types of existing CPI prediction models. Source code, datasets and related documents of PUCPI are available at: http://admis.fudan.edu.cn/projects/pucpi.html.

Automatic derivation of natural and artificial lineaments from ALS point clouds in floodplains

NASA Astrophysics Data System (ADS)

Mandlburger, G.; Briese, C.

2009-04-01

Water flow is one of the most important driving forces in geomorphology and river systems have ever since formed our landscapes. With increasing urbanisation fertile flood plains were more and more cultivated and the defence of valuable settlement areas by dikes and dams became an important issue. Today, we are dealing with landscapes built up by natural as well as man-made artificial forces. In either case the general shape of the terrain can be portrayed by lineaments representing discontinuities of the terrain slope. Our contribution, therefore, presents an automatic method for delineating natural and artificial structure lines based on randomly distributed point data with high density of more than one point/m2. Preferably, the last echoes of airborne laser scanning (ALS) point clouds are used, since the laser signal is able to penetrate vegetation through small gaps in the foliage. Alternatively, point clouds from (multi) image matching can be employed, but poor ground point coverage in vegetated areas is often the limiting factor. Our approach is divided into three main steps: First, potential 2D start segments are detected by analyzing the surface curvature in the vicinity of each data point, second, the detailed 3D progression of each structure line is modelled patch-wise by intersecting surface pairs (e.g. planar patch pairs) based on the detected start segments and by performing line growing and, finally, post-processing like line cleaning, smoothing and networking is carried out in a last step. For the initial detection of start segments a best fitting two dimensional polynomial surface (quadric) is computed in each data point based on a set of neighbouring points, from which the minimum and maximum curvature is derived. Patches showing high maximum and low minimum curvatures indicate linear discontinuities in the surface slope and serve as start segments for the subsequent 3D modelling. Based on the 2D location and orientation of the start segments, surface patches can be identified as to the left or the right of the structure line. For each patch pair the intersection line is determined by least squares adjustment. The stochastic model considers the planimetric accuracy of the start segments, and the vertical measurement errors in the data points. A robust estimation approach is embedded in the patch adjustment for elimination of off-terrain ALS last echo points. Starting from an initial patch pair, structure line modelling is continued in forward and backward direction as long as certain thresholds (e.g. minimum surface intersection angles) are fulfilled. In the final post-processing step the resulting line set is cleaned by connecting corresponding line parts, by removing short line strings of minor relevance, and by thinning the resulting line set with respect to a certain approximation tolerance in order to reduce the amount of line data. Thus, interactive human verification and editing is limited to a minimum. In a real-world example structure lines were computed for a section of the river Main (ALS, last echoes, 4 points/m2) demonstrating the high potential of the proposed method with respect to accuracy and completeness. Terrestrial control measurements have confirmed the high accuracy expectations both in planimetry (<0.4m) and height (<0.2m).

How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome

PubMed Central

Noel, Jeffrey K.; Whitford, Paul C.

2016-01-01

It has long been recognized that the thermodynamics of mRNA–tRNA base pairing is insufficient to explain the high fidelity and efficiency of aminoacyl-tRNA (aa-tRNA) selection by the ribosome. To rationalize this apparent inconsistency, Hopfield proposed that the ribosome may improve accuracy by utilizing a multi-step kinetic proofreading mechanism. While biochemical, structural and single-molecule studies have provided a detailed characterization of aa-tRNA selection, there is a limited understanding of how the physical–chemical properties of the ribosome enable proofreading. To this end, we probe the role of EF-Tu during aa-tRNA accommodation (the proofreading step) through the use of energy landscape principles, molecular dynamics simulations and kinetic models. We find that the steric composition of EF-Tu can reduce the free-energy barrier associated with the first step of accommodation: elbow accommodation. We interpret this effect within an extended kinetic model of accommodation and show how EF-Tu can contribute to efficient and accurate proofreading. PMID:27796304

Lagrangian simulation of mixing and reactions in complex geochemical systems

NASA Astrophysics Data System (ADS)

Engdahl, Nicholas B.; Benson, David A.; Bolster, Diogo

2017-04-01

Simulations of detailed geochemical systems have traditionally been restricted to Eulerian reactive transport algorithms. This note introduces a Lagrangian method for modeling multicomponent reaction systems. The approach uses standard random walk-based methods for the particle motion steps but allows the particles to interact with each other by exchanging mass of their various chemical species. The colocation density of each particle pair is used to calculate the mass transfer rate, which creates a local disequilibrium that is then relaxed back toward equilibrium using the reaction engine PhreeqcRM. The mass exchange is the only step where the particles interact and the remaining transport and reaction steps are entirely independent for each particle. Several validation examples are presented, which reproduce well-known analytical solutions. These are followed by two demonstration examples of a competitive decay chain and an acid-mine drainage system. The source code, entitled Complex Reaction on Particles (CRP), and files needed to run these examples are hosted openly on GitHub (https://github.com/nbengdahl/CRP), so as to enable interested readers to readily apply this approach with minimal modifications.

Lifting scheme-based method for joint coding 3D stereo digital cinema with luminace correction and optimized prediction

NASA Astrophysics Data System (ADS)

Darazi, R.; Gouze, A.; Macq, B.

2009-01-01

Reproducing a natural and real scene as we see in the real world everyday is becoming more and more popular. Stereoscopic and multi-view techniques are used for this end. However due to the fact that more information are displayed requires supporting technologies such as digital compression to ensure the storage and transmission of the sequences. In this paper, a new scheme for stereo image coding is proposed. The original left and right images are jointly coded. The main idea is to optimally exploit the existing correlation between the two images. This is done by the design of an efficient transform that reduces the existing redundancy in the stereo image pair. This approach was inspired by Lifting Scheme (LS). The novelty in our work is that the prediction step is been replaced by an hybrid step that consists in disparity compensation followed by luminance correction and an optimized prediction step. The proposed scheme can be used for lossless and for lossy coding. Experimental results show improvement in terms of performance and complexity compared to recently proposed methods.

Photonic Quantum Networks formed from NV− centers

PubMed Central

Nemoto, Kae; Trupke, Michael; Devitt, Simon J.; Scharfenberger, Burkhard; Buczak, Kathrin; Schmiedmayer, Jörg; Munro, William J.

2016-01-01

In this article we present a simple repeater scheme based on the negatively-charged nitrogen vacancy centre in diamond. Each repeater node is built from modules comprising an optical cavity containing a single NV−, with one nuclear spin from 15N as quantum memory. The module uses only deterministic processes and interactions to achieve high fidelity operations (>99%), and modules are connected by optical fiber. In the repeater node architecture, the processes between modules by photons can be in principle deterministic, however current limitations on optical components lead the processes to be probabilistic but heralded. Our resource-modest repeater architecture contains two modules at each node, and the repeater nodes are then connected by entangled photon pairs. We discuss the performance of such a quantum repeater network with modest resources and then incorporate more resource-intense strategies step by step. Our architecture should allow large-scale quantum information networks with existing or near future technology. PMID:27215433

Nonequilibrium thermodynamics and a fluctuation theorem for individual reaction steps in a chemical reaction network

NASA Astrophysics Data System (ADS)

Pal, Krishnendu; Das, Biswajit; Banerjee, Kinshuk; Gangopadhyay, Gautam

2015-09-01

We have introduced an approach to nonequilibrium thermodynamics of an open chemical reaction network in terms of the propensities of the individual elementary reactions and the corresponding reverse reactions. The method is a microscopic formulation of the dissipation function in terms of the relative entropy or Kullback-Leibler distance which is based on the analogy of phase space trajectory with the path of elementary reactions in a network of chemical process. We have introduced here a fluctuation theorem valid for each opposite pair of elementary reactions which is useful in determining the contribution of each sub-reaction on the nonequilibrium thermodynamics of overall reaction. The methodology is applied to an oligomeric enzyme kinetics at a chemiostatic condition that leads the reaction to a nonequilibrium steady state for which we have estimated how each step of the reaction is energy driven or entropy driven to contribute to the overall reaction.

Photonic Quantum Networks formed from NV(-) centers.

PubMed

Nemoto, Kae; Trupke, Michael; Devitt, Simon J; Scharfenberger, Burkhard; Buczak, Kathrin; Schmiedmayer, Jörg; Munro, William J

2016-05-24

In this article we present a simple repeater scheme based on the negatively-charged nitrogen vacancy centre in diamond. Each repeater node is built from modules comprising an optical cavity containing a single NV(-), with one nuclear spin from (15)N as quantum memory. The module uses only deterministic processes and interactions to achieve high fidelity operations (>99%), and modules are connected by optical fiber. In the repeater node architecture, the processes between modules by photons can be in principle deterministic, however current limitations on optical components lead the processes to be probabilistic but heralded. Our resource-modest repeater architecture contains two modules at each node, and the repeater nodes are then connected by entangled photon pairs. We discuss the performance of such a quantum repeater network with modest resources and then incorporate more resource-intense strategies step by step. Our architecture should allow large-scale quantum information networks with existing or near future technology.

Dual-energy contrast-enhanced digital mammography (DE-CEDM): optimization on digital subtraction with practical x-ray low/high-energy spectra

NASA Astrophysics Data System (ADS)

Chen, Biao; Jing, Zhenxue; Smith, Andrew P.; Parikh, Samir; Parisky, Yuri

2006-03-01

Dual-energy contrast enhanced digital mammography (DE-CEDM), which is based upon the digital subtraction of low/high-energy image pairs acquired before/after the administration of contrast agents, may provide physicians physiologic and morphologic information of breast lesions and help characterize their probability of malignancy. This paper proposes to use only one pair of post-contrast low / high-energy images to obtain digitally subtracted dual-energy contrast-enhanced images with an optimal weighting factor deduced from simulated characteristics of the imaging chain. Based upon our previous CEDM framework, quantitative characteristics of the materials and imaging components in the x-ray imaging chain, including x-ray tube (tungsten) spectrum, filters, breast tissues / lesions, contrast agents (non-ionized iodine solution), and selenium detector, were systemically modeled. Using the base-material (polyethylene-PMMA) decomposition method based on entrance low / high-energy x-ray spectra and breast thickness, the optimal weighting factor was calculated to cancel the contrast between fatty and glandular tissues while enhancing the contrast of iodized lesions. By contrast, previous work determined the optimal weighting factor through either a calibration step or through acquisition of a pre-contrast low/high-energy image pair. Computer simulations were conducted to determine weighting factors, lesions' contrast signal values, and dose levels as functions of x-ray techniques and breast thicknesses. Phantom and clinical feasibility studies were performed on a modified Selenia full field digital mammography system to verify the proposed method and computer-simulated results. The resultant conclusions from the computer simulations and phantom/clinical feasibility studies will be used in the upcoming clinical study.

Small RNA-mediated regulation in bacteria: A growing palette of diverse mechanisms.

PubMed

Dutta, Tanmay; Srivastava, Shubhangi

2018-05-20

Small RNAs (sRNAs) in bacteria have evolved with diverse mechanisms to balance their target gene expression in response to changes in the environment. Accumulating studies on bacterial regulatory processes firmly established that sRNAs modulate their target gene expression generally at the posttranscriptional level. Identification of large number of sRNAs by advanced technologies, like deep sequencing, tilling microarray, indicates the existence of a plethora of distinctive sRNA-mediated regulatory mechanisms in bacteria. Types of the novel mechanisms are increasing with the discovery of new sRNAs. Complementary base pairing between sRNAs and target RNAs assisted by RNA chaperones like Hfq and ProQ, in many occasions, to regulate the cognate gene expression is prevalent in sRNA mechanisms. sRNAs, in most studied cases, can directly base pair with target mRNA to remodel its expression. Base pairing can happen either in the untranslated regions or in the coding regions of mRNA to activate/repress its translation. sRNAs also act as target mimic to titrate away different regulatory RNAs from its target. Other mechanism includes the sequestration of regulatory proteins, especially transcription factors, by sRNAs. Numerous sRNAs, following analogous mechanism, are widespread in bacteria, and thus, has drawn immense attention for the development of RNA-based technologies. Nevertheless, typical sRNA mechanisms are also discovered to be confined in some bacteria. Analysis of the sRNA mechanisms unravels their existence in both the single step processes and the complex regulatory networks with a global effect on cell physiology. This review deals with the diverse array of mechanisms, which sRNAs follow to maintain bacterial lifestyle. Copyright © 2018 Elsevier B.V. All rights reserved.

Incorporating evolution of transcription factor binding sites into annotated alignments.

PubMed

Bais, Abha S; Grossmann, Stefen; Vingron, Martin

2007-08-01

Identifying transcription factor binding sites (TFBSs) is essential to elucidate putative regulatory mechanisms. A common strategy is to combine cross-species conservation with single sequence TFBS annotation to yield "conserved TFBSs". Most current methods in this field adopt a multi-step approach that segregates the two aspects. Again, it is widely accepted that the evolutionary dynamics of binding sites differ from those of the surrounding sequence. Hence, it is desirable to have an approach that explicitly takes this factor into account. Although a plethora of approaches have been proposed for the prediction of conserved TFBSs, very few explicitly model TFBS evolutionary properties, while additionally being multi-step. Recently, we introduced a novel approach to simultaneously align and annotate conserved TFBSs in a pair of sequences. Building upon the standard Smith-Waterman algorithm for local alignments, SimAnn introduces additional states for profiles to output extended alignments or annotated alignments. That is, alignments with parts annotated as gaplessly aligned TFBSs (pair-profile hits)are generated. Moreover,the pair- profile related parameters are derived in a sound statistical framework. In this article, we extend this approach to explicitly incorporate evolution of binding sites in the SimAnn framework. We demonstrate the extension in the theoretical derivations through two position-specific evolutionary models, previously used for modelling TFBS evolution. In a simulated setting, we provide a proof of concept that the approach works given the underlying assumptions,as compared to the original work. Finally, using a real dataset of experimentally verified binding sites in human-mouse sequence pairs,we compare the new approach (eSimAnn) to an existing multi-step tool that also considers TFBS evolution. Although it is widely accepted that binding sites evolve differently from the surrounding sequences, most comparative TFBS identification methods do not explicitly consider this.Additionally, prediction of conserved binding sites is carried out in a multi-step approach that segregates alignment from TFBS annotation. In this paper, we demonstrate how the simultaneous alignment and annotation approach of SimAnn can be further extended to incorporate TFBS evolutionary relationships. We study how alignments and binding site predictions interplay at varying evolutionary distances and for various profile qualities.

Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes: implications for classification of enzyme function.

PubMed

Almonacid, Daniel E; Yera, Emmanuel R; Mitchell, John B O; Babbitt, Patricia C

2010-03-12

Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.

Quantitative Comparison of Catalytic Mechanisms and Overall Reactions in Convergently Evolved Enzymes: Implications for Classification of Enzyme Function

PubMed Central

Almonacid, Daniel E.; Yera, Emmanuel R.; Mitchell, John B. O.; Babbitt, Patricia C.

2010-01-01

Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation. PMID:20300652

Negative refraction and planar focusing based on parity-time symmetric metasurfaces.

PubMed

Fleury, Romain; Sounas, Dimitrios L; Alù, Andrea

2014-07-11

We introduce a new mechanism to realize negative refraction and planar focusing using a pair of parity-time symmetric metasurfaces. In contrast to existing solutions that achieve these effects with negative-index metamaterials or phase conjugating surfaces, the proposed parity-time symmetric lens enables loss-free, all-angle negative refraction and planar focusing in free space, without relying on bulk metamaterials or nonlinear effects. This concept may represent a pivotal step towards loss-free negative refraction and highly efficient planar focusing by exploiting the largely uncharted scattering properties of parity-time symmetric systems.

Beauty is in the 'we' of the beholder: greater agreement on facial attractiveness among close relations.

PubMed

Bronstad, P Matthew; Russell, Richard

2007-01-01

Scientific research on facial attractiveness has focused primarily on elucidating universal factors to which all raters respond consistently. However, recent work has shown that there is also substantial disagreement between raters, highlighting the importance of determining how attractiveness preferences vary among different individuals. We conducted a typical attractiveness ratings study, but took the unusual step of recruiting pairs of subjects who were spouses, siblings, or close friends. The agreement between pairs of affiliated friends, siblings, and spouses was significantly greater than between pairs of strangers drawn from the same race and culture, providing evidence that facial-attractiveness preferences are socially organized.

Registration of 3D spectral OCT volumes combining ICP with a graph-based approach

NASA Astrophysics Data System (ADS)

Niemeijer, Meindert; Lee, Kyungmoo; Garvin, Mona K.; Abràmoff, Michael D.; Sonka, Milan

2012-02-01

The introduction of spectral Optical Coherence Tomography (OCT) scanners has enabled acquisition of high resolution, 3D cross-sectional volumetric images of the retina. 3D-OCT is used to detect and manage eye diseases such as glaucoma and age-related macular degeneration. To follow-up patients over time, image registration is a vital tool to enable more precise, quantitative comparison of disease states. In this work we present a 3D registrationmethod based on a two-step approach. In the first step we register both scans in the XY domain using an Iterative Closest Point (ICP) based algorithm. This algorithm is applied to vessel segmentations obtained from the projection image of each scan. The distance minimized in the ICP algorithm includes measurements of the vessel orientation and vessel width to allow for a more robust match. In the second step, a graph-based method is applied to find the optimal translation along the depth axis of the individual A-scans in the volume to match both scans. The cost image used to construct the graph is based on the mean squared error (MSE) between matching A-scans in both images at different translations. We have applied this method to the registration of Optic Nerve Head (ONH) centered 3D-OCT scans of the same patient. First, 10 3D-OCT scans of 5 eyes with glaucoma imaged in vivo were registered for a qualitative evaluation of the algorithm performance. Then, 17 OCT data set pairs of 17 eyes with known deformation were used for quantitative assessment of the method's robustness.

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.

Methods of operation of apparatus measuring formation resistivity from within a cased well having one measurement and two compensation steps

DOEpatents

Vail, III, William B.

1993-01-01

Methods of operation of an apparatus having at least two pairs of voltage measurement electrodes vertically disposed in a cased well to measure the resistivity of adjacent geological formations from inside the cased well. During stationary measurements with the apparatus at a fixed vertical depth within the cased well, the invention herein discloses methods of operation which include a measurement step and subsequent first and second compensation steps respectively resulting in improved accuracy of measurement. First and second order errors of measurement are identified, and the measurement step and two compensation steps provide methods to substantially eliminate their influence on the results. A multiple frequency apparatus adapted to movement within the well is described which simultaneously provide the measurement and two compensation steps.

High-Resolution Crystal Structure of a Silver(I)-RNA Hybrid Duplex Containing Watson-Crick-like C-Silver(I)-C Metallo-Base Pairs.

PubMed

Kondo, Jiro; Tada, Yoshinari; Dairaku, Takenori; Saneyoshi, Hisao; Okamoto, Itaru; Tanaka, Yoshiyuki; Ono, Akira

2015-11-02

Metallo-base pairs have been extensively studied for applications in nucleic acid-based nanodevices and genetic code expansion. Metallo-base pairs composed of natural nucleobases are attractive because nanodevices containing natural metallo-base pairs can be easily prepared from commercially available sources. Previously, we have reported a crystal structure of a DNA duplex containing T-Hg(II)-T base pairs. Herein, we have determined a high-resolution crystal structure of the second natural metallo-base pair between pyrimidine bases C-Ag(I)-C formed in an RNA duplex. One Ag(I) occupies the center between two cytosines and forms a C-Ag(I)-C base pair through N3-Ag(I)-N3 linear coordination. The C-Ag(I)-C base pair formation does not disturb the standard A-form conformation of RNA. Since the C-Ag(I)-C base pair is structurally similar to the canonical Watson-Crick base pairs, it can be a useful building block for structure-based design and fabrication of nucleic acid-based nanodevices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Learning to Predict Chemical Reactions

PubMed Central

Kayala, Matthew A.; Azencott, Chloé-Agathe; Chen, Jonathan H.

2011-01-01

Being able to predict the course of arbitrary chemical reactions is essential to the theory and applications of organic chemistry. Approaches to the reaction prediction problems can be organized around three poles corresponding to: (1) physical laws; (2) rule-based expert systems; and (3) inductive machine learning. Previous approaches at these poles respectively are not high-throughput, are not generalizable or scalable, or lack sufficient data and structure to be implemented. We propose a new approach to reaction prediction utilizing elements from each pole. Using a physically inspired conceptualization, we describe single mechanistic reactions as interactions between coarse approximations of molecular orbitals (MOs) and use topological and physicochemical attributes as descriptors. Using an existing rule-based system (Reaction Explorer), we derive a restricted chemistry dataset consisting of 1630 full multi-step reactions with 2358 distinct starting materials and intermediates, associated with 2989 productive mechanistic steps and 6.14 million unproductive mechanistic steps. And from machine learning, we pose identifying productive mechanistic steps as a statistical ranking, information retrieval, problem: given a set of reactants and a description of conditions, learn a ranking model over potential filled-to-unfilled MO interactions such that the top ranked mechanistic steps yield the major products. The machine learning implementation follows a two-stage approach, in which we first train atom level reactivity filters to prune 94.00% of non-productive reactions with a 0.01% error rate. Then, we train an ensemble of ranking models on pairs of interacting MOs to learn a relative productivity function over mechanistic steps in a given system. Without the use of explicit transformation patterns, the ensemble perfectly ranks the productive mechanism at the top 89.05% of the time, rising to 99.86% of the time when the top four are considered. Furthermore, the system is generalizable, making reasonable predictions over reactants and conditions which the rule-based expert does not handle. A web interface to the machine learning based mechanistic reaction predictor is accessible through our chemoinformatics portal (http://cdb.ics.uci.edu) under the Toolkits section. PMID:21819139

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.

Scanning tunneling microscope with a rotary piezoelectric stepping motor

NASA Astrophysics Data System (ADS)

Yakimov, V. N.

1996-02-01

A compact scanning tunneling microscope (STM) with a novel rotary piezoelectric stepping motor for coarse positioning has been developed. An inertial method for rotating of the rotor by the pair of piezoplates has been used in the piezomotor. Minimal angular step size was about several arcsec with the spindle working torque up to 1 N×cm. Design of the STM was noticeably simplified by utilization of the piezomotor with such small step size. A shaft eccentrically attached to the piezomotor spindle made it possible to push and pull back the cylindrical bush with the tubular piezoscanner. A linear step of coarse positioning was about 50 nm. STM resolution in vertical direction was better than 0.1 nm without an external vibration isolation.

[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.

Comparison of the DNA extraction methods for polymerase chain reaction amplification from formalin-fixed and paraffin-embedded tissues.

PubMed

Sato, Y; Sugie, R; Tsuchiya, B; Kameya, T; Natori, M; Mukai, K

2001-12-01

To obtain an adequate quality and quantity of DNA from formalin-fixed and paraffin-embedded tissue, six different DNA extraction methods were compared. Four methods used deparaffinization by xylene followed by proteinase K digestion and phenol-chloroform extraction. The temperature of the different steps was changed to obtain higher yields and improved quality of extracted DNA. The remaining two methods used microwave heating for deparaffinization. The best DNA extraction method consisted of deparaffinization by microwave irradiation, protein digestion with proteinase K at 48 degrees C overnight, and no further purification steps. By this method, the highest DNA yield was obtained and the amplification of a 989-base pair beta-globin gene fragment was achieved. Furthermore, DNA extracted by means of this procedure from five gastric carcinomas was successfully used for single strand conformation polymorphism and direct sequencing assays of the beta-catenin gene. Because the microwave-based DNA extraction method presented here is simple, has a lower contamination risk, and results in a higher yield of DNA compared with the ordinary organic chemical reagent-based extraction method, it is considered applicable to various clinical and basic fields.

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

An Embedded Professional Paired Placement Model: "I Know I Am Not an Expert, but I Am at a Point Now Where I Could Step into the Classroom and Be Responsible for the Learning"

ERIC Educational Resources Information Center

Lang, Catherine; Neal, Deborah; Karvouni, Maria; Chandler, Debbie

2015-01-01

We present a sustainable and innovative model for pre-service teacher paired professional placements called the Teaching School model. The Teaching School model was piloted initially in partnership with a Metropolitan University and a P-12 College located in Melbourne's northern suburbs in 2013. It was expanded in 2014 to capitalise on an existing…

High-resolution inchworm linear motor based on electrostatic twisting microactuators

NASA Astrophysics Data System (ADS)

Kim, Sang-Ho; Hwang, Il-Han; Jo, Kyoung-Woo; Yoon, Eui-Sung; Lee, Jong-Hyun

2005-09-01

A new inchworm micromotor using new electrostatic in-plane twisting microactuators has been designed, fabricated and characterized for nano-resolution manipulators. The proposed twisting mechanism was implemented employing a pair of differential electrostatic actuators with a high stiffness in the driving direction for stable positioning. The electromechanically coupled motion of the voltage-displacement relation was analyzed using a finite element method (FEM), confirming that the twisting actuator makes a tiny step movement efficiently. The proposed actuator was fabricated on a silicon-on-insulator (SOI) wafer with the device footprint of 2.2 × 2.8 mm2, and its nano-stepping characteristics were measured by an optical interferometer consisting of an integrated micromirror and optical fiber. The fabricated inchworm motor showed a minimum step displacement of 5.2 ± 3.8 nm (2σ) and 4.1 ± 2.9 nm (2σ) for cyclic motion in the +y- and the -y-directions, respectively, with the gripping voltage of 15 V and differential voltage of 1 V. As a result, the proposed inchworm micromotor could operate with a stroke of 3 µm and a bi-directional step displacement of less than 10 nm. The step displacement is the smallest value of in-plane-type micromotors so far, and its magnitude was controllable up to 120 nm/cycle by changing the differential voltage.

Matt: local flexibility aids protein multiple structure alignment.

PubMed

Menke, Matthew; Berger, Bonnie; Cowen, Lenore

2008-01-01

Even when there is agreement on what measure a protein multiple structure alignment should be optimizing, finding the optimal alignment is computationally prohibitive. One approach used by many previous methods is aligned fragment pair chaining, where short structural fragments from all the proteins are aligned against each other optimally, and the final alignment chains these together in geometrically consistent ways. Ye and Godzik have recently suggested that adding geometric flexibility may help better model protein structures in a variety of contexts. We introduce the program Matt (Multiple Alignment with Translations and Twists), an aligned fragment pair chaining algorithm that, in intermediate steps, allows local flexibility between fragments: small translations and rotations are temporarily allowed to bring sets of aligned fragments closer, even if they are physically impossible under rigid body transformations. After a dynamic programming assembly guided by these "bent" alignments, geometric consistency is restored in the final step before the alignment is output. Matt is tested against other recent multiple protein structure alignment programs on the popular Homstrad and SABmark benchmark datasets. Matt's global performance is competitive with the other programs on Homstrad, but outperforms the other programs on SABmark, a benchmark of multiple structure alignments of proteins with more distant homology. On both datasets, Matt demonstrates an ability to better align the ends of alpha-helices and beta-strands, an important characteristic of any structure alignment program intended to help construct a structural template library for threading approaches to the inverse protein-folding problem. The related question of whether Matt alignments can be used to distinguish distantly homologous structure pairs from pairs of proteins that are not homologous is also considered. For this purpose, a p-value score based on the length of the common core and average root mean squared deviation (RMSD) of Matt alignments is shown to largely separate decoys from homologous protein structures in the SABmark benchmark dataset. We postulate that Matt's strong performance comes from its ability to model proteins in different conformational states and, perhaps even more important, its ability to model backbone distortions in more distantly related proteins.

Infant stepping: a method to study the sensory control of human walking

PubMed Central

Yang, Jaynie F; Stephens, Marilee J; Vishram, Rosie

1998-01-01

Stepping responses were studied in infants between the ages of 10 days and 10 months while they were supported to step on a slowly moving treadmill belt. Surface electromyography (EMG) from muscles in the lower limb, force exerted by the feet on the treadmill belt, and the motion of the lower limbs were recorded. Two groups of infants were studied, those who had a small amount of daily practice in stepping and those who did not. Practice resulted in a dramatic increase in the incidence of stepping recorded in the laboratory, particularly for the periods between 1 and 6 months of age. The majority of infants showed clear alternation between the flexor and extensor muscles during walking, regardless of age. Co-contraction between flexors and extensors, estimated by the overlap in area between rectified and smoothed EMG from a muscle pair, was greater for some muscle groups in the infant compared with the adult. Practice resulted in a significantly lower co-contraction index for the tibialis anterior- quadriceps muscle pair. Practice did not affect the mean step cycle duration. Infants of all ages could step at a range of treadmill speeds by adjusting their step cycle duration. The relationship between the treadmill speed and cycle duration was well fitted by a power function, similar to those reported for intact cats and adult humans. The change in step cycle duration resulted almost entirely from a change in the extensor burst duration, whereas the flexor burst duration remained constant. Airstepping could be elicited in some infants. The cycle durations for airstepping were close to the shortest cycles recorded on the treadmill. In conclusion, the system for generating rhythmic, alternating activity of the lower limbs for stepping is clearly developed by birth. The stepping is sustained and regular, particularly if stepping practice is incorporated briefly each day. The infant population provides a good subject pool for studying the afferent control of walking in the human, before cerebral influences are fully developed. The characteristics and maturity of the system remain to be determined. PMID:9508851

A fast method for searching for repeating earthquakes, applied to the northern San Francisco Bay area

NASA Astrophysics Data System (ADS)

Shakibay Senobari, N.; Funning, G.

2016-12-01

Repeating earthquakes (REs) are the regular or semi-regular failures of the same patch on a fault, producing near-identical waveforms at a given station. Sequences of REs are commonly interpreted as slip on small locked patches surrounded by large areas of fault that are creeping (Nadeau and McEvilly, 1999). Detecting them, therefore, places important constraints on the extent of fault creep at depth. In addition, the magnitude and recurrence interval of these RE sequences can be related to the creep rate and used as constraints on slip models. In this study we search for REs in northern California fault systems upon which creep is suspected, but not well constrained, including the Rodgers Creek, Maacama, Bartlett Springs, Concord-Green Valley, West Napa and Greenville faults, targeting events recorded at stations where the instrument was not changed for 10 years or more. A pair of events can be identified as REs based on a high cross-correlation coefficient (CCC) between their waveforms. Thus a fundamental step in RE searches is calculating the CCC for all event waveform pairs recorded at common stations. This becomes computationally expensive for large data sets. To expedite our search, we use a fast and accurate similarity search algorithm developed by the computer science community (Mueen et al., 2015; Zhu et al., 2016). Our initial tests on a data set including 1500 waveforms suggest it is around 40 times faster than the algorithm that we used previously (Shakibay Senobari and Funning, AGU Fall Meeting 2014). We search for event pairs with CCC>0.85 and cluster them based on their similarity. A second, location based filter, based on the differential S-P times for each event pair at 5 or more stations, is used as an independent check. We consider a cluster of events a RE sequence if the source location separation distance for each pair is less than the estimated circular size of the source (e.g. Chen et al., 2008); these are gathered into an RE catalogue. In future, we plan to use this information in combination with geodetic data to produce a robust creep distribution model for all of the faults in this region.

Self-stabilized narrow-bandwidth and high-fidelity entangled photons generated from cold atoms

NASA Astrophysics Data System (ADS)

Yu, Y. C.; Ding, D. S.; Dong, M. X.; Shi, S.; Zhang, W.; Shi, B. S.

2018-04-01

Entangled photon pairs are critically important in fundamental quantum mechanics research as well as in many areas within the field of quantum information, such as quantum communication, quantum computation, and quantum cryptography. Previous demonstrations of entangled photons based on atomic ensembles were achieved by using a reference laser to stabilize the phase of two spontaneous four-wave mixing paths. Here, we demonstrate a convenient and efficient scheme to generate polarization-entangled photons with a narrow bandwidth of 57.2 ±1.6 MHz and a high-fidelity of 96.3 ±0.8 % by using a phase self-stabilized multiplexing system formed by two beam displacers and two half-wave plates where the relative phase between the different signal paths can be eliminated completely. It is possible to stabilize an entangled photon pair for a long time with this system and produce all four Bell states, making this a vital step forward in the field of quantum information.

Two- and Three-Dimensional Numerical Experiments Representing Two Limiting Cases of an In-Line Pair of Finger Seal Components

NASA Technical Reports Server (NTRS)

Braun, M. J.; Steinetz, B. M.; Kudriavtsev, V. V.; Proctor, M. P.; Kiraly, L. James (Technical Monitor)

2002-01-01

The work presented here concerns the numerical development and simulation of the flow, pressure patterns and motion of a pair of fingers arranged behind each other and axially aligned in-line. The fingers represent the basic elemental component of a Finger Seal (FS) and form a tight seal around the rotor. Yet their flexibility allows compliance with rotor motion and in a passive-adaptive mode complies also with the hydrodynamic forces induced by the flowing fluid. While the paper does not treat the actual staggered configuration of a finger seal, the inline arrangement represents a first step towards that final goal. The numerical 2-D (axial-radial) and 3-D results presented herein were obtained using a commercial package (CFD-ACE+). Both models use an integrated numerical approach, which couples the hydrodynamic fluid model (Navier-Stokes based) to the solid mechanics code that models the compliance of the fingers.

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.

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.

Polyelectrolyte properties of single stranded DNA measured using SAXS and single molecule FRET: beyond the wormlike chain model

PubMed Central

Meisburger, Steve P.; Sutton, Julie L.; Chen, Huimin; Pabit, Suzette A.; Kirmizialtin, Serdal; Elber, Ron; Pollack, Lois

2013-01-01

Nucleic acids are highly charged polyelectrolytes that interact strongly with salt ions. Rigid, base-paired regions are successfully described with worm like chain models, but non base-paired single stranded regions have fundamentally different polymer properties because of their greater flexibility. Recently, attention has turned to single stranded nucleic acids due to the growing recognition of their biological importance, as well as the availability of sophisticated experimental techniques sensitive to the conformation of individual molecules. We investigate polyelectrolyte properties of poly(dT), an important and widely studied model system for flexible single stranded nucleic acids, in physiologically important mixed mono- and di-valent salt. We report measurements of the form factor and interparticle interactions using SAXS, end to end distances using smFRET, and number of excess ions using ASAXS. We present a coarse-grained model that accounts for flexibility, excluded volume, and electrostatic interactions in these systems. Predictions of the model are validated against experiment. We also discuss the state of all-atom, explicit solvent Molecular Dynamics simulations of poly(dT), the next step in understanding the complexities of ion interactions with these highly charged and flexible polymers. PMID:23606337

Supervised Clustering Based on DPClusO: Prediction of Plant-Disease Relations Using Jamu Formulas of KNApSAcK Database

PubMed Central

Husnawati, Husnawati; Afendi, Farit Mochamad; Darusman, Latifah K.; Altaf-Ul-Amin, Md.; Sato, Tetsuo; Ono, Naoaki; Sugiura, Tadao; Kanaya, Shigehiko

2014-01-01

Indonesia has the largest medicinal plant species in the world and these plants are used as Jamu medicines. Jamu medicines are popular traditional medicines from Indonesia and we need to systemize the formulation of Jamu and develop basic scientific principles of Jamu to meet the requirement of Indonesian Healthcare System. We propose a new approach to predict the relation between plant and disease using network analysis and supervised clustering. At the preliminary step, we assigned 3138 Jamu formulas to 116 diseases of International Classification of Diseases (ver. 10) which belong to 18 classes of disease from National Center for Biotechnology Information. The correlation measures between Jamu pairs were determined based on their ingredient similarity. Networks are constructed and analyzed by selecting highly correlated Jamu pairs. Clusters were then generated by using the network clustering algorithm DPClusO. By using matching score of a cluster, the dominant disease and high frequency plant associated to the cluster are determined. The plant to disease relations predicted by our method were evaluated in the context of previously published results and were found to produce around 90% successful predictions. PMID:24804251

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

Step-doubling at Vicinal Ni(111) Surfaces Investigated with a Curved Crystal

DOE PAGES

Ilyn, Max; Magana, Ana; Walter, Andrew Leigh; ...

2017-01-25

Here, vicinal surfaces may undergo structural transformations as a function of temperature or in the presence of adsorbates. Step-doubling, in which monatomic steps pair up forming double-atom high staircases, is the simplest example. Here we investigate the case of Ni(111) using a curved crystal surface, which allows us to explore the occurrence of step-doubling as a function of temperature and vicinal plane (miscut α and step type). We find a striking A-type ({100}-like microfacets) versus B-type ({111}-like) asymmetry towards step-doubling. The terrace-width distribution analysis performed from Scanning Tunneling Microscopy data points to elastic step interactions overcoming entropic effects at verymore » small miscut α in A-type vicinals, as compared to B-type steps. For A-type vicinals, we elaborate the temperature/miscut phase diagram, on which we establish a critical miscut α c = 9.3° for step-doubling to take place.« less

Step-doubling at Vicinal Ni(111) Surfaces Investigated with a Curved Crystal

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

Ilyn, Max; Magana, Ana; Walter, Andrew Leigh

Here, vicinal surfaces may undergo structural transformations as a function of temperature or in the presence of adsorbates. Step-doubling, in which monatomic steps pair up forming double-atom high staircases, is the simplest example. Here we investigate the case of Ni(111) using a curved crystal surface, which allows us to explore the occurrence of step-doubling as a function of temperature and vicinal plane (miscut α and step type). We find a striking A-type ({100}-like microfacets) versus B-type ({111}-like) asymmetry towards step-doubling. The terrace-width distribution analysis performed from Scanning Tunneling Microscopy data points to elastic step interactions overcoming entropic effects at verymore » small miscut α in A-type vicinals, as compared to B-type steps. For A-type vicinals, we elaborate the temperature/miscut phase diagram, on which we establish a critical miscut α c = 9.3° for step-doubling to take place.« less

On Electron-Positron Pair Production by a Spatially Inhomogeneous Electric Field

NASA Astrophysics Data System (ADS)

Chervyakov, A.; Kleinert, H.

2018-05-01

A detailed analysis of electron-positron pair creation induced by a spatially non-uniform and static electric field from vacuum is presented. A typical example is provided by the Sauter potential. For this potential, we derive the analytic expressions for vacuum decay and pair production rate accounted for the entire range of spatial variations. In the limit of a sharp step, we recover the divergent result due to the singular electric field at the origin. The limit of a constant field reproduces the classical result of Euler, Heisenberg and Schwinger, if the latter is properly averaged over the width of a spatial variation. The pair production by the Sauter potential is described for different regimes from weak to strong fields. For all these regimes, the locally constant-field rate is shown to be the upper limit.

Clinical Gait Evaluation of Patients with Lumbar Spine Stenosis.

PubMed

Sun, Jun; Liu, Yan-Cheng; Yan, Song-Hua; Wang, Sha-Sha; Lester, D Kevin; Zeng, Ji-Zhou; Miao, Jun; Zhang, Kuan

2018-02-01

The third generation Intelligent Device for Energy Expenditure and Activity (IDEEA3, MiniSun, CA) has been developed for clinical gait evaluation, and this study was designed to evaluate the accuracy and reliability of IDEEA3 for the gait measurement of lumbar spinal stenosis (LSS) patients. Twelve healthy volunteers were recruited to compare gait cycle, cadence, step length, velocity, and number of steps between a motion analysis system and a high-speed video camera. Twenty hospitalized LSS patients were recruited for the comparison of the five parameters between the IDEEA3 and GoPro camera. Paired t-test, intraclass correlation coefficient, concordance correlation coefficient, and Bland-Altman plots were used for the data analysis. The ratios of GoPro camera results to motion analysis system results, and the ratios of IDEEA3 results to GoPro camera results were all around 1.00. All P-values of paired t-tests for gait cycle, cadence, step length, and velocity were greater than 0.05, while all the ICC and CCC results were above 0.950 with P < 0.001. The measurements for gait cycle, cadence, step length, velocity, and number of steps with the GoPro camera are highly consistent with the measurements with the motion analysis system. The measurements for IDEEA3 are consistent with those for the GoPro camera. IDEEA3 can be effectively used in the gait measurement of LSS patients. © 2018 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

A morphing-based scheme for large deformation analysis with stereo-DIC

NASA Astrophysics Data System (ADS)

Genovese, Katia; Sorgente, Donato

2018-05-01

A key step in the DIC-based image registration process is the definition of the initial guess for the non-linear optimization routine aimed at finding the parameters describing the pixel subset transformation. This initialization may result very challenging and possibly fail when dealing with pairs of largely deformed images such those obtained from two angled-views of not-flat objects or from the temporal undersampling of rapidly evolving phenomena. To address this problem, we developed a procedure that generates a sequence of intermediate synthetic images for gradually tracking the pixel subset transformation between the two extreme configurations. To this scope, a proper image warping function is defined over the entire image domain through the adoption of a robust feature-based algorithm followed by a NURBS-based interpolation scheme. This allows a fast and reliable estimation of the initial guess of the deformation parameters for the subsequent refinement stage of the DIC analysis. The proposed method is described step-by-step by illustrating the measurement of the large and heterogeneous deformation of a circular silicone membrane undergoing axisymmetric indentation. A comparative analysis of the results is carried out by taking as a benchmark a standard reference-updating approach. Finally, the morphing scheme is extended to the most general case of the correspondence search between two largely deformed textured 3D geometries. The feasibility of this latter approach is demonstrated on a very challenging case: the full-surface measurement of the severe deformation (> 150% strain) suffered by an aluminum sheet blank subjected to a pneumatic bulge test.

Dual-channel detection of metallothioneins and mercury based on a mercury-mediated aptamer beacon using thymidine-mercury-thymidine complex as a quencher.

PubMed

Chen, Si-Han; Wang, Yong-Sheng; Chen, Yun-Sheng; Tang, Xian; Cao, Jin-Xiu; Li, Ming-Hui; Wang, Xiao-Feng; Zhu, Yu-Feng; Huang, Yan-Qin

2015-01-01

A novel dual-channel strategy for the detection of metallothioneins (MTs) and Hg(2+) has been developed based on a mercury-mediated aptamer beacon (MAB) using thymidine-mercury-thymidine complex as a quencher for the first time. In the presence of Hg(2+), the T-rich oligonucleotide with a 6-carboxyfluorescein (TRO-FAM) can form an aptamer beacon via the formation of T-Hg(2+)-T base pairs, which results in a fluorescence quenching of the sensing system owing to the fluorescence resonance energy transfer (FRET) from the fluorophore of FAM to the terminated T-Hg(2+)-T base pair. The addition of MTs into this solution leads to the disruption of the T-Hg(2+)-T complex, resulting in an increase of the fluorescent signal of the system. In the optimizing condition, ΔF was directly proportional to the concentrations ranging from 5.63 nM to 0.275 μM for MTs, and 14.2 nM to 0.30 μM for Hg(2+) with the detection limits of 1.69 nM and 4.28 nM, respectively. The proposed dual-channel method avoids the label steps of a quencher in common molecular beacon strategies, without tedious procedure or the requirement of sophisticated equipment, and is rapid, inexpensive and sensitive. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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.

De novo peptide sequencing using CID and HCD spectra pairs.

PubMed

Yan, Yan; Kusalik, Anthony J; Wu, Fang-Xiang

2016-10-01

In tandem mass spectrometry (MS/MS), there are several different fragmentation techniques possible, including, collision-induced dissociation (CID) higher energy collisional dissociation (HCD), electron-capture dissociation (ECD), and electron transfer dissociation (ETD). When using pairs of spectra for de novo peptide sequencing, the most popular methods are designed for CID (or HCD) and ECD (or ETD) spectra because of the complementarity between them. Less attention has been paid to the use of CID and HCD spectra pairs. In this study, a new de novo peptide sequencing method is proposed for these spectra pairs. This method includes a CID and HCD spectra merging criterion and a parent mass correction step, along with improvements to our previously proposed algorithm for sequencing merged spectra. Three pairs of spectral datasets were used to investigate and compare the performance of the proposed method with other existing methods designed for single spectrum (HCD or CID) sequencing. Experimental results showed that full-length peptide sequencing accuracy was increased significantly by using spectra pairs in the proposed method, with the highest accuracy reaching 81.31%. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular mechanisms of homologous chromosome pairing and segregation in plants.

PubMed

Zhang, Jing; Zhang, Bing; Su, Handong; Birchler, James A; Han, Fangpu

2014-03-20

In most eukaryotic species, three basic steps of pairing, recombination and synapsis occur during prophase of meiosis I. Homologous chromosomal pairing and recombination are essential for accurate segregation of chromosomes. In contrast to the well-studied processes such as recombination and synapsis, many aspects of chromosome pairing are still obscure. Recent progress in several species indicates that the telomere bouquet formation can facilitate homologous chromosome pairing by bringing chromosome ends into close proximity, but the sole presence of telomere clustering is not sufficient for recognizing homologous pairs. On the other hand, accurate segregation of the genetic material from parent to offspring during meiosis is dependent on the segregation of homologs in the reductional meiotic division (MI) with sister kinetochores exhibiting mono-orientation from the same pole, and the segregation of sister chromatids during the equational meiotic division (MII) with kinetochores showing bi-orientation from the two poles. The underlying mechanism of orientation and segregation is still unclear. Here we focus on recent studies in plants and other species that provide insight into how chromosomes find their partners and mechanisms mediating chromosomal segregation. Copyright © 2013. Published by Elsevier Ltd.

Efficient CRISPR/Cas9-Mediated Versatile, Predictable, and Donor-Free Gene Knockout in Human Pluripotent Stem Cells.

PubMed

Liu, Zhongliang; Hui, Yi; Shi, Lei; Chen, Zhenyu; Xu, Xiangjie; Chi, Liankai; Fan, Beibei; Fang, Yujiang; Liu, Yang; Ma, Lin; Wang, Yiran; Xiao, Lei; Zhang, Quanbin; Jin, Guohua; Liu, Ling; Zhang, Xiaoqing

2016-09-13

Loss-of-function studies in human pluripotent stem cells (hPSCs) require efficient methodologies for lesion of genes of interest. Here, we introduce a donor-free paired gRNA-guided CRISPR/Cas9 knockout strategy (paired-KO) for efficient and rapid gene ablation in hPSCs. Through paired-KO, we succeeded in targeting all genes of interest with high biallelic targeting efficiencies. More importantly, during paired-KO, the cleaved DNA was repaired mostly through direct end joining without insertions/deletions (precise ligation), and thus makes the lesion product predictable. The paired-KO remained highly efficient for one-step targeting of multiple genes and was also efficient for targeting of microRNA, while for long non-coding RNA over 8 kb, cleavage of a short fragment of the core promoter region was sufficient to eradicate downstream gene transcription. This work suggests that the paired-KO strategy is a simple and robust system for loss-of-function studies for both coding and non-coding genes in hPSCs. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

Improving strand pairing prediction through exploring folding cooperativity

PubMed Central

Jeong, Jieun; Berman, Piotr; Przytycka, Teresa M.

2008-01-01

The topology of β-sheets is defined by the pattern of hydrogen-bonded strand pairing. Therefore, predicting hydrogen bonded strand partners is a fundamental step towards predicting β-sheet topology. At the same time, finding the correct partners is very difficult due to long range interactions involved in strand pairing. Additionally, patterns of aminoacids observed in β-sheet formations are very general and therefore difficult to use for computational recognition of specific contacts between strands. In this work, we report a new strand pairing algorithm. To address above mentioned difficulties, our algorithm attempts to mimic elements of the folding process. Namely, in addition to ensuring that the predicted hydrogen bonded strand pairs satisfy basic global consistency constraints, it takes into account hypothetical folding pathways. Consistently with this view, introducing hydrogen bonds between a pair of strands changes the probabilities of forming hydrogen bonds between other pairs of strand. We demonstrate that this approach provides an improvement over previously proposed algorithms. We also compare the performance of this method to that of a global optimization algorithm that poses the problem as integer linear programming optimization problem and solves it using ILOG CPLEX™ package. PMID:18989036

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.

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.

Reactivity of chemisorbed oxygen atoms and their catalytic consequences during CH4-O2 catalysis on supported Pt clusters.

PubMed

Chin, Ya-Huei Cathy; Buda, Corneliu; Neurock, Matthew; Iglesia, Enrique

2011-10-12

Kinetic and isotopic data and density functional theory treatments provide evidence for the elementary steps and the active site requirements involved in the four distinct kinetic regimes observed during CH(4) oxidation reactions using O(2), H(2)O, or CO(2) as oxidants on Pt clusters. These four regimes exhibit distinct rate equations because of the involvement of different kinetically relevant steps, predominant adsorbed species, and rate and equilibrium constants for different elementary steps. Transitions among regimes occur as chemisorbed oxygen (O*) coverages change on Pt clusters. O* coverages are given, in turn, by a virtual O(2) pressure, which represents the pressure that would give the prevalent steady-state O* coverages if their adsorption-desorption equilibrium was maintained. The virtual O(2) pressure acts as a surrogate for oxygen chemical potentials at catalytic surfaces and reflects the kinetic coupling between C-H and O═O activation steps. O* coverages and virtual pressures depend on O(2) pressure when O(2) activation is equilibrated and on O(2)/CH(4) ratios when this step becomes irreversible as a result of fast scavenging of O* by CH(4)-derived intermediates. In three of these kinetic regimes, C-H bond activation is the sole kinetically relevant step, but occurs on different active sites, which evolve from oxygen-oxygen (O*-O*), to oxygen-oxygen vacancy (O*-*), and to vacancy-vacancy (*-*) site pairs as O* coverages decrease. On O*-saturated cluster surfaces, O*-O* site pairs activate C-H bonds in CH(4) via homolytic hydrogen abstraction steps that form CH(3) groups with significant radical character and weak interactions with the surface at the transition state. In this regime, rates depend linearly on CH(4) pressure but are independent of O(2) pressure. The observed normal CH(4)/CD(4) kinetic isotope effects are consistent with the kinetic-relevance of C-H bond activation; identical (16)O(2)-(18)O(2) isotopic exchange rates in the presence or absence of CH(4) show that O(2) activation steps are quasi-equilibrated during catalysis. Measured and DFT-derived C-H bond activation barriers are large, because of the weak stabilization of the CH(3) fragments at transition states, but are compensated by the high entropy of these radical-like species. Turnover rates in this regime decrease with increasing Pt dispersion, because low-coordination exposed Pt atoms on small clusters bind O* more strongly than those that reside at low-index facets on large clusters, thus making O* less effective in H-abstraction. As vacancies (*, also exposed Pt atoms) become available on O*-covered surfaces, O*-* site pairs activate C-H bonds via concerted oxidative addition and H-abstraction in transition states effectively stabilized by CH(3) interactions with the vacancies, which lead to much higher turnover rates than on O*-O* pairs. In this regime, O(2) activation becomes irreversible, because fast C-H bond activation steps scavenge O* as it forms. Thus, O* coverages are set by the prevalent O(2)/CH(4) ratios instead of the O(2) pressures. CH(4)/CD(4) kinetic isotope effects are much larger for turnovers mediated by O*-* than by O*-O* site pairs, because C-H (and C-D) activation steps are required to form the * sites involved in C-H bond activation. Turnover rates for CH(4)-O(2) reactions mediated by O*-* pairs decrease with increasing Pt dispersion, as in the case of O*-O* active structures, because stronger O* binding on small clusters leads not only to less reactive O* atoms, but also to lower vacancy concentrations at cluster surfaces. As O(2)/CH(4) ratios and O* coverages become smaller, O(2) activation on bare Pt clusters becomes the sole kinetically relevant step; turnover rates are proportional to O(2) pressures and independent of CH(4) pressure and no CH(4)/CD(4) kinetic isotope effects are observed. In this regime, turnover rates become nearly independent of Pt dispersion, because the O(2) activation step is essentially barrierless. In the absence of O(2), alternate weaker oxidants, such as H(2)O or CO(2), lead to a final kinetic regime in which C-H bond dissociation on *-* pairs at bare cluster surfaces limit CH(4) conversion rates. Rates become first-order in CH(4) and independent of coreactant and normal CH(4)/CD(4) kinetic isotope effects are observed. In this case, turnover rates increase with increasing dispersion, because low-coordination Pt atoms stabilize the C-H bond activation transition states more effectively via stronger binding to CH(3) and H fragments. These findings and their mechanistic interpretations are consistent with all rate and isotopic data and with theoretical estimates of activation barriers and of cluster size effects on transition states. They serve to demonstrate the essential role of the coverage and reactivity of chemisorbed oxygen in determining the type and effectiveness of surface structures in CH(4) oxidation reactions using O(2), H(2)O, or CO(2) as oxidants, as well as the diversity of rate dependencies, activation energies and entropies, and cluster size effects that prevail in these reactions. These results also show how theory and experiments can unravel complex surface chemistries on realistic catalysts under practical conditions and provide through the resulting mechanistic insights specific predictions for the effects of cluster size and surface coordination on turnover rates, the trends and magnitude of which depend sensitively on the nature of the predominant adsorbed intermediates and the kinetically relevant steps.

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

Mechanism for verification of mismatched and homoduplex DNAs by nucleotides-bound MutS analyzed by molecular dynamics simulations.

PubMed

Ishida, Hisashi; Matsumoto, Atsushi

2016-09-01

In order to understand how MutS recognizes mismatched DNA and induces the reaction of DNA repair using ATP, the dynamics of the complexes of MutS (bound to the ADP and ATP nucleotides, or not) and DNA (with mismatched and matched base-pairs) were investigated using molecular dynamics simulations. As for DNA, the structure of the base-pairs of the homoduplex DNA which interacted with the DNA recognition site of MutS was intermittently disturbed, indicating that the homoduplex DNA was unstable. As for MutS, the disordered loops in the ATPase domains, which are considered to be necessary for the induction of DNA repair, were close to (away from) the nucleotide-binding sites in the ATPase domains when the nucleotides were (not) bound to MutS. This indicates that the ATPase domains changed their structural stability upon ATP binding using the disordered loop. Conformational analysis by principal component analysis showed that the nucleotide binding changed modes which have structurally solid ATPase domains and the large bending motion of the DNA from higher to lower frequencies. In the MutS-mismatched DNA complex bound to two nucleotides, the bending motion of the DNA at low frequency modes may play a role in triggering the formation of the sliding clamp for the following DNA-repair reaction step. Moreover, MM-PBSA/GBSA showed that the MutS-homoduplex DNA complex bound to two nucleotides was unstable because of the unfavorable interactions between MutS and DNA. This would trigger the ATP hydrolysis or separation of MutS and DNA to continue searching for mismatch base-pairs. Proteins 2016; 84:1287-1303. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A long baseline global stereo matching based upon short baseline estimation

NASA Astrophysics Data System (ADS)

Li, Jing; Zhao, Hong; Li, Zigang; Gu, Feifei; Zhao, Zixin; Ma, Yueyang; Fang, Meiqi

2018-05-01

In global stereo vision, balancing the matching efficiency and computing accuracy seems to be impossible because they contradict each other. In the case of a long baseline, this contradiction becomes more prominent. In order to solve this difficult problem, this paper proposes a novel idea to improve both the efficiency and accuracy in global stereo matching for a long baseline. In this way, the reference images located between the long baseline image pairs are firstly chosen to form the new image pairs with short baselines. The relationship between the disparities of pixels in the image pairs with different baselines is revealed by considering the quantized error so that the disparity search range under the long baseline can be reduced by guidance of the short baseline to gain matching efficiency. Then, the novel idea is integrated into the graph cuts (GCs) to form a multi-step GC algorithm based on the short baseline estimation, by which the disparity map under the long baseline can be calculated iteratively on the basis of the previous matching. Furthermore, the image information from the pixels that are non-occluded under the short baseline but are occluded for the long baseline can be employed to improve the matching accuracy. Although the time complexity of the proposed method depends on the locations of the chosen reference images, it is usually much lower for a long baseline stereo matching than when using the traditional GC algorithm. Finally, the validity of the proposed method is examined by experiments based on benchmark datasets. The results show that the proposed method is superior to the traditional GC method in terms of efficiency and accuracy, and thus it is suitable for long baseline stereo matching.

Identification of stepped changes of binding affinity during interactions between the disintegrin rhodostomin and integrin αIIbβ3 in living cells using optical tweezers

NASA Astrophysics Data System (ADS)

Hsieh, Chia-Fen; Chang, Bo-Jui; Pai, Chyi-Huey; Chen, Hsuan-Yi; Chi, Sien; Hsu, Long; Tsai, Jin-Wu; Lin, Chi-Hung

2004-10-01

Integrin receptors serve as both mechanical links and signal transduction mediators between the cell and its environment. Experimental evidence demonstrates that conformational changes and lateral clustering of the integrin proteins may affect their binding to ligands and regulate downstream cellular responses; however, experimental links between the structural and functional correlations of the ligand-receptor interactions are not yet elucidated. In the present report, we utilized optical tweezers to measure the dynamic binding between the snake venom rhodostomin, coated on a microparticle and functioned as a ligand, and the membrane receptor integrin alpha(IIb)beta(3) expressed on a Chinese Hamster Ovary (CHO) cell. A progressive increase of total binding affinity was found between the bead and CHO cell in the first 300 sec following optical tweezers-guided contact. Further analysis of the cumulative data revealed the presence of "unit binding force" presumably exerted by a single rhodostomin-integrin pair. Interestingly, two such units were found. Among the measurements of less total binding forces, presumably taken at the early stage of ligand-receptor interactions, a unit of 4.15 pN per molecule pair was derived. This unit force dropped to 2.54 pN per molecule pair toward the later stage of interactions when the total binding forces were relatively large. This stepped change of single molecule pair binding affinity was not found when mutant rhodostomin proteins were used as ligands (a single unit of 1.81 pN per pair was found). These results were interpreted along with the current knowledge about the conformational changes of integrins during the "molecule activation" process.

N(4)C-ethyl-N(4)C cross-linked DNA: synthesis and characterization of duplexes with interstrand cross-links of different orientations.

PubMed

Noronha, Anne M; Noll, David M; Wilds, Christopher J; Miller, Paul S

2002-01-22

The preparation and physical properties of short DNA duplexes that contain a N(4)C-ethyl-N(4)C interstrand cross-link are described. Duplexes that contain an interstrand cross-link between mismatched C-C residues and duplexes in which the C residues of a -CG- or -GC- step are linked to give "staggered" interstrand cross-links were prepared using a novel N(4)C-ethyl-N(4)C phosphoramidite reagent. Duplexes with the C-C mismatch cross-link have UV thermal transition temperatures that are 25 degrees C higher than the melting temperatures of control duplexes in which the cross-link is replaced with a G-C base pair. It appears that this cross-link stabilizes adjacent base pairs and does not perturb the structure of the helix, a conclusion that is supported by the CD spectrum of this duplex and by molecular models. An even higher level of stabilization, 49 degrees C, is seen with the duplex that contains a -CG- staggered cross-link. Molecular models suggest that this cross-link may induce propeller twisting in the cross-linked base pairs, and the CD spectrum of this duplex exhibits an unusual negative band at 298 nm, although the remainder of the spectrum is similar to that of B-form DNA. Mismatched C-C or -CG- staggered cross-linked duplexes that have complementary overhanging ends can undergo self-ligation catalyzed by T4 DNA ligase. Analysis of the ligated oligomers by nondenaturing polyacrylamide gel electrophoresis shows that the resulting oligomers migrate in a manner similar to that of a mixture of non-cross-linked control oligomers and suggests that these cross-links do not result in significant bending of the helix. However, the orientation of the staggered cross-link can have a significant effect on the structure and stability of the cross-linked duplex. Thus, the thermal stability of the duplex that contains a -GC- staggered cross-link is 10 degrees C lower than the melting temperature of the control, non-cross-linked duplex. Unlike the -CG- staggered cross-link, in which the cross-linked base pairs can still maintain hydrogen bond contacts, molecular models suggest that formation of the -GC- staggered cross-link disrupts hydrogen bonding and may also perturb adjacent base pairs leading to an overall reduction in helix stability. Duplexes with specifically positioned and oriented cross-links can be used as substrates to study DNA repair mechanisms.

Vision Based Localization in Urban Environments

NASA Technical Reports Server (NTRS)

McHenry, Michael; Cheng, Yang; Matthies, Larry

2005-01-01

As part of DARPA's MARS2020 program, the Jet Propulsion Laboratory developed a vision-based system for localization in urban environments that requires neither GPS nor active sensors. System hardware consists of a pair of small FireWire cameras and a standard Pentium-based computer. The inputs to the software system consist of: 1) a crude grid-based map describing the positions of buildings, 2) an initial estimate of robot location and 3) the video streams produced by each camera. At each step during the traverse the system: captures new image data, finds image features hypothesized to lie on the outside of a building, computes the range to those features, determines an estimate of the robot's motion since the previous step and combines that data with the map to update a probabilistic representation of the robot's location. This probabilistic representation allows the system to simultaneously represent multiple possible locations, For our testing, we have derived the a priori map manually using non-orthorectified overhead imagery, although this process could be automated. The software system consists of two primary components. The first is the vision system which uses binocular stereo ranging together with a set of heuristics to identify features likely to be part of building exteriors and to compute an estimate of the robot's motion since the previous step. The resulting visual features and the associated range measurements are software component, a particle-filter based localization system. This system uses the map and the then fed to the second primary most recent results from the vision system to update the estimate of the robot's location. This report summarizes the design of both the hardware and software and will include the results of applying the system to the global localization of a robot over an approximately half-kilometer traverse across JPL'S Pasadena campus.

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.

Introducing a model of pairing based on base pair specific interactions between identical DNA sequences

NASA Astrophysics Data System (ADS)

(O' Lee, Dominic J.

2018-02-01

At present, there have been suggested two types of physical mechanism that may facilitate preferential pairing between DNA molecules, with identical or similar base pair texts, without separation of base pairs. One mechanism solely relies on base pair specific patterns of helix distortion being the same on the two molecules, discussed extensively in the past. The other mechanism proposes that there are preferential interactions between base pairs of the same composition. We introduce a model, built on this second mechanism, where both thermal stretching and twisting fluctuations are included, as well as the base pair specific helix distortions. Firstly, we consider an approximation for weak pairing interactions, or short molecules. This yields a dependence of the energy on the square root of the molecular length, which could explain recent experimental data. However, analysis suggests that this approximation is no longer valid at large DNA lengths. In a second approximation, for long molecules, we define two adaptation lengths for twisting and stretching, over which the pairing interaction can limit the accumulation of helix disorder. When the pairing interaction is sufficiently strong, both adaptation lengths are finite; however, as we reduce pairing strength, the stretching adaptation length remains finite but the torsional one becomes infinite. This second state persists to arbitrarily weak values of the pairing strength; suggesting that, if the molecules are long enough, the pairing energy scales as length. To probe differences between the two pairing mechanisms, we also construct a model of similar form. However, now, pairing between identical sequences solely relies on the intrinsic helix distortion patterns. Between the two models, we see interesting qualitative differences. We discuss our findings, and suggest new work to distinguish between the two mechanisms.

Observing Holliday junction branch migration one step at a time

NASA Astrophysics Data System (ADS)

Ha, Taekjip

2004-03-01

During genetic recombination, two homologous DNA molecules undergo strand exchange to form a four-way DNA (Holliday) junction and the recognition and processing of this species by branch migration and junction resolving enzymes determine the outcome. We have used single molecule fluorescence techniques to study two intrinsic structural dynamics of the Holliday junction, stacking conformer transitions and spontaneous branch migration. Our studies show that the dynamics of branch migration, resolved with one base pair resolution, is determined by the stability of conformers which in turn depends on the local DNA sequences. Therefore, the energy landscape of Holliday junction branch migation is not uniform, but is rugged.

Polyaniline nanowires-gold nanoparticles hybrid network based chemiresistive hydrogen sulfide sensor

NASA Astrophysics Data System (ADS)

Shirsat, Mahendra D.; Bangar, Mangesh A.; Deshusses, Marc A.; Myung, Nosang V.; Mulchandani, Ashok

2009-02-01

We report a sensitive, selective, and fast responding room temperature chemiresistive sensor for hydrogen sulfide detection and quantification using polyaniline nanowires-gold nanoparticles hybrid network. The sensor was fabricated by facile electrochemical technique. Initially, polyaniline nanowires with a diameter of 250-320 nm bridging the gap between a pair of microfabricated gold electrodes were synthesized using templateless electrochemical polymerization using a two step galvanostatic technique. Polyaniline nanowires were then electrochemically functionalized with gold nanoparticles using cyclic voltammetry technique. These chemiresistive sensors show an excellent limit of detection (0.1 ppb), wide dynamic range (0.1-100 ppb), and very good selectivity and reproducibility.

PCR-Based Method for the Detection of Toxic Mushrooms Causing Food-Poisoning Incidents.

PubMed

Nomura, Chie; Masayama, Atsushi; Yamaguchi, Mizuka; Sakuma, Daisuke; Kajimura, Keiji

2017-01-01

In this study, species-specific identification of five toxic mushrooms, Chlorophyllum molybdites, Gymnopilus junonius, Hypholoma fasciculare, Pleurocybella porrigens, and Tricholoma ustale, which have been involved in food-poisoning incidents in Japan, was investigated. Specific primer pairs targeting internal transcribed spacer (ITS) regions were designed for PCR detection. The specific amplicons were obtained from fresh, cooked, and simulated gastric fluid (SGF)-treated samples. No amplicons were detected from other mushrooms with similar morphology. Our method using one-step extraction of mushrooms allows rapid detection within 2.5 hr. It could be utilized for rapid identification or screening of toxic mushrooms.

Payment reform to finance a medical home: comment on "Achieving cost control, care coordination, and quality improvement through incremental payment system reform".

PubMed

McGuire, Thomas G

2010-01-01

This commentary on R. F. Averill et al. (2010) addresses their idea of risk and quality adjusting fee-for-service payments to primary care physicians in order to improve the efficiency of primary care and take a step toward financing a "medical home"for patients. I show how their idea can create incentives for efficient practice styles. Pairing this with an active beneficiary choice of primary care physician with an enrollment fee would make the idea easier to implement and provide an incentive and the financing for elements of service not covered by procedure-based fees.

Intermediate Templates Guided Groupwise Registration of Diffusion Tensor Images

PubMed Central

Jia, Hongjun; Yap, Pew-Thian; Wu, Guorong; Wang, Qian; Shen, Dinggang

2010-01-01

Registration of a population of diffusion tensor images (DTIs) is one of the key steps in medical image analysis, and it plays an important role in the statistical analysis of white matter related neurological diseases. However, pairwise registration with respect to a pre-selected template may not give precise results if the selected template deviates significantly from the distribution of images. To cater for more accurate and consistent registration, a novel framework is proposed for groupwise registration with the guidance from one or more intermediate templates determined from the population of images. Specifically, we first use a Euclidean distance, defined as a combinative measure based on the FA map and ADC map, for gauging the similarity of each pair of DTIs. A fully connected graph is then built with each node denoting an image and each edge denoting the distance between a pair of images. The root template image is determined automatically as the image with the overall shortest path length to all other images on the minimum spanning tree (MST) of the graph. Finally, a sequence of registration steps is applied to progressively warping each image towards the root template image with the help of intermediate templates distributed along its path to the root node on the MST. Extensive experimental results using diffusion tensor images of real subjects indicate that registration accuracy and fiber tract alignment are significantly improved, compared with the direct registration from each image to the root template image. PMID:20851197

Novel keyword co-occurrence network-based methods to foster systematic reviews of scientific literature.

PubMed

Radhakrishnan, Srinivasan; Erbis, Serkan; Isaacs, Jacqueline A; Kamarthi, Sagar

2017-01-01

Systematic reviews of scientific literature are important for mapping the existing state of research and highlighting further growth channels in a field of study, but systematic reviews are inherently tedious, time consuming, and manual in nature. In recent years, keyword co-occurrence networks (KCNs) are exploited for knowledge mapping. In a KCN, each keyword is represented as a node and each co-occurrence of a pair of words is represented as a link. The number of times that a pair of words co-occurs in multiple articles constitutes the weight of the link connecting the pair. The network constructed in this manner represents cumulative knowledge of a domain and helps to uncover meaningful knowledge components and insights based on the patterns and strength of links between keywords that appear in the literature. In this work, we propose a KCN-based approach that can be implemented prior to undertaking a systematic review to guide and accelerate the review process. The novelty of this method lies in the new metrics used for statistical analysis of a KCN that differ from those typically used for KCN analysis. The approach is demonstrated through its application to nano-related Environmental, Health, and Safety (EHS) risk literature. The KCN approach identified the knowledge components, knowledge structure, and research trends that match with those discovered through a traditional systematic review of the nanoEHS field. Because KCN-based analyses can be conducted more quickly to explore a vast amount of literature, this method can provide a knowledge map and insights prior to undertaking a rigorous traditional systematic review. This two-step approach can significantly reduce the effort and time required for a traditional systematic literature review. The proposed KCN-based pre-systematic review method is universal. It can be applied to any scientific field of study to prepare a knowledge map.

Novel keyword co-occurrence network-based methods to foster systematic reviews of scientific literature

PubMed Central

Isaacs, Jacqueline A.

2017-01-01

Systematic reviews of scientific literature are important for mapping the existing state of research and highlighting further growth channels in a field of study, but systematic reviews are inherently tedious, time consuming, and manual in nature. In recent years, keyword co-occurrence networks (KCNs) are exploited for knowledge mapping. In a KCN, each keyword is represented as a node and each co-occurrence of a pair of words is represented as a link. The number of times that a pair of words co-occurs in multiple articles constitutes the weight of the link connecting the pair. The network constructed in this manner represents cumulative knowledge of a domain and helps to uncover meaningful knowledge components and insights based on the patterns and strength of links between keywords that appear in the literature. In this work, we propose a KCN-based approach that can be implemented prior to undertaking a systematic review to guide and accelerate the review process. The novelty of this method lies in the new metrics used for statistical analysis of a KCN that differ from those typically used for KCN analysis. The approach is demonstrated through its application to nano-related Environmental, Health, and Safety (EHS) risk literature. The KCN approach identified the knowledge components, knowledge structure, and research trends that match with those discovered through a traditional systematic review of the nanoEHS field. Because KCN-based analyses can be conducted more quickly to explore a vast amount of literature, this method can provide a knowledge map and insights prior to undertaking a rigorous traditional systematic review. This two-step approach can significantly reduce the effort and time required for a traditional systematic literature review. The proposed KCN-based pre-systematic review method is universal. It can be applied to any scientific field of study to prepare a knowledge map. PMID:28328983

Using an isomorphic problem pair to learn introductory physics: Transferring from a two-step problem to a three-step problem

NASA Astrophysics Data System (ADS)

Lin, Shih-Yin; Singh, Chandralekha

2013-12-01

In this study, we examine introductory physics students’ ability to perform analogical reasoning between two isomorphic problems which employ the same underlying physics principles but have different surface features. 382 students from a calculus-based and an algebra-based introductory physics course were administered a quiz in the recitation in which they had to learn from a solved problem provided and take advantage of what they learned from it to solve another isomorphic problem (which we call the quiz problem). The solved problem provided has two subproblems while the quiz problem has three subproblems, which is known from previous research to be challenging for introductory students. In addition to the solved problem, students also received extra scaffolding supports that were intended to help them discern and exploit the underlying similarities of the isomorphic solved and quiz problems. The data analysis suggests that students had great difficulty in transferring what they learned from a two-step problem to a three-step problem. Although most students were able to learn from the solved problem to some extent with the scaffolding provided and invoke the relevant principles in the quiz problem, they were not necessarily able to apply the principles correctly. We also conducted think-aloud interviews with six introductory students in order to understand in depth the difficulties they had and explore strategies to provide better scaffolding. The interviews suggest that students often superficially mapped the principles employed in the solved problem to the quiz problem without necessarily understanding the governing conditions underlying each principle and examining the applicability of the principle in the new situation in an in-depth manner. Findings suggest that more scaffolding is needed to help students in transferring from a two-step problem to a three-step problem and applying the physics principles appropriately. We outline a few possible strategies for future investigation.

A problem-solving approach to nutrition education with Filipino mothers.

PubMed

Ticao, C J; Aboud, F E

1998-06-01

The study examined Filipino mothers' problem solving on issues related to child feeding, using a dyadic, peer-help approach. The participants were mothers of children under 6 yr of age from a village in the southern Philippines, where malnutrition among children is prevalent. Mothers were paired with a mutual friend (each nominated the other as a best friend) or a unilateral friend (only one nominated the other as a best friend) to discuss a feeding problem to which they initially gave similar solutions (agreed) and one to which they gave different solutions (disagreed). In the final step, they were asked to give privately the solutions they considered best for the problem. The number and quality of these final-step solutions were analyzed as a function of the friend relation, the level of initial agreement with their friend partner, and the source of the solution. Results indicated that the quantity and quality of solutions increased from before to after the dyadic discussion, especially among mothers paired with a mutual friend with whom they agreed. Most of their final-step solutions came from ones they themselves had generated during the discussion, not ones their friend partner had proposed. There was also evidence that high quality solutions were generated by mothers paired with a disagreeing unilateral friend. Implications for nutrition education concern the benefits of a peer-help, dyadic problem-solving approach, taking into account the role of a friend in facilitating a mother's production of new solutions to child feeding problems. The procedure may be used by health promoters who want to build capacities and self-reliance through collective problem solving.

Illusory spirals and loops in crystal growth

PubMed Central

Shtukenberg, Alexander G.; Zhu, Zina; Bhandari, Misha; Song, Pengcheng; Kahr, Bart; Ward, Michael D.

2013-01-01

The theory of dislocation-controlled crystal growth identifies a continuous spiral step with an emergent lattice displacement on a crystal surface; a mechanistic corollary is that closely spaced, oppositely winding spirals merge to form concentric loops. In situ atomic force microscopy of step propagation on pathological l-cystine crystals did indeed show spirals and islands with step heights of one lattice displacement. We show by analysis of the rates of growth of smaller steps only one molecule high that the major morphological spirals and loops are actually consequences of the bunching of the smaller steps. The morphology of the bunched steps actually inverts the predictions of the theory: Spirals arise from pairs of dislocations, loops from single dislocations. Only through numerical simulation of the growth is it revealed how normal growth of anisotropic layers of molecules within the highly symmetrical crystals can conspire to create features in apparent violation of the classic theory. PMID:24101507

Uncovering the Atomistic Mechanism for Calcite Step Growth

DOE PAGES

De La Pierre, Marco; Raiteri, Paolo; Stack, Andrew G.; ...

2017-04-13

Determining a complete atomic-level picture of how minerals grow from aqueous solution remains a challenge as macroscopic rates can be a convolution of many reactions. For the case of calcite (CaCO 3) in water, computer simulations have been used in this paper to map the complex thermodynamic landscape leading to growth of the two distinct steps, acute and obtuse, on the basal surface. The carbonate ion is found to preferentially adsorb at the upper edge of acute steps while Ca 2+ only adsorbs after CO 3 2-. In contrast to the conventional picture, ion pairs prefer to bind at themore » upper edge of the step with only one ion, at most, coordinated to the step and lower terrace. Finally, migration of the first carbonate ion to a growth site is found to be rate-limiting for kink nucleation, with this process having a lower activation energy on the obtuse step.« less

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.

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.

A Pharmacovigilance Signaling System Based on FDA Regulatory Action and Post-Marketing Adverse Event Reports.

PubMed

Hoffman, Keith B; Dimbil, Mo; Tatonetti, Nicholas P; Kyle, Robert F

2016-06-01

Many serious drug adverse events (AEs) only manifest well after regulatory approval. Therefore, the development of signaling methods to use with post-approval AE databases appears vital to comprehensively assess real-world drug safety. However, with millions of potential drug-AE pairs to analyze, the issue of focus is daunting. Our objective was to develop a signaling platform that focuses on AEs with historically demonstrated regulatory interest and to analyze such AEs with a disproportional reporting method that offers broad signal detection and acceptable false-positive rates. We analyzed over 1500 US FDA regulatory actions (safety communications and drug label changes) from 2008 to 2015 to construct a list of eligible signal AEs. The FDA Adverse Event Reporting System (FAERS) was used to evaluate disproportional reporting rates, constrained by minimum case counts and confidence interval limits, of these selected AEs for 109 training drugs. This step led to 45 AEs that appeared to have a low likelihood of being added to a label by FDA, so they were removed from the signal eligible list. We measured disproportional reporting for the final group of eligible AEs on a test group of 29 drugs that were not used in either the eligible list construction or the training steps. In a group of 29 test drugs, our model reduced the number of potential drug-AE signals from 41,834 to 97 and predicted 73 % of individual drug label changes. The model also predicted at least one AE-drug pair label change in 66 % of all the label changes for the test drugs. By concentrating on AE types with already demonstrated interest to FDA, we constructed a signaling system that provided focus regarding drug-AE pairs and suitable accuracy with regard to the issuance of FDA labeling changes. We suggest that focus on historical regulatory actions may increase the utility of pharmacovigilance signaling systems.

Numerical simulation of turbulent flow affected by vortex generators in straight channel

NASA Astrophysics Data System (ADS)

Souckova, Natalie; Simurda, David; Uruba, Vaclav

2012-04-01

The presented work is the next step after several experimental examinations of the vortex generator (VG) influence on flow separation occurring on a model of the NACA 63A421 airfoil with a deflected simple flap. The other purpose of this simulation is to obtain beneficial information that can be utilized for the preparation of the experimental investigation of the same configuration using Particle image Velocimetry method (PIV) in the future. The numerical simulation was performed for one single pair and two pairs of low-profile VGs of the same size, whose heights were smaller than the boundary layer thickness. The rectangular vane type VGs in such configuration, which generates counter-rotating vortices, was examined. The behaviour of vortices produced by VG pair or pairs in several positions downstream the VGs is investigated and will be used as a background of the measurement.

Comparative evaluation of border molding using two different techniques in maxillary edentulous arches: A clinical study

PubMed Central

Qanungo, Anchal; Aras, Meena Ajay; Chitre, Vidya; Coutinho, Ivy; Rajagopal, Praveen; Mysore, Ashwin

2016-01-01

Purpose: The aim of this in vivo study was to compare the single-step border molding technique using injectable heavy viscosity addition silicone with sectional border molding technique using low fusing impression compound by evaluating the retention of heat cure trial denture bases. Materials and Methods: Ten completely edentulous patients in need of prostheses were included in this study. Two border molding techniques, single-step (Group 1) and sectional (Group 2), were compared for retention. Both border molding techniques were performed in each patient. In both techniques, definitive wash impression was made with light viscosity addition silicone. The final results were analyzed using paired t-test to determine whether significant differences existed between the groups. Results: The t-value (3.031) infers that there was a significant difference between Group 1 and Group 2 (P = 0.014). The retention obtained in Group 2 (mean = 9.05 kgf) was significantly higher than that of Group 1 (mean = 8.26 kgf). Conclusion: Sectional border molding technique proved to be more retentive as compared to single-step border molding although clinically the retention appeared comparable. PMID:27746597

Joint Extraction of Entities and Relations Using Reinforcement Learning and Deep Learning.

PubMed

Feng, Yuntian; Zhang, Hongjun; Hao, Wenning; Chen, Gang

2017-01-01

We use both reinforcement learning and deep learning to simultaneously extract entities and relations from unstructured texts. For reinforcement learning, we model the task as a two-step decision process. Deep learning is used to automatically capture the most important information from unstructured texts, which represent the state in the decision process. By designing the reward function per step, our proposed method can pass the information of entity extraction to relation extraction and obtain feedback in order to extract entities and relations simultaneously. Firstly, we use bidirectional LSTM to model the context information, which realizes preliminary entity extraction. On the basis of the extraction results, attention based method can represent the sentences that include target entity pair to generate the initial state in the decision process. Then we use Tree-LSTM to represent relation mentions to generate the transition state in the decision process. Finally, we employ Q -Learning algorithm to get control policy π in the two-step decision process. Experiments on ACE2005 demonstrate that our method attains better performance than the state-of-the-art method and gets a 2.4% increase in recall-score.

Joint Extraction of Entities and Relations Using Reinforcement Learning and Deep Learning

PubMed Central

Zhang, Hongjun; Chen, Gang

2017-01-01

We use both reinforcement learning and deep learning to simultaneously extract entities and relations from unstructured texts. For reinforcement learning, we model the task as a two-step decision process. Deep learning is used to automatically capture the most important information from unstructured texts, which represent the state in the decision process. By designing the reward function per step, our proposed method can pass the information of entity extraction to relation extraction and obtain feedback in order to extract entities and relations simultaneously. Firstly, we use bidirectional LSTM to model the context information, which realizes preliminary entity extraction. On the basis of the extraction results, attention based method can represent the sentences that include target entity pair to generate the initial state in the decision process. Then we use Tree-LSTM to represent relation mentions to generate the transition state in the decision process. Finally, we employ Q-Learning algorithm to get control policy π in the two-step decision process. Experiments on ACE2005 demonstrate that our method attains better performance than the state-of-the-art method and gets a 2.4% increase in recall-score. PMID:28894463

Discovering functional interdependence relationship in PPI networks for protein complex identification.

PubMed

Lam, Winnie W M; Chan, Keith C C

2012-04-01

Protein molecules interact with each other in protein complexes to perform many vital functions, and different computational techniques have been developed to identify protein complexes in protein-protein interaction (PPI) networks. These techniques are developed to search for subgraphs of high connectivity in PPI networks under the assumption that the proteins in a protein complex are highly interconnected. While these techniques have been shown to be quite effective, it is also possible that the matching rate between the protein complexes they discover and those that are previously determined experimentally be relatively low and the "false-alarm" rate can be relatively high. This is especially the case when the assumption of proteins in protein complexes being more highly interconnected be relatively invalid. To increase the matching rate and reduce the false-alarm rate, we have developed a technique that can work effectively without having to make this assumption. The name of the technique called protein complex identification by discovering functional interdependence (PCIFI) searches for protein complexes in PPI networks by taking into consideration both the functional interdependence relationship between protein molecules and the network topology of the network. The PCIFI works in several steps. The first step is to construct a multiple-function protein network graph by labeling each vertex with one or more of the molecular functions it performs. The second step is to filter out protein interactions between protein pairs that are not functionally interdependent of each other in the statistical sense. The third step is to make use of an information-theoretic measure to determine the strength of the functional interdependence between all remaining interacting protein pairs. Finally, the last step is to try to form protein complexes based on the measure of the strength of functional interdependence and the connectivity between proteins. For performance evaluation, PCIFI was used to identify protein complexes in real PPI network data and the protein complexes it found were matched against those that were previously known in MIPS. The results show that PCIFI can be an effective technique for the identification of protein complexes. The protein complexes it found can match more known protein complexes with a smaller false-alarm rate and can provide useful insights into the understanding of the functional interdependence relationships between proteins in protein complexes.

Phase-stepping fiber-optic projected fringe system for surface topography measurements

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R. (Inventor); Beheim, Glenn (Inventor)

1992-01-01

A projected fringe interferometer for measuring the topography of an object is presented. The interferometer periodically steps the phase angle between a pair of light beams emanating from a common source. The steps are pi/2 radians (90 deg) apart, and at each step a video image of the fringes is recorded and stored. Photodetectors measure either the phase and theta of the beams or 2(theta). Either of the measures can be used to control one of the light beams so that the 90 deg theta is accurately maintained. A camera, a computer, a phase controller, and a phase modulator established closed-loop control of theta. Measuring the phase map of a flat surface establishes a calibration reference.

Learning to predict chemical reactions.

PubMed

Kayala, Matthew A; Azencott, Chloé-Agathe; Chen, Jonathan H; Baldi, Pierre

2011-09-26

Being able to predict the course of arbitrary chemical reactions is essential to the theory and applications of organic chemistry. Approaches to the reaction prediction problems can be organized around three poles corresponding to: (1) physical laws; (2) rule-based expert systems; and (3) inductive machine learning. Previous approaches at these poles, respectively, are not high throughput, are not generalizable or scalable, and lack sufficient data and structure to be implemented. We propose a new approach to reaction prediction utilizing elements from each pole. Using a physically inspired conceptualization, we describe single mechanistic reactions as interactions between coarse approximations of molecular orbitals (MOs) and use topological and physicochemical attributes as descriptors. Using an existing rule-based system (Reaction Explorer), we derive a restricted chemistry data set consisting of 1630 full multistep reactions with 2358 distinct starting materials and intermediates, associated with 2989 productive mechanistic steps and 6.14 million unproductive mechanistic steps. And from machine learning, we pose identifying productive mechanistic steps as a statistical ranking, information retrieval problem: given a set of reactants and a description of conditions, learn a ranking model over potential filled-to-unfilled MO interactions such that the top-ranked mechanistic steps yield the major products. The machine learning implementation follows a two-stage approach, in which we first train atom level reactivity filters to prune 94.00% of nonproductive reactions with a 0.01% error rate. Then, we train an ensemble of ranking models on pairs of interacting MOs to learn a relative productivity function over mechanistic steps in a given system. Without the use of explicit transformation patterns, the ensemble perfectly ranks the productive mechanism at the top 89.05% of the time, rising to 99.86% of the time when the top four are considered. Furthermore, the system is generalizable, making reasonable predictions over reactants and conditions which the rule-based expert does not handle. A web interface to the machine learning based mechanistic reaction predictor is accessible through our chemoinformatics portal ( http://cdb.ics.uci.edu) under the Toolkits section.

Single-Trial Classification of Multi-User P300-Based Brain-Computer Interface Using Riemannian Geometry.

PubMed

Korczowski, L; Congedo, M; Jutten, C

2015-08-01

The classification of electroencephalographic (EEG) data recorded from multiple users simultaneously is an important challenge in the field of Brain-Computer Interface (BCI). In this paper we compare different approaches for classification of single-trials Event-Related Potential (ERP) on two subjects playing a collaborative BCI game. The minimum distance to mean (MDM) classifier in a Riemannian framework is extended to use the diversity of the inter-subjects spatio-temporal statistics (MDM-hyper) or to merge multiple classifiers (MDM-multi). We show that both these classifiers outperform significantly the mean performance of the two users and analogous classifiers based on the step-wise linear discriminant analysis. More importantly, the MDM-multi outperforms the performance of the best player within the pair.

Single-fluorophore monitoring of DNA hybridization for investigating the effect of secondary structure on the nucleation step.

PubMed

Jo, Joon-Jung; Kim, Min-Ji; Son, Jung-Tae; Kim, Jandi; Shin, Jong-Shik

2009-07-17

Nucleic acid hybridization is one of the essential biological processes involved in storage and transmission of genetic information. Here we quantitatively determined the effect of secondary structure on the hybridization activation energy using structurally defined oligonucleotides. It turned out that activation energy is linearly proportional to the length of a single-stranded region flanking a nucleation site, generating a 0.18 kcal/mol energy barrier per nucleotide. Based on this result, we propose that the presence of single-stranded segments available for non-productive base pairing with a nucleation counterpart extends the searching process for nucleation sites to find a perfect match. This result may provide insights into rational selection of a target mRNA site for siRNA and antisense gene silencing.

Exploring the sequential lineup advantage using WITNESS.

PubMed

Goodsell, Charles A; Gronlund, Scott D; Carlson, Curt A

2010-12-01

Advocates claim that the sequential lineup is an improvement over simultaneous lineup procedures, but no formal (quantitatively specified) explanation exists for why it is better. The computational model WITNESS (Clark, Appl Cogn Psychol 17:629-654, 2003) was used to develop theoretical explanations for the sequential lineup advantage. In its current form, WITNESS produced a sequential advantage only by pairing conservative sequential choosing with liberal simultaneous choosing. However, this combination failed to approximate four extant experiments that exhibited large sequential advantages. Two of these experiments became the focus of our efforts because the data were uncontaminated by likely suspect position effects. Decision-based and memory-based modifications to WITNESS approximated the data and produced a sequential advantage. The next step is to evaluate the proposed explanations and modify public policy recommendations accordingly.

HLA mismatches and hematopoietic cell transplantation: structural simulations assess the impact of changes in peptide binding specificity on transplant outcome

PubMed Central

Yanover, Chen; Petersdorf, Effie W.; Malkki, Mari; Gooley, Ted; Spellman, Stephen; Velardi, Andrea; Bardy, Peter; Madrigal, Alejandro; Bignon, Jean-Denis; Bradley, Philip

2013-01-01

The success of hematopoietic cell transplantation from an unrelated donor depends in part on the degree of Human Histocompatibility Leukocyte Antigen (HLA) matching between donor and patient. We present a structure-based analysis of HLA mismatching, focusing on individual amino acid mismatches and their effect on peptide binding specificity. Using molecular modeling simulations of HLA-peptide interactions, we find evidence that amino acid mismatches predicted to perturb peptide binding specificity are associated with higher risk of mortality in a large and diverse dataset of patient-donor pairs assembled by the International Histocompatibility Working Group in Hematopoietic Cell Transplantation consortium. This analysis may represent a first step toward sequence-based prediction of relative risk for HLA allele mismatches. PMID:24482668

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.

Raman-tailored photonic crystal fiber for telecom band photon-pair generation.

PubMed

Cordier, M; Orieux, A; Gabet, R; Harlé, T; Dubreuil, N; Diamanti, E; Delaye, P; Zaquine, I

2017-07-01

We report on the experimental characterization of a novel nonlinear liquid-filled hollow-core photonic crystal fiber for the generation of photon pairs at a telecommunication wavelength through spontaneous four-wave mixing (SFWM). We show that the optimization procedure in view of this application links the choice of the nonlinear liquid to the design parameters of the fiber, and we give an example of such an optimization at telecom wavelengths. Combining the modeling of the fiber and classical characterization techniques at these wavelengths, we identify for the chosen fiber and liquid combination SFWM phase-matching frequency ranges with no Raman scattering noise contamination. This is a first step toward obtaining a telecom band fibered photon-pair source with a high signal-to-noise ratio.

Studies on thermokinetic of Chlorella pyrenoidosa devolatilization via different models.

PubMed

Chen, Zhihua; Lei, Jianshen; Li, Yunbei; Su, Xianfa; Hu, Zhiquan; Guo, Dabin

2017-11-01

The thermokinetics of Chlorella pyrenoidosa (CP) devolatilization were investigated based on iso-conversional model and different distributed activation energy models (DAEM). Iso-conversional process result showed that CP devolatilization roughly followed a single-step with mechanism function of f(α)=(1-α) 3 , and kinetic parameters pair of E 0 =180.5kJ/mol and A 0 =1.5E+13s -1 . Logistic distribution was the most suitable activation energy distribution function for CP devolatilization. Although reaction order n=3.3 was in accordance with iso-conversional process, Logistic DAEM could not detail the weight loss features since it presented as single-step reaction. The un-uniform feature of activation energy distribution in Miura-Maki DAEM, and weight fraction distribution in discrete DAEM reflected weight loss features. Due to the un-uniform distribution of activation and weight fraction, Miura-Maki DAEM and discreted DAEM could describe weight loss features. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pronounced Photovoltaic Response from Multi-layered MoTe2 Phototransistor with Asymmetric Contact Form.

PubMed

Liu, Junku; Guo, Nan; Xiao, Xiaoyang; Zhang, Kenan; Jia, Yi; Zhou, Shuyun; Wu, Yang; Li, Qunqing; Xiao, Lin

2017-11-22

In this study, we fabricate air-stable p-type multi-layered MoTe 2 phototransistor using Au as electrodes, which shows pronounced photovoltaic response in off-state with asymmetric contact form. By analyzing the spatially resolved photoresponse using scanning photocurrent microscopy, we found that the potential steps are formed in the vicinity of the electrodes/MoTe 2 interface due to the doping of the MoTe 2 by the metal contacts. The potential step dominates the separation of photoexcited electron-hole pairs in short-circuit condition or with small V sd biased. Based on these findings, we infer that the asymmetric contact cross-section between MoTe 2 -source and MoTe 2 -drain electrodes is the reason to form non-zero net current and photovoltaic response. Furthermore, MoTe 2 phototransistor shows a faster response in short-circuit condition than that with higher biased V sd within sub-millisecond, and its spectral range can be extended to the infrared end of 1550 nm.

The one step fermionic ladder

NASA Astrophysics Data System (ADS)

Das, Joy Prakash; Setlur, Girish S.

2017-10-01

The one step fermionic ladder refers to two parallel Luttinger Liquids (poles of the ladder) placed such that there is a finite probability of electrons hopping between the two poles at a pair of opposing points along each of the poles. The many-body Green function for such a system is calculated in presence of forward scattering interactions using the powerful non-chiral bosonization technique (NCBT). This technique is based on a non-standard harmonic analysis of the rapidly varying parts of the density fields appropriate for the study of strongly inhomogeneous ladder systems. The closed analytical expression for the correlation function obtained from NCBT is nothing but the series involving the RPA (Random Phase Approximation) diagrams in powers of the forward scattering coupling strength resummed to include only the most singular terms with the source of inhomogeneities treated exactly. Finally the correlation functions are used to study physical phenomena such as Friedel oscillations and the conductance of such systems with the potential difference applied across various ends.

Pronounced Photovoltaic Response from Multi-layered MoTe2 Phototransistor with Asymmetric Contact Form

NASA Astrophysics Data System (ADS)

Liu, Junku; Guo, Nan; Xiao, Xiaoyang; Zhang, Kenan; Jia, Yi; Zhou, Shuyun; Wu, Yang; Li, Qunqing; Xiao, Lin

2017-11-01

In this study, we fabricate air-stable p-type multi-layered MoTe2 phototransistor using Au as electrodes, which shows pronounced photovoltaic response in off-state with asymmetric contact form. By analyzing the spatially resolved photoresponse using scanning photocurrent microscopy, we found that the potential steps are formed in the vicinity of the electrodes/MoTe2 interface due to the doping of the MoTe2 by the metal contacts. The potential step dominates the separation of photoexcited electron-hole pairs in short-circuit condition or with small V sd biased. Based on these findings, we infer that the asymmetric contact cross-section between MoTe2-source and MoTe2-drain electrodes is the reason to form non-zero net current and photovoltaic response. Furthermore, MoTe2 phototransistor shows a faster response in short-circuit condition than that with higher biased V sd within sub-millisecond, and its spectral range can be extended to the infrared end of 1550 nm.

Observation of Stronger-than-Binary Correlations with Entangled Photonic Qutrits

NASA Astrophysics Data System (ADS)

Hu, Xiao-Min; Liu, Bi-Heng; Guo, Yu; Xiang, Guo-Yong; Huang, Yun-Feng; Li, Chuan-Feng; Guo, Guang-Can; Kleinmann, Matthias; Vértesi, Tamás; Cabello, Adán

2018-05-01

We present the first experimental confirmation of the quantum-mechanical prediction of stronger-than-binary correlations. These are correlations that cannot be explained under the assumption that the occurrence of a particular outcome of an n ≥3 -outcome measurement is due to a two-step process in which, in the first step, some classical mechanism precludes n -2 of the outcomes and, in the second step, a binary measurement generates the outcome. Our experiment uses pairs of photonic qutrits distributed between two laboratories, where randomly chosen three-outcome measurements are performed. We report a violation by 9.3 standard deviations of the optimal inequality for nonsignaling binary correlations.

Fostering supportive learning environments in long-term care: the case of WIN A STEP UP.

PubMed

Craft Morgan, Jennifer; Haviland, Sara B; Woodside, M Allyson; Konrad, Thomas R

2007-01-01

The education of direct care workers (DCWs) is key to improving job quality and the quality of care in long-term care (LTC). This paper describes the successful integration of a supervisory training program into a continuing education intervention (WIN A STEP UP) for DCWs, identifies the factors that appear to influence the integration of the learning into practice, and discusses the implications for educators. The WIN A STEP UP program achieved its strongest results when the DCW curriculum was paired with Coaching Supervision. Attention to pre-training, training and post-training conditions is necessary to successfully integrate learning into practice in LTC.

Inclusive heavy flavor hadroproduction in NLO QCD: The exact analytic result

NASA Astrophysics Data System (ADS)

Czakon, M.; Mitov, A.

2010-01-01

We present the first exact analytic result for all partonic channels contributing to the total cross section for the production of a pair of heavy flavors in hadronic collisions in NLO QCD. Our calculation is a step in the derivation of the top quark pair production cross section at NNLO in QCD, which is a cornerstone of the precision LHC program. Our results uncover the analytical structures behind observables with heavy flavors at higher orders. They also reveal surprising and non-trivial implications for kinematics close to partonic threshold.

A quick response four decade logarithmic high-voltage stepping supply

NASA Technical Reports Server (NTRS)

Doong, H.

1978-01-01

An improved high-voltage stepping supply, for space instrumentation is described where low power consumption and fast settling time between steps are required. The high-voltage stepping supply, utilizing an average power of 750 milliwatts, delivers a pair of mirror images with 64 level logarithmic outputs. It covers a four decade range of + or - 2500 to + or - 0.29 volts having an output stability of + or - 0.5 percent or + or - 20 millivolts for all line load and temperature variations. The supply provides a typical step setting time of 1 millisecond with 100 microseconds for the lower two decades. The versatile design features of the high-voltage stepping supply provides a quick response staircase generator as described or a fixed voltage with the option to change levels as required over large dynamic ranges without circuit modifications. The concept can be implemented up to + or - 5000 volts. With these design features, the high-voltage stepping supply should find numerous applications where charged particle detection, electro-optical systems, and high voltage scientific instruments are used.

Genetic dissection of the consensus sequence for the class 2 and class 3 flagellar promoters

PubMed Central

Wozniak, Christopher E.; Hughes, Kelly T.

2008-01-01

Summary Computational searches for DNA binding sites often utilize consensus sequences. These search models make assumptions that the frequency of a base pair in an alignment relates to the base pair’s importance in binding and presume that base pairs contribute independently to the overall interaction with the DNA binding protein. These two assumptions have generally been found to be accurate for DNA binding sites. However, these assumptions are often not satisfied for promoters, which are involved in additional steps in transcription initiation after RNA polymerase has bound to the DNA. To test these assumptions for the flagellar regulatory hierarchy, class 2 and class 3 flagellar promoters were randomly mutagenized in Salmonella. Important positions were then saturated for mutagenesis and compared to scores calculated from the consensus sequence. Double mutants were constructed to determine how mutations combined for each promoter type. Mutations in the binding site for FlhD4C2, the activator of class 2 promoters, better satisfied the assumptions for the binding model than did mutations in the class 3 promoter, which is recognized by the σ28 transcription factor. These in vivo results indicate that the activator sites within flagellar promoters can be modeled using simple assumptions but that the DNA sequences recognized by the flagellar sigma factor require more complex models. PMID:18486950

Quantitative analysis of task selection for brain-computer interfaces

NASA Astrophysics Data System (ADS)

Llera, Alberto; Gómez, Vicenç; Kappen, Hilbert J.

2014-10-01

Objective. To assess quantitatively the impact of task selection in the performance of brain-computer interfaces (BCI). Approach. We consider the task-pairs derived from multi-class BCI imagery movement tasks in three different datasets. We analyze for the first time the benefits of task selection on a large-scale basis (109 users) and evaluate the possibility of transferring task-pair information across days for a given subject. Main results. Selecting the subject-dependent optimal task-pair among three different imagery movement tasks results in approximately 20% potential increase in the number of users that can be expected to control a binary BCI. The improvement is observed with respect to the best task-pair fixed across subjects. The best task-pair selected for each subject individually during a first day of recordings is generally a good task-pair in subsequent days. In general, task learning from the user side has a positive influence in the generalization of the optimal task-pair, but special attention should be given to inexperienced subjects. Significance. These results add significant evidence to existing literature that advocates task selection as a necessary step towards usable BCIs. This contribution motivates further research focused on deriving adaptive methods for task selection on larger sets of mental tasks in practical online scenarios.

Feature-based pairwise retinal image registration by radial distortion correction

NASA Astrophysics Data System (ADS)

Lee, Sangyeol; Abràmoff, Michael D.; Reinhardt, Joseph M.

2007-03-01

Fundus camera imaging is widely used to document disorders such as diabetic retinopathy and macular degeneration. Multiple retinal images can be combined together through a procedure known as mosaicing to form an image with a larger field of view. Mosaicing typically requires multiple pairwise registrations of partially overlapped images. We describe a new method for pairwise retinal image registration. The proposed method is unique in that the radial distortion due to image acquisition is corrected prior to the geometric transformation. Vessel lines are detected using the Hessian operator and are used as input features to the registration. Since the overlapping region is typically small in a retinal image pair, only a few correspondences are available, thus limiting the applicable model to an afine transform at best. To recover the distortion due to curved-surface of retina and lens optics, a combined approach of an afine model with a radial distortion correction is proposed. The parameters of the image acquisition and radial distortion models are estimated during an optimization step that uses Powell's method driven by the vessel line distance. Experimental results using 20 pairs of green channel images acquired from three subjects with a fundus camera confirmed that the afine model with distortion correction could register retinal image pairs to within 1.88+/-0.35 pixels accuracy (mean +/- standard deviation) assessed by vessel line error, which is 17% better than the afine-only approach. Because the proposed method needs only two correspondences, it can be applied to obtain good registration accuracy even in the case of small overlap between retinal image pairs.

An efficient, large-scale, non-lattice-detection algorithm for exhaustive structural auditing of biomedical ontologies.

PubMed

Zhang, Guo-Qiang; Xing, Guangming; Cui, Licong

2018-04-01

One of the basic challenges in developing structural methods for systematic audition on the quality of biomedical ontologies is the computational cost usually involved in exhaustive sub-graph analysis. We introduce ANT-LCA, a new algorithm for computing all non-trivial lowest common ancestors (LCA) of each pair of concepts in the hierarchical order induced by an ontology. The computation of LCA is a fundamental step for non-lattice approach for ontology quality assurance. Distinct from existing approaches, ANT-LCA only computes LCAs for non-trivial pairs, those having at least one common ancestor. To skip all trivial pairs that may be of no practical interest, ANT-LCA employs a simple but innovative algorithmic strategy combining topological order and dynamic programming to keep track of non-trivial pairs. We provide correctness proofs and demonstrate a substantial reduction in computational time for two largest biomedical ontologies: SNOMED CT and Gene Ontology (GO). ANT-LCA achieved an average computation time of 30 and 3 sec per version for SNOMED CT and GO, respectively, about 2 orders of magnitude faster than the best known approaches. Our algorithm overcomes a fundamental computational barrier in sub-graph based structural analysis of large ontological systems. It enables the implementation of a new breed of structural auditing methods that not only identifies potential problematic areas, but also automatically suggests changes to fix the issues. Such structural auditing methods can lead to more effective tools supporting ontology quality assurance work. Copyright © 2018 Elsevier Inc. All rights reserved.

High salt solution structure of a left-handed RNA double helix

PubMed Central

Popenda, Mariusz; Milecki, Jan; Adamiak, Ryszard W.

2004-01-01

Right-handed RNA duplexes of (CG)n sequence undergo salt-induced helicity reversal, forming left-handed RNA double helices (Z-RNA). In contrast to the thoroughly studied Z-DNA, no Z-RNA structure of natural origin is known. Here we report the NMR structure of a half-turn, left-handed RNA helix (CGCGCG)2 determined in 6 M NaClO4. This is the first nucleic acid motif determined at such high salt. Sequential assignments of non-exchangeable proton resonances of the Z-form were based on the hitherto unreported NOE connectivity path [H6(n)-H5′/H5″(n)-H8(n+1)-H1′(n+1)-H6(n+2)] found for left-handed helices. Z-RNA structure shows several conformational features significantly different from Z-DNA. Intra-strand but no inter-strand base stacking was observed for both CpG and GpC steps. Helical twist angles for CpG steps have small positive values (4–7°), whereas GpC steps have large negative values (−61°). In the full-turn model of Z-RNA (12.4 bp per turn), base pairs are much closer to the helix axis than in Z-DNA, thus both the very deep, narrow minor groove with buried cytidine 2′-OH groups, and the major groove are well defined. The 2′-OH group of cytidines plays a crucial role in the Z-RNA structure and its formation; 2′-O-methylation of cytidine, but not of guanosine residues prohibits A to Z helicity reversal. PMID:15292450

Step-by-Step Simulation of Radiation Chemistry Using Green Functions for Diffusion-Influenced Reactions

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cucinotta, Francis A.

2011-01-01

Radiolytic species are formed approximately 1 ps after the passage of ionizing radiation through matter. After their formation, they diffuse and chemically react with other radiolytic species and neighboring biological molecules, leading to various oxidative damage. Therefore, the simulation of radiation chemistry is of considerable importance to understand how radiolytic species damage biological molecules [1]. The step-by-step simulation of chemical reactions is difficult, because the radiolytic species are distributed non-homogeneously in the medium. Consequently, computational approaches based on Green functions for diffusion-influenced reactions should be used [2]. Recently, Green functions for more complex type of reactions have been published [3-4]. We have developed exact random variate generators of these Green functions [5], which will allow us to use them in radiation chemistry codes. Moreover, simulating chemistry using the Green functions is which is computationally very demanding, because the probabilities of reactions between each pair of particles should be evaluated at each timestep [2]. This kind of problem is well adapted for General Purpose Graphic Processing Units (GPGPU), which can handle a large number of similar calculations simultaneously. These new developments will allow us to include more complex reactions in chemistry codes, and to improve the calculation time. This code should be of importance to link radiation track structure simulations and DNA damage models.

Seismic Travel Time Tomography in Modeling Low Velocity Anomalies between the Boreholes

NASA Astrophysics Data System (ADS)

Octova, A.; Sule, R.

2018-04-01

Travel time cross-hole seismic tomography is applied to describing the structure of the subsurface. The sources are placed at one borehole and some receivers are placed in the others. First arrival travel time data that received by each receiver is used as the input data in seismic tomography method. This research is devided into three steps. The first step is reconstructing the synthetic model based on field parameters. Field parameters are divided into 24 receivers and 45 receivers. The second step is applying inversion process for the field data that consists of five pairs bore holes. The last step is testing quality of tomogram with resolution test. Data processing using FAST software produces an explicit shape and resemble the initial model reconstruction of synthetic model with 45 receivers. The tomography processing in field data indicates cavities in several place between the bore holes. Cavities are identified on BH2A-BH1, BH4A-BH2A and BH4A-BH5 with elongated and rounded structure. In resolution tests using a checker-board, anomalies still can be identified up to 2 meter x 2 meter size. Travel time cross-hole seismic tomography analysis proves this mothod is very good to describing subsurface structure and boundary layer. Size and anomalies position can be recognized and interpreted easily.

Two-step electrodeposition to fabricate the p-n heterojunction of a Cu2O/BiVO4 photoanode for the enhancement of photoelectrochemical water splitting.

PubMed

Bai, Shouli; Liu, Jingchao; Cui, Meng; Luo, Ruixian; He, Jing; Chen, Aifan

2018-05-15

A Cu2O/BiVO4 p-n heterojunction based photoanode in photoelectrochemical (PEC) water splitting is fabricated by a two-step electrodeposition method on an FTO substrate followed by annealing treatment. The structures and properties of the samples are characterized by XRD, FESEM, HRTEM, XPS and UV-visible spectra. The photoelectrochemical activity of the photoanode in water oxidation has been investigated and measured in a three electrode quartz cell system; the obtained maximum photocurrent density of 1.72 mA cm-2 at 1.23 V vs. RHE is 4.5 times higher than that of pristine BiVO4 thin films (∼0.38 mA cm-2). The heterojunction based photoanode also exhibits a tremendous cathodic shift of the onset potential (∼420 mV) and enhancement in the IPCE value by more than 4-fold. The enhanced photoelectrochemical properties of the Cu2O/BiVO4 photoelectrode are attributed to the efficient separation of the photoexcited electron-hole pairs caused by the inner electronic field (IEF) of the p-n heterojunction.

Comparing the Behavior of Polarimetric SAR Imagery (TerraSAR-X and Radarsat-2) for Automated Sea Ice Classification

NASA Astrophysics Data System (ADS)

Ressel, Rudolf; Singha, Suman; Lehner, Susanne

2016-08-01

Arctic Sea ice monitoring has attracted increasing attention over the last few decades. Besides the scientific interest in sea ice, the operational aspect of ice charting is becoming more important due to growing navigational possibilities in an increasingly ice free Arctic. For this purpose, satellite borne SAR imagery has become an invaluable tool. In past, mostly single polarimetric datasets were investigated with supervised or unsupervised classification schemes for sea ice investigation. Despite proven sea ice classification achievements on single polarimetric data, a fully automatic, general purpose classifier for single-pol data has not been established due to large variation of sea ice manifestations and incidence angle impact. Recently, through the advent of polarimetric SAR sensors, polarimetric features have moved into the focus of ice classification research. The higher information content four polarimetric channels promises to offer greater insight into sea ice scattering mechanism and overcome some of the shortcomings of single- polarimetric classifiers. Two spatially and temporally coincident pairs of fully polarimetric acquisitions from the TerraSAR-X/TanDEM-X and RADARSAT-2 satellites are investigated. Proposed supervised classification algorithm consists of two steps: The first step comprises a feature extraction, the results of which are ingested into a neural network classifier in the second step. Based on the common coherency and covariance matrix, we extract a number of features and analyze the relevance and redundancy by means of mutual information for the purpose of sea ice classification. Coherency matrix based features which require an eigendecomposition are found to be either of low relevance or redundant to other covariance matrix based features. Among the most useful features for classification are matrix invariant based features (Geometric Intensity, Scattering Diversity, Surface Scattering Fraction).

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.

Optimization and quality control of genome-wide Hi-C library preparation.

PubMed

Zhang, Xiang-Yuan; He, Chao; Ye, Bing-Yu; Xie, De-Jian; Shi, Ming-Lei; Zhang, Yan; Shen, Wen-Long; Li, Ping; Zhao, Zhi-Hu

2017-09-20

Highest-throughput chromosome conformation capture (Hi-C) is one of the key assays for genome- wide chromatin interaction studies. It is a time-consuming process that involves many steps and many different kinds of reagents, consumables, and equipments. At present, the reproducibility is unsatisfactory. By optimizing the key steps of the Hi-C experiment, such as crosslinking, pretreatment of digestion, inactivation of restriction enzyme, and in situ ligation etc., we established a robust Hi-C procedure and prepared two biological replicates of Hi-C libraries from the GM12878 cells. After preliminary quality control by Sanger sequencing, the two replicates were high-throughput sequenced. The bioinformatics analysis of the raw sequencing data revealed the mapping-ability and pair-mate rate of the raw data were around 90% and 72%, respectively. Additionally, after removal of self-circular ligations and dangling-end products, more than 96% of the valid pairs were reached. Genome-wide interactome profiling shows clear topological associated domains (TADs), which is consistent with previous reports. Further correlation analysis showed that the two biological replicates strongly correlate with each other in terms of both bin coverage and all bin pairs. All these results indicated that the optimized Hi-C procedure is robust and stable, which will be very helpful for the wide applications of the Hi-C assay.

Predicting Bond Dissociation Energies of Transition-Metal Compounds by Multiconfiguration Pair-Density Functional Theory and Second-Order Perturbation Theory Based on Correlated Participating Orbitals and Separated Pairs.

PubMed

Bao, Junwei Lucas; Odoh, Samuel O; Gagliardi, Laura; Truhlar, Donald G

2017-02-14

We study the performance of multiconfiguration pair-density functional theory (MC-PDFT) and multireference perturbation theory for the computation of the bond dissociation energies in 12 transition-metal-containing diatomic molecules and three small transition-metal-containing polyatomic molecules and in two transition-metal dimers. The first step is a multiconfiguration self-consistent-field calculation, for which two choices must be made: (i) the active space and (ii) its partition into subspaces, if the generalized active space formulation is used. In the present work, the active space is chosen systematically by using three correlated-participating-orbitals (CPO) schemes, and the partition is chosen by using the separated-pair (SP) approximation. Our calculations show that MC-PDFT generally has similar accuracy to CASPT2, and the active-space dependence of MC-PDFT is not very great for transition-metal-ligand bond dissociation energies. We also find that the SP approximation works very well, and in particular SP with the fully translated BLYP functional SP-ftBLYP is more accurate than CASPT2. SP greatly reduces the number of configuration state functions relative to CASSCF. For the cases of FeO and NiO with extended-CPO active space, for which complete active space calculations are unaffordable, SP calculations are not only affordable but also of satisfactory accuracy. All of the MC-PDFT results are significantly better than the corresponding results with broken-symmetry spin-unrestricted Kohn-Sham density functional theory. Finally we test a perturbation theory method based on the SP reference and find that it performs slightly worse than CASPT2 calculations, and for most cases of the nominal-CPO active space, the approximate SP perturbation theory calculations are less accurate than the much less expensive SP-PDFT calculations.

ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism.

PubMed

Parke, Courtney L; Wojcik, Edward J; Kim, Sunyoung; Worthylake, David K

2010-02-19

Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin.AMPPPNP crystal structure, closure of the active site results in structural transformations appropriate for microtubule binding and organizes an orthosteric two-water cluster. We conclude that a proton is shared between the lytic water, positioned for gamma-phosphate attack, and a second water that serves as a general base. To our knowledge, this is the first experimental detection of the catalytic base for any ATPase. Deprotonation of the second water by switch residues likely triggers subsequent large scale structural rearrangements. Therefore, the catalytic base is responsible for initiating nucleophilic attack of ATP and for relaying the positive charge over long distances to initiate mechanotransduction. Coordination of switch movements via sequential proton transfer along paired water clusters may be universal for nucleotide triphosphatases with conserved active sites, such as myosins and G-proteins.

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.

Anisotropic nanomaterials: Synthesis, optical and magnetic properties, and applications

NASA Astrophysics Data System (ADS)

Banholzer, Matthew John

As nanoscience and nanotechnology mature, anisotropic metal nanostructures are emerging in a variety of contexts as valuable class of nanostructures due to their distinctive attributes. With unique properties ranging from optical to magnetic and beyond, these structures are useful in many new applications. Chapter two discusses the nanodisk code: a linear array of metal disk pairs that serve as surface-enhanced Raman scattering substrates. These multiplexing structures employ a binary encoding scheme, perform better than previous nanowires designs (in the context of SERS) and are useful for both convert encoding and tagging of substrates (based both on spatial disk position and spectroscopic response) as well as biomolecule detection (e.g. DNA). Chapter three describes the development of improved, silver-based nanodisk code structures. Work was undertaken to generate structures with high yield and reproducibility and to reoptimize the geometry of each disk pair for maximum Raman enhancement. The improved silver structures exhibit greater enhancement than Au structures (leading to lower DNA detection limits), convey additional flexibility, and enable trinary encoding schemes where far more unique structures can be created. Chapter four considers the effect of roughness on the plasmonic properties of nanorod structures and introduces a novel method to smooth the end-surfaces of nanorods structures. The smoothing technique is based upon a two-step process relying upon diffusion control during nanowires growth and selective oxidation after each step of synthesis is complete. Empirical and theoretical work show that smoothed nanostructures have superior and controllable optical properties. Chapter five concerns silica-encapsulated gold nanoprisms. This encapsulation allows these highly sensitive prisms to remain stable and protected in solution, enabling their use as class-leading sensors. Theoretical study complements the empirical work, exploring the effect of encapsulation on the SPR of these structures. Chapter six focuses on the magnetic properties of Au-Ni heterostructures. In addition to demonstration of nanoconfinement effects based upon the anisotropy of the nanorods/nanodisk structure, the magnetic coupling of rod-disk heterostructures is examined. Subsequent investigations suggest that the magnetic behavior of disks can be influenced by nearby rod segments, leading to the creation of a three-state spin system that may prove useful in device applications.

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

Distinct dissociation kinetics between ion pairs: Solvent-coordinate free-energy landscape analysis.

PubMed

Yonetani, Yoshiteru

2015-07-28

Different ion pairs exhibit different dissociation kinetics; however, while the nature of this process is vital for understanding various molecular systems, the underlying mechanism remains unclear. In this study, to examine the origin of different kinetic rate constants for this process, molecular dynamics simulations were conducted for LiCl, NaCl, KCl, and CsCl in water. The results showed substantial differences in dissociation rate constant, following the trend kLiCl < kNaCl < kKCl < kCsCl. Analysis of the free-energy landscape with a solvent reaction coordinate and subsequent rate component analysis showed that the differences in these rate constants arose predominantly from the variation in solvent-state distribution between the ion pairs. The formation of a water-bridging configuration, in which the water molecule binds to an anion and a cation simultaneously, was identified as a key step in this process: water-bridge formation lowers the related dissociation free-energy barrier, thereby increasing the probability of ion-pair dissociation. Consequently, a higher probability of water-bridge formation leads to a higher ion-pair dissociation rate.

An ensemble of SVM classifiers based on gene pairs.

PubMed

Tong, Muchenxuan; Liu, Kun-Hong; Xu, Chungui; Ju, Wenbin

2013-07-01

In this paper, a genetic algorithm (GA) based ensemble support vector machine (SVM) classifier built on gene pairs (GA-ESP) is proposed. The SVMs (base classifiers of the ensemble system) are trained on different informative gene pairs. These gene pairs are selected by the top scoring pair (TSP) criterion. Each of these pairs projects the original microarray expression onto a 2-D space. Extensive permutation of gene pairs may reveal more useful information and potentially lead to an ensemble classifier with satisfactory accuracy and interpretability. GA is further applied to select an optimized combination of base classifiers. The effectiveness of the GA-ESP classifier is evaluated on both binary-class and multi-class datasets. Copyright © 2013 Elsevier Ltd. All rights reserved.

Novel techniques for data decomposition and load balancing for parallel processing of vision systems: Implementation and evaluation using a motion estimation system

NASA Technical Reports Server (NTRS)

Choudhary, Alok Nidhi; Leung, Mun K.; Huang, Thomas S.; Patel, Janak H.

1989-01-01

Computer vision systems employ a sequence of vision algorithms in which the output of an algorithm is the input of the next algorithm in the sequence. Algorithms that constitute such systems exhibit vastly different computational characteristics, and therefore, require different data decomposition techniques and efficient load balancing techniques for parallel implementation. However, since the input data for a task is produced as the output data of the previous task, this information can be exploited to perform knowledge based data decomposition and load balancing. Presented here are algorithms for a motion estimation system. The motion estimation is based on the point correspondence between the involved images which are a sequence of stereo image pairs. Researchers propose algorithms to obtain point correspondences by matching feature points among stereo image pairs at any two consecutive time instants. Furthermore, the proposed algorithms employ non-iterative procedures, which results in saving considerable amounts of computation time. The system consists of the following steps: (1) extraction of features; (2) stereo match of images in one time instant; (3) time match of images from consecutive time instants; (4) stereo match to compute final unambiguous points; and (5) computation of motion parameters.

The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors

PubMed Central

Mi, Zhibao; Novitzky, Dimitri; Collins, Joseph F; Cooper, David KC

2015-01-01

The management of brain-dead organ donors is complex. The use of inotropic agents and replacement of depleted hormones (hormonal replacement therapy) is crucial for successful multiple organ procurement, yet the optimal hormonal replacement has not been identified, and the statistical adjustment to determine the best selection is not trivial. Traditional pair-wise comparisons between every pair of treatments, and multiple comparisons to all (MCA), are statistically conservative. Hsu’s multiple comparisons with the best (MCB) – adapted from the Dunnett’s multiple comparisons with control (MCC) – has been used for selecting the best treatment based on continuous variables. We selected the best hormonal replacement modality for successful multiple organ procurement using a two-step approach. First, we estimated the predicted margins by constructing generalized linear models (GLM) or generalized linear mixed models (GLMM), and then we applied the multiple comparison methods to identify the best hormonal replacement modality given that the testing of hormonal replacement modalities is independent. Based on 10-year data from the United Network for Organ Sharing (UNOS), among 16 hormonal replacement modalities, and using the 95% simultaneous confidence intervals, we found that the combination of thyroid hormone, a corticosteroid, antidiuretic hormone, and insulin was the best modality for multiple organ procurement for transplantation. PMID:25565890

Simultaneous binding to the tracking strand, displaced strand and the duplex of a DNA fork enhances unwinding by Dda helicase

PubMed Central

Aarattuthodiyil, Suja; Byrd, Alicia K.; Raney, Kevin D.

2014-01-01

Interactions between helicases and the tracking strand of a DNA substrate are well-characterized; however, the role of the displaced strand is a less understood characteristic of DNA unwinding. Dda helicase exhibited greater processivity when unwinding a DNA fork compared to a ss/ds DNA junction substrate. The lag phase in the unwinding progress curve was reduced for the forked DNA compared to the ss/ds junction. Fewer kinetic steps were required to unwind the fork compared to the ss/ds junction, suggesting that binding to the fork leads to disruption of the duplex. DNA footprinting confirmed that interaction of Dda with a fork leads to two base pairs being disrupted whereas no disruption of base pairing was observed with the ss/ds junction. Neutralization of the phosphodiester backbone resulted in a DNA-footprinting pattern similar to that observed with the ss/ds junction, consistent with disruption of the interaction between Dda and the displaced strand. Several basic residues in the 1A domain which were previously proposed to bind to the incoming duplex DNA were replaced with alanines, resulting in apparent loss of interaction with the duplex. Taken together, these results suggest that Dda interaction with the tracking strand, displaced strand and duplex coordinates DNA unwinding. PMID:25249618

Solid-phase proximity ligation assays for individual or parallel protein analyses with readout via real-time PCR or sequencing.

PubMed

Nong, Rachel Yuan; Wu, Di; Yan, Junhong; Hammond, Maria; Gu, Gucci Jijuan; Kamali-Moghaddam, Masood; Landegren, Ulf; Darmanis, Spyros

2013-06-01

Solid-phase proximity ligation assays share properties with the classical sandwich immunoassays for protein detection. The proteins captured via antibodies on solid supports are, however, detected not by single antibodies with detectable functions, but by pairs of antibodies with attached DNA strands. Upon recognition by these sets of three antibodies, pairs of DNA strands brought in proximity are joined by ligation. The ligated reporter DNA strands are then detected via methods such as real-time PCR or next-generation sequencing (NGS). We describe how to construct assays that can offer improved detection specificity by virtue of recognition by three antibodies, as well as enhanced sensitivity owing to reduced background and amplified detection. Finally, we also illustrate how the assays can be applied for parallel detection of proteins, taking advantage of the oligonucleotide ligation step to avoid background problems that might arise with multiplexing. The protocol for the singleplex solid-phase proximity ligation assay takes ~5 h. The multiplex version of the assay takes 7-8 h depending on whether quantitative PCR (qPCR) or sequencing is used as the readout. The time for the sequencing-based protocol includes the library preparation but not the actual sequencing, as times may vary based on the choice of sequencing platform.

Genetic mapping of 15 human X chromosomal forensic short tandem repeat (STR) loci by means of multi-core parallelization.

PubMed

Diegoli, Toni Marie; Rohde, Heinrich; Borowski, Stefan; Krawczak, Michael; Coble, Michael D; Nothnagel, Michael

2016-11-01

Typing of X chromosomal short tandem repeat (X STR) markers has become a standard element of human forensic genetic analysis. Joint consideration of many X STR markers at a time increases their discriminatory power but, owing to physical linkage, requires inter-marker recombination rates to be accurately known. We estimated the recombination rates between 15 well established X STR markers using genotype data from 158 families (1041 individuals) and following a previously proposed likelihood-based approach that allows for single-step mutations. To meet the computational requirements of this family-based type of analysis, we modified a previous implementation so as to allow multi-core parallelization on a high-performance computing system. While we obtained recombination rate estimates larger than zero for all but one pair of adjacent markers within the four previously proposed linkage groups, none of the three X STR pairs defining the junctions of these groups yielded a recombination rate estimate of 0.50. Corroborating previous studies, our results therefore argue against a simple model of independent X chromosomal linkage groups. Moreover, the refined recombination fraction estimates obtained in our study will facilitate the appropriate joint consideration of all 15 investigated markers in forensic analysis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Development of a multiplex PCR assay for the detection and differentiation of Burkholderia pseudomallei, Burkholderia mallei, Burkholderia thailandensis, and Burkholderia cepacia complex.

PubMed

Zakharova, Irina; Teteryatnikova, Natalya; Toporkov, Andrey; Viktorov, Dmitry

2017-10-01

Two species of Burkholderia pseudomallei complex (Bpc), B. pseudomallei and B. mallei, can cause severe life-threatening infections. Rapidly discerning individual species within the group and separating them from other opportunistic pathogens of the Burkholderia cepacia complex (Bcc) is essential to establish a correct diagnosis and for epidemiological surveillance. In this study, a multiplex PCR assay based on the detection of an individual set of chromosomal beta-lactamase genes for single-step identification and differentiation of B. pseudomallei, B. mallei, B. thailandensis, and Bcc was developed. Two pairs of primers specific to a distinct class of B metallo-beta-lactamase genes and a pair of primers specific to the oxacillin-hydrolyzing class D beta-lactamase gene were demonstrated to successfully discriminate species within Bpc and from Bcc. The assay sensitivity was 9561 genomic equivalents (GE) for B. pseudomallei, 7827 GE for B. mallei, 8749 GE for B. thailandensis and 6023 GE for B. cepacia. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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.

Optimization of the nanotwin-induced zigzag surface of copper by electromigration

NASA Astrophysics Data System (ADS)

Chen, Hsin-Ping; Huang, Chun-Wei; Wang, Chun-Wen; Wu, Wen-Wei; Liao, Chien-Neng; Chen, Lih-Juann; Tu, King-Ning

2016-01-01

By adding nanotwins to Cu, the surface electromigration (EM) slows down. The atomic mobility of the surface step-edges is retarded by the triple points where a twin meets a free surface to form a zigzag-type surface. We observed that EM can alter the zigzag surface structure to optimize the reduction of EM, according to Le Chatelier's principle. Statistically, the optimal alternation is to change an arbitrary (111)/(hkl) zigzag pair to a pair having a very low index (hkl) plane, especially the (200) plane. Using in situ ultrahigh vacuum and high-resolution transmission electron microscopy, we examined the effects of different zigzag surfaces on the rate of EM. The calculated rate of surface EM can be decreased by a factor of ten.By adding nanotwins to Cu, the surface electromigration (EM) slows down. The atomic mobility of the surface step-edges is retarded by the triple points where a twin meets a free surface to form a zigzag-type surface. We observed that EM can alter the zigzag surface structure to optimize the reduction of EM, according to Le Chatelier's principle. Statistically, the optimal alternation is to change an arbitrary (111)/(hkl) zigzag pair to a pair having a very low index (hkl) plane, especially the (200) plane. Using in situ ultrahigh vacuum and high-resolution transmission electron microscopy, we examined the effects of different zigzag surfaces on the rate of EM. The calculated rate of surface EM can be decreased by a factor of ten. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05418d

A rapid and efficient newly established method to detect COL1A1-PDGFB gene fusion in dermatofibrosarcoma protuberans

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

Yokoyama, Yoko; Shimizu, Akira; Okada, Etsuko

Highlights: Black-Right-Pointing-Pointer We developed new method to rapidly identify COL1A1-PDGFB fusion in DFSP. Black-Right-Pointing-Pointer New PCR method using a single primer pair detected COL1A1-PDGFB fusion in DFSP. Black-Right-Pointing-Pointer This is the first report of DFSP with a novel COL1A1 breakpoint in exon 5. -- Abstract: The detection of fusion transcripts of the collagen type 1{alpha}1 (COL1A1) and platelet-derived growth factor-BB (PDGFB) genes by genetic analysis has recognized as a reliable and valuable molecular tool for the diagnosis of dermatofibrosarcoma protuberans (DFSP). To detect the COL1A1-PDGFB fusion, almost previous reports performed reverse transcription polymerase chain reaction (RT-PCR) using multiplex forward primersmore » from COL1A1. However, it has possible technical difficulties with respect to the handling of multiple primers and reagents in the procedure. The objective of this study is to establish a rapid, easy, and efficient one-step method of PCR using only a single primer pair to detect the fusion transcripts of the COL1A1 and PDGFB in DFSP. To validate new method, we compared the results of RT-PCR in five patients of DFSP between the previous method using multiplex primers and our established one-step RT-PCR using a single primer pair. In all cases of DFSP, the COL1A1-PDGFB fusion was detected by both previous method and newly established one-step PCR. Importantly, we detected a novel COL1A1 breakpoint in exon 5. The newly developed method is valuable to rapidly identify COL1A1-PDGFB fusion transcripts in DFSP.« less

Limits of variation, specific infectivity, and genome packaging of massively recoded poliovirus genomes.

PubMed

Song, Yutong; Gorbatsevych, Oleksandr; Liu, Ying; Mugavero, JoAnn; Shen, Sam H; Ward, Charles B; Asare, Emmanuel; Jiang, Ping; Paul, Aniko V; Mueller, Steffen; Wimmer, Eckard

2017-10-10

Computer design and chemical synthesis generated viable variants of poliovirus type 1 (PV1), whose ORF (6,189 nucleotides) carried up to 1,297 "Max" mutations (excess of overrepresented synonymous codon pairs) or up to 2,104 "SD" mutations (randomly scrambled synonymous codons). "Min" variants (excess of underrepresented synonymous codon pairs) are nonviable except for P2 Min , a variant temperature-sensitive at 33 and 39.5 °C. Compared with WT PV1, P2 Min displayed a vastly reduced specific infectivity (si) (WT, 1 PFU/118 particles vs. P2 Min , 1 PFU/35,000 particles), a phenotype that will be discussed broadly. Si of haploid PV presents cellular infectivity of a single genotype. We performed a comprehensive analysis of sequence and structures of the PV genome to determine if evolutionary conserved cis-acting packaging signal(s) were preserved after recoding. We showed that conserved synonymous sites and/or local secondary structures that might play a role in determining packaging specificity do not survive codon pair recoding. This makes it unlikely that numerous "cryptic, sequence-degenerate, dispersed RNA packaging signals mapping along the entire viral genome" [Patel N, et al. (2017) Nat Microbiol 2:17098] play the critical role in poliovirus packaging specificity. Considering all available evidence, we propose a two-step assembly strategy for +ssRNA viruses: step I, acquisition of packaging specificity, either ( a ) by specific recognition between capsid protein(s) and replication proteins (poliovirus), or ( b ) by the high affinity interaction of a single RNA packaging signal (PS) with capsid protein(s) (most +ssRNA viruses so far studied); step II, cocondensation of genome/capsid precursors in which an array of hairpin structures plays a role in virion formation.

Measurement of hyperpolarized gas diffusion at very short time scales

PubMed Central

Carl, Michael; Wilson Miller, G.; Mugler, John P.; Rohrbaugh, Scott; Tobias, William A.; Cates, Gordon D.

2007-01-01

We present a new pulse sequence for measuring very-short-time-scale restricted diffusion of hyperpolarized noble gases. The pulse sequence is based on concatenating a large number of bipolar diffusion-sensitizing gradients to increase the diffusion attenuation of the MR signal while maintaining a fundamentally short diffusion time. However, it differs in several respects from existing methods that use oscillating diffusion gradients for this purpose. First, a wait time is inserted between neighboring pairs of gradient pulses; second, consecutive pulse pairs may be applied along orthogonal axes; and finally, the diffusion-attenuated signal is not simply read out at the end of the gradient train but is periodically sampled during the wait times between neighboring pulse pairs. The first two features minimize systematic differences between the measured (apparent) diffusion coefficient and the actual time-dependent diffusivity, while the third feature optimizes the use of the available MR signal to improve the precision of the diffusivity measurement in the face of noise. The benefits of this technique are demonstrated using theoretical calculations, Monte-Carlo simulations of gas diffusion in simple geometries, and experimental phantom measurements in a glass sphere containing hyperpolarized 3He gas. The advantages over the conventional single-bipolar approach were found to increase with decreasing diffusion time, and thus represent a significant step toward making accurate surface-to-volume measurements in the lung airspaces. PMID:17936048

Iterative metal artifact reduction for x-ray computed tomography using unmatched projector/backprojector pairs

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

Zhang, Hanming; Wang, Linyuan; Li, Lei

2016-06-15

Purpose: Metal artifact reduction (MAR) is a major problem and a challenging issue in x-ray computed tomography (CT) examinations. Iterative reconstruction from sinograms unaffected by metals shows promising potential in detail recovery. This reconstruction has been the subject of much research in recent years. However, conventional iterative reconstruction methods easily introduce new artifacts around metal implants because of incomplete data reconstruction and inconsistencies in practical data acquisition. Hence, this work aims at developing a method to suppress newly introduced artifacts and improve the image quality around metal implants for the iterative MAR scheme. Methods: The proposed method consists of twomore » steps based on the general iterative MAR framework. An uncorrected image is initially reconstructed, and the corresponding metal trace is obtained. The iterative reconstruction method is then used to reconstruct images from the unaffected sinogram. In the reconstruction step of this work, an iterative strategy utilizing unmatched projector/backprojector pairs is used. A ramp filter is introduced into the back-projection procedure to restrain the inconsistency components in low frequencies and generate more reliable images of the regions around metals. Furthermore, a constrained total variation (TV) minimization model is also incorporated to enhance efficiency. The proposed strategy is implemented based on an iterative FBP and an alternating direction minimization (ADM) scheme, respectively. The developed algorithms are referred to as “iFBP-TV” and “TV-FADM,” respectively. Two projection-completion-based MAR methods and three iterative MAR methods are performed simultaneously for comparison. Results: The proposed method performs reasonably on both simulation and real CT-scanned datasets. This approach could reduce streak metal artifacts effectively and avoid the mentioned effects in the vicinity of the metals. The improvements are evaluated by inspecting regions of interest and by comparing the root-mean-square errors, normalized mean absolute distance, and universal quality index metrics of the images. Both iFBP-TV and TV-FADM methods outperform other counterparts in all cases. Unlike the conventional iterative methods, the proposed strategy utilizing unmatched projector/backprojector pairs shows excellent performance in detail preservation and prevention of the introduction of new artifacts. Conclusions: Qualitative and quantitative evaluations of experimental results indicate that the developed method outperforms classical MAR algorithms in suppressing streak artifacts and preserving the edge structural information of the object. In particular, structures lying close to metals can be gradually recovered because of the reduction of artifacts caused by inconsistency effects.« 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

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.

Self-Organization of Vocabularies under Different Interaction Orders.

PubMed

Vera, Javier

2017-01-01

Traditionally, the formation of vocabularies has been studied by agent-based models (primarily, the naming game) in which random pairs of agents negotiate word-meaning associations at each discrete time step. This article proposes a first approximation to a novel question: To what extent is the negotiation of word-meaning associations influenced by the order in which agents interact? Automata networks provide the adequate mathematical framework to explore this question. Computer simulations suggest that on two-dimensional lattices the typical features of the formation of word-meaning associations are recovered under random schemes that update small fractions of the population at the same time; by contrast, if larger subsets of the population are updated, a periodic behavior may appear.

Structure and Dynamics of DNA and RNA Double Helices Obtained from the CCG and GGC Trinucleotide Repeats.

PubMed

Pan, Feng; Man, Viet Hoang; Roland, Christopher; Sagui, Celeste

2018-04-26

Expansions of both GGC and CCG sequences lead to a number of expandable, trinucleotide repeat (TR) neurodegenerative diseases. Understanding of these diseases involves, among other things, the structural characterization of the atypical DNA and RNA secondary structures. We have performed molecular dynamics simulations of (GCC) n and (GGC) n homoduplexes in order to characterize their conformations, stability, and dynamics. Each TR has two reading frames, which results in eight nonequivalent RNA/DNA homoduplexes, characterized by CpG or GpC steps between the Watson-Crick base pairs. Free energy maps for the eight homoduplexes indicate that the C-mismatches prefer anti-anti conformations, while G-mismatches prefer anti-syn conformations. Comparison between three modifications of the DNA AMBER force field shows good agreement for the mismatch free energy maps. The mismatches in DNA-GCC (but not CCG) are extrahelical, forming an extended e-motif. The mismatched duplexes exhibit characteristic sequence-dependent step twist, with strong variations in the G-rich sequences and the e-motif. The distribution of Na + is highly localized around the mismatches, especially G-mismatches. In the e-motif, there is strong Na + binding by two G(N7) atoms belonging to the pseudo GpC step created when cytosines are extruded and by extrahelical cytosines. Finally, we used a novel technique based on fast melting by means of an infrared laser pulse to classify the relative stability of the different DNA-CCG and -GGC homoduplexes.

Event-Triggered Distributed Average Consensus Over Directed Digital Networks With Limited Communication Bandwidth.

PubMed

Li, Huaqing; Chen, Guo; Huang, Tingwen; Dong, Zhaoyang; Zhu, Wei; Gao, Lan

2016-12-01

In this paper, we consider the event-triggered distributed average-consensus of discrete-time first-order multiagent systems with limited communication data rate and general directed network topology. In the framework of digital communication network, each agent has a real-valued state but can only exchange finite-bit binary symbolic data sequence with its neighborhood agents at each time step due to the digital communication channels with energy constraints. Novel event-triggered dynamic encoder and decoder for each agent are designed, based on which a distributed control algorithm is proposed. A scheme that selects the number of channel quantization level (number of bits) at each time step is developed, under which all the quantizers in the network are never saturated. The convergence rate of consensus is explicitly characterized, which is related to the scale of network, the maximum degree of nodes, the network structure, the scaling function, the quantization interval, the initial states of agents, the control gain and the event gain. It is also found that under the designed event-triggered protocol, by selecting suitable parameters, for any directed digital network containing a spanning tree, the distributed average consensus can be always achieved with an exponential convergence rate based on merely one bit information exchange between each pair of adjacent agents at each time step. Two simulation examples are provided to illustrate the feasibility of presented protocol and the correctness of the theoretical results.

The extension of a DNA double helix by an additional Watson-Crick base pair on the same backbone.

PubMed

Kumar, Pawan; Sharma, Pawan K; Madsen, Charlotte S; Petersen, Michael; Nielsen, Poul

2013-06-17

Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Deterministic multi-step rotation of magnetic single-domain state in Nickel nanodisks using multiferroic magnetoelastic coupling

NASA Astrophysics Data System (ADS)

Sohn, Hyunmin; Liang, Cheng-yen; Nowakowski, Mark E.; Hwang, Yongha; Han, Seungoh; Bokor, Jeffrey; Carman, Gregory P.; Candler, Robert N.

2017-10-01

We demonstrate deterministic multi-step rotation of a magnetic single-domain (SD) state in Nickel nanodisks using the multiferroic magnetoelastic effect. Ferromagnetic Nickel nanodisks are fabricated on a piezoelectric Lead Zirconate Titanate (PZT) substrate, surrounded by patterned electrodes. With the application of a voltage between opposing electrode pairs, we generate anisotropic in-plane strains that reshape the magnetic energy landscape of the Nickel disks, reorienting magnetization toward a new easy axis. By applying a series of voltages sequentially to adjacent electrode pairs, circulating in-plane anisotropic strains are applied to the Nickel disks, deterministically rotating a SD state in the Nickel disks by increments of 45°. The rotation of the SD state is numerically predicted by a fully-coupled micromagnetic/elastodynamic finite element analysis (FEA) model, and the predictions are experimentally verified with magnetic force microscopy (MFM). This experimental result will provide a new pathway to develop energy efficient magnetic manipulation techniques at the nanoscale.

Mechanism of duplex DNA destabilization by RNA-guided Cas9 nuclease during target interrogation

PubMed Central

Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

2017-01-01

The prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) endonuclease cleaves double-stranded DNA sequences specified by guide RNA molecules and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various organisms. The RNA-programmed Cas9 locates the target site by scanning genomic DNA. We sought to elucidate the mechanism of initial DNA interrogation steps that precede the pairing of target DNA with guide RNA. Using fluorometric and biochemical assays, we studied Cas9/guide RNA complexes with model DNA substrates that mimicked early intermediates on the pathway to the final Cas9/guide RNA–DNA complex. The results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial target interrogation by guide RNA. The duplex destabilization is mediated, in part, by Cas9/guide RNA affinity for unpaired segments of nontarget strand DNA close to PAM. Furthermore, our data indicate that the entry of double-stranded DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is hindered. We suggest that the interactions unfavorable for duplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA–DNA complex formation, thus additionally destabilizing the protospacer duplex. The mechanism that emerges from our analysis explains how the Cas9/sgRNA complex is able to locate the correct target sequence efficiently while interrogating numerous nontarget sequences associated with correct PAMs. PMID:28484024

Mechanism of duplex DNA destabilization by RNA-guided Cas9 nuclease during target interrogation.

PubMed

Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

2017-05-23

The prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) endonuclease cleaves double-stranded DNA sequences specified by guide RNA molecules and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various organisms. The RNA-programmed Cas9 locates the target site by scanning genomic DNA. We sought to elucidate the mechanism of initial DNA interrogation steps that precede the pairing of target DNA with guide RNA. Using fluorometric and biochemical assays, we studied Cas9/guide RNA complexes with model DNA substrates that mimicked early intermediates on the pathway to the final Cas9/guide RNA-DNA complex. The results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial target interrogation by guide RNA. The duplex destabilization is mediated, in part, by Cas9/guide RNA affinity for unpaired segments of nontarget strand DNA close to PAM. Furthermore, our data indicate that the entry of double-stranded DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is hindered. We suggest that the interactions unfavorable for duplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA-DNA complex formation, thus additionally destabilizing the protospacer duplex. The mechanism that emerges from our analysis explains how the Cas9/sgRNA complex is able to locate the correct target sequence efficiently while interrogating numerous nontarget sequences associated with correct PAMs.

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.

Human-Human Interaction Forces and Interlimb Coordination During Side-by-Side Walking With Hand Contact.

PubMed

Sylos-Labini, Francesca; d'Avella, Andrea; Lacquaniti, Francesco; Ivanenko, Yury

2018-01-01

Handholding can naturally occur between two walkers. When people walk side-by-side, either with or without hand contact, they often synchronize their steps. However, despite the importance of haptic interaction in general and the natural use of hand contact between humans during walking, few studies have investigated forces arising from physical interactions. Eight pairs of adult subjects participated in this study. They walked on side-by-side treadmills at 4 km/h independently and with hand contact. Only hand contact-related sensory information was available for unintentional synchronization, while visual and auditory communication was obstructed. Subjects walked at their natural cadences or following a metronome. Limb kinematics, hand contact 3D interaction forces and EMG activity of 12 upper limb muscles were recorded. Overall, unintentional step frequency locking was observed during about 40% of time in 88% of pairs walking with hand contact. On average, the amplitude of contact arm oscillations decreased while the contralateral (free) arm oscillated in the same way as during normal walking. Interestingly, EMG activity of the shoulder muscles of the contact arm did not decrease, and their synergistic pattern remained similar. The amplitude of interaction forces and of trunk oscillations was similar for synchronized and non-synchronized steps, though the synchronized steps were characterized by significantly more regular orientations of interaction forces. Our results further support the notion that gait synchronization during natural walking is common, and that it may occur through interaction forces. Conservation of the proximal muscle activity of the contact (not oscillating) arm is consistent with neural coupling between cervical and lumbosacral pattern generation circuitries ("quadrupedal" arm-leg coordination) during human gait. Overall, the findings suggest that individuals might integrate force interaction cues to communicate and coordinate steps during walking.

Human-Human Interaction Forces and Interlimb Coordination During Side-by-Side Walking With Hand Contact

PubMed Central

Sylos-Labini, Francesca; d'Avella, Andrea; Lacquaniti, Francesco; Ivanenko, Yury

2018-01-01

Handholding can naturally occur between two walkers. When people walk side-by-side, either with or without hand contact, they often synchronize their steps. However, despite the importance of haptic interaction in general and the natural use of hand contact between humans during walking, few studies have investigated forces arising from physical interactions. Eight pairs of adult subjects participated in this study. They walked on side-by-side treadmills at 4 km/h independently and with hand contact. Only hand contact-related sensory information was available for unintentional synchronization, while visual and auditory communication was obstructed. Subjects walked at their natural cadences or following a metronome. Limb kinematics, hand contact 3D interaction forces and EMG activity of 12 upper limb muscles were recorded. Overall, unintentional step frequency locking was observed during about 40% of time in 88% of pairs walking with hand contact. On average, the amplitude of contact arm oscillations decreased while the contralateral (free) arm oscillated in the same way as during normal walking. Interestingly, EMG activity of the shoulder muscles of the contact arm did not decrease, and their synergistic pattern remained similar. The amplitude of interaction forces and of trunk oscillations was similar for synchronized and non-synchronized steps, though the synchronized steps were characterized by significantly more regular orientations of interaction forces. Our results further support the notion that gait synchronization during natural walking is common, and that it may occur through interaction forces. Conservation of the proximal muscle activity of the contact (not oscillating) arm is consistent with neural coupling between cervical and lumbosacral pattern generation circuitries (“quadrupedal” arm-leg coordination) during human gait. Overall, the findings suggest that individuals might integrate force interaction cues to communicate and coordinate steps during walking. PMID:29563883

Method to improve cancerous lesion detection sensitivity in a dedicated dual-head scintimammography system

DOEpatents

Kieper, Douglas Arthur [Seattle, WA; Majewski, Stanislaw [Morgantown, WV; Welch, Benjamin L [Hampton, VA

2012-07-03

An improved method for enhancing the contrast between background and lesion areas of a breast undergoing dual-head scintimammographic examination comprising: 1) acquiring a pair of digital images from a pair of small FOV or mini gamma cameras compressing the breast under examination from opposing sides; 2) inverting one of the pair of images to align or co-register with the other of the images to obtain co-registered pixel values; 3) normalizing the pair of images pixel-by-pixel by dividing pixel values from each of the two acquired images and the co-registered image by the average count per pixel in the entire breast area of the corresponding detector; and 4) multiplying the number of counts in each pixel by the value obtained in step 3 to produce a normalization enhanced two dimensional contrast map. This enhanced (increased contrast) contrast map enhances the visibility of minor local increases (uptakes) of activity over the background and therefore improves lesion detection sensitivity, especially of small lesions.

Method to improve cancerous lesion detection sensitivity in a dedicated dual-head scintimammography system

DOEpatents

Kieper, Douglas Arthur [Newport News, VA; Majewski, Stanislaw [Yorktown, VA; Welch, Benjamin L [Hampton, VA

2008-10-28

An improved method for enhancing the contrast between background and lesion areas of a breast undergoing dual-head scintimammographic examination comprising: 1) acquiring a pair of digital images from a pair of small FOV or mini gamma cameras compressing the breast under examination from opposing sides; 2) inverting one of the pair of images to align or co-register with the other of the images to obtain co-registered pixel values; 3) normalizing the pair of images pixel-by-pixel by dividing pixel values from each of the two acquired images and the co-registered image by the average count per pixel in the entire breast area of the corresponding detector; and 4) multiplying the number of counts in each pixel by the value obtained in step 3 to produce a normalization enhanced two dimensional contrast map. This enhanced (increased contrast) contrast map enhances the visibility of minor local increases (uptakes) of activity over the background and therefore improves lesion detection sensitivity, especially of small lesions.

Regularization of Mickelsson generators for nonexceptional quantum groups

NASA Astrophysics Data System (ADS)

Mudrov, A. I.

2017-08-01

Let g' ⊂ g be a pair of Lie algebras of either symplectic or orthogonal infinitesimal endomorphisms of the complex vector spaces C N-2 ⊂ C N and U q (g') ⊂ U q (g) be a pair of quantum groups with a triangular decomposition U q (g) = U q (g-) U q (g+) U q (h). Let Z q (g, g') be the corresponding step algebra. We assume that its generators are rational trigonometric functions h ∗ → U q (g±). We describe their regularization such that the resulting generators do not vanish for any choice of the weight.

COMPACT CASCADE IMPACTS

DOEpatents

Lippmann, M.

1964-04-01

A cascade particle impactor capable of collecting particles and distributing them according to size is described. In addition the device is capable of collecting on a pair of slides a series of different samples so that less time is required for the changing of slides. Other features of the device are its compactness and its ruggedness making it useful under field conditions. Essentially the unit consists of a main body with a series of transverse jets discharging on a pair of parallel, spaced glass plates. The plates are capable of being moved incremental in steps to obtain the multiple samples. (AEC)

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

Evaluation of the pair-culture effect in Ophryotrocha puerilis (Polychaeta: Dorvilleidae). I. Pair-culture effect and sex ratio

NASA Astrophysics Data System (ADS)

Kegel, B.; Pfannenstiel, H.-D.

1983-06-01

Pairs and larger groups of female Ophryotrocha puerilis puerilis were formed from formerly isolated specimens. Neither the diameter of the oocytes present in the coelomic fluid nor the number of setigerous segments (ss) of the partners of a newly formed pair allow us to predict which one of the two animals will exhibit sex reversal. Amputation of the palps showed that these ventrolateral appendages of the prostomium are not responsible for the transmission of the mutual influence which is exerted during the pair-culture effect. Isolated females do not produce egg masses but keep their oocytes in the body cavity until they are eventually resorbed. The shedding of oocytes in one of the females of a newly formed pair was formerly considered to be the first step in the pair-culture effect. The present results demonstrate that egg laying in these cases is unspecific and due rather to the end of isolation than to specific interactions with the partner. In groups consisting of up to 50 animals the sex ratio oscillates around 1:1. The presence of primary males does not influence the sex ratio of adult specimens, although these males are capable of fertilizing egg masses produced by adult females. As a result, a high percentage of both young and old males are found in densely populated bowls. The significance of the pair-culture effect in natural populations is discussed in the light of these findings.

On the Tracy-Widomβ Distribution for β=6

NASA Astrophysics Data System (ADS)

Grava, Tamara; Its, Alexander; Kapaev, Andrei; Mezzadri, Francesco

2016-11-01

We study the Tracy-Widom distribution function for Dyson's β-ensemble with β = 6. The starting point of our analysis is the recent work of I. Rumanov where he produces a Lax-pair representation for the Bloemendal-Virág equation. The latter is a linear PDE which describes the Tracy-Widom functions corresponding to general values of β. Using his Lax pair, Rumanov derives an explicit formula for the Tracy-Widom β=6 function in terms of the second Painlevé transcendent and the solution of an auxiliary ODE. Rumanov also shows that this formula allows him to derive formally the asymptotic expansion of the Tracy-Widom function. Our goal is to make Rumanov's approach and hence the asymptotic analysis it provides rigorous. In this paper, the first one in a sequel, we show that Rumanov's Lax-pair can be interpreted as a certain gauge transformation of the standard Lax pair for the second Painlevé equation. This gauge transformation though contains functional parameters which are defined via some auxiliary nonlinear ODE which is equivalent to the auxiliary ODE of Rumanov's formula. The gauge-interpretation of Rumanov's Lax-pair allows us to highlight the steps of the original Rumanov's method which needs rigorous justifications in order to make the method complete. We provide a rigorous justification of one of these steps. Namely, we prove that the Painlevé function involved in Rumanov's formula is indeed, as it has been suggested by Rumanov, the Hastings-McLeod solution of the second Painlevé equation. The key issue which we also discuss and which is still open is the question of integrability of the auxiliary ODE in Rumanov's formula. We note that this question is crucial for the rigorous asymptotic analysis of the Tracy-Widom function. We also notice that our work is a partial answer to one of the problems related to the β-ensembles formulated by Percy Deift during the June 2015 Montreal Conference on integrable systems.

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

Colorimetric Sensor for Label Free Detection of Porcine PCR Product (ID: 18)

NASA Astrophysics Data System (ADS)

Ali, M. E.; Hashim, U.; Bari, M. F.; Dhahi, Th. S.

2011-05-01

This report described the use of 40±5 nm in diameter citrate-coated gold nanoparticles (GNPs) as colorimetric sensor to visually detect the presence of a 17-base swine specific conserved sequence and nucleotide mismatch in the mixed PCR products of pig, deer and shad cytochrome b genes. The size of these PCR amplicons was 109 base-pair and was amplified with a pair of common primers. Colloidal GNPs changed color from pinkish- red to purple-gray in 2 mM PBS buffer by losing its characteristic surface plasmon resonance peak at 530 nm and gaining new features between 620 and 800 nm in the absorption spectrum indicating strong aggregation. The particles were stabilized against salt induced aggregation, retained spectral features and characteristic color upon adsorption of single-stranded DNA. The PCR products without any additional processing were hybridized with a 17-nucleotide swine probe prior to exposure to GNPs. At a critical annealing temperature (55° C) that differentiated between the match and mismatch pairing, the probe was hybridized with the pig PCR product and dehybridized from the deer's and shad's. The interaction of dehybridized probe to GNPs prevented them from salt-induced aggregation, retaining their characteristic red color. The assay did not need any surface modification chemistry or labeling steps. The results were determined visually and validated by absorption spectroscopy. The entire assay (hybridization plus visual detection) was performed in less than 10 min. The assay obviated the need of complex RFLP, sequencing or blotting to differentiate the same size PCR products. We find the application of the assay for species assignment in food analysis, mismatch detection in genetic screening and homology study among closely related species.

UltiMatch-NL: A Web Service Matchmaker Based on Multiple Semantic Filters

PubMed Central

Mohebbi, Keyvan; Ibrahim, Suhaimi; Zamani, Mazdak; Khezrian, Mojtaba

2014-01-01

In this paper, a Semantic Web service matchmaker called UltiMatch-NL is presented. UltiMatch-NL applies two filters namely Signature-based and Description-based on different abstraction levels of a service profile to achieve more accurate results. More specifically, the proposed filters rely on semantic knowledge to extract the similarity between a given pair of service descriptions. Thus it is a further step towards fully automated Web service discovery via making this process more semantic-aware. In addition, a new technique is proposed to weight and combine the results of different filters of UltiMatch-NL, automatically. Moreover, an innovative approach is introduced to predict the relevance of requests and Web services and eliminate the need for setting a threshold value of similarity. In order to evaluate UltiMatch-NL, the repository of OWLS-TC is used. The performance evaluation based on standard measures from the information retrieval field shows that semantic matching of OWL-S services can be significantly improved by incorporating designed matching filters. PMID:25157872

FPGA-based Trigger System for the Fermilab SeaQuest Experimentz

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

Shiu, Shiuan-Hal; Wu, Jinyuan; McClellan, Randall Evan

The SeaQuest experiment (Fermilab E906) detects pairs of energetic μ + and μ -produced in 120 GeV/c proton–nucleon interactions in a high rate environment. The trigger system we used consists of several arrays of scintillator hodoscopes and a set of field-programmable gate array (FPGA) based VMEbus modules. Signals from up to 96 channels of hodoscope are digitized by each FPGA with a 1-ns resolution using the time-to-digital convertor (TDC) firmware. The delay of the TDC output can be adjusted channel-by-channel in 1-ns step and then re-aligned with the beam RF clock. The hit pattern on the hodoscope planes is thenmore » examined against pre-determined trigger matrices to identify candidate muon tracks. Finally, information on the candidate tracks is sent to the 2nd-level FPGA-based track correlator to find candidate di-muon events. The design and implementation of the FPGA-based trigger system for SeaQuest experiment are presented.« less

FPGA-based trigger system for the Fermilab SeaQuest experimentz

NASA Astrophysics Data System (ADS)

Shiu, Shiuan-Hal; Wu, Jinyuan; McClellan, Randall Evan; Chang, Ting-Hua; Chang, Wen-Chen; Chen, Yen-Chu; Gilman, Ron; Nakano, Kenichi; Peng, Jen-Chieh; Wang, Su-Yin

2015-12-01

The SeaQuest experiment (Fermilab E906) detects pairs of energetic μ+ and μ- produced in 120 GeV/c proton-nucleon interactions in a high rate environment. The trigger system consists of several arrays of scintillator hodoscopes and a set of field-programmable gate array (FPGA) based VMEbus modules. Signals from up to 96 channels of hodoscope are digitized by each FPGA with a 1-ns resolution using the time-to-digital convertor (TDC) firmware. The delay of the TDC output can be adjusted channel-by-channel in 1-ns step and then re-aligned with the beam RF clock. The hit pattern on the hodoscope planes is then examined against pre-determined trigger matrices to identify candidate muon tracks. Information on the candidate tracks is sent to the 2nd-level FPGA-based track correlator to find candidate di-muon events. The design and implementation of the FPGA-based trigger system for SeaQuest experiment are presented.

FPGA-based Trigger System for the Fermilab SeaQuest Experimentz

DOE PAGES

Shiu, Shiuan-Hal; Wu, Jinyuan; McClellan, Randall Evan; ...

2015-09-10

The SeaQuest experiment (Fermilab E906) detects pairs of energetic μ + and μ -produced in 120 GeV/c proton–nucleon interactions in a high rate environment. The trigger system we used consists of several arrays of scintillator hodoscopes and a set of field-programmable gate array (FPGA) based VMEbus modules. Signals from up to 96 channels of hodoscope are digitized by each FPGA with a 1-ns resolution using the time-to-digital convertor (TDC) firmware. The delay of the TDC output can be adjusted channel-by-channel in 1-ns step and then re-aligned with the beam RF clock. The hit pattern on the hodoscope planes is thenmore » examined against pre-determined trigger matrices to identify candidate muon tracks. Finally, information on the candidate tracks is sent to the 2nd-level FPGA-based track correlator to find candidate di-muon events. The design and implementation of the FPGA-based trigger system for SeaQuest experiment are presented.« less

UltiMatch-NL: a Web service matchmaker based on multiple semantic filters.

PubMed

Mohebbi, Keyvan; Ibrahim, Suhaimi; Zamani, Mazdak; Khezrian, Mojtaba

2014-01-01

In this paper, a Semantic Web service matchmaker called UltiMatch-NL is presented. UltiMatch-NL applies two filters namely Signature-based and Description-based on different abstraction levels of a service profile to achieve more accurate results. More specifically, the proposed filters rely on semantic knowledge to extract the similarity between a given pair of service descriptions. Thus it is a further step towards fully automated Web service discovery via making this process more semantic-aware. In addition, a new technique is proposed to weight and combine the results of different filters of UltiMatch-NL, automatically. Moreover, an innovative approach is introduced to predict the relevance of requests and Web services and eliminate the need for setting a threshold value of similarity. In order to evaluate UltiMatch-NL, the repository of OWLS-TC is used. The performance evaluation based on standard measures from the information retrieval field shows that semantic matching of OWL-S services can be significantly improved by incorporating designed matching filters.

Methylated nucleosides in tRNA and tRNA methyltransferases

PubMed Central

Hori, Hiroyuki

2014-01-01

To date, more than 90 modified nucleosides have been found in tRNA and the biosynthetic pathways of the majority of tRNA modifications include a methylation step(s). Recent studies of the biosynthetic pathways have demonstrated that the availability of methyl group donors for the methylation in tRNA is important for correct and efficient protein synthesis. In this review, I focus on the methylated nucleosides and tRNA methyltransferases. The primary functions of tRNA methylations are linked to the different steps of protein synthesis, such as the stabilization of tRNA structure, reinforcement of the codon-anticodon interaction, regulation of wobble base pairing, and prevention of frameshift errors. However, beyond these basic functions, recent studies have demonstrated that tRNA methylations are also involved in the RNA quality control system and regulation of tRNA localization in the cell. In a thermophilic eubacterium, tRNA modifications and the modification enzymes form a network that responses to temperature changes. Furthermore, several modifications are involved in genetic diseases, infections, and the immune response. Moreover, structural, biochemical, and bioinformatics studies of tRNA methyltransferases have been clarifying the details of tRNA methyltransferases and have enabled these enzymes to be classified. In the final section, the evolution of modification enzymes is discussed. PMID:24904644

Lewis Acid Pairs for the Activation of Biomass-derived Oxygenates in Aqueous Media

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

Roman, Yuriy

2015-09-14

The objective of this project is to understand the mechanistic aspects behind the cooperative activation of oxygenates by catalytic pairs in aqueous media. Specifically, we will investigate how the reactivity of a solid Lewis acid can be modulated by pairing the active site with other catalytic sites at the molecular level, with the ultimate goal of enhancing activation of targeted functional groups. Although unusual catalytic properties have been attributed to the cooperative effects promoted by such catalytic pairs, virtually no studies exist detailing the use heterogeneous water-tolerant Lewis pairs. A main goal of this work is to devise rational pathwaysmore » for the synthesis of porous heterogeneous catalysts featuring isolated Lewis pairs that are active in the transformation of biomass-derived oxygenates in the presence of bulk water. Achieving this technical goal will require closely linking advanced synthesis techniques; detailed kinetic and mechanistic investigations; strict thermodynamic arguments; and comprehensive characterization studies of both materials and reaction intermediates. For the last performance period (2014-2015), two technical aims were pursued: 1) C-C coupling using Lewis acid and base pairs in Lewis acidic zeolites. Tin-, zirconium-, and hafnium containing zeolites (e.g., Sn-, Zr-, and Hf-Beta) are versatile solid Lewis acids that selectively activate carbonyl functional groups. In this aim, we demonstrate that these zeolites catalyze the cross-aldol condensation of aromatic aldehydes with acetone under mild reaction conditions with near quantitative yields. NMR studies with isotopically labeled molecules confirm that acid-base pairs in the Si-O-M framework ensemble promote soft enolization through α-proton abstraction. The Lewis acidic zeolites maintain activity in the presence of water and, unlike traditional base catalysts, in acidic solutions. 2) One-pot synthesis of MWW zeolite nanosheets for activation of bulky substrates. Through post-synthetic modifications, layered zeolite precursors can be transformed into 2-dimensional (2D), zeolites with open architectures. These novel hierarchical microporous/mesoporous materials with exposed active sites can facilitate the conversion of bulky substrates while maintaining higher stability than amorphous mesoporous materials. However, post-synthetic exfoliation techniques are energy intensive, multi-step and require highly alkaline conditions that result in low silica yields and a partially amorphous product. In this aim, we demonstrate an effective one-pot synthesis method to generate exfoliated single-unit-cell thick MWW nanosheets. The new material, named MIT-1, is synthesized using a rationally-designed OSDA and results in a material with high crystallinity, surface area, and acidity that does not require post-synthetic treatments other than calcination. A parametric study of Al, Na, and water content reveals that MIT-1 crystallizes over a wide synthetic window. Characterization data show that MIT-1 has high mesoporosity with an external surface area exceeding 500 m2g-1 and a high external acid site density of 21 x 10-5 mol g-1. Catalytic tests demonstrate that MIT-1 has three-fold higher catalytic activity for the Friedel-Crafts alkylation of benzene with benzyl alcohol as compared to that of other 3D MWW topology zeolites.« less

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

A two-step ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry with mass defect filtering method for rapid identification of analogues from known components of different chemical structure types in Fructus Gardeniae-Fructus Forsythiae herb pair extract and in rat's blood.

PubMed

Zhou, Wei; Shan, Jinjun; Meng, Minxin

2018-08-17

Fructus Gardeniae-Fructus Forsythiae herb pair is an herbal formula used extensively to treat inflammation and fever, but few systematic identification studies of the bioactive components have been reported. Herein, the unknown analogues in the first-step screening were rapidly identified from representative compounds in different structure types (geniposide as iridoid type, crocetin as crocetin type, jasminoside B as monocyclic monoterpene type, oleanolic acid as saponin type, 3-caffeoylquinic acid as organic acid type, forsythoside A as phenylethanoid type, phillyrin as lignan type and quercetin 3-rutinoside as flavonoid type) by UPLC-Q-Tof/MS combined with mass defect filtering (MDF), and further confirmed with reference standards and published literatures. Similarly, in the second step, other unknown components were rapidly discovered from the compounds identified in the first step by MDF. Using the two-step screening method, a total of 58 components were characterized in Fructus Gardeniae-Fructus Forsythiae (FG-FF) decoction. In rat's blood, 36 compounds in extract and 16 metabolites were unambiguously or tentatively identified. Besides, we found the principal metabolites were glucuronide conjugates, with the glucuronide conjugates of caffeic acid, quercetin and kaempferol confirmed as caffeic acid 3-glucuronide, quercetin 3-glucuronide and kaempferol 3-glucuronide by reference standards, respectively. Additionally, most of them bound more strongly to human serum albumin than their respective prototypes, predicted by Molecular Docking and Simulation, indicating that they had lower blood clearance in vivo and possibly more contribution to pharmacological effects. This study developed a novel two-step screening method in addressing how to comprehensively screen components in herbal medicine by UPLC-Q-Tof/MS with MDF. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

The first steps towards a de minimus, affordable NEA exploration architecture

NASA Astrophysics Data System (ADS)

Landis, Rob R.; Abell, Paul A.; Adamo, Daniel R.; Barbee, Brent W.; Johnson, Lindley N.

2013-03-01

The impetus for asteroid exploration is scientific, political, and pragmatic. The notion of sending human explorers to asteroids is not new. Piloted missions to these primitive bodies were first discussed in the 1960s, pairing Saturn V rockets with enhanced Apollo spacecraft to explore what were then called "Earth-approaching asteroids." Two decades ago, NASA's Space Exploration Initiative (SEI) also briefly examined the possibility of visiting these small celestial bodies. Most recently, the US Human Space Flight Review Committee (the second Augustine Commission) suggested that near-Earth objects (NEOs) represent a target-rich environment for exploration via the "Flexible Path" option. However, prior to seriously considering human missions to NEOs, it has become clear that we currently lack a robust catalog of human-accessible targets. The majority of the known NEOs identified by a study team across several NASA centers as "human-accessible" are probably too small and have orbits that are too uncertain to consider mounting piloted expeditions to these small worlds. The first step in developing a comprehensive catalog is, therefore, to complete a space-based NEO survey. The resulting catalog of candidate NEOs would then be transformed into a matrix of opportunities for robotic and human missions for the next several decades and shared with the international community. This initial step of a space-based NEO survey is therefore the linchpin to laying the foundation of a low-risk architecture to venture out and explore these primitive bodies. We suggest such a minimalist framework architecture from (1) extensive ground-based and precursor spacecraft investigations (while applying operational knowledge from science-driven robotic missions), (2) astronaut servicing of spacecraft operating at geosynchronous Earth orbit to retain essential skills and experience, and (3) applying the sum of these skills, knowledge and experience to piloted missions to NEOs.

A family of four stages embedded explicit six-step methods with eliminated phase-lag and its derivatives for the numerical solution of the second order problems

NASA Astrophysics Data System (ADS)

Simos, T. E.

2017-11-01

A family of four stages high algebraic order embedded explicit six-step methods, for the numerical solution of second order initial or boundary-value problems with periodical and/or oscillating solutions, are studied in this paper. The free parameters of the new proposed methods are calculated solving the linear system of equations which is produced by requesting the vanishing of the phase-lag of the methods and the vanishing of the phase-lag's derivatives of the schemes. For the new obtained methods we investigate: • Its local truncation error (LTE) of the methods.• The asymptotic form of the LTE obtained using as model problem the radial Schrödinger equation.• The comparison of the asymptotic forms of LTEs for several methods of the same family. This comparison leads to conclusions on the efficiency of each method of the family.• The stability and the interval of periodicity of the obtained methods of the new family of embedded finite difference pairs.• The applications of the new obtained family of embedded finite difference pairs to the numerical solution of several second order problems like the radial Schrödinger equation, astronomical problems etc. The above applications lead to conclusion on the efficiency of the methods of the new family of embedded finite difference pairs.

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

Fast algorithms for evaluating the stress field of dislocation lines in anisotropic elastic media

NASA Astrophysics Data System (ADS)

Chen, C.; Aubry, S.; Oppelstrup, T.; Arsenlis, A.; Darve, E.

2018-06-01

In dislocation dynamics (DD) simulations, the most computationally intensive step is the evaluation of the elastic interaction forces among dislocation ensembles. Because the pair-wise interaction between dislocations is long-range, this force calculation step can be significantly accelerated by the fast multipole method (FMM). We implemented and compared four different methods in isotropic and anisotropic elastic media: one based on the Taylor series expansion (Taylor FMM), one based on the spherical harmonics expansion (Spherical FMM), one kernel-independent method based on the Chebyshev interpolation (Chebyshev FMM), and a new kernel-independent method that we call the Lagrange FMM. The Taylor FMM is an existing method, used in ParaDiS, one of the most popular DD simulation softwares. The Spherical FMM employs a more compact multipole representation than the Taylor FMM does and is thus more efficient. However, both the Taylor FMM and the Spherical FMM are difficult to derive in anisotropic elastic media because the interaction force is complex and has no closed analytical formula. The Chebyshev FMM requires only being able to evaluate the interaction between dislocations and thus can be applied easily in anisotropic elastic media. But it has a relatively large memory footprint, which limits its usage. The Lagrange FMM was designed to be a memory-efficient black-box method. Various numerical experiments are presented to demonstrate the convergence and the scalability of the four methods.

Multi-Sensor Fusion of Infrared and Electro-Optic Signals for High Resolution Night Images

PubMed Central

Huang, Xiaopeng; Netravali, Ravi; Man, Hong; Lawrence, Victor

2012-01-01

Electro-optic (EO) image sensors exhibit the properties of high resolution and low noise level at daytime, but they do not work in dark environments. Infrared (IR) image sensors exhibit poor resolution and cannot separate objects with similar temperature. Therefore, we propose a novel framework of IR image enhancement based on the information (e.g., edge) from EO images, which improves the resolution of IR images and helps us distinguish objects at night. Our framework superimposing/blending the edges of the EO image onto the corresponding transformed IR image improves their resolution. In this framework, we adopt the theoretical point spread function (PSF) proposed by Hardie et al. for the IR image, which has the modulation transfer function (MTF) of a uniform detector array and the incoherent optical transfer function (OTF) of diffraction-limited optics. In addition, we design an inverse filter for the proposed PSF and use it for the IR image transformation. The framework requires four main steps: (1) inverse filter-based IR image transformation; (2) EO image edge detection; (3) registration; and (4) blending/superimposing of the obtained image pair. Simulation results show both blended and superimposed IR images, and demonstrate that blended IR images have better quality over the superimposed images. Additionally, based on the same steps, simulation result shows a blended IR image of better quality when only the original IR image is available. PMID:23112602

Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for -1 ribosomal frameshifting stimulation

NASA Astrophysics Data System (ADS)

Zhong, Zhensheng; Yang, Lixia; Zhang, Haiping; Shi, Jiahao; Vandana, J. Jeya; Lam, Do Thuy Uyen Ha; Olsthoorn, René C. L.; Lu, Lanyuan; Chen, Gang

2016-12-01

Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins. An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting. However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking. Here, we report the results of our single-molecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics. Our results directly reveal that the energetic coupling between loop 2 and stem 1 via minor-groove base triple formation enhances the mechanical stability. The terminal base pair in stem 1 (directly in contact with a translating ribosome at the slippery site) also affects the mechanical stability of the pseudoknot. The -1 frameshifting efficiency is positively correlated with the cooperative one-step unfolding force and inversely correlated with the one-step mechanical unfolding rate at zero force. A significantly improved correlation was observed between -1 frameshifting efficiency and unfolding rate at forces of 15-35 pN, consistent with the fact that the ribosome is a force-generating molecular motor with helicase activity. No correlation was observed between thermal stability and -1 frameshifting efficiency.

Multi-sensor fusion of infrared and electro-optic signals for high resolution night images.

PubMed

Huang, Xiaopeng; Netravali, Ravi; Man, Hong; Lawrence, Victor

2012-01-01

Electro-optic (EO) image sensors exhibit the properties of high resolution and low noise level at daytime, but they do not work in dark environments. Infrared (IR) image sensors exhibit poor resolution and cannot separate objects with similar temperature. Therefore, we propose a novel framework of IR image enhancement based on the information (e.g., edge) from EO images, which improves the resolution of IR images and helps us distinguish objects at night. Our framework superimposing/blending the edges of the EO image onto the corresponding transformed IR image improves their resolution. In this framework, we adopt the theoretical point spread function (PSF) proposed by Hardie et al. for the IR image, which has the modulation transfer function (MTF) of a uniform detector array and the incoherent optical transfer function (OTF) of diffraction-limited optics. In addition, we design an inverse filter for the proposed PSF and use it for the IR image transformation. The framework requires four main steps: (1) inverse filter-based IR image transformation; (2) EO image edge detection; (3) registration; and (4) blending/superimposing of the obtained image pair. Simulation results show both blended and superimposed IR images, and demonstrate that blended IR images have better quality over the superimposed images. Additionally, based on the same steps, simulation result shows a blended IR image of better quality when only the original IR image is available.

Luminescence resonance energy transfer-based nucleic acid hybridization assay on cellulose paper with upconverting phosphor as donors.

PubMed

Zhou, Feng; Noor, M Omair; Krull, Ulrich J

2014-03-04

A bioassay based on DNA hybridization on cellulose paper is a promising format for gene fragment detection that may be suited for in-field and rapid diagnostic applications. We demonstrate for the first time that luminescence resonance energy transfer (LRET) associated with upconverting phosphors (UCPs) can be used to develop a paper-based DNA hybridization assay with high sensitivity, selectivity and fast response. UCPs with strong green emission were synthesized and subsequently functionalized with streptavidin (UCP-strep). UCP-strep particles were immobilized on cellulose paper, and then biotinylated single-stranded oligonucleotide probes were conjugated onto the UCPs via streptavidin-biotin linkage. The UCPs served as donors that were LRET-paired with Cy3-labeled target DNA. Selective DNA hybridization enabled the proximity required for LRET-sensitized emission from Cy3, which was used as the detection signal. Hybridization was complete within 2 min, and the limit of detection of the method was 34 fmol, which is a significant improvement in comparison to an analogous fluorescence resonance energy transfer (FRET) assay based on quantum dots. The assay exhibited excellent resistance to nonspecific adsorption of noncomplementary short/long DNA and protein. The selectivity of the assay was further evaluated by one base pair mismatched (1BPM) DNA detection, where a maximum signal ratio of 3.1:1 was achieved between fully complementary and 1BPM samples. This work represents a preliminary but significant step for the development of paper-based UCP-LRET nucleic acid hybridization assays, which offer potential for lowering the limit of detection of luminescent hybridization assays due to the negligible background signal associated with optical excitation by near-infrared (NIR) light.

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?

Substrate Induced Ordering of Molecular Absorbates on Au(111)

DTIC Science & Technology

1992-02-27

the right in Fig.1), crossing, apparently unperturbed, monoatomic steps (not shown here). In addition, line pairs are organized in domains, separated...following immersion of a gold -electrode in a DMF solution containing I(x=5) and after rinsing with acetone; and, 4) a detailed STM investigation of the

A non-multimacrocyclic heteroditopic receptor that cooperatively binds and effectively extracts KAcO salt.

PubMed

Zakrzewski, Maciej; Kwietniewska, Natalia; Walczak, Wojciech; Piątek, Piotr

2018-06-06

Prepared in only three synthetic steps, a non-multimacrocyclic heteroditopic receptor binds potassium salts of halides and carboxylates with unusually high cooperativity, suggesting salt binding as associated ion-pairs. Unprecedented extraction of highly hydrophilic KAcO salt from water to organic solution is also demonstrated.

Escape of anions from geminate recombination in THF due to charge delocalization

DOE PAGES

Chen, Hung -Cheng; Cook, Andrew R.; Asaoka, Sadayuki; ...

2017-11-24

Geminate recombination of 24 radical anions (M˙ –) with solvated protons (RH 2 +) was studied in tetrahydrofuran (THF) with pulse radiolysis. The recombination has two steps: (1) diffusion of M˙ – and RH 2 + together to form intimate (contact and solvent separated) ion pairs, driven by Coulomb attraction; (2) annihilation of anions due to proton transfer (PT) from RH 2 + to M˙ –. The non-exponential time-dependence of the geminate diffusion was determined. For all molecules protonated on O or N atoms the subsequent PT step is too fast (<0.2 ns) to measure, except for the anion ofmore » TCNE which did not undergo proton transfer. PT to C atoms was as slow as 70 ns and was always slow enough to be observable. A possible effect of charge delocalization on the PT rates could not be clearly separated from other factors. For 21 of the 24 molecules studied here, a free ion yield (71.6 ± 6.2 nmol J –1) comprising ~29% of the total, was formed. This yield of “Type I” free ions is independent of the PT rate because it arises entirely by escape from the initial distribution of ion pair distances without forming intimate ion pairs. Furthermore, three anions of oligo(9,9-dihexyl)fluorenes, F n˙ – (n = 2–4) were able to escape from intimate ion-pairs to form additional yields of “Type II” free ions with escape rate constants near 3 × 10 6 s –1. These experiments find no evidence for an inverted region for proton transfer.« less

A fast and fully automatic registration approach based on point features for multi-source remote-sensing images

NASA Astrophysics Data System (ADS)

Yu, Le; Zhang, Dengrong; Holden, Eun-Jung

2008-07-01

Automatic registration of multi-source remote-sensing images is a difficult task as it must deal with the varying illuminations and resolutions of the images, different perspectives and the local deformations within the images. This paper proposes a fully automatic and fast non-rigid image registration technique that addresses those issues. The proposed technique performs a pre-registration process that coarsely aligns the input image to the reference image by automatically detecting their matching points by using the scale invariant feature transform (SIFT) method and an affine transformation model. Once the coarse registration is completed, it performs a fine-scale registration process based on a piecewise linear transformation technique using feature points that are detected by the Harris corner detector. The registration process firstly finds in succession, tie point pairs between the input and the reference image by detecting Harris corners and applying a cross-matching strategy based on a wavelet pyramid for a fast search speed. Tie point pairs with large errors are pruned by an error-checking step. The input image is then rectified by using triangulated irregular networks (TINs) to deal with irregular local deformations caused by the fluctuation of the terrain. For each triangular facet of the TIN, affine transformations are estimated and applied for rectification. Experiments with Quickbird, SPOT5, SPOT4, TM remote-sensing images of the Hangzhou area in China demonstrate the efficiency and the accuracy of the proposed technique for multi-source remote-sensing image registration.

Impact of correlated magnetic noise on the detection of stochastic gravitational waves: Estimation based on a simple analytical model

NASA Astrophysics Data System (ADS)

Himemoto, Yoshiaki; Taruya, Atsushi

2017-07-01

After the first direct detection of gravitational waves (GW), detection of the stochastic background of GWs is an important next step, and the first GW event suggests that it is within the reach of the second-generation ground-based GW detectors. Such a GW signal is typically tiny and can be detected by cross-correlating the data from two spatially separated detectors if the detector noise is uncorrelated. It has been advocated, however, that the global magnetic fields in the Earth-ionosphere cavity produce the environmental disturbances at low-frequency bands, known as Schumann resonances, which potentially couple with GW detectors. In this paper, we present a simple analytical model to estimate its impact on the detection of stochastic GWs. The model crucially depends on the geometry of the detector pair through the directional coupling, and we investigate the basic properties of the correlated magnetic noise based on the analytic expressions. The model reproduces the major trend of the recently measured global correlation between the GW detectors via magnetometer. The estimated values of the impact of correlated noise also match those obtained from the measurement. Finally, we give an implication to the detection of stochastic GWs including upcoming detectors, KAGRA and LIGO India. The model suggests that LIGO Hanford-Virgo and Virgo-KAGRA pairs are possibly less sensitive to the correlated noise and can achieve a better sensitivity to the stochastic GW signal in the most pessimistic case.

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

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

Shape Effect Undermined by Surface Reconstruction: Ethanol Dehydrogenation over Shape-Controlled SrTiO 3 Nanocrystals

DOE PAGES

Foo, Guo Shiou; Hood, Zachary D.; Wu, Zili

2017-12-05

For this research, to gain an in-depth understanding of the surface properties relevant for catalysis using ternary oxides, we report the acid–base pair reactivity of shape-controlled SrTiO 3 (STO) nanocrystals for the dehydrogenation of ethanol. Cubes, truncated cubes, dodecahedra, and etched cubes of STO with varying ratios of (001) and (110) crystal facets were synthesized using a hydrothermal method. Low-energy ion scattering (LEIS) analysis revealed that the (001) surface on cubes of STO is enriched with SrO due to surface reconstruction, resulting in a high ratio of strong base sites. Chemical treatment with dilute nitric acid to form etched cubesmore » of STO resulted in a surface enriched with Ti cations and strong acidity. Furthermore, the strength and distribution of surface acidic sites increase with the ratio of (110) facet from cubes to truncated cubes to dodecahedra for STO. Kinetic, isotopic, and spectroscopy methods show that the dehydrogenation of ethanol proceeds through the facile dissociation of the alcohol group, followed by the cleavage of the C α–H bond, which is the rate-determining step. Co-feeding of various probe molecules during catalysis, such as NH 3, 2,6-di-tert-butylpyridine, CO 2, and SO 2, reveals that a pair of Lewis acid site and basic surface oxygen atom is involved in the dehydrogenation reaction. The surface density of acid–base site pairs was measured using acetic acid as a probe molecule, allowing initial acetaldehyde formation turnover rates to be obtained. Comparison among various catalysts reveals no simple correlation between ethanol turnover rate and the percentage of either surface facet ((001) or (110)) of the STO nanocrystals. Instead, the reaction rate is found to increase with the strength of acid sites but reversely with the strength of base sites. The acid–base property is directly related to the surface composition as a result from different surface reconstruction behaviors of the shaped STO nanocrystals. Lastly, the finding in this work underscores the importance of characterizing the top surface compositions and sites properties when assessing the catalytic performance of shape-controlled complex oxides such as perovskites.« less

Shape Effect Undermined by Surface Reconstruction: Ethanol Dehydrogenation over Shape-Controlled SrTiO 3 Nanocrystals

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

Foo, Guo Shiou; Hood, Zachary D.; Wu, Zili

For this research, to gain an in-depth understanding of the surface properties relevant for catalysis using ternary oxides, we report the acid–base pair reactivity of shape-controlled SrTiO 3 (STO) nanocrystals for the dehydrogenation of ethanol. Cubes, truncated cubes, dodecahedra, and etched cubes of STO with varying ratios of (001) and (110) crystal facets were synthesized using a hydrothermal method. Low-energy ion scattering (LEIS) analysis revealed that the (001) surface on cubes of STO is enriched with SrO due to surface reconstruction, resulting in a high ratio of strong base sites. Chemical treatment with dilute nitric acid to form etched cubesmore » of STO resulted in a surface enriched with Ti cations and strong acidity. Furthermore, the strength and distribution of surface acidic sites increase with the ratio of (110) facet from cubes to truncated cubes to dodecahedra for STO. Kinetic, isotopic, and spectroscopy methods show that the dehydrogenation of ethanol proceeds through the facile dissociation of the alcohol group, followed by the cleavage of the C α–H bond, which is the rate-determining step. Co-feeding of various probe molecules during catalysis, such as NH 3, 2,6-di-tert-butylpyridine, CO 2, and SO 2, reveals that a pair of Lewis acid site and basic surface oxygen atom is involved in the dehydrogenation reaction. The surface density of acid–base site pairs was measured using acetic acid as a probe molecule, allowing initial acetaldehyde formation turnover rates to be obtained. Comparison among various catalysts reveals no simple correlation between ethanol turnover rate and the percentage of either surface facet ((001) or (110)) of the STO nanocrystals. Instead, the reaction rate is found to increase with the strength of acid sites but reversely with the strength of base sites. The acid–base property is directly related to the surface composition as a result from different surface reconstruction behaviors of the shaped STO nanocrystals. Lastly, the finding in this work underscores the importance of characterizing the top surface compositions and sites properties when assessing the catalytic performance of shape-controlled complex oxides such as perovskites.« less

Control in the Rate-Determining Step Provides a Promising Strategy To Develop New Catalysts for CO2 Hydrogenation: A Local Pair Natural Orbital Coupled Cluster Theory Study.

PubMed

Mondal, Bhaskar; Neese, Frank; Ye, Shengfa

2015-08-03

The development of efficient catalysts with base metals for CO2 hydrogenation has always been a major thrust of interest. A series of experimental and theoretical work has revealed that the catalytic cycle typically involves two key steps, namely, base-promoted heterolytic H2 splitting and hydride transfer to CO2, either of which can be the rate-determining step (RDS) of the entire reaction. To explore the determining factor for the nature of RDS, we present herein a comparative mechanistic investigation on CO2 hydrogenation mediated by [M(H)(η(2)-H2)(PP3(Ph))](n+) (M = Fe(II), Ru(II), and Co(III); PP3(Ph) = tris(2-(diphenylphosphino)phenyl)phosphine) type complexes. In order to construct reliable free energy profiles, we used highly correlated wave function based ab initio methods of the coupled cluster type alongside the standard density functional theory. Our calculations demonstrate that the hydricity of the metal-hydride intermediate generated by H2 splitting dictates the nature of the RDS for the Fe(II) and Co(III) systems, while the RDS for the Ru(II) catalyst appears to be ambiguous. CO2 hydrogenation catalyzed by the Fe(II) complex that possesses moderate hydricity traverses an H2-splitting RDS, whereas the RDS for the high-hydricity Co(III) species is found to be the hydride transfer. Thus, our findings suggest that hydricity can be used as a practical guide in future catalyst design. Enhancing the electron-accepting ability of low-hydricity catalysts is likely to improve their catalytic performance, while increasing the electron-donating ability of high-hydricity complexes may speed up CO2 conversion. Moreover, we also established the active roles of base NEt3 in directing the heterolytic H2 splitting and assisting product release through the formation of an acid-base complex.

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.

Recognition of platinum-DNA adducts by HMGB1a.

PubMed

Ramachandran, Srinivas; Temple, Brenda; Alexandrova, Anastassia N; Chaney, Stephen G; Dokholyan, Nikolay V

2012-09-25

Cisplatin (CP) and oxaliplatin (OX), platinum-based drugs used widely in chemotherapy, form adducts on intrastrand guanines (5'GG) in genomic DNA. DNA damage recognition proteins, transcription factors, mismatch repair proteins, and DNA polymerases discriminate between CP- and OX-GG DNA adducts, which could partly account for differences in the efficacy, toxicity, and mutagenicity of CP and OX. In addition, differential recognition of CP- and OX-GG adducts is highly dependent on the sequence context of the Pt-GG adduct. In particular, DNA binding protein domain HMGB1a binds to CP-GG DNA adducts with up to 53-fold greater affinity than to OX-GG adducts in the TGGA sequence context but shows much smaller differences in binding in the AGGC or TGGT sequence contexts. Here, simulations of the HMGB1a-Pt-DNA complex in the three sequence contexts revealed a higher number of interface contacts for the CP-DNA complex in the TGGA sequence context than in the OX-DNA complex. However, the number of interface contacts was similar in the TGGT and AGGC sequence contexts. The higher number of interface contacts in the CP-TGGA sequence context corresponded to a larger roll of the Pt-GG base pair step. Furthermore, geometric analysis of stacking of phenylalanine 37 in HMGB1a (Phe37) with the platinated guanines revealed more favorable stacking modes correlated with a larger roll of the Pt-GG base pair step in the TGGA sequence context. These data are consistent with our previous molecular dynamics simulations showing that the CP-TGGA complex was able to sample larger roll angles than the OX-TGGA complex or either CP- or OX-DNA complexes in the AGGC or TGGT sequences. We infer that the high binding affinity of HMGB1a for CP-TGGA is due to the greater flexibility of CP-TGGA compared to OX-TGGA and other Pt-DNA adducts. This increased flexibility is reflected in the ability of CP-TGGA to sample larger roll angles, which allows for a higher number of interface contacts between the Pt-DNA adduct and HMGB1a.

Scattering of surface electrons by isolated steps versus periodic step arrays

NASA Astrophysics Data System (ADS)

Ortega, J. E.; Lobo-Checa, J.; Peschel, G.; Schirone, S.; Abd El-Fattah, Z. M.; Matena, M.; Schiller, F.; Borghetti, P.; Gambardella, P.; Mugarza, A.

2013-03-01

We investigate the scattering of electrons belonging to Shockley states of (111)-oriented noble metal surfaces using angle-resolved photoemission (ARPES) and scanning tunneling microscopy (STM). Both ARPES and STM indicate that monatomic steps on a noble metal surface may act either as strongly repulsive or highly transmissive barriers for surface electrons, depending on the coherence of the step lattice, and irrespectively of the average step spacing. By measuring curved crystal surfaces with terrace length ranging from 30 to 180 Å, we show that vicinal surfaces of Au and Ag with periodic step arrays exhibit a remarkable wave function coherence beyond 100 Å step spacings, well beyond the Fermi wavelength limit and independently of the projection of the bulk band gap on the vicinal plane. In contrast, the analysis of transmission resonances investigated by STM shows that a pair of isolated parallel steps defining a 58 Å wide terrace confines and decouples the surface state of the small terrace from that of the (111) surface. We conclude that the formation of laterally confined quantum well states in vicinal surfaces as opposed to propagating superlattice states depends on the loss of coherence driven by imperfection in the superlattice order.

[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.

Use of a twin dataset to identify AMD-related visual patterns controlled by genetic factors

NASA Astrophysics Data System (ADS)

Quellec, Gwénolé; Abràmoff, Michael D.; Russell, Stephen R.

2010-03-01

The mapping of genotype to the phenotype of age-related macular degeneration (AMD) is expected to improve the diagnosis and treatment of the disease in a near future. In this study, we focused on the first step to discover this mapping: we identified visual patterns related to AMD which seem to be controlled by genetic factors, without explicitly relating them to the genes. For this purpose, we used a dataset of eye fundus photographs from 74 twin pairs, either monozygotic twins, who have the same genotype, or dizygotic twins, whose genes responsible for AMD are less likely to be identical. If we are able to differentiate monozygotic twins from dizygotic twins, based on a given visual pattern, then this pattern is likely to be controlled by genetic factors. The main visible consequence of AMD is the apparition of drusen between the retinal pigment epithelium and Bruch's membrane. We developed two automated drusen detectors based on the wavelet transform: a shape-based detector for hard drusen, and a texture- and color- based detector for soft drusen. Forty visual features were evaluated at the location of the automatically detected drusen. These features characterize the texture, the shape, the color, the spatial distribution, or the amount of drusen. A distance measure between twin pairs was defined for each visual feature; a smaller distance should be measured between monozygotic twins for visual features controlled by genetic factors. The predictions of several visual features (75.7% accuracy) are comparable or better than the predictions of human experts.

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

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.

Structure/cleavage-based insights into helical perturbations at bulge sites within T. thermophilus Argonaute silencing complexes

PubMed Central

Sheng, Gang; Gogakos, Tasos; Wang, Jiuyu; Zhao, Hongtu; Serganov, Artem; Juranek, Stefan

2017-01-01

Abstract We have undertaken a systematic structural study of Thermus thermophilus Argonaute (TtAgo) ternary complexes containing single-base bulges positioned either within the seed segment of the guide or target strands and at the cleavage site. Our studies establish that single-base bulges 7T8, 5A6 and 4A5 on the guide strand are stacked-into the duplex, with conformational changes localized to the bulge site, thereby having minimal impact on the cleavage site. By contrast, single-base bulges 6’U7’ and 6’A7’ on the target strand are looped-out of the duplex, with the resulting conformational transitions shifting the cleavable phosphate by one step. We observe a stable alignment for the looped-out 6’N7’ bulge base, which stacks on the unpaired first base of the guide strand, with the looped-out alignment facilitated by weakened Watson–Crick and reversed non-canonical flanking pairs. These structural studies are complemented by cleavage assays that independently monitor the impact of bulges on TtAgo-mediated cleavage reaction. PMID:28911094

Writing Electron Dot Structures: Abstract of Issue 9905M

NASA Astrophysics Data System (ADS)

Magnell, Kenneth R.

1999-10-01

Writing Electron Dot Structures is a computer program for Mac OS that provides drill with feedback for students learning to write electron dot structures. While designed for students in the first year of college general chemistry it may also be used by high school chemistry students. A systematic method similar to that found in many general chemistry texts is employed:

1. determine the number of valence shell electrons,
2. select the central atom,
3. construct a skeleton,
4. add electrons to complete octets,
5. examine the structure for resonance forms.

Systematic assessment of benefits and risks: study protocol for a multi-criteria decision analysis using the Analytic Hierarchy Process for comparative effectiveness research

PubMed Central

Singh, Sonal

2013-01-01

Background: Regulatory decision-making involves assessment of risks and benefits of medications at the time of approval or when relevant safety concerns arise with a medication. The Analytic Hierarchy Process (AHP) facilitates decision-making in complex situations involving tradeoffs by considering risks and benefits of alternatives. The AHP allows a more structured method of synthesizing and understanding evidence in the context of importance assigned to outcomes. Our objective is to evaluate the use of an AHP in a simulated committee setting selecting oral medications for type 2 diabetes.  Methods: This study protocol describes the AHP in five sequential steps using a small group of diabetes experts representing various clinical disciplines. The first step will involve defining the goal of the decision and developing the AHP model. In the next step, we will collect information about how well alternatives are expected to fulfill the decision criteria. In the third step, we will compare the ability of the alternatives to fulfill the criteria and judge the importance of eight criteria relative to the decision goal of the optimal medication choice for type 2 diabetes. We will use pairwise comparisons to sequentially compare the pairs of alternative options regarding their ability to fulfill the criteria. In the fourth step, the scales created in the third step will be combined to create a summary score indicating how well the alternatives met the decision goal. The resulting scores will be expressed as percentages and will indicate the alternative medications' relative abilities to fulfill the decision goal. The fifth step will consist of sensitivity analyses to explore the effects of changing the estimates. We will also conduct a cognitive interview and process evaluation.  Discussion: Multi-criteria decision analysis using the AHP will aid, support and enhance the ability of decision makers to make evidence-based informed decisions consistent with their values and preferences. PMID:24555077

Systematic assessment of benefits and risks: study protocol for a multi-criteria decision analysis using the Analytic Hierarchy Process for comparative effectiveness research.

PubMed

Maruthur, Nisa M; Joy, Susan; Dolan, James; Segal, Jodi B; Shihab, Hasan M; Singh, Sonal

2013-01-01

Regulatory decision-making involves assessment of risks and benefits of medications at the time of approval or when relevant safety concerns arise with a medication. The Analytic Hierarchy Process (AHP) facilitates decision-making in complex situations involving tradeoffs by considering risks and benefits of alternatives. The AHP allows a more structured method of synthesizing and understanding evidence in the context of importance assigned to outcomes. Our objective is to evaluate the use of an AHP in a simulated committee setting selecting oral medications for type 2 diabetes.  This study protocol describes the AHP in five sequential steps using a small group of diabetes experts representing various clinical disciplines. The first step will involve defining the goal of the decision and developing the AHP model. In the next step, we will collect information about how well alternatives are expected to fulfill the decision criteria. In the third step, we will compare the ability of the alternatives to fulfill the criteria and judge the importance of eight criteria relative to the decision goal of the optimal medication choice for type 2 diabetes. We will use pairwise comparisons to sequentially compare the pairs of alternative options regarding their ability to fulfill the criteria. In the fourth step, the scales created in the third step will be combined to create a summary score indicating how well the alternatives met the decision goal. The resulting scores will be expressed as percentages and will indicate the alternative medications' relative abilities to fulfill the decision goal. The fifth step will consist of sensitivity analyses to explore the effects of changing the estimates. We will also conduct a cognitive interview and process evaluation.  Multi-criteria decision analysis using the AHP will aid, support and enhance the ability of decision makers to make evidence-based informed decisions consistent with their values and preferences.

Interacting steps with finite-range interactions: Analytical approximation and numerical results

NASA Astrophysics Data System (ADS)

Jaramillo, Diego Felipe; Téllez, Gabriel; González, Diego Luis; Einstein, T. L.

2013-05-01

We calculate an analytical expression for the terrace-width distribution P(s) for an interacting step system with nearest- and next-nearest-neighbor interactions. Our model is derived by mapping the step system onto a statistically equivalent one-dimensional system of classical particles. The validity of the model is tested with several numerical simulations and experimental results. We explore the effect of the range of interactions q on the functional form of the terrace-width distribution and pair correlation functions. For physically plausible interactions, we find modest changes when next-nearest neighbor interactions are included and generally negligible changes when more distant interactions are allowed. We discuss methods for extracting from simulated experimental data the characteristic scale-setting terms in assumed potential forms.

From Understanding the Development Landscape of the Canonical Fate-Switch Pair to Constructing a Dynamic Landscape for Two-Step Neural Differentiation

PubMed Central

2012-01-01

Abstract Recent progress in stem cell biology, notably cell fate conversion, calls for novel theoretical understanding for cell differentiation. The existing qualitative concept of Waddington’s “epigenetic landscape” has attracted particular attention because it captures subsequent fate decision points, thus manifesting the hierarchical (“tree-like”) nature of cell fate diversification. Here, we generalized a recent work and explored such a developmental landscape for a two-gene fate decision circuit by integrating the underlying probability landscapes with different parameters (corresponding to distinct developmental stages). The change of entropy production rate along the parameter changes indicates which parameter changes can represent a normal developmental process while other parameters’ change can not. The transdifferentiation paths over the landscape under certain conditions reveal the possibility of a direct and reversible phenotypic conversion. As the intensity of noise increases, we found that the landscape becomes flatter and the dominant paths more straight, implying the importance of biological noise processing mechanism in development and reprogramming. We further extended the landscape of the one-step fate decision to that for two-step decisions in central nervous system (CNS) differentiation. A minimal network and dynamic model for CNS differentiation was firstly constructed where two three-gene motifs are coupled. We then implemented the SDEs (Stochastic Differentiation Equations) simulation for the validity of the network and model. By integrating the two landscapes for the two switch gene pairs, we constructed the two-step development landscape for CNS differentiation. Our work provides new insights into cellular differentiation and important clues for better reprogramming strategies. PMID:23300518

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

Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange

PubMed Central

Hmelo, Laura R.; Borlee, Bradley R.; Almblad, Henrik; Love, Michelle E.; Randall, Trevor E.; Tseng, Boo Shan; Lin, Chuyang; Irie, Yasuhiko; Storek, Kelly M.; Yang, Jaeun Jane; Siehnel, Richard J.; Howell, P. Lynne; Singh, Pradeep K.; Tolker-Nielsen, Tim; Parsek, Matthew R.; Schweizer, Herbert P.; Harrison, Joe J.

2016-01-01

Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knockins, as well as single nucleotide insertions, deletions and substitutions in Pseudomonas aeruginosa. Unlike other approaches to allelic exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selection are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions of homology to the recipient chromosome, are synthesized in vitro and then cloned into allelic exchange vectors using standard procedures. These suicide vectors are then introduced into recipient cells by conjugation. Homologous recombination then results in antibiotic resistant single-crossover mutants in which the plasmid has integrated site-specifically into the chromosome. Subsequently, unmarked double-crossover mutants are isolated directly using sucrose-mediated counter-selection. This two-step process yields seamless mutations that are precise to a single base pair of DNA. The entire procedure requires ~2 weeks. PMID:26492139

The Connection Between Sediment Supply and Paired Strath Terrace Formation at Arroyo Seco, CA, USA.

NASA Astrophysics Data System (ADS)

Finnegan, N. J.

2015-12-01

Although wide, longitudinally traceable, paired strath terraces in river canyons are frequently argued to reflect periods of higher sediment supply, there is no consensus on how changes in sediment supply translate into dramatic changes in valley morphology. Here, quantitative analysis of LiDAR data is combined with field observations in Arroyo Seco, in the Santa Lucia Range of Central California, to develop a conceptual model for paired bedrock terrace formation and its connection to sediment supply. The most recently formed bedrock terrace in Arroyo Seco grades onto a prominent alluvial fan surface, suggesting that planation of straths in Arroyo Seco occurs as downstream alluvial fans aggrade. This aggradation apparently buffers Arroyo Seco's bedrock channel from base level fall on the Reliz Canyon Fault, which separates the bedrock and alluvial sections of the river. Notably, despite the fact that bedrock terraces grade smoothly onto alluvial fan surfaces, the deep aggradation of sediment downstream is not seen upstream in bedrock channel sections. Gravel on straths is typically only 0.5-1 m thick. Instead, excess gravel appears to be accommodated by the lateral planation of the wide strath itself. LiDAR evidence suggests that strath planation is associated with braiding, which is often triggered by increases in sediment supply. Given the high lateral mobility of braided streams and the extremely fractured (and hence easily detached) mudstone valley walls along Arroyo Seco, braiding provides a simple connection between sediment supply and lateral planation in Arroyo Seco. In Arroyo Seco, fan incision (under decreased sediment supply) should exhume a bedrock step whose height represents the accumulated fault slip during fan aggradation. The upstream propagation of this exhumed step as a knickpoint provides a simple mechanism to connect drops in sediment supply to rapid vertical incision, valley narrowing and strath terrace formation. Long profile data for Arroyo Seco shows clear evidence that the last two generations of strath terraces terminate upstream at knickpoints. OSL dating (Taylor and Sweetkind, 2014) constrains the formation of the two most recent strath terraces to the last ~ 35 kyr, implying at least two reductions in sediment supply relative to capacity during this interval.

Improved results of LINE-1 methylation analysis in formalin-fixed, paraffin-embedded tissues with the application of a heating step during the DNA extraction process.

PubMed

Wen, Xianyu; Jeong, Seorin; Kim, Younghoon; Bae, Jeong Mo; Cho, Nam Yun; Kim, Jung Ho; Kang, Gyeong Hoon

2017-01-01

Formalin-fixed, paraffin-embedded (FFPE) tissues are important resources for profiling DNA methylation changes and for studying a variety of diseases. However, formalin fixation introduces inter-strand crosslinking, which might cause incomplete bisulfite conversion of unmethylated cytosines, which might lead to falsely elevated measurements of methylation levels in pyrosequencing assays. Long interspersed nucleotide element-1 (LINE-1) is a major constituent of repetitive transposable DNA elements, and its methylation is referred to correlates with global DNA methylation. To identify whether formalin fixation might impact the measured values of methylation in LINE-1 repetitive elements and whether prolonged heat-induced denaturation of DNA might reduce the artificial increases in measured values caused by formalin fixation, we analyzed paired fresh-frozen (FF) and FFPE xenograft tissue samples for their methylation levels in LINE-1 using a pyrosequencing assay. To further confirm the effect of a heating step in the measurement of LINE-1 or single gene methylation levels, we analyzed FFPE tissue samples of gastric cancer and colorectal cancer for their methylation status in LINE-1 and eight single genes, respectively. Formalin fixation led to an increase in the measured values of LINE-1 methylation regardless of the duration of fixation. Prolonged heating of the DNA at 95 °C for 30 min before bisulfite conversion was found (1) to decrease the discrepancy in the measured values between the paired FF and FFPE tissue samples, (2) to decrease the standard deviation of the measured value of LINE-1 methylation levels in FFPE tissue samples of gastric cancer, and (3) to improve the performance in the measurement of single gene methylation levels in FFPE tissue samples of colorectal cancer. Formalin fixation leads to artificial increases in the measured values of LINE-1 methylation, and the application of prolonged heating of DNA samples decreases the discrepancy in the measured values of LINE-1 methylation between paired FF and FFPE tissue samples. The application of prolonged heating of DNA samples improves bisulfite conversion-based measurement of LINE-1 or single gene methylation levels in FFPE tissue samples.

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.

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

“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

Complete Hexose Isomer Identification with Mass Spectrometry

NASA Astrophysics Data System (ADS)

Nagy, Gabe; Pohl, Nicola L. B.

2015-04-01

The first analytical method is presented for the identification and absolute configuration determination of all 24 aldohexose and 2-ketohexose isomers, including the D and L enantiomers for allose, altrose, galactose, glucose, gulose, idose, mannose, talose, fructose, psicose, sorbose, and tagatose. Two unique fixed ligand kinetic method combinations were discovered to create significant enough energetic differences to achieve chiral discrimination among all 24 hexoses. Each of these 24 hexoses yields unique ratios of a specific pair of fragment ions that allows for simultaneous determination of identification and absolute configuration. This mass spectrometric-based methodology can be readily employed for accurate identification of any isolated monosaccharide from an unknown biological source. This work provides a key step towards the goal of complete de novo carbohydrate analysis.

Iterative Refinement of Transmission Map for Stereo Image Defogging Using a Dual Camera Sensor.

PubMed

Kim, Heegwang; Park, Jinho; Park, Hasil; Paik, Joonki

2017-12-09

Recently, the stereo imaging-based image enhancement approach has attracted increasing attention in the field of video analysis. This paper presents a dual camera-based stereo image defogging algorithm. Optical flow is first estimated from the stereo foggy image pair, and the initial disparity map is generated from the estimated optical flow. Next, an initial transmission map is generated using the initial disparity map. Atmospheric light is then estimated using the color line theory. The defogged result is finally reconstructed using the estimated transmission map and atmospheric light. The proposed method can refine the transmission map iteratively. Experimental results show that the proposed method can successfully remove fog without color distortion. The proposed method can be used as a pre-processing step for an outdoor video analysis system and a high-end smartphone with a dual camera system.

A comparison of older adults' subjective experiences with virtual and real environments during dynamic balance activities.

PubMed

Proffitt, Rachel; Lange, Belinda; Chen, Christina; Winstein, Carolee

2015-01-01

The purpose of this study was to explore the subjective experience of older adults interacting with both virtual and real environments. Thirty healthy older adults engaged with real and virtual tasks of similar motor demands: reaching to a target in standing and stepping stance. Immersive tendencies and absorption scales were administered before the session. Game engagement and experience questionnaires were completed after each task, followed by a semistructured interview at the end of the testing session. Data were analyzed respectively using paired t tests and grounded theory methodology. Participants preferred the virtual task over the real task. They also reported an increase in presence and absorption with the virtual task, describing an external focus of attention. Findings will be used to inform future development of appropriate game-based balance training applications that could be embedded in the home or community settings as part of evidence-based fall prevention programs.

Iterative Refinement of Transmission Map for Stereo Image Defogging Using a Dual Camera Sensor

PubMed Central

Park, Jinho; Park, Hasil

2017-01-01

Recently, the stereo imaging-based image enhancement approach has attracted increasing attention in the field of video analysis. This paper presents a dual camera-based stereo image defogging algorithm. Optical flow is first estimated from the stereo foggy image pair, and the initial disparity map is generated from the estimated optical flow. Next, an initial transmission map is generated using the initial disparity map. Atmospheric light is then estimated using the color line theory. The defogged result is finally reconstructed using the estimated transmission map and atmospheric light. The proposed method can refine the transmission map iteratively. Experimental results show that the proposed method can successfully remove fog without color distortion. The proposed method can be used as a pre-processing step for an outdoor video analysis system and a high-end smartphone with a dual camera system. PMID:29232826

Nanomaterials Based on DNA

PubMed Central

Seeman, Nadrian C.

2012-01-01

The combination of synthetic stable branched DNA and sticky ended cohesion has led to the development of structural DNA nanotechnology over the past 30 years. The basis of this enterprise is that it is possible to construct novel DNA-based materials by combining these features in a self-assembly protocol. Thus, simple branched molecules lead directly to the construction of polyhedra whose edges consist of double helical DNA, and whose vertices correspond to the branch points. Stiffer branched motifs can be used to produce self-assembled two-dimensional and three-dimensional periodic lattices of DNA (crystals). DNA has also been used to make a variety of nanomechanical devices, including molecules that change their shapes, and molecules that can walk along a DNA sidewalk. Devices have been incorporated into two-dimensional DNA arrangements; sequence-dependent devices are driven by increases in nucleotide pairing at each step in their machine cycles. PMID:20222824

An Enzyme-Catalyzed Multistep DNA Refolding Mechanism in Hairpin Telomere Formation

PubMed Central

Shi, Ke; Huang, Wai Mun; Aihara, Hideki

2013-01-01

Hairpin telomeres of bacterial linear chromosomes are generated by a DNA cutting–rejoining enzyme protelomerase. Protelomerase resolves a concatenated dimer of chromosomes as the last step of chromosome replication, converting a palindromic DNA sequence at the junctions between chromosomes into covalently closed hairpins. The mechanism by which protelomerase transforms a duplex DNA substrate into the hairpin telomeres remains largely unknown. We report here a series of crystal structures of the protelomerase TelA bound to DNA that represent distinct stages along the reaction pathway. The structures suggest that TelA converts a linear duplex substrate into hairpin turns via a transient strand-refolding intermediate that involves DNA-base flipping and wobble base-pairs. The extremely compact di-nucleotide hairpin structure of the product is fully stabilized by TelA prior to strand ligation, which drives the reaction to completion. The enzyme-catalyzed, multistep strand refolding is a novel mechanism in DNA rearrangement reactions. PMID:23382649

M&A For Lithography Of Sparse Arrays Of Sub-Micrometer Features

DOEpatents

Brueck, Steven R.J.; Chen, Xiaolan; Zaidi, Saleem; Devine, Daniel J.

1998-06-02

Methods and apparatuses are disclosed for the exposure of sparse hole and/or mesa arrays with line:space ratios of 1:3 or greater and sub-micrometer hole and/or mesa diameters in a layer of photosensitive material atop a layered material. Methods disclosed include: double exposure interferometric lithography pairs in which only those areas near the overlapping maxima of each single-period exposure pair receive a clearing exposure dose; double interferometric lithography exposure pairs with additional processing steps to transfer the array from a first single-period interferometric lithography exposure pair into an intermediate mask layer and a second single-period interferometric lithography exposure to further select a subset of the first array of holes; a double exposure of a single period interferometric lithography exposure pair to define a dense array of sub-micrometer holes and an optical lithography exposure in which only those holes near maxima of both exposures receive a clearing exposure dose; combination of a single-period interferometric exposure pair, processing to transfer resulting dense array of sub-micrometer holes into an intermediate etch mask, and an optical lithography exposure to select a subset of initial array to form a sparse array; combination of an optical exposure, transfer of exposure pattern into an intermediate mask layer, and a single-period interferometric lithography exposure pair; three-beam interferometric exposure pairs to form sparse arrays of sub-micrometer holes; five- and four-beam interferometric exposures to form a sparse array of sub-micrometer holes in a single exposure. Apparatuses disclosed include arrangements for the three-beam, five-beam and four-beam interferometric exposures.

Structural requirements for protein-catalyzed annealing of U4 and U6 RNAs during di-snRNP assembly

PubMed Central

Didychuk, Allison L.; Montemayor, Eric J.; Brow, David A.; Butcher, Samuel E.

2016-01-01

Base-pairing of U4 and U6 snRNAs during di-snRNP assembly requires large-scale remodeling of RNA structure that is chaperoned by the U6 snRNP protein Prp24. We investigated the mechanism of U4/U6 annealing in vitro using an assay that enables visualization of ribonucleoprotein complexes and faithfully recapitulates known in vivo determinants for the process. We find that annealing, but not U6 RNA binding, is highly dependent on the electropositive character of a 20 Å-wide groove on the surface of Prp24. During annealing, we observe the formation of a stable ternary complex between U4 and U6 RNAs and Prp24, indicating that displacement of Prp24 in vivo requires additional factors. Mutations that stabilize the U6 ‘telestem’ helix increase annealing rates by up to 15-fold, suggesting that telestem formation is rate-limiting for U4/U6 pairing. The Lsm2–8 complex, which binds adjacent to the telestem at the 3′ end of U6, provides a comparable rate enhancement. Collectively, these data identify domains of the U6 snRNP that are critical for one of the first steps in assembly of the megaDalton U4/U6.U5 tri-snRNP complex, and lead to a dynamic model for U4/U6 pairing that involves a striking degree of evolved cooperativity between protein and RNA. PMID:26673715

Activity and milk compositional changes following experimentally induced Streptococcus uberis bovine mastitis.

PubMed

Kester, H J; Sorter, D E; Hogan, J S

2015-02-01

Milk constituents and physical activity of cows experimentally infected with Streptococcus uberis mastitis were compared with those of uninfected cows. Twelve late-lactation Holsteins cows were paired based on milk production and parity. One cow in each pair was experimentally infected in the right front mammary gland with Strep. uberis. The remaining cow in each pair served as an uninfected control. Real-time analyses of milk constituents provided fat, protein, and lactose percentages at each milking. Pedometers were placed on the left front leg of all cows and activity was measured. Intramammary infections with Strep. uberis reduced milk yield in experimental cows by approximately 1.6kg/d in the first week after challenge compared with control cows. Lactose percentage in milk was reduced on d 3, 4, 5, and 6 after challenge in treatment cows compared with controls. Percentages of fat and protein in milk did not differ between infected and uninfected cows the week after infections were induced. Total steps per day were reduced and minutes resting per day were increased the week after experimental challenge in infected cows compared with control cows. The number of resting bouts did not differ between infected and uninfected cows. Changes in percentage of lactose in milk and animal activity caused by experimentally induced Strep. uberis mastitis were detected by the automated milk analyzer and pedometer systems. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Partial hyperbolicity and attracting regions in 3-dimensional manifolds

NASA Astrophysics Data System (ADS)

Potrie, Rafael

The need for reliable, fiber-based sources of entangled and paired photons has intensified in recent years because of potential uses in optical quantum communication and computing. In particular, indistinguishable photon sources are an inherent part of several quantum communication protocols and are needed to establish the viability of quantum communication networks. This thesis is centered around the development of such sources at telecommunication-band wavelengths. In this thesis, we describe experiments on entangled photon generation and the creation of quantum logic gates in the C-band, and on photon indistinguishability in the O-band. These experiments utilize the four-wave mixing process in fiber which occurs as a result of the Kerr nonlinearity, to create paired photons. To begin, we report the development of a source of 1550-nm polarization entangled photons in fiber. We then interface this source with a quantum Controlled-NOT gate, which is a universal quantum logic gate. We set experimental bounds on the process fidelity of the Controlled-NOT gate. Next, we report a demonstration of quantum interference between 1310-nm photons produced in independent sources. We demonstrate high quantum interference visibility, a signature of quantum indistinguishability, while using distinguishable pump photons. Together, these efforts constitute preliminary steps toward establishing the viability of fiber-based quantum communication, which will allow us to utilize existing infrastructure for implementing quantum communication protocols.

Analysis of Structural Flexibility of Damaged DNA Using Thiol-Tethered Oligonucleotide Duplexes

PubMed Central

Fujita, Masashi; Watanabe, Shun; Yoshizawa, Mariko; Yamamoto, Junpei; Iwai, Shigenori

2015-01-01

Bent structures are formed in DNA by the binding of small molecules or proteins. We developed a chemical method to detect bent DNA structures. Oligonucleotide duplexes in which two mercaptoalkyl groups were attached to the positions facing each other across the major groove were prepared. When the duplex contained the cisplatin adduct, which was proved to induce static helix bending, interstrand disulfide bond formation under an oxygen atmosphere was detected by HPLC analyses, but not in the non-adducted duplex, when the two thiol-tethered nucleosides were separated by six base pairs. When the insert was five and seven base pairs, the disulfide bond was formed and was not formed, respectively, regardless of the cisplatin adduct formation. The same reaction was observed in the duplexes containing an abasic site analog and the (6–4) photoproduct. Compared with the cisplatin case, the disulfide bond formation was slower in these duplexes, but the reaction rate was nearly independent of the linker length. These results indicate that dynamic structural changes of the abasic site- and (6–4) photoproduct-containing duplexes could be detected by our method. It is strongly suggested that the UV-damaged DNA-binding protein, which specifically binds these duplexes and functions at the first step of global-genome nucleotide excision repair, recognizes the easily bendable nature of damaged DNA. PMID:25679955

Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus

PubMed Central

Tuplin, A.; Evans, D. J.; Buckley, A.; Jones, I. M.; Gould, E. A.; Gritsun, T. S.

2011-01-01

We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents. PMID:21622960

Light focusing through a multiple scattering medium: ab initio computer simulation

NASA Astrophysics Data System (ADS)

Danko, Oleksandr; Danko, Volodymyr; Kovalenko, Andrey

2018-01-01

The present study considers ab initio computer simulation of the light focusing through a complex scattering medium. The focusing is performed by shaping the incident light beam in order to obtain a small focused spot on the opposite side of the scattering layer. MSTM software (Auburn University) is used to simulate the propagation of an arbitrary monochromatic Gaussian beam and obtain 2D distribution of the optical field in the selected plane of the investigated volume. Based on the set of incident and scattered fields, the pair of right and left eigen bases and corresponding singular values were calculated. The pair of right and left eigen modes together with the corresponding singular value constitute the transmittance eigen channel of the disordered media. Thus, the scattering process is described in three steps: 1) initial field decomposition in the right eigen basis; 2) scaling of decomposition coefficients for the corresponding singular values; 3) assembling of the scattered field as the composition of the weighted left eigen modes. Basis fields are represented as a linear combination of the original Gaussian beams and scattered fields. It was demonstrated that 60 independent control channels provide focusing the light into a spot with the minimal radius of approximately 0.4 μm at half maximum. The intensity enhancement in the focal plane was equal to 68 that coincided with theoretical prediction.

Accurate indel prediction using paired-end short reads

PubMed Central

2013-01-01

Background One of the major open challenges in next generation sequencing (NGS) is the accurate identification of structural variants such as insertions and deletions (indels). Current methods for indel calling assign scores to different types of evidence or counter-evidence for the presence of an indel, such as the number of split read alignments spanning the boundaries of a deletion candidate or reads that map within a putative deletion. Candidates with a score above a manually defined threshold are then predicted to be true indels. As a consequence, structural variants detected in this manner contain many false positives. Results Here, we present a machine learning based method which is able to discover and distinguish true from false indel candidates in order to reduce the false positive rate. Our method identifies indel candidates using a discriminative classifier based on features of split read alignment profiles and trained on true and false indel candidates that were validated by Sanger sequencing. We demonstrate the usefulness of our method with paired-end Illumina reads from 80 genomes of the first phase of the 1001 Genomes Project ( http://www.1001genomes.org) in Arabidopsis thaliana. Conclusion In this work we show that indel classification is a necessary step to reduce the number of false positive candidates. We demonstrate that missing classification may lead to spurious biological interpretations. The software is available at: http://agkb.is.tuebingen.mpg.de/Forschung/SV-M/. PMID:23442375

Coupled dictionary learning for joint MR image restoration and segmentation

NASA Astrophysics Data System (ADS)

Yang, Xuesong; Fan, Yong

2018-03-01

To achieve better segmentation of MR images, image restoration is typically used as a preprocessing step, especially for low-quality MR images. Recent studies have demonstrated that dictionary learning methods could achieve promising performance for both image restoration and image segmentation. These methods typically learn paired dictionaries of image patches from different sources and use a common sparse representation to characterize paired image patches, such as low-quality image patches and their corresponding high quality counterparts for the image restoration, and image patches and their corresponding segmentation labels for the image segmentation. Since learning these dictionaries jointly in a unified framework may improve the image restoration and segmentation simultaneously, we propose a coupled dictionary learning method to concurrently learn dictionaries for joint image restoration and image segmentation based on sparse representations in a multi-atlas image segmentation framework. Particularly, three dictionaries, including a dictionary of low quality image patches, a dictionary of high quality image patches, and a dictionary of segmentation label patches, are learned in a unified framework so that the learned dictionaries of image restoration and segmentation can benefit each other. Our method has been evaluated for segmenting the hippocampus in MR T1 images collected with scanners of different magnetic field strengths. The experimental results have demonstrated that our method achieved better image restoration and segmentation performance than state of the art dictionary learning and sparse representation based image restoration and image segmentation methods.

A theoretical thermochemical study of solute-solvent dielectric effects in the displacement of codon-anticodon base pairs

NASA Astrophysics Data System (ADS)

Monajjemi, M.; Razavian, M. H.; Mollaamin, F.; Naderi, F.; Honarparvar, B.

2008-12-01

Quantum-chemical solvent effect theories describe the electronic structure of a molecular subsystem embedded in a solvent or other molecular environment. The solvation of biomolecules is important in molecular biology, since numerous processes involve proteins interacting in changing solvent-solute systems. In this theoretical study, we focus on mRNA-tRNA base pairs as a fundamental step in protein synthesis influenced by hydrogen bonding between two antiparallel trinucleotides, namely, the mRNA codon and tRNA anticodon. We use the mean reaction field theories, which describe electrostatic and polarization interactions between solute and solvent in the AAA, UUU, AAG, and UUC triplex sequences optimized in various solvent media such as water, dimethylsulfoxide, methanol, ethanol, and cyclopean using the self-consistent reaction field model. This process depends on either the reaction potential function of the solvent or charge transfer operators that appear in solute-solvent interaction. Because of codon and anticodon biological criteria, we performed nonempirical quantum-mechanical calculations at the BLYP and B3LYP/3-21G, 6-31G, and 6-31G* levels of theory in the gas phase and five solvents at three temperatures. Finally, to obtain more information, we calculated thermochemical parameters to find that the dielectric constant of solvents plays an important role in the displacement of amino acid sequences on codon-anticodon residues in proteins, which can cause some mutations in humans.

Critical cladding radius for hybrid cladding modes

NASA Astrophysics Data System (ADS)

Guyard, Romain; Leduc, Dominique; Lupi, Cyril; Lecieux, Yann

2018-05-01

In this article we explore some properties of the cladding modes guided by a step-index optical fiber. We show that the hybrid modes can be grouped by pairs and that it exists a critical cladding radius for which the modes of a pair share the same electromagnetic structure. We propose a robust method to determine the critical cladding radius and use it to perform a statistical study on the influence of the characteristics of the fiber on the critical cladding radius. Finally we show the importance of the critical cladding radius with respect to the coupling coefficient between the core mode and the cladding modes inside a long period grating.

Distillation of multipartite entanglement by complementary stabilizer measurements.

PubMed

Miyake, Akimasa; Briegel, Hans J

2005-11-25

We propose a scheme of multipartite entanglement distillation driven by a complementary pair of stabilizer measurements to distill directly a wider range of states beyond the stabilizer code states (such as the Greenberger-Horne-Zeilinger states). We make our idea explicit by constructing a recurrence protocol for the 3-qubit state [formula: see text]. Noisy states resulting from typical decoherence can be directly purified in a few steps, if their initial fidelity is larger than a threshold. For general input mixed states, we observe distillations to hierarchical fixed points, i.e., not only to the state but also to the 2-qubit Bell pair, depending on their initial entanglement.

Equalizer tap length requirement for mode group delay-compensated fiber link with weakly random mode coupling.

PubMed

Bai, Neng; Li, Guifang

2014-02-24

The equalizer tap length requirement is investigated analytically and numerically for differential modal group delay (DMGD) compensated fiber link with weakly random mode coupling. Each span of the DMGD compensated link comprises multiple pairs of fibers which have opposite signs of DMGD. The result reveals that under weak random mode coupling, the required tap length of the equalizer is proportional to modal group delay of a single DMGD compensated pair, instead of the total modal group delay (MGD) of the entire link. By using small DMGD compensation step sizes, the required tap length (RTL) can be potentially reduced by 2 orders of magnitude.

Two-step forecast of geomagnetic storm using coronal mass ejection and solar wind condition

PubMed Central

Kim, R-S; Moon, Y-J; Gopalswamy, N; Park, Y-D; Kim, Y-H

2014-01-01

To forecast geomagnetic storms, we had examined initially observed parameters of coronal mass ejections (CMEs) and introduced an empirical storm forecast model in a previous study. Now we suggest a two-step forecast considering not only CME parameters observed in the solar vicinity but also solar wind conditions near Earth to improve the forecast capability. We consider the empirical solar wind criteria derived in this study (Bz ≤ −5 nT or Ey ≥ 3 mV/m for t≥ 2 h for moderate storms with minimum Dst less than −50 nT) and a Dst model developed by Temerin and Li (2002, 2006) (TL model). Using 55 CME-Dst pairs during 1997 to 2003, our solar wind criteria produce slightly better forecasts for 31 storm events (90%) than the forecasts based on the TL model (87%). However, the latter produces better forecasts for 24 nonstorm events (88%), while the former correctly forecasts only 71% of them. We then performed the two-step forecast. The results are as follows: (i) for 15 events that are incorrectly forecasted using CME parameters, 12 cases (80%) can be properly predicted based on solar wind conditions; (ii) if we forecast a storm when both CME and solar wind conditions are satisfied (∩), the critical success index becomes higher than that from the forecast using CME parameters alone, however, only 25 storm events (81%) are correctly forecasted; and (iii) if we forecast a storm when either set of these conditions is satisfied (∪), all geomagnetic storms are correctly forecasted. PMID:26213515

Transcriptome Profiling of Khat (Catha edulis) and Ephedra sinica Reveals Gene Candidates Potentially Involved in Amphetamine-Type Alkaloid Biosynthesis

PubMed Central

Groves, Ryan A.; Hagel, Jillian M.; Zhang, Ye; Kilpatrick, Korey; Levy, Asaf; Marsolais, Frédéric; Lewinsohn, Efraim; Sensen, Christoph W.; Facchini, Peter J.

2015-01-01

Amphetamine analogues are produced by plants in the genus Ephedra and by khat (Catha edulis), and include the widely used decongestants and appetite suppressants (1S,2S)-pseudoephedrine and (1R,2S)-ephedrine. The production of these metabolites, which derive from L-phenylalanine, involves a multi-step pathway partially mapped out at the biochemical level using knowledge of benzoic acid metabolism established in other plants, and direct evidence using khat and Ephedra species as model systems. Despite the commercial importance of amphetamine-type alkaloids, only a single step in their biosynthesis has been elucidated at the molecular level. We have employed Illumina next-generation sequencing technology, paired with Trinity and Velvet-Oases assembly platforms, to establish data-mining frameworks for Ephedra sinica and khat plants. Sequence libraries representing a combined 200,000 unigenes were subjected to an annotation pipeline involving direct searches against public databases. Annotations included the assignment of Gene Ontology (GO) terms used to allocate unigenes to functional categories. As part of our functional genomics program aimed at novel gene discovery, the databases were mined for enzyme candidates putatively involved in alkaloid biosynthesis. Queries used for mining included enzymes with established roles in benzoic acid metabolism, as well as enzymes catalyzing reactions similar to those predicted for amphetamine alkaloid metabolism. Gene candidates were evaluated based on phylogenetic relationships, FPKM-based expression data, and mechanistic considerations. Establishment of expansive sequence resources is a critical step toward pathway characterization, a goal with both academic and industrial implications. PMID:25806807

Two-step forecast of geomagnetic storm using coronal mass ejection and solar wind condition.

PubMed

Kim, R-S; Moon, Y-J; Gopalswamy, N; Park, Y-D; Kim, Y-H

2014-04-01

To forecast geomagnetic storms, we had examined initially observed parameters of coronal mass ejections (CMEs) and introduced an empirical storm forecast model in a previous study. Now we suggest a two-step forecast considering not only CME parameters observed in the solar vicinity but also solar wind conditions near Earth to improve the forecast capability. We consider the empirical solar wind criteria derived in this study ( B z  ≤ -5 nT or E y  ≥ 3 mV/m for t ≥ 2 h for moderate storms with minimum Dst less than -50 nT) and a Dst model developed by Temerin and Li (2002, 2006) (TL model). Using 55 CME- Dst pairs during 1997 to 2003, our solar wind criteria produce slightly better forecasts for 31 storm events (90%) than the forecasts based on the TL model (87%). However, the latter produces better forecasts for 24 nonstorm events (88%), while the former correctly forecasts only 71% of them. We then performed the two-step forecast. The results are as follows: (i) for 15 events that are incorrectly forecasted using CME parameters, 12 cases (80%) can be properly predicted based on solar wind conditions; (ii) if we forecast a storm when both CME and solar wind conditions are satisfied (∩), the critical success index becomes higher than that from the forecast using CME parameters alone, however, only 25 storm events (81%) are correctly forecasted; and (iii) if we forecast a storm when either set of these conditions is satisfied (∪), all geomagnetic storms are correctly forecasted.

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.

Functional connectivity analysis in resting state fMRI with echo-state networks and non-metric clustering for network structure recovery

NASA Astrophysics Data System (ADS)

Wismüller, Axel; DSouza, Adora M.; Abidin, Anas Z.; Wang, Xixi; Hobbs, Susan K.; Nagarajan, Mahesh B.

2015-03-01

Echo state networks (ESN) are recurrent neural networks where the hidden layer is replaced with a fixed reservoir of neurons. Unlike feed-forward networks, neuron training in ESN is restricted to the output neurons alone thereby providing a computational advantage. We demonstrate the use of such ESNs in our mutual connectivity analysis (MCA) framework for recovering the primary motor cortex network associated with hand movement from resting state functional MRI (fMRI) data. Such a framework consists of two steps - (1) defining a pair-wise affinity matrix between different pixel time series within the brain to characterize network activity and (2) recovering network components from the affinity matrix with non-metric clustering. Here, ESNs are used to evaluate pair-wise cross-estimation performance between pixel time series to create the affinity matrix, which is subsequently subject to non-metric clustering with the Louvain method. For comparison, the ground truth of the motor cortex network structure is established with a task-based fMRI sequence. Overlap between the primary motor cortex network recovered with our model free MCA approach and the ground truth was measured with the Dice coefficient. Our results show that network recovery with our proposed MCA approach is in close agreement with the ground truth. Such network recovery is achieved without requiring low-pass filtering of the time series ensembles prior to analysis, an fMRI preprocessing step that has courted controversy in recent years. Thus, we conclude our MCA framework can allow recovery and visualization of the underlying functionally connected networks in the brain on resting state fMRI.

A one-step duplex rRT-PCR assay for the simultaneous detection of duck hepatitis A virus genotypes 1 and 3.

PubMed

Hu, Qin; Zhu, Dekang; Ma, Guangpeng; Cheng, Anchun; Wang, Mingshu; Chen, Shun; Jia, Renyong; Liu, Mafeng; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue

2016-10-01

Duck hepatitis A virus (DHAV) is a highly infectious pathogen that causes significant bleeding lesions in the viscera of ducklings less than 3 weeks old. There are three serotypes of DHAV: serotype 1 (DHAV-1), serotype 2 (DHAV-2) and serotype 3 (DHAV-3). These serotypes have no cross-antigenicity with each other. To establish an rRT-PCR assay for the rapid detection of a mixed infection of DHAV-1 and DHAV-3, two pairs of primers and a pair of matching TaqMan probes were designed based on conserved regions of DHAV-1 VP0 and DHAV-3 VP3. Finally, we established a one-step duplex rRT-PCR assay with high specificity and sensitivity for the simultaneous detection of DHAV-1 and DHAV-3. This method showed no cross-antigenicity with the other pathogens tested, including duck plague virus, Muscovy duck parvovirus, Riemerella anatipestifer, and pathogenic E. coli from ducks. Sensitivity tests identified the minimum detection limits of this method as 98 (DHAV-1) and 10 (DHAV-3) copies/reaction. To validate the method, thirty-eight clinical samples and thirty artificially infected samples collected from dead duck embryos were studied. Thirty-seven samples were positive for DHAV-1, seventeen samples were positive for DHAV-3, and fourteen samples were positive for a mixed infection using the duplex rRT-PCR method. The method established in this study is specific, sensitive, convenient and timesaving and is a powerful tool for detecting DHAV-1, DHAV-3, and their mixed infection and for conducting surveys of pandemic virus strains. Copyright © 2016. Published by Elsevier B.V.

Opera: reconstructing optimal genomic scaffolds with high-throughput paired-end sequences.

PubMed

Gao, Song; Sung, Wing-Kin; Nagarajan, Niranjan

2011-11-01

Scaffolding, the problem of ordering and orienting contigs, typically using paired-end reads, is a crucial step in the assembly of high-quality draft genomes. Even as sequencing technologies and mate-pair protocols have improved significantly, scaffolding programs still rely on heuristics, with no guarantees on the quality of the solution. In this work, we explored the feasibility of an exact solution for scaffolding and present a first tractable solution for this problem (Opera). We also describe a graph contraction procedure that allows the solution to scale to large scaffolding problems and demonstrate this by scaffolding several large real and synthetic datasets. In comparisons with existing scaffolders, Opera simultaneously produced longer and more accurate scaffolds demonstrating the utility of an exact approach. Opera also incorporates an exact quadratic programming formulation to precisely compute gap sizes (Availability: http://sourceforge.net/projects/operasf/ ).

Opera: Reconstructing Optimal Genomic Scaffolds with High-Throughput Paired-End Sequences

PubMed Central

Gao, Song; Sung, Wing-Kin

2011-01-01

Abstract Scaffolding, the problem of ordering and orienting contigs, typically using paired-end reads, is a crucial step in the assembly of high-quality draft genomes. Even as sequencing technologies and mate-pair protocols have improved significantly, scaffolding programs still rely on heuristics, with no guarantees on the quality of the solution. In this work, we explored the feasibility of an exact solution for scaffolding and present a first tractable solution for this problem (Opera). We also describe a graph contraction procedure that allows the solution to scale to large scaffolding problems and demonstrate this by scaffolding several large real and synthetic datasets. In comparisons with existing scaffolders, Opera simultaneously produced longer and more accurate scaffolds demonstrating the utility of an exact approach. Opera also incorporates an exact quadratic programming formulation to precisely compute gap sizes (Availability: http://sourceforge.net/projects/operasf/). PMID:21929371

Entropy of finite random binary sequences with weak long-range correlations.

PubMed

Melnik, S S; Usatenko, O V

2014-11-01

We study the N-step binary stationary ergodic Markov chain and analyze its differential entropy. Supposing that the correlations are weak we express the conditional probability function of the chain through the pair correlation function and represent the entropy as a functional of the pair correlator. Since the model uses the two-point correlators instead of the block probability, it makes it possible to calculate the entropy of strings at much longer distances than using standard methods. A fluctuation contribution to the entropy due to finiteness of random chains is examined. This contribution can be of the same order as its regular part even at the relatively short lengths of subsequences. A self-similar structure of entropy with respect to the decimation transformations is revealed for some specific forms of the pair correlation function. Application of the theory to the DNA sequence of the R3 chromosome of Drosophila melanogaster is presented.

Nanocrystal waveguide (NOW) laser

DOEpatents

Simpson, John T.; Simpson, Marcus L.; Withrow, Stephen P.; White, Clark W.; Jaiswal, Supriya L.

2005-02-08

A solid state laser includes an optical waveguide and a laser cavity including at least one subwavelength mirror disposed in or on the optical waveguide. A plurality of photoluminescent nanocrystals are disposed in the laser cavity. The reflective subwavelength mirror can be a pair of subwavelength resonant gratings (SWG), a pair of photonic crystal structures (PC), or a distributed feedback structure. In the case of a pair of mirrors, a PC which is substantially transmissive at an operating wavelength of the laser can be disposed in the laser cavity between the subwavelength mirrors to improve the mode structure, coherence and overall efficiency of the laser. A method for forming a solid state laser includes the steps of providing an optical waveguide, creating a laser cavity in the optical waveguide by disposing at least one subwavelength mirror on or in the waveguide, and positioning a plurality of photoluminescent nanocrystals in the laser cavity.

Entropy of finite random binary sequences with weak long-range correlations

NASA Astrophysics Data System (ADS)

Melnik, S. S.; Usatenko, O. V.

2014-11-01

We study the N -step binary stationary ergodic Markov chain and analyze its differential entropy. Supposing that the correlations are weak we express the conditional probability function of the chain through the pair correlation function and represent the entropy as a functional of the pair correlator. Since the model uses the two-point correlators instead of the block probability, it makes it possible to calculate the entropy of strings at much longer distances than using standard methods. A fluctuation contribution to the entropy due to finiteness of random chains is examined. This contribution can be of the same order as its regular part even at the relatively short lengths of subsequences. A self-similar structure of entropy with respect to the decimation transformations is revealed for some specific forms of the pair correlation function. Application of the theory to the DNA sequence of the R3 chromosome of Drosophila melanogaster is presented.

A novel in situ device based on a bionic piezoelectric actuator to study tensile and fatigue properties of bulk materials.

PubMed

Wang, Shupeng; Zhang, Zhihui; Ren, Luquan; Zhao, Hongwei; Liang, Yunhong; Zhu, Bing

2014-06-01

In this work, a miniaturized device based on a bionic piezoelectric actuator was developed to investigate the static tensile and dynamic fatigue properties of bulk materials. The device mainly consists of a bionic stepping piezoelectric actuator based on wedge block clamping, a pair of grippers, and a set of precise signal test system. Tensile and fatigue examinations share a set of driving system and a set of signal test system. In situ tensile and fatigue examinations under scanning electron microscope or metallographic microscope could be carried out due to the miniaturized dimensions of the device. The structure and working principle of the device were discussed and the effects of output difference between two piezoelectric stacks on the device were theoretically analyzed. The tensile and fatigue examinations on ordinary copper were carried out using this device and its feasibility was verified through the comparison tests with a commercial tensile examination instrument.

A novel in situ device based on a bionic piezoelectric actuator to study tensile and fatigue properties of bulk materials

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

Wang, Shupeng; Zhang, Zhihui, E-mail: zhzh@jlu.edu.cn; Ren, Luquan

2014-06-15

In this work, a miniaturized device based on a bionic piezoelectric actuator was developed to investigate the static tensile and dynamic fatigue properties of bulk materials. The device mainly consists of a bionic stepping piezoelectric actuator based on wedge block clamping, a pair of grippers, and a set of precise signal test system. Tensile and fatigue examinations share a set of driving system and a set of signal test system. In situ tensile and fatigue examinations under scanning electron microscope or metallographic microscope could be carried out due to the miniaturized dimensions of the device. The structure and working principlemore » of the device were discussed and the effects of output difference between two piezoelectric stacks on the device were theoretically analyzed. The tensile and fatigue examinations on ordinary copper were carried out using this device and its feasibility was verified through the comparison tests with a commercial tensile examination instrument.« less

a New ER Fluid Based Haptic Actuator System for Virtual Reality

NASA Astrophysics Data System (ADS)

Böse, H.; Baumann, M.; Monkman, G. J.; Egersdörfer, S.; Tunayar, A.; Freimuth, H.; Ermert, H.; Khaled, W.

The concept and some steps in the development of a new actuator system which enables the haptic perception of mechanically inhomogeneous virtual objects are introduced. The system consists of a two-dimensional planar array of actuator elements containing an electrorheological (ER) fluid. When a user presses his fingers onto the surface of the actuator array, he perceives locally variable resistance forces generated by vertical pistons which slide in the ER fluid through the gaps between electrode pairs. The voltage in each actuator element can be individually controlled by a novel sophisticated switching technology based on optoelectric gallium arsenide elements. The haptic information which is represented at the actuator array can be transferred from a corresponding sensor system based on ultrasonic elastography. The combined sensor-actuator system may serve as a technology platform for various applications in virtual reality, like telemedicine where the information on the consistency of tissue of a real patient is detected by the sensor part and recorded by the actuator part at a remote location.

Waste-based alternative adsorbents for the remediation of pharmaceutical contaminated waters: Has a step forward already been taken?

PubMed

Silva, Carla Patrícia; Jaria, Guilaine; Otero, Marta; Esteves, Valdemar I; Calisto, Vânia

2018-02-01

When adsorption is considered for water treatment, commercial activated carbon is usually the chosen adsorbent for the removal of pollutants from the aqueous phase, particularly pharmaceuticals. In order to decrease costs and save natural resources, attempts have been made to use wastes as raw materials for the production of alternative carbon adsorbents. This approach intends to increase efficiency, cost-effectiveness, and also to propose an alternative and sustainable way for the valorization/management of residues. This review aims to provide an overview on waste-based adsorbents used on pharmaceuticals' adsorption. Experimental facts related to the adsorption behaviour of each adsorbent/pharmaceutical pair and some key factors were addressed. Also, research gaps that subsist in this research area, as well as future needs, were identified. Simultaneously, this review aims to clarify the current status of the research on pharmaceuticals' adsorption by waste-based adsorbents in order to recognize if the right direction is being taken. Copyright © 2017 Elsevier Ltd. All rights reserved.

The trans-activator RNF12 and cis-acting elements effectuate X chromosome inactivation independent of X-pairing.

PubMed

Barakat, Tahsin Stefan; Loos, Friedemann; van Staveren, Selma; Myronova, Elvira; Ghazvini, Mehrnaz; Grootegoed, J Anton; Gribnau, Joost

2014-03-20

X chromosome inactivation (XCI) in female placental mammals is a vital mechanism for dosage compensation between X-linked and autosomal genes. XCI starts with activation of Xist and silencing of the negative regulator Tsix, followed by cis spreading of Xist RNA over the future inactive X chromosome (Xi). Here, we show that XCI does not require physical contact between the two X chromosomes (X-pairing) but is regulated by trans-acting diffusible factors. We found that the X-encoded trans-acting and dose-dependent XCI-activator RNF12 acts in concert with the cis-regulatory region containing Jpx, Ftx, and Xpr to activate Xist and to overcome repression by Tsix. RNF12 acts at two subsequent steps; two active copies of Rnf12 drive initiation of XCI, and one copy needs to remain active to maintain XCI toward establishment of the Xi. This two-step mechanism ensures that XCI is very robust and fine-tuned, preventing XCI of both X chromosomes. Copyright © 2014 Elsevier Inc. All rights reserved.