WorldWideScience

Sample records for basic oligonucleotide alignment

  1. Short Oligonucleotides Aligned in Stretched Humid Matrix: Secondary DNA Structure in Poly(vinyl alcohol) Environment

    KAUST Repository

    Hanczyc, Piotr

    2012-04-24

    We report that short, synthetic, double- as well as single-stranded DNA can be aligned in stretched humid poly(vinyl alcohol) (PVA) matrix, and the secondary structure (nucleobase orientation) can be characterized with linear dichroism (LD) spectroscopy. Oligonucleotides of lengths varying between 10 (3.4 nm) and 60 bases (20.4 nm) were investigated with respect to structural properties in the gel-like polymer environment. The DNA conformation as a function of relative humidity reveals a strong dependence of helical structure of DNA on PVA hydration level, results of relevance for nanotechnical studies of DNA-based supramolecular systems. Also, the PVA gel could provide possibilities to test models for nucleic acid interactions and distribution in cell contexts, including structural stability of genetic material in the cell and PVA-packaging for gene delivery. A method by which duplex oligonucleotides, with sequences designed to provide specific binding sites, become amenable to polarized-light spectroscopy opens up new possibilities for studying structure in DNA complexes with small adduct molecules as well as proteins. © 2012 American Chemical Society.

  2. Clay catalysis of oligonucleotide formation: kinetics of the reaction of the 5'-phosphorimidazolides of nucleotides with the non-basic heterocycles uracil and hypoxanthine

    Science.gov (United States)

    Kawamura, K.; Ferris, J. P.

    1999-01-01

    The montmorillonite clay catalyzed condensation of activated monocleotides to oligomers of RNA is a possible first step in the formation of the proposed RNA world. The rate constants for the condensation of the phosphorimidazolide of adenosine were measured previously and these studies have been extended to the phosphorimidazolides of inosine and uridine in the present work to determine of substitution of neutral heterocycles for the basic adenine ring changes the reaction rate or regioselectivity. The oligomerization reactions of the 5'-phosphoromidazolides of uridine (ImpU) and inosine (ImpI) on montmorillonite yield oligo(U)s and oligo(I)s as long as heptamers. The rate constants for oligonucleotide formation were determined by measuring the rates of formation of the oligomers by HPLC. Both the apparent rate constants in the reaction mixture and the rate constants on the clay surface were calculated using the partition coefficients of the oligomers between the aqueous and clay phases. The rate constants for trimer formation are much greater than those dimer synthesis but there was little difference in the rate constants for the formation of trimers and higher oligomers. The overall rates of oligomerization of the phosphorimidazolides of purine and pyrimidine nucleosides in the presence of montmorillonite clay are the same suggesting that RNA formed on the primitive Earth could have contained a variety of heterocyclic bases. The rate constants for oligomerization of pyrimidine nucleotides on the clay surface are significantly higher than those of purine nucleotides since the pyrimidine nucleotides bind less strongly to the clay than do the purine nucleotides. The differences in the binding is probably due to Van der Waals interactions between the purine bases and the clay surface. Differences in the basicity of the heterocyclic ring in the nucleotide have little effect on the oligomerization process.

  3. Windows .NET Network Distributed Basic Local Alignment Search Toolkit (W.ND-BLAST

    Directory of Open Access Journals (Sweden)

    Oliver Melvin J

    2005-04-01

    Full Text Available Abstract Background BLAST is one of the most common and useful tools for Genetic Research. This paper describes a software application we have termed Windows .NET Distributed Basic Local Alignment Search Toolkit (W.ND-BLAST, which enhances the BLAST utility by improving usability, fault recovery, and scalability in a Windows desktop environment. Our goal was to develop an easy to use, fault tolerant, high-throughput BLAST solution that incorporates a comprehensive BLAST result viewer with curation and annotation functionality. Results W.ND-BLAST is a comprehensive Windows-based software toolkit that targets researchers, including those with minimal computer skills, and provides the ability increase the performance of BLAST by distributing BLAST queries to any number of Windows based machines across local area networks (LAN. W.ND-BLAST provides intuitive Graphic User Interfaces (GUI for BLAST database creation, BLAST execution, BLAST output evaluation and BLAST result exportation. This software also provides several layers of fault tolerance and fault recovery to prevent loss of data if nodes or master machines fail. This paper lays out the functionality of W.ND-BLAST. W.ND-BLAST displays close to 100% performance efficiency when distributing tasks to 12 remote computers of the same performance class. A high throughput BLAST job which took 662.68 minutes (11 hours on one average machine was completed in 44.97 minutes when distributed to 17 nodes, which included lower performance class machines. Finally, there is a comprehensive high-throughput BLAST Output Viewer (BOV and Annotation Engine components, which provides comprehensive exportation of BLAST hits to text files, annotated fasta files, tables, or association files. Conclusion W.ND-BLAST provides an interactive tool that allows scientists to easily utilizing their available computing resources for high throughput and comprehensive sequence analyses. The install package for W.ND-BLAST is

  4. Cytokines and therapeutic oligonucleotides.

    Science.gov (United States)

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  5. Aligning CASAS Competencies and Assessments to Basic Skills Content Standards. Second Edition

    Science.gov (United States)

    CASAS - Comprehensive Adult Student Assessment Systems (NJ1), 2009

    2009-01-01

    Since its inception, the Comprehensive Adult Student Assessment System (CASAS) has focused on teaching and assessing basic skills in contexts that are relevant and important to adult learners. CASAS has developed and continues to refine a highly formalized hierarchy of competencies, the application of basic skills that adults need to be fully…

  6. HBLAST: Parallelised sequence similarity--A Hadoop MapReducable basic local alignment search tool.

    Science.gov (United States)

    O'Driscoll, Aisling; Belogrudov, Vladislav; Carroll, John; Kropp, Kai; Walsh, Paul; Ghazal, Peter; Sleator, Roy D

    2015-04-01

    The recent exponential growth of genomic databases has resulted in the common task of sequence alignment becoming one of the major bottlenecks in the field of computational biology. It is typical for these large datasets and complex computations to require cost prohibitive High Performance Computing (HPC) to function. As such, parallelised solutions have been proposed but many exhibit scalability limitations and are incapable of effectively processing "Big Data" - the name attributed to datasets that are extremely large, complex and require rapid processing. The Hadoop framework, comprised of distributed storage and a parallelised programming framework known as MapReduce, is specifically designed to work with such datasets but it is not trivial to efficiently redesign and implement bioinformatics algorithms according to this paradigm. The parallelisation strategy of "divide and conquer" for alignment algorithms can be applied to both data sets and input query sequences. However, scalability is still an issue due to memory constraints or large databases, with very large database segmentation leading to additional performance decline. Herein, we present Hadoop Blast (HBlast), a parallelised BLAST algorithm that proposes a flexible method to partition both databases and input query sequences using "virtual partitioning". HBlast presents improved scalability over existing solutions and well balanced computational work load while keeping database segmentation and recompilation to a minimum. Enhanced BLAST search performance on cheap memory constrained hardware has significant implications for in field clinical diagnostic testing; enabling faster and more accurate identification of pathogenic DNA in human blood or tissue samples. PMID:25625550

  7. Cooperative Effects in Aligned and Opposed Multicomponent Charge Gradients Containing Strongly Acidic, Weakly Acidic, and Basic Functional Groups.

    Science.gov (United States)

    Ashraf, Kayesh M; Giri, Dipak; Wynne, Kenneth J; Higgins, Daniel A; Collinson, Maryanne M

    2016-04-26

    Bifunctionalized surface charge gradients in which the individual component gradients either align with or oppose each other have been prepared. The multicomponent gradients contain strongly acidic, weakly acidic, and basic functionalities that cooperatively interact to define surface wettability, nanoparticle binding, and surface charge. The two-step process for gradient formation begins by modifying a siloxane coated silicon wafer in a spatially dependent fashion first with an aminoalkoxysilane and then with a mercapto-functionalized alkoxysilane. Immersion in hydrogen peroxide leads to oxidation of the surface immobilized sulfhydryl groups and subsequent protonation of the surface immobilized amines. Very different surface chemistries were obtained from gradients that either align with or oppose each other. X-ray photoelectron spectroscopy (XPS) data show that the degree of amine group protonation depends on the local concentration of sulfonate groups, which form ion pairs with the resulting ammonium ions. Contact angle measurements show that these ion pairs greatly enhance the wettability of the gradient surface. Finally, studies of colloidal gold binding show that the presence of both amine and thiol moieties enhance colloid binding, which is also influenced by surface charge. Cooperativity is also revealed in the distribution of charges on uniform samples used as models of the gradient surfaces, as evaluated via zeta potential measurements. Most significantly, the net surface charge and how it changes with distance and solution pH strongly depend on whether the gradients in amine and thiol align or oppose each other. The aligned multicomponent gradients show the most interesting behavior in that there appears to be a point at pH ∼ 6.5 where surface charge remains constant with distance. Setting the pH above or below this transition point leads to changes in the direction of charge variation along the length of the substrate. PMID:27073019

  8. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte; Wengel, Jesper

    2013-01-01

    Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical...

  9. Optimizing the design of oligonucleotides for homology directed gene targeting.

    Directory of Open Access Journals (Sweden)

    Judith Miné-Hattab

    Full Text Available BACKGROUND: Gene targeting depends on the ability of cells to use homologous recombination to integrate exogenous DNA into their own genome. A robust mechanistic model of homologous recombination is necessary to fully exploit gene targeting for therapeutic benefit. METHODOLOGY/PRINCIPAL FINDINGS: In this work, our recently developed numerical simulation model for homology search is employed to develop rules for the design of oligonucleotides used in gene targeting. A Metropolis Monte-Carlo algorithm is used to predict the pairing dynamics of an oligonucleotide with the target double-stranded DNA. The model calculates the base-alignment between a long, target double-stranded DNA and a probe nucleoprotein filament comprised of homologous recombination proteins (Rad51 or RecA polymerized on a single strand DNA. In this study, we considered different sizes of oligonucleotides containing 1 or 3 base heterologies with the target; different positions on the probe were tested to investigate the effect of the mismatch position on the pairing dynamics and stability. We show that the optimal design is a compromise between the mean time to reach a perfect alignment between the two molecules and the stability of the complex. CONCLUSION AND SIGNIFICANCE: A single heterology can be placed anywhere without significantly affecting the stability of the triplex. In the case of three consecutive heterologies, our modeling recommends using long oligonucleotides (at least 35 bases in which the heterologous sequences are positioned at an intermediate position. Oligonucleotides should not contain more than 10% consecutive heterologies to guarantee a stable pairing with the target dsDNA. Theoretical modeling cannot replace experiments, but we believe that our model can considerably accelerate optimization of oligonucleotides for gene therapy by predicting their pairing dynamics with the target dsDNA.

  10. Working with Oligonucleotide Arrays.

    Science.gov (United States)

    Carvalho, Benilton S

    2016-01-01

    Preprocessing microarray data consists of a number of statistical procedures that convert the observed intensities into quantities that represent biological events of interest, like gene expression and allele-specific abundances. Here, we present a summary of the theory behind microarray data preprocessing for expression, whole transcriptome and SNP designs and focus on the computational protocol used to obtain processed data that will be used on downstream analyses. We describe the main features of the oligo Bioconductor package, an application designed to support oligonucleotide microarrays using the R statistical environment and the infrastructure provided by Bioconductor, allowing the researcher to handle probe-level data and interface with advanced statistical tools under a simplified framework. We demonstrate the use of the package by preprocessing data originated from three different designs. PMID:27008013

  11. Fully automated parallel oligonucleotide synthesizer

    Czech Academy of Sciences Publication Activity Database

    Lebl, M.; Burger, Ch.; Ellman, B.; Heiner, D.; Ibrahim, G.; Jones, A.; Nibbe, M.; Thompson, J.; Mudra, Petr; Pokorný, Vít; Poncar, Pavel; Ženíšek, Karel

    2001-01-01

    Roč. 66, č. 8 (2001), s. 1299-1314. ISSN 0010-0765 Institutional research plan: CEZ:AV0Z4055905 Keywords : automated oligonucleotide synthesizer Subject RIV: CC - Organic Chemistry Impact factor: 0.778, year: 2001

  12. SOAP2: an improved ultrafast tool for short read alignment

    DEFF Research Database (Denmark)

    Li, Ruiqiang; Yu, Chang; Li, Yingrui;

    2009-01-01

    SUMMARY: SOAP2 is a significantly improved version of the short oligonucleotide alignment program that both reduces computer memory usage and increases alignment speed at an unprecedented rate. We used a Burrows Wheeler Transformation (BWT) compression index to substitute the seed strategy for in...

  13. Thermodynamics of Oligonucleotide Duplex Melting

    Science.gov (United States)

    Schreiber-Gosche, Sherrie; Edwards, Robert A.

    2009-01-01

    Melting temperatures of oligonucleotides are useful for a number of molecular biology applications, such as the polymerase chain reaction (PCR). Although melting temperatures are often calculated with simplistic empirical equations, application of thermodynamics provides more accurate melting temperatures and an opportunity for students to apply…

  14. Antisense Oligonucleotides: Treating Neurodegeneration at the Level of RNA

    OpenAIRE

    DeVos, Sarah L.; Miller, Timothy M.

    2013-01-01

    Adequate therapies are lacking for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases. The ability to use antisense oligonucleotides (ASOs) to target disease-associated genes by means of RNA may offer a potent approach for the treatment of these, and other, neurodegenerative disorders. In modifying the basic backbone chemistry, chemical groups, and target sequence, ASOs can act through numerous mechanisms to decr...

  15. [Study toward practical use of oligonucleotide therapeutics].

    Science.gov (United States)

    Inoue, Takao; Yoshida, Tokuyuki

    2014-01-01

    Over the past decade, oligonucleotide-based therapeutics such as antisense oligonucleotides and small interfering RNAs (siRNAs) have been developed extensively. For example, mipomersen (Kynamro; ISIS Pharmaceuticals), which is a second-generation antisense oligonucleotide administered by subcutaneous injection, has recently been approved by the FDA for the treatment of homozygous familial hypercholesterolemia. On the other hands, methods for the evaluation of quality, efficacy and safety of oligonucleotide therapeutics have not been fully discussed. Furthermore, the regulatory guidance specific for oligonucleotide therapeutics has not been established yet. Under these circumstances, we started to collaborate with Osaka University and PMDA to discuss regulatory science focused on oligonucleotide therapeutics. Through the collaboration, we would like to propose the possible design of quality evaluation and preclinical safety-evaluation of oligonucleotide therapeutics. PMID:25707197

  16. Targeted Delivery of a Splice-Switching Oligonucleotide by Cationic Polyplexes of RGD-Oligonucleotide Conjugate

    OpenAIRE

    Ming, Xin; Feng, Lan

    2012-01-01

    Nanoparticle-based delivery has become an important strategy to advance therapeutic oligonucleotides into clinical reality. Delivery by nanocarriers can enhance access of oligonucleotides to their pharmacological targets within cells; preferably, targeting ligands are incorporated into nanoparticles for targeting oligonucleotides to disease sites, often by conjugation to delivery carriers. In this study, a splice-switching oligonucleotide (SSO) was conjugated to a bivalent RGD peptide, and th...

  17. GPCODON ALIGNMENT: A GLOBAL PAIRWISE CODON BASED SEQUENCE ALIGNMENT APPROACH

    Directory of Open Access Journals (Sweden)

    Zeinab A. Fareed

    2016-02-01

    Full Text Available The alignment of two DNA sequences is a basic step in the analysis of biological data. Sequencing a long DNA sequence is one of the most interesting problems in bioinformatics. Several techniques have been developed to solve this sequence alignment problem like dynamic programming and heuristic algorithms. In this paper, we introduce (GPCodon alignment a pairwise DNA-DNA method for global sequence alignment that improves the accuracy of pairwise sequence alignment. We use a new scoring matrix to produce the final alignment called the empirical codon substitution matrix. Using this matrix in our technique enabled the discovery of new relationships between sequences that could not be discovered using traditional matrices. In addition, we present experimental results that show the performance of the proposed technique over eleven datasets of average length of 2967 bps. We compared the efficiency and accuracy of our techniques against a comparable tool called “Pairwise Align Codons” [1].

  18. Alignment validation

    CERN Document Server

    Golling, T

    2007-01-01

    The four experiments, ALICE, ATLAS, CMS and LHCb are currently under construction at CERN. They will study the products of proton-proton collisions at the Large Hadron Collider. All experiments are equipped with sophisticated tracking systems, unprecedented in size and complexity. Full exploitation of both the inner detector and the muon system requires an accurate alignment of all detector elements. Alignment information is deduced from dedicated hardware alignment systems and the reconstruction of charged particles. However, the system is degenerate which means the data is insufficient to constrain all alignment degrees of freedom, so the techniques are prone to converging on wrong geometries. This deficiency necessitates validation and monitoring of the alignment. An exhaustive discussion of means to validate is subject to this document, including examples and plans from all four LHC experiments, as well as other high energy experiments.

  19. Synthesis of 5'-Aldehyde Oligonucleotide.

    Science.gov (United States)

    Lartia, Rémy

    2016-01-01

    Synthesis of oligonucleotide ending with an aldehyde functional group at their 5'-end (5'-AON) is possible for both DNA (5'-AODN) and RNA (5'-AORN) series irrespectively of the nature of the last nucleobase. The 5'-alcohol of on-support ODN is mildly oxidized under Moffat conditions. Transient protection of the resulting aldehyde by N,N'-diphenylethylenediamine derivatives allows cleavage, deprotection, and RP-HPLC purification of the protected 5'-AON. Finally, 5'-AON is deprotected by usual acetic acid treatment. In the aggregates, 5'-AON can be now synthesized and purified as routinely as non-modified ODNs, following procedures similar to the well-known "DMT-On" strategy. PMID:26967469

  20. Basic Local Alignment Search Tool (BLAST)

    Data.gov (United States)

    U.S. Department of Health & Human Services — BLAST finds regions of similarity between biological sequences. The program compares nucleotide or protein sequences to sequence databases and calculates the...

  1. A Tandem Oligonucleotide Approach for SNP-Selective RNA Degradation Using Modified Antisense Oligonucleotides

    OpenAIRE

    Magner, Dorota; Biala, Ewa; Lisowiec-Wachnicka, Jolanta; Kierzek, Elzbieta; Kierzek, Ryszard

    2015-01-01

    Antisense oligonucleotides have been studied for many years as a tool for gene silencing. One of the most difficult cases of selective RNA silencing involves the alleles of single nucleotide polymorphisms, in which the allele sequence is differentiated by a single nucleotide. A new approach to improve the performance of allele selectivity for antisense oligonucleotides is proposed. It is based on the simultaneous application of two oligonucleotides. One is complementary to the mutated form of...

  2. Hardware Acceleration of Bioinformatics Sequence Alignment Applications

    OpenAIRE

    Hasan, L.

    2011-01-01

    Biological sequence alignment is an important and challenging task in bioinformatics. Alignment may be defined as an arrangement of two or more DNA or protein sequences to highlight the regions of their similarity. Sequence alignment is used to infer the evolutionary relationship between a set of protein or DNA sequences. An accurate alignment can provide valuable information for experimentation on the newly found sequences. It is indispensable in basic research as well as in practical applic...

  3. The use of oligonucleotide probes for meningococcal serotype characterization

    Directory of Open Access Journals (Sweden)

    SACCHI Claudio Tavares

    1998-01-01

    Full Text Available In the present study we examine the potential use of oligonucleotide probes to characterize Neisseria meningitidis serotypes without the use of monoclonal antibodies (MAbs. Antigenic diversity on PorB protein forms the bases of serotyping method. However, the current panel of MAbs underestimated, by at least 50% the PorB variability, presumably because reagents for several PorB variable regions (VRs are lacking, or because a number of VR variants are not recognized by serotype-defining MAbs12. We analyzed the use of oligonucleotide probes to characterize serotype 10 and serotype 19 of N. meningitidis. The porB gene sequence for the prototype strain of serotype 10 was determined, aligned with 7 other porB sequences from different serotypes, and analysis of individual VRs were performed. The results of DNA probes 21U (VR1-A and 615U (VR3-B used against 72 N. meningitidis strains confirm that VR1 type A and VR3 type B encode epitopes for serotype-defined MAbs 19 and 10, respectively. The use of probes for characterizing serotypes possible can type 100% of the PorB VR diversity. It is a simple and rapid method specially useful for analysis of large number of samples.

  4. Antisense oligonucleotides as therapeutics for malignant diseases.

    Science.gov (United States)

    Ho, P T; Parkinson, D R

    1997-04-01

    The continued progress in our understanding of the biology of neoplasia and in the identification, cloning, and sequencing of genes critical to tumor cell function permits the exploitation of this information to develop specific agents that may directly modulate the function of these genes or their protein products. Antisense oligonucleotides are being investigated as a potential therapeutic modality that takes direct advantage of molecular sequencing. The antisense approach uses short oligonucleotides designed to hybridize to a target mRNA transcript through Watson-Crick base pairing. The formation of this oligonucleotide: RNA heteroduplex results in mRNA inactivation and consequent inhibition of synthesis of the protein product. A fundamental attraction of the antisense approach is that this method potentially may be applied to any gene product, in theory, for the treatment of malignant and non-malignant diseases. However, this simple and attractive model has proven to be much more complex in practice. A number of important challenges in the preclinical development of antisense oligonucleotides have been identified, including stability, sequence length, cellular uptake, target sequence selection, appropriate negative controls, oligonucleotide: protein interactions, and cost of manufacture. Although the biological activity of an oligonucleotide against its molecular target is theoretically sequence-dependent, the animal pharmacokinetics and toxicology of phosphorothioate analogues directed against vastly disparate gene products appear relatively non-sequence-specific. In oncology, a number of clinical trials have been initiated with antisense oligonucleotides directed against molecular targets including: p53; bcl-2; raf kinase; protein kinase C-alpha; c-myb. The experience gained from these early clinical trials will be applicable to the next generation of antisense agents in development. These may include molecules with novel backbones or other structural

  5. Beyond Alignment

    DEFF Research Database (Denmark)

    Beyond Alignment: Applying Systems Thinking to Architecting Enterprises is a comprehensive reader about how enterprises can apply systems thinking in their enterprise architecture practice, for business transformation and for strategic execution. The book's contributors find that systems thinking...... is a valuable way of thinking about the viable enterprise and how to architect it....

  6. Image alignment

    Science.gov (United States)

    Dowell, Larry Jonathan

    2014-04-22

    Disclosed is a method and device for aligning at least two digital images. An embodiment may use frequency-domain transforms of small tiles created from each image to identify substantially similar, "distinguishing" features within each of the images, and then align the images together based on the location of the distinguishing features. To accomplish this, an embodiment may create equal sized tile sub-images for each image. A "key" for each tile may be created by performing a frequency-domain transform calculation on each tile. A information-distance difference between each possible pair of tiles on each image may be calculated to identify distinguishing features. From analysis of the information-distance differences of the pairs of tiles, a subset of tiles with high discrimination metrics in relation to other tiles may be located for each image. The subset of distinguishing tiles for each image may then be compared to locate tiles with substantially similar keys and/or information-distance metrics to other tiles of other images. Once similar tiles are located for each image, the images may be aligned in relation to the identified similar tiles.

  7. Jet activity versus alignment

    CERN Document Server

    Lokhtin, I P; Sarycheva, L I; Snigirev, A M

    2005-01-01

    The hypothesis about the relation between the observed alignment of spots in the x-ray film in cosmic ray emulsion experiments and the features of events in which jets prevail at super high energies is tested. Due to strong correlation between jet axis directions and that between momenta (almost collinearity) of jet particles, the evaluated degree of alignment is considerably larger than that at randomly selected chaoticly located spots in the x-ray film. It appears comparable with experimental data provided that the height of primary interaction, the collision energy and the total energy of selected clusters meet certain conditions. The Monte Carlo generator PYTHIA, which basically well describes jet events in hadron-hadron interactions, was used for the analysis.

  8. Oligonucleotide-based therapy for neurodegenerative diseases.

    Science.gov (United States)

    Magen, Iddo; Hornstein, Eran

    2014-10-10

    Molecular genetics insight into the pathogenesis of several neurodegenerative diseases, such as Alzheimer׳s disease, Parkinson׳s disease, Huntington׳s disease and amyotrophic lateral sclerosis, encourages direct interference with the activity of neurotoxic genes or the molecular activation of neuroprotective pathways. Oligonucleotide-based therapies are recently emerging as an efficient strategy for drug development and these can be employed as new treatments of neurodegenerative states. Here we review advances in this field in recent years which suggest an encouraging assessment that oligonucleotide technologies for targeting of RNAs will enable the development of new therapies and will contribute to preservation of brain integrity. PMID:24727531

  9. Radio-marking and in vivo imagery of oligonucleotides

    International Nuclear Information System (INIS)

    This research thesis is part of activities aimed at the development of new molecules like oligonucleotides. Its first objective was the development and validation of a marking method with fluorine-18 of oligonucleotides for their in-vivo pharmacological assessment with positron emission tomography (PET). Further investigations addressed the use of iodine-125 for oligonucleotide marking purpose. This radio-marking, and in vivo and ex vivo imagery techniques are described, and their potential is highlighted for the pharmacological assessment of different oligonucleotides

  10. Synthesis of oligonucleotide conjugates carrying viologen and fluorescent compounds

    OpenAIRE

    Alvira, Margarita; Quinn, Susan J.; Aviñó, Anna; Fitzmaurice, Donald; Eritja Casadellà, Ramón

    2008-01-01

    The preparation of oligonucleotide conjugates carrying viologen and fluorescein is described. Reaction of the appropriate carboxyl derivatives with oligonucleotides carrying aliphatic amino groups gave the desired compounds. A simple method for the introduction of the amino group at the 5'-end of the oligonucleotides is reported.

  11. Inhibition of certain strains of HIV-1 by cell surface polyanions in the form of cholesterol-labeled oligonucleotides

    International Nuclear Information System (INIS)

    Cholesterol-labeled oligonucleotides were found several years ago to inhibit HIV-1 in tissue culture at nanomolar concentrations. We present evidence that this is mainly due to an electrostatic interaction between polyanionic oligonucleotide concentrated at the cell surface and a positively charged region in the V3 loop of the HIV-1 envelope protein. When added to tissue culture, cholesterol-labeled oligonucleotides became concentrated at the plasma membrane and potently inhibited virus entry and cell fusion mediated by the envelope protein of some X4 strains of HIV-1, but had little effect on fusion mediated by R5 strains of HIV-1, amphotropic MLV envelope protein, or VSV-G protein. Noncholesterol-labeled oligonucleotides did not bind to the cell surface or inhibit fusion. The pattern of susceptibility to cholesterol-labeled oligonucleotides among HIV-1 strains was the same as reported for nonmembrane-associating polyanions such as dextran sulfate, but the cholesterol-labeled oligonucleotides were effective at lower concentrations. Substitution of a basic 33 amino acid V3 loop sequence from the envelope protein of a resistant strain into a susceptible strain made the envelope protein resistant to inhibition. Inhibition by cholesterol-labeled oligonucleotides was abrogated by the polycation DEAE-dextran. Cholesterol-labeled oligonucleotides bound to nonraft regions of the plasma membrane and did not inhibit HIV virus binding to cells. Many infectious agents first associate with target cells via relatively nonspecific charge interactions; our data suggest that molecules that combine a membrane-targeting motif with multiple negative charges might be useful to modify these interactions

  12. In vivo imaging of oligonucleotidic aptamers

    Energy Technology Data Exchange (ETDEWEB)

    Tavitian, B.; Boisgard, R. [Inserm U803, Laboratoire d' Imagerie Moleculaire Experimentale, Service hospitalier Frederic joliot, Intitut d' Imagerie Biomedicale, CEA, Orsay (France); Duconge, F.; Dolle, F. [Groupe de Radiochimie, Laboratoire d' Imagerie Moleculaire Experimentale, Service hospitalier Frederic joliot, Intitut d' Imagerie Biomedicale, CEA, Orsay (France)

    2009-07-01

    In this chapter we present the methods developed in our laboratory for in vivo imaging of oligonucleotidic aptamers. These methods relate to (i) the labelling of aptamers with fluorine-18, a positron emitter (ii) Positron Emission Tomography imaging of laboratory animals with [({sup 18})F]aptamers and (iii) labelling with fluorescent dyes and optical imaging of aptamers in mice. (authors)

  13. Triplex-forming ability of modified oligonucleotides

    DEFF Research Database (Denmark)

    Højland, Torben; Babu, Bolle Ravindra; Bryld, Torsten;

    2007-01-01

    We present our studies on the ability of several different nucleotide analogs as triplex-forming oligonucleotides. The modifications tested include 4'-C-hydroxymethyl, LNA, 2'-amino-LNA and N2'-functionalized 2'-amino-LNA. Triplexes containing monomers of N2'-glycyl-functionalized 2'-amino-LNA are...

  14. Spatially Defined Oligonucleotide Arrays. Technical Report for Phase II; FINAL

    International Nuclear Information System (INIS)

    The goal of the Human Genome Project is to sequence all 3 billion base pairs of the human genome. Progress in this has been rapid; GenBank(regsign) finished 1994 with 286 million bases of sequence and grew by 2470 in the first quarter of 1995. The challenge to the scientific community is to understand the biological relevance of this genetic information. In most cases the sequence being generated for any single region of the genome represents the genotype of a single individual. A complete understanding of the function of specific genes and other regions of the genome and their role in human disease and development will only become apparent when the sequence of many more individuals is known. Access to genetic information is ultimately limited by the ability to screen DNA sequence. Although the pioneering sequencing methods of Sanger et al. (15) and Maxam and Gilbert (11) have become standard in virtually all molecular biology laboratories, the basic protocols remain largely unchanged. The throughput of this sequencing technology is now becoming the rate-limiting step in both large-scale sequencing projects such as the Human Genome Project and the subsequent efforts to understand genetic diversity. This has inspired the development of advanced DNA sequencing technologies (9), Incremental improvements to Sanger sequencing have been made in DNA labeling and detection. High-speed electrophoresis methods using ultrathin gels or capillary arrays are now being more widely employed. However, these methods are throughput-limited by their sequential nature and the speed and resolution of separations. This limitation will become more pronounced as the need to rapidly screen newly discovered genes for biologically relevant polymorphisms increases. An alternative to gel-based sequencing is to use high-density oligonucleotide probe arrays. Oligonucleotide probe arrays display specific oligonucleotide probes at precise locations in a high density, information-rich format (5

  15. Electrochemical behavior of G-rich oligonucleotides

    Czech Academy of Sciences Publication Activity Database

    Havran, Luděk; Vidláková, Pavlína; Pivoňková, Hana; Kejnovská, Iva; Vorlíčková, Michaela; Fojta, Miroslav

    Beijing, 2009. s. 1. [The 60th Annual Meeting of the International Society of Electrochemistry. 16.08.2009-21.08.2009, Beijing] R&D Projects: GA AV ČR(CZ) IAA400040903; GA MŠk(CZ) LC06035 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : oligonucleotides * electrochemical behavior * DNA secondary structures Subject RIV: BO - Biophysics

  16. Electrochemical behavior of oligonucleotides containing guanine stretches

    Czech Academy of Sciences Publication Activity Database

    Havran, Luděk; Vidláková, Pavlína; Pivoňková, Hana; Kejnovská, Iva; Vorlíčková, Michaela; Fojta, Miroslav

    Jětřichovice, 2009. s. 33. ISBN 978-80-254-3997-5. [XXIX. Moderní elektrochemické metody. 25.05.2009-29.05.2009, Jetřichovice] R&D Projects: GA AV ČR(CZ) IAA400040903; GA MŠk(CZ) LC06035 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : oligonucleotides * electrochemical behavior * DNA secondary structures Subject RIV: BO - Biophysics

  17. DNA Align Editor: DNA Alignment Editor Tool

    Science.gov (United States)

    The SNPAlignEditor is a DNA sequence alignment editor that runs on Windows platforms. The purpose of the program is to provide an intuitive, user-friendly tool for manual editing of multiple sequence alignments by providing functions for input, editing, and output of nucleotide sequence alignments....

  18. AFM phase lag mapping for protein-DNA oligonucleotide complexes

    International Nuclear Information System (INIS)

    Atomic force microscope phase lag imaging of protein-DNA oligonucleotide complexes has been performed to visualize the immobilized oligonucleotides on the protein surface. In normal sample conditions, neither the topographic nor phase lag images show any discriminate signals for the immobilized oligonucleotides. Use of a highly humid incubator, controls the surface humidity of the sample. Thereby, the phase lag image reveals the oligonucleotide location by the local difference of tip adhesion distribution. The resultant phase lag image shows extremely strong signals in the center of the protein surface, indicating the location of the oligonucleotides with resolution better than 20 nm. The signal frequency was strongly influenced by the used oligonucleotide concentration in the range 5 nM-50 μM

  19. Dendritische Polythioetherliganden zur Synthese von Goldnanopartikel-Oligonucleotid-Monokonjugaten

    OpenAIRE

    Mönninghoff, Sven

    2009-01-01

    Basierend auf der Entwicklung des Rubigoldes als thermostabilem Marker für Biomoleküle wurden in dieser Arbeit Polythioether-Liganden zur Synthese von monofunktionalen Cluster-Oligonucleotid-Konjugaten (COK) entwickelt. Zum Aufbau der Liganden wurden 2,4,6-substituierte Phenole als zentrales Strukturmotiv eingesetzt. Durch Konjugation der Ligandensysteme an Oligonucleotide wurden Ligand-Oligonucleotid-Konjugate (LOK) hergestellt, die durch Reduktion von Au (III)-Ionen in Anwesenhe...

  20. Investigations of oligonucleotide usage variance within and between prokaryotes

    DEFF Research Database (Denmark)

    Bohlin, J.; Skjerve, E.; Ussery, David

    2008-01-01

    different DNA 'word-sizes' and explore how oligonucleotide frequencies differ in coding and non-coding regions. In addition, we used oligonucleotide frequencies to investigate DNA composition and how DNA sequence patterns change within and between prokaryotic organisms. Among the results found was that...... prokaryotic chromosomes can be described by hexanucleotide frequencies, suggesting that prokaryotic DNA is predominantly short range correlated, i. e., information in prokaryotic genomes is encoded in short oligonucleotides. Oligonucleotide usage varied more within AT-rich and host-associated genomes than in...

  1. Optically Triggered Immune Response through Photocaged Oligonucleotides

    Science.gov (United States)

    Govan, Jeane M.; Young, Douglas D.; Lively, Mark O.

    2015-01-01

    Bacterial and viral CpG oligonculeotides are unmethylated cytosine-phosphate-guanosine dinucleotide sequences and trigger an innate immune response through activation of the toll-like receptor 9 (TLR9). We have developed synthetic photocaged CpGs via site-specific incorporation of nitropiperonyloxymethyl (NPOM)-caged thymidine residues. These oligonucleotides enable the optical control of TLR9 function and thereby provide light-activation of an immune response. We provide a proof-of-concept model by applying a reporter assay in live cells and by quantification of endogenous production of interleukin 6. PMID:26034339

  2. Brain Basics

    Medline Plus

    Full Text Available ... Neurons & Neural Circuits Neurons are the basic working unit of the brain and nervous system. These cells ... A nerve cell that is the basic, working unit of the brain and nervous system, which processes ...

  3. Brain Basics

    Medline Plus

    Full Text Available ... as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the brain ... specialized for the function of conducting messages. A neuron has three basic parts: Cell body which includes ...

  4. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of ...

  5. Backpack Basics

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Backpack Basics KidsHealth > For Teens > Backpack Basics Print A ... it can cause back problems or even injury. Backpacks Are Best Backpacks can't be beat for ...

  6. Asthma Basics

    Science.gov (United States)

    ... Tropical Delight: Melon Smoothie Pregnant? Your Baby's Growth Asthma Basics KidsHealth > For Parents > Asthma Basics Print A ... Asthma Categories en español Asma: aspectos fundamentales About Asthma Asthma is a common lung condition in kids ...

  7. Hygiene Basics

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Hygiene Basics KidsHealth > For Teens > Hygiene Basics Print A A A Text Size What's ... smell, anyway? Read below for information on some hygiene basics — and learn how to deal with greasy ...

  8. Gene cloning based on long oligonucleotide probes

    International Nuclear Information System (INIS)

    The most commonly used technique for gene cloning has been to utilize oligonucleotide probe based on protein sequence data. Of course this approach requires characterized and purified protein so that at least a portion of amino acid sequence can be determined and used to infer the corresponding DNA sequence. Based on the amino acid sequence information, either short or long oligonucleotide probes can be synthesized chemically. Long probes are typically 30-100 nucleotides long and are a single sequence based on a best guess for each codon. The long probe approach was first used to screen for three different genes: bovine trypsin inhibitor, human insulin-like growth factor I, and human factor IX. There are three advantages of long probes. (1) Any stretch of amino acid sequence 10 or longer can be used. (2) The amino acid sequence need not be absolutely correct. (3) These probes can be used to screen high-complexity libraries with fewer false positives. In spite of the uncertainties over codon selection, the long probe approach is currently the method of choice in screening for genes based on protein sequence data

  9. Bioconjugation of oligonucleotides for treating liver fibrosis.

    Science.gov (United States)

    Ye, Zhaoyang; Houssein, Houssam S Hajj; Mahato, Ram I

    2007-01-01

    Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is urgently needed to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remain the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of alpha1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in-depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed. PMID:18154454

  10. Novel oligonucleotides modified with acyclic nucleoside phosphonate units

    Czech Academy of Sciences Publication Activity Database

    Janeba, Zlatko; Hocková, Dana; Kaiser, Martin Maxmilian; Ménová, Petra; Novák, Pavel; Rosenbergová, Šárka; Páv, Ondřej; Pohl, Radek; Poštová Slavětínská, Lenka; Rosenberg, Ivan

    Newport : Gordon Research Conference, 2015. [Nucleosides, Nucleotides & Oligonucleotides. Gordon Research Conference 2015. 28.06.2015-03.07.2015, Newport] R&D Projects: GA ČR GA13-26526S Institutional support: RVO:61388963 Keywords : nucleotide analogues * modified oligonucleotides Subject RIV: CC - Organic Chemistry

  11. Voltage-gated calcium channel and antisense oligonucleotides thereto

    Science.gov (United States)

    Hruska, Keith A. (Inventor); Friedman, Peter A. (Inventor); Barry, Elizabeth L. R. (Inventor); Duncan, Randall L. (Inventor)

    1998-01-01

    An antisense oligonucleotide of 10 to 35 nucleotides in length that can hybridize with a region of the .alpha..sub.1 subunit of the SA-Cat channel gene DNA or mRNA is provided, together with pharmaceutical compositions containing and methods utilizing such antisense oligonucleotide.

  12. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez.

    Since June of 2009, the muon alignment group has focused on providing new alignment constants and on finalizing the hardware alignment reconstruction. Alignment constants for DTs and CSCs were provided for CRAFT09 data reprocessing. For DT chambers, the track-based alignment was repeated using CRAFT09 cosmic ray muons and validated using segment extrapolation and split cosmic tools. One difference with respect to the previous alignment is that only five degrees of freedom were aligned, leaving the rotation around the local x-axis to be better determined by the hardware system. Similarly, DT chambers poorly aligned by tracks (due to limited statistics) were aligned by a combination of photogrammetry and hardware-based alignment. For the CSC chambers, the hardware system provided alignment in global z and rotations about local x. Entire muon endcap rings were further corrected in the transverse plane (global x and y) by the track-based alignment. Single chamber track-based alignment suffers from poor statistic...

  13. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez and J. Pivarski

    2011-01-01

    Alignment efforts in the first few months of 2011 have shifted away from providing alignment constants (now a well established procedure) and focussed on some critical remaining issues. The single most important task left was to understand the systematic differences observed between the track-based (TB) and hardware-based (HW) barrel alignments: a systematic difference in r-φ and in z, which grew as a function of z, and which amounted to ~4-5 mm differences going from one end of the barrel to the other. This difference is now understood to be caused by the tracker alignment. The systematic differences disappear when the track-based barrel alignment is performed using the new “twist-free” tracker alignment. This removes the largest remaining source of systematic uncertainty. Since the barrel alignment is based on hardware, it does not suffer from the tracker twist. However, untwisting the tracker causes endcap disks (which are aligned ...

  14. Use of nanoparticles to deliver immunomodulatory oligonucleotides.

    Science.gov (United States)

    Klinman, Dennis M; Sato, Takashi; Shimosato, Takeshi

    2016-07-01

    Synthetic oligonucleotides (ODNs) containing unmethylated 'CpG motifs' stimulate the innate immune system to produce cytokines, chemokines, and polyreactive antibodies. CpG ODNs have shown promise as vaccine adjuvants and for the treatment of infectious diseases and cancer. The immunostimulatory activity of CpG ODNs is inhibited by DNA-containing 'suppressive' motifs. ODNs expressing suppressive motifs (Sup ODNs) reduce ongoing immune reactions and show promise in the treatment of autoimmune and inflammatory diseases. This work reviews recent progress in the use of nanoparticles as carriers of CpG and Sup ODNs to target their delivery to the GI tract and lungs. WIREs Nanomed Nanobiotechnol 2016, 8:631-637. doi: 10.1002/wnan.1382 For further resources related to this article, please visit the WIREs website. PMID:26663867

  15. Hole hopping rates in single strand oligonucleotides

    Science.gov (United States)

    Borrelli, Raffaele; Capobianco, Amedeo; Peluso, Andrea

    2014-08-01

    The rates of hole transfer between guanine and adenine in single strand DNA have been evaluated by using Fermi’s golden rule and Kubo’s generating function approach for the Franck-Condon weighted density of states. The whole sets of the normal modes and vibrational frequencies of the two nucleobases, obtained at DFT/B3LYP level of calculation, have been considered in computations. The results show that in single strand the pyramidalization/planarization mode of the amino groups of both nucleobases plays the major role. At room temperature, the Franck-Condon density of states extends over a wide range of hole site energy difference, 0-1 eV, giving some hints about the design of oligonucleotides of potential technological interest.

  16. Basic electrotechnology

    CERN Document Server

    Ashen, R A

    2013-01-01

    BASIC Electrotechnology discusses the applications of Beginner's All-purpose Symbolic Instruction Code (BASIC) in engineering, particularly in solving electrotechnology-related problems. The book is comprised of six chapters that cover several topics relevant to BASIC and electrotechnology. Chapter 1 provides an introduction to BASIC, and Chapter 2 talks about the use of complex numbers in a.c. circuit analysis. Chapter 3 covers linear circuit analysis with d.c. and sinusoidal a.c. supplies. The book also discusses the elementary magnetic circuit theory. The theory and performance of two windi

  17. Fast statistical alignment.

    Directory of Open Access Journals (Sweden)

    Robert K Bradley

    2009-05-01

    Full Text Available We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment--previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches--yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/.

  18. Fast statistical alignment.

    Science.gov (United States)

    Bradley, Robert K; Roberts, Adam; Smoot, Michael; Juvekar, Sudeep; Do, Jaeyoung; Dewey, Colin; Holmes, Ian; Pachter, Lior

    2009-05-01

    We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment--previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches--yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/. PMID:19478997

  19. Preparation and application of triple helix forming oligonucleotides and single strand oligonucleotide donors for gene correction.

    Science.gov (United States)

    Alam, Rowshon; Thazhathveetil, Arun Kalliat; Li, Hong; Seidman, Michael M

    2014-01-01

    Strategies for site-specific modulation of genomic sequences in mammalian cells require two components. One must be capable of recognizing and activating a specific target sequence in vivo, driving that site into an exploitable repair pathway. Information is transferred to the site via participation in the pathway by the second component, a donor nucleic acid, resulting in a permanent change in the target sequence. We have developed biologically active triple helix forming oligonucleotides (TFOs) as site-specific gene targeting reagents. These TFOs, linked to DNA reactive compounds (such as a cross-linking agent), activate pathways that can engage informational donors. We have used the combination of a psoralen-TFO and single strand oligonucleotide donors to generate novel cell lines with directed sequence changes at the target site. Here we describe the synthesis and purification of bioactive psoralen-linked TFOs, their co-introduction into mammalian cells with donor nucleic acids, and the identification of cells with sequence conversion of the target site. We have emphasized details in the synthesis and purification of the oligonucleotides that are essential for preparation of reagents with optimal activity. PMID:24557899

  20. Ca2+ enrichment in culture medium potentiates effect of oligonucleotides.

    Science.gov (United States)

    Hori, Shin-Ichiro; Yamamoto, Tsuyoshi; Waki, Reiko; Wada, Shunsuke; Wada, Fumito; Noda, Mio; Obika, Satoshi

    2015-10-30

    Antisense and RNAi-related oligonucleotides have gained attention as laboratory tools and therapeutic agents based on their ability to manipulate biological events in vitro and in vivo. We show that Ca(2+) enrichment of medium (CEM) potentiates the in vitro activity of multiple types of oligonucleotides, independent of their net charge and modifications, in various cells. In addition, CEM reflects in vivo silencing activity more consistently than conventional transfection methods. Microscopic analysis reveals that CEM provides a subcellular localization pattern of oligonucleotides resembling that obtained by unassisted transfection, but with quantitative improvement. Highly monodispersed nanoparticles ~100 nm in size are found in Ca(2+)-enriched serum-containing medium regardless of the presence or absence of oligonucleotides. Transmission electron microscopy analysis reveals that the 100-nm particles are in fact an ensemble of much smaller nanoparticles (ϕ ∼ 15 nm). The presence of these nanoparticles is critical for the efficient uptake of various oligonucleotides. In contrast, CEM is ineffective for plasmids, which are readily transfected via the conventional calcium phosphate method. Collectively, CEM enables a more accurate prediction of the systemic activity of therapeutic oligonucleotides, while enhancing the broad usability of oligonucleotides in the laboratory. PMID:26101258

  1. Design and analysis of mismatch probes for long oligonucleotide microarrays

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Ye; He, Zhili; Van Nostrand, Joy D.; Zhou, Jizhong

    2008-08-15

    Nonspecific hybridization is currently a major concern with microarray technology. One of most effective approaches to estimating nonspecific hybridizations in oligonucleotide microarrays is the utilization of mismatch probes; however, this approach has not been used for longer oligonucleotide probes. Here, an oligonucleotide microarray was constructed to evaluate and optimize parameters for 50-mer mismatch probe design. A perfect match (PM) and 28 mismatch (MM) probes were designed for each of ten target genes selected from three microorganisms. The microarrays were hybridized with synthesized complementary oligonucleotide targets at different temperatures (e.g., 42, 45 and 50 C). In general, the probes with evenly distributed mismatches were more distinguishable than those with randomly distributed mismatches. MM probes with 3, 4 and 5 mismatched nucleotides were differentiated for 50-mer oligonucleotide probes hybridized at 50, 45 and 42 C, respectively. Based on the experimental data generated from this study, a modified positional dependent nearest neighbor (MPDNN) model was constructed to adjust the thermodynamic parameters of matched and mismatched dimer nucleotides in the microarray environment. The MM probes with four flexible positional mismatches were designed using the newly established MPDNN model and the experimental results demonstrated that the redesigned MM probes could yield more consistent hybridizations. Conclusions: This study provides guidance on the design of MM probes for long oligonucleotides (e.g., 50 mers). The novel MPDNN model has improved the consistency for long MM probes, and this modeling method can potentially be used for the prediction of oligonucleotide microarray hybridizations.

  2. Nucleic acid sequence detection using multiplexed oligonucleotide PCR

    Science.gov (United States)

    Nolan, John P.; White, P. Scott

    2006-12-26

    Methods for rapidly detecting single or multiple sequence alleles in a sample nucleic acid are described. Provided are all of the oligonucleotide pairs capable of annealing specifically to a target allele and discriminating among possible sequences thereof, and ligating to each other to form an oligonucleotide complex when a particular sequence feature is present (or, alternatively, absent) in the sample nucleic acid. The design of each oligonucleotide pair permits the subsequent high-level PCR amplification of a specific amplicon when the oligonucleotide complex is formed, but not when the oligonucleotide complex is not formed. The presence or absence of the specific amplicon is used to detect the allele. Detection of the specific amplicon may be achieved using a variety of methods well known in the art, including without limitation, oligonucleotide capture onto DNA chips or microarrays, oligonucleotide capture onto beads or microspheres, electrophoresis, and mass spectrometry. Various labels and address-capture tags may be employed in the amplicon detection step of multiplexed assays, as further described herein.

  3. Antisense oligonucleotide induction of progerin in human myogenic cells.

    Directory of Open Access Journals (Sweden)

    Yue-Bei Luo

    Full Text Available We sought to use splice-switching antisense oligonucleotides to produce a model of accelerated ageing by enhancing expression of progerin, translated from a mis-spliced lamin A gene (LMNA transcript in human myogenic cells. The progerin transcript (LMNA Δ150 lacks the last 150 bases of exon 11, and is translated into a truncated protein associated with the severe premature ageing disease, Hutchinson-Gilford progeria syndrome (HGPS. HGPS arises from de novo mutations that activate a cryptic splice site in exon 11 of LMNA and result in progerin accumulation in tissues of mesodermal origin. Progerin has also been proposed to play a role in the 'natural' ageing process in tissues. We sought to test this hypothesis by producing a model of accelerated muscle ageing in human myogenic cells. A panel of splice-switching antisense oligonucleotides were designed to anneal across exon 11 of the LMNA pre-mRNA, and these compounds were transfected into primary human myogenic cells. RT-PCR showed that the majority of oligonucleotides were able to modify LMNA transcript processing. Oligonucleotides that annealed within the 150 base region of exon 11 that is missing in the progerin transcript, as well as those that targeted the normal exon 11 donor site induced the LMNA Δ150 transcript, but most oligonucleotides also generated variable levels of LMNA transcript missing the entire exon 11. Upon evaluation of different oligomer chemistries, the morpholino phosphorodiamidate oligonucleotides were found to be more efficient than the equivalent sequences prepared as oligonucleotides with 2'-O-methyl modified bases on a phosphorothioate backbone. The morpholino oligonucleotides induced nuclear localised progerin, demonstrated by immunostaining, and morphological nuclear changes typical of HGPS cells. We show that it is possible to induce progerin expression in myogenic cells using splice-switching oligonucleotides to redirect splicing of LMNA. This may offer a model

  4. Brain Basics

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    Full Text Available ... in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video ... early brain development, and may also assist in learning and memory. ... rise to disabilities or diseases. neural circuit —A network of neurons ...

  5. Brain Basics

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    Full Text Available ... pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah ... having trouble coping with the stresses in her life. She began to think of suicide because she ...

  6. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of the brain communicate and work with each other How changes in the brain ...

  7. Brain Basics

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    Full Text Available ... Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She was happily married and successful in business. Then, after a serious setback at work, she lost interest ...

  8. BASIC Programming.

    Science.gov (United States)

    Jennings, Carol Ann

    Designed for use by both secondary- and postsecondary-level business teachers, this curriculum guide consists of 10 units of instructional materials dealing with Beginners All-Purpose Symbol Instruction Code (BASIC) programing. Topics of the individual lessons are numbering BASIC programs and using the PRINT, END, and REM statements; system…

  9. Brain Basics

    Medline Plus

    Full Text Available ... Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... medical history. Epigenetic changes from stress or early-life experiences ... In contrast, major depression is a serious disorder that lasts for weeks. ...

  10. Optical Characterization of Oligonucleotide DNA Influenced by Magnetic Fields

    Directory of Open Access Journals (Sweden)

    Seyedeh Maryam Banihashemian

    2013-09-01

    Full Text Available UV-VIS spectroscopic analysis of oligonucleotide DNA exposed to different magnetic fields was performed in order to investigate the relationship between DNA extinction coefficients and optical parameters according to magnetic-field strength. The results with the oligonucleotides adenine-thymine 100 mer (AT-100 DNA and cytosine-guanine 100 mer (CG-100 DNA indicate that the magnetic field influences DNA molar extinction coefficients and refractive indexes. The imaginary parts of the refractive index and molar extinction coefficients of the AT-100 and CG-100 DNA decreased after exposure to a magnetic field of 750 mT due to cleavage of the DNA oligonucleotides into smaller segments.

  11. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez

    2010-01-01

    The main developments in muon alignment since March 2010 have been the production, approval and deployment of alignment constants for the ICHEP data reprocessing. In the barrel, a new geometry, combining information from both hardware and track-based alignment systems, has been developed for the first time. The hardware alignment provides an initial DT geometry, which is then anchored as a rigid solid, using the link alignment system, to a reference frame common to the tracker. The “GlobalPositionRecords” for both the Tracker and Muon systems are being used for the first time, and the initial tracker-muon relative positioning, based on the link alignment, yields good results within the photogrammetry uncertainties of the Tracker and alignment ring positions. For the first time, the optical and track-based alignments show good agreement between them; the optical alignment being refined by the track-based alignment. The resulting geometry is the most complete to date, aligning all 250 DTs, ...

  12. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    Z. Szillasi and G. Gomez.

    2013-01-01

    When CMS is opened up, major components of the Link and Barrel Alignment systems will be removed. This operation, besides allowing for maintenance of the detector underneath, is needed for making interventions that will reinforce the alignment measurements and make the operation of the alignment system more reliable. For that purpose and also for their general maintenance and recalibration, the alignment components will be transferred to the Alignment Lab situated in the ISR area. For the track-based alignment, attention is focused on the determination of systematic uncertainties, which have become dominant, since now there is a large statistics of muon tracks. This will allow for an improved Monte Carlo misalignment scenario and updated alignment position errors, crucial for high-momentum muon analysis such as Z′ searches.

  13. Basic hydraulics

    CERN Document Server

    Smith, P D

    2013-01-01

    BASIC Hydraulics aims to help students both to become proficient in the BASIC programming language by actually using the language in an important field of engineering and to use computing as a means of mastering the subject of hydraulics. The book begins with a summary of the technique of computing in BASIC together with comments and listing of the main commands and statements. Subsequent chapters introduce the fundamental concepts and appropriate governing equations. Topics covered include principles of fluid mechanics; flow in pipes, pipe networks and open channels; hydraulic machinery;

  14. Sequence-dependent theory of oligonucleotide hybridization kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Marimuthu, Karthikeyan [Department of Chemical Engineering and Center for Advanced Process Decision-Making, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States); Chakrabarti, Raj, E-mail: raj@pmc-group.com, E-mail: rajc@andrew.cmu.edu [Department of Chemical Engineering and Center for Advanced Process Decision-Making, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States); Division of Fundamental Research, PMC Advanced Technology, Mount Laurel, New Jersey 08054 (United States)

    2014-05-07

    A theoretical approach to the prediction of the sequence and temperature-dependent rate constants for oligonucleotide hybridization reactions has been developed based on the theory of relaxation kinetics. One-sided and two-sided melting reaction mechanisms for oligonucleotide hybridization reactions have been considered, analyzed, modified, and compared to select a physically consistent as well as robust model for prediction of the relaxation times of DNA hybridization reactions that agrees with the experimental evidence. The temperature- and sequence-dependent parameters of the proposed model have been estimated using available experimental data. The relaxation time model that we developed has been combined with the nearest neighbor model of hybridization thermodynamics to estimate the temperature- and sequence-dependent rate constants of an oligonucleotide hybridization reaction. The model-predicted rate constants are compared to experimentally determined rate constants for the same oligonucleotide hybridization reactions. Finally, we consider a few important applications of kinetically controlled DNA hybridization reactions.

  15. Oligonucleotide-based theranostic nanoparticles in cancer therapy.

    Science.gov (United States)

    Shahbazi, Reza; Ozpolat, Bulent; Ulubayram, Kezban

    2016-05-01

    Theranostic approaches, combining the functionality of both therapy and imaging, have shown potential in cancer nanomedicine. Oligonucleotides such as small interfering RNA and microRNA, which are powerful therapeutic agents, have been effectively employed in theranostic systems against various cancers. Nanoparticles are used to deliver oligonucleotides into tumors by passive or active targeting while protecting the oligonucleotides from nucleases in the extracellular environment. The use of quantum dots, iron oxide nanoparticles and gold nanoparticles and tagging with contrast agents, like fluorescent dyes, optical or magnetic agents and various radioisotopes, has facilitated early detection of tumors and evaluation of therapeutic efficacy. In this article, we review the advantages of theranostic applications in cancer therapy and imaging, with special attention to oligonucleotide-based therapeutics. PMID:27102380

  16. The nonenzymatic template-directed ligation of oligonucleotides

    Directory of Open Access Journals (Sweden)

    A.V. Lutay

    2006-01-01

    Full Text Available The nonenzymatic template-directed ligation of oligonucleotides containing 2',3'-cyclic phosphate was investigated in the presence of divalent cations. Ligation of the oligonucleotides readily occurred in the presence of Mg2+, Mn2+, Co2+, Zn2+, Pb2+. Efficacy of the metal ion catalysts inversely correlated with pKa values of the metal-bound water molecules. The intermolecular transesterification reaction yielded at least 95% of 2',5'-phosphodiester bonds independently on the nature of the metal ion. Relatively high reaction yields (up to 15% suggest, that RNA fragmentation to oligonucleotides with 2',3'-cyclic phosphates, followed by reactions of those oligonucleotides could provide a source of new RNA molecules under prebiotic conditions.

  17. Brain Basics

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    Full Text Available ... The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the ... distant nerve cells (via axons) to form brain circuits. These circuits control specific body functions such as ...

  18. Brain Basics

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    Full Text Available ... the anatomy, physiology, and chemistry of the nervous system. When the brain cannot effectively coordinate the billions ... basic working unit of the brain and nervous system. These cells are highly specialized for the function ...

  19. Brain Basics

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    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  20. Brain Basics

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    Full Text Available ... Trials — Participants Statistics Help for Mental Illnesses Outreach Research Priorities Funding Labs at NIMH News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The ...

  1. Brain Basics

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    Full Text Available ... normal brain development and function can go awry, leading to mental illnesses. Brain Basics will introduce you ... of DNA. Sometimes this copying process is imperfect, leading to a gene mutation that causes the gene ...

  2. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics will introduce you to some of this science, such as: How the brain develops How ... cell, and responds to signals from the environment; this all helps the cell maintain its balance with ...

  3. Brain Basics

    Medline Plus

    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... However, recent research points to a possible new class of antidepressants that can relieve symptoms of the ...

  4. Brain Basics

    Medline Plus

    Full Text Available ... for the function of conducting messages. A neuron has three basic parts: Cell body which includes the ... disorder (ADHD) . Glutamate —the most common neurotransmitter, glutamate has many roles throughout the brain and nervous system. ...

  5. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... others live with symptoms of mental illness every day. They can be moderate, or serious and cause ...

  6. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  7. Brain Basics

    Medline Plus

    Full Text Available ... the function of conducting messages. A neuron has three basic parts: Cell body which includes the nucleus, ... Plan in 2016 August 31, 2016, 2:00-3:00 PM ET Recovery Month September 2016 National ...

  8. Basic Finance

    Science.gov (United States)

    Vittek, J. F.

    1972-01-01

    A discussion of the basic measures of corporate financial strength, and the sources of the information is reported. Considered are: balance sheet, income statement, funds and cash flow, and financial ratios.

  9. Cancer Basics

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  10. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...

  11. Blood Basics

    Science.gov (United States)

    ... Patient Group Links Advocacy Toolkit Home For Patients Blood Basics Blood is a specialized body fluid. It ... about 9 pints. Jump To: The Components of Blood and Their Importance Many people have undergone blood ...

  12. Brain Basics

    Medline Plus

    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... volunteers PubMed Central: An archive of life sciences journals NIH Research Fact Sheets NIH Office of Science ...

  13. Brain Basics

    Medline Plus

    Full Text Available ... How the brain develops How genes and the environment affect the brain The basic structure of the ... inside contents of the cell from its surrounding environment and controls what enters and leaves the cell, ...

  14. Brain Basics

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    Full Text Available ... and the environment affect the brain The basic structure of the brain How different parts of the ... for the cell to work properly including small structures called cell organelles. Dendrites branch off from the ...

  15. Brain Basics

    Medline Plus

    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... interconnections. neuron —A nerve cell that is the basic, working unit of the brain and nervous system, which processes and transmits information. neurotransmitter —A chemical produced by ...

  17. Brain Basics

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    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... blues" from time to time. In contrast, major depression is a serious disorder that lasts for weeks. ...

  18. Body Basics

    Science.gov (United States)

    ... about how the body works, what basic human anatomy is, and what happens when parts of the body don't function properly. Blood Bones, Muscles, and Joints Brain and Nervous System Digestive System Endocrine System Eyes Female Reproductive System ...

  19. Brain Basics

    Medline Plus

    Full Text Available ... Health & Education Mental Health Information Publications Educational Resources Clinical Trials — Participants Statistics Help for Mental Illnesses Outreach Research Priorities Funding Labs at NIMH News About Us Home > Health & Education > Educational Resources Brain Basics Introduction ...

  20. Tracing magnetic fields with aligned grains

    Energy Technology Data Exchange (ETDEWEB)

    Lazarian, A. [Astronomy Department, University of Wisconsin-Madison, 475 N. Charter St., Madison, WI 53706 (United States)]. E-mail: lazarian@astro.wisc.edu

    2007-07-15

    Magnetic fields play a crucial role in various astrophysical processes, including star formation, accretion of matter, transport processes (e.g., transport of heat), and cosmic rays. One of the easiest ways to determine the magnetic field direction is via polarization of radiation resulting from extinction or/and emission by aligned dust grains. Reliability of interpretation of the polarization maps in terms of magnetic fields depends on how well we understand the grain-alignment theory. Explaining what makes grains aligned has been one of the big issues of the modern astronomy. Numerous exciting physical effects have been discovered in the course of research undertaken in this field. As both the theory and observations matured, it became clear that the grain-alignment phenomenon is inherent not only in diffuse interstellar medium or molecular clouds but also is a generic property of the dust in circumstellar regions, interplanetary space and cometary comae. Currently the grain-alignment theory is a predictive one, and its results nicely match observations. Among its predictions is a subtle phenomenon of radiative torques. This phenomenon, after having stayed in oblivion for many years after its discovery, is currently viewed as the most powerful means of alignment. In this article, I shall review the basic physical processes involved in grain alignment, and the currently known mechanisms of alignment. I shall also discuss possible niches for different alignment mechanisms. I shall dwell on the importance of the concept of grain helicity for understanding of many properties of grain alignment, and shall demonstrate that rather arbitrarily shaped grains exhibit helicity when they interact with gaseous and radiative flows.

  1. Synthesis and applications of oligonucleotides containing 2'-modified nucleosides

    OpenAIRE

    Shelbourne, Montserrat

    2012-01-01

    This thesis describes the synthesis and applications of chemically modified oligonucleotides, principally those containing modifications at the 2?-position of ribose. One application is their use in triplex-forming oligonucleotides (TFOs). DNA triplexes are formed by the binding of a TFO to a DNA duplex. TFOs are potential therapeutic agents against cancer and viral infections. TFOs containing 2?-aminoethoxy-T and 5-MeC were shown by UV melting studies to strongly stabilise parallel triple...

  2. Electron migration in oligonucleotides upon γ-irradiation in solution

    International Nuclear Information System (INIS)

    Electron migration in irradiated solutions of DNA was investigated using 5-bromouracil synthetically incorporated into oligonucleotides of defined base composition as a molecular indicator of electron interactions. Solvated electrons interact quantitatively with 5-bromouracil, leading to a highly reactive 5-yl radical which can abstract an adjacent hydrogen atom to yield uracil. Yields of uracil, or loss of 5-bromouracil, from irradiated oligonucleotide samples were measured using gas chromatography-mass spectrometric analysis of their trimethylsilylated acid hydrolysates. (author)

  3. Portable System for Microbial Sample Preparation and Oligonucleotide Microarray Analysis

    OpenAIRE

    Bavykin, Sergei G.; Akowski, James P.; Zakhariev, Vladimir M.; Barsky, Viktor E.; Perov, Alexander N.; Mirzabekov, Andrei D.

    2001-01-01

    We have developed a three-component system for microbial identification that consists of (i) a universal syringe-operated silica minicolumn for successive DNA and RNA isolation, fractionation, fragmentation, fluorescent labeling, and removal of excess free label and short oligonucleotides; (ii) microarrays of immobilized oligonucleotide probes for 16S rRNA identification; and (iii) a portable battery-powered device for imaging the hybridization of fluorescently labeled RNA fragments with the ...

  4. Sequencing of oligonucleotide phosphorothioates based on solid-supported desulfurization.

    OpenAIRE

    Wyrzykiewicz, T K; Cole, D L

    1994-01-01

    We described a solid-supported desulfurization procedure allowing easy access to the sequence analysis of oligonucleotide phosphorothioates. The described method is based upon selective removal of the 2-cyanoethyl phosphate protecting groups, followed by iodine-promoted desulfurization of the resulting phosphorothioate diesters. Automatic oxidation of oligonucleotide phosphorothioates, anchored via an ester linkage to a standard solid support (LCAA/CPG), is combined with Maxam-Gilbert solid-s...

  5. An algorithm and program for finding sequence specific oligo-nucleotide probes for species identification

    Directory of Open Access Journals (Sweden)

    Tautz Diethard

    2002-03-01

    Full Text Available Abstract Background The identification of species or species groups with specific oligo-nucleotides as molecular signatures is becoming increasingly popular for bacterial samples. However, it shows also great promise for other small organisms that are taxonomically difficult to tract. Results We have devised here an algorithm that aims to find the optimal probes for any given set of sequences. The program requires only a crude alignment of these sequences as input and is optimized for performance to deal also with very large datasets. The algorithm is designed such that the position of mismatches in the probes influences the selection and makes provision of single nucleotide outloops. Program implementations are available for Linux and Windows.

  6. Oligonucleotide conjugates - Candidates for gene silencing therapeutics.

    Science.gov (United States)

    Gooding, Matt; Malhotra, Meenakshi; Evans, James C; Darcy, Raphael; O'Driscoll, Caitriona M

    2016-10-01

    The potential therapeutic and diagnostic applications of oligonucleotides (ONs) have attracted great attention in recent years. The capability of ONs to selectively inhibit target genes through antisense and RNA interference mechanisms, without causing un-intended sideeffects has led them to be investigated for various biomedical applications, especially for the treatment of viral diseases and cancer. In recent years, many researchers have focused on enhancing the stability and target specificity of ONs by encapsulating/complexing them with polymers or lipid chains to formulate nanoparticles/nanocomplexes/micelles. Also, chemical modification of nucleic acids has emerged as an alternative to impart stability to ONs against nucleases and other degrading enzymes and proteins found in blood. In addition to chemically modifying the nucleic acids directly, another strategy that has emerged, involves conjugating polymers/peptide/aptamers/antibodies/proteins, preferably to the sense strand (3'end) of siRNAs. Conjugation to the siRNA not only enhances the stability and targeting specificity of the siRNA, but also allows for the development of self-administering siRNA formulations, with a much smaller size than what is usually observed for nanoparticle (∼200nm). This review concentrates mainly on approaches and studies involving ON-conjugates for biomedical applications. PMID:27521696

  7. Oligonucleotide and Long Polymeric DNA Encoding

    Energy Technology Data Exchange (ETDEWEB)

    Miller, E; Mariella Jr., R P; Christian, A T; Gardner, S N; Williams, J M

    2003-11-24

    This report summarizes the work done at Lawrence Livermore National Laboratory for the Oligonucleotide and Long Polymeric DNA Encoding project, part of the Microelectronic Bioprocesses Program at DARPA. The goal of the project was to develop a process by which long (circa 10,000 base-pair) synthetic DNA molecules could be synthesized in a timely and economic manner. During construction of the long molecule, errors in DNA sequence occur during hybridization and/or the subsequent enzymatic process. The work done on this project has resulted in a novel synthesis scheme that we call the parallel pyramid synthesis protocol, the development of a suit of computational tools to minimize and quantify errors in the synthesized DNA sequence, and experimental proof of this technique. The modeling consists of three interrelated modules: the bioinformatics code which determines the specifics of parallel pyramid synthesis for a given chain of long DNA, the thermodynamics code which tracks the products of DNA hybridization and polymerase extension during the later steps in the process, and the kinetics model which examines the temporal and spatial processes during one thermocycle. Most importantly, we conducted the first successful syntheses of a gene using small starting oligomers (tetramers). The synthesized sequence, 813 base pairs long, contained a 725 base pair gene, modified green fluorescent protein (mGFP), which has been shown to be a functional gene by cloning into cells and observing its green fluorescent product.

  8. Antisense Oligonucleotide Therapy for Inherited Retinal Dystrophies.

    Science.gov (United States)

    Gerard, Xavier; Garanto, Alejandro; Rozet, Jean-Michel; Collin, Rob W J

    2016-01-01

    Inherited retinal dystrophies (IRDs) are an extremely heterogeneous group of genetic diseases for which currently no effective treatment strategies exist. Over the last decade, significant progress has been made utilizing gene augmentation therapy for a few genetic subtypes of IRD, although several technical challenges so far prevent a broad clinical application of this approach for other forms of IRD. Many of the mutations leading to these retinal diseases affect pre-mRNA splicing of the mutated genes . Antisense oligonucleotide (AON)-mediated splice modulation appears to be a powerful approach to correct the consequences of such mutations at the pre-mRNA level , as demonstrated by promising results in clinical trials for several inherited disorders like Duchenne muscular dystrophy, hypercholesterolemia and various types of cancer. In this mini-review, we summarize ongoing pre-clinical research on AON-based therapy for a few genetic subtypes of IRD , speculate on other potential therapeutic targets, and discuss the opportunities and challenges that lie ahead to translate splice modulation therapy for retinal disorders to the clinic. PMID:26427454

  9. Optimizing antisense oligonucleotides using phosphorodiamidate morpholino oligomers.

    Science.gov (United States)

    Popplewell, Linda J; Malerba, Alberto; Dickson, George

    2012-01-01

    Duchenne muscular dystrophy (DMD) is caused by mutations that disrupt the reading frame of the human DMD gene. Selective removal of exons flanking an out-of-frame DMD mutation can result in an in-frame mRNA transcript that may be translated into an internally deleted Becker muscular dystrophy-like functionally active dystrophin protein with therapeutic activity. Antisense oligonucleotides (AOs) can be designed to bind to complementary sequences in the targeted mRNA and modify pre-mRNA splicing to correct the reading frame of a mutated transcript. AO-induced exon skipping resulting in functional truncated dystrophin has been demonstrated in animal models of DMD both in vitro and in vivo, in DMD patient cells in vitro in culture, and in DMD muscle explants. The recent advances made in this field suggest that it is likely that AO-induced exon skipping will be the first gene therapy for DMD to reach the clinic. However, it should be noted that personalized molecular medicine may be necessary, since the various reading frame-disrupting mutations are spread across the DMD gene. The different deletions that cause DMD would require skipping of different exons, which would require the optimization and clinical trial workup of many specific AOs. This chapter describes the methodologies available for the optimization of AOs, in particular phosphorodiamidate morpholino oligomers, for the targeted skipping of specific exons on the DMD gene. PMID:22454060

  10. Hole hopping rates in single strand oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Borrelli, Raffaele [Dipartimento di Scienze Agrarie, Forestali e Alimentari, Università di Torino, Largo Paolo Braccini 2, I-10095 Grugliasco, TO (Italy); Capobianco, Amedeo [Dipartimento di Chimica e Biologia, Università di Salerno, Via Giovanni Paolo II, I-84084 Fisciano, SA (Italy); Peluso, Andrea, E-mail: apeluso@unisa.it [Dipartimento di Chimica e Biologia, Università di Salerno, Via Giovanni Paolo II, I-84084 Fisciano, SA (Italy)

    2014-08-31

    Highlights: • DNA hole transfer rates have been computed. • Delocalized adenine domains significantly affect hole transfer rates in DNA. • Franck–Condon weighted density of state from DFT normal modes. • DNA application in molecular electronics. - Abstract: The rates of hole transfer between guanine and adenine in single strand DNA have been evaluated by using Fermi’s golden rule and Kubo’s generating function approach for the Franck–Condon weighted density of states. The whole sets of the normal modes and vibrational frequencies of the two nucleobases, obtained at DFT/B3LYP level of calculation, have been considered in computations. The results show that in single strand the pyramidalization/planarization mode of the amino groups of both nucleobases plays the major role. At room temperature, the Franck–Condon density of states extends over a wide range of hole site energy difference, 0–1 eV, giving some hints about the design of oligonucleotides of potential technological interest.

  11. Fast Statistical Alignment

    OpenAIRE

    Bradley, Robert K.; Adam Roberts; Michael Smoot; Sudeep Juvekar; Jaeyoung Do; Colin Dewey; Ian Holmes; Lior Pachter

    2009-01-01

    We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multi...

  12. An enhanced algorithm for multiple sequence alignment of protein sequences using genetic algorithm

    OpenAIRE

    Kumar, Manish

    2015-01-01

    One of the most fundamental operations in biological sequence analysis is multiple sequence alignment (MSA). The basic of multiple sequence alignment problems is to determine the most biologically plausible alignments of protein or DNA sequences. In this paper, an alignment method using genetic algorithm for multiple sequence alignment has been proposed. Two different genetic operators mainly crossover and mutation were defined and implemented with the proposed method in order to know the pop...

  13. Horizontal carbon nanotube alignment.

    Science.gov (United States)

    Cole, Matthew T; Cientanni, Vito; Milne, William I

    2016-09-21

    The production of horizontally aligned carbon nanotubes offers a rapid means of realizing a myriad of self-assembled near-atom-scale technologies - from novel photonic crystals to nanoscale transistors. The ability to reproducibly align anisotropic nanostructures has huge technological value. Here we review the present state-of-the-art in horizontal carbon nanotube alignment. For both in and ex situ approaches, we quantitatively assess the reported linear packing densities alongside the degree of alignment possible for each of these core methodologies. PMID:27546174

  14. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez

    2010-01-01

    Most of the work in muon alignment since December 2009 has focused on the geometry reconstruction from the optical systems and improvements in the internal alignment of the DT chambers. The barrel optical alignment system has progressively evolved from reconstruction of single active planes to super-planes (December 09) to a new, full barrel reconstruction. Initial validation studies comparing this full barrel alignment at 0T with photogrammetry provide promising results. In addition, the method has been applied to CRAFT09 data, and the resulting alignment at 3.8T yields residuals from tracks (extrapolated from the tracker) which look smooth, suggesting a good internal barrel alignment with a small overall offset with respect to the tracker. This is a significant improvement, which should allow the optical system to provide a start-up alignment for 2010. The end-cap optical alignment has made considerable progress in the analysis of transfer line data. The next set of alignment constants for CSCs will there...

  15. Orthodontics and Aligners

    Science.gov (United States)

    ... Repairing Chipped Teeth Teeth Whitening Tooth-Colored Fillings Orthodontics and Aligners Straighten teeth for a healthier smile. Orthodontics When consumers think about orthodontics, braces are the ...

  16. Conformational fluctuations affect protein alignment in dilute liquid crystal media

    DEFF Research Database (Denmark)

    Louhivuori, M.; Otten, R.; Lindorff-Larsen, Kresten;

    2006-01-01

    The discovery of dilute liquid crystalline media to align biological macromolecules has opened many new possibilities to study protein and nucleic acid structures by NMR spectroscopy. We inspect the basic alignment phenomenon for an ensemble of protein conformations to deduce relative contributions...

  17. Basic electronics

    CERN Document Server

    Holbrook, Harold D

    1971-01-01

    Basic Electronics is an elementary text designed for basic instruction in electricity and electronics. It gives emphasis on electronic emission and the vacuum tube and shows transistor circuits in parallel with electron tube circuits. This book also demonstrates how the transistor merely replaces the tube, with proper change of circuit constants as required. Many problems are presented at the end of each chapter. This book is comprised of 17 chapters and opens with an overview of electron theory, followed by a discussion on resistance, inductance, and capacitance, along with their effects on t

  18. Efficient oligonucleotide probe selection for pan-genomic tiling arrays

    Directory of Open Access Journals (Sweden)

    Zhang Wei

    2009-09-01

    Full Text Available Abstract Background Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. Results This paper presents a new probe selection algorithm (PanArray that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pan-genome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. Conclusion PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on

  19. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    Gervasio Gomez

    The main progress of the muon alignment group since March has been in the refinement of both the track-based alignment for the DTs and the hardware-based alignment for the CSCs. For DT track-based alignment, there has been significant improvement in the internal alignment of the superlayers inside the DTs. In particular, the distance between superlayers is now corrected, eliminating the residual dependence on track impact angles, and good agreement is found between survey and track-based corrections. The new internal geometry has been approved to be included in the forthcoming reprocessing of CRAFT samples. The alignment of DTs with respect to the tracker using global tracks has also improved significantly, since the algorithms use the latest B-field mapping, better run selection criteria, optimized momentum cuts, and an alignment is now obtained for all six degrees of freedom (three spatial coordinates and three rotations) of the aligned DTs. This work is ongoing and at a stage where we are trying to unders...

  20. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez

    2011-01-01

    The Muon Alignment work now focuses on producing a new track-based alignment with higher track statistics, making systematic studies between the results of the hardware and track-based alignment methods and aligning the barrel using standalone muon tracks. Currently, the muon track reconstruction software uses a hardware-based alignment in the barrel (DT) and a track-based alignment in the endcaps (CSC). An important task is to assess the muon momentum resolution that can be achieved using the current muon alignment, especially for highly energetic muons. For this purpose, cosmic ray muons are used, since the rate of high-energy muons from collisions is very low and the event statistics are still limited. Cosmics have the advantage of higher statistics in the pT region above 100 GeV/c, but they have the disadvantage of having a mostly vertical topology, resulting in a very few global endcap muons. Only the barrel alignment has therefore been tested so far. Cosmic muons traversing CMS from top to bottom are s...

  1. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez

    Since December, the muon alignment community has focused on analyzing the data recorded so far in order to produce new DT and CSC Alignment Records for the second reprocessing of CRAFT data. Two independent algorithms were developed which align the DT chambers using global tracks, thus providing, for the first time, a relative alignment of the barrel with respect to the tracker. These results are an important ingredient for the second CRAFT reprocessing and allow, for example, a more detailed study of any possible mis-modelling of the magnetic field in the muon spectrometer. Both algorithms are constructed in such a way that the resulting alignment constants are not affected, to first order, by any such mis-modelling. The CSC chambers have not yet been included in this global track-based alignment due to a lack of statistics, since only a few cosmics go through the tracker and the CSCs. A strategy exists to align the CSCs using the barrel as a reference until collision tracks become available. Aligning the ...

  2. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  3. Oligonucleotide recombination in corynebacteria without the expression of exogenous recombinases.

    Science.gov (United States)

    Krylov, Alexander A; Kolontaevsky, Egor E; Mashko, Sergey V

    2014-10-01

    Brevibacterium lactofermentum and Corynebacterium glutamicum are important biotechnology species of the genus Corynebacterium. The single-strand DNA annealing protein (SSAP)-independent oligonucleotide-mediated recombination procedure was successfully applied to the commonly used wild-type strains B. lactofermentum AJ1511 and C. glutamicum ATCC13032. When the rpsL gene was used as a target, the optimized protocol yielded up to (1.4±0.3)×10(3) and (6.7±1.3)×10(3) streptomycin-resistant colonies per 10(8) viable cells for the corresponding strains. We tested the influence of several parameters that are known to enhance the efficiency of oligonucleotide-mediated recombination in other bacterial species. Among them, increasing the concentration of oligonucleotides and targeting the lagging strand of the chromosome have proven to have positive effects on both of the tested species. No difference in the efficiency of recombination was observed between the oligonucleotides phosphorothiorated at the 5' ends and the unmodified oligonucleotides or between the oligonucleotides with four mutated nucleotides and those with one mutated nucleotide. The described approach demonstrates that during the adaptation of the recombineering technique, testing SSAP-independent oligonucleotide-mediated recombination could be a good starting point. Such testing could decrease the probability of an incorrect interpretation of the effect of exogenous protein factors (such as SSAP and/or corresponding exonucleases) due to non-optimal experimental conditions. In addition, SSAP-independent recombination itself could be useful in combination with suitable selection/enrichment methods. PMID:25087479

  4. Brain Basics

    Medline Plus

    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman ... new memories. hypothalmic-pituitary-adrenal (HPA) axis —A brain-body ... stress. impulse —An electrical communication signal sent between neurons ...

  5. Basic Skills.

    Science.gov (United States)

    Luparelli, Augustus N.; And Others

    1981-01-01

    These four articles focus on developing basic reading, science, and job search skills: "Reading Program for Vocational Classes" by Augustus Luparelli; "Why Teach Employability Skills?" by Larry Siefferman; "Improving Vocabulary and Reading Skills" by Edythe Conway; and "Science in Everyday Life" by Virginia Eleazer and George Carney. (SK)

  6. Brain Basics

    Medline Plus

    Full Text Available ... will fire. This enhances the electrical flow among brain cells required for normal function and plays an important ... of neurons and their interconnections. neuron —A nerve cell that is the basic, working unit of the brain and nervous system, which processes and transmits information. ...

  7. Brain Basics

    Medline Plus

    Full Text Available ... Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ...

  8. Ethanol Basics

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-01-30

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  9. Basic Backwardness.

    Science.gov (United States)

    Weingartner, Charles

    This paper argues that the "back to basics" movement is regressive and that regression is the characteristic mode of fear-ridden personalities. It is argued that many people in American society today have lost their ability to laugh and do not have the sense of humor which is crucial to a healthy mental state. Such topics as necrophilia, mental…

  10. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez

    2011-01-01

    A new set of muon alignment constants was approved in August. The relative position between muon chambers is essentially unchanged, indicating good detector stability. The main changes concern the global positioning of the barrel and of the endcap rings to match the new Tracker geometry. Detailed studies of the differences between track-based and optical alignment of DTs have proven to be a valuable tool for constraining Tracker alignment weak modes, and this information is now being used as part of the alignment procedure. In addition to the “split-cosmic” analysis used to investigate the muon momentum resolution at high momentum, a new procedure based on reconstructing the invariant mass of di-muons from boosted Zs is under development. Both procedures show an improvement in the momentum precision of Global Muons with respect to Tracker-only Muons. Recent developments in track-based alignment include a better treatment of the tails of residual distributions and accounting for correla...

  11. Real Interference Alignment

    CERN Document Server

    Motahari, Abolfazl Seyed; Maddah-Ali, Mohammad-Ali; Khandani, Amir Keyvan

    2010-01-01

    In this paper, we show that the total Degrees-Of-Freedoms (DOF) of the $K$-user Gaussian Interference Channel (GIC) can be achieved by incorporating a new alignment technique known as \\emph{real interference alignment}. This technique compared to its ancestor \\emph{vector interference alignment} performs on a single real line and exploits the properties of real numbers to provide optimal signaling. The real interference alignment relies on a new coding scheme in which several data streams having fractional multiplexing gains are sent by transmitters and interfering streams are aligned at receivers. The coding scheme is backed up by a recent result in the field of Diophantine approximation, which states that the convergence part of the Khintchine-Groshev theorem holds for points on non-degenerate manifolds.

  12. Inhibition of hepatitis B virus in vitro by antisense oligonucleotides

    International Nuclear Information System (INIS)

    A series of antisense phosphorothioate oligodeoxynucleotides against hepatitis B virus (HBV) were synthesized and evaluated for their antiviral effect in Hep-G2 cells transfected with HBV genome. The inhibitor effect of the tested antisense oligonucleotides was sequence-specific, dose- and time-dependent, and synergistic for certain combinations. In virus-inhibitory concentrations the oligonucleotides were harmless to 2.2.15 cells. The most effective antisense oligonucleotides were found directed against the HBV mRNA transcribed from the cap site of SP II promoter, the portion of polyadenylation signal and the initiation region of gene S, with an inhibition of the HBsAg and HBeAg production by 85 - 95 % and 50 - 60 %, respectively. To our surprise, antisense oligonucleotides directed against three key sites of HBV X gene blocked the expression of HBsAg, HBeAg and HBxAg. This fact might be related to the trans-activation of HBV X protein. Using radioisotope labelling, we demonstrated that Lipofectin promoted the cellular uptake and antiviral effect of antisense oligomers in 2.2.15 cells. These results suggest a therapeutic potential of antisense oligonucleotides in the treatment of patients chronically infected with HBV. (author)

  13. Stability measurements of antisense oligonucleotides by capillary gel electrophoresis.

    Science.gov (United States)

    Bruin, G J; Börnsen, K O; Hüsken, D; Gassmann, E; Widmer, H M; Paulus, A

    1995-08-11

    The approach of using antisense oligonucleotides as potential drugs is based on hybridization of a short chemically-modified oligonucleotide with complementary cellular DNA or RNA sequences. A critical question is the stability of chemically modified antisense oligonucleotides in cellular environments. In a model system, resistance against various nucleases was evaluated by capillary gel electrophoresis (CGE). For some of the samples, matrix assisted laser desorption and ionization mass spectrometry (MALDI-MS) was used as an additional analytical tool to perform stability measurements. Using CGE, the enzymatic degradation of single nucleotides from the oligomer can be followed after different incubation times. 10% T polyacrylamide gels give baseline resolution for oligonucleotides ranging between 5 and 30 bases in length. The kinetic influence of a specific nuclease concentration and the antisense oligonucleotide structure on the cleavage reaction are discussed. Also, a simple desalting method to improve the injection efficiency and sensitivity of the method are described. Examples of measurements of chemically modified antisense 19-mers are presented. PMID:7581844

  14. Alignment for CSR

    International Nuclear Information System (INIS)

    Cooled Storage Ring of Heavy Ion Research Facility in Lanzhou (HIRFL-CSR) belongs to China great scientific project in China. The alignment for it is very difficult because of very large area and very high accuracy. For the special case in HIRFL-CSR, some new methods and new instruments are used, including the construction of survey control network, the usage of laser tracker, and CSR alignment database system with applications developed to store and analyze data. The author describes the whole procedure of CSR alignment

  15. Galaxy alignments: An overview

    CERN Document Server

    Joachimi, Benjamin; Kitching, Thomas D; Leonard, Adrienne; Mandelbaum, Rachel; Schäfer, Björn Malte; Sifón, Cristóbal; Hoekstra, Henk; Kiessling, Alina; Kirk, Donnacha; Rassat, Anais

    2015-01-01

    The alignments between galaxies, their underlying matter structures, and the cosmic web constitute vital ingredients for a comprehensive understanding of gravity, the nature of matter, and structure formation in the Universe. We provide an overview on the state of the art in the study of these alignment processes and their observational signatures, aimed at a non-specialist audience. The development of the field over the past one hundred years is briefly reviewed. We also discuss the impact of galaxy alignments on measurements of weak gravitational lensing, and discuss avenues for making theoretical and observational progress over the coming decade.

  16. Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Goyenvalle Aurélie

    2011-02-01

    Full Text Available Abstract Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.

  17. Oligonucleotide probes for the screening of recombinant DNA libraries

    International Nuclear Information System (INIS)

    Oligonucleotides of unique sequence are also useful for screening recombinant DNA libraries. The hybridization specificity of oligonucleotide probes allows one to use unique sequences probes to screen for genomic clones or cDNAs encoding a specific number of a multigene family, to screen for a new allele when the sequence of one allele is known, to screen for a specific region of a gene, to screen for specific mutants created by site-directed mutagenesis, or to screen libraries with probes whose sequence represents a consensus coding sequence. This chapter deals with procedures for the use of oligonucleotides as hybridization probes including probe design, labeling, and hybridization to colonies, phage plaques, DNA, and RNA

  18. Delivery of RNAi-Based Oligonucleotides by Electropermeabilization

    Directory of Open Access Journals (Sweden)

    Muriel Golzio

    2013-04-01

    Full Text Available For more than a decade, understanding of RNA interference (RNAi has been a growing field of interest. The potent gene silencing ability that small oligonucleotides have offers new perspectives for cancer therapeutics. One of the present limits is that many biological barriers exist for their efficient delivery into target cells or tissues. Electropermeabilization (EP is one of the physical methods successfully used to transfer small oligonucleotides into cells or tissues. EP consists in the direct application of calibrated electric pulses to cells or tissues that transiently permeabilize the plasma membranes, allowing efficient in vitro and in vivo. cytoplasmic delivery of exogenous molecules. The present review reports on the type of therapeutic RNAi-based oligonucleotides that can be electrotransferred, the mechanism(s of their electrotransfer and the technical settings for pre-clinical purposes.

  19. Tidal alignment of galaxies

    CERN Document Server

    Blazek, Jonathan; Seljak, Uroš

    2015-01-01

    We develop an analytic model for galaxy intrinsic alignments (IA) based on the theory of tidal alignment. We calculate all relevant nonlinear corrections at one-loop order, including effects from nonlinear density evolution, galaxy biasing, and source density weighting. Contributions from density weighting are found to be particularly important and lead to bias dependence of the IA amplitude, even on large scales. This effect may be responsible for much of the luminosity dependence in IA observations. The increase in IA amplitude for more highly biased galaxies reflects their locations in regions with large tidal fields. We also consider the impact of smoothing the tidal field on halo scales. We compare the performance of this consistent nonlinear model in describing the observed alignment of luminous red galaxies with the linear model as well as the frequently used "nonlinear alignment model," finding a significant improvement on small and intermediate scales. We also show that the cross-correlation between ...

  20. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez

    Since September, the muon alignment system shifted from a mode of hardware installation and commissioning to operation and data taking. All three optical subsystems (Barrel, Endcap and Link alignment) have recorded data before, during and after CRAFT, at different magnetic fields and during ramps of the magnet. This first data taking experience has several interesting goals: •    study detector deformations and movements under the influence of the huge magnetic forces; •    study the stability of detector structures and of the alignment system over long periods, •    study geometry reproducibility at equal fields (specially at 0T and 3.8T); •    reconstruct B=0T geometry and compare to nominal/survey geometries; •    reconstruct B=3.8T geometry and provide DT and CSC alignment records for CMSSW. However, the main goal is to recons...

  1. Basic electronics

    CERN Document Server

    Tayal, DC

    2010-01-01

    The second edition of this book incorporates the comments and suggestions of my friends and students who have critically studied the first edition. In this edition the changes and additions have been made and subject matter has been rearranged at some places. The purpose of this text is to provide a comprehensive and up-to-date study of the principles of operation of solid state devices, their basic circuits and application of these circuits to various electronic systems, so that it can serve as a standard text not only for universities and colleges but also for technical institutes. This book

  2. Regression Basics

    CERN Document Server

    Kahane, Leo H

    2007-01-01

    Using a friendly, nontechnical approach, the Second Edition of Regression Basics introduces readers to the fundamentals of regression. Accessible to anyone with an introductory statistics background, this book builds from a simple two-variable model to a model of greater complexity. Author Leo H. Kahane weaves four engaging examples throughout the text to illustrate not only the techniques of regression but also how this empirical tool can be applied in creative ways to consider a broad array of topics. New to the Second Edition Offers greater coverage of simple panel-data estimation:

  3. Silver and Cyanine Staining of Oligonucleotides in Polyacrylamide Gel

    OpenAIRE

    Tang, Weizhong; Zhou, Huafu; Li, Wei

    2015-01-01

    To explore why some oligonucleotides in denaturing polyacrylamide gel could not be silver-stained, 134 different oligonucleotides were analyzed using denaturing polyacrylamide gel electrophoresis stained with silver and asymmetric cyanine. As a result, we found that the sensitivity of oligos (dA), (dC), (dG) and (dT) to silver staining could be ranged as (dA) > (dG) > (dC) > (dT) from high to low. It was unexpected that oligo (dT) was hard to be silver-stained. Moreover, the silver staining o...

  4. Versatile functionalization of nanoelectrodes by oligonucleotides via pyrrole electrochemistry.

    Science.gov (United States)

    Descamps, Emeline; Nguyen, Khoa; Bouchain-Gautier, Christelle; Filoramo, Arianna; Goux-Capes, Laurence; Goffman, Marcello; Bourgoin, Jean-Philippe; Mailley, Pascal; Livache, Thierry

    2010-11-15

    Surface modification at the nanometer scale is a challenge for the future of molecular electronics. In particular, the precise anchoring and electrical addressing of biological scaffolds such as complex DNA nanonetworks is of importance for generating bio-directed assemblies of nano-objects for nanocircuit purposes. Herein, we consider the individual modification of nanoelectrodes with different oligonucleotide sequences by an electrochemically driven co-polymerization process of pyrrole and modified oligonucleotide sequences bearing pyrrole monomers. We demonstrate that this one-step technique presents the advantages of simplicity, localization of surface modification, mechanical, biological and chemical stability of the coatings, and high lateral resolution. PMID:20973021

  5. Introduction of radiolabeled therapeutic oligonucleotides as nanonuclear explosive gene therapy

    International Nuclear Information System (INIS)

    The synthetic oligonucleotide technology is also at early trial points in human testing against HIV, leukemia, Herpes virus, and other diseases, whose outcome will remain for the future. The current status of these varied approaches is presented in later parts in this article: What are therapeutic oligonucleotides?, Why Auger-emitters are useful in gene therapy?, What is the synergistic effect on combining Auger emitter and Triplex-forming ODN?, How have TFO researches evolved from the starting point?, In which areas of clinical research will this research illuminating?

  6. VirOligo: a database of virus-specific oligonucleotides

    OpenAIRE

    Onodera, Kenji; Melcher, Ulrich

    2002-01-01

    VirOligo is a database of virus-specific oligonucleotides. The VirOligo database consists of two tables, Common data and Oligo data. The Oligo data table contains PCR primers and hybridization probes used for detection of viral nucleic acids and the Common data table contains the experimental conditions used in their detection. Each oligonucleotide entry contains links to PubMed, GenBank, NCBI Taxonomy databases and BLAST. As of July 2001, the VirOligo database contains a complete listing of ...

  7. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    S. Szillasi

    2013-01-01

    The CMS detector has been gradually opened and whenever a wheel became exposed the first operation was the removal of the MABs, the sensor structures of the Hardware Barrel Alignment System. By the last days of June all 36 MABs have arrived at the Alignment Lab at the ISR where, as part of the Alignment Upgrade Project, they are refurbished with new Survey target holders. Their electronic checkout is on the way and finally they will be recalibrated. During LS1 the alignment system will be upgraded in order to allow more precise reconstruction of the MB4 chambers in Sector 10 and Sector 4. This requires new sensor components, so called MiniMABs (pictured below), that have already been assembled and calibrated. Image 6: Calibrated MiniMABs are ready for installation For the track-based alignment, the systematic uncertainties of the algorithm are under scrutiny: this study will enable the production of an improved Monte Carlo misalignment scenario and to update alignment position errors eventually, crucial...

  8. ATLAS Muon Endcap Alignment

    CERN Document Server

    Bensinger, J R

    2005-01-01

    To align the endcap muon chambers of the ATLAS experiment, an optical grid is set up between aluminum “alignment bars” nested in each layer of chambers. Optical lines are made of laser diodes and CCD cameras that form an alignment grid. The alignment bars are self-aligning. They are then carefully measured using a large coordinate measuring machine (CMM). The subsequent shape changes of the bar are determined by calculations that are corrected by the readings of the internal monitors. The relationship between the bars is then established by a network of sensors that measure the bearing angle of light sources on the other parts of the system. The system is over-determined and the location and orientation of each bar is determined using a fitting program. Chambers are then referenced to the alignment grid using proximity sensors. This information is used to provide corrections to the nominal chamber positions before calculating track momentum. The performance of the system has been validated in a test beam ...

  9. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez

    2012-01-01

      A new muon alignment has been produced for 2012 A+B data reconstruction. It uses the latest Tracker alignment and single-muon data samples to align both DTs and CSCs. Physics validation has been performed and shows a modest improvement in stand-alone muon momentum resolution in the barrel, where the alignment is essentially unchanged from the previous version. The reference-target track-based algorithm using only collision muons is employed for the first time to align the CSCs, and a substantial improvement in resolution is observed in the endcap and overlap regions for stand-alone muons. This new alignment is undergoing the approval process and is expected to be deployed as part of a new global tag in the beginning of December. The pT dependence of the φ-bias in curvature observed in Monte Carlo was traced to a relative vertical misalignment between the Tracker and barrel muon systems. Moving the barrel as a whole to match the Tracker cures this pT dependence, leaving only the &phi...

  10. Enzymatic Synthesis of Modified Oligonucleotides by PEAR Using Phusion and KOD DNA Polymerases

    OpenAIRE

    Wang, Xuxiang; Zhang, Jianye; Li, Yingjia; Chen, Gang; Wang, Xiaolong

    2015-01-01

    Antisense synthetic oligonucleotides have been developed as potential gene-targeted therapeutics. We previously reported polymerase–endonuclease amplification reaction (PEAR) for amplification of natural and 5′-O-(1-thiotriphosphate) (S)-modified oligonucleotides. Here, we extended the PEAR technique for enzymatic preparation of 2′-deoxy-2′-fluoro-(2′-F) and 2′-F/S double-modified oligonucleotides. The result showed that KOD and Phusion DNA polymerase could synthesize oligonucleotides with on...

  11. Curriculum Alignment Research Suggests that Alignment Can Improve Student Achievement

    Science.gov (United States)

    Squires, David

    2012-01-01

    Curriculum alignment research has developed showing the relationship among three alignment categories: the taught curriculum, the tested curriculum and the written curriculum. Each pair (for example, the taught and the written curriculum) shows a positive impact for aligning those results. Following this, alignment results from the Third…

  12. Fabrication of oligonucleotide microarray for the detection of Japanese encephalitis virus

    Institute of Scientific and Technical Information of China (English)

    HAI YAN ZHANG; WEN LI MA; XIAO MING ZHANG; WEN LING ZHENG

    2006-01-01

    A low-density oligonucleotide microarray was used for the detection of Japanese encephalitis virus (JEV), combining with restriction display PCR labeling method. The hybridization targets were amplified from 6 plasmids containing several JEV gene fragments. Corresponding oligonucleotide probe spots were detected unambiguously. We claim that the oligonucleotide microarray technology is feasible and may have potential for clinical laboratory application.

  13. Determination of the basic density of cedro wood (Cedrela fissilis Vell. along the stem

    align=justify>Determinação da densidade básica da madeira de cedro (Cedrela fissilis Vell. ao longo do fuste

    Directory of Open Access Journals (Sweden)

    Alváro Felipe Valério

    2009-03-01

    Full Text Available O presente estudo teve como objetivo determinar e comparar a variação da densidade básica da madeira de Cedrela fi ssilis, espécie pertencente a família Meliaceae e conhecida popularmente como Cedro, ao longo do fuste. A amostragem foi realizada em três árvores selecionadas de forma aleatória na Floresta Ombrófi la Densa, nos municípios Apiuna e Presidente Nereu Ramos, no estado de Santa Catarina - SC. As árvores foram abatidas e tiveram suas variáveis dendrométricas medidas. A densidade básica foi determinada em amostras de 1,5 x 1,5 x 5 cm, retiradas da parte interna do disco (cerne e da parte externa (alburno, sendo estas coletadas à altura do peito (DAP, 0%, 10%, 50%,75%, 95% do ponto de inversão morfológica e, acima deste, coletou-se duas amostras de galhos, denominadas como G1 e G2. A densidade básica foi obtida através da relação entre o peso seco e o volume verde das amostras, mostrando-se decrescente da base para o topo da árvore. Na realização da Análise de Variância (ANOVA, puderam ser constatadas diferenças estatisticamente signifi cativas entre as médias das densidades ao longo do tronco e dos galhos: a densidade básica média foi de 431,06 kg m3. A uniformidade encontrada na densidade básica ao longo do fuste é uma característica que confere à espécie estabilidade e segurança para sua utilização em projetos estruturais, porém são necessários estudos mais aprofundados para melhor fundamentação cientifi ca de suas propriedades físicas e tecnológicas.

    align="left">The e objective of this work was to determine and compare the variation of basic density of the wood throughout the stem of Cedrela fissilis Vell., specie belonging to the Meliaceae family and known popularly as Cedro. The sample was performed in three selected trees at random in dense ombrophila forest, in the Municipal District of Apiuna and

  14. MaxAlign: maximizing usable data in an alignment

    OpenAIRE

    Pedersen Anders G; Sackett Peter W; Gouveia-Oliveira Rodrigo

    2007-01-01

    Abstract Background The presence of gaps in an alignment of nucleotide or protein sequences is often an inconvenience for bioinformatical studies. In phylogenetic and other analyses, for instance, gapped columns are often discarded entirely from the alignment. Results MaxAlign is a program that optimizes the alignment prior to such analyses. Specifically, it maximizes the number of nucleotide (or amino acid) symbols that are present in gap-free columns – the alignment area – by selecting the ...

  15. Intracellular Uptake of Modified Oligonucleotide Studied by Two Fluorescence Techniques

    Czech Academy of Sciences Publication Activity Database

    Kočišová, E.; Praus, P.; Rosenberg, Ivan; Seksek, O.; Sureau, F.; Štěpánek, J.; Turpin, P. Y.

    2004-01-01

    Roč. 74, - (2004), s. 110-114. ISSN 0006-3525 R&D Projects: GA ČR GA203/01/1166; GA ČR GP202/03/D118 Institutional research plan: CEZ:AV0Z4055905 Keywords : cellular uptake * antisense oligonucleotide * flluorescence microimagigng Subject RIV: CC - Organic Chemistry Impact factor: 2.863, year: 2004

  16. Oligonucleotide-directed mutagenesis for precision gene editing.

    Science.gov (United States)

    Sauer, Noel J; Mozoruk, Jerry; Miller, Ryan B; Warburg, Zachary J; Walker, Keith A; Beetham, Peter R; Schöpke, Christian R; Gocal, Greg F W

    2016-02-01

    Differences in gene sequences, many of which are single nucleotide polymorphisms, underlie some of the most important traits in plants. With humanity facing significant challenges to increase global agricultural productivity, there is an urgent need to accelerate the development of these traits in plants. oligonucleotide-directed mutagenesis (ODM), one of the many tools of Cibus' Rapid Trait Development System (RTDS(™) ) technology, offers a rapid, precise and non-transgenic breeding alternative for trait improvement in agriculture to address this urgent need. This review explores the application of ODM as a precision genome editing technology, with emphasis on using oligonucleotides to make targeted edits in plasmid, episomal and chromosomal DNA of bacterial, fungal, mammalian and plant systems. The process of employing ODM by way of RTDS technology has been improved in many ways by utilizing a fluorescence conversion system wherein a blue fluorescent protein (BFP) can be changed to a green fluorescent protein (GFP) by editing a single nucleotide of the BFP gene (CAC→TAC; H66 to Y66). For example, dependent on oligonucleotide length, applying oligonucleotide-mediated technology to target the BFP transgene in Arabidopsis thaliana protoplasts resulted in up to 0.05% precisely edited GFP loci. Here, the development of traits in commercially relevant plant varieties to improve crop performance by genome editing technologies such as ODM, and by extension RTDS, is reviewed. PMID:26503400

  17. Systematic design of mouse Vh gene family-specific oligonucleotides

    NARCIS (Netherlands)

    Seijen, AM; Seijen, HG; Bos, NA

    2001-01-01

    Kabat's database has often been used to design mouse Vh gene-specific 5 ' primers. The emphasis was mostly on constructing a universal (degenerate) 5 ' primer or 5 ' primer set, which would be able to match every mouse Vh gene. We were interested in finding oligonucleotides that could be used as pri

  18. Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

    Directory of Open Access Journals (Sweden)

    Tatyana V. Abramova

    2014-05-01

    Full Text Available An efficient solid-phase-supported peptide synthesis (SPPS of morpholinoglycine oligonucleotide (MorGly mimics has been developed. The proposed strategy includes a novel specially designed labile linker group containing the oxalyl residue and the 2-aminomethylmorpholino nucleoside analogues as first subunits.

  19. Summarization on the synthesis and radionuclide-labeling of peptide nucleic acid for an oligonucleotide analogue

    International Nuclear Information System (INIS)

    Peptide nucleic acid (PNA), which is one kind of antisense nucleic acid compounds and an oligonucleotide analogue that binds strongly to DNA and RNA in a sequence specific manner, has its unique advantages in the field of molecular diagnostics and treatment of diseases. Now, people gradually attach more importance to PNA. To optimize the application of PNA in genetic re- search and therapy, a great number of backbone modifications on the newly- type structures of PNA were synthesized to improve its physicochemical proper- ties, such as hybridization speciality, solubility in biofluid, or cell permeability. The modified PNA labeled with radionuclides, which can obtain the aim at specific target and minimal non-target trauma, has important role in research and application of tumorous genitherapy. Here a review on the basic synthesis idea and several primary synthetic methods of PNA analogs was given, and also correlative studies and expectation on the compounds belonging to PNA series labeled with radionuclides were included. (authors)

  20. Ergodic Secret Alignment

    CERN Document Server

    Bassily, Raef

    2010-01-01

    In this paper, we introduce two new achievable schemes for the fading multiple access wiretap channel (MAC-WT). In the model that we consider, we assume that perfect knowledge of the state of all channels is available at all the nodes in a causal fashion. Our schemes use this knowledge together with the time varying nature of the channel model to align the interference from different users at the eavesdropper perfectly in a one-dimensional space while creating a higher dimensionality space for the interfering signals at the legitimate receiver hence allowing for better chance of recovery. While we achieve this alignment through signal scaling at the transmitters in our first scheme (scaling based alignment (SBA)), we let nature provide this alignment through the ergodicity of the channel coefficients in the second scheme (ergodic secret alignment (ESA)). For each scheme, we obtain the resulting achievable secrecy rate region. We show that the secrecy rates achieved by both schemes scale with SNR as 1/2log(SNR...

  1. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez

    2010-01-01

    For the last three months, the Muon Alignment group has focussed on providing a new, improved set of alignment constants for the end-of-year data reprocessing. These constants were delivered on time and approved by the CMS physics validation team on November 17. The new alignment incorporates several improvements over the previous one from March for nearly all sub-systems. Motivated by the loss of information from a hardware failure in May (an entire MAB was lost), the optical barrel alignment has moved from a modular, super-plane reconstruction, to a full, single loop calculation of the entire geometry for all DTs in stations 1, 2 and 3. This makes better use of the system redundancy, mitigating the effect of the information loss. Station 4 is factorised and added afterwards to make the system smaller (and therefore faster to run), and also because the MAB calibration at the MB4 zone is less precise. This new alignment procedure was tested at 0 T against photogrammetry resulting in precisions of the order...

  2. Alignment telescope for Antares

    International Nuclear Information System (INIS)

    The Antares Automatic Alignment System employs a specially designed telescope for alignment of its laser beamlines. There are two telescopes in the system, and since each telescope is a primary alignment reference, stringent boresight accuracy and stability over the focus range were required. Optical and mechanical designs, which meet this requirement as well as that of image quality over a wide wavelength band, are described. Special test techniques for initial assembly and alignment of the telescope are also presented. The telescope, which has a 180-mm aperture FK51-KZF2 type glass doublet objective, requires a boresight accuracy of 2.8 μrad at two focal lengths, and object distances between 11 meters and infinity. Travel of a smaller secondary doublet provides focus from 11 m to infinity with approximately 7.8 m effective focal length. By flipping in a third doublet, the effective focal length is reduced to 2.5 m. Telescope alignment was accomplished by using a rotary air bearing to establish an axis in front of the system and placing the focus of a Laser Unequal Path Interferometer (LUPI) at the image plane

  3. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    Gervasio Gomez

    2012-01-01

      The new alignment for the DT chambers has been successfully used in physics analysis starting with the 52X Global Tag. The remaining main areas of development over the next few months will be preparing a new track-based CSC alignment and producing realistic APEs (alignment position errors) and MC misalignment scenarios to match the latest muon alignment constants. Work on these items has been delayed from the intended timeline, mostly due to a large involvement of the muon alignment man-power in physics analyses over the first half of this year. As CMS keeps probing higher and higher energies, special attention must be paid to the reconstruction of very-high-energy muons. Recent muon POG reports from mid-June show a φ-dependence in curvature bias in Monte Carlo samples. This bias is observed already at the tracker level, where it is constant with muon pT, while it grows with pT as muon chamber information is added to the tracks. Similar studies show a much smaller effect in data, at le...

  4. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    M. Dallavalle

    2013-01-01

    A new Muon misalignment scenario for 2011 (7 TeV) Monte Carlo re-processing was re-leased. The scenario is based on running of standard track-based reference-target algorithm (exactly as in data) using single-muon simulated sample (with the transverse-momentum spectrum matching data). It used statistics similar to what was used for alignment with 2011 data, starting from an initially misaligned Muon geometry from uncertainties of hardware measurements and using the latest Tracker misalignment geometry. Validation of the scenario (with muons from Z decay and high-pT simulated muons) shows that it describes data well. The study of systematic uncertainties (dominant by now due to huge amount of data collected by CMS and used for muon alignment) is finalised. Realistic alignment position errors are being obtained from the estimated uncertainties and are expected to improve the muon reconstruction performance. Concerning the Hardware Alignment System, the upgrade of the Barrel Alignment is in progress. By now, d...

  5. The CMS Tracker Alignment Strategy

    CERN Document Server

    Weber, Martin

    2006-01-01

    CMS silicon Tracker alignment consists of three key components: Survey during tracker construction, measurements with the Laser Alignment System during operation and track based alignment. Methods and results are explained in detail, with a special focus on track based alignment due to its enormous complexity and numerical challenges.

  6. RNA Structural Alignments, Part I

    DEFF Research Database (Denmark)

    Havgaard, Jakob Hull; Gorodkin, Jan

    Simultaneous alignment and secondary structure prediction of RNA sequences is often referred to as "RNA structural alignment." A class of the methods for structural alignment is based on the principles proposed by Sankoff more than 25 years ago. The Sankoff algorithm simultaneously folds and aligns...

  7. MUSE optical alignment procedure

    Science.gov (United States)

    Laurent, Florence; Renault, Edgard; Loupias, Magali; Kosmalski, Johan; Anwand, Heiko; Bacon, Roland; Boudon, Didier; Caillier, Patrick; Daguisé, Eric; Dubois, Jean-Pierre; Dupuy, Christophe; Kelz, Andreas; Lizon, Jean-Louis; Nicklas, Harald; Parès, Laurent; Remillieux, Alban; Seifert, Walter; Valentin, Hervé; Xu, Wenli

    2012-09-01

    MUSE (Multi Unit Spectroscopic Explorer) is a second generation VLT integral field spectrograph (1x1arcmin² Field of View) developed for the European Southern Observatory (ESO), operating in the visible wavelength range (0.465-0.93 μm). A consortium of seven institutes is currently assembling and testing MUSE in the Integration Hall of the Observatoire de Lyon for the Preliminary Acceptance in Europe, scheduled for 2013. MUSE is composed of several subsystems which are under the responsibility of each institute. The Fore Optics derotates and anamorphoses the image at the focal plane. A Splitting and Relay Optics feed the 24 identical Integral Field Units (IFU), that are mounted within a large monolithic instrument mechanical structure. Each IFU incorporates an image slicer, a fully refractive spectrograph with VPH-grating and a detector system connected to a global vacuum and cryogenic system. During 2011, all MUSE subsystems were integrated, aligned and tested independently in each institute. After validations, the systems were shipped to the P.I. institute at Lyon and were assembled in the Integration Hall This paper describes the end-to-end optical alignment procedure of the MUSE instrument. The design strategy, mixing an optical alignment by manufacturing (plug and play approach) and few adjustments on key components, is presented. We depict the alignment method for identifying the optical axis using several references located in pupil and image planes. All tools required to perform the global alignment between each subsystem are described. The success of this alignment approach is demonstrated by the good results for the MUSE image quality. MUSE commissioning at the VLT (Very Large Telescope) is planned for 2013.

  8. Strategic Alignment of Business Intelligence

    OpenAIRE

    Cederberg, Niclas

    2010-01-01

    This thesis is about the concept of strategic alignment of business intelligence. It is based on a theoretical foundation that is used to define and explain business intelligence, data warehousing and strategic alignment. By combining a number of different methods for strategic alignment a framework for alignment of business intelligence is suggested. This framework addresses all different aspects of business intelligence identified as relevant for strategic alignment of business intelligence...

  9. RHIC survey and alignment

    International Nuclear Information System (INIS)

    The Relativistic Heavy Ion Collider consists of two interlaced plane rings, a pair of mirror-symmetric beam injection arcs, a spatially curved beam transfer line from the Alternating Gradient Synchrotron, and a collection of precisely positioned and aligned magnets, on appropriately positioned support stands, threaded on those arcs. RHIC geometry is defined by six beam crossing points exactly in a plane, lying precisely at the vertices of a regular hexagon of specified size position and orientation of this hexagon are defined geodetically. Survey control and alignment procedures, currently in use to construct RHIC, are described

  10. Biophysical and RNA Interference Inhibitory Properties of Oligonucleotides Carrying Tetrathiafulvalene Groups at Terminal Positions

    Directory of Open Access Journals (Sweden)

    Sónia Pérez-Rentero

    2013-01-01

    Full Text Available Oligonucleotide conjugates carrying a single functionalized tetrathiafulvalene (TTF unit linked through a threoninol molecule to the 3′ or 5′ ends were synthesized together with their complementary oligonucleotides carrying a TTF, pyrene, or pentafluorophenyl group. TTF-oligonucleotide conjugates formed duplexes with higher thermal stability than the corresponding unmodified oligonucleotides and pyrene- and pentafluorophenyl-modified oligonucleotides. TTF-modified oligonucleotides are able to bind to citrate-stabilized gold nanoparticles (AuNPs and produce stable gold AuNPs functionalized with oligonucleotides. Finally, TTF-oligoribonucleotides have been synthesized to produce siRNA duplexes carrying TTF units. The presence of the TTF molecule is compatible with the RNA interference mechanism for gene inhibition.

  11. Discriminative Shape Alignment

    DEFF Research Database (Denmark)

    Loog, M.; de Bruijne, M.

    taking into account that eventually the shapes are to be assigned to two or more different classes. This work introduces a discriminative variation to well-known Procrustes alignment and demonstrates its benefit over this classical method in shape classification tasks. The focus is on two...

  12. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez and Y. Pakhotin

    2012-01-01

      A new track-based alignment for the DT chambers is ready for deployment: an offline tag has already been produced which will become part of the 52X Global Tag. This alignment was validated within the muon alignment group both at low and high momentum using a W/Z skim sample. It shows an improved mass resolution for pairs of stand-alone muons, improved curvature resolution at high momentum, and improved DT segment extrapolation residuals. The validation workflow for high-momentum muons used to depend solely on the “split cosmics” method, looking at the curvature difference between muon tracks reconstructed in the upper or lower half of CMS. The validation has now been extended to include energetic muons decaying from heavily boosted Zs: the di-muon invariant mass for global and stand-alone muons is reconstructed, and the invariant mass resolution is compared for different alignments. The main areas of development over the next few months will be preparing a new track-based C...

  13. Aligning Mental Representations

    DEFF Research Database (Denmark)

    Kano Glückstad, Fumiko

    2013-01-01

    This work introduces a framework that implements asymmetric communication theory proposed by Sperber and Wilson [1]. The framework applies a generalization model known as the Bayesian model of generalization (BMG) [2] for aligning knowledge possessed by two communicating parties. The work focuses...

  14. Observability of Strapdown INS Alignment: A Global Perspective

    CERN Document Server

    Wu, Yuanxin; Wu, Meiping; Hu, Xiaoping; Hu, Dewen

    2011-01-01

    Alignment of the strapdown inertial navigation system (INS) has strong nonlinearity, even worse when maneuvers, e.g., tumbling techniques, are employed to improve the alignment. There is no general rule to attack the observability of a nonlinear system, so most previous works addressed the observability of the corresponding linearized system by implicitly assuming that the original nonlinear system and the linearized one have identical observability characteristics. Strapdown INS alignment is a nonlinear system that has its own characteristics. Using the inherent properties of strapdown INS, e.g., the attitude evolution on the SO(3) manifold, we start from the basic definition and develop a global and constructive approach to investigate the observability of strapdown INS static and tumbling alignment, highlighting the effects of the attitude maneuver on observability. We prove that strapdown INS alignment, considering the unknown constant sensor biases, will be completely observable if the strapdown INS is r...

  15. Fast global sequence alignment technique

    KAUST Repository

    Bonny, Mohamed Talal

    2011-11-01

    Bioinformatics database is growing exponentially in size. Processing these large amount of data may take hours of time even if super computers are used. One of the most important processing tool in Bioinformatics is sequence alignment. We introduce fast alignment algorithm, called \\'Alignment By Scanning\\' (ABS), to provide an approximate alignment of two DNA sequences. We compare our algorithm with the wellknown sequence alignment algorithms, the \\'GAP\\' (which is heuristic) and the \\'Needleman-Wunsch\\' (which is optimal). The proposed algorithm achieves up to 51% enhancement in alignment score when it is compared with the GAP Algorithm. The evaluations are conducted using different lengths of DNA sequences. © 2011 IEEE.

  16. ABS: Sequence alignment by scanning

    KAUST Repository

    Bonny, Mohamed Talal

    2011-08-01

    Sequence alignment is an essential tool in almost any computational biology research. It processes large database sequences and considered to be high consumers of computation time. Heuristic algorithms are used to get approximate but fast results. We introduce fast alignment algorithm, called Alignment By Scanning (ABS), to provide an approximate alignment of two DNA sequences. We compare our algorithm with the well-known alignment algorithms, the FASTA (which is heuristic) and the \\'Needleman-Wunsch\\' (which is optimal). The proposed algorithm achieves up to 76% enhancement in alignment score when it is compared with the FASTA Algorithm. The evaluations are conducted using different lengths of DNA sequences. © 2011 IEEE.

  17. REALITY OF ALIGNING IT WITH BUSINESS IN CZECH ORGANIZATIONS

    Directory of Open Access Journals (Sweden)

    Renata Kunstova

    2012-01-01

    Full Text Available Information technologies (IT supporting business strategies and business processes are often the most important factor for successful organizations. Aligning IT with the business depends on many factors, including communication and cooperation between the top management of organizations and the top management of IT departments in strategic decision making and planning. This paper discusses the outcomes of a survey conducted in six hundred organizations operating on the Czech market. The aim of the survey was to verify whether organizations operating on the Czech market meet basic assumptions for business/IT alignment or, in other words, to find out the reality of business/IT alignment in practice.

  18. MaxAlign: maximizing usable data in an alignment

    Directory of Open Access Journals (Sweden)

    Pedersen Anders G

    2007-08-01

    Full Text Available Abstract Background The presence of gaps in an alignment of nucleotide or protein sequences is often an inconvenience for bioinformatical studies. In phylogenetic and other analyses, for instance, gapped columns are often discarded entirely from the alignment. Results MaxAlign is a program that optimizes the alignment prior to such analyses. Specifically, it maximizes the number of nucleotide (or amino acid symbols that are present in gap-free columns – the alignment area – by selecting the optimal subset of sequences to exclude from the alignment. MaxAlign can be used prior to phylogenetic and bioinformatical analyses as well as in other situations where this form of alignment improvement is useful. In this work we test MaxAlign's performance in these tasks and compare the accuracy of phylogenetic estimates including and excluding gapped columns from the analysis, with and without processing with MaxAlign. In this paper we also introduce a new simple measure of tree similarity, Normalized Symmetric Similarity (NSS that we consider useful for comparing tree topologies. Conclusion We demonstrate how MaxAlign is helpful in detecting misaligned or defective sequences without requiring manual inspection. We also show that it is not advisable to exclude gapped columns from phylogenetic analyses unless MaxAlign is used first. Finally, we find that the sequences removed by MaxAlign from an alignment tend to be those that would otherwise be associated with low phylogenetic accuracy, and that the presence of gaps in any given sequence does not seem to disturb the phylogenetic estimates of other sequences. The MaxAlign web-server is freely available online at http://www.cbs.dtu.dk/services/MaxAlign where supplementary information can also be found. The program is also freely available as a Perl stand-alone package.

  19. Generating highly labeled oligonucleotides for DNA-protein interaction

    International Nuclear Information System (INIS)

    We developed a new strategy to prepare double-stranded oligonucleotides containing recognition sites for specific binding proteins to examine DNA-protein interactions in various assays (gel mobility shift, UV-crosslinking, and affinity chromatography). The advantages of our procedures are as follows. Only one strand needs to be synthesized using a commercial oligonucleotide synthesizer. The probes can be labeled to a high specific activity and the exact position of labeling can be chosen, which is necessary for UV-crosslinking studies. Furthermore, multimeric binding sites for efficient DNA affinity chromatography can easily be generated. It is also possible to precisely place modified bases without the need for chemical precursors. Using this protocol, more detailed information about the binding protein factors and their behavior in interaction with recognition sites can be obtained

  20. One-oligonucleotide method for constructing vectors for RNA interference

    Institute of Scientific and Technical Information of China (English)

    Carlos Fabian FLORES-JASSO; Ines VELAZQUEZ-QUESADA; Carlos LANDA-SOLIS; Andres A GUTIERREZ; Luis VACA

    2005-01-01

    Aim: To develop an easy, fast, automated, and inexpensive method for constructing short-hairpin-RNA cassettes for RNAi studies. Methods: Using single oligonucleotides, a variety of DNA cassettes for RNAi vectors were constructed in only few minutes in an automated manner. The cassettes, targeting the eGFP,were cloned into plasmids driven by RNA polymerase Ⅲ promoter H 1. Then, the plasmids were transfected into HeLa cells that were later infected with a recombinant adenovirus encoding the eGFP gene. The level of eGFP fluorescence was evaluated by confocal imaging and flow cytometry. Results: The plasmids constructed with the DNA cassettes made by the one-oligonucleotide method inhibited eGFP with different potencies, ranging from 55% to 75%. Conclusion: By using the method reported here, it is possible to simultaneously construct hundreds of different DNA cassettes for RNAi experiments in an inexpensive, automated way. This method will facilitate functional genomics studies on mammalian cells.

  1. Fluorescence quenching of TMR by guanosine in oligonucleotides

    Institute of Scientific and Technical Information of China (English)

    QU Peng; CHEN XuDong; ZHOU XiaoXue; LI Xun; ZHAO XinSheng

    2009-01-01

    Nucleotide-specific fluorescence quenching in fluorescently labeled DNA has many applications in biotechnology. We have studied the inter- and intra-molecular quenching of tetramethylrhodamine (TMR) by nucleotides to better understand their quenching mechanism and influencing factors. In agreement with previous work, dGMP can effectively quench TMR, while the quenching of TMR by other nucleotides is negligible. The Stern-Volmer plot between TMR and dGMP delivers a bimolecular quenching constant of Ks= 52.3 M~(-1). The fluorescence of TMR in labeled oligonucleotides decreases efficiently through photoinduced electron transfer by guanosine. The quenching rate constant between TMR and guanosine was measured using fluorescence correlation spectroscopy (FCS). In addition, our data show that the steric hindrance by bases around guanosine has significant effect on the G-quenching. The availability of these data should be useful in designing fluorescent oligonucleotides and understanding the G-quenching process.

  2. Fluorescence quenching of TMR by guanosine in oligonucleotides

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Nucleotide-specific fluorescence quenching in fluorescently labeled DNA has many applications in biotechnology. We have studied the inter-and intra-molecular quenching of tetramethylrhodamine (TMR) by nucleotides to better understand their quenching mechanism and influencing factors. In agreement with previous work, dGMP can effectively quench TMR, while the quenching of TMR by other nucleotides is negligible. The Stern-Volmer plot between TMR and dGMP delivers a bimolecular quenching constant of Ks=52.3 M-1. The fluorescence of TMR in labeled oligonucleotides decreases efficiently through photoinduced electron transfer by guanosine. The quenching rate constant between TMR and guanosine was measured using fluorescence correlation spectroscopy (FCS). In addition, our data show that the steric hindrance by bases around guanosine has significant effect on the G-quenching. The availability of these data should be useful in designing fluorescent oligonucleotides and understanding the G-quenching process.

  3. Chiral phosphonate internucleotide linkage: A promising modification for chimeric oligonucleotides?

    Czech Academy of Sciences Publication Activity Database

    Liboska, Radek; Petrová, Magdalena; Pohl, Radek; Buděšínský, Miloš; Hurychová, Vladimíra; Rosenberg, Ivan

    -, č. 52 (2008), s. 317-318. ISSN 0261-3166. [Joint Symposium of the International Roundtable on Nucleosides, Nucleotides and Nucleic Acids /18./ and the International Symposium on Nucleic Acid Chemistry /35./. Kyoto, 08.09.2008-12.09.2008] R&D Projects: GA MŠk(CZ) LC06061 Grant ostatní: EMIL-FP6(XE) 503569 Institutional research plan: CEZ:AV0Z40550506 Keywords : oligonucleotide phosphonate Subject RIV: CC - Organic Chemistry

  4. The strand transfer oligonucleotide inhibitors of HIV-integrase

    Czech Academy of Sciences Publication Activity Database

    Snášel, Jan; Rosenberg, Ivan; Pačes, Ondřej; Pichová, Iva

    2009-01-01

    Roč. 24, č. 1 (2009), s. 241-246. ISSN 1475-6366 R&D Projects: GA MŠk 1M0508; GA ČR GA203/05/0827; GA ČR GP203/05/P557; GA AV ČR IAA4055304 Institutional research plan: CEZ:AV0Z40550506 Keywords : HIV-1 integrase * inhibition * phosphonate oligonucleotides Subject RIV: CE - Biochemistry Impact factor: 1.496, year: 2009

  5. Integrated Microfluidic Isolation of Aptamers Using Electrophoretic Oligonucleotide Manipulation

    OpenAIRE

    Jinho Kim; Olsen, Timothy R.; Jing Zhu; Hilton, John P.; Kyung-Ae Yang; Renjun Pei; Stojanovic, Milan N.; Qiao Lin

    2016-01-01

    We present a microfluidic approach to integrated isolation of DNA aptamers via systematic evolution of ligands by exponential enrichment (SELEX). The approach employs a microbead-based protocol for the processes of affinity selection and amplification of target-binding oligonucleotides, and an electrophoretic DNA manipulation scheme for the coupling of these processes, which are required to occur in different buffers. This achieves the full microfluidic integration of SELEX, thereby enabling ...

  6. Molecular Selection, Modification and Development of Therapeutic Oligonucleotide Aptamers

    OpenAIRE

    Yuanyuan Yu; Chao Liang; Quanxia Lv; Defang Li; Xuegong Xu; Baoqin Liu; Aiping Lu; Ge Zhang

    2016-01-01

    Monoclonal antibodies are the dominant agents used in inhibition of biological target molecules for disease therapeutics, but there are concerns of immunogenicity, production, cost and stability. Oligonucleotide aptamers have comparable affinity and specificity to targets with monoclonal antibodies whilst they have minimal immunogenicity, high production, low cost and high stability, thus are promising inhibitors to rival antibodies for disease therapy. In this review, we will compare the det...

  7. Oligonucleotide-based strategies to combat polyglutamine diseases

    OpenAIRE

    Fiszer, Agnieszka; Krzyzosiak, Wlodzimierz J.

    2014-01-01

    Considerable advances have been recently made in understanding the molecular aspects of pathogenesis and in developing therapeutic approaches for polyglutamine (polyQ) diseases. Studies on pathogenic mechanisms have extended our knowledge of mutant protein toxicity, confirmed the toxicity of mutant transcript and identified other toxic RNA and protein entities. One very promising therapeutic strategy is targeting the causative gene expression with oligonucleotide (ON) based tools. This straig...

  8. Phosphorothioate Antisense Oligonucleotides Induce the Formation of Nuclear Bodies

    OpenAIRE

    Lorenz, Peter; Baker, Brenda F.; Bennett, C. Frank; Spector, David L.

    1998-01-01

    Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20–30 bright spherical foci designated phosphorothioate bodies (PS bodies), w...

  9. Thermoplastic polymers surfaces for Dip-Pen Nanolithography of oligonucleotides

    International Nuclear Information System (INIS)

    Different thermoplastic polymers were spin-coated to prepare smooth surfaces for the direct deposition of end-group modified oligonucleotides by Dip-Pen Nanolithography. A study of the diffusion process was done in order to investigate the dependence of calibration coefficient and quality of deposited features on environmental parameters (temperature, relative humidity) and ink's molecular weight and functionality. The optimization of the process parameters led to the realization of high quality and density nanoarrays on plastics.

  10. On the rapid deprotection of synthetic oligonucleotides and analogs.

    OpenAIRE

    Polushin, N N; Morocho, A M; Chen, B. C.; Cohen, J. S.

    1994-01-01

    The efficiency of oligodeoxynucleotide deprotection is greatly enhanced using a combination of: (a) ethanolamine, and especially a mixture of hydrazine, ethanolamine and methanol, in place of the usual aqueous ammonia; (b) tert-butylphenoxyacetyl amino protecting groups, and (c) oxalyl link between the first nucleotide and the polymeric support. The extent of base modification, particularly of C, is shown to be extremely low, and the quality of deprotected oligonucleotides is as high as in th...

  11. Oligonucleotide-mediated gene editing of Apolipoprotein A-I.

    OpenAIRE

    Disterer, P

    2008-01-01

    Apolipoprotein A-I (ApoA-I) is the major protein constituent of high density lipoprotein (HDL) and controls reverse cholesterol transport, an important process in preventing atherosclerosis. A natural point mutation, ApoA-lMiiano (ApoA-Im) enhances the atheroprotective potential of HDL. Here, I attempt to introduce this specific modification into the genome of mammalian cells using the gene therapy strategy of oligonucleotide-mediated gene editing. I showed successful APOA-I gene editing in r...

  12. Repair of DNA lesions associated with triplex-forming oligonucleotides

    OpenAIRE

    Chin, Joanna Y; Glazer, Peter M.

    2009-01-01

    Triplex-forming oligonucleotides (TFOs) are gene targeting tools that can bind in the major groove of duplex DNA in a sequence-specific manner. When bound to DNA, TFOs can inhibit gene expression, can position DNA-reactive agents to specific locations in the genome, or can induce targeted mutagenesis and recombination. There is evidence that third strand binding, alone or with an associated cross-link, is recognized and metabolized by DNA repair factors, particularly the nucleotide excision r...

  13. Thermoplastic polymers surfaces for Dip-Pen Nanolithography of oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Suriano, Raffaella [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Biella, Serena, E-mail: serena.biella@polimi.it [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Cesura, Federico; Levi, Marinella; Turri, Stefano [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2013-05-15

    Different thermoplastic polymers were spin-coated to prepare smooth surfaces for the direct deposition of end-group modified oligonucleotides by Dip-Pen Nanolithography. A study of the diffusion process was done in order to investigate the dependence of calibration coefficient and quality of deposited features on environmental parameters (temperature, relative humidity) and ink's molecular weight and functionality. The optimization of the process parameters led to the realization of high quality and density nanoarrays on plastics.

  14. Oligonucleotides modified with acyclic nucleoside phosphonate (HPEP) units

    Czech Academy of Sciences Publication Activity Database

    Kaiser, Martin Maxmilian; Novák, Pavel; Rosenbergová, Šárka; Poštová Slavětínská, Lenka; Rosenberg, Ivan; Janeba, Zlatko

    Praha: Institute of Organic Chemistry and Biochemistry AS CR, v. v. i, 2014 - (Hocek, M.), s. 293-294. (Collection Symposium Series. 14). ISBN 978-80-86241-50-0. [Symposium on Chemistry of Nucleic Acid Components /16./. Český Krumlov (CZ), 08.06.2014-13.06.2014] R&D Projects: GA TA ČR TA03010598 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate * HPEP * oligonucleotides Subject RIV: CC - Organic Chemistry

  15. Cationic carbosilane dendrimers and oligonucleotide binding: an energetic affair

    Science.gov (United States)

    Marson, D.; Laurini, E.; Posocco, P.; Fermeglia, M.; Pricl, S.

    2015-02-01

    Generation 2 cationic carbosilane dendrimers hold great promise as internalizing agents for gene therapy as they present low toxicity and retain and internalize the genetic material as an oligonucleotide or siRNA. In this work we carried out complete in silico structural and energetical characterization of the interactions of a set of G2 carbosilane dendrimers, showing different affinity towards two single strand oligonucleotide (ODN) sequences in vitro. Our simulations predict that these four dendrimers and the relevant ODN complexes are characterized by similar size and shape, and that the molecule-specific ODN binding ability can be rationalized only by considering a critical molecular design parameter: the normalized effective binding energy ΔGbind,eff/Neff, i.e. the performance of each active individual dendrimer branch directly involved in a binding interaction.Generation 2 cationic carbosilane dendrimers hold great promise as internalizing agents for gene therapy as they present low toxicity and retain and internalize the genetic material as an oligonucleotide or siRNA. In this work we carried out complete in silico structural and energetical characterization of the interactions of a set of G2 carbosilane dendrimers, showing different affinity towards two single strand oligonucleotide (ODN) sequences in vitro. Our simulations predict that these four dendrimers and the relevant ODN complexes are characterized by similar size and shape, and that the molecule-specific ODN binding ability can be rationalized only by considering a critical molecular design parameter: the normalized effective binding energy ΔGbind,eff/Neff, i.e. the performance of each active individual dendrimer branch directly involved in a binding interaction. Electronic supplementary information (ESI) available: Additional figures and tables. See DOI: 10.1039/c4nr04510f

  16. Antitumor Activity of a Novel Antisense Oligonucleotide Against Akt1

    OpenAIRE

    Yoon, Heejeong; Kim, Deog Joong; Ahn, Eun Hyun; Gellert, Ginelle C.; Shay, Jerry W.; Ahn, Chang-Ho; Lee, Young Bok

    2009-01-01

    The AKT pathway is an important therapeutic target for cancer drug discovery as it functions as a main point for transducing extracellular and intracellular oncogenic signals. Moreover, alternations of the AKT pathway have been found in a wide range of cancers. In the present study, we found that an Akt1 antisense oligonucleotide (Akt1 AO) significantly downregulated the expression of AKT1 at both the mRNA and protein levels and inhibited cellular growth at nanomolar concentrations in various...

  17. Long range clustering of oligonucleotides containing the CG signal

    OpenAIRE

    Katsaloulis, P.; T. Theoharis; A. Provata

    2009-01-01

    Abstract The distance distributions between successive occurrences of the same oligonucleotides in chromosomal DNA are studied, in different classes of higher eucaryotic organisms. A two-parameter modeling is undertaken and applied on the distance distribution of quintuplets (sequences of size five bps) and hexaplets (sequences of size six bps); the first parameter k refers to the short range exponential decay of the distributions, whereas the second parameter m refers to the power...

  18. Inflation by alignment

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, C.P. [PH -TH Division, CERN,CH-1211, Genève 23 (Switzerland); Department of Physics & Astronomy, McMaster University,1280 Main Street West, Hamilton ON (Canada); Perimeter Institute for Theoretical Physics,31 Caroline Street North, Waterloo ON (Canada); Roest, Diederik [Van Swinderen Institute for Particle Physics and Gravity, University of Groningen,Nijenborgh 4, 9747 AG Groningen (Netherlands)

    2015-06-08

    Pseudo-Goldstone bosons (pGBs) can provide technically natural inflatons, as has been comparatively well-explored in the simplest axion examples. Although inflationary success requires trans-Planckian decay constants, f≳M{sub p}, several mechanisms have been proposed to obtain this, relying on (mis-)alignments between potential and kinetic energies in multiple-field models. We extend these mechanisms to a broader class of inflationary models, including in particular the exponential potentials that arise for pGB potentials based on noncompact groups (and so which might apply to moduli in an extra-dimensional setting). The resulting potentials provide natural large-field inflationary models and can predict a larger primordial tensor signal than is true for simpler single-field versions of these models. In so doing we provide a unified treatment of several alignment mechanisms, showing how each emerges as a limit of the more general setup.

  19. Alignments of RNA structures.

    Science.gov (United States)

    Blin, Guillaume; Denise, Alain; Dulucq, Serge; Herrbach, Claire; Touzet, Hélène

    2010-01-01

    We describe a theoretical unifying framework to express the comparison of RNA structures, which we call alignment hierarchy. This framework relies on the definition of common supersequences for arc-annotated sequences and encompasses the main existing models for RNA structure comparison based on trees and arc-annotated sequences with a variety of edit operations. It also gives rise to edit models that have not been studied yet. We provide a thorough analysis of the alignment hierarchy, including a new polynomial-time algorithm and an NP-completeness proof. The polynomial-time algorithm involves biologically relevant edit operations such as pairing or unpairing nucleotides. It has been implemented in a software, called gardenia, which is available at the Web server http://bioinfo.lifl.fr/RNA/gardenia. PMID:20431150

  20. Gene expression profiling in peanut using high density oligonucleotide microarrays

    Directory of Open Access Journals (Sweden)

    Burow Mark

    2009-06-01

    Full Text Available Abstract Background Transcriptome expression analysis in peanut to date has been limited to a relatively small set of genes and only recently has a significant number of ESTs been released into the public domain. Utilization of these ESTs for oligonucleotide microarrays provides a means to investigate large-scale transcript responses to a variety of developmental and environmental signals, ultimately improving our understanding of plant biology. Results We have developed a high-density oligonucleotide microarray for peanut using 49,205 publicly available ESTs and tested the utility of this array for expression profiling in a variety of peanut tissues. To identify putatively tissue-specific genes and demonstrate the utility of this array for expression profiling in a variety of peanut tissues, we compared transcript levels in pod, peg, leaf, stem, and root tissues. Results from this experiment showed 108 putatively pod-specific/abundant genes, as well as transcripts whose expression was low or undetected in pod compared to peg, leaf, stem, or root. The transcripts significantly over-represented in pod include genes responsible for seed storage proteins and desiccation (e.g., late-embryogenesis abundant proteins, aquaporins, legumin B, oil production, and cellular defense. Additionally, almost half of the pod-abundant genes represent unknown genes allowing for the possibility of associating putative function to these previously uncharacterized genes. Conclusion The peanut oligonucleotide array represents the majority of publicly available peanut ESTs and can be used as a tool for expression profiling studies in diverse tissues.

  1. Rapid bacterial identification using evanescent-waveguide oligonucleotide microarray classification.

    Science.gov (United States)

    Francois, Patrice; Charbonnier, Yvan; Jacquet, Jean; Utinger, Dominic; Bento, Manuela; Lew, Daniel; Kresbach, Gerhard M; Ehrat, Markus; Schlegel, Werner; Schrenzel, Jacques

    2006-06-01

    Bacterial identification relies primarily on culture-based methodologies and requires 48-72 h to deliver results. We developed and used i) a bioinformatics strategy to select oligonucleotide signature probes, ii) a rapid procedure for RNA labelling and hybridization, iii) an evanescent-waveguide oligoarray with exquisite signal/noise performance, and iv) informatics methods for microarray data analysis. Unique 19-mer signature oligonucleotides were selected in the 5'-end of 16s rDNA genes of human pathogenic bacteria. Oligonucleotides spotted onto a Ta(2)O(5)-coated microarray surface were incubated with chemically labelled total bacterial RNA. Rapid hybridization and stringent washings were performed before scanning and analyzing the slide. In the present paper, the eight most abundant bacterial pathogens representing >54% of positive blood cultures were selected. Hierarchical clustering analysis of hybridization data revealed characteristic patterns, even for closely related species. We then evaluated artificial intelligence-based approaches that outperformed conventional threshold-based identification schemes on cognate probes. At this stage, the complete procedure applied to spiked blood cultures was completed in less than 6 h. In conclusion, when coupled to optimal signal detection strategy, microarrays provide bacterial identification within a few hours post-sampling, allowing targeted antimicrobial prescription. PMID:16216356

  2. Therapeutic Antisense Oligonucleotides against Cancer: Hurdling to the Clinic

    Science.gov (United States)

    Moreno, Pedro; Pêgo, Ana

    2014-10-01

    Under clinical development since the early 90’s and with two successfully approved drugs (Fomivirsen and Mipomersen), oligonucleotide-based therapeutics have not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinical setting. Namely, effective drug vectorization, careful choice of target gene or synergistic multi-gene targeting are surely decisive, while caution must be exerted to avoid potential toxic, often misleading off-target-effects. Here a brief overview will be given on the nucleic acid chemistry advances that established oligonucleotide technologies as a promising therapeutic alternative and ongoing cancer related clinical trials. Special attention will be given towards a perspective on the hurdles encountered specifically in the cancer field by this class of therapeutic oligonucleotides and a view on possible avenues for success is presented, with particular focus on the contribution from nanotechnology to the field.

  3. Particle-Based Microarrays of Oligonucleotides and Oligopeptides

    Directory of Open Access Journals (Sweden)

    Alexander Nesterov-Mueller

    2014-10-01

    Full Text Available In this review, we describe different methods of microarray fabrication based on the use of micro-particles/-beads and point out future tendencies in the development of particle-based arrays. First, we consider oligonucleotide bead arrays, where each bead is a carrier of one specific sequence of oligonucleotides. This bead-based array approach, appearing in the late 1990s, enabled high-throughput oligonucleotide analysis and had a large impact on genome research. Furthermore, we consider particle-based peptide array fabrication using combinatorial chemistry. In this approach, particles can directly participate in both the synthesis and the transfer of synthesized combinatorial molecules to a substrate. Subsequently, we describe in more detail the synthesis of peptide arrays with amino acid polymer particles, which imbed the amino acids inside their polymer matrix. By heating these particles, the polymer matrix is transformed into a highly viscous gel, and thereby, imbedded monomers are allowed to participate in the coupling reaction. Finally, we focus on combinatorial laser fusing of particles for the synthesis of high-density peptide arrays. This method combines the advantages of particles and combinatorial lithographic approaches.

  4. Properties of hybrid TiO2 -oligonucleotide nanocomposites

    International Nuclear Information System (INIS)

    Recent advancements in hybrid nanotechnology involving nucleic acids and inorganic molecules/structures are predominantly oriented towards cellular imaging or DNA microarray development or for nanoconstruction (such as assembly of ordered patterns of nanocrystals). Nevertheless, in this evolving field there is little work reported yet about the development of nanoparticles that can be used to manipulate biological materials in a novel way. We have synthesized TiO2 -DNA nanocomposites as new vehicles for biotechnology that express new biochemical properties, in an attempt to develop them into nanodevices that would be able to enter cells and conduct their functions in vivo and in situ. Absorption of light and ionizing radiation leads to charge separation in TiO2 , and nanocrystallites modified by the presence of oligonucleotides exhibit semiconducting through both constituents. In such a system charge pairs are instantaneously separated and electropositive holes accumulate on the oligonucleotide DNA, leading to a photo-/radio- catalytic DNA endonuclease reaction. In addition, hybrid nanocomposites of 4.5 nm TiO2 nanoparticles covalently attached to DNA oligonucleotides can be transferred across cellular and nuclear membranes using standard transfection techniques and retained inside mammalian cells. Therefore, TiO2 nanoparticles-biopolymer nanocomposites integrate intrinsic biological/ electrochemical (DNA) and photoelectrical (TiO2 ) properties of the biomolecule and inorganic components, which makes them suitable for development of new tools for biology and medicine

  5. Differentiation of regions with atypical oligonucleotide composition in bacterial genomes

    Directory of Open Access Journals (Sweden)

    Reva Oleg N

    2005-10-01

    Full Text Available Abstract Background Complete sequencing of bacterial genomes has become a common technique of present day microbiology. Thereafter, data mining in the complete sequence is an essential step. New in silico methods are needed that rapidly identify the major features of genome organization and facilitate the prediction of the functional class of ORFs. We tested the usefulness of local oligonucleotide usage (OU patterns to recognize and differentiate types of atypical oligonucleotide composition in DNA sequences of bacterial genomes. Results A total of 163 bacterial genomes of eubacteria and archaea published in the NCBI database were analyzed. Local OU patterns exhibit substantial intrachromosomal variation in bacteria. Loci with alternative OU patterns were parts of horizontally acquired gene islands or ancient regions such as genes for ribosomal proteins and RNAs. OU statistical parameters, such as local pattern deviation (D, pattern skew (PS and OU variance (OUV enabled the detection and visualization of gene islands of different functional classes. Conclusion A set of approaches has been designed for the statistical analysis of nucleotide sequences of bacterial genomes. These methods are useful for the visualization and differentiation of regions with atypical oligonucleotide composition prior to or accompanying gene annotation.

  6. Alignment of concerns

    DEFF Research Database (Denmark)

    Andersen, Tariq Osman; Bansler, Jørgen P.; Kensing, Finn; Moll, Jonas; Nielsen, Karen Dam

    E-health promises to enable and support active patient participation in chronic care. However, these fairly recent innovations are complicated matters and emphasize significant challenges, such as patients’ and clinicians’ different ways of conceptualizing disease and illness. Informed by insights...... from medical phenomenology and our own empirical work in telemonitoring and medical care of heart patients, we propose a design rationale for e-health systems conceptualized as the ‘alignment of concerns’....

  7. Nuclear reactor alignment plate configuration

    Science.gov (United States)

    Altman, David A; Forsyth, David R; Smith, Richard E; Singleton, Norman R

    2014-01-28

    An alignment plate that is attached to a core barrel of a pressurized water reactor and fits within slots within a top plate of a lower core shroud and upper core plate to maintain lateral alignment of the reactor internals. The alignment plate is connected to the core barrel through two vertically-spaced dowel pins that extend from the outside surface of the core barrel through a reinforcement pad and into corresponding holes in the alignment plate. Additionally, threaded fasteners are inserted around the perimeter of the reinforcement pad and into the alignment plate to further secure the alignment plate to the core barrel. A fillet weld also is deposited around the perimeter of the reinforcement pad. To accomodate thermal growth between the alignment plate and the core barrel, a gap is left above, below and at both sides of one of the dowel pins in the alignment plate holes through with the dowel pins pass.

  8. Seeking the perfect alignment

    CERN Multimedia

    2002-01-01

    The first full-scale tests of the ATLAS Muon Spectrometer are about to begin in Prévessin. The set-up includes several layers of Monitored Drift Tubes Chambers (MDTs) and will allow tests of the performance of the detectors and of their highly accurate alignment system.   Monitored Drift Chambers in Building 887 in Prévessin, where they are just about to be tested. Muon chambers are keeping the ATLAS Muon Spectrometer team quite busy this summer. Now that most people go on holiday, the beam and alignment tests for these chambers are just starting. These chambers will measure with high accuracy the momentum of high-energy muons, and this implies very demanding requirements for their alignment. The MDT chambers consist of drift tubes, which are gas-filled metal tubes, 3 cm in diameter, with wires running down their axes. With high voltage between the wire and the tube wall, the ionisation due to traversing muons is detected as electrical pulses. With careful timing of the pulses, the position of the muon t...

  9. Alignment at the ESRF

    International Nuclear Information System (INIS)

    The ESRF Survey and Alignment group is responsible for the installation, control and periodic realignment of the accelerators and experiments which produce high quality x-rays used by scientists from Europe and around the world. Alignment tolerances are typically less than one millimetre and often in the order of several micrometers. The group is composed of one engineer, five highly trained survey technicians, one electronic and one computer technician. This team is fortified during peak periods by technicians from an external survey company. First an overview and comparative study of the main large-scale survey instrumentation and methods used by the group is made. Secondly a discussion of long term deformation on the ESRF site is presented. This is followed by presentation of the methods used in the realignment of the various machines. Two important aspects of our work, beamline and front-end alignment, and the so-called machine exotic devices are briefly discussed. Finally, the ESRF calibration bench is presented. (authors)

  10. Semiautomated improvement of RNA alignments

    DEFF Research Database (Denmark)

    Andersen, Ebbe Sloth; Lind-Thomsen, Allan; Knudsen, Bjarne;

    2007-01-01

    We have developed a semiautomated RNA sequence editor (SARSE) that integrates tools for analyzing RNA alignments. The editor highlights different properties of the alignment by color, and its integrated analysis tools prevent the introduction of errors when doing alignment editing. SARSE readily...... the SARSE editor makes it a flexible tool to improve all RNA alignments with relatively little human intervention. Online documentation and software are available at (http://sarse.ku.dk)....

  11. A new oligonucleotide microarray for detection of pathogenic and non-pathogenic Legionella spp.

    Directory of Open Access Journals (Sweden)

    Boyang Cao

    Full Text Available Legionella pneumophila has been recognized as the major cause of legionellosis since the discovery of the deadly disease. Legionella spp. other than L. pneumophila were later found to be responsible to many non-pneumophila infections. The non-L. pneumophila infections are likely under-detected because of a lack of effective diagnosis. In this report, we have sequenced the 16S-23S rRNA gene internal transcribed spacer (ITS of 10 Legionella species and subspecies, including L. anisa, L. bozemanii, L. dumoffii, L. fairfieldensis, L. gormanii, L. jordanis, L. maceachernii, L. micdadei, L. pneumophila subspp. fraseri and L. pneumophila subspp. pasculleii, and developed a rapid oligonucleotide microarray detection technique accordingly to identify 12 most common Legionella spp., which consist of 11 pathogenic species of L. anisa, L. bozemanii, L. dumoffii, L. gormanii, L. jordanis, L. longbeachae, L. maceachernii, L. micdadei, and L. pneumophila (including subspp. pneumophila, subspp. fraseri, and subspp. pasculleii and one non-pathogenic species, L. fairfieldensis. Twenty-nine probes that reproducibly detected multiple Legionella species with high specificity were included in the array. A total of 52 strains, including 30 target pathogens and 22 non-target bacteria, were used to verify the oligonucleotide microarray assay. The sensitivity of the detection was at 1.0 ng with genomic DNA or 13 CFU/100 mL with Legionella cultures. The microarray detected seven samples of air conditioner-condensed water with 100% accuracy, validating the technique as a promising method for applications in basic microbiology, clinical diagnosis, food safety, and epidemiological surveillance. The phylogenetic study based on the ITS has also revealed that the non-pathogenic L. fairfieldensis is the closest to L. pneumophila than the nine other pathogenic Legionella spp.

  12. Alignment as a Teacher Variable

    Science.gov (United States)

    Porter, Andrew C.; Smithson, John; Blank, Rolf; Zeidner, Timothy

    2007-01-01

    With the exception of the procedures developed by Porter and colleagues (Porter, 2002), other methods of defining and measuring alignment are essentially limited to alignment between tests and standards. Porter's procedures have been generalized to investigating the alignment between content standards, tests, textbooks, and even classroom…

  13. Tracing magnetic fields with ground state alignment

    International Nuclear Information System (INIS)

    states exhibit the alignment and the resulting polarization degree in some cases exceeds 20%. A unique feature of the atomic realignment is that they can reveal the 3D orientation of magnetic field. In this paper, we shall review the basic physical processes involved in atomic realignment. We shall also discuss its applications to interplanetary, circumstellar and interstellar magnetic fields. In addition, our research reveals that the polarization of the radiation arising from the transitions between fine and hyperfine states of the ground level can provide a unique diagnostics of magnetic fields, including those in the early universe.

  14. Alignment procedures for the CMS silicon tracker

    CERN Document Server

    Behr, Joerg

    2012-01-01

    The CMS all-silicon tracker consists of 16588 modules. Therefore its alignment procedures require sophisticated algorithms. Advanced tools of computing, tracking and data analysis have been deployed for reaching the targeted performance. Ultimate local precision is now achieved by the determination of sensor curvatures, challenging the algorithms to determine about 200k parameters simultaneously. Systematic biases in the geometry are controlled by adding further information into the alignment workflow, e.g. the mass of decaying resonances. The orientation of the tracker with respect to the magnetic field of CMS is determined with a stand-alone chi-square minimization procedure. The geometries are finally carefully validated. The monitored quantities include the basic track quantities for tracks from both collisions and cosmic muons and physics observables.

  15. Alignment procedures for the CMS silicon tracker

    International Nuclear Information System (INIS)

    The CMS all-silicon tracker consists of 16588 modules. Therefore its alignment procedures require sophisticated algorithms. Advanced tools of computing, tracking and data analysis have been deployed for reaching the targeted performance. Ultimate local precision is now achieved by the determination of sensor curvatures, challenging the algorithms to determine about 200k parameters simultaneously. Systematic biases in the geometry are controlled by adding further information into the alignment workflow, e.g. the mass of decaying resonances. The orientation of the tracker with respect to the magnetic field of CMS is determined with a stand-alone chi-square minimization procedure. The geometries are finally carefully validated. The monitored quantities include the basic track quantities for tracks from both collisions and cosmic muons and physics observables.

  16. An enhanced algorithm for multiple sequence alignment of protein sequences using genetic algorithm.

    Science.gov (United States)

    Kumar, Manish

    2015-01-01

    One of the most fundamental operations in biological sequence analysis is multiple sequence alignment (MSA). The basic of multiple sequence alignment problems is to determine the most biologically plausible alignments of protein or DNA sequences. In this paper, an alignment method using genetic algorithm for multiple sequence alignment has been proposed. Two different genetic operators mainly crossover and mutation were defined and implemented with the proposed method in order to know the population evolution and quality of the sequence aligned. The proposed method is assessed with protein benchmark dataset, e.g., BALIBASE, by comparing the obtained results to those obtained with other alignment algorithms, e.g., SAGA, RBT-GA, PRRP, HMMT, SB-PIMA, CLUSTALX, CLUSTAL W, DIALIGN and PILEUP8 etc. Experiments on a wide range of data have shown that the proposed algorithm is much better (it terms of score) than previously proposed algorithms in its ability to achieve high alignment quality. PMID:27065770

  17. Discrimination of oligonucleotides of different lengths with a wild-type aerolysin nanopore.

    Science.gov (United States)

    Cao, Chan; Ying, Yi-Lun; Hu, Zheng-Li; Liao, Dong-Fang; Tian, He; Long, Yi-Tao

    2016-08-01

    Protein nanopores offer an inexpensive, label-free method of analysing single oligonucleotides. The sensitivity of the approach is largely determined by the characteristics of the pore-forming protein employed, and typically relies on nanopores that have been chemically modified or incorporate molecular motors. Effective, high-resolution discrimination of oligonucleotides using wild-type biological nanopores remains difficult to achieve. Here, we show that a wild-type aerolysin nanopore can resolve individual short oligonucleotides that are 2 to 10 bases long. The sensing capabilities are attributed to the geometry of aerolysin and the electrostatic interactions between the nanopore and the oligonucleotides. We also show that the wild-type aerolysin nanopores can distinguish individual oligonucleotides from mixtures and can monitor the stepwise cleavage of oligonucleotides by exonuclease I. PMID:27111839

  18. Scalable amplification of strand subsets from chip-synthesized oligonucleotide libraries

    Science.gov (United States)

    Schmidt, Thorsten L.; Beliveau, Brian J.; Uca, Yavuz O.; Theilmann, Mark; Da Cruz, Felipe; Wu, Chao-Ting; Shih, William M.

    2015-01-01

    Synthetic oligonucleotides are the main cost factor for studies in DNA nanotechnology, genetics and synthetic biology, which all require thousands of these at high quality. Inexpensive chip-synthesized oligonucleotide libraries can contain hundreds of thousands of distinct sequences, however only at sub-femtomole quantities per strand. Here we present a selective oligonucleotide amplification method, based on three rounds of rolling-circle amplification, that produces nanomole amounts of single-stranded oligonucleotides per millilitre reaction. In a multistep one-pot procedure, subsets of hundreds or thousands of single-stranded DNAs with different lengths can selectively be amplified and purified together. These oligonucleotides are used to fold several DNA nanostructures and as primary fluorescence in situ hybridization probes. The amplification cost is lower than other reported methods (typically around US$ 20 per nanomole total oligonucleotides produced) and is dominated by the use of commercial enzymes. PMID:26567534

  19. Statistical Algorithms for Long DNA Sequences: Oligonucleotide Distributions and Homogeneity Maps

    Directory of Open Access Journals (Sweden)

    P. Katsaloulis

    2005-01-01

    Full Text Available The statistical properties of oligonucleotide appearances within long DNA sequences often reveal useful characteristics of the corresponding DNA areas. Two algorithms to statistically analyze oligonucleotide appearances within long DNA sequences in genome banks are presented. The first algorithm determines statistical indices for arbitrary length oligonucleotides within arbitrary length DNA sequences. The critical exponent μ of the distance distribution between consecutive occurrences of the same oligonucleotide is calculated and its value is shown to characterize the functionality of the oligonucleotide. The second algorithm searches for areas with variable homogeneity, based on the density of oligonucleotides. The two algorithms have been applied to representative eucaryotes (the animal Mus musculusand the plant Arabidopsis thaliana and interesting results were obtained, confirmed by biological observations. All programs are open source and publicly available on our web site.

  20. Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

    Science.gov (United States)

    Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

    2016-03-01

    Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (Pgene transfer.

  1. The CMS Muon System Alignment

    CERN Document Server

    Martinez Ruiz-Del-Arbol, P

    2009-01-01

    The alignment of the muon system of CMS is performed using different techniques: photogrammetry measurements, optical alignment and alignment with tracks. For track-based alignment, several methods are employed, ranging from a hit and impact point (HIP) algorithm and a procedure exploiting chamber overlaps to a global fit method based on the Millepede approach. For start-up alignment as long as available integrated luminosity is still significantly limiting the size of the muon sample from collisions, cosmic muon and beam halo signatures play a very strong role. During the last commissioning runs in 2008 the first aligned geometries have been produced and validated with data. The CMS offline computing infrastructure has been used in order to perform improved reconstructions. We present the computational aspects related to the calculation of alignment constants at the CERN Analysis Facility (CAF), the production and population of databases and the validation and performance in the official reconstruction. Also...

  2. Nucleoside phosphonic acids in oligonucleotide chemistry: Structural diversity versus properties of isopolar phosphonate internucleotide linkages

    Czech Academy of Sciences Publication Activity Database

    Hurychová, Vladimíra; Kóšiová, Ivana; Kovačková, Soňa; Králíková, Šárka; Liboska, Radek; Pačes, Ondřej; Páv, Ondřej; Petrová, Magdalena; Rejman, Dominik; Rosenberg, Ivan; Točík, Zdeněk

    Berlin : Oligonucleotide Therapeutic Society, 2007. s. 244-245. [Annual Meeting of the Oligonucleotide Therapeutics Society /3./. 04.10.2007-06.10.2007, Berlin] R&D Projects: GA MŠk(CZ) LC06077; GA MŠk(CZ) LC06061; GA ČR GA203/05/0827; GA ČR GA202/05/0628 Institutional research plan: CEZ:AV0Z40550506 Keywords : phosphonic acids * oligonucleotides * isopolar phosphonate * internucleotide linkage Subject RIV: CC - Organic Chemistry

  3. Recruitment of transcription factors to the target site by triplex-forming oligonucleotides.

    OpenAIRE

    Svinarchuk, F; Nagibneva, I; Cherny, D; Ait-Si-Ali, S; Pritchard, L.L.; Robin, P.; Malvy, C; Harel-Bellan, A; Chern, D

    1997-01-01

    Triplex-forming oligonucleotides (TFOs) are generally designed to inhibit transcription or DNA replication but can be used for more diverse purposes. Here we have designed a hairpin-TFO able to recruit transcription factors to a target DNA. The designed oligonucleotide contains a triplex-forming sequence, linked through a nucleotide loop to a double-stranded hairpin including the SRE enhancer of the c-fos gene promoter. We show here that this oligonucleotide can specifically recognise its DNA...

  4. Cationic oligonucleotides can mediate specific inhibition of gene expression in Xenopus oocytes.

    OpenAIRE

    Bailey, C P; Dagle, J M; Weeks, D L

    1998-01-01

    Base-specific hydrogen bonding between an oligonucleotide and the purines in the major groove of a DNA duplex provide an approach to selective inhibition of gene expression. Oligonucleotide-mediated triplex formation in vivo may be enhanced by a number of different chemical modifications. We have previously described an in vitro analysis of triplex formation using oligonucleotides containing internucleoside phosphate linkages modified with the cation N , N -diethyl-ethylenediamine (DEED). Whe...

  5. Coupling Strategies for the Synthesis of Peptide-Oligonucleotide Conjugates for Patterned Synthetic Biomineralization

    OpenAIRE

    Joshua D. Carter; LaBean, Thomas H.

    2011-01-01

    This work describes preparation strategies for peptide-oligonucleotide conjugates that combine the self-assembling behavior of DNA oligonucleotides with the molecular recognition capabilities of peptides. The syntheses include a solution-phase fragment coupling reaction and a solid-phase fragment coupling strategy where the oligonucleotide has been immobilized on DEAE Sepharose. The yield of four coupling reagents is evaluated, two reagents in water, EDC (1-ethyl-3-(3-dimethylaminopropyl) car...

  6. Oligonucleotide-directed mutagenesis by microscale 'shot-gun' gene synthesis.

    OpenAIRE

    Grundström, T; Zenke, W M; Wintzerith, M; Matthes, H W; Staub, A; Chambon, P

    1985-01-01

    We describe a rapid and efficient microscale method for in vitro site-directed mutagenesis by gene synthesis. Mutants are constructed by "shot-gun ligation" of overlapping synthetic oligonucleotides yielding double stranded synthetic DNA of more than 120 nucleotides in length. The terminal oligonucleotides of the DNA segment to be synthesized are designed to create sticky ends complementary to unique restriction sites of a polylinker present in an M13 vector. The oligonucleotides are hybridiz...

  7. TmPrime: fast, flexible oligonucleotide design software for gene synthesis

    OpenAIRE

    Bode, Marcus; Khor, Samuel; Ye, Hongye; Li, Mo-Huang; Ying, Jackie Y.

    2009-01-01

    Herein we present TmPrime, a computer program to design oligonucleotide sets for gene assembly by both ligase chain reaction (LCR) and polymerase chain reaction (PCR). TmPrime offers much flexibility with no constraints on the gene and oligonucleotide lengths. The program divides the long input DNA sequence based on the input desired melting temperature, and dynamically optimizes the length of oligonucleotides to achieve homologous melting temperatures. The output reports the melting temperat...

  8. Beam alignment system

    International Nuclear Information System (INIS)

    A patent is claimed for the invention of a beam alignment system. The aim of the invention is the obtention of an accurate monitoring of the beam position and direction. It is of great interest in the nuclear industry. The invention can be applied in an infrared laser beam for welding operations. An auxiliar radiation source is incorporated to the device. The system's configuration allows a simultaneous and separated utilisation of two beams. The description and the design of the proposed system are provided

  9. Alignment in hadronic interactions

    CERN Document Server

    Wibig, T

    2000-01-01

    The alignment of the products of very high energy interactions seen in mountain altitude experiments is one of the most puzzling phenomena in cosmic ray physics for quite a long time. The observations of the Pamir and Chacaltaya emulsion chamber groups and by the Tien-Shan extensive air shower experiment, together with a very clear event seen in the Concorde French-Japanese experiment in the stratosphere, makes the experimental basis very substantial. In the present paper a novel possible explanation is put forward.

  10. All about alignment

    CERN Multimedia

    2006-01-01

    The ALICE absorbers, iron wall and superstructure have been installed with great precision. The ALICE front absorber, positioned in the centre of the detector, has been installed and aligned. Weighing more than 400 tonnes, the ALICE absorbers and the surrounding support structures have been installed and aligned with a precision of 1-2 mm, hardly an easy task but a very important one. The ALICE absorbers are made of three parts: the front absorber, a 35-tonne cone-shaped structure, and two small-angle absorbers, long straight cylinder sections weighing 18 and 40 tonnes. The three pieces lined up have a total length of about 17 m. In addition to these, ALICE technicians have installed a 300-tonne iron filter wall made of blocks that fit together like large Lego pieces and a surrounding metal support structure to hold the tracking and trigger chambers. The absorbers house the vacuum chamber and are also the reference surface for the positioning of the tracking and trigger chambers. For this reason, the ab...

  11. Computing alignment plots efficiently

    CERN Document Server

    Krusche, Peter

    2009-01-01

    Dot plots are a standard method for local comparison of biological sequences. In a dot plot, a substring to substring distance is computed for all pairs of fixed-size windows in the input strings. Commonly, the Hamming distance is used since it can be computed in linear time. However, the Hamming distance is a rather crude measure of string similarity, and using an alignment-based edit distance can greatly improve the sensitivity of the dot plot method. In this paper, we show how to compute alignment plots of the latter type efficiently. Given two strings of length m and n and a window size w, this problem consists in computing the edit distance between all pairs of substrings of length w, one from each input string. The problem can be solved by repeated application of the standard dynamic programming algorithm in time O(mnw^2). This paper gives an improved data-parallel algorithm, running in time $O(mnw/\\gamma/p)$ using vector operations that work on $\\gamma$ values in parallel and $p$ processors. We show ex...

  12. Conditional alignment random fields for multiple motion sequence alignment.

    Science.gov (United States)

    Kim, Minyoung

    2013-11-01

    We consider the multiple time-series alignment problem, typically focusing on the task of synchronizing multiple motion videos of the same kind of human activity. Finding an optimal global alignment of multiple sequences is infeasible, while there have been several approximate solutions, including iterative pairwise warping algorithms and variants of hidden Markov models. In this paper, we propose a novel probabilistic model that represents the conditional densities of the latent target sequences which are aligned with the given observed sequences through the hidden alignment variables. By imposing certain constraints on the target sequences at the learning stage, we have a sensible model for multiple alignments that can be learned very efficiently by the EM algorithm. Compared to existing methods, our approach yields more accurate alignment while being more robust to local optima and initial configurations. We demonstrate its efficacy on both synthetic and real-world motion videos including facial emotions and human activities. PMID:24051737

  13. Oligonucleotide microarray for subtyping of influenza A viruses

    Science.gov (United States)

    Klotchenko, S. A.; Vasin, A. V.; Sandybaev, N. T.; Plotnikova, M. A.; Chervyakova, O. V.; Smirnova, E. A.; Kushnareva, E. V.; Strochkov, V. M.; Taylakova, E. T.; Egorov, V. V.; Koshemetov, J. K.; Kiselev, O. I.; Sansyzbay, A. R.

    2012-02-01

    Influenza is one of the most widespread respiratory viral diseases, infecting humans, horses, pigs, poultry and some other animal populations. Influenza A viruses (IAV) are classified into subtypes on the basis of the surface hemagglutinin (H1 to H16) and neuraminidase (N1 to N9) glycoproteins. The correct determination of IAV subtype is necessary for clinical and epidemiological studies. In this article we propose an oligonucleotide microarray for subtyping of IAV using universal one-step multisegment RT-PCR fluorescent labeling of viral gene segments. It showed to be an advanced approach for fast detection and identification of IAV.

  14. A convenient and efficient purification method for chemically labeled oligonucleotides.

    Science.gov (United States)

    Hwang, Jihee; Kang, Junhee; Kim, Seong Keun; Kim, Younggyu

    2013-05-01

    We developed an efficient, cost-effective, and rapid purification method for chemically-labeled oligonucleotides that requires less time than conventional procedures such as ethanol precipitation or size-exclusion chromatography. Based on the hydrophilic and hydrophobic properties of DNA and amine-reactive fluorophores, we show that n-butanol saturated with distilled water may be used to remove unreacted fluorophores by sequestering them in the organic phase, while labeled DNA remains in the aqueous phase. This phase extraction method is simple, fast, and allows for processing multiple samples simultaneously, a necessity for high-throughput labeling strategies. PMID:23662899

  15. Elimination and adsorptive transfer techniques in an oligonucleotide analysis

    Czech Academy of Sciences Publication Activity Database

    Jelen, František; Trnková, L.; Kouřilová, Alena; Kejnovská, Iva; Vorlíčková, Michaela

    Xi' an, 2009. P12. [International Symposium on Frontiers of Electrochemical Science and Technology . 12.08.2009-15.08.2009, Xi' an] R&D Projects: GA AV ČR(CZ) IAA400040804; GA AV ČR(CZ) IAA100040701; GA AV ČR(CZ) KAN200040651; GA MŠk(CZ) LC06035 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : elimination voltammetry * transfer techniques * analysis of oligonucleotides Subject RIV: BO - Biophysics

  16. Characterization of peptide-oligonucleotide heteroconjugates by mass spectrometry.

    OpenAIRE

    Jensen, O N; Kulkarni, S; Aldrich, J V; Barofsky, D F

    1996-01-01

    Two peptide-oligothymidylic acids, prepared by joining an 11 residue synthetic peptide containing one internal carboxyl group (Asp side chain) to amino-linker-5'pdT6 and amino-linker-5'pdT10 oligonucleotides, were analyzed by matrix-assisted laser desorption/ionization (MALDI) on a linear time-of-flight mass spectrometer and by electrospray ionization (ESI) on a triple-quadrupole system. These synthetic compounds model peptide-nucleic acid heteroconjugates encountered in antisense research an...

  17. Sulfur-containing phosphonate monomers for oligonucleotide synthesis

    Czech Academy of Sciences Publication Activity Database

    Kostov, Ondřej; Zborníková, Eva; Buděšínský, Miloš; Novák, Pavel; Rosenberg, Ivan

    Praha : Institute of Organic Chemistry and Biochemistry AS CR, v. v. i, 2014 - (Hocek, M.), s. 308-309 ISBN 978-80-86241-50-0. - (Collection Symposium Series. 14). [Symposium on Chemistry of Nucleic Acid Components /16./. Český Krumlov (CZ), 08.06.2014-13.06.2014] R&D Projects: GA ČR GA13-26526S; GA ČR GA13-24880S Institutional support: RVO:61388963 Keywords : S-MOP * oligonucleotides Subject RIV: CC - Organic Chemistry

  18. Oligonucleotide microarray for subtyping of influenza A viruses

    International Nuclear Information System (INIS)

    Influenza is one of the most widespread respiratory viral diseases, infecting humans, horses, pigs, poultry and some other animal populations. Influenza A viruses (IAV) are classified into subtypes on the basis of the surface hemagglutinin (H1 to H16) and neuraminidase (N1 to N9) glycoproteins. The correct determination of IAV subtype is necessary for clinical and epidemiological studies. In this article we propose an oligonucleotide microarray for subtyping of IAV using universal one-step multisegment RT-PCR fluorescent labeling of viral gene segments. It showed to be an advanced approach for fast detection and identification of IAV.

  19. Repair of DNA lesions associated with triplex-forming oligonucleotides.

    Science.gov (United States)

    Chin, Joanna Y; Glazer, Peter M

    2009-04-01

    Triplex-forming oligonucleotides (TFOs) are gene targeting tools that can bind in the major groove of duplex DNA in a sequence-specific manner. When bound to DNA, TFOs can inhibit gene expression, can position DNA-reactive agents to specific locations in the genome, or can induce targeted mutagenesis and recombination. There is evidence that third strand binding, alone or with an associated cross-link, is recognized and metabolized by DNA repair factors, particularly the nucleotide excision repair pathway. This review examines the evidence for DNA repair of triplex-associated lesions. PMID:19072762

  20. PCR amplification on microarrays of gel immobilized oligonucleotides

    Science.gov (United States)

    Strizhkov, Boris; Tillib, Sergei; Mikhailovich, Vladimir; Mirzabekov, Andrei

    2003-11-04

    The invention relates two general methods for performing PCR amplification, combined with the detection and analysis of the PCR products on a microchip. In the first method, the amplification occurs both outside and within a plurality of gel pads on a microchip, with at least one oligonucleotide primer immobilized in a gel pad. In the second method, PCR amplification also takes place within gel pads on a microchip, but the pads are surrounded by a hydrophobic liquid such as that which separates the individual gel pads into environments which resemble micro-miniaturized test tubes.

  1. Where Does the Alignment Score Distribution Shape Come from?

    Science.gov (United States)

    Ortet, Philippe; Bastien, Olivier

    2010-01-01

    Alignment algorithms are powerful tools for searching for homologous proteins in databases, providing a score for each sequence present in the database. It has been well known for 20 years that the shape of the score distribution looks like an extreme value distribution. The extremely large number of times biologists face this class of distributions raises the question of the evolutionary origin of this probability law. We investigated the possibility of deriving the main properties of sequence alignment score distributions from a basic evolutionary process: a duplication-divergence protein evolution process in a sequence space. Firstly, the distribution of sequences in this space was defined with respect to the genetic distance between sequences. Secondly, we derived a basic relation between the genetic distance and the alignment score. We obtained a novel score probability distribution which is qualitatively very similar to that of Karlin-Altschul but performing better than all other previous model. PMID:21258650

  2. Thermo-Hydrodynamical Alignment Effect, Conditions of Realization

    International Nuclear Information System (INIS)

    Conditions are considered of rapid intensification of a tropical hurricane. Characteristic range is determined of equilibrium translation speed. Dependence is considered of intensity of a opical hurricane from alignment number and hurricane heat potential. The basic assumption is confirmed of developed previously equilibrium translation model. (authors)

  3. Dust alignment in astrophysical environments

    Science.gov (United States)

    Lazarian, Alex; Thiem Hoang, Chi

    Dust is known to be aligned in interstellar medium and the arising polarization is extensively used to trace magnetic fields. What process aligns dust grains was one of the most long-standing problems of astrophysics in spite of the persistent efforts to solve it. For years the Davis-Greenstein paramagnetic alignment was the primary candidate for explaining grain alignment. However, the situation is different now and the most promising mechanism is associated with radiative torques (RATs) acting on irregular grains. I shall present the analytical theory of RAT alignment, discuss the observational tests that support this theory. I shall also discuss in what situations we expect to see the dominance of paramagnetic alignment.

  4. Nova laser alignment control system

    International Nuclear Information System (INIS)

    Alignment of the Nova laser requires control of hundreds of optical components in the ten beam paths. Extensive application of computer technology makes daily alignment practical. The control system is designed in a manner which provides both centralized and local manual operator controls integrated with automatic closed loop alignment. Menudriven operator consoles using high resolution color graphics displays overlaid with transport touch panels allow laser personnel to interact efficiently with the computer system. Automatic alignment is accomplished by using image analysis techniques to determine beam references points from video images acquired along the laser chain. A major goal of the design is to contribute substantially to rapid experimental turnaround and consistent alignment results. This paper describes the computer-based control structure and the software methods developed for aligning this large laser system

  5. Nuclear reactor internals alignment configuration

    Science.gov (United States)

    Gilmore, Charles B.; Singleton, Norman R.

    2009-11-10

    An alignment system that employs jacking block assemblies and alignment posts around the periphery of the top plate of a nuclear reactor lower internals core shroud to align an upper core plate with the lower internals and the core shroud with the core barrel. The distal ends of the alignment posts are chamfered and are closely received within notches machined in the upper core plate at spaced locations around the outer circumference of the upper core plate. The jacking block assemblies are used to center the core shroud in the core barrel and the alignment posts assure the proper orientation of the upper core plate. The alignment posts may alternately be formed in the upper core plate and the notches may be formed in top plate.

  6. An Overview of DNA Microarray Grid Alignment and Foreground Separation Approaches

    OpenAIRE

    Bajcsy Peter

    2006-01-01

    This paper overviews DNA microarray grid alignment and foreground separation approaches. Microarray grid alignment and foreground separation are the basic processing steps of DNA microarray images that affect the quality of gene expression information, and hence impact our confidence in any data-derived biological conclusions. Thus, understanding microarray data processing steps becomes critical for performing optimal microarray data analysis. In the past, the grid alignment and foreground s...

  7. Catalyzing alignment processes

    DEFF Research Database (Denmark)

    Lauridsen, Erik Hagelskjær; Jørgensen, Ulrik

    2004-01-01

    time and in combination with other social processes establish more aligned and standardized environmental performance between countries. However, examples of the introduction of environmental management suggests that EMS’ only plays a minor role in developing the actual environmental objectives......This paper describes how environmental management systems (EMS) spur the circulation of processes that support the constitution of environmental issues as specific environ¬mental objects and objectives. EMS catalyzes alignmentprocesses that produce coherence among the different elements involved...... they are implemented in and how the changing context is reflected in the environmental objectives that are established and prioritised. Our argument is, that the ability of the standard to achieve an impact is dependant on the constitution of ’coherent’ environmental issues in the context, where the management system...

  8. On aligning trees

    CERN Document Server

    Calder, J

    1997-01-01

    The increasing availability of corpora annotated for linguistic structure prompts the question: if we have the same texts, annotated for phrase structure under two different schemes, to what extent do the annotations agree on structuring within the text? We suggest the term tree alignment to indicate the situation where two markup schemes choose to bracket off the same text elements. We propose a general method for determining agreement between two analyses. We then describe an efficient implementation, which is also modular in that the core of the implementation can be reused regardless of the format of markup used in the corpora. The output of the implementation on the Susanne and Penn treebank corpora is discussed.

  9. GraphAlignment: Bayesian pairwise alignment of biological networks

    Directory of Open Access Journals (Sweden)

    Kolář Michal

    2012-11-01

    Full Text Available Abstract Background With increased experimental availability and accuracy of bio-molecular networks, tools for their comparative and evolutionary analysis are needed. A key component for such studies is the alignment of networks. Results We introduce the Bioconductor package GraphAlignment for pairwise alignment of bio-molecular networks. The alignment incorporates information both from network vertices and network edges and is based on an explicit evolutionary model, allowing inference of all scoring parameters directly from empirical data. We compare the performance of our algorithm to an alternative algorithm, Græmlin 2.0. On simulated data, GraphAlignment outperforms Græmlin 2.0 in several benchmarks except for computational complexity. When there is little or no noise in the data, GraphAlignment is slower than Græmlin 2.0. It is faster than Græmlin 2.0 when processing noisy data containing spurious vertex associations. Its typical case complexity grows approximately as O(N2.6. On empirical bacterial protein-protein interaction networks (PIN and gene co-expression networks, GraphAlignment outperforms Græmlin 2.0 with respect to coverage and specificity, albeit by a small margin. On large eukaryotic PIN, Græmlin 2.0 outperforms GraphAlignment. Conclusions The GraphAlignment algorithm is robust to spurious vertex associations, correctly resolves paralogs, and shows very good performance in identification of homologous vertices defined by high vertex and/or interaction similarity. The simplicity and generality of GraphAlignment edge scoring makes the algorithm an appropriate choice for global alignment of networks.

  10. The CMS tracker alignment in pp collisions

    International Nuclear Information System (INIS)

    The CMS all-silicon tracker consists of 16,588 modules. Aligning these with the desired precision of a few micrometers is only feasible using track based alignment procedures. Ultimate local precision is now achieved by the determination of sensor curvatures. This faces the algorithms with about 200,000 parameters to be calculated simultaneously. The Millipede II program interfaced with CMS software is optimized to provide solution in one step. The main remaining challenges are systematic distortions in the achieved geometry that are systematically biasing the track parameters like the track momenta. These distortions are controlled by adding further information into the alignment workflow, e.g. the mass of decaying resonances. In addition, the orientation of the tracker with respect to the magnetic field of CMS is determined with a stand-alone chi-square minimization procedure. The geometries are finally carefully validated. The monitored quantities include the basic track quantities for tracks from both collisions and cosmic muons and physics observables like resonance masses

  11. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available Experts \\ The Basics of Spinal Cord Injury Rehabilitation Topics Adult Injuries Spinal Cord Injury 101 Spinal Cord Injury 101 The Basics of Spinal Cord Injury Rehabilitation The Basics ...

  12. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available Experts \\ The Basics of Spinal Cord Injury Rehabilitation Topics Adult Injuries Spinal Cord Injury 101 Spinal Cord Injury 101 The Basics of Spinal Cord Injury Rehabilitation The Basics of Spinal Cord ...

  13. Stem Cell Basics

    Science.gov (United States)

    ... Information Stem Cell Basics Stem Cell Basics: Introduction Stem Cell Information General Information Clinical Trials Funding Information Current Research Policy Glossary Site Map Stem Cell Basics Introduction: What are stem cells, and why ...

  14. Basics of SCI Rehabilitation

    Science.gov (United States)

    Experts \\ The Basics of Spinal Cord Injury Rehabilitation Topics Adult Injuries Spinal Cord Injury 101 Spinal Cord Injury 101 The Basics of Spinal Cord Injury Rehabilitation The Basics of Spinal Cord ...

  15. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available Experts \\ The Basics of Spinal Cord Injury Rehabilitation Topics Adult Injuries Spinal Cord Injury 101 Spinal Cord Injury 101 The Basics of Spinal Cord Injury Rehabilitation The Basics of ...

  16. Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective

    Directory of Open Access Journals (Sweden)

    Stephanie A. Fernandes

    2013-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive and lethal disease of motor neuron degeneration, leading to paralysis of voluntary muscles and death by respiratory failure within five years of onset. Frontotemporal dementia (FTD is characterised by degeneration of frontal and temporal lobes, leading to changes in personality, behaviour, and language, culminating in death within 5–10 years. Both of these diseases form a clinical, pathological, and genetic continuum of diseases, and this link has become clearer recently with the discovery of a hexanucleotide repeat expansion in the C9orf72 gene that causes the FTD/ALS spectrum, that is, c9FTD/ALS. Two basic mechanisms have been proposed as being potentially responsible for c9FTD/ALS: loss-of-function of the protein encoded by this gene (associated with aberrant DNA methylation and gain of function through the formation of RNA foci or protein aggregates. These diseases currently lack any cure or effective treatment. Antisense oligonucleotides (ASOs are modified nucleic acids that are able to silence targeted mRNAs or perform splice modulation, and the fact that they have proved efficient in repeat expansion diseases including myotonic dystrophy type 1 makes them ideal candidates for c9FTD/ALS therapy. Here, we discuss potential mechanisms and challenges for developing oligonucleotide-based therapy for c9FTD/ALS.

  17. SOMA: a single oligonucleotide mutagenesis and cloning approach.

    Directory of Open Access Journals (Sweden)

    Thorsten Pfirrmann

    Full Text Available Modern biology research requires simple techniques for efficient and restriction site-independent modification of genetic material. Classical cloning and mutagenesis strategies are limited by their dependency on restriction sites and the use of complementary primer pairs. Here, we describe the Single Oligonucleotide Mutagenesis and Cloning Approach (SOMA that is independent of restriction sites and only requires a single mutagenic oligonucleotide to modify a plasmid. We demonstrate the broad application spectrum of SOMA with three examples. First, we present a novel plasmid that in a standardized and rapid fashion can be used as a template for SOMA to generate GFP-reporters. We successfully use such a reporter to assess the in vivo knock-down quality of morpholinos in Xenopus laevis embryos. In a second example, we show how to use a SOMA-based protocol for restriction-site independent cloning to generate chimeric proteins by domain swapping between the two human hRMD5a and hRMD5b isoforms. Last, we show that SOMA simplifies the generation of randomized single-site mutagenized gene libraries. As an example we random-mutagenize a single codon affecting the catalytic activity of the yeast Ssy5 endoprotease and identify a spectrum of tolerated and non-tolerated substitutions. Thus, SOMA represents a highly efficient alternative to classical cloning and mutagenesis strategies.

  18. Fast comparison of DNA sequences by oligonucleotide profiling

    Directory of Open Access Journals (Sweden)

    Marín Ignacio

    2008-02-01

    Full Text Available Abstract Background The comparison of DNA sequences is a traditional problem in genomics and bioinformatics. Many new opportunities emerge due to the improvement of personal computers, allowing the implementation of novel strategies of analysis. Findings We describe a new program, called UVWORD, which determines the number of times that each DNA word present in a sequence (target is found in a second sequence (source, a procedure that we have called oligonucleotide profiling. On a standard computer, the user may search for words of a size ranging from k = 1 to k = 14 nucleotides. Average counts for groups of contiguous words may also be established. The rate of analysis on standard computers is from 3.4 (k = 14 to 16 millions of words per second (1 ≤ k ≤ 8. This makes feasible the fast screening of even the longest known DNA molecules. Discussion We show that the combination of the ability of analyzing words of relatively long size, which occur very rarely by chance, and the fast speed of the program allows to perform novel types of screenings, complementary to those provided by standard programs such as BLAST. This method can be used to determine oligonucleotide content, to characterize the distribution of repetitive sequences in chromosomes, to determine the evolutionary conservation of sequences in different species, to establish regions of similar DNA among chromosomes or genomes, etc.

  19. In vivo delivery of transcription factors with multifunctional oligonucleotides

    Science.gov (United States)

    Lee, Kunwoo; Rafi, Mohammad; Wang, Xiaojian; Aran, Kiana; Feng, Xuli; Lo Sterzo, Carlo; Tang, Richard; Lingampalli, Nithya; Kim, Hyun Jin; Murthy, Niren

    2015-07-01

    Therapeutics based on transcription factors have the potential to revolutionize medicine but have had limited clinical success as a consequence of delivery problems. The delivery of transcription factors is challenging because it requires the development of a delivery vehicle that can complex transcription factors, target cells and stimulate endosomal disruption, with minimal toxicity. Here, we present a multifunctional oligonucleotide, termed DARTs (DNA assembled recombinant transcription factors), which can deliver transcription factors with high efficiency in vivo. DARTs are composed of an oligonucleotide that contains a transcription-factor-binding sequence and hydrophobic membrane-disruptive chains that are masked by acid-cleavable galactose residues. DARTs have a unique molecular architecture, which allows them to bind transcription factors, trigger endocytosis in hepatocytes, and stimulate endosomal disruption. The DARTs have enhanced uptake in hepatocytes as a result of their galactose residues and can disrupt endosomes efficiently with minimal toxicity, because unmasking of their hydrophobic domains selectively occurs in the acidic environment of the endosome. We show that DARTs can deliver the transcription factor nuclear erythroid 2-related factor 2 (Nrf2) to the liver, catalyse the transcription of Nrf2 downstream genes, and rescue mice from acetaminophen-induced liver injury.

  20. MaxAlign: maximizing usable data in an alignment

    DEFF Research Database (Denmark)

    Oliveira, Rodrigo Gouveia; Sackett, Peter Wad; Pedersen, Anders Gorm

    2007-01-01

    of gaps in any given sequence does not seem to disturb the phylogenetic estimates of other sequences. The MaxAlign web-server is freely available online at http://www.cbs.dtu.dk/services/MaxAlign where supplementary information can also be found. The program is also freely available as a Perl stand...

  1. Studies on the Syntheses and Properties of 5'-Branched-sugar Isonucleosides and the Related Oligonucleotides

    Institute of Scientific and Technical Information of China (English)

    Tian Xiaobing; Zhang Lihe; Min Jimei

    2001-01-01

    @@ The chemistry of nucleosides and oligonucleotides is an actively investigated field in the search for new drugs. Thesyntheses and the properties of isonucleosides and oligonucleotides have been investigated to improve their stability,antitumor and antiviral activities, and to reduce their toxicity.

  2. Synthesis of 3'-, or 5'-, or internal methacrylamido-modified oligonucleotides

    Science.gov (United States)

    Golova, Julia B.; Chernov, Boris K.

    2010-04-27

    New modifiers were synthesized for incorporation of a methacrylic function in 3'-, 5'- and internal positions of oligonucleotides during solid phase synthesis. A modifier was used for synthesis of 5'-methacrylated oligonucleotides for preparation of microarrays by a co-polymerization method.

  3. Mass spectrometry of nucleic acids components. Nucleotides, oligonucleotides and application to sequence determination

    International Nuclear Information System (INIS)

    The application of the various ionization techniques to the analysis of nucleotides and oligonucleotides is reviewed. The sequence determination of oligonucleotides was chosen to present the growing possibilities of mass spectrometry due to development of new ''soft ionization'' techniques. 119 refs., 6 figs., 2 tabs. (author)

  4. Long-range order of organized oligonucleotide monolayers on Au(111) electrodes

    DEFF Research Database (Denmark)

    Wackerbarth, Hainer; Grubb, Mikala; Zhang, Jingdong; Hansen, Allan Glargaard; Ulstrup, Jens

    2004-01-01

    Oligonucleotides modified by a hexamethylene linker group adsorb on gold electrodes via Au-S bond formation. We have obtained novel data for adsorption of thiol-modified (HS) single-strand HS-10A and double-stranded HS-10AT oligonucleotides and for analogous thiol-free 10A (A = adenine) and 10T (T...

  5. Pyro-Align: Sample-Align based Multiple Alignment system for Pyrosequencing Reads of Large Number

    CERN Document Server

    Saeed, Fahad

    2009-01-01

    Pyro-Align is a multiple alignment program specifically designed for pyrosequencing reads of huge number. Multiple sequence alignment is shown to be NP-hard and heuristics are designed for approximate solutions. Multiple sequence alignment of pyrosequenceing reads is complex mainly because of 2 factors. One being the huge number of reads, making the use of traditional heuristics,that scale very poorly for large number, unsuitable. The second reason is that the alignment cannot be performed arbitrarily, because the position of the reads with respect to the original genome is important and has to be taken into account.In this report we present a short description of the multiple alignment system for pyrosequencing reads.

  6. Using structure to explore the sequence alignment space of remote homologs.

    Directory of Open Access Journals (Sweden)

    Andrew Kuziemko

    2011-10-01

    Full Text Available Protein structure modeling by homology requires an accurate sequence alignment between the query protein and its structural template. However, sequence alignment methods based on dynamic programming (DP are typically unable to generate accurate alignments for remote sequence homologs, thus limiting the applicability of modeling methods. A central problem is that the alignment that is "optimal" in terms of the DP score does not necessarily correspond to the alignment that produces the most accurate structural model. That is, the correct alignment based on structural superposition will generally have a lower score than the optimal alignment obtained from sequence. Variations of the DP algorithm have been developed that generate alternative alignments that are "suboptimal" in terms of the DP score, but these still encounter difficulties in detecting the correct structural alignment. We present here a new alternative sequence alignment method that relies heavily on the structure of the template. By initially aligning the query sequence to individual fragments in secondary structure elements and combining high-scoring fragments that pass basic tests for "modelability", we can generate accurate alignments within a small ensemble. Our results suggest that the set of sequences that can currently be modeled by homology can be greatly extended.

  7. Stable dye-labelled oligonucleotide-nanoparticle conjugates for nucleic acid detection

    Science.gov (United States)

    Barrett, Lee; Dougan, Jennifer A.; Faulds, Karen; Graham, Duncan

    2011-08-01

    Metallic nanoparticles functionalized with oligonucleotides are used for a number of nucleic acid detection strategies. However, oligonucleotide-nanoparticle conjugates suffer from a lack of stability when exposed to certain conditions associated with DNA detection assays. In this study, we report the synthesis of thiol and thioctic acid-modified oligonucleotide gold nanoparticle (OGNs) conjugates functionalized with a dye label and varying spacer groups. The thioctic acid-modified conjugates exhibit increased stability when treated with dithiothreitol (DTT) compared to the more commonly used thiol modification. When the dye labelled oligonucleotide nanoparticle conjugates are exposed to the same conditions there is a pronounced increase in the stability for both thioctic acid and thiol modified sequences. These results open up the possibility of simply using a dye label to enhance the stability of oligonucleotide-nanoparticle conjugates in DNA detection assays where the enhanced stability of the conjugate system can be advantageous in more complex biological environments.

  8. Design of oligonucleotides for microarrays and perspectives for design of multi-transcriptome arrays

    DEFF Research Database (Denmark)

    Nielsen, Henrik Bjørn; Wernersson, Rasmus; Knudsen, Steen

    2003-01-01

    with an overview of these parameters. We present here a flexible tool named OligoWiz for designing oligonucleotides for multiple purposes. OligoWiz presents a set of parameter scores in a graphical interface to facilitate an overview for the user. Additional custom parameter scores can easily be added......Optimal design of oligonucleotides for microarrays involves tedious and laborious work evaluating potential oligonucleotides relative to a series of parameters. The currently available tools for this purpose are limited in their flexibility and do not present the oligonucleotide designer...... to the program to extend the default parameters: homology, DeltaTm, low-complexity, position and GATC-only. Furthermore we present an analysis of the limitations in designing oligonucleotide sets that can detect transcripts from multiple organisms. OligoWiz is available at www.cbs.dtu.dk/services/OligoWiz/....

  9. Design of oligonucleotides for microarrays and perspectives for design of multi-transcriptome arrays

    DEFF Research Database (Denmark)

    Nielsen, Henrik Bjørn; Wernersson, Rasmus; Knudsen, Steen

    2003-01-01

    overview of these parameters. We present here a flexible tool named OligoWiz for designing oligonucleotides for multiple purposes. OligoWiz presents a set of parameter scores in a graphical interface to facilitate an overview for the user. Additional custom parameter scores can easily be added to the......Optimal design of oligonucleotides for microarrays involves tedious and laborious work evaluating potential oligonucleotides relative to a series of parameters. The currently available tools for this purpose are limited in their flexibility and do not present the oligonucleotide designer with an...... program to extend the default parameters: homology, DeltaTm, low-complexity, position and GATC-only. Furthermore we present an analysis of the limitations in designing oligonucleotide sets that can detect transcripts from multiple organisms. OligoWiz is available at www.cbs.dtu.dk/services/OligoWiz/....

  10. Lexical alignment in triadic communication

    Directory of Open Access Journals (Sweden)

    Anouschka eFoltz

    2015-02-01

    Full Text Available Lexical alignment refers to the adoption of one’s interlocutor’s lexical items. Accounts of the mechanisms underlying such lexical alignment differ (among other aspects in the role assigned to addressee-centered behavior. In this study, we used a triadic communicative situation to test which factors may modulate the extent to which participants’ lexical alignment reflects addressee-centered behavior. Pairs of naïve participants played a picture matching game and received information about the order in which pictures were to be matched from a voice over headphones. On critical trials, participants did or did not hear a name for the picture to be matched next over headphones. Importantly, when the voice over headphones provided a name, it did not match the name that the interlocutor had previously used to describe the object. Participants overwhelmingly used the word that the voice over headphones provided. This result points to non-addressee-centered behavior and is discussed in terms of disrupting alignment with the interlocutor as well as in terms of establishing alignment with the voice over headphones. In addition, the type of picture (line drawing vs. tangram shape independently modulated lexical alignment, such that participants showed more lexical alignment to their interlocutor for (more ambiguous tangram shapes compared to line drawings. Overall, the results point to a rather large role for non-addressee-centered behavior during lexical alignment.

  11. Alignments in the nobelium isotopes

    Institute of Scientific and Technical Information of China (English)

    ZHENG Shi-Zie; XU Fu-Rong; YUAN Cen-Xi; QI Chong

    2009-01-01

    Total-Routhian-Surface calculations have been performed to investigate the deformation and align-ment properties of the No isotopes. It is found that normal deformed and superdeformed states in these nuclei can coexist at low excitation energies. In neutron-deficient No isotopes, the superdeformed shapes can even become the ground states. Moreover, we plotted the kinematic moments of inertia of the No isotopes, which follow very nicely available experimental data. It is noted that, as the rotational frequency increases, align-ments develop at hω=0.2-0.3 MeV. Our calculations show that the occupation of the vj orbital plays an important role in the alignments of the No isotopes.

  12. The CMS Silicon Tracker Alignment

    CERN Document Server

    Castello, R

    2008-01-01

    The alignment of the Strip and Pixel Tracker of the Compact Muon Solenoid experiment, with its large number of independent silicon sensors and its excellent spatial resolution, is a complex and challenging task. Besides high precision mounting, survey measurements and the Laser Alignment System, track-based alignment is needed to reach the envisaged precision.\\\\ Three different algorithms for track-based alignment were successfully tested on a sample of cosmic-ray data collected at the Tracker Integration Facility, where 15\\% of the Tracker was tested. These results, together with those coming from the CMS global run, will provide the basis for the full-scale alignment of the Tracker, which will be carried out with the first \\emph{p-p} collisions.

  13. Testing the tidal alignment model of galaxy intrinsic alignment

    International Nuclear Information System (INIS)

    Weak gravitational lensing has become a powerful probe of large-scale structure and cosmological parameters. Precision weak lensing measurements require an understanding of the intrinsic alignment of galaxy ellipticities, which can in turn inform models of galaxy formation. It is hypothesized that elliptical galaxies align with the background tidal field and that this alignment mechanism dominates the correlation between ellipticities on cosmological scales (in the absence of lensing). We use recent large-scale structure measurements from the Sloan Digital Sky Survey to test this picture with several statistics: (1) the correlation between ellipticity and galaxy overdensity, wg+; (2) the intrinsic alignment auto-correlation functions; (3) the correlation functions of curl-free, E, and divergence-free, B, modes, the latter of which is zero in the linear tidal alignment theory; (4) the alignment correlation function, wg(rp,θ), a recently developed statistic that generalizes the galaxy correlation function to account for the angle between the galaxy separation vector and the principle axis of ellipticity. We show that recent measurements are largely consistent with the tidal alignment model and discuss dependence on galaxy luminosity. In addition, we show that at linear order the tidal alignment model predicts that the angular dependence of wg(rp,θ) is simply wg+(rp)cos (2θ) and that this dependence is consistent with recent measurements. We also study how stochastic nonlinear contributions to galaxy ellipticity impact these statistics. We find that a significant fraction of the observed LRG ellipticity can be explained by alignment with the tidal field on scales ∼> 10 \\hMpc. These considerations are relevant to galaxy formation and evolution

  14. [Research progress of probe design software of oligonucleotide microarrays].

    Science.gov (United States)

    Chen, Xi; Wu, Zaoquan; Liu, Zhengchun

    2014-02-01

    DNA microarray has become an essential medical genetic diagnostic tool for its high-throughput, miniaturization and automation. The design and selection of oligonucleotide probes are critical for preparing gene chips with high quality. Several sets of probe design software have been developed and are available to perform this work now. Every set of the software aims to different target sequences and shows different advantages and limitations. In this article, the research and development of these sets of software are reviewed in line with three main criteria, including specificity, sensitivity and melting temperature (Tm). In addition, based on the experimental results from literatures, these sets of software are classified according to their applications. This review will be helpful for users to choose an appropriate probe-design software. It will also reduce the costs of microarrays, improve the application efficiency of microarrays, and promote both the research and development (R&D) and commercialization of high-performance probe design software. PMID:24804514

  15. Direct microcontact printing of oligonucleotides for biochip applications

    Directory of Open Access Journals (Sweden)

    Trévisiol E

    2005-07-01

    Full Text Available Abstract Background A critical step in the fabrication of biochips is the controlled placement of probes molecules on solid surfaces. This is currently performed by sequential deposition of probes on a target surface with split or solid pins. In this article, we present a cost-effective procedure namely microcontact printing using stamps, for a parallel deposition of probes applicable for manufacturing biochips. Results Contrary to a previous work, we showed that the stamps tailored with an elastomeric poly(dimethylsiloxane material did not require any surface modification to be able to adsorb oligonucleotides or PCR products. The adsorbed DNA molecules are subsequently printed efficiently on a target surface with high sub-micron resolution. Secondly, we showed that successive stamping is characterized by an exponential decay of the amount of transferred DNA molecules to the surface up the 4th print, then followed by a second regime of transfer that was dependent on the contact time and which resulted in reduced quality of the features. Thus, while consecutive stamping was possible, this procedure turned out to be less reproducible and more time consuming than simply re-inking the stamps between each print. Thirdly, we showed that the hybridization signals on arrays made by microcontact printing were 5 to 10-times higher than those made by conventional spotting methods. Finally, we demonstrated the validity of this microcontact printing method in manufacturing oligonucleotides arrays for mutations recognition in a yeast gene. Conclusion The microcontact printing can be considered as a new potential technology platform to pattern DNA microarrays that may have significant advantages over the conventional spotting technologies as it is easy to implement, it uses low cost material to make the stamp, and the arrays made by this technology are 10-times more sensitive in term of hybridization signals than those manufactured by conventional spotting

  16. Aligning for Innovation - Alignment Strategy to Drive Innovation

    Science.gov (United States)

    Johnson, Hurel; Teltschik, David; Bussey, Horace, Jr.; Moy, James

    2010-01-01

    With the sudden need for innovation that will help the country achieve its long-term space exploration objectives, the question of whether NASA is aligned effectively to drive the innovation that it so desperately needs to take space exploration to the next level should be entertained. Authors such as Robert Kaplan and David North have noted that companies that use a formal system for implementing strategy consistently outperform their peers. They have outlined a six-stage management systems model for implementing strategy, which includes the aligning of the organization towards its objectives. This involves the alignment of the organization from the top down. This presentation will explore the impacts of existing U.S. industrial policy on technological innovation; assess the current NASA organizational alignment and its impacts on driving technological innovation; and finally suggest an alternative approach that may drive the innovation needed to take the world to the next level of space exploration, with NASA truly leading the way.

  17. Enzymatic synthesis of modified oligonucleotides by PEAR using Phusion and KOD DNA polymerases.

    Science.gov (United States)

    Wang, Xuxiang; Zhang, Jianye; Li, Yingjia; Chen, Gang; Wang, Xiaolong

    2015-02-01

    Antisense synthetic oligonucleotides have been developed as potential gene-targeted therapeutics. We previously reported polymerase-endonuclease amplification reaction (PEAR) for amplification of natural and 5'-O-(1-thiotriphosphate) (S)-modified oligonucleotides. Here, we extended the PEAR technique for enzymatic preparation of 2'-deoxy-2'-fluoro-(2'-F) and 2'-F/S double-modified oligonucleotides. The result showed that KOD and Phusion DNA polymerase could synthesize oligonucleotides with one or two modified nucleotides, and KOD DNA polymerase is more suitable than Phusion DNA polymerase for PEAR amplification of 2'-F and 2'-F/S double modified oligonucleotides. The composition of PEAR products were analyzed by electrospray ionization liquid chromatography mass spectrometry (ESI/LC/MS) detection and showed that the sequence of the PEAR products are maintained at an extremely high accuracy (>99.9%), and after digestion the area percent of full-length modified oligonucleotides reaches 89.24%. PEAR is suitable for synthesis of modified oligonucleotides efficiently and with high purity. PMID:25517220

  18. Muon System alignment with tracks

    CERN Document Server

    Calderón, Alicia; Virto, A L; Martínez, P; Martínez-Rivero, C; Matorras, Francisco; Rodrigo, Teresa; Sobron, M; Vila, Ivan

    2006-01-01

    We describe here some of the techniques foreseen to align the Muon System with muon tracks. Two methods are proposed, one based on the Tracker which measures the position of a Muon chamber with respect to the Tracker, and another one which aligns internally the Muon System. A mathematical model is described for the general case. It is simplified for several particular cases of the Muon System alignment and applied to realistic examples on full simulation. Some estimates of the expected precision and limitation of the method are presented.

  19. Tracking and Alignment in the CMS detector

    CERN Document Server

    Ronga, Frederic Jean

    2007-01-01

    This Report summarises the alignment strategy of the CMS detector. Track reconstruction in the silicon tracker and muon chambers is briefly described. We then present the different sources of alignment information, in particular alignment algorithms using reconstructed tracks.

  20. The Use of Gel Electrophoresis to Study the Reactions of Activated Amino Acids with Oligonucleotides

    Science.gov (United States)

    Zieboll, Gerhard; Orgel, Leslie E.

    1994-01-01

    We have used gel electrophoresis to study the primary covalent addition of amino acids to oligonu-cleotides or their analogs and the subsequent addition of further molecules of the amino acids to generate peptides covalently linked to the oligonucleotides. We have surveyed the reactions of a variety of amino acids with the phosphoramidates derived from oligonucleotide 5 inches phosphates and ethylenediamine. We find that arginine and amino acids can interact with oligonucleotidesl through stacking interactions react most efficiently. D- and L-amino acids give indistinguishable families of products.

  1. Structure of the oligonucleotide d(CGTATATACG) as a site-specific complex with nickel ions.

    OpenAIRE

    Abrescia, N. G.; Malinina, L.; Fernandez, L. G.; Huynh-Dinh, T.; Neidle, S; Subirana, J A

    1999-01-01

    In this paper we explore the application of Ni2+to the crystallization of oligonucleotides. We have determined in this way the structure of a fully alternating (Y-R) decanucleotide d(CGTATATACG) by single crystal X-ray diffraction. This is the first oligonucleotide crystal structure with an alternating 5'-(TA)3-3' central part. Alternating oligonucleotides have a particular interest since they often have a unique structure. In this case the general conformation is B-like with an alternating t...

  2. Transfection Efficiency Comparison of Oligonucleotide and Plasmid to the HL-60 Cell Line with Liposomes

    Institute of Scientific and Technical Information of China (English)

    TANG Yi; LIU Wenli; ZHOU Jianfeng; XU Huizhen; LU Wu

    2005-01-01

    The transfection efficiency of oligonucleotide and plasmid to the HL-60 cell line with lipofectaminePLUS was compared through observing the transfection rate and the expression duration of exogenous gene in the target cells. The results showed that the transfection rate of oligonucleotide to the HL-60 was about 90 %-95 % and it had no obvious attenuation within 84 h. However,the plasmid transfection rate was only 5 %-25 % and it was decreased significantly within 60 h. It was suggested that the transfection of oligonucleotide with liposomes was better than that of plasmid.

  3. Modulating anti-MicroRNA-21 activity and specificity using oligonucleotide derivatives and length optimization

    DEFF Research Database (Denmark)

    Munoz-Alarcon, Andres; Guterstam, Peter; Romero, Cristian;

    2012-01-01

    MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation of gene expression vital for many developmental and cellular functions. Implicated in the pathogenesis of several human diseases, this group of RNAs provides interesting targets for therapeutic intervention. Anti......-microRNA oligonucleotides constitute a class of synthetic antisense oligonucleotides used to interfere with microRNAs. In this study, we investigate the effects of chemical modifications and truncations on activity and specificity of anti-microRNA oligonucleotides targeting microRNA-21. We observed an increased activity...

  4. VIP grafted long-circulation liposome for targeted delivery of oligonucleotide to breast cancer cells

    International Nuclear Information System (INIS)

    Purpose: To investigate the use of long-circulation liposome (LCL) for the delivery of encapsulated oligonucleotide with or without radioiodine-125 (125I) to MCF-7 breast cancer cells in vitro. Methods: (1) Oligonucleotide was labeled with 125I using thallium chloride tetrahydrate (TICL3) as an oxidant. 125I-oligonucleotide was separated from free oligonucleotide or 125I by column chromatography (Sephadex G-25). The efficiency of labeling and the radiochemistry purity were obtained using chromatography of paper. (2) Oligonucleotide with or without 125I encapsulating LCL were prepared in the means of reverse-phase evaporation. The crude LCL were then repeatedly extruded through 400 nm, 200 nm, 100 nm polycarbonate membranes consecutively. Uncapsulated oligonucleotide with or without 125I was separated from LCL formulations by passing down a sephadex G-50 column in 0.01 M HEPES buffer. Pooled LCL encapsulated oligonucleotide with or without 125I fractions were sterile through 0.22 μm filters prior to use. The method of protamine sulfate precipitation was utilized to gain the efficiency of encapsulation. (3) MCF-7 cells were grown in RPMI1640 media containing 10% heat-inactivated fetal calf serum. (4)Time-dependent uptake of 125I-oligonucleotide was studied by measuring the radioactivity of MCF-7 cells. Results: The efficiency of labeling and radiochemistry purity of bcl-2 antisense-, sense- and nonsense-oligonucleotide were 84.52% and 97.49%, 58.05% and 95.40%, 74.6% and 98.7%, respectively. The efficiency of encapsulation of bcl-2 antisense-, sense- and nonsense-oligonucleotide is 77.58%, 45.98%, 38.2%, respectively. (3) The par cle size of LCL formulations(∼120 nm) was determined by laser scattering techniques. During the period of observation from 20 min to 300 min, the radioactivity of tumor cells was almost as same as the background. Conclusions: LCL can not effectively deliver oligonucleotide with 125I into MCF-7 cells in vitro. To achieve the active

  5. Harmonic Analysis of Linac Alignment

    CERN Document Server

    McCrady, Rodney C

    2005-01-01

    We have analyzed the requirements on alignment of the focusing elements (quadrupole doublets) in the Los Alamos Neutron Science Center (LANSCE) side coupled linac. The analysis is performed in terms of harmonics of the quardrupole spacing. This allows us to determine the effect of intentional deviations from a straight line, such as following the curvature of the Earth, and of unintentional deviations introduced by measurement and alignment errors. Results are compared to measured positions of the doublets.

  6. Expressive alignment language and implementation

    OpenAIRE

    Euzenat, Jérôme; Scharffe, François; Zimmermann, Antoine

    2007-01-01

    euzenat2007e This deliverable provides the description of an alignment language which is both expressive and independent from ontology languages. It defines the language through its abstract syntax and semantics depending on ontology language semantics. It then describes two concrete syntax: an exchange syntax in RDF/XML and a surface syntax for human consumption. Finally, it presents the current implementation of this expressive language within the Alignment API taking advantage of the OM...

  7. Basic Research Firing Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Basic Research Firing Facility is an indoor ballistic test facility that has recently transitioned from a customer-based facility to a dedicated basic research...

  8. Health Insurance Basics

    Science.gov (United States)

    ... Can I Help a Friend Who Cuts? Health Insurance Basics KidsHealth > For Teens > Health Insurance Basics Print ... advanced calculus was confusing. What Exactly Is Health Insurance? Health insurance is a plan that people buy ...

  9. Climate Change: Basic Information

    Science.gov (United States)

    ... are here: EPA Home Climate Change Basic Information Climate Change: Basic Information On This Page Climate change ... We can make a difference How is the climate changing in the U.S.? Observations across the United ...

  10. The CMS Tracker alignment in p-p collisions

    CERN Document Server

    Bhardwaj, Ashutosh

    2012-01-01

    The CMS all-silicon tracker consists of 16588 modules. Aligning these with the desired precision of a few micrometers is only feasible using track based alignment procedures. Ultimate local precision is now achieved by the determination of sensor curvatures. This leads to about 200 000 parameters to be calculated simultaneously. The Millepede II program interfaced with CMS software is optimized to provide solution in one step. The main remaining challenges are systematic distortions in the achieved geometry that are systematically biasing the track parameters like the track momenta. These distortions are controlled by adding further information into the alignment workflow, e.g. the mass of decaying resonances. In addition, the orientation of the tracker with respect to the magnetic field of CMS is determined with a stand-alone chi-square minimization procedure. The geometries are finally carefully validated. The monitored quantities include the basic track quantities for tracks from both collisions and cosmic...

  11. Body Basics Library

    Science.gov (United States)

    ... a Friend Who Cuts? About the Body Basics Library KidsHealth > For Teens > About the Body Basics Library Print A A A Text Size Did you ... system, part, and process works. Use this medical library to find out about basic human anatomy, how ...

  12. Basic Cake Decorating Workbook.

    Science.gov (United States)

    Bogdany, Mel

    Included in this student workbook for basic cake decorating are the following: (1) Drawings of steps in a basic way to ice a layer cake, how to make a paper cone, various sizes of flower nails, various sizes and types of tin pastry tubes, and special rose tubes; (2) recipes for basic decorating icings (buttercream, rose paste, and royal icing);…

  13. Carboranyl Nucleosides & Oligonucleotides for Neutron Capture Therapy Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Schinazi, Raymond F.

    2004-12-01

    This proposal enabled us to synthesize and develop boron-rich nucleosides and oligonucleotide analogues for boron neutron capture therapy (BNCT) and the treatment of various malignancies. First, we determined the relationship between structure, cellular accumulation and tissue distribution of 5-o-carboranyl-2'-deoxyuridine (D-CDU) and its derivatives D-ribo-CU and 5-o-carboranyluracil (CU), to potentially target brain and other solid tumors for neutron capture therapy. Synthesized carborane containing nucleoside derivatives of CDU, D- and L-enantiomers of CDU, D-ribo-CU and CU were used. We measured tissue disposition in xenografted mice bearing 9479 human prostate tumors xenografts and in rats bearing 9L gliosarcoma isografts in their flanks and intracranially. The accumulation of D-CDU, 1-({beta}-L-arabinosyl)-5-o-carboranyluracil, D-ribo-CU, and CU were also studied in LnCap human prostate tumor cells and their retention was measured in male nude mice bearing LnCap and 9479 human prostate tumor xenografts. D-CDU, D-ribo-CU and CU levels were measured after administration in mice bearing 9479 human prostate tumors in their flanks. D-CDU achieved high cellular concentrations in LnCap cells and up to 2.5% of the total cellular compound was recovered in the 5'-monophosphorylated form. D-CDU cellular concentrations were similar in LnCap and 9479 tumor xenografts. Studies in tumor bearing animals indicated that increasing the number of hydroxyl moieties in the sugar constituent of the carboranyl nucleosides lead to increased rate and extent of renal elimination, a decrease in serum half-lives and an increased tissue specificity. Tumor/brain ratios were greatest for CDU and D-ribo-CU, while tumor/prostate ratios were greatest with CU. CDU and D-ribo-CU have potential for BNCT of brain malignancies, while CU may be further developed for prostate cancer. A method was developed for the solid phase synthesis of oligonucleotides containing (ocarboran-1-yl

  14. Carboranyl Oligonucleotides for Neutron Capture Therapy Final Report

    International Nuclear Information System (INIS)

    This proposal enabled us to synthesize and develop boron-rich nucleosides and oligonucleotide analogues for boron neutron capture therapy (BNCT) and the treatment of various malignancies. First, we determined the relationship between structure, cellular accumulation and tissue distribution of 5-o-carboranyl-2'-deoxyuridine (D-CDU) and its derivatives D-ribo-CU and 5-o-carboranyluracil (CU), to potentially target brain and other solid tumors for neutron capture therapy. Synthesized carborane containing nucleoside derivatives of CDU, D- and L-enantiomers of CDU, D-ribo-CU and CU were used. We measured tissue disposition in xenografted mice bearing 9479 human prostate tumors xenografts and in rats bearing 9L gliosarcoma isografts in their flanks and intracranially. The accumulation of D-CDU, 1-(β-L-arabinosyl)-5-o-carboranyluracil, D-ribo-CU, and CU were also studied in LnCap human prostate tumor cells and their retention was measured in male nude mice bearing LnCap and 9479 human prostate tumor xenografts. D-CDU, D-ribo-CU and CU levels were measured after administration in mice bearing 9479 human prostate tumors in their flanks. D-CDU achieved high cellular concentrations in LnCap cells and up to 2.5% of the total cellular compound was recovered in the 5'-monophosphorylated form. D-CDU cellular concentrations were similar in LnCap and 9479 tumor xenografts. Studies in tumor bearing animals indicated that increasing the number of hydroxyl moieties in the sugar constituent of the carboranyl nucleosides lead to increased rate and extent of renal elimination, a decrease in serum half-lives and an increased tissue specificity. Tumor/brain ratios were greatest for CDU and D-ribo-CU, while tumor/prostate ratios were greatest with CU. CDU and D-ribo-CU have potential for BNCT of brain malignancies, while CU may be further developed for prostate cancer. A method was developed for the solid phase synthesis of oligonucleotides containing (ocarboran-1-yl

  15. Cleavage of Oligonucleotides Containing a P3’→N5’ Phosphoramidate Linkage Mediated by Single-Stranded Oligonucleotide Templates

    Directory of Open Access Journals (Sweden)

    Takeshi Imanishi

    2011-12-01

    Full Text Available Double-stranded DNA (dsDNA templates can hybridize to and accelerate cleavage of oligonucleotides containing a P3’→N5’ phosphoramidate (P-N linkage. This dsDNA-templated cleavage of P-N linkages could be due to conformational strain placed on the linkage upon triplex formation. To determine whether duplex formation also induced conformational strain, we examined the reactivity of the oligonucleotides with a P-N linkage in the presence of single-stranded templates, and compared these reactions to those with dsDNA templates. P-N oligonucleotides that are cleaved upon duplex formation could be used as probes to detect single-stranded nucleic acids.

  16. Beginning Visual Basic 2010

    CERN Document Server

    Willis, Thearon

    2010-01-01

    A focused, step-by-step approach to Visual Basic for new programmers. What better way to get started with Visual Basic than with this essential Wrox beginner's guide? Beginning Microsoft Visual Basic 2010 not only shows you how to write Windows applications, Web applications with ASP.NET, and Windows mobile and embedded CE apps with Visual Basic 2010, but you'll also get a thorough grounding in the basic nuts-and-bolts of writing good code. You'll be exposed to the very latest VB tools and techniques with coverage of both the Visual Studio 2010 and .NET 4 releases. Plus, the book walks you ste

  17. Exploiting Protected Maleimides to Modify Oligonucleotides, Peptides and Peptide Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Clément Paris

    2015-04-01

    Full Text Available This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected maleimides. Suitably derivatized building blocks incorporating the exo Diels-Alder cycloadduct can be introduced at any position of oligonucleotides, peptide nucleic acids, peptides and peptoids, making use of standard solid-phase procedures. Maleimide deprotection takes place upon heating, which can be followed by either Michael-type or Diels-Alder click conjugation reactions. However, the one-pot procedure in which maleimide deprotection and conjugation are simultaneously carried out provides the target conjugate more quickly and, more importantly, in better yield. This procedure is compatible with conjugates involving oligonucleotides, peptides and peptide nucleic acids. A variety of cyclic peptides and oligonucleotides can be obtained from peptide and oligonucleotide precursors incorporating protected maleimides and thiols.

  18. Oligonucleotides with rapid turnover of the phosphate groups occur endogenously in eukaryotic cells

    International Nuclear Information System (INIS)

    Endogenous oligonucleotides were found in trichloroacetic acid extracts of hamster lung fibroblasts and Tetrahymena cells. Peaks of radioactivity that eluted with retention times similar to oligonucleotide markers (5- to 50-mer) were found by HPLC in cells labeled briefly with 32Pi. Only minute amounts of UV-absorbing material were detected, consistent with a rapid turnover of phosphate groups. The 32P-labeled material also migrated as oligonucleotides on 20% polyacrylamide gels; it was not hydrolyzed by alkaline phosphatase but was digested by snake venom phosphodiesterase, S1 nuclease, and pancreatic RNase and was phosphorylated by T4 polynucleotide kinase. The 32P-labeled material isolated by HPLC was alkali labile and the hydrolyzate ran as nucleotides on paper chromatography. It is concluded that the oligonucleotides are mainly oligoribonucleotides, but it is possible that oligodeoxynucleotides are also present

  19. Fast, copper-free click chemistry: a convenient solid-phase approach to oligonucleotide conjugation

    OpenAIRE

    Singh, Ishwar; Vyle, Joseph S.; Heaney, Frances

    2009-01-01

    Solid-phase oligonucleotide conjugation by nitrile oxide–alkyne click cycloaddition chemistry has been successfully demonstrated; the reaction, compatible with all nucleobases, requires no metal catalyst and proceeds under physiological conditions.

  20. Use of synthetic oligonucleotides for genomic DNA dot hybridization to split the DQw3 haplotype.

    Science.gov (United States)

    Martell, M; Le Gall, I; Millasseau, P; Dausset, J; Cohen, D

    1988-01-01

    Comparison of two different HLA-DQ beta gene sequences from two DR4 individuals, probably corresponding to DQw3.2 (DQR4) and DQw3.1 (DQR5) specificities, has shown several nucleotide variations. Eight oligonucleotides (24 bases long), derived from these polymorphic areas, have been synthesized. Each oligonucleotide was hybridized to BamHI-digested DNA samples from eight families with HLA-DR4 individuals. Four polymorphic BamHI fragments were detected. Two of eight oligonucleotides gave a single signal (8.9 kilobases) on DQw3.2-positive haplotypes. We used one of these oligonucleotides in a genomic DNA dot hybridization and detected a hybridization signal only in DQw3.2-positive individuals. A very simple test like this allows the screening of a large population sample within a very short period. Images PMID:2895927

  1. On-line coupling of capillary gel electrophoresis with electrospray mass spectrometry for oligonucleotide analysis.

    Science.gov (United States)

    Freudemann, T; von Brocke, A; Bayer, E

    2001-06-01

    Homooligodeoxyribonucleotides differing one nucleotide in length from 12- to 15-mer and from 17- to 20-mer were separated by size with capillary gel electrophoresis (CGE) using an entangled polymer solution in coated capillaries. The resolved components were analyzed by on-line coupling of CGE with electrospray mass spectrometry (ES-MS), denoted as CGE/ES-MS, in the full-scan negative ion detection mode. Baseline separation was achieved for the 12-15-mer oligonucleotide mixtures. Both synthetic phosphodiester oligonucleotide mixtures as well as their phosphorothioate analogues, serving as model compounds for antisense oligonucleotides, could be analyzed by on-line CGE/ES-MS coupling. Terminally phosphorylated and nonphosphorylated synthetic failure sequences could be electrophoretically separated and mass spectrometically characterized as well. This methodology might be a useful tool for synthesis control of phosphodiester oligonucleotides as well as for analysis of phosphorothioate analogues as they are used in antisense drug development. PMID:11403304

  2. P123-T Oligonucleotide Purification Strategies using a New High-Capacity Anion Exchange Resin

    OpenAIRE

    Deetz, M.; Fisher, J. R.; Gehris, A.; Maikner, J.; Kinzey, M.

    2007-01-01

    With the advent of nucleic acid silencing technologies and the need for high purity diagnostic and therapeutic oligonucleotides, there is a need for high-capacity chromatographic supports that can deliver economic purification processes. A new, 30 micron, mono-sized, polymeric resin has been recently developed that provides high resolution and high capacity for synthetic oligonucleotides. Physical properties of this new resin will be described, including particle size uniformity, ion exchange...

  3. Ligation of oligonucleotides to nucleic acids or proteins via disulfide bonds.

    OpenAIRE

    Chu, B C; Orgel, L E

    1988-01-01

    We have developed general methods for joining together, via cleavable disulfide bonds, either two unprotected polynucleotides or a polynucleotide and a peptide or protein. To join two oligonucleotides, each is first converted to an adduct in which cystamine is joined to the 5'-terminal phosphate of the oligonucleotide by a phosphoramidate bond. The adducts are mixed and reduced with dithiothreitol. The dithiothreitol is then removed by dialysis. Oxidation by atmospheric oxygen occurs to yield...

  4. Design and synthesis of polyacrylamide-based oligonucleotide supports for use in nucleic acid diagnostics.

    OpenAIRE

    Fahy, E.; Davis, G R; DiMichele, L J; Ghosh, S. S.

    1993-01-01

    Polyacrylamide supports, in a range of pore sizes, were investigated as nucleic acid affinity matrices for the detection of target DNA or RNA sequences using a sandwich hybridization format. Bromoacetyl and thiol oligonucleotide derivatives were covalently linked to sulfhydryl- and bromoacetyl-polyacrylamide supports with greater than 95% end-attachment efficiencies. These polyacrylamide-oligonucleotide supports were further derivatized with anionic residues to provide multi-functional suppor...

  5. Microinjection of antisense c-mos oligonucleotides prevents meiosis II in the maturing mouse egg.

    OpenAIRE

    O'Keefe, S J; Wolfes, H; Kiessling, A A; Cooper, G M

    1989-01-01

    Injection of antisense oligonucleotides was used to investigate the function of c-mos in murine oocytes. Oocytes injected with antisense c-mos oligonucleotides completed the first meiotic division but failed to initiate meiosis II. Instead, loss of c-mos function led to chromosome decondensation, reformation of a nucleus after meiosis I, and cleavage to two cells. Therefore, c-mos is required for meiosis II during murine oocyte maturation.

  6. Development, Characterization and Experimental Validation of a Cultivated Sunflower (Helianthus annuus L.) Gene Expression Oligonucleotide Microarray

    OpenAIRE

    Fernandez, Paula; Soria, Marcelo; Blesa, David; DiRienzo, Julio; Moschen, Sebastian; Rivarola, Maximo; Clavijo, Bernardo Jose; Gonzalez, Sergio; Peluffo, Lucila; Príncipi, Dario; Dosio, Guillermo; Aguirrezabal, Luis; García-García, Francisco; Conesa, Ana; Hopp, Esteban

    2012-01-01

    Oligonucleotide-based microarrays with accurate gene coverage represent a key strategy for transcriptional studies in orphan species such as sunflower, H. annuus L., which lacks full genome sequences. The goal of this study was the development and functional annotation of a comprehensive sunflower unigene collection and the design and validation of a custom sunflower oligonucleotide-based microarray. A large scale EST (>130,000 ESTs) curation, assembly and sequence annotation was performed us...

  7. Synthesis and Properties of Oligonucleotides Carrying Isoquinoline Imidazo[1,2-a]azine Fluorescent Units

    OpenAIRE

    Pérez-Rentero, Sonia; Kielland, Nicola; Terrazas, Montserrat; Lavilla, Rodolfo; Eritja Casadellà, Ramón

    2010-01-01

    Oligonucleotides carrying novel fluorescent compounds with a dipolar isoquinoline imidazo[1,2-a]azine core were prepared. Analysis of the melting curves demonstrates that DNA duplexes carrying these fluorescent labels at their ends have a slight increase in DNA duplex stability. The UV absorption and fluorescent properties of the oligonucleotide conjugates were analyzed. The fluorescent label is sensitive to duplex formation, as cooperative melting curves are also observed at 366 nm and fluor...

  8. Improved bioactivity of G-rich triplex-forming oligonucleotides containing modified guanine bases

    OpenAIRE

    Rogers, Faye A.; Lloyd, Janice A; Tiwari, Meetu Kaushik

    2014-01-01

    Triplex structures generated by sequence-specific triplex-forming oligonucleotides (TFOs) have proven to be promising tools for gene targeting strategies. In addition, triplex technology has been highly utilized to study the molecular mechanisms of DNA repair, recombination and mutagenesis. However, triplex formation utilizing guanine-rich oligonucleotides as third strands can be inhibited by potassium-induced self-association resulting in G-quadruplex formation. We report here that guanine-r...

  9. Understanding oligonucleotide-mediated inhibition of gene expression in Xenopus laevis oocytes

    OpenAIRE

    Bailey, Cheryl; Weeks, Daniel L.

    2000-01-01

    Triplex-forming oligonucleotides (TFOs) modified with N,N-diethylethylenediamine can inhibit the expression of a reporter plasmid in Xenopus oocytes if the triplex is preformed prior to injection while unmodified oligonucleotides cannot. Here we show that merely forming a triplex in a reporter plasmid does not disrupt transcription, but when TFOs are targeted to sites within the transcribed region of a reporter gene then gene activity is inhibited. TFO-based inhibition did not lead to large s...

  10. Positively charged oligonucleotides overcome potassium-mediated inhibition of triplex DNA formation.

    OpenAIRE

    Dagle, J M; Weeks, D L

    1996-01-01

    The formation of triplex DNA using unmodified, purine-rich oligonucleotides (ODNs) is inhibited by physiologic levels of potassium. Changing negative phosphodiester bonds in a triplex forming oligonucleotide (TFO) to neutral linkages causes a small increase in triplex formation. When phosphodiester bonds in a TFO are converted to positively-charged linkages the formation of triplex DNA increases dramatically. In the absence of KCl, a 17mer TFO containing 11 positively-charged linkages at a co...

  11. Synthesis and properties of triplex-forming oligonucleotides containing 2'-modified nucleoside analogues

    OpenAIRE

    Lou, Chenguang

    2011-01-01

    Triplex-forming oligonucleotides (TFOs) bind to the major groove of the DNA duplex via the Hoogsteen interactions to generate triple helices. Potential applications of triplex technology are in regulation of gene expression, site-directed gene-knockout, mutation correction and as tools in molecular biotechnology. The presence of 2’-modified nucleosides in therapeutic oligonucleotides inhibits enzymatic degradation in vivo. Therefore such sugar modifications have the potential to improve the b...

  12. Targeted inhibition of transcription elongation in cells mediated by triplex-forming oligonucleotides

    OpenAIRE

    Faria, M.; Wood, C. D.; Perrouault, L; Nelson, J. S.; Winter, A.; White, M. R. H.; Hélène, C; Giovannangeli, C.

    2000-01-01

    Triple-helix-forming oligonucleotides (TFOs) bind in the major groove of double-stranded DNA at oligopyrimidine⋅oligopurine sequences and therefore are candidate molecules for artificial gene regulation, in vitro and in vivo. We recently have described oligonucleotide analogues containing N3′-P5′ phosphoramidate (np) linkages that exhibited efficient inhibition of transcription elongation in vitro. In the present work we provide conclusive evidence that np-modified TFOs targeted to the HIV-1 ...

  13. In vivo stability and kinetics of absorption and disposition of 3' phosphopropyl amine oligonucleotides.

    OpenAIRE

    Zendegui, J G; Vasquez, K M; Tinsley, J H; Kessler, D J; Hogan, M E

    1992-01-01

    Development of oligonucleotide derivatives as therapeutic agents requires an understanding of their pharmacokinetic behavior. The in vivo disposition and stability of a prototype of such compounds are reported here. The compound studied, a relatively G-rich 38 base 3' phosphopropyl amine oligonucleotide (TFO-1), was cleared from the circulation with a half-life of approximately 10 minutes, displaying distribution kinetics consistent with a two compartment model. TFO-1 was also readily absorbe...

  14. Spatial organization of topoisomerase I-mediated DNA cleavage induced by camptothecin–oligonucleotide conjugates

    OpenAIRE

    Arimondo, Paola B.; Angenault, Stéphane; Halby, Ludovic; Boutorine, Alexandre; Schmidt, Frédéric; Monneret, Claude; Garestier, Thérèse; Sun, Jian-Sheng; Bailly, Christian; Hélène, Claude

    2003-01-01

    Triple helix-forming oligonucleotides covalently linked to topoisomerase I inhibitors, in particular the antitumor agent camptothecin, trigger topoisomerase I-mediated DNA cleavage selectively in the proximity of the binding site of the oligonucleotide vector. In the present study, we have performed a systematic analysis of the DNA cleavage efficiency as a function of the positioning of the camptothecin derivative, either on the 3′ or the 5′ side of the triplex, and the location of the cleava...

  15. A New Achiral Linker Reagent for the Incorporation of Multiple Amino Groups Into Oligonucleotides

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a new functionalized achiral linker reagent for incorporating multiple primary amino groups or reporter groups into oligonucleotides following the phosphoramidite methodology. It is possible to substitute any ribodeoxynucleotide, deoxynucleotide, or nucleotide with...... the linker in conventional phosphoamidite or H-phosphonate DNA syntheses. Directly, or via a post modification step, an oligonucleotide is labelled with one or more reporter moieties, e.g. dansyl (5-dimethylamino)-1-naphthalenesulfonyl), biotin, digoxigenin, DOXYL (N-oxyl-4,4-dimethyloxazolidine...

  16. Complexes of carbon nanotubes with oligonucleotides in thin Langmuir-Blodgett films to detect electrochemically hybridization

    Science.gov (United States)

    Egorov, A. S.; Egorova, V. P.; Krylova, H. V.; Lipnevich, I. V.; Orekhovskaya, T. I.; Veligura, A. A.; Govorov, M. I.; Shulitsky, B. G.

    2014-10-01

    Self-assembled complexes consisting of thin multi-walled carbon nanotubes (MWCNTs) and DNA-oligonucleotides which are able to a cooperative binding to complementary oligonucleotides have been investigated. It was establised a high-performance charge transport in nanostructured Langmuir-Blodgett complexes thin MWCNTs/DNA. A method to electrochemically detect DNA hybridization on the self-organized structures has been proposed.

  17. A basic analysis toolkit for biological sequences

    Directory of Open Access Journals (Sweden)

    Siragusa Enrico

    2007-09-01

    Full Text Available Abstract This paper presents a software library, nicknamed BATS, for some basic sequence analysis tasks. Namely, local alignments, via approximate string matching, and global alignments, via longest common subsequence and alignments with affine and concave gap cost functions. Moreover, it also supports filtering operations to select strings from a set and establish their statistical significance, via z-score computation. None of the algorithms is new, but although they are generally regarded as fundamental for sequence analysis, they have not been implemented in a single and consistent software package, as we do here. Therefore, our main contribution is to fill this gap between algorithmic theory and practice by providing an extensible and easy to use software library that includes algorithms for the mentioned string matching and alignment problems. The library consists of C/C++ library functions as well as Perl library functions. It can be interfaced with Bioperl and can also be used as a stand-alone system with a GUI. The software is available at http://www.math.unipa.it/~raffaele/BATS/ under the GNU GPL.

  18. Fragment-based solid-phase assembly of oligonucleotide conjugates with peptide and polyethylene glycol ligands.

    Science.gov (United States)

    Dirin, Mehrdad; Urban, Ernst; Noe, Christian R; Winkler, Johannes

    2016-10-01

    Ligand conjugation to oligonucleotides is an attractive strategy for enhancing the therapeutic potential of antisense and siRNA agents by inferring properties such as improved cellular uptake or better pharmacokinetic properties. Disulfide linkages enable dissociation of ligands and oligonucleotides in reducing environments found in endosomal compartments after cellular uptake. Solution-phase fragment coupling procedures for producing oligonucleotide conjugates are often tedious, produce moderate yields and reaction byproducts are frequently difficult to remove. We have developed an improved method for solid-phase coupling of ligands to oligonucleotides via disulfides directly after solid-phase synthesis. A 2'-thiol introduced using a modified nucleotide building block was orthogonally deprotected on the controlled pore glass solid support with N-butylphosphine. Oligolysine peptides and a short monodisperse ethylene glycol chain were successfully coupled to the deprotected thiol. Cleavage from the resin and full removal of oligonucleotide protection groups were achieved using methanolic ammonia. After standard desalting, and without further purification, homogenous conjugates were obtained as demonstrated by HPLC, gel electrophoresis, and mass spectrometry. The attachment of both amphiphilic and cationic ligands proves the versatility of the conjugation procedure. An antisense oligonucleotide conjugate with hexalysine showed pronounced gene silencing in a cell culture tumor model in the absence of a transfection reagent and the corresponding ethylene glycol conjugate resulted in down regulation of the target gene to nearly 50% after naked application. PMID:27236069

  19. Chromosome-Specific Painting in Cucumis Species Using Bulked Oligonucleotides.

    Science.gov (United States)

    Han, Yonghua; Zhang, Tao; Thammapichai, Paradee; Weng, Yiqun; Jiang, Jiming

    2015-07-01

    Chromosome-specific painting is a powerful technique in molecular cytogenetic and genome research. We developed an oligonucleotide (oligo)-based chromosome painting technique in cucumber (Cucumis sativus) that will be applicable in any plant species with a sequenced genome. Oligos specific to a single chromosome of cucumber were identified using a newly developed bioinformatic pipeline and then massively synthesized de novo in parallel. The synthesized oligos were amplified and labeled with biotin or digoxigenin for use in fluorescence in situ hybridization (FISH). We developed three different probes with each containing 23,000-27,000 oligos. These probes spanned 8.3-17 Mb of DNA on targeted cucumber chromosomes and had the densities of 1.5-3.2 oligos per kilobases. These probes produced FISH signals on a single cucumber chromosome and were used to paint homeologous chromosomes in other Cucumis species diverged from cucumber for up to 12 million years. The bulked oligo probes allowed us to track a single chromosome in early stages during meiosis. We were able to precisely map the pairing between cucumber chromosome 7 and chromosome 1 of Cucumis hystrix in a F1 hybrid. These two homeologous chromosomes paired in 71% of prophase I cells but only 25% of metaphase I cells, which may provide an explanation of the higher recombination rates compared to the chiasma frequencies between homeologous chromosomes reported in plant hybrids. PMID:25971668

  20. Respirable antisense oligonucleotides: a new drug class for respiratory disease

    Directory of Open Access Journals (Sweden)

    Tanaka Makoto

    2000-12-01

    Full Text Available Abstract Respirable antisense oligonucleotides (RASONs, which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery.

  1. Characterization of adjacent breast tumors using oligonucleotide microarrays

    International Nuclear Information System (INIS)

    Current methodology often cannot distinguish second primary breast cancers from multifocal disease, a potentially important distinction for clinical management. In the present study we evaluated the use of oligonucleotide-based microarray analysis in determining the clonality of tumors by comparing gene expression profiles. Total RNA was extracted from two tumors with no apparent physical connection that were located in the right breast of an 87-year-old woman diagnosed with invasive ductal carcinoma (IDC). The RNA was hybridized to the Affymetrix Human Genome U95A Gene Chip® (12,500 known human genes) and analyzed using the Gene Chip Analysis Suite® 3.3 (Affymetrix, Inc, Santa Clara, CA, USA) and JMPIN® 3.2.6 (SAS Institute, Inc, Cary, NC, USA). Gene expression profiles of tumors from five additional patients were compared in order to evaluate the heterogeneity in gene expression between tumors with similar clinical characteristics. The adjacent breast tumors had a pairwise correlation coefficient of 0.987, and were essentially indistinguishable by microarray analysis. Analysis of gene expression profiles from different individuals, however, generated a pairwise correlation coefficient of 0.710. Transcriptional profiling may be a useful diagnostic tool for determining tumor clonality and heterogeneity, and may ultimately impact on therapeutic decision making

  2. Advancements of antisense oligonucleotides in treatment of breast cancer

    Institute of Scientific and Technical Information of China (English)

    YANGShuan-Ping; SONGSan-Tai; 等

    2003-01-01

    Breast cancer is one kind of multi-gene related malignancy.Overexpression of some oncogenes such as HER-2(c-erbB-2,Neu),bcl-2/bcl-xL,protein kinase A(PKA),and transferrin receptor gene(TfR gene),etc significantly affect the prognosis of breast cancer.It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer.Antisense interference.one of useful tools for inhibiting the overexpression of specific oncogenes,was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides(ON)could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases;some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts.Furthermore,the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects,which was probably the best utilization of antisense ON in the treatment of breast cancer.

  3. Integrated Microfluidic Isolation of Aptamers Using Electrophoretic Oligonucleotide Manipulation

    Science.gov (United States)

    Kim, Jinho; Olsen, Timothy R.; Zhu, Jing; Hilton, John P.; Yang, Kyung-Ae; Pei, Renjun; Stojanovic, Milan N.; Lin, Qiao

    2016-05-01

    We present a microfluidic approach to integrated isolation of DNA aptamers via systematic evolution of ligands by exponential enrichment (SELEX). The approach employs a microbead-based protocol for the processes of affinity selection and amplification of target-binding oligonucleotides, and an electrophoretic DNA manipulation scheme for the coupling of these processes, which are required to occur in different buffers. This achieves the full microfluidic integration of SELEX, thereby enabling highly efficient isolation of aptamers in drastically reduced times and with minimized consumption of biological material. The approach as such also offers broad target applicability by allowing selection of aptamers with respect to targets that are either surface-immobilized or solution-borne, potentially allowing aptamers to be developed as readily available affinity reagents for a wide range of targets. We demonstrate the utility of this approach on two different procedures, respectively for isolating aptamers against a surface-immobilized protein (immunoglobulin E) and a solution-phase small molecule (bisboronic acid in the presence of glucose). In both cases aptamer candidates were isolated in three rounds of SELEX within a total process time of approximately 10 hours.

  4. Nanoexplosive gene therapy using triplex-forming oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Eun Jung; Min, Hye Jung; Choe, Jae Gol; Park, Gil Hong; Kim, Meyoung Kon [College of Medicine, Korea Univ., Seoul (Korea, Republic of)

    2001-07-01

    Triplex forming oligonucleotides (TFO) labeled with Auger emitter could be ideal vehicles for delivering radiation energy to specific DNA sequences, and followed by double-stranded DNA breaks and subsequent inactivation of targeted genes. We designed TFOs targeting the selected DNA fragments (i.e., estrogen receptors and N-myc promoter) and labeled with {sup 125}I and {sup 111}In. Various Cancer cells, e.g., MCF-7 (breast adenocarcinoma), MCF-10A (immortalized breast cells), Jurkat (T-cell leukemia), ARO (thyroid cancer), SNU-449 (Colon Caner), and HL-60 (polymyelocytic leukemia), were prepared and treated with radiolabeled TFO for 24 h. After the incubation, subcellular fractions (i.e., cell nucleus, cytoplasm and cultured medium) were collected and measured radioactivity by a gamma scintillation counter, respectively. The mean value of % injected dose for each fraction was ranged as follows: nucleus, 4.4-20%; cytoplasm, 8.2-29%; and medium, 64-87%. Therefore, we speculated that TFO labeled with Auger emitter could be a next-generation therapeutic tool in nanoexplosive gene therapy.

  5. Triplex formation on DNA targets: how to choose the oligonucleotide.

    Science.gov (United States)

    Vekhoff, Pierre; Ceccaldi, Alexandre; Polverari, David; Pylouster, Jean; Pisano, Claudio; Arimondo, Paola B

    2008-11-25

    Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA binders. TFOs provide a tool for controlling gene expression or, when attached to an appropriate chemical reagent, for directing DNA damage. Here, we report a set of rules for predicting the best out of five different triple-helical binding motifs (TM, UM, GA, GT, and GU, where M is 5-methyldeoxycytidine and U is deoxyuridine) by taking into consideration the sequence composition of the underlying duplex target. We tested 11 different triplex targets present in genes having an oncogenic role. The rules have predictive power and are very useful in the design of TFOs for antigene applications. Briefly, we retained motifs GU and TM, and when they do form a triplex, TFOs containing G and U are preferred over those containing T and M. In the case of the G-rich TFOs, triplex formation is principally dependent on the percentage of G and the length of the TFO. In the case of the pyrimidine motif, replacement of T with U is destabilizing; triplex formation is dependent on the percentage of T and destabilized by the presence of several contiguous M residues. An equation to choose between a GU and TM motif is given. PMID:18954091

  6. Nanoexplosive gene therapy using triplex-forming oligonucleotides

    International Nuclear Information System (INIS)

    Triplex forming oligonucleotides (TFO) labeled with Auger emitter could be ideal vehicles for delivering radiation energy to specific DNA sequences, and followed by double-stranded DNA breaks and subsequent inactivation of targeted genes. We designed TFOs targeting the selected DNA fragments (i.e., estrogen receptors and N-myc promoter) and labeled with 125I and 111In. Various Cancer cells, e.g., MCF-7 (breast adenocarcinoma), MCF-10A (immortalized breast cells), Jurkat (T-cell leukemia), ARO (thyroid cancer), SNU-449 (Colon Caner), and HL-60 (polymyelocytic leukemia), were prepared and treated with radiolabeled TFO for 24 h. After the incubation, subcellular fractions (i.e., cell nucleus, cytoplasm and cultured medium) were collected and measured radioactivity by a gamma scintillation counter, respectively. The mean value of % injected dose for each fraction was ranged as follows: nucleus, 4.4-20%; cytoplasm, 8.2-29%; and medium, 64-87%. Therefore, we speculated that TFO labeled with Auger emitter could be a next-generation therapeutic tool in nanoexplosive gene therapy

  7. Preparation and detection of nonradioactive nucleic acid and oligonucleotide

    International Nuclear Information System (INIS)

    There is increasing interest worldwide in the development of nucleic acid probes which are detected by nonradioactive means. In the research laboratory, the use of 32P for detection is undoubtedly the method of choice and is likely to remain so for the forseeable future, in spite of the half life of only 14 days for 32P. In the diagnostic laboratory on the other hand, the use of nonradioactive probes has many potential advantages. Perhaps the major one is that nonradioactive probes are stable for at least 6 to 12 months, and probably much longer if properly stored, thus leading to a substantial reduction in cost by obviating the need to prepare them every 2 to 3 weeks. In addition, there is no radiation exposure from routine daily use and there are no storage and disposal problems. Numerous methods are described in this chapter for the preparation by enzymatic and chemical techniques of nonradioactive nucleic acid and oligonucleotide probes. In many cases, the resulting probes have yet to be fully tested under hybridization conditions. In others, initial results look very promising since some nonradioactive probes can provide a sensitivity of detection of target sequences similar to that provided by 32P-labeled probes

  8. Quality assurance of radiolabeled proteins, peptides and antisense oligonucleotides

    International Nuclear Information System (INIS)

    Radiopharmaceuticals (RP) labeled with nonmetallic (I-123, C-11, F-18) and metallic radionuclides (Tc-99m, Ga-67, In-111) are used for diagnosis and therapy; they could be classified as blood flow markers, metabolic substrates, receptor ligands, peptide/proteins and antisense oligonucleotide analogs (I-123, In-111). For safety and efficacy of the test using these tracers, quality assurance (QA) of RP (Chemical, radionuclidic, radiochemical impurities, enantiomers, immunoreactivity, sterility, apyrogenicity, cell-viability) is required. This test is more critical for the RP under clinical investigations. FDA allows a maximum permissible limit of 10% of the injected radionuclide as impurity. Quality assurance of RP is carried out by thin-layer, size-exclusion and high pressure liquid chromatography. For therapeutic RP labeled with I-131 (β,γ), Re-186 (β,γ), Re-188 (β), Y-90 (β), Y-90 (β), At-211(α) and Bi-212 (α), etc., the level of chemical alterations/degradations, directly by energetic particles or indirectly by free-radicals, is higher for the α-,β- than γ-emitting RP and chemical alterations are time-dependent processes. Considering the adverse reactions (marrow-suppression), unnecessary radiation due to unbound tracers and impurities, QA of RP should be performed and impurities eliminated before RP administration

  9. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    Science.gov (United States)

    Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

  10. Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

  11. Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation.

    Science.gov (United States)

    Pietralik, Zuzanna; Skrzypczak, Andrzej; Kozak, Maciej

    2016-08-01

    Gemini surfactants are good candidates to bind, protect, and deliver nucleic acids. Herein, the concept of amino acids (namely glycine) as counter ions of gemini surfactants for gene therapy application was explored. This study was conducted on DNA and RNA oligomers and two quaternary bis-imidazolium salts, having 2,5-dioxahexane and 2,8-dioxanonane spacer groups. The toxicity level of surfactants was assessed by an MTT assay, and their ability to bind nucleic acids was tested through electrophoresis. The nucleic acid conformation was established based on circular dichroism and infrared spectroscopic analyses. The structures of the formed complexes were characterized by small-angle scattering of synchrotron radiation. Both studied surfactants appear to be suitable for gene therapy; however, although they vary by only three methylene groups in the spacer, they differ in binding ability and toxicity. The tested oligonucleotides maintained their native conformations upon surfactant addition and the studied lipoplexes formed a variety of structures. In systems based on a 2,5-dioxahexane spacer, a hexagonal phase was observed for DNA-surfactant complexes and a micellar phase was dominant with RNA. For the surfactant with a 2,8-dioxanonane spacer group, the primitive cubic phase prevailed. PMID:27214208

  12. Overlay improvement by ASML HOWA 5th alignment strategy

    Science.gov (United States)

    Wang, Raf; Chiang, CY; Hsu, Wilson; Yang, Richer; Shih, Todd; Chen, Jackie; Chiu, Jonathan; Lin, Wythe

    2009-12-01

    Overlay control is more challenging when DRAM volume production continues to shrink its critical dimention (CD) to 70nm and beyond. Effected by process, the overlay behavior at wafer edge is quite different from wafer center. The big contribution to worse overlay at wafer edge which causes yield loss is misalignment. The analysis in wafer edge suggests that high order uncorrectable overlay residuals are often observed by certain process impact. Therefore, the basic linear model used for alignment correction is not sufficient and it is necessary to introduce an advanced alignment correction model for wafer edge overlay improvement. In this study, we demonstrated the achievement of moderating the poor overlay at wafer edge area by using a high order wafer alignment strategy. The mechanism is to use non-linear correction methods of high order models ( up to 5th order), with support by the function High Order Wafer Alignment (known as HOWA) in scanner. Instead of linear model for the 6 overlay parameters which come from average result, HOWA alignment strategy can do high order fitting through the wafer to get more accurate overlay parameters which represent the local wafer grid distortion better. As a result, the overlay improvement for wafer edge is achieved. Since alignment is a wafer dependent correction, with HOWA the wafer to wafer overlay variation can be improved dynamically as well. In addition, the effects of different mark quantity and sampling distribution from HOWA are also introduced in this paper. The results of this study indicate that HOWA can reduce uncorrectable overlay residual by 30~40% and improve wafer-to-wafer overlay variation significantly. We conclude that HOWA is a noteworthy strategy for overlay improvement. Moreover, optimized alignment mark numbers and distribution layout are also key factors to make HOWA successful.

  13. Geodetic alignment of laser power installations

    International Nuclear Information System (INIS)

    Main problems occuring in applied geodesy under initial alignment of laser power installation optical channel are considered. Attention is paid to alignment of lens beamguide telescopic pairs and alignment quality control. Methods and means of geodetic measurements under alignment are indicated. Conclusions are made about the degree of working through certain aspects of the problem

  14. Basics of Bayesian Learning - Basically Bayes

    DEFF Research Database (Denmark)

    Larsen, Jan

    Tutorial presented at the IEEE Machine Learning for Signal Processing Workshop 2006, Maynooth, Ireland, September 8, 2006. The tutorial focuses on the basic elements of Bayesian learning and its relation to classical learning paradigms. This includes a critical discussion of the pros and cons. The...

  15. Adaptive Processing for Sequence Alignment

    KAUST Repository

    Zidan, Mohammed Affan

    2012-01-26

    Disclosed are various embodiments for adaptive processing for sequence alignment. In one embodiment, among others, a method includes obtaining a query sequence and a plurality of database sequences. A first portion of the plurality of database sequences is distributed to a central processing unit (CPU) and a second portion of the plurality of database sequences is distributed to a graphical processing unit (GPU) based upon a predetermined splitting ratio associated with the plurality of database sequences, where the database sequences of the first portion are shorter than the database sequences of the second portion. A first alignment score for the query sequence is determined with the CPU based upon the first portion of the plurality of database sequences and a second alignment score for the query sequence is determined with the GPU based upon the second portion of the plurality of database sequences.

  16. Strategic Alignment and New Product Development

    DEFF Research Database (Denmark)

    Acur, Nuran; Kandemir, Destan; Boer, Harry

    2012-01-01

    Strategic alignment is widely accepted as a prerequisite for a firm’s success, but insight into the role of alignment in, and its impact on, the new product evelopment (NPD) process and its performance is less well developed. Most publications on this topic either focus on one form of alignment or...... of NPD performance indicators. Strategic planning and innovativeness appear to affect technological, market, and NPD-marketing alignment positively. Environmental munificence is negatively associated with NPD-marketing alignment, but has no effect on the two other forms of alignment. Technological...... change has a positive effect on technological alignment, a negative effect on NPD-marketing alignment, but no effect on market alignment. These findings suggest that internal capabilities are more likely to be associated with the development of strategic alignment than environmental factors are...

  17. Fr-TM-align: a new protein structural alignment method based on fragment alignments and the TM-score

    Directory of Open Access Journals (Sweden)

    Skolnick Jeffrey

    2008-12-01

    Full Text Available Abstract Background Protein tertiary structure comparisons are employed in various fields of contemporary structural biology. Most structure comparison methods involve generation of an initial seed alignment, which is extended and/or refined to provide the best structural superposition between a pair of protein structures as assessed by a structure comparison metric. One such metric, the TM-score, was recently introduced to provide a combined structure quality measure of the coordinate root mean square deviation between a pair of structures and coverage. Using the TM-score, the TM-align structure alignment algorithm was developed that was often found to have better accuracy and coverage than the most commonly used structural alignment programs; however, there were a number of situations when this was not true. Results To further improve structure alignment quality, the Fr-TM-align algorithm has been developed where aligned fragment pairs are used to generate the initial seed alignments that are then refined using dynamic programming to maximize the TM-score. For the assessment of the structural alignment quality from Fr-TM-align in comparison to other programs such as CE and TM-align, we examined various alignment quality assessment scores such as PSI and TM-score. The assessment showed that the structural alignment quality from Fr-TM-align is better in comparison to both CE and TM-align. On average, the structural alignments generated using Fr-TM-align have a higher TM-score (~9% and coverage (~7% in comparison to those generated by TM-align. Fr-TM-align uses an exhaustive procedure to generate initial seed alignments. Hence, the algorithm is computationally more expensive than TM-align. Conclusion Fr-TM-align, a new algorithm that employs fragment alignment and assembly provides better structural alignments in comparison to TM-align. The source code and executables of Fr-TM-align are freely downloadable at: http://cssb.biology.gatech.edu/skolnick/files/FrTMalign/.

  18. Topology independent protein structural alignment

    Directory of Open Access Journals (Sweden)

    DasGupta Bhaskar

    2007-10-01

    Full Text Available Abstract Background Identifying structurally similar proteins with different chain topologies can aid studies in homology modeling, protein folding, protein design, and protein evolution. These include circular permuted protein structures, and the more general cases of non-cyclic permutations between similar structures, which are related by non-topological rearrangement beyond circular permutation. We present a method based on an approximation algorithm that finds sequence-order independent structural alignments that are close to optimal. We formulate the structural alignment problem as a special case of the maximum-weight independent set problem, and solve this computationally intensive problem approximately by iteratively solving relaxations of a corresponding integer programming problem. The resulting structural alignment is sequence order independent. Our method is also insensitive to insertions, deletions, and gaps. Results Using a novel similarity score and a statistical model for significance p-value, we are able to discover previously unknown circular permuted proteins between nucleoplasmin-core protein and auxin binding protein, between aspartate rasemase and 3-dehydrogenate dehydralase, as well as between migration inhibition factor and arginine repressor which involves an additional strand-swapping. We also report the finding of non-cyclic permuted protein structures existing in nature between AML1/core binding factor and ribofalvin synthase. Our method can be used for large scale alignment of protein structures regardless of the topology. Conclusion The approximation algorithm introduced in this work can find good solutions for the problem of protein structure alignment. Furthermore, this algorithm can detect topological differences between two spatially similar protein structures. The alignment between MIF and the arginine repressor demonstrates our algorithm's ability to detect structural similarities even when spatial

  19. Basic digital signal processing

    CERN Document Server

    Lockhart, Gordon B

    1985-01-01

    Basic Digital Signal Processing describes the principles of digital signal processing and experiments with BASIC programs involving the fast Fourier theorem (FFT). The book reviews the fundamentals of the BASIC program, continuous and discrete time signals including analog signals, Fourier analysis, discrete Fourier transform, signal energy, power. The text also explains digital signal processing involving digital filters, linear time-variant systems, discrete time unit impulse, discrete-time convolution, and the alternative structure for second order infinite impulse response (IIR) sections.

  20. Basic molecular spectroscopy

    CERN Document Server

    Gorry, PA

    1985-01-01

    BASIC Molecular Spectroscopy discusses the utilization of the Beginner's All-purpose Symbolic Instruction Code (BASIC) programming language in molecular spectroscopy. The book is comprised of five chapters that provide an introduction to molecular spectroscopy through programs written in BASIC. The coverage of the text includes rotational spectra, vibrational spectra, and Raman and electronic spectra. The book will be of great use to students who are currently taking a course in molecular spectroscopy.

  1. Aligned Layers of Silver Nano-Fibers

    OpenAIRE

    Golovin, Andrii B.; Liubov Kreminska; Jeremy Stromer

    2012-01-01

    We describe a new dichroic polarizers made by ordering silver nano-fibers to aligned layers. The aligned layers consist of nano-fibers and self-assembled molecular aggregates of lyotropic liquid crystals. Unidirectional alignment of the layers is achieved by means of mechanical shearing. Aligned layers of silver nano-fibers are partially transparent to a linearly polarized electromagnetic radiation. The unidirectional alignment and density of the silver nano-fibers determine degree of polariz...

  2. Hardware Accelerated Sequence Alignment with Traceback

    OpenAIRE

    Scott Lloyd; Snell, Quinn O

    2009-01-01

    Biological sequence alignment is an essential tool used in molecular biology and biomedical applications. The growing volume of genetic data and the complexity of sequence alignment present a challenge in obtaining alignment results in a timely manner. Known methods to accelerate alignment on reconfigurable hardware only address sequence comparison, limit the sequence length, or exhibit memory and I/O bottlenecks. A space-efficient, global sequence alignment algorithm and architecture is pres...

  3. Measurements of magnetic field alignment

    International Nuclear Information System (INIS)

    The procedure for installing Superconducting Super Collider (SSC) dipoles in their respective cryostats involves aligning the average direction of their field with the vertical to an accuracy of 0.5 mrad. The equipment developed for carrying on these measurements is described and the measurements performed on the first few prototypes SSC magnets are presented. The field angle as a function of position in these 16.6 m long magnets is a characteristic of the individual magnet with possible feedback information to its manufacturing procedure. A comparison of this vertical alignment characteristic with a magnetic field intensity (by NMR) characteristic for one of the prototypes is also presented. 5 refs., 7 figs

  4. XUV ionization of aligned molecules

    Energy Technology Data Exchange (ETDEWEB)

    Kelkensberg, F.; Siu, W.; Gademann, G. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Rouzee, A.; Vrakking, M. J. J. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Max-Born-Institut, Max-Born Strasse 2A, D-12489 Berlin (Germany); Johnsson, P. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Department of Physics, Lund University, Post Office Box 118, SE-221 00 Lund (Sweden); Lucchini, M. [Department of Physics, Politecnico di Milano, Istituto di Fotonica e Nanotecnologie CNR-IFN, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Lucchese, R. R. [Department of Chemistry, Texas A and M University, College Station, Texas 77843-3255 (United States)

    2011-11-15

    New extreme-ultraviolet (XUV) light sources such as high-order-harmonic generation (HHG) and free-electron lasers (FELs), combined with laser-induced alignment techniques, enable novel methods for making molecular movies based on measuring molecular frame photoelectron angular distributions. Experiments are presented where CO{sub 2} molecules were impulsively aligned using a near-infrared laser and ionized using femtosecond XUV pulses obtained by HHG. Measured electron angular distributions reveal contributions from four orbitals and the onset of the influence of the molecular structure.

  5. Position list word aligned hybrid

    DEFF Research Database (Denmark)

    Deliege, Francois; Pedersen, Torben Bach

    2010-01-01

    Compressed bitmap indexes are increasingly used for efficiently querying very large and complex databases. The Word Aligned Hybrid (WAH) bitmap compression scheme is commonly recognized as the most efficient compression scheme in terms of CPU efficiency. However, WAH compressed bitmaps use a lot...... of storage space. This paper presents the Position List Word Aligned Hybrid (PLWAH) compression scheme that improves significantly over WAH compression by better utilizing the available bits and new CPU instructions. For typical bit distributions, PLWAH compressed bitmaps are often half the size of WAH...

  6. Polymorphism in Sahiwal breed of zebu cattle revealed using synthetic oligonucleotide markers

    International Nuclear Information System (INIS)

    Full text: Livestock improvement greatly depends on the exploitation of DNA level polymorphisms. Specific sequences of DNA are being used as genetic markers to identify loci responsible for expression of complex traits both in man and animals. Presently several classes of markers are available namely RFLPs, AFLPs, VNTRs, STRs, SNPs etc. DNA Sequences with basic repeat motifs of two to six nucleotides can be synthesized and hybridized to genomic sequences from a variety of species to produce multilocus band patterns. Several such oligonucleotide sequences have been reported to be useful in producing highly polymorphic DNA fingerprints in a variety of species. These markers have short-range uses such as parentage determination, individual identification, detection of twin zygosity, etc., and long-range applications such as gene mapping and marker assisted selection The degree of polymorphism elucidated from a probe or a marker may differ from species to species depending on probe-species combination. It is important to screen DNA markers for their informativeness and polymorphism for various domestic species of animals before considering them for further use. In literature several synthetic probes having the core sequences of (AT) (GT), (GC), (CAC), (GAA), (GGAT), (GACA), (TGG), and (GATA) have been reported for DNA fingerprinting of a variety of species of animals. However, the indigenous Zebu cattle, which constitute major proportion of Indian cattle population has poorly been explored with DNA-based markers. In this study, four different oligonucleotide markers were screened for their usefulness as markers in Zebu cattle. The investigations were carried out on genomic DNA of randomly selected unrelated (15 animals) and from two sire families (11 animals) of Sahiwal breed of Zebu cattle maintained in a herd at National Dairy Research Institute, Karnal. Oligonucleotide probes were custom synthesised and used after radio-isotopic labelling with (γ''3''2P) dATP ''3

  7. Diffusion of Oligonucleotides from within Iron-Crosslinked Polyelectrolyte-Modified Alginate Beads: A Model System for Drug Release

    CERN Document Server

    Privman, Vladimir; Luz, Roberto A S; Guz, Nataliia; Glasser, M Lawrence; Katz, Evgeny

    2016-01-01

    We developed and experimentally verified an analytical model to describe diffusion of oligonucleotides from stable hydrogel beads. The synthesized alginate beads are Fe3+-cross-linked as well as polyelectrolyte-doped for uniformity and stability at physiological pH. Data on diffusion of oligonucleotides from inside the beads provide physical insights into the volume nature of the immobilization of a fraction of oligonucleotides due to polyelectrolyte cross-linking, i.e., the absence of the surface-layer barrier in this case. Furthermore, our results suggest a new simple approach to measuring the diffusion coefficient of the mobile oligonucleotide molecules inside hydrogel. The considered alginate beads provide a model for a well-defined component in drug release systems and for the oligonucleotide-release transduction steps in drug-delivering and biocomputing applications. This is illustrated by destabilizing the beads with citrate that induces full oligonucleotide release with non-diffusional kinetics.

  8. Diffusion of Oligonucleotides from within Iron-Cross-Linked, Polyelectrolyte-Modified Alginate Beads: A Model System for Drug Release.

    Science.gov (United States)

    Privman, Vladimir; Domanskyi, Sergii; Luz, Roberto A S; Guz, Nataliia; Glasser, M Lawrence; Katz, Evgeny

    2016-04-01

    An analytical model to describe diffusion of oligonucleotides from stable hydrogel beads is developed and experimentally verified. The synthesized alginate beads are Fe(3+) -cross-linked and polyelectrolyte-doped for uniformity and stability at physiological pH. Data on diffusion of oligonucleotides from inside the beads provide physical insights into the volume nature of the immobilization of a fraction of oligonucleotides due to polyelectrolyte cross-linking, that is, the absence of a surface-layer barrier in this case. Furthermore, the results suggest a new simple approach to measuring the diffusion coefficient of mobile oligonucleotide molecules inside hydrogels. The considered alginate beads provide a model for a well-defined component in drug-release systems and for the oligonucleotide-release transduction steps in drug-delivering and biocomputing applications. This is illustrated by destabilizing the beads with citrate, which induces full oligonucleotide release with nondiffusional kinetics. PMID:26762598

  9. Antitumor effects of radioiodinated antisense oligonucleotide mediated by VIP receptor

    International Nuclear Information System (INIS)

    Purpose: we had constructed a targeting delivery system based on intestinal peptide (VIP) for antisense oligonucleotide (ASON) transfer into VIP receptor-positive cells in previous study. The aims of present studies are to observe the antitumor effect of VIP-131I-ASON in HT29 human colon adenocarcinoma xenografts. Methods: A 15-met phosphorothioate ASON, which was complementary to the translation start region of the C-myc oncogene mRNA, was labeled with 131I and the labelled compound was linked to the VIP bound covalently 'to a polylysine chain so as to deliver oligonucleotide into tumor cells. Distribution experiments for evaluating the radiolabeled antisense complexe uptake in tumor tissue were performed in BALB/c nude mice bearing with HT29 tumor xenografts. Nude mice beating HT29 tumor xenografts were adminstered VIP-131I-ASON (3.7,7.4 MBq) or 131I-ASON (3.7 MBq), 131I labeled control sense and nosense DNA (3.7 MBq), or saline. Antitumor effects were assessed using endpoints of tumor growth delay. C-myc-encoded protein expression of tumor was measured by immunocytohistochemical staining. Results: Distribution experiment performed with athymic mice bearing human colon tumor xenografts revealed maximal accumulation of conjugated ASON in the tumor tissue 2 h after administration and significantly higher than that in nude mice injected unconjngated ASON [(5.89±1.03)%ID/g and(1.56±0.31)%ID/g, respectively; t=7.7954 P<0.001]. The radioratio of tumor to muscle was peaked 4h after administration. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing their growth rate 7-fold compare with that in saline-treated mice(tumor growth delay, 25.4±0.89 day). The antitumor effects of unconjugated 131I-ASON were much less profound than VIP-131I-ASON (tumor growth delay, 3.2±1.3 and 25.4±0.89 day, respectively; q=51.4126 P<0.01). Sense, nosense control ON with VIP carder caused no therapeutic effect. There was no progressive weight loss or

  10. Modified oligonucleotides for triple helix studies and for the obtention of structures with biomedical and technological interest

    OpenAIRE

    Alvira Torre, Margarita

    2010-01-01

    [eng] Oligonucleotides are short fragments of DNA (10-100nt) which are of great interest because their applications in molecular biology, biomedicine and nanotechnology. As a result of their ability to base pairing, oligonucleotides can be used as primers, hybridization probes in biosensors, agents for controlling gene expression, structural material in nanotechnology or as substrates for a variety of biochemical and biophysical studies. Chemical modification of oligonucleotides as well as co...

  11. Application of heteronuclear couplings to conformational analysis of oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, G. [Univ. of Maryland, College Park, MD (United States); Live, D. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Bax, A. [NIDDK National Institutes of Health, Bethesda, MD (United States)

    1994-12-01

    The value of vicinal coupling constants extracted from NMR spectra in deducing torsion angles for conformational analysis is well recognized. Due to the abundance of protons, their couplings have been mostly widely used. In many instances, couplings between protons and other nuclei may be a valuable complement to proton-proton couplings or, in some instances, may be the only coupling available to characterize the torsion angle about a bond. Recently, heteronuclear couplings have been used to great benefit in studies of isotopically enriched proteins, and this general approach has been extended to peptides at natural abundance. The possibility of using this approach to study oligonucleotides is also attractive but has not as yet been widely exploited. With the development of strategies for labeling such molecules, particularly RNAs, this may become an important component in conformational analysis. For DNA, labeling is less accessible, but sufficient quantities of unlabeled material are readily available for measuring these couplings at natural abundance. We chose several DNA systems to explore the usefulness of heteronuclear couplings in addressing the sugar conformation and the glycosidic torsion angle. Intensities of cross peaks in long-range HMQC experiments can be related to the couplings. Crosspeaks involving H1{prime} and C1{prime} atoms have been emphasized because of the superior shift dispersion at these positions between sugar protons and carbon atoms. Results will be shown for the self-complementary Dickerson duplex dodecamer sequence d(CGCGAATTCGCG) and for d(GGTCGG), which dimerizes to form a G-tetrad structure incorporating both syn and anti base orientations. The couplings provide a clear discrimination between presence of C3{prime}-endo and C2{prime}-endo conformations of the sugars and syn and anti bases arrangements.

  12. Inhibition of transcription by platinated triplex-forming oligonucleotides.

    Science.gov (United States)

    Graham, Mindy K; Miller, Paul S

    2012-12-01

    Platinated triplex-forming oligonucleotides (TFOs) consisting of 2'-methoxythymidine and 2'-methoxy-5-methylcytidine and an N-7 platinated deoxyguanosine ((Pt)G) at the 5'-((Pt)G-TFO), 3'-(TFO-G(Pt)), or 3'- and 5'-((Pt)G-TFO-G(Pt)) ends of the TFO form mono-((Pt)G-TFO and TFO-G(Pt)) and interstrand ((Pt)G-TFO-G(Pt)) cross-links with target DNA as a result of reaction of the (Pt)G with guanines adjacent to the homopurine TFO binding site in the target. The extent of cross-linking is greatest when the (Pt)G is located on the 3' end of the TFO and the target guanine is on the same strand as the TFO binding site. Multiple, contiguous deoxyguanosines in the TFO binding site or a cytosine adjacent to the G(Pt) of the TFO significantly reduce cross-linking. DNA reporter plasmids in which platinated TFOs were cross-linked at a site in the transcribed region between a CMV promoter and a luciferase reporter gene were transfected into Chinese hamster ovary cells, and luciferase expression was compared with that for the corresponding non-cross-linked plasmid. Luciferase expression was inhibited 95 % when TFO-G(Pt) was bound and cross-linked to the transcribed strand, demonstrating that the cross-linked TFO was able to block transcription elongation. Further inhibition (99 %) was observed in nucleotide excision repair (NER) deficient cells, suggesting that NER may repair this lesion. The 3'-G(Pt) group of TFO-G(Pt) protects the TFO from degradation by exonucleases found in mammalian serum. Taken together, these results suggest that platinated TFOs of the type TFO-G(Pt) may find applications as agents for suppressing DNA transcription and consequently inhibiting gene expression in mammalian cells. PMID:22965663

  13. Aligned natural inflation with modulations

    Science.gov (United States)

    Choi, Kiwoon; Kim, Hyungjin

    2016-08-01

    The weak gravity conjecture applied for the aligned natural inflation indicates that generically there can be a modulation of the inflaton potential, with a period determined by sub-Planckian axion scale. We study the oscillations in the primordial power spectrum induced by such modulation, and discuss the resulting observational constraints on the model.

  14. Aligned natural inflation with modulations

    CERN Document Server

    Choi, Kiwoon

    2015-01-01

    The weak gravity conjecture applied for the aligned natural inflation indicates that generically there can be a modulation of the inflaton potential, with a period determined by sub-Planckian axion scale. We study the oscillations in the primordial power spectrum induced by such modulation, and discuss the resulting observational constraints on the model.

  15. Aligned natural inflation with modulations

    Directory of Open Access Journals (Sweden)

    Kiwoon Choi

    2016-08-01

    Full Text Available The weak gravity conjecture applied for the aligned natural inflation indicates that generically there can be a modulation of the inflaton potential, with a period determined by sub-Planckian axion scale. We study the oscillations in the primordial power spectrum induced by such modulation, and discuss the resulting observational constraints on the model.

  16. Aligned natural inflation with modulations

    OpenAIRE

    Kiwoon Choi; Hyungjin Kim

    2016-01-01

    The weak gravity conjecture applied for the aligned natural inflation indicates that generically there can be a modulation of the inflaton potential, with a period determined by sub-Planckian axion scale. We study the oscillations in the primordial power spectrum induced by such modulation, and discuss the resulting observational constraints on the model.

  17. Basic principle of superconductivity

    OpenAIRE

    De Cao, Tian

    2007-01-01

    The basic principle of superconductivity is suggested in this paper. There have been two vital wrong suggestions on the basic principle, one is the relation between superconductivity and the Bose-Einstein condensation (BEC), and another is the relation between superconductivity and pseudogap.

  18. Exponentiation: A New Basic?

    Science.gov (United States)

    Davis, Brent

    2015-01-01

    For centuries, the basic operations of school mathematics have been identified as addition, subtraction, multiplication, and division. Notably, these operations are "basic," not because they are foundational to mathematics knowledge, but because they were vital to a newly industrialized and market-driven economy several hundred years…

  19. Turkey's Basic Education Programme

    OpenAIRE

    A. Remzi Sezgin

    2000-01-01

    In August 1997, the Government of Turkey greatly increased its efforts to implement eight-year obligatory education, through parliamentary approval of Law No. 4306 for Basic Education. The law mobilises significant resources for a major investment in school facilities through earmarked taxes, establishes a timetable for the Basic Education Programme and streamlines procedures to allow for swift action and implementation.

  20. Bracken Basic Concept Scale.

    Science.gov (United States)

    Naglieri, Jack A.; Bardos, Achilles N.

    1990-01-01

    The Bracken Basic Concept Scale, for use with preschool and primary-aged children, determines a child's school readiness and knowledge of English-language verbal concepts. The instrument measures 258 basic concepts in such categories as comparisons, time, quantity, and letter identification. This paper describes test administration, scoring and…

  1. Basic Research Objectives Reaffirmed

    Institute of Scientific and Technical Information of China (English)

    Guo Haiyan; Zhao Baohua

    2002-01-01

    @@ As a national institution for scientific research and a component of the national innovation system, CAS should and must make key contributions to the great national rejuvenation of the country. Keeping this in mind, CAS has developed four developmental targets for its basic research. This was revealed at a CAS conference on basic research held June 11-12 in Beijing.

  2. ABC: software for interactive browsing of genomic multiple sequence alignment data

    Directory of Open Access Journals (Sweden)

    Singaravelu Senthil AG

    2004-12-01

    Full Text Available Abstract Background Alignment and comparison of related genome sequences is a powerful method to identify regions likely to contain functional elements. Such analyses are data intensive, requiring the inclusion of genomic multiple sequence alignments, sequence annotations, and scores describing regional attributes of columns in the alignment. Visualization and browsing of results can be difficult, and there are currently limited software options for performing this task. Results The Application for Browsing Constraints (ABC is interactive Java software for intuitive and efficient exploration of multiple sequence alignments and data typically associated with alignments. It is used to move quickly from a summary view of the entire alignment via arbitrary levels of resolution to individual alignment columns. It allows for the simultaneous display of quantitative data, (e.g., sequence similarity or evolutionary rates and annotation data (e.g. the locations of genes, repeats, and constrained elements. It can be used to facilitate basic comparative sequence tasks, such as export of data in plain-text formats, visualization of phylogenetic trees, and generation of alignment summary graphics. Conclusions The ABC is a lightweight, stand-alone, and flexible graphical user interface for browsing genomic multiple sequence alignments of specific loci, up to hundreds of kilobases or a few megabases in length. It is coded in Java for cross-platform use and the program and source code are freely available under the General Public License. Documentation and a sample data set are also available http://mendel.stanford.edu/sidowlab/downloads.html.

  3. Grain Alignment and CMB Polarization Studies

    CERN Document Server

    Lazarian, A

    2008-01-01

    Polarized microwave emission from dust is an important foreground that may contaminate polarized CMB studies unless carefully accounted for. Modeling of polarization from dust requires a quantitative understanding of grain alignment. I review the current status of grain alignment theory outlining recent advances in quantitative description of the alignment. In particular, I show that the grain-alignment theory is a predictive one, and its results nicely match observations. Those indicate that the most important process of alignment is related to radiative torques acting on irregular grains. The recently developed analytical model of radiative torque alignment has proven to be a very efficient tool for predicting the degree of grain alignment. We expect the alignment theory to further mature before CMBPol flight, which would ensure a better accounting for the dust-related polarization. At the same time, CMBPol should provide the additional testing of grain alignment, clarifying the reliability of polarimetry f...

  4. 2'-O-[2-(guanidinium)ethyl]-modified oligonucleotides: stabilizing effect on duplex and triplex structures

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, T.P.; Puschl, A.; Lesnik, E.; Mohan, V.; Tereshko, V.; Egli, M.; Manoharan, M. (Vanderbilt); (UC)

    2010-03-08

    Oligonucleotides with a novel 2'-O-[2-(guanidinium)ethyl] (2'-O-GE) modification have been synthesized using a novel protecting group strategy for the guanidinium group. This modification enhances the binding affinity of oligonucleotides to RNA as well as duplex DNA ({Delta}T{sub m} 3.2 C per modification). The 2'-O-GE modified oligonucleotides exhibited exceptional resistance to nuclease degradation. The crystal structure of a palindromic duplex formed by a DNA oligonucleotide with a single 2'-O-GE modification was solved at 1.16 {angstrom} resolution.

  5. A weakly-supervised discriminative model for audio-to-score alignment

    OpenAIRE

    Lajugie, Rémi; Bojanowski, Piotr; Cuvillier, Philippe; Arlot, Sylvain; Bach, Francis

    2016-01-01

    In this paper, we consider a new discriminative approach to the problem of audio-to-score alignment. We consider the two distinct informations provided by the music scores: (i) an exact ordered list of musical events and (ii) an approximate prior information about relative duration of events. We extend the basic dynamic time warping algorithm to a convex problem that learns optimal classifiers for all events while jointly aligning files, using this weak supervision only. We show that the rela...

  6. Experimental analysis of oligonucleotide microarray design criteria to detect deletions by comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Moerman Donald G

    2008-10-01

    Full Text Available Abstract Background Microarray comparative genomic hybridization (CGH is currently one of the most powerful techniques to measure DNA copy number in large genomes. In humans, microarray CGH is widely used to assess copy number variants in healthy individuals and copy number aberrations associated with various diseases, syndromes and disease susceptibility. In model organisms such as Caenorhabditis elegans (C. elegans the technique has been applied to detect mutations, primarily deletions, in strains of interest. Although various constraints on oligonucleotide properties have been suggested to minimize non-specific hybridization and improve the data quality, there have been few experimental validations for CGH experiments. For genomic regions where strict design filters would limit the coverage it would also be useful to quantify the expected loss in data quality associated with relaxed design criteria. Results We have quantified the effects of filtering various oligonucleotide properties by measuring the resolving power for detecting deletions in the human and C. elegans genomes using NimbleGen microarrays. Approximately twice as many oligonucleotides are typically required to be affected by a deletion in human DNA samples in order to achieve the same statistical confidence as one would observe for a deletion in C. elegans. Surprisingly, the ability to detect deletions strongly depends on the oligonucleotide 15-mer count, which is defined as the sum of the genomic frequency of all the constituent 15-mers within the oligonucleotide. A similarity level above 80% to non-target sequences over the length of the probe produces significant cross-hybridization. We recommend the use of a fairly large melting temperature window of up to 10°C, the elimination of repeat sequences, the elimination of homopolymers longer than 5 nucleotides, and a threshold of -1 kcal/mol on the oligonucleotide self-folding energy. We observed very little difference in data

  7. Pin-Align: A New Dynamic Programming Approach to Align Protein-Protein Interaction Networks

    OpenAIRE

    Farid Amir-Ghiasvand; Abbas Nowzari-Dalini; Vida Momenzadeh

    2014-01-01

    To date, few tools for aligning protein-protein interaction networks have been suggested. These tools typically find conserved interaction patterns using various local or global alignment algorithms. However, the improvement of the speed, scalability, simplification, and accuracy of network alignment tools is still the target of new researches. In this paper, we introduce Pin-Align, a new tool for local alignment of protein-protein interaction networks. Pin-Align accuracy is tested on protein...

  8. Directed basic research

    International Nuclear Information System (INIS)

    In its execution, and in the requirement of no other deliverables than knowledge generation, directed basic research is no different from conventional (self-directed) basic research. The selected areas are determined in a national perspective. Directed Basic Research may be in an area where the knowledge generation would benefit Indian Society in the long term, or it may be in an area where the results of the research would benefit Indian Industry or our strategic interests in the long term. India can become a global innovation leader provided we have technology foresight to make the right technology choices, provided we introduce coherent synergy (a phrase I coined a few years back in this context) in our science and technology related activities and provided we establish an effective innovation ecosystem. We must also selectively promote some technology areas through directed basic research. Sustainable economic development in the future requires strong and increased funding of basic research. While directed basic research should be encouraged, self-directed basic research should also receive substantially increased support. (author)

  9. Conjugates of Phthalocyanines With Oligonucleotides as Reagents for Sensitized or Catalytic DNA Modification

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Several conjugates of metallophthalocyanines with deoxyribooligonucleotides were synthesized to investigate sequence-specific modification of DNA by them. Oligonucleotide parts of these conjugates were responsible for the recognition of selected complementary sequences on the DNA target. Metallophthalocyanines were able to induce the DNA modification: phthalocyanines of Zn(II and Al(III were active as photosensitizers in the generation of singlet oxygen 1 O 2 , while phthalocyanine of Co(II promoted DNA oxidation by molecular oxygen through the catalysis of formation of reactive oxygen species ( ⋅ O 2 − , O 2 H 2 , OH. Irradiation of the reaction mixture containing either Zn(II- or Al(III-tetracarboxyphthalocyanine conjugates of oligonucleotide pd(TCTTCCCA with light of > 340 nm wavelength (Hg lamp or He/Ne laser resulted in the modification of the 22-nucleotide target d(TGAATGGGAAGAGGGTCAGGTT. A conjugate of Co(II-tetracarboxyphthalocyanine with the oligonucleotide was found to modify the DNA target in the presence of O 2 and 2-mercaptoethanol or in the presence of O 2 H 2 . Under both sensitized and catalyzed conditions, the nucleotides G 13 – G 15 were mainly modified, providing evidence that the reaction proceeded in the double-stranded oligonucleotide. These results suggest the possible use of phthalocyanine-oligonucleotide conjugates as novel artificial regulators of gene expression and therapeutic agents for treatment of cancer.

  10. Liposome-encapsulated polyethylenimine/oligonucleotide polyplexes prepared by reverse-phase evaporation technique.

    Science.gov (United States)

    Ko, Young Tag; Bickel, Ulrich

    2012-06-01

    Liposome-encapsulated polyplex system represents a promising delivery system for oligonucleotide-based therapeutics such as siRNA and asODN. Here, we report a novel method to prepare liposome-encapsulated cationic polymer/oligonucleotide polyplexes based on the reverse-phase evaporation following organic extraction of the polyplexes. The polyplexes of polyethylenimine and oligonucleotide were first formed in aqueous buffer at an N/P ratio of 6. The overall positively charged polyplexes were then mixed with the anionic phospholipids in overall organic media. The overall organic environment and electrostatic interaction between anionic phospholipids and positively charged polyplexes resulted in inverted micelle-like particles with the polyplexes in the core. After phase separation, the hydrophobic particles were recovered in organic phase. Reverse-phase evaporation of the organic solvent in the presence of hydrophilic polymer-grafted lipids resulted in a stable aqueous dispersion of hydrophilic lipid-coated particles with the polyplex in the core. Transmission electron microscopy visualization revealed spherical structures with heavily stained polyplex cores surrounded by lightly stained lipid coats. The lipid-coated polyplex particles showed colloidal stability, complete protection of the loaded oligonucleotide molecules from enzymatic degradation, and high loading efficiency of more than 80%. Thus, this technique represents an alternative method to prepare lipid-coated polyplex particles as a delivery system of oligonucleotide therapeutics. PMID:22328240

  11. Oligonucleotide delivery with cell surface binding and cell penetrating Peptide amphiphile nanospheres.

    Science.gov (United States)

    Mumcuoglu, Didem; Sardan, Melis; Tekinay, Turgay; Guler, Mustafa O; Tekinay, Ayse B

    2015-05-01

    A drug delivery system designed specifically for oligonucleotide therapeutics can ameliorate the problems associated with the in vivo delivery of these molecules. The internalization of free oligonucleotides is challenging, and cytotoxicity is the main obstacle for current transfection vehicles. To develop nontoxic delivery vehicles for efficient transfection of oligonucleotides, we designed a self-assembling peptide amphiphile (PA) nanosphere delivery system decorated with cell penetrating peptides (CPPs) containing multiple arginine residues (R4 and R8), and a cell surface binding peptide (KRSR), and report the efficiency of this system in delivering G-3129, a Bcl-2 antisense oligonucleotide (AON). PA/AON (peptide amphiphile/antisense oligonucleotide) complexes were characterized with regards to their size and secondary structure, and their cellular internalization efficiencies were evaluated. The effect of the number of arginine residues on the cellular internalization was investigated by both flow cytometry and confocal imaging, and the results revealed that uptake efficiency improved as the number of arginines in the sequence increased. The combined effect of cell penetration and surface binding property on the cellular internalization and its uptake mechanism was also evaluated by mixing R8-PA and KRSR-PA. R8 and R8/KRSR decorated PAs were found to drastically increase the internalization of AONs compared to nonbioactive PA control. Overall, the KRSR-decorated self-assembled PA nanospheres were demonstrated to be noncytotoxic delivery vectors with high transfection rates and may serve as a promising delivery system for AONs. PMID:25828697

  12. LNA-modified isothermal oligonucleotide microarray for differentiating bacilli of similar origin

    Indian Academy of Sciences (India)

    Jing Yan; Ying Yuan; Runqing Mu; Hong Shang; Yifu Guan

    2014-12-01

    Oligonucleotide microarray has been one of the most powerful tools in the ‘Post-Genome Era’ for its high sensitivity, high throughput and parallel processing capability. To achieve high detection specificity, we fabricated an isothermal microarray using locked nucleic acid (LNA)-modified oligonucleotide probes, since LNA has demonstrated the advanced ability to enhance the binding affinity toward their complementary nucleotides. After designing the nucleotide sequences of these oligonucleotide probes for gram-positive bacilli of similar origin (Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus megaterium and Bacillus circulans), we unified the melting temperatures of these oligonucleotide probes by modifying some nucleotides using LNA. Furthermore, we optimized the experimental procedures of hydrating microarray slides, blocking side surface as well as labelling the PCR products. Experimental results revealed that KOD Dash DNA polymerase could efficiently incorporate Cy3-dCTP into the PCR products, and the LNA-isothermal oligonucleotide microarray were able to distinguish the bacilli of similar origin with a high degree of accuracy and specificity under the optimized experimental condition.

  13. An Overview of DNA Microarray Grid Alignment and Foreground Separation Approaches

    Science.gov (United States)

    Bajcsy, Peter

    2006-12-01

    This paper overviews DNA microarray grid alignment and foreground separation approaches. Microarray grid alignment and foreground separation are the basic processing steps of DNA microarray images that affect the quality of gene expression information, and hence impact our confidence in any data-derived biological conclusions. Thus, understanding microarray data processing steps becomes critical for performing optimal microarray data analysis. In the past, the grid alignment and foreground separation steps have not been covered extensively in the survey literature. We present several classifications of existing algorithms, and describe the fundamental principles of these algorithms. Challenges related to automation and reliability of processed image data are outlined at the end of this overview paper.

  14. Quantum electronics basic theory

    CERN Document Server

    Fain, V M; Sanders, J H

    1969-01-01

    Quantum Electronics, Volume 1: Basic Theory is a condensed and generalized description of the many research and rapid progress done on the subject. It is translated from the Russian language. The volume describes the basic theory of quantum electronics, and shows how the concepts and equations followed in quantum electronics arise from the basic principles of theoretical physics. The book then briefly discusses the interaction of an electromagnetic field with matter. The text also covers the quantum theory of relaxation process when a quantum system approaches an equilibrium state, and explai

  15. Basic stress analysis

    CERN Document Server

    Iremonger, M J

    2013-01-01

    BASIC Stress Analysis aims to help students to become proficient at BASIC programming by actually using it in an important engineering subject. It also enables the student to use computing as a means of learning stress analysis because writing a program is analogous to teaching-it is necessary to understand the subject matter. The book begins by introducing the BASIC approach and the concept of stress analysis at first- and second-year undergraduate level. Subsequent chapters contain a summary of relevant theory, worked examples containing computer programs, and a set of problems. Topics c

  16. DNA hosted and aligned in aqueous interstitia of a lamellar liquid crystal – a membrane–biomacromolecule interaction model system

    KAUST Repository

    Carlsson, Nils

    2013-01-01

    We report that DNA molecules can be intercalated and macroscopically oriented in the aqueous interstitia of a lyotropic lamellar liquid crystal. Using UV-vis linear dichroism and fluorescence spectroscopy we show that double-stranded oligonucleotides (25 base pairs) in the water-octanoate-decanol system remain base-paired in the B conformation and are confined in two dimensions, with the helix axis preferentially parallel to the lipid bilayer surfaces but free to rotate within this plane. The degree of helix confinement and the corresponding 2-D orientation can be improved by decreasing the thickness of the water interstitia via the fraction of water in the ternary mixture. Not surprisingly, the corresponding single-stranded oligonucleotides are not aligned, with their persistence length being short in comparison to the lamellar interstitium thickness. We propose this as a model system for studying interactions of DNA-ligand complexes near a lipid bilayer membrane which we demonstrate by using dye probes that are either covalently attached to one end of the oligonucleotide or reversibly bound by intercalation between the base pairs. Three cationic dyes, all strongly bound by intercalation to DNA when free in solution, are found to not bind to DNA but to prefer the membrane surface. The covalently attached Cy5 also binds to the bilayer while Cy3 tends to end-stack to the oligonucleotide duplex. The orientation of Cy5 parallel to the membrane indicates that electrostatic surface binding predominates over insertion into the hydrophobic interior of the membrane. Anionic and zwitterionic dyes (FAM and ROX) are found to remain randomly oriented in the water between the lipid bilayer surfaces. © The Royal Society of Chemistry.

  17. A novel multifunctional oligonucleotide microarray for Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Chen Feng

    2010-10-01

    Full Text Available Abstract Background Microarrays are invaluable tools for genome interrogation, SNP detection, and expression analysis, among other applications. Such broad capabilities would be of value to many pathogen research communities, although the development and use of genome-scale microarrays is often a costly undertaking. Therefore, effective methods for reducing unnecessary probes while maintaining or expanding functionality would be relevant to many investigators. Results Taking advantage of available genome sequences and annotation for Toxoplasma gondii (a pathogenic parasite responsible for illness in immunocompromised individuals and Plasmodium falciparum (a related parasite responsible for severe human malaria, we designed a single oligonucleotide microarray capable of supporting a wide range of applications at relatively low cost, including genome-wide expression profiling for Toxoplasma, and single-nucleotide polymorphism (SNP-based genotyping of both T. gondii and P. falciparum. Expression profiling of the three clonotypic lineages dominating T. gondii populations in North America and Europe provides a first comprehensive view of the parasite transcriptome, revealing that ~49% of all annotated genes are expressed in parasite tachyzoites (the acutely lytic stage responsible for pathogenesis and 26% of genes are differentially expressed among strains. A novel design utilizing few probes provided high confidence genotyping, used here to resolve recombination points in the clonal progeny of sexual crosses. Recent sequencing of additional T. gondii isolates identifies >620 K new SNPs, including ~11 K that intersect with expression profiling probes, yielding additional markers for genotyping studies, and further validating the utility of a combined expression profiling/genotyping array design. Additional applications facilitating SNP and transcript discovery, alternative statistical methods for quantifying gene expression, etc. are also pursued at

  18. Comparison of gene coverage of mouse oligonucleotide microarray platforms

    Directory of Open Access Journals (Sweden)

    Medrano Juan F

    2006-03-01

    Full Text Available Abstract Background The increasing use of DNA microarrays for genetical genomics studies generates a need for platforms with complete coverage of the genome. We have compared the effective gene coverage in the mouse genome of different commercial and noncommercial oligonucleotide microarray platforms by performing an in-house gene annotation of probes. We only used information about probes that is available from vendors and followed a process that any researcher may take to find the gene targeted by a given probe. In order to make consistent comparisons between platforms, probes in each microarray were annotated with an Entrez Gene id and the chromosomal position for each gene was obtained from the UCSC Genome Browser Database. Gene coverage was estimated as the percentage of Entrez Genes with a unique position in the UCSC Genome database that is tested by a given microarray platform. Results A MySQL relational database was created to store the mapping information for 25,416 mouse genes and for the probes in five microarray platforms (gene coverage level in parenthesis: Affymetrix430 2.0 (75.6%, ABI Genome Survey (81.24%, Agilent (79.33%, Codelink (78.09%, Sentrix (90.47%; and four array-ready oligosets: Sigma (47.95%, Operon v.3 (69.89%, Operon v.4 (84.03%, and MEEBO (84.03%. The differences in coverage between platforms were highly conserved across chromosomes. Differences in the number of redundant and unspecific probes were also found among arrays. The database can be queried to compare specific genomic regions using a web interface. The software used to create, update and query the database is freely available as a toolbox named ArrayGene. Conclusion The software developed here allows researchers to create updated custom databases by using public or proprietary information on genes for any organisms. ArrayGene allows easy comparisons of gene coverage between microarray platforms for any region of the genome. The comparison presented here

  19. Understanding Infertility - The Basics

    Medline Plus

    Full Text Available ... here . Basic Infertility Evaluation 450 x 274 | Running Time: 3 min 40 sec Dr. Roger Lobo of ... Causes of Female Infertility 450 x 274 | Running Time: 2 min 35 sec Dr. Roger Lobo, of ...

  20. HIV Treatment: The Basics

    Science.gov (United States)

    HIV Treatment HIV Treatment: The Basics (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Antiretroviral therapy (ART) ... reduces the risk of HIV transmission . How do HIV medicines work? HIV attacks and destroys the infection- ...

  1. Basic Information about Mercury

    Science.gov (United States)

    ... Twitter Google+ Pinterest Contact Us Basic Information about Mercury On this page: What is mercury? Emissions of ... Consumer products that traditionally contain mercury What is Mercury? Mercury is a naturally-occurring chemical element found ...

  2. Basic Financial Accounting

    DEFF Research Database (Denmark)

    Wiborg, Karsten

    This textbook on Basic Financial Accounting is targeted students in the economics studies at universities and business colleges having an introductory subject in the external dimension of the company's economic reporting, including bookkeeping, etc. The book includes the following subjects...

  3. Understanding Infertility - The Basics

    Medline Plus

    Full Text Available ... Smoking Cessation Links to Professional Societies and Organizations Home › Understanding Infertility - The Basics A series of patient ... Find a Health Care Provider Back to Top Home | About Us | Reproductive Health Topics | News & Publications | Resources ...

  4. Brain Basics: Preventing Stroke

    Science.gov (United States)

    ... free mailed brochure Cómo Prevenir un Accidente Cerebrovascular Brain Basics: Preventing Stroke Request free mailed brochure Table ... Americans are protecting their most important asset—their brain. Are you? Stroke ranks as the fourth leading ...

  5. Understanding Infertility - The Basics

    Medline Plus

    Full Text Available ... Basic Infertility Evaluation 450 x 274 | Running Time: 3 min 40 sec Dr. Roger Lobo of the ... Coping With Infertility 450 x 274 | Running Time: 3 min 31 sec Dr. Roger Lobo of the ...

  6. Understanding Infertility - The Basics

    Medline Plus

    Full Text Available ... and Smoking Cessation Links to Professional Societies and Organizations Home › Understanding Infertility - The Basics A series of ... Site Terms & Conditions of Use | Web Design and Development by The Berndt Group

  7. Understanding Infertility - The Basics

    Medline Plus

    Full Text Available ... Videos here . Basic Infertility Evaluation 450 x 274 | Running Time: 3 min 40 sec Dr. Roger Lobo ... infertility. Causes of Female Infertility 450 x 274 | Running Time: 2 min 35 sec Dr. Roger Lobo, ...

  8. EHR/PHR Basics

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues EHR EHR/PHR Basics Past Issues / Summer 2009 Table of ... information to it. With an electronic health record (EHR) or electronic medical record (EMR), your doctor (or ...

  9. Video Screen Capture Basics

    Science.gov (United States)

    Dunbar, Laura

    2014-01-01

    This article is an introduction to video screen capture. Basic information of two software programs, QuickTime for Mac and BlueBerry Flashback Express for PC, are also discussed. Practical applications for video screen capture are given.

  10. Prism Window for Optical Alignment

    Science.gov (United States)

    Tang, Hong

    2008-01-01

    A prism window has been devised for use, with an autocollimator, in aligning optical components that are (1) required to be oriented parallel to each other and/or at a specified angle of incidence with respect to a common optical path and (2) mounted at different positions along the common optical path. The prism window can also be used to align a single optical component at a specified angle of incidence. Prism windows could be generally useful for orienting optical components in manufacture of optical instruments. "Prism window" denotes an application-specific unit comprising two beam-splitter windows that are bonded together at an angle chosen to obtain the specified angle of incidence.

  11. Aligning seminars with Bologna requirements

    DEFF Research Database (Denmark)

    Lueg, Klarissa; Lueg, Rainer; Lauridsen, Ole

    2015-01-01

    Changes in public policy, such as the Bologna Process, require students to be equipped with multifunctional competencies to master relevant tasks in unfamiliar situations. Achieving this goal might imply a change in many curricula toward deeper learning. As a didactical means to achieve deep...... learning results, the authors suggest reciprocal peer tutoring (RPT); as a conceptual framework the authors suggest the SOLO (Structure of Observed Learning Outcomes) taxonomy and constructive alignment as suggested by Biggs and Tang. Our study presents results from the introduction of RPT in a large...... course. The authors find that RPT produces satisfying learning outcomes, active students, and ideal constructive alignments of the seminar content with the exam, the intended learning outcomes, and the requirements of the Bologna Process. Our data, which comprise surveys and evaluations from both faculty...

  12. Aligned mesoporous architectures and devices.

    Energy Technology Data Exchange (ETDEWEB)

    Brinker, C. Jeffrey; Lu, Yunfeng (University of California Los Angeles, Los Angeles, CA)

    2011-03-01

    This is the final report for the Presidential Early Career Award for Science and Engineering - PECASE (LDRD projects 93369 and 118841) awarded to Professor Yunfeng Lu (Tulane University and University of California-Los Angeles). During the last decade, mesoporous materials with tunable periodic pores have been synthesized using surfactant liquid crystalline as templates, opening a new avenue for a wide spectrum of applications. However, the applications are somewhat limited by the unfavorabe pore orientation of these materials. Although substantial effort has been devoted to align the pore channels, fabrication of mesoporous materials with perpendicular pore channels remains challenging. This project focused on fabrication of mesoporous materials with perpendicularly aligned pore channels. We demonstrated structures for use in water purification, separation, sensors, templated synthesis, microelectronics, optics, controlled release, and highly selective catalysts.

  13. From Word Alignment to Word Senses, via Multilingual Wordnets

    Directory of Open Access Journals (Sweden)

    Dan Tufis

    2006-05-01

    Full Text Available Most of the successful commercial applications in language processing (text and/or speech dispense with any explicit concern on semantics, with the usual motivations stemming from the computational high costs required for dealing with semantics, in case of large volumes of data. With recent advances in corpus linguistics and statistical-based methods in NLP, revealing useful semantic features of linguistic data is becoming cheaper and cheaper and the accuracy of this process is steadily improving. Lately, there seems to be a growing acceptance of the idea that multilingual lexical ontologisms might be the key towards aligning different views on the semantic atomic units to be used in characterizing the general meaning of various and multilingual documents. Depending on the granularity at which semantic distinctions are necessary, the accuracy of the basic semantic processing (such as word sense disambiguation can be very high with relatively low complexity computing. The paper substantiates this statement by presenting a statistical/based system for word alignment and word sense disambiguation in parallel corpora. We describe a word alignment platform which ensures text pre-processing (tokenization, POS-tagging, lemmatization, chunking, sentence and word alignment as required by an accurate word sense disambiguation.

  14. High-harmonic generation in aligned water molecules

    Science.gov (United States)

    Wang, Song; Devin, Julien; Hoffmann, Matthias; Cryan, James; Kaldun, Andreas; Bucksbaum, Philip

    2016-05-01

    In recent years, the use of high harmonic generation (HHG) in aligned molecular vapors has become a powerful tool to study ultrafast dynamics of electronic and nuclear wave packets. In our new experimental setup, we are able to orient H2 O and D2 O molecules using a single cycle terahertz (THz) pulse. Aligning water is especially interesting as the highest occupied molecular orbital (HOMO) of water contains a node in the xz plane of the molecular frame, allowing us to perform HHG from second highest occupied molecular orbital (HOMO-1) only, by setting the polarization of the fundamental laser along the z-axis of the aligned water molecules. We are particularly interested in the HOMO-1 state, as there is fast motion of the H-O-H angle leading to sub-wavelength dynamics. On this poster we present our all-optical alignment setup where HHG and single-cycle THz generation take place in high-vacuum, where measurements with arbitrary polarization angles between the two are possible. In addition, we discuss the effects of the molecular orientation on HHG, including symmetry breaking that could produce even harmonics and isotope effects between H2 O and D2 O due to different vibrational energies. This work was supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division.

  15. Basics of Quantum Computation

    OpenAIRE

    Vedral, Vlatko; Martin B. Plenio

    1998-01-01

    Quantum computers require quantum logic, something fundamentally different to classical Boolean logic. This difference leads to a greater efficiency of quantum computation over its classical counter-part. In this review we explain the basic principles of quantum computation, including the construction of basic gates, and networks. We illustrate the power of quantum algorithms using the simple problem of Deutsch, and explain, again in very simple terms, the well known algorithm of Shor for fac...

  16. Basic Concurrency Theory

    DEFF Research Database (Denmark)

    Løvengreen, Hans Henrik

    2002-01-01

    In this set of notes, we present some of the basic theory underlying the discipline of programming with concurrent processes/threads. The notes are intended to supplement a standard textbook on concurrent programming.......In this set of notes, we present some of the basic theory underlying the discipline of programming with concurrent processes/threads. The notes are intended to supplement a standard textbook on concurrent programming....

  17. RDF Graph Alignment with Bisimulation

    OpenAIRE

    Buneman, Peter; Staworko, Sławek

    2016-01-01

    We investigate the problem of aligning two RDF databases, an essential problem in understanding the evolution of ontologies. Our approaches address three fundamental challenges: 1) the use of "blank" (null) names, 2) ontology changes in which different names are used to identify the same entity, and 3) small changes in the data values as well as small changes in the graph structure of the RDF database. We propose approaches inspired by the classical notion of graph bisimulation and extend the...

  18. Interest alignment and competitive advantage

    OpenAIRE

    Gottschalg, Oliver; Zollo, Mauricio

    2006-01-01

    This paper articulates a theory of the conditions under which the alignment between individual and collective interests generates sustainable competitive advantage. The theory is based on the influence of tacitness, context-specificity and casual ambiguity in the determinants of different types of motivation (extrinsic, normative intrinsic and hedonic intrinsic), under varying conditions of environmental dynamism. The analysis indicates the need to consider mitivational processes as a complem...

  19. SIM Lite: ground alignment of the instrument

    Science.gov (United States)

    Dekens, Frank G.; Goullioud, Renaud; Nicaise, Fabien; Kuan, Gary; Morales, Mauricio

    2010-07-01

    We present the start of the ground alignment plan for the SIM Lite Instrument. We outline the integration and alignment of the individual benches on which all the optics are mounted, and then the alignment of the benches to form the Science and Guide interferometers. The Instrument has a guide interferometer with only a 40 arc-seconds field of regard, and 200 arc-seconds of alignment adjustability. This requires each sides of the interferometer to be aligned to a fraction of that, while at the same time be orthogonal to the baseline defined by the External Metrology Truss. The baselines of the Science and Guide interferometers must also be aligned to be parallel. The start of these alignment plans is captured in a SysML Instrument System model, in the form of activity diagrams. These activity diagrams are then related to the hardware design and requirements. We finish with future plans for the alignment and integration activities and requirements.

  20. Intrinsic Galaxy Alignments and Weak Gravitational Lensing

    CERN Document Server

    Heavens, A F

    2001-01-01

    Gravitational lensing causes background galaxy images to become aligned, and the statistical characteristics of the image alignments can then be used to constrain the power spectrum of mass fluctuations. Analyses of gravitational lensing assume that intrinsic galaxy alignments are negligible, but if this assumption does not hold, then the interpretation of image alignments will be in error. As gravitational lensing experiments become more ambitious and seek very low-level alignments arising from lensing by large-scale structure, it becomes more important to estimate the level of intrinsic alignment in the galaxy population. In this article, I review the cluster of independent theoretical studies of this issue, as well as the current observational status. Theoretically, the calculation of intrinsic alignments is by no means straightforward, but some consensus has emerged from the existing works, despite each making very different assumptions. This consensus is that a) intrinsic alignments are a small but non-n...

  1. Polymorphism identification and quantitative detection of genomic DNA by invasive cleavage of oligonucleotide probes

    Energy Technology Data Exchange (ETDEWEB)

    Lyamichev, V.; Mast, A.L.; Hall, J.G. [Third Wave Technologies, Madison, WI (United States)] [and others

    1999-03-01

    Flap endonucleases (FENs) isolated from archaea are shown to recognize and cleave a structure formed when two overlapping oligonucleotides hybridize to a target DNA strand. The downstream oligonucleotide probe is cleaved, and the precise site of cleavage is dependent on the amount of overlap with the upstream oligonucleotide. The authors have demonstrated that use of thermostable archaeal FENs allows the reaction to be performed at temperatures that promote probe turnover without the need for temperature cycling. The resulting amplification of the cleavage signal enables the detection of specific DNA targets at sub-attomole levels within complex mixtures. Moreover, the authors provide evidence that this cleavage is sufficiently specific to enable discrimination of single-base differences and can differentiate homozygotes from heterozygotes in single-copy genes in genomic DNA.

  2. Study of the simultaneous preparation of oligopeptides and oligonucleotides under prebiotic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Caroon, J.M.

    1975-08-01

    The effect of imidazole in promoting the formation of biopolymers under chemical evolutionary conditions was investigated. At the onset of this work, it was known that short-chain oligonucleotides formed in aqueous solutions of ATP, imidazole, and MgCl/sub 2/; in addition, short peptides had been shown to form in aqueous solutions of aminoacylimidazolides and MgCl/sub 2/. The products formed in an aqueous solution of ATP, imidazole, alanine, and MgCl/sub 2/ was investigated and it was found that, under plausible prebiotic conditions, the formation of representatives of both peptides and oligonucleotides could be demonstrated. Furthermore, it was shown that the simultaneous formation of peptides increased the formation of oligonucleotides. A preliminary study was made on the possibility of inducing asymmetry in the clay catalyzed polymerization of peptides, but the results were discouraging. (auth)

  3. Study of HIV-2 primer-template initiation complex using antisense oligonucleotides

    DEFF Research Database (Denmark)

    Boulmé, F; Freund, F; Gryaznov, S;

    2000-01-01

    HIV-2 reverse transcription is initiated by the retroviral DNA polymerase (reverse transcriptase) from a cellular tRNALys3 partially annealed to the primer binding site in the 5'-region of viral RNA. The HIV-2 genome has two A-rich regions upstream of the primer binding site. In contrast to HIV-1...... approach, first validated in our in vitro HIV-1 reverse transcription system. Annealing of the antisense oligonucleotides to the pre-primer binding site (the upstream region contiguous to the HIV-2 primer binding site) was determined in the presence of native tRNALys3 or synthetic primers. Using natural...... and chemically modified antisense oligonucleotides we found that interactions between the anticodon of tRNALys3 and an A-rich loop of viral RNA led to an important destabilization of the pre-primer binding site; this region became accessible to anti-pre-primer binding site oligonucleotides in a...

  4. Hydrolysis of microporous polyamide-6 membranes as substrate for in situ synthesis of oligonucleotides

    Science.gov (United States)

    Tang, Jianxin; He, Nongyue; Nie, Libo; Xiao, Pengfeng; Chen, Hong

    2004-02-01

    This article provides a novel method of preparing substrate for in situ synthesis of oligonucleotide by hydrolyzing microporous polyamide-6 membranes in a 0.01 mol/l/NaOH/(H 2O-CH 3OH) mixture medium with refluxing about 36 h. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) demonstrated the emergence of amines (NH 2) on the surface. Optimum hydrolyzing conditions were determined through the ultra-violet (UV) spectra. A pH value of 12 and a hydrolysis time of 36 h are the preferred conditions for the modification. The treated membrane can be applied to in situ synthesis of oligonucleotide and, for example, the oligonucleotide probes of 5 '-AAC CAC CAA ACA CAC-3 ' were successfully synthesized on the hydrolyzed membrane. The single step coupling efficiency determined by ultraviolet (UV) spectra is above 98%.

  5. Potent triple helix stabilization by 5',3'-modified triplex-forming oligonucleotides.

    Science.gov (United States)

    Ben Gaied, Nouha; Zhao, Zhengyun; Gerrard, Simon R; Fox, Keith R; Brown, Tom

    2009-07-20

    Anthraquinone and pyrene analogues attached to the 3' and/or 5' termini of triplex-forming oligonucleotides (TFOs) by various linkers increased the stability of parallel triple helices. The modifications are simple to synthesize and can be introduced during standard solid-phase oligonucleotide synthesis. Potent triplex stability was achieved by using doubly modified TFOs, which in the most favourable cases gave an increase in melting temperature of 30 degrees C over the unmodified counterparts and maintained their selectivity for the correct target duplex. Such TFOs can produce triplexes with melting temperatures of 40 degrees C at pH 7 even though they do not contain any triplex-stabilizing base analogues. These studies have implications for the design of triplex-forming oligonucleotides for use in biology and nanotechnology. PMID:19554592

  6. Smart polymeric micelles as nanocarriers for oligonucleotides and siRNA delivery.

    Science.gov (United States)

    Kataoka, Kazunori; Itaka, Keiji; Nishiyama, Nobuhiro; Yamasaki, Yuichi; Oishi, Motoi; Nagasaki, Yukio

    2005-01-01

    The development of in vivo delivery systems for oligonucleotides and siRNA is strongly desired to achieve their clinical applications. Recently, polyplex micelles, which are formed through an electrostatic interaction between nucleic acid compounds (DNA and RNA) and poly(ethylene glycol) (PEG)-polycation block copolymers, have received much attention due to their nanometric-scaled size and excellent biocompatibility. Here, three types of newly engineered block copolymers were developed to construct polyplex micelles useful for oligonucleotides and siRNA delivery: (1) PEG-polycation diblock copolymers possessing diamine side-chain with distinctive pKa for siRNA encapsulation into polyplex micelles with high endosomal escaping ability, (2) Lactosylated PEG-(oligonucleotide or siRNA) conjugate through acid-labile beta-thiopropionate linkage to construct pH-sensitive PIC micelles, and (3) PEG-poly(methacrylic acid) block copolymer for the construction of organic/inorganic hybrid nanoparticles encapsulating siRNA. PMID:17150611

  7. Hydration-dependent dynamics of human telomeric oligonucleotides in the picosecond timescale: A neutron scattering study

    International Nuclear Information System (INIS)

    The dynamics of the human oligonucleotide AG3(T2AG3)3 has been investigated by incoherent neutron scattering in the sub-nanosecond timescale. A hydration-dependent dynamical activation of thermal fluctuations in weakly hydrated samples was found, similar to that of protein powders. The amplitudes of such thermal fluctuations were evaluated in two different exchanged wave-vector ranges, so as to single out the different contributions from intra- and inter-nucleotide dynamics. The activation energy was calculated from the temperature-dependent characteristic times of the corresponding dynamical processes. The trends of both amplitudes and activation energies support a picture where oligonucleotides possess a larger conformational flexibility than long DNA sequences. This additional flexibility, which likely results from a significant relative chain-end contribution to the average chain dynamics, could be related to the strong structural polymorphism of the investigated oligonucleotides

  8. Repair of Thalassemic Human β -globin mRNA in Mammalian Cells by Antisense Oligonucleotides

    Science.gov (United States)

    Sierakowska, Halina; Sambade, Maria J.; Agrawal, Sudhir; Kole, Ryszard

    1996-11-01

    In one form of β -thalassemia, a genetic blood disorder, a mutation in intron 2 of the β -globin gene (IVS2-654) causes aberrant splicing of β -globin pre-mRNA and, consequently, β -globin deficiency. Treatment of mammalian cells stably expressing the IVS2-654 human β -globin gene with antisense oligonucleotides targeted at the aberrant splice sites restored correct splicing in a dose-dependent fashion, generating correct human β -globin mRNA and polypeptide. Both products persisted for up to 72 hr posttreatment. The oligonucleotides modified splicing by a true antisense mechanism without overt unspecific effects on cell growth and splicing of other pre-mRNAs. This novel approach in which antisense oligonucleotides are used to restore rather than to down-regulate the activity of the target gene is applicable to other splicing mutants and is of potential clinical interest.

  9. Hydration-dependent dynamics of human telomeric oligonucleotides in the picosecond timescale: A neutron scattering study

    Energy Technology Data Exchange (ETDEWEB)

    Sebastiani, F.; Comez, L.; Sacchetti, F. [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); CNR, Istituto Officina dei Materiali, Unità di Perugia, c/o Dipartimento di Fisica e Geologia, Università di Perugia, 06123 Perugia (Italy); Longo, M. [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); Elettra—Sincrotrone Trieste, 34149 Basovizza, Trieste (Italy); Orecchini, A.; Petrillo, C.; Paciaroni, A., E-mail: alessandro.paciaroni@fisica.unipg.it [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); De Francesco, A. [CNR-IOM OGG c/o Institut Laue-Langevin, 71 Avenue des Martyrs, CS20156, 38042 Grenoble Cedex 9 (France); Muthmann, M. [Jülich Centre for Neutron Science, Forschungszentrum Jülich GmbH, Outstation at Heinz Maier-Leibnitz Zentrum, Lichtenbergstrasse 1, 85747 Garching (Germany); Teixeira, S. C. M. [EPSAM, Keele University, Staffordshire ST5 5BG (United Kingdom); Institut Laue–Langevin, 71 Avenue des Martyrs, CS20156, 38042 Grenoble Cedex 9 (France)

    2015-07-07

    The dynamics of the human oligonucleotide AG{sub 3}(T{sub 2}AG{sub 3}){sub 3} has been investigated by incoherent neutron scattering in the sub-nanosecond timescale. A hydration-dependent dynamical activation of thermal fluctuations in weakly hydrated samples was found, similar to that of protein powders. The amplitudes of such thermal fluctuations were evaluated in two different exchanged wave-vector ranges, so as to single out the different contributions from intra- and inter-nucleotide dynamics. The activation energy was calculated from the temperature-dependent characteristic times of the corresponding dynamical processes. The trends of both amplitudes and activation energies support a picture where oligonucleotides possess a larger conformational flexibility than long DNA sequences. This additional flexibility, which likely results from a significant relative chain-end contribution to the average chain dynamics, could be related to the strong structural polymorphism of the investigated oligonucleotides.

  10. Ultramild protein-mediated click chemistry creates efficient oligonucleotide probes for targeting and detecting nucleic acids

    DEFF Research Database (Denmark)

    Nåbo, Lina J.; Madsen, Charlotte Stahl; Jensen, Knud Jørgen;

    2015-01-01

    Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid...... targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides. This was performed under ultramild...... conditions with fluorophore, peptide, and carbohydrate azide derivatives. In thermal denaturation studies, the modified probes showed specific binding to complementary DNA and RNA targets. Finally, we demonstrated the pH sensitivity of the new rhodamine-based fluorescent probes in vitro and rationalize our...

  11. Structural analysis of aligned RNAs.

    Science.gov (United States)

    Voss, Björn

    2006-01-01

    The knowledge about classes of non-coding RNAs (ncRNAs) is growing very fast and it is mainly the structure which is the common characteristic property shared by members of the same class. For correct characterization of such classes it is therefore of great importance to analyse the structural features in great detail. In this manuscript I present RNAlishapes which combines various secondary structure analysis methods, such as suboptimal folding and shape abstraction, with a comparative approach known as RNA alignment folding. RNAlishapes makes use of an extended thermodynamic model and covariance scoring, which allows to reward covariation of paired bases. Applying the algorithm to a set of bacterial trp-operon leaders using shape abstraction it was able to identify the two alternating conformations of this attenuator. Besides providing in-depth analysis methods for aligned RNAs, the tool also shows a fairly well prediction accuracy. Therefore, RNAlishapes provides the community with a powerful tool for structural analysis of classes of RNAs and is also a reasonable method for consensus structure prediction based on sequence alignments. RNAlishapes is available for online use and download at http://rna.cyanolab.de. PMID:17020924

  12. Suspended photonic waveguide arrays for submicrometer alignment

    OpenAIRE

    Peters, T. J.; Tichem, M.; Staufer, U.

    2014-01-01

    This paper presents a new alignment concept for the alignment of multichannel photonic intergrated circuits (PICs) using flexible photonic waveguides on one of the PICs that are positionable by integrated micro electro mechanical system (MEMS) actuators. The concept aims for high precision and high degree of assembly process automation. The proposed concept includes pre-alignment of both PICs on a common substrate followed by fine-alignment using the on-chip flexible waveguides and MEMS funct...

  13. Trust and Transparency from an Alignment Perspective

    OpenAIRE

    Gryning, Morten

    2015-01-01

    The academic literature suggests that firms cannot stay competitive if their business and IT departments are not aligned. Several theories have provided insights into how to achieve alignment, yet most IT and business departments still struggle to fulfill each other’s expectations, with dissatisfaction and low trust as a result. Some scholars argue that alignment is about finding the right mechanical configuration for a given organization. Others argue that alignment theory should...

  14. Inferring comprehensible business/ICT alignment rules.

    OpenAIRE

    Cumps, Bjorn; Martens, David; De Backer, Manu; Haesen, Raf; Viaene, Stijn; Dedene, Guido; Baesens, Bart; Snoeck, Monique

    2009-01-01

    We inferred business rules for business/ICT alignment by applying a novel rule induction algorithm on a data set containing rich alignment information polled from 641 organisations in 7 European countries. The alignment rule set was created using AntMiner+, a rule induction technique with a reputation of inducing accurate, comprehensible, and intuitive predictive models from data. Our data set consisted of 18 alignment practices distilled from an analysis of relevant publications and validate...

  15. Bolaamphiphile-based nanocomplex delivery of phosphorothioate gapmer antisense oligonucleotides as a treatment for Clostridium difficile

    Science.gov (United States)

    Hegarty, John P; Krzeminski, Jacek; Sharma, Arun K; Guzman-Villanueva, Diana; Weissig, Volkmar; Stewart, David B

    2016-01-01

    Despite being a conceptually appealing alternative to conventional antibiotics, a major challenge toward the successful implementation of antisense treatments for bacterial infections is the development of efficient oligonucleotide delivery systems. Cationic vesicles (bolasomes) composed of dequalinium chloride (“DQAsomes”) have been used to deliver plasmid DNA across the cardiolipin-rich inner membrane of mitochondria. As cardiolipin is also a component of many bacterial membranes, we investigated the application of cationic bolasomes to bacteria as an oligonucleotide delivery system. Antisense sequences designed in silico to target the expression of essential genes of the bacterial pathogen, Clostridium difficile, were synthesized as 2′-O-methyl phosphorothioate gapmer antisense oligonucleotides (ASO). These antisense gapmers were quantitatively assessed for their ability to block mRNA translation using luciferase reporter and C. difficile protein expression plasmid constructs in a coupled transcription–translation system. Cationic bolaamphiphile compounds (dequalinium derivatives) of varying alkyl chain length were synthesized and bolasomes were prepared via probe sonication of an aqueous suspension. Bolasomes were characterized by particle size distribution, zeta potential, and binding capacities for anionic oligonucleotide. Bolasomes and antisense gapmers were combined to form antisense nanocomplexes. Anaerobic C. difficile log phase cultures were treated with serial doses of gapmer nanocomplexes or equivalent amounts of empty bolasomes for 24 hours. Antisense gapmers for four gene targets achieved nanomolar minimum inhibitory concentrations for C. difficile, with the lowest values observed for oligonucleotides targeting polymerase genes rpoB and dnaE. No inhibition of bacterial growth was observed from treatments at matched dosages of scrambled gapmer nanocomplexes or plain, oligonucleotide-free bolasomes compared to untreated control cultures. We

  16. Beam alignment system for laser welding system

    International Nuclear Information System (INIS)

    The patent describes a beam alignment system for laser welding work pieces, such as fuel rod grids for nuclear fuel assemblies. The apparatus for performing various laser-machining comprises a beam alignment system including alignment target means, as well as means for emitting, directing and focusing the laser beam. (U.K.)

  17. Physician-Hospital Alignment in Orthopedic Surgery.

    Science.gov (United States)

    Bushnell, Brandon D

    2015-09-01

    The concept of "alignment" between physicians and hospitals is a popular buzzword in the age of health care reform. Despite their often tumultuous histories, physicians and hospitals find themselves under increasing pressures to work together toward common goals. However, effective alignment is more than just simple cooperation between parties. The process of achieving alignment does not have simple, universal steps. Alignment will differ based on individual situational factors and the type of specialty involved. Ultimately, however, there are principles that underlie the concept of alignment and should be a part of any physician-hospital alignment efforts. In orthopedic surgery, alignment involves the clinical, administrative, financial, and even personal aspects of a surgeon's practice. It must be based on the principles of financial interest, clinical authority, administrative participation, transparency, focus on the patient, and mutual necessity. Alignment can take on various forms as well, with popular models consisting of shared governance and comanagement, gainsharing, bundled payments, accountable care organizations, and other methods. As regulatory and financial pressures continue to motivate physicians and hospitals to develop alignment relationships, new and innovative methods of alignment will also appear. Existing models will mature and evolve, with individual variability based on local factors. However, certain trends seem to be appearing as time progresses and alignment relationships deepen, including regional and national collaboration, population management, and changes in the legal system. This article explores the history, principles, and specific methods of physician-hospital alignment and its critical importance for the future of health care delivery. PMID:26375539

  18. Vertically aligned nanostructure scanning probe microscope tips

    Science.gov (United States)

    Guillorn, Michael A.; Ilic, Bojan; Melechko, Anatoli V.; Merkulov, Vladimir I.; Lowndes, Douglas H.; Simpson, Michael L.

    2006-12-19

    Methods and apparatus are described for cantilever structures that include a vertically aligned nanostructure, especially vertically aligned carbon nanofiber scanning probe microscope tips. An apparatus includes a cantilever structure including a substrate including a cantilever body, that optionally includes a doped layer, and a vertically aligned nanostructure coupled to the cantilever body.

  19. Ultrafast electron diffraction from aligned molecules

    Energy Technology Data Exchange (ETDEWEB)

    Centurion, Martin [Univ. of Nebraska, Lincoln, NE (United States)

    2015-08-17

    The aim of this project was to record time-resolved electron diffraction patterns of aligned molecules and to reconstruct the 3D molecular structure. The molecules are aligned non-adiabatically using a femtosecond laser pulse. A femtosecond electron pulse then records a diffraction pattern while the molecules are aligned. The diffraction patterns are then be processed to obtain the molecular structure.

  20. Silica nanoparticles surface-modified with thiacalixarenes selectively adsorb oligonucleotides and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Yuskova, Elena A. [Kazan (Volga Region) Federal University, Department of Chemistry, A. M. Butlerov Chemical Institute (Russian Federation); Ignacio-de Leon, Patricia Anne A.; Khabibullin, Amir [University of Utah, Department of Chemistry (United States); Stoikov, Ivan I., E-mail: ivan.stoikov@mail.ru [Kazan (Volga Region) Federal University, Department of Chemistry, A. M. Butlerov Chemical Institute (Russian Federation); Zharov, Ilya, E-mail: i.zharov@utah.edu [University of Utah, Department of Chemistry (United States)

    2013-10-15

    We prepared silica nanospheres 360 nm in diameter surface-modified with p-tert-butylthiacalix[4]arenes containing amine, carboxyl, and guanidinium groups. We found that these silica nanoparticles selectively adsorb model oligonucleotides and proteins. The particles modified with the macrocycle containing guanidinium fragments selectively adsorbed long-chain oligonucleotides and those modified with the macrocycle containing amine groups adsorbed BSA and hemoglobin with pH-dependent selectivity. We compared this behavior with that of silica nanoparticles carrying amine and carboxyl groups, and concluded that both electrostatic interactions and specific binding are responsible for the observed selectivity.

  1. Effects of HSP70 Antisense Oligonucleotide on the Proliferation and Apoptosis of Human Hepatocellular Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    杨雪; 贺海斌; 杨威; 宋涛; 郭成; 郑鑫; 刘青光

    2010-01-01

    The study investigated the effects of heat shock protein 70(HSP70) antisense oligonucleotide(ASODN) on the proliferation and apoptosis of a human hepatocellular carcinoma cell line(SMMC-7721 cells) in vitro.HSP70 oligonucleotide was transfected into SMMC-7721 cells by the mediation of SofastTM transfection reagent.Inhibition rate of SMMC-7721 cells was determined by using MTT method.Apoptosis rate and cell cycle distribution were measured by flow cytometry.Immunocytochemistry staining was used to observe th...

  2. Oligonucleotide Fingerprinting of rRNA Genes for Analysis of Fungal Community Composition

    OpenAIRE

    Valinsky, Lea; Della Vedova, Gianluca; Jiang, Tao; Borneman, James

    2002-01-01

    Thorough assessments of fungal diversity are currently hindered by technological limitations. Here we describe a new method for identifying fungi, oligonucleotide fingerprinting of rRNA genes (OFRG). ORFG sorts arrayed rRNA gene (ribosomal DNA [rDNA]) clones into taxonomic clusters through a series of hybridization experiments, each using a single oligonucleotide probe. A simulated annealing algorithm was used to design an OFRG probe set for fungal rDNA. Analysis of 1,536 fungal rDNA clones d...

  3. An Oligonucleotide Microarray for High-Throughput Sequencing of the Mitochondrial Genome

    OpenAIRE

    Zhou, Shaoyu; Kassauei, Keyaunoosh; Cutler, David J.; Kennedy, Giulia C; Sidransky, David; Maitra, Anirban; Califano, Joseph

    2006-01-01

    Previously we developed an oligonucleotide sequencing microarray (MitoChip) as an array-based sequencing platform for rapid and high-throughput analysis of mitochondrial DNA. The first generation MitoChip, however, was not tiled with probes for the noncoding D-loop region, a site frequently mutated in human cancers. Here we report the development of a second-generation MitoChip (v2.0) with oligonucleotide probes to sequence the entire mitochondrial genome. In addition, the MitoChip v2.0 conta...

  4. Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

    DEFF Research Database (Denmark)

    Andersson, A M; Gaardsvoll, H; Giladi, E; Dahl, B; Bock, Elisabeth Marianne

    1990-01-01

    A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA...... oligonucleotides, that hybridize to different exons in the NCAM gene. Furthermore we have constructed three oligonucleotides, that exclusively hybridize to mRNAs lacking certain exons, by letting them consist of sequences adjacent to both sides of the splice sites. By means of these probes we have characterized...

  5. A Vondrak Low Pass Filter for IMU Sensor Initial Alignment on a Disturbed Base

    Directory of Open Access Journals (Sweden)

    Zengke Li

    2014-12-01

    Full Text Available The initial alignment of the Inertial Measurement Unit (IMU is an important process of INS to determine the coordinate transformation matrix which is used in the integration of Global Positioning Systems (GPS with Inertial Navigation Systems (INS. In this paper a novel alignment method for a disturbed base, such as a vehicle disturbed by wind outdoors, implemented with the aid of a Vondrak low pass filter, is proposed. The basic principle of initial alignment including coarse alignment and fine alignment is introduced first. The spectral analysis is processed to compare the differences between the characteristic error of INS force observation on a stationary base and on disturbed bases. In order to reduce the high frequency noise in the force observation more accurately and more easily, a Vondrak low pass filter is constructed based on the spectral analysis result. The genetic algorithms method is introduced to choose the smoothing factor in the Vondrak filter and the corresponding objective condition is built. The architecture of the proposed alignment method with the Vondrak low pass filter is shown. Furthermore, simulated experiments and actual experiments were performed to validate the new algorithm. The results indicate that, compared with the conventional alignment method, the Vondrak filter could eliminate the high frequency noise in the force observation and the proposed alignment method could improve the attitude accuracy. At the same time, only one parameter needs to be set, which makes the proposed method easier to implement than other low-pass filter methods.

  6. Basic electrical installation work

    CERN Document Server

    Linsley, Trevor

    2011-01-01

    This textbook covers all the material you need to pass the first part of the new City & Guilds 2357 Diploma in Electrotechnical Technology Aligned with the 17th edition IEE Wiring Regulations, this new edition has been thoroughly updated to cover the 'knowledge' section of the latest 2357 course. Written in an accessible style and with a separate chapter for each unit, this book helps you to master each topic before moving on to the next. End of chapter revision questions help you to check your understanding and consolidate the key concepts learned in each chapter.

  7. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method

    Directory of Open Access Journals (Sweden)

    Lund Ole

    2007-07-01

    Full Text Available Abstract Background Antigen presenting cells (APCs sample the extra cellular space and present peptides from here to T helper cells, which can be activated if the peptides are of foreign origin. The peptides are presented on the surface of the cells in complex with major histocompatibility class II (MHC II molecules. Identification of peptides that bind MHC II molecules is thus a key step in rational vaccine design and developing methods for accurate prediction of the peptide:MHC interactions play a central role in epitope discovery. The MHC class II binding groove is open at both ends making the correct alignment of a peptide in the binding groove a crucial part of identifying the core of an MHC class II binding motif. Here, we present a novel stabilization matrix alignment method, SMM-align, that allows for direct prediction of peptide:MHC binding affinities. The predictive performance of the method is validated on a large MHC class II benchmark data set covering 14 HLA-DR (human MHC and three mouse H2-IA alleles. Results The predictive performance of the SMM-align method was demonstrated to be superior to that of the Gibbs sampler, TEPITOPE, SVRMHC, and MHCpred methods. Cross validation between peptide data set obtained from different sources demonstrated that direct incorporation of peptide length potentially results in over-fitting of the binding prediction method. Focusing on amino terminal peptide flanking residues (PFR, we demonstrate a consistent gain in predictive performance by favoring binding registers with a minimum PFR length of two amino acids. Visualizing the binding motif as obtained by the SMM-align and TEPITOPE methods highlights a series of fundamental discrepancies between the two predicted motifs. For the DRB1*1302 allele for instance, the TEPITOPE method favors basic amino acids at most anchor positions, whereas the SMM-align method identifies a preference for hydrophobic or neutral amino acids at the anchors. Conclusion

  8. Aligning molecules with intense nonresonant laser fields

    DEFF Research Database (Denmark)

    Larsen, J.J.; Safvan, C.P.; Sakai, H.;

    1999-01-01

    Molecules in a seeded supersonic beam are aligned by the interaction between an intense nonresonant linearly polarized laser field and the molecular polarizability. We demonstrate the general applicability of the scheme by aligning I2, ICl, CS2, CH3I, and C6H5I molecules. The alignment is probed by...... mass selective two dimensional imaging of the photofragment ions produced by femtosecond laser pulses. Calculations on the degree of alignment of I2 are in good agreement with the experiments. We discuss some future applications of laser aligned molecules....

  9. How accurately is ncRNA aligned within whole-genome multiple alignments?

    Directory of Open Access Journals (Sweden)

    Ruzzo Walter L

    2007-10-01

    Full Text Available Abstract Background Multiple alignment of homologous DNA sequences is of great interest to biologists since it provides a window into evolutionary processes. At present, the accuracy of whole-genome multiple alignments, particularly in noncoding regions, has not been thoroughly evaluated. Results We evaluate the alignment accuracy of certain noncoding regions using noncoding RNA alignments from Rfam as a reference. We inspect the MULTIZ 17-vertebrate alignment from the UCSC Genome Browser for all the human sequences in the Rfam seed alignments. In particular, we find 638 instances of chimeric and partial alignments to human noncoding RNA elements, of which at least 225 can be improved by straightforward means. As a byproduct of our procedure, we predict many novel instances of known ncRNA families that are suggested by the alignment. Conclusion MULTIZ does a fairly accurate job of aligning these genomes in these difficult regions. However, our experiments indicate that better alignments exist in some regions.

  10. Nuclear multifragmentation: Basic concepts

    Indian Academy of Sciences (India)

    G Chaudhuri; S Mallik; S Das Gupta

    2014-05-01

    We present a brief overview of nuclear multifragmentation reaction. Basic formalism of canonical thermodynamical model based on equilibrium statistical mechanics is described. This model is used to calculate basic observables of nuclear multifragmentation like mass distribution, fragment multiplicity, isotopic distribution and isoscaling. Extension of canonical thermodynamical model to a projectile fragmentation model is outlined. Application of the projectile fragmentation model for calculating average number of intermediate mass fragments and the average size of the largest cluster at different bound, differential charge distribution and cross-section of neutron-rich nuclei of different projectile fragmentation reactions at different energies are described. Application of nuclear multifragmentation reaction in basic research as well as in other domains is outlined.

  11. Basic Electromagnetism and Materials

    CERN Document Server

    Moliton, André

    2007-01-01

    Basic Electromagnetism and Materials is the product of many years of teaching basic and applied electromagnetism. This textbook can be used to teach electromagnetism to a wide range of undergraduate science majors in physics, electrical engineering or materials science. However, by making lesser demands on mathematical knowledge than competing texts, and by emphasizing electromagnetic properties of materials and their applications, this textbook is uniquely suited to students of materials science. Many competing texts focus on the study of propagation waves either in the microwave or optical domain, whereas Basic Electromagnetism and Materials covers the entire electromagnetic domain and the physical response of materials to these waves. Professor André Moliton is Director of the Unité de Microélectronique, Optoélectronique et Polymères (Université de Limoges, France), which brings together three groups studying the optoelectronics of molecular and polymer layers, micro-optoelectronic systems for teleco...

  12. Comprehensive basic mathematics

    CERN Document Server

    Veena, GR

    2005-01-01

    Salient Features As per II PUC Basic Mathematics syllabus of Karnataka. Provides an introduction to various basic mathematical techniques and the situations where these could be usefully employed. The language is simple and the material is self-explanatory with a large number of illustrations. Assists the reader in gaining proficiency to solve diverse variety of problems. A special capsule containing a gist and list of formulae titled ''REMEMBER! Additional chapterwise arranged question bank and 3 model papers in a separate section---''EXAMINATION CORNER''.

  13. Basic properties of semiconductors

    CERN Document Server

    Landsberg, PT

    2013-01-01

    Since Volume 1 was published in 1982, the centres of interest in the basic physics of semiconductors have shifted. Volume 1 was called Band Theory and Transport Properties in the first edition, but the subject has broadened to such an extent that Basic Properties is now a more suitable title. Seven chapters have been rewritten by the original authors. However, twelve chapters are essentially new, with the bulk of this work being devoted to important current topics which give this volume an almost encyclopaedic form. The first three chapters discuss various aspects of modern band theory and the

  14. Basic set theory

    CERN Document Server

    Levy, Azriel

    2002-01-01

    An advanced-level treatment of the basics of set theory, this text offers students a firm foundation, stopping just short of the areas employing model-theoretic methods. Geared toward upper-level undergraduate and graduate students, it consists of two parts: the first covers pure set theory, including the basic motions, order and well-foundedness, cardinal numbers, the ordinals, and the axiom of choice and some of it consequences; the second deals with applications and advanced topics such as point set topology, real spaces, Boolean algebras, and infinite combinatorics and large cardinals. An

  15. Multiscale peak alignment for chromatographic datasets.

    Science.gov (United States)

    Zhang, Zhi-Min; Liang, Yi-Zeng; Lu, Hong-Mei; Tan, Bin-Bin; Xu, Xiao-Na; Ferro, Miguel

    2012-02-01

    Chromatography has been extensively applied in many fields, such as metabolomics and quality control of herbal medicines. Preprocessing, especially peak alignment, is a time-consuming task prior to the extraction of useful information from the datasets by chemometrics and statistics. To accurately and rapidly align shift peaks among one-dimensional chromatograms, multiscale peak alignment (MSPA) is presented in this research. Peaks of each chromatogram were detected based on continuous wavelet transform (CWT) and aligned against a reference chromatogram from large to small scale gradually, and the aligning procedure is accelerated by fast Fourier transform cross correlation. The presented method was compared with two widely used alignment methods on chromatographic dataset, which demonstrates that MSPA can preserve the shapes of peaks and has an excellent speed during alignment. Furthermore, MSPA method is robust and not sensitive to noise and baseline. MSPA was implemented and is available at http://code.google.com/p/mspa. PMID:22222564

  16. Antares beam-alignment-system performance

    International Nuclear Information System (INIS)

    The beam alignment system for the 24-beam-sector Antares CO2 fusion laser automatically aligns more than 200 optical elements. A visible-wavelength alignment technique is employed which uses a telescope/TV system to view point-light sources appropriately located down the beamline. The centroids of the light spots are determined by a video tracker, which generates error signals used by the computer control system to move appropriate mirrors in a closed-loop system. Final touch-up alignment is accomplished by projecting a CO2 alignment laser beam through the system and sensing its position at the target location. The techniques and control algorithms employed have resulted in alignment accuracies exceeding design requirements. By employing video processing to determine the centroids of diffraction images and by averaging over multiple TV frames, we achieve alignment accuracies better than 0.1 times system diffraction limits in the presence of air turbulence

  17. Pupil Alignment Measuring Technique and Alignment Reference for Instruments or Optical Systems

    Science.gov (United States)

    Hagopian, John G.

    2010-01-01

    A technique was created to measure the pupil alignment of instruments in situ by measuring calibrated pupil alignment references (PARs) in instruments. The PAR can also be measured using an alignment telescope or an imaging system. PAR allows the verification of the science instrument (SI) pupil alignment at the integrated science instrument module (ISIM) level of assembly at ambient and cryogenic operating temperature. This will allow verification of the ISIM+SI alignment, and provide feedback to realign the SI if necessary.

  18. How accurately is ncRNA aligned within whole-genome multiple alignments?

    OpenAIRE

    Ruzzo Walter L; Wang Adrienne X; Tompa Martin

    2007-01-01

    Abstract Background Multiple alignment of homologous DNA sequences is of great interest to biologists since it provides a window into evolutionary processes. At present, the accuracy of whole-genome multiple alignments, particularly in noncoding regions, has not been thoroughly evaluated. Results We evaluate the alignment accuracy of certain noncoding regions using noncoding RNA alignments from Rfam as a reference. We inspect the MULTIZ 17-vertebrate alignment from the UCSC Genome Browser for...

  19. NON-ALIGNEMENT IN AFRICA

    Directory of Open Access Journals (Sweden)

    G. Jacobs

    2012-02-01

    Full Text Available The first indications to the Western world that African non-alignment had achieved conscious political form became apparent only in the late 1940's. This strand of thought within the tapestry of Africanism reached its zenith with the declarations of Kwame Nkrumah, Jomo Kenyatta and Julius Nyerere in the years after the Pan-African Congress in Manchester in 1945. The causes of the movement go back far beyond the first official expressions of an African solidarity in the 1940's. As a mature expression of group attitudes tqwards foreign pol icy, nonalignment can be traced back to the roots of African nationalism.

  20. The Cluster Substructure - Alignment Connection

    CERN Document Server

    Plionis, M

    2002-01-01

    Using the APM cluster data we investigate whether the dynamical status of clusters is related to the large-scale structure of the Universe. We find that cluster substructure is strongly correlated with the tendency of clusters to be aligned with their nearest neighbour and in general with the nearby clusters that belong to the same supercluster. Furthermore, dynamically young clusters are more clustered than the overall cluster population. These are strong indications that cluster develop in a hierarchical fashion by anisotropy merging along the large-scale filamentary superclusters within which they are embedded.

  1. The Substructure-Alignment Connection

    CERN Document Server

    Plionis, M; Plionis, Manolis; Basilakos, Spyros

    2001-01-01

    Using a sample of 903 APM clusters we investigate whether their dynamical status, as evidenced by the presence of significant substructures, is related to the large-scale structure of the Universe. We find that the cluster dynamical activity is strongly correlated with the tendency of clusters to be aligned with their nearest neighbour and in general with the nearby clusters that belong to the same supercluster. Furthermore, dynamically active clusters are more clustered than the overall cluster population. These are strong indications that clusters develop in a hierarchical fashion by anisotropic merging along the large-scale filaments within which they are embedded.

  2. Aligned interactions in cosmic rays

    Science.gov (United States)

    Kempa, J.

    2015-12-01

    The first clean Centauro was found in cosmic rays years many ago at Mt Chacaltaya experiment. Since that time, many people have tried to find this type of interaction, both in cosmic rays and at accelerators. But no one has found a clean cases of this type of interaction.It happened finally in the last exposure of emulsion at Mt Chacaltaya where the second clean Centauro has been found. The experimental data for both the Centauros and STRANA will be presented and discussed in this paper. We also present our comments to the intriguing question of the existence of a type of nuclear interactions at high energy with alignment.

  3. Aligned interactions in cosmic rays

    Energy Technology Data Exchange (ETDEWEB)

    Kempa, J., E-mail: kempa@pw.plock.pl [Warsaw University of Technology Branch Plock (Poland)

    2015-12-15

    The first clean Centauro was found in cosmic rays years many ago at Mt Chacaltaya experiment. Since that time, many people have tried to find this type of interaction, both in cosmic rays and at accelerators. But no one has found a clean cases of this type of interaction.It happened finally in the last exposure of emulsion at Mt Chacaltaya where the second clean Centauro has been found. The experimental data for both the Centauros and STRANA will be presented and discussed in this paper. We also present our comments to the intriguing question of the existence of a type of nuclear interactions at high energy with alignment.

  4. Strategies for active alignment of lenses

    Science.gov (United States)

    Langehanenberg, Patrik; Heinisch, Josef; Wilde, Chrisitan; Hahne, Felix; Lüerß, Bernd

    2015-10-01

    Today's optical systems require up-to-date assembly and joining technology. The trend of keeping dimensions as small as possible while maintaining or increasing optical imaging performance leaves little to no room for mechanical lens adjustment equipment that may remain in the final product. In this context active alignment of optical elements opens up possibilities for the fast and cost-economic manufacturing of lenses and lens assemblies with highest optical performance. Active alignment for lens manufacturing is the precise alignment of the optical axis of a lens with respect to an optical or mechanical reference axis (e.g. housing) including subsequent fixation by glue. In this contribution we will describe different approaches for active alignment and outline strengths and limitations of the different methods. Using the SmartAlign principle, highest quality cemented lenses can be manufactured without the need for high precision prealignment, while the reduction to a single alignment step greatly reduces the cycle time. The same strategies can also be applied to bonding processes. Lenses and lens groups can be aligned to both mechanical and optical axes to maximize the optical performance of a given assembly. In hybrid assemblies using both mechanical tolerances and active alignment, SmartAlign can be used to align critical lens elements anywhere inside the system for optimized total performance. Since all geometrical parameters are re-measured before each alignment, this process is especially suited for complex and time-consuming production processes where the stability of the reference axis would otherwise be critical. For highest performance, lenses can be actively aligned using up to five degrees of freedom. In this way, SmartAlign enables the production of ultra-precise mounted lenses with an alignment precision below 1 μm.

  5. Mapping of HIV-1 integrase preferences for target site selection with various oligonucleotides

    Czech Academy of Sciences Publication Activity Database

    Snášel, Jan; Rosenberg, Ivan; Pačes, Ondřej; Pichová, Iva

    2009-01-01

    Roč. 488, č. 2 (2009), s. 153-162. ISSN 0003-9861 R&D Projects: GA MŠk 1M0508; GA MŠk(CZ) LC06077 Institutional research plan: CEZ:AV0Z40550506 Keywords : HIV integrase * strand transfer reaction * oligonucleotide substrates Subject RIV: CE - Biochemistry Impact factor: 3.046, year: 2009

  6. A pilot study of transcription unit analysis in rice using oligonucleotide tiling-path microarray

    DEFF Research Database (Denmark)

    Stolc, Viktor; Li, Lei; Wang, Xiangfeng; Li, Xueyong; Su, Ning; Tongprasit, Waraporn; Han, Bin; Xue, Yongbiao; Li, Jiayang; Snyder, Michael; Gerstein, Mark; Wang, Jun; Deng, Xing Wang

    2005-01-01

    As the international efforts to sequence the rice genome are completed, an immediate challenge and opportunity is to comprehensively and accurately define all transcription units in the rice genome. Here we describe a strategy of using high-density oligonucleotide tiling-path microarrays to map t...

  7. nuID: a universal naming scheme of oligonucleotides for Illumina, Affymetrix, and other microarrays

    Directory of Open Access Journals (Sweden)

    Kibbe Warren A

    2007-05-01

    Full Text Available Abstract Background Oligonucleotide probes that are sequence identical may have different identifiers between manufacturers and even between different versions of the same company's microarray; and sometimes the same identifier is reused and represents a completely different oligonucleotide, resulting in ambiguity and potentially mis-identification of the genes hybridizing to that probe. Results We have devised a unique, non-degenerate encoding scheme that can be used as a universal representation to identify an oligonucleotide across manufacturers. We have named the encoded representation 'nuID', for nucleotide universal identifier. Inspired by the fact that the raw sequence of the oligonucleotide is the true definition of identity for a probe, the encoding algorithm uniquely and non-degenerately transforms the sequence itself into a compact identifier (a lossless compression. In addition, we added a redundancy check (checksum to validate the integrity of the identifier. These two steps, encoding plus checksum, result in an nuID, which is a unique, non-degenerate, permanent, robust and efficient representation of the probe sequence. For commercial applications that require the sequence identity to be confidential, we have an encryption schema for nuID. We demonstrate the utility of nuIDs for the annotation of Illumina microarrays, and we believe it has universal applicability as a source-independent naming convention for oligomers. Reviewers This article was reviewed by Itai Yanai, Rong Chen (nominated by Mark Gerstein, and Gregory Schuler (nominated by David Lipman.

  8. A new achiral reagent for the incorporation of multiple amino groups into oligonucleotides

    DEFF Research Database (Denmark)

    Behrens, Carsten; Petersen, Kenneth H.; Egholm, Michael; Nielsen, John; Buchard, Ole; Dahl, Otto

    1995-01-01

    The synthesis of a new functionalized achiral linker reagent (10) for the incorporation of multiple primary amino groups into oligonucleotides is described. The linker reagent is compatible with conventional DNA-synthesis following the phosphoramidite methodology, and the linker can be incorporat...

  9. Efficient large-scale preparation and purification of short single-stranded RNA oligonucleotides.

    Science.gov (United States)

    Zlobina, Maria; Sedo, Ondrej; Chou, Ming-Yuan; Slepankova, Lucia; Lukavsky, Peter J

    2016-01-01

    Sequence-specific RNA recognition by RNA-binding proteins plays a crucial role in the post-translational regulation of gene expression. Biophysical and biochemical studies help to unravel the principles of sequence-specific RNA recognition, but the methods used require large amounts of single-stranded RNA (ssRNA). Here we present a fast and robust method for large-scale preparation and purification of short ssRNA oligonucleotides for biochemical, biophysical, and structural studies. We designed an efficiently folding, self-cleaving hammerhead (HH) ribozyme to prepare ssRNA oligonucleotides. Hammerhead ribozyme RNAs self-cleave with over 95% efficiency during in vitro transcription as a function of magnesium concentration to produce high yields of the desired ssRNA products. The resulting ssRNAs can be purified from crude transcription reactions by denaturing anion-exchange chromatography and then desalted by weak anion-exchange chromatography using volatile ammonium bicarbonate buffer solutions. The ssRNA oligonucleotides produced this way are homogenous, as judged by mass spectrometry (MS), and are suitable for biochemical and biophysical studies. Moreover, for high-resolution NMR structure determination of RNA-protein complexes, our protocol enables efficient preparation of ssRNA oligonucleotides with various isotope-labeling schemes which are not commercially available. PMID:26842352

  10. Design and analysis of effects of triplet repeat oligonucleotides in cell models for myotonic dystrophy

    NARCIS (Netherlands)

    Gonzalez-Barriga, A.; Mulders, S.A.M.; Giessen, J. van der; Hooijer, J.D.; Bijl, S.; Kessel, I.D.G. van; Beers, J. van; Deutekom, J.C. van; Fransen, J.A.M.; Wieringa, B.; Wansink, D.G.

    2013-01-01

    Myotonic dystrophy type 1 (DM1) is caused by DM protein kinase (DMPK) transcripts containing an expanded (CUG)n repeat. Antisense oligonucleotide (AON)-mediated suppression of these mutant RNAs is considered a promising therapeutic strategy for this severe disorder. Earlier, we identified a 2'-O-met

  11. Oligo switches: photoresponsive oligonucleotide conjugates by solid-supported click chemistry

    OpenAIRE

    Freeman, Colin; Vyle, Joseph S; Heaney, Frances

    2013-01-01

    Photoresponsive oligonucleotides (ONs) incorporating isoxazole-linked azobenzene (AB) moieties were prepared by resin-supported nitrile oxide-alkyne cycloaddition (NOAC) chemistry. The thermal and photochromic properties of the modified ONs were significantly influenced by the extent of π-conjugation between the isoxazole and the AB modules

  12. Cell penetrating peptide delivery of splice directing oligonucleotides as a treatment for Duchenne muscular dystrophy.

    Science.gov (United States)

    Betts, Corinne A; Wood, Matthew J A

    2013-01-01

    Duchenne muscular dystrophy is a severe, X-linked muscle wasting disorder caused by the absence of an integral structural protein called dystrophin. This is caused by mutations or deletions in the dystrophin gene which disrupt the reading frame, thereby halting the production of a functional protein. A number of potential therapies have been investigated for the treatment of this disease including utrophin upregulation, 'stop-codon read through' aminoglycosides and adeno-associated virus gene replacement as well as stem cell therapy. However, the most promising treatment to date is the use of antisense oligonucleotides which cause exon skipping by binding to a specific mRNA sequence, skipping the desired exon, thereby restoring the reading frame and producing a truncated yet functional protein. The results from recent 2'OMePS and morpholino clinical trials have renewed hope for Duchenne patients; however in vivo studies in a mouse model, mdx, have revealed low systemic distribution and poor delivery of oligonucleotides to affected tissues such as the brain and heart. However a variety of cell penetrating peptides directly conjugated to antisense oligonucleotides have been shown to enhance delivery in Duchenne model systems with improved systemic distribution and greater efficacy compared to 'naked' antisense oligonucleotides. These cell penetrating peptides, combined with an optimised dose and dosing regimen, as well as thorough toxicity profile have the potential to be developed into a promising treatment which may be progressed to clinical trial. PMID:23140454

  13. A triple-helix forming oligonucleotide targeting genomic DNA fails to induce mutation.

    Science.gov (United States)

    Reshat, Reshat; Priestley, Catherine C; Gooderham, Nigel J

    2012-11-01

    Purine tracts in duplex DNA can bind oligonucleotide strands in a sequence specific manner to form triple-helix structures. Triple-helix forming oligonucleotides (TFOs) targeting supFG1 constructs have previously been shown to be mutagenic raising safety concerns for oligonucleotide-based pharmaceuticals. We have engineered a TFO, TFO27, to target the genomic Hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus to define the mutagenic potential of such structures at genomic DNA. We report that TFO27 was resistant to nuclease degradation and readily binds to its target motif in a cell free system. Contrary to previous studies using the supFG1 reporter construct, TFO27 failed to induce mutation within the genomic HPRT locus. We suggest that it is possible that previous reports of triplex-mediated mutation using the supFG1 reporter construct could be confounded by DNA quadruplex formation. Although the present study indicates that a TFO targeting a genomic locus lacks mutagenic activity, it is unclear if this finding can be generalised to all TFOs and their targets. For the present, we suggest that it is prudent to avoid large purine stretches in oligonucleotide pharmaceutical design to minimise concern regarding off-target genotoxicity. PMID:22914677

  14. Oligonucleotide fishing for STAT6: cross-talk between IL-4 and chemokines

    DEFF Research Database (Denmark)

    Eriksen, K W; Nielsen, M; Kaltoft, K; Svejgaard, A; Nissen, Mogens Holst; Röpke, C; Ødum, N

    2001-01-01

    -stranded oligonucleotide probes containing a STAT6-binding gene-sequence from the promotor of the immunoglobulin heavy chain germline epsilon transcript to study the IL-4-induced DNA binding of STAT6. Using these probes, we show that repeated adjacent STAT6-binding sites result in enhanced STAT6-DNA binding. Moreover, the...

  15. Comparison of small molecules and oligonucleotides that target a toxic, non-coding RNA.

    Science.gov (United States)

    Costales, Matthew G; Rzuczek, Suzanne G; Disney, Matthew D

    2016-06-01

    Potential RNA targets for chemical probes and therapeutic modalities are pervasive in the transcriptome. Oligonucleotide-based therapeutics are commonly used to target RNA sequence. Small molecules are emerging as a modality to target RNA structures selectively, but their development is still in its infancy. In this work, we compare the activity of oligonucleotides and several classes of small molecules that target the non-coding r(CCUG) repeat expansion (r(CCUG)(exp)) that causes myotonic dystrophy type 2 (DM2), an incurable disease that is the second-most common cause of adult onset muscular dystrophy. Small molecule types investigated include monomers, dimers, and multivalent compounds synthesized on-site by using RNA-templated click chemistry. Oligonucleotides investigated include phosphorothioates that cleave their target and vivo-morpholinos that modulate target RNA activity via binding. We show that compounds assembled on-site that recognize structure have the highest potencies amongst small molecules and are similar in potency to a vivo-morpholino modified oligonucleotide that targets sequence. These studies are likely to impact the design of therapeutic modalities targeting other repeats expansions that cause fragile X syndrome and amyotrophic lateral sclerosis, for example. PMID:27117425

  16. Labelling of nucleosides and oligonucleotides by solvatochromic 4-aminophthalimide fluorophore for studying DNA–protein interactions

    Czech Academy of Sciences Publication Activity Database

    Riedl, Jan; Pohl, Radek; Ernsting, N. P.; Orság, Petr; Fojta, Miroslav; Hocek, Michal

    2012-01-01

    Roč. 3, č. 9 (2012), s. 2797-2806. ISSN 2041-6520 R&D Projects: GA ČR GA203/09/0317; GA ČR GBP206/12/G151 Institutional support: RVO:61388963 ; RVO:68081707 Keywords : DNA * oligonucleotides * polymerase * phthalimide * nucleotides * fluorescent labeling Subject RIV: CC - Organic Chemistry Impact factor: 8.314, year: 2012

  17. Long-range order of organized oligonucleotide monolayers on Au(111) electrodes

    DEFF Research Database (Denmark)

    Wackerbarth, Hainer; Grubb, Mikala; Zhang, Jingdong;

    2004-01-01

    -S bond. The coverage is high and in keeping with dense monolayers of adsorbed HS-10A and HS-10AT in an upright or tilted orientation, with the oligonucleotide backbone repelled from the strongly negatively charged electrode surface. Adsorbed thiol-free 10A only gives aAu(111)-reconstruction peak, while...

  18. TmPrime: fast, flexible oligonucleotide design software for gene synthesis

    Science.gov (United States)

    Bode, Marcus; Khor, Samuel; Ye, Hongye; Li, Mo-Huang; Ying, Jackie Y.

    2009-01-01

    Herein we present TmPrime, a computer program to design oligonucleotide sets for gene assembly by both ligase chain reaction (LCR) and polymerase chain reaction (PCR). TmPrime offers much flexibility with no constraints on the gene and oligonucleotide lengths. The program divides the long input DNA sequence based on the input desired melting temperature, and dynamically optimizes the length of oligonucleotides to achieve homologous melting temperatures. The output reports the melting temperatures, oligonucleotide sequences and potential formation of secondary structures. Our program also provides functions on sequence pooling to separate long genes into smaller pieces for multi-pool assembly and codon optimization for expression. The software has been successfully used in the design and synthesis of green fluorescent protein fragment (GFPuv) (760 bp), human protein kinase B-2 (PKB2) (1446 bp) and the promoter of human calcium-binding protein A4 (S100A4) (752 bp) using real-time PCR assembly with LCGreen I, which offers a novel approach to compare the efficiency of gene synthesis. The purity of assembled products is successfully estimated with the use of melting curve analysis, which would potentially eliminate the necessity for agarose gel electrophoresis. This program is freely available at http://prime.ibn.a-star.edu.sg. PMID:19515937

  19. MOLECULAR-MODELLING AND BIOPHYSICAL STUDIES ON MODIFIED AND UNMODIFIED OLIGONUCLEOTIDES

    OpenAIRE

    GUNNING, J.; CUTBUSH, S.; Kuroda, R; Neidle, S

    1984-01-01

    Computer graphics modelling and energy calculations have been carried out on a series of modified and unmodified oligonucleotides to investigate the effects of base deletion, base substitution and base methylation, particularly 06-methylguanine and 5-methylcytosine, as well as the substitution of bases by analogues.

  20. N-Branched acyclic nucleoside phosphonates as monomers for the synthesis of modified oligonucleotides

    Czech Academy of Sciences Publication Activity Database

    Hocková, Dana; Rosenbergová, Šárka; Ménová, Petra; Páv, Ondřej; Pohl, Radek; Novák, Pavel; Rosenberg, Ivan

    2015-01-01

    Roč. 13, č. 15 (2015), s. 4449-4458. ISSN 1477-0520 R&D Projects: GA ČR GAP207/11/0108; GA ČR GA13-26526S Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * oligonucleotides * solid phase synthesis Subject RIV: CC - Organic Chemistry Impact factor: 3.562, year: 2014

  1. Prophylactic vaccines mimic synthetic CpG oligonucleotides in their ability to modulate immune responses

    NARCIS (Netherlands)

    Vries, I.J.M. de; Tel, J.; Benitez-Ribas, D.; Torensma, R.; Figdor, C.G.

    2011-01-01

    Synthetic oligonucleotide ligands that bind to toll-like receptors are known to modulate the immune response via the activation of antigen presenting cells, and were therefore proposed as a novel form of vaccine adjuvant. Clinical-grade they are, however, not readily available. Here, we show that co

  2. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates

    DEFF Research Database (Denmark)

    Lindholm, Marie W; Elmén, Joacim; Fisker, Niels; Hansen, Henrik; Persson, Hans Egon Robert; Møller, Dorte Marianne; Rosenbohm, Christoph; Ørum, Henrik; Straarup, Ellen Marie; Koch, Troels

    2012-01-01

    locked nucleic acid (LNA) antisense oligonucleotides targeting PCSK9 produce sustained reduction of LDL-C in nonhuman primates after a loading dose (20 mg/kg) and four weekly maintenance doses (5 mg/kg). PCSK9 messenger RNA (mRNA) and serum PCSK9 protein were reduced by 85% which resulted in a 50...

  3. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available ... Fertility After Spinal Cord Injury Coping with a New Injury Coping with a New Injury Adjusting to Social Life in a Wheelchair ... The Basics of Pediatric SCI Rehabilitation Transitions for Children with Spinal Cord Injury Transitions for Children with ...

  4. Hindi Basic Reader.

    Science.gov (United States)

    Harter, J. Martin; And Others

    This reader is intended to accompany the Basic Course in Spoken Hindi. Following an outline of the Devanagari script, 20 lessons are presented. Each consists of a reading selection, several illustrative sentences in English and Hindi, and a series of questions. Most of the reading selections were adapted from the magazine "Bal-Bharati." (RM)

  5. Basic Drafting: Book One.

    Science.gov (United States)

    Davis, Ronald; And Others

    The first of a two-book course in drafting, this manual consists of 13 topics in the following units: introduction to drafting, general safety, basic tools and lines, major equipment, applying for a job, media, lettering, reproduction, drawing sheet layout, architect's scale usage, civil engineer's scale usage, mechanical engineer's scale usage,…

  6. Basic Tuberculosis Facts

    Centers for Disease Control (CDC) Podcasts

    2012-03-12

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses basic TB prevention, testing, and treatment information.  Created: 3/12/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 3/12/2012.

  7. Portuguese Basic Courses.

    Science.gov (United States)

    Defense Language Inst., Washington, DC.

    This basic course in Brazilian Portuguese consists of 75 lessons in six volumes. Volume I is in two parts, with the dialogs, questions and exercises presented in Portuguese in the first part, and the intonation patterns and English translations presented in the second. The general format follows the Defense Language Institute format, employing…

  8. Basic physics for all

    CERN Document Server

    Kumar, B N

    2012-01-01

    This is a simple, concise book for both student and non-physics students, presenting basic facts in straightforward form and conveying fundamental principles and theories of physics. This book will be helpful as a supplement to class teaching and to aid those who have difficulty in mastering concepts and principles.

  9. Ethanol Basics (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2015-01-01

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  10. IGBO, BASIC COURSE.

    Science.gov (United States)

    SWIFT, LLOYD B.; AND OTHERS

    A BASIC COURSE WAS PREPARED ON THE SPEECH OF TWO MEMBERS OF THE EZINEHITE GROUP OF IGBOS IN EASTERN NIGERIA. THE ESSENTIAL PHONOLOGICAL AND GRAMMATICAL STRUCTURES OF IGBO ARE PRESENTED WITHIN A SMALL VOCABULARY OF APPROXIMATELY 600 ITEMS. THE COURSE MATERIALS CONSIST OF (1) TONE DRILLS, (2) 24 UNITS OF DIALOGS, NOTES, AND DRILLS, (3) SIX UNITS OF…

  11. Basic Microfluidics Theory

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith

    2015-01-01

    ,000 m−1, which is a huge difference and has a large impact on flow behavior. In this chapter the basic microfluidic theory will be presented, enabling the reader to gain a comprehensive understanding of how liquids behave at the microscale, enough to be able to engage in design of micro systems and to...

  12. A highly sensitive and selective viral protein detection method based on RNA oligonucleotide nanoparticle

    Directory of Open Access Journals (Sweden)

    Changhyun Roh

    2010-04-01

    Full Text Available Changhyun Roh1, Ho-Young Lee2, Sang-Eun Kim2, Sung-Kee Jo11Radiation Research Division for Biotechnology, Advanced Radiation Technology Institute (ARTI, Korea Atomic Energy Research Institute (KAERI, Sinjeong-dong, Jeongeup, Jeonbuk, South Korea; 2Department of Nuclear Medicine, College of Medicine, Seoul National University, South KoreaAbstract: Globally, approximately 170 million people (representing approximately 3% of the population worldwide, are infected with hepatitis C virus (HCV and at risk of serious liver disease, including chronic hepatitis. We propose a new quantum dots (QDs-supported RNA oligonucleotide approach for the specific and sensitive detection of viral protein using a biochip. This method was developed by immobilizing a HCV nonstructural protein 5B (NS5B on the surface of a glass chip via the formation of a covalent bond between an amine protein group and a ProLinkerTM glass chip. The QDs-supported RNA oligonucleotide was conjugated via an amide formation reaction from coupling of a 5′-end-amine-modified RNA oligonucleotide on the surface of QDs displaying carboxyl groups via standard EDC coupling. The QDs-conjugated RNA oligonucleotide was interacted to immobilized viral protein NS5B on the biochip. The detection is based on the variation of signal of QDs-supported RNA oligonucleotide bound on an immobilized biochip. It was demonstrated that the value of the signal has a linear relationship with concentrations of the HCV NS5B viral protein in the 1 μg mL-1 to 1 ng mL-1 range with a detection limit of 1 ng mL-1. The major advantages of this RNA-oligonucleotide nanoparticle assay are its good specificity, ease of performance, and ability to perform one-spot monitoring. The proposed method could be used as a general method of HCV detection and is expected to be applicable to other types of diseases as well.Keywords: hepatitis C virus, viral protein, RNA oligonucleotide, quantum dots, biochip

  13. Visa undulator fiducialization and alignment

    International Nuclear Information System (INIS)

    As part of the R and D program towards a fourth generation light source, a Self-Amplified Spontaneous Emission (SASE) demonstration is being prepared. The Visible-Infrared SASE Amplifier (VISA) undulator will be installed at Brookhaven National Laboratory by the end of the year. The VISA undulator is an in-vacuum, 4-meter long, 1.8 cm period, pure-permanent magnet device, with a novel, strong focusing, permanent magnet FODO array included within the fixed, 6 mm undulator gap. The undulator is constructed of 99 cm long segments. To attain maximum SASE gain requires establishing overlap of electron and photon beams to within 50 μm rms. This imposes challenging tolerances on mechanical fabrication and magnetic field quality, and necessitates use of laser straightness interferometry for calibration and alignment of the magnetic axes of the undulator segments. This paper describes the magnetic centerline determination, and the fiducialization and alignment processes which were performed to meet the tolerance goal. (authors)

  14. Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Parekh-Olmedo Hetal

    2006-10-01

    Full Text Available Abstract Background Huntington's Disease (HD is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions. Results As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP. Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene. Conclusion Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease.

  15. Phage annealing proteins promote oligonucleotide-directed mutagenesis in Escherichia coli and mouse ES cells

    Directory of Open Access Journals (Sweden)

    Muyrers Joep PP

    2003-01-01

    Full Text Available Abstract Background The phage protein pairs, RecE/RecT from Rac or Redα/Redβ from λ, initiate efficient double strand break repair (DSBR in Escherichia coli that has proven very useful for DNA engineering. These phage pairs initiate DSBR either by annealing or by another mechanism that is not defined. Results Here we report that these proteins also mediate single strand oligonucleotide repair (ssOR at high efficiencies. The ssOR activity, unlike DSBR, does not require a phage exonuclease (RecE or Redα but only requires a phage annealing protein (RecT or Redβ. Notably, the P22 phage annealing protein Erf, which does not mediate the same DSBR reactions, also delivers ssOR activity. By altering aspects of the oligonucleotides, we document length and design parameters that affect ssOR efficiency to show a simple relationship to homologies either side of the repair site. Notably, ssOR shows strand bias. Oligonucleotides that can prime lagging strand replication deliver more ssOR than their leading complements. This suggests a model in which the annealing proteins hybridize the oligonucleotides to single stranded regions near the replication fork. We also show that ssOR is a highly efficient way to engineer BACs and can be detected in a eukaryotic cell upon expression of a phage annealing protein. Conclusion Phage annealing proteins can initiate the recombination of single stranded oligonucleotides into endogenous targets in Escherichia coli at very high efficiencies. This expands the repertoire of useful DNA engineering strategies, shows promise for applications in eukaryotic cells, and has implications for the unanswered questions regarding DSBR mediated by RecE/RecT and Redα/Redβ.

  16. Modulation of 5' splice site selection using tailed oligonucleotides carrying splicing signals

    Directory of Open Access Journals (Sweden)

    Elela Sherif

    2006-01-01

    Full Text Available Abstract Background We previously described the use of tailed oligonucleotides as a means of reprogramming alternative pre-mRNA splicing in vitro and in vivo. The tailed oligonucleotides that were used interfere with splicing because they contain a portion complementary to sequences immediately upstream of the target 5' splice site combined with a non-hybridizing 5' tail carrying binding sites for the hnRNP A1/A2 proteins. In the present study, we have tested the inhibitory activity of RNA oligonucleotides carrying different tail structures. Results We show that an oligonucleotide with a 5' tail containing the human β-globin branch site sequence inhibits the use of the 5' splice site of Bcl-xL, albeit less efficiently than a tail containing binding sites for the hnRNP A1/A2 proteins. A branch site-containing tail positioned at the 3' end of the oligonucleotide also elicited splicing inhibition but not as efficiently as a 5' tail. The interfering activity of a 3' tail was improved by adding a 5' splice site sequence next to the branch site sequence. A 3' tail carrying a Y-shaped branch structure promoted similar splicing interference. The inclusion of branch site or 5' splice site sequences in the Y-shaped 3' tail further improved splicing inhibition. Conclusion Our in vitro results indicate that a variety of tail architectures can be used to elicit splicing interference at low nanomolar concentrations, thereby broadening the scope and the potential impact of this antisense technology.

  17. Development, Characterization and Experimental Validation of a Cultivated Sunflower (Helianthus annuus L.) Gene Expression Oligonucleotide Microarray

    Science.gov (United States)

    Fernandez, Paula; Soria, Marcelo; Blesa, David; DiRienzo, Julio; Moschen, Sebastian; Rivarola, Maximo; Clavijo, Bernardo Jose; Gonzalez, Sergio; Peluffo, Lucila; Príncipi, Dario; Dosio, Guillermo; Aguirrezabal, Luis; García-García, Francisco; Conesa, Ana; Hopp, Esteban; Dopazo, Joaquín; Heinz, Ruth Amelia; Paniego, Norma

    2012-01-01

    Oligonucleotide-based microarrays with accurate gene coverage represent a key strategy for transcriptional studies in orphan species such as sunflower, H. annuus L., which lacks full genome sequences. The goal of this study was the development and functional annotation of a comprehensive sunflower unigene collection and the design and validation of a custom sunflower oligonucleotide-based microarray. A large scale EST (>130,000 ESTs) curation, assembly and sequence annotation was performed using Blast2GO (www.blast2go.de). The EST assembly comprises 41,013 putative transcripts (12,924 contigs and 28,089 singletons). The resulting Sunflower Unigen Resource (SUR version 1.0) was used to design an oligonucleotide-based Agilent microarray for cultivated sunflower. This microarray includes a total of 42,326 features: 1,417 Agilent controls, 74 control probes for sunflower replicated 10 times (740 controls) and 40,169 different non-control probes. Microarray performance was validated using a model experiment examining the induction of senescence by water deficit. Pre-processing and differential expression analysis of Agilent microarrays was performed using the Bioconductor limma package. The analyses based on p-values calculated by eBayes (p<0.01) allowed the detection of 558 differentially expressed genes between water stress and control conditions; from these, ten genes were further validated by qPCR. Over-represented ontologies were identified using FatiScan in the Babelomics suite. This work generated a curated and trustable sunflower unigene collection, and a custom, validated sunflower oligonucleotide-based microarray using Agilent technology. Both the curated unigene collection and the validated oligonucleotide microarray provide key resources for sunflower genome analysis, transcriptional studies, and molecular breeding for crop improvement. PMID:23110046

  18. Coupling strategies for the synthesis of Peptide-oligonucleotide conjugates for patterned synthetic biomineralization.

    Science.gov (United States)

    Carter, Joshua D; Labean, Thomas H

    2011-01-01

    This work describes preparation strategies for peptide-oligonucleotide conjugates that combine the self-assembling behavior of DNA oligonucleotides with the molecular recognition capabilities of peptides. The syntheses include a solution-phase fragment coupling reaction and a solid-phase fragment coupling strategy where the oligonucleotide has been immobilized on DEAE Sepharose. The yield of four coupling reagents is evaluated, two reagents in water, EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride) and DMTMM (4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium chloride), and two in dimethylformamide (DMF), PyBOP ((Benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate) and HBTU (O-benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate), while the oligonucleotide fragment is either in solution or immobilized on DEAE. These coupling strategies rely on an unprotected 5' amino linker on the oligonucleotide reacting with the peptide C-terminus. The peptide, selected from a combinatorial library for its gold-binding behavior, was 12 amino acids long with an N-terminus acetyl cap. Formation of the conjugates was confirmed by gel electrophoresis and mass spectrometry while molecular recognition functionality of the peptide portion was verified using atomic force microscopy. Solution-phase yields were superior to their solid-phase counterparts. EDC resulted in the highest yield for both solution-phase (95%) and solid-phase strategies (24%), while the DMF-based reagents, PyBOP and HBTU, resulted in low yields with reduced recovery. All recoverable conjugates demonstrated gold nanoparticle templating capability. PMID:22007290

  19. Coupling Strategies for the Synthesis of Peptide-Oligonucleotide Conjugates for Patterned Synthetic Biomineralization

    Directory of Open Access Journals (Sweden)

    Joshua D. Carter

    2011-01-01

    Full Text Available This work describes preparation strategies for peptide-oligonucleotide conjugates that combine the self-assembling behavior of DNA oligonucleotides with the molecular recognition capabilities of peptides. The syntheses include a solution-phase fragment coupling reaction and a solid-phase fragment coupling strategy where the oligonucleotide has been immobilized on DEAE Sepharose. The yield of four coupling reagents is evaluated, two reagents in water, EDC (1-ethyl-3-(3-dimethylaminopropyl carbodiimide hydrochloride and DMTMM (4-(4,6-dimethoxy[1,3,5]triazin-2-yl-4-methyl-morpholinium chloride, and two in dimethylformamide (DMF, PyBOP ((Benzotriazol-1-yloxy tripyrrolidinophosphonium hexafluorophosphate and HBTU (O-benzotriazole-N,N,N′,N′-tetramethyluronium hexafluorophosphate, while the oligonucleotide fragment is either in solution or immobilized on DEAE. These coupling strategies rely on an unprotected 5′ amino linker on the oligonucleotide reacting with the peptide C-terminus. The peptide, selected from a combinatorial library for its gold-binding behavior, was 12 amino acids long with an N-terminus acetyl cap. Formation of the conjugates was confirmed by gel electrophoresis and mass spectrometry while molecular recognition functionality of the peptide portion was verified using atomic force microscopy. Solution-phase yields were superior to their solid-phase counterparts. EDC resulted in the highest yield for both solution-phase (95% and solid-phase strategies (24%, while the DMF-based reagents, PyBOP and HBTU, resulted in low yields with reduced recovery. All recoverable conjugates demonstrated gold nanoparticle templating capability.

  20. Development, characterization and experimental validation of a cultivated sunflower (Helianthus annuus L. gene expression oligonucleotide microarray.

    Directory of Open Access Journals (Sweden)

    Paula Fernandez

    Full Text Available Oligonucleotide-based microarrays with accurate gene coverage represent a key strategy for transcriptional studies in orphan species such as sunflower, H. annuus L., which lacks full genome sequences. The goal of this study was the development and functional annotation of a comprehensive sunflower unigene collection and the design and validation of a custom sunflower oligonucleotide-based microarray. A large scale EST (>130,000 ESTs curation, assembly and sequence annotation was performed using Blast2GO (www.blast2go.de. The EST assembly comprises 41,013 putative transcripts (12,924 contigs and 28,089 singletons. The resulting Sunflower Unigen Resource (SUR version 1.0 was used to design an oligonucleotide-based Agilent microarray for cultivated sunflower. This microarray includes a total of 42,326 features: 1,417 Agilent controls, 74 control probes for sunflower replicated 10 times (740 controls and 40,169 different non-control probes. Microarray performance was validated using a model experiment examining the induction of senescence by water deficit. Pre-processing and differential expression analysis of Agilent microarrays was performed using the Bioconductor limma package. The analyses based on p-values calculated by eBayes (p<0.01 allowed the detection of 558 differentially expressed genes between water stress and control conditions; from these, ten genes were further validated by qPCR. Over-represented ontologies were identified using FatiScan in the Babelomics suite. This work generated a curated and trustable sunflower unigene collection, and a custom, validated sunflower oligonucleotide-based microarray using Agilent technology. Both the curated unigene collection and the validated oligonucleotide microarray provide key resources for sunflower genome analysis, transcriptional studies, and molecular breeding for crop improvement.

  1. Molecular Alignment and Orientation From Laser-Induced Mechanisms to Optimal Control

    CERN Document Server

    Atabek, O

    2002-01-01

    Genetic algorithms, as implemented in optimal control strategies, are currently successfully exploited in a wide range of problems in molecular physics. In this context, laser control of molecular alignment and orientation remains a very promising issue with challenging applications extending from chemical reactivity to nanoscale design. We emphasize the complementarity between basic quantum mechanisms monitoring alignment/orientation processes and optimal control scenarios. More explicitly, if on one hand we can help the optimal control scheme to take advantage of such mechanisms by appropriately building the targets and delineating the parameter sampling space, on the other hand we expect to learn, from optimal control results, some robust and physically sound dynamical mechanisms. We present basic mechanisms for alignment and orientation, such as pendular states accommodated by the molecule-plus-field effective potential and the "kick" mechanism obtained by a sudden excitation. Very interestingly, an optim...

  2. Aligned carbon nanotube thin films for DNA electrochemical sensing

    Energy Technology Data Exchange (ETDEWEB)

    Berti, F. [Department of Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino, Firenze 50019 (Italy); Lozzi, L. [Department of Physics, University of L' Aquila, Coppito, L' Aquila 67100 (Italy); Palchetti, I. [Department of Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino, Firenze 50019 (Italy); Santucci, S. [Department of Physics, University of L' Aquila, Coppito, L' Aquila 67100 (Italy); Marrazza, G. [Department of Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino, Firenze 50019 (Italy)], E-mail: giovanna.marrazza@unifi.it

    2009-09-01

    Carbon nanotubes are interesting materials for DNA electrochemical sensing due to their unique electric properties: high surface area, fast heterogeneous electron transfer, and electrochemical stability. In this work aligned Carbon NanoTube (CNT) thin films were designed and tested as candidate platforms for DNA immobilization and for the development of an electrochemical genosensor. The films were prepared by Chemical Vapor Deposition (CVD) using acetylene and ammonia as precursor gases and nickel particles as catalyst. A preliminary electrochemical characterization was performed using cyclic voltammetry since, so far, these films have been used only for gas sensing. The surfaces were then covalently functionalized with a DNA oligonucleotide probe, complementary to the sequence of the most common inserts in the GMOs: the Promoter 35S. The genosensor format involved the immobilization of the probe onto the sensor surface, the hybridization with the target-sequence and the electrochemical detection of the duplex formation. Careful attention was paid to the probe immobilization conditions in order to minimize the signal due to non-specifically adsorbed sequences. For the detection of the hybridization event both label-free and enzyme-labelled methods were investigated. In case of the enzyme-labelled method a target concentration at nanomolar level can be easily detected, with a linear response from 50 nM to 200 nM, whereas the label-free method showed a linear response between 0.5 {mu}M and 10 {mu}M. The reproducibility was 11% and 20% with the enzyme-labelled method and the label-free method, respectively. The batch-to-batch reproducibility of the different sensors was also evaluated.

  3. Effect of CD44 Suppression by Antisense Oligonucleotide on Attachment of Human Trabecular Meshwork Cells to HA

    Institute of Scientific and Technical Information of China (English)

    李中国; 张虹

    2004-01-01

    The effects of suppression of CD44 by CD44-specific antisense oligonucleotide on attachment of human trabecular meshwork cells to hyaluronic acid (HA) were observed and the possible relationship between CD44 and primary open-angle glaucoma (POAG) investigated. CD44-specific antisense oligonucleotide was delivered with cationic lipid to cultured human trabecular meshwork cells. The expression of CD44 suppressed by CD44-specific antisense oligonucleotide was detected by RT-PCR and Western blotting. The effect of CD44 suppression by specific antisense oligonucleotide on attachment of trabecular meshwork cells to HA was measured by MTT assay. Results showed that expression of CD44 was suppressed by CD4, specific antisense oligonucleotide. Antisense oligonucleotide also suppressed the adhesion of human trabecular meshwork cells to HA in a concentration dependent manner. It was concluded that attachment of human trabecular meshwork cells to HA was decreased when CD44 was suppressed by specific antisense oligonucleotide. CD44might play a role in pathogenesis of POAG by affecting the adhesion of trabecular meshwork cells to HA.

  4. Emulsion Science Basic Principles

    CERN Document Server

    Leal-Calderon, Fernando; Schmitt, Véronique

    2007-01-01

    Emulsions are generally made out of two immiscible fluids like oil and water, one being dispersed in the second in the presence of surface-active compounds.They are used as intermediate or end products in a huge range of areas including the food, chemical, cosmetic, pharmaceutical, paint, and coating industries. Besides the broad domain of technological interest, emulsions are raising a variety of fundamental questions at the frontier between physics and chemistry. This book aims to give an overview of the most recent advances in emulsion science. The basic principles, covering aspects of emulsions from their preparation to their destruction, are presented in close relation to both the fundamental physics and the applications of these materials. The book is intended to help scientists and engineers in formulating new materials by giving them the basics of emulsion science.

  5. Basic electronic circuits

    CERN Document Server

    Buckley, P M

    1980-01-01

    In the past, the teaching of electricity and electronics has more often than not been carried out from a theoretical and often highly academic standpoint. Fundamentals and basic concepts have often been presented with no indication of their practical appli­ cations, and all too frequently they have been illustrated by artificially contrived laboratory experiments bearing little relationship to the outside world. The course comes in the form of fourteen fairly open-ended constructional experiments or projects. Each experiment has associated with it a construction exercise and an explanation. The basic idea behind this dual presentation is that the student can embark on each circuit following only the briefest possible instructions and that an open-ended approach is thereby not prejudiced by an initial lengthy encounter with the theory behind the project; this being a sure way to dampen enthusiasm at the outset. As the investigation progresses, questions inevitably arise. Descriptions of the phenomena encounte...

  6. Basics of statistical physics

    CERN Document Server

    Müller-Kirsten, Harald J W

    2013-01-01

    Statistics links microscopic and macroscopic phenomena, and requires for this reason a large number of microscopic elements like atoms. The results are values of maximum probability or of averaging. This introduction to statistical physics concentrates on the basic principles, and attempts to explain these in simple terms supplemented by numerous examples. These basic principles include the difference between classical and quantum statistics, a priori probabilities as related to degeneracies, the vital aspect of indistinguishability as compared with distinguishability in classical physics, the differences between conserved and non-conserved elements, the different ways of counting arrangements in the three statistics (Maxwell-Boltzmann, Fermi-Dirac, Bose-Einstein), the difference between maximization of the number of arrangements of elements, and averaging in the Darwin-Fowler method. Significant applications to solids, radiation and electrons in metals are treated in separate chapters, as well as Bose-Eins...

  7. Basic plasma physics

    CERN Document Server

    Ghosh, Basudev

    2014-01-01

    Basic Plasma Physics is designed to serve as an introductory compact textbook for advanced undergraduate, postgraduate and research students taking plasma physics as one of their subject of study for the first time. It covers the current syllabus of plasma physics offered by the most universities and technical institutions. The book requires no background in plasma physics but only elementary knowledge of basic physics and mathematics. Emphasis has been given on the analytical approach. Topics are developed from first principle so that the students can learn through self-study. One chapter has been devoted to describe some practical aspects of plasma physics. Each chapter contains a good number of solved and unsolved problems and a variety of review questions, mostly taken from recent examination papers. Some classroom experiments described in the book will surely help students as well as instructors.

  8. Basic linear algebra

    CERN Document Server

    Blyth, T S

    2002-01-01

    Basic Linear Algebra is a text for first year students leading from concrete examples to abstract theorems, via tutorial-type exercises. More exercises (of the kind a student may expect in examination papers) are grouped at the end of each section. The book covers the most important basics of any first course on linear algebra, explaining the algebra of matrices with applications to analytic geometry, systems of linear equations, difference equations and complex numbers. Linear equations are treated via Hermite normal forms which provides a successful and concrete explanation of the notion of linear independence. Another important highlight is the connection between linear mappings and matrices leading to the change of basis theorem which opens the door to the notion of similarity. This new and revised edition features additional exercises and coverage of Cramer's rule (omitted from the first edition). However, it is the new, extra chapter on computer assistance that will be of particular interest to readers:...

  9. Simple Method To Prepare Oligonucleotide-Conjugated Antibodies and Its Application in Multiplex Protein Detection in Single Cells.

    Science.gov (United States)

    Gong, Haibiao; Holcomb, Ilona; Ooi, Aik; Wang, Xiaohui; Majonis, Daniel; Unger, Marc A; Ramakrishnan, Ramesh

    2016-01-20

    The diversity of nucleic acid sequences enables genomics studies in a highly multiplexed format. Since multiplex protein detection is still a challenge, it would be useful to use genomics tools for this purpose. This can be accomplished by conjugating specific oligonucleotides to antibodies. Upon binding of the oligonucleotide-conjugated antibodies to their targets, the protein levels can be converted to oligonucleotide levels. In this report we describe a simple method for preparing oligonucleotide-conjugated antibodies and discuss this method's application in oligonucleotide extension reaction (OER) for multiplex protein detection. Conjugation is based on strain-promoted alkyne-azide cycloaddition (the Cu-free click reaction), in which the antibody is activated with a dibenzocyclooctyne (DBCO) moiety and subsequently linked covalently with an azide-modified oligonucleotide. In the functional test, the reaction conditions and purification processes were optimized to achieve maximum yield and best performance. The OER assay employs a pair of antibody binders (two antibodies, each conjugated with its own oligonucleotide) developed for each protein target. The two oligonucleotides contain unique six-base complementary regions at their 3' prime ends to allow annealing and extension by DNA synthesis enzymes to form a DNA template. Following preamplification, the DNA template is detected by qPCR. Distinct oligonucleotide sequences are assigned to different antibody binders to enable multiplex protein detection. When tested using recombinant proteins, some antibody binders, such as those specific to CSTB, MET, EpCAM, and CASP3, had dynamic ranges of 5-6 logs. The antibody binders were also used in a multiplexed format in OER assays, and the binders successfully detected their protein targets in cell lysates, and in single cells in combination with the C1 system. This click reaction-based antibody conjugation procedure is cost-effective, needs minimal hands-on time, and

  10. Galaxy alignments: Observations and impact on cosmology

    CERN Document Server

    Kirk, Donnacha; Hoekstra, Henk; Joachimi, Benjamin; Kitching, Thomas D; Mandelbaum, Rachel; Sifón, Cristóbal; Cacciato, Marcello; Choi, Ami; Kiessling, Alina; Leonard, Adrienne; Rassat, Anais; Schäfer, Björn Malte

    2015-01-01

    Galaxy shapes are not randomly oriented, rather they are statistically aligned in a way that can depend on formation environment, history and galaxy type. Studying the alignment of galaxies can therefore deliver important information about the astrophysics of galaxy formation and evolution as well as the growth of structure in the Universe. In this review paper we summarise key measurements of intrinsic alignments, divided by galaxy type, scale and environment. We also cover the statistics and formalism necessary to understand the observations in the literature. With the emergence of weak gravitational lensing as a precision probe of cosmology, galaxy alignments took on an added importance because they can mimic cosmic shear, the effect of gravitational lensing by large-scale structure on observed galaxy shapes. This makes intrinsic alignments an important systematic effect in weak lensing studies. We quantify the impact of intrinsic alignments on cosmic shear surveys and finish by reviewing practical mitigat...

  11. Magnetic alignment and patterning of cellulose fibers

    International Nuclear Information System (INIS)

    The alignment and patterning of cellulose fibers under magnetic fields are reported. Static and rotating magnetic fields were used to align cellulose fibers with sizes ranging from millimeter to nanometer sizes. Cellulose fibers of the millimeter order, which were prepared for papermaking, and much smaller fibers with micrometer to nanometer sizes prepared by the acid hydrolysis of larger ones underwent magnetic alignment. Under a rotating field, a uniaxial alignment of fibers was achieved. The alignment was successfully fixed by the photopolymerization of a UV-curable resin precursor used as matrix. A monodomain chiral nematic film was prepared from an aqueous suspension of nanofibers. Using a field modulator inserted in a homogeneous magnetic field, simultaneous alignment and patterning were achieved

  12. Magnetic alignment and patterning of cellulose fibers

    Directory of Open Access Journals (Sweden)

    Fumiko Kimura and Tsunehisa Kimura

    2008-01-01

    Full Text Available The alignment and patterning of cellulose fibers under magnetic fields are reported. Static and rotating magnetic fields were used to align cellulose fibers with sizes ranging from millimeter to nanometer sizes. Cellulose fibers of the millimeter order, which were prepared for papermaking, and much smaller fibers with micrometer to nanometer sizes prepared by the acid hydrolysis of larger ones underwent magnetic alignment. Under a rotating field, a uniaxial alignment of fibers was achieved. The alignment was successfully fixed by the photopolymerization of a UV-curable resin precursor used as matrix. A monodomain chiral nematic film was prepared from an aqueous suspension of nanofibers. Using a field modulator inserted in a homogeneous magnetic field, simultaneous alignment and patterning were achieved

  13. Magnetic alignment and patterning of cellulose fibers

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Fumiko; Kimura, Tsunehisa [Division of Forest and Biomaterials Science, Graduate School of Agriculture, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan)], E-mail: tkimura@kais.kyoto-u.ac.jp

    2008-04-01

    The alignment and patterning of cellulose fibers under magnetic fields are reported. Static and rotating magnetic fields were used to align cellulose fibers with sizes ranging from millimeter to nanometer sizes. Cellulose fibers of the millimeter order, which were prepared for papermaking, and much smaller fibers with micrometer to nanometer sizes prepared by the acid hydrolysis of larger ones underwent magnetic alignment. Under a rotating field, a uniaxial alignment of fibers was achieved. The alignment was successfully fixed by the photopolymerization of a UV-curable resin precursor used as matrix. A monodomain chiral nematic film was prepared from an aqueous suspension of nanofibers. Using a field modulator inserted in a homogeneous magnetic field, simultaneous alignment and patterning were achieved.

  14. Innovative optical alignment technique for CMP wafers

    Science.gov (United States)

    Sugaya, Ayako; Kanaya, Yuho; Nakajima, Shinichi; Nagayama, Tadashi; Shiraishi, Naomasa

    2002-07-01

    Detecting position of the wafers such as after CMP process is critical theme of current and forthcoming IC manufacturing. The alignment system must be with high accuracy for any process. To satisfy such requirements, we have studied and analyzed factors that have made alignment difficult. From the result of the studies, we have developed new optical alignment techniques which improve the accuracy of FIA (alignment sensor of Nikon's NSR series) and examined them. The approaches are optimizing the focus position, developing an advanced algorithm for position detection, and selecting a suitable mark design. For experiment, we have developed the special wafers that make it possible to evaluate the influence of CMP processes. The experimental results show that the overlay errors decrease dramatically with the new alignment techniques. FIA with these new techniques will be much accurate and suitable alignment sensor for CMP and other processes of future generation ULSI production.

  15. Basics of Computer Networking

    CERN Document Server

    Robertazzi, Thomas

    2012-01-01

    Springer Brief Basics of Computer Networking provides a non-mathematical introduction to the world of networks. This book covers both technology for wired and wireless networks. Coverage includes transmission media, local area networks, wide area networks, and network security. Written in a very accessible style for the interested layman by the author of a widely used textbook with many years of experience explaining concepts to the beginner.

  16. Decision support basics

    CERN Document Server

    Power, Daniel J

    2009-01-01

    This book is targeted to busy managers and MBA students who need to grasp the basics of computerized decision support. Some of the topics covered include: What is a DSS? What do managers need to know about computerized decision support? And how can managers identify opportunities to create innovative DSS? Overall the book addresses 35 fundamental questions that are relevant to understanding computerized decision support.

  17. Risk communication basics

    Energy Technology Data Exchange (ETDEWEB)

    Corrado, P.G. [Lawrence Livermore National Laboratory, CA (United States)

    1995-12-31

    In low-trust, high-concern situations, 50% of your credibility comes from perceived empathy and caring, demonstrated in the first 30 s you come in contact with someone. There is no second chance for a first impression. These and other principles contained in this paper provide you with a basic level of understanding of risk communication. The principles identified are time-tested caveats and will assist you in effectively communicating technical information.

  18. Risk communication basics

    International Nuclear Information System (INIS)

    In low-trust, high-concern situations, 50% of your credibility comes from perceived empathy and caring, demonstrated in the first 30 s you come in contact with someone. There is no second chance for a first impression. These and other principles contained in this paper provide you with a basic level of understanding of risk communication. The principles identified are time-tested caveats and will assist you in effectively communicating technical information

  19. Basic Financial Accounting

    DEFF Research Database (Denmark)

    Wiborg, Karsten

    This textbook on Basic Financial Accounting is targeted students in the economics studies at universities and business colleges having an introductory subject in the external dimension of the company's economic reporting, including bookkeeping, etc. The book includes the following subjects......: business entities, the transformation process, types of businesses, stakeholders, legislation, the annual report, the VAT system, double-entry bookkeeping, inventories, and year-end cast flow analysis....

  20. Basic concepts in oceanography

    International Nuclear Information System (INIS)

    Basic concepts in oceanography include major wind patterns that drive ocean currents, and the effects that the earth's rotation, positions of land masses, and temperature and salinity have on oceanic circulation and hence global distribution of radioactivity. Special attention is given to coastal and near-coastal processes such as upwelling, tidal effects, and small-scale processes, as radionuclide distributions are currently most associated with coastal regions. (author)