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. Identification of regions in multiple sequence alignments thermodynamically suitable for targeting by consensus oligonucleotides: application to HIV genome

    Directory of Open Access Journals (Sweden)

    Matveeva Olga V

    2004-04-01

    Full Text Available Abstract Background Computer programs for the generation of multiple sequence alignments such as "Clustal W" allow detection of regions that are most conserved among many sequence variants. However, even for regions that are equally conserved, their potential utility as hybridization targets varies. Mismatches in sequence variants are more disruptive in some duplexes than in others. Additionally, the propensity for self-interactions amongst oligonucleotides targeting conserved regions differs and the structure of target regions themselves can also influence hybridization efficiency. There is a need to develop software that will employ thermodynamic selection criteria for finding optimal hybridization targets in related sequences. Results A new scheme and new software for optimal detection of oligonucleotide hybridization targets common to families of aligned sequences is suggested and applied to aligned sequence variants of the complete HIV-1 genome. The scheme employs sequential filtering procedures with experimentally determined thermodynamic cut off points: 1 creation of a consensus sequence of RNA or DNA from aligned sequence variants with specification of the lengths of fragments to be used as oligonucleotide targets in the analyses; 2 selection of DNA oligonucleotides that have pairing potential, greater than a defined threshold, with all variants of aligned RNA sequences; 3 elimination of DNA oligonucleotides that have self-pairing potentials for intra- and inter-molecular interactions greater than defined thresholds. This scheme has been applied to the HIV-1 genome with experimentally determined thermodynamic cut off points. Theoretically optimal RNA target regions for consensus oligonucleotides were found. They can be further used for improvement of oligo-probe based HIV detection techniques. Conclusions A selection scheme with thermodynamic thresholds and software is presented in this study. The package can be used for any purpose

  3. 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.

  4. 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

  5. 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

  6. 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…

  7. 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

  8. 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

  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. 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…

  12. 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...

  13. [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

  14. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

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

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...... improve biomolecular recognition by synthetic nucleic acid analogues. Circular dichroism (CD) measurements showed no distortion of the duplex structure by the incorporated peptide chains while studies in human serum indicated superior stability of the POCs compared to LNA/DNA mixmers and unmodified DNA...

  15. 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].

  16. Oligonucleotide therapeutics: chemistry, delivery and clinical progress.

    Science.gov (United States)

    Sharma, Vivek K; Watts, Jonathan K

    2015-01-01

    Oligonucleotide therapeutics have the potential to become a third pillar of drug development after small molecules and protein therapeutics. However, the three approved oligonucleotide drugs over the past 17 years have not proven to be highly successful in a commercial sense. These trailblazer drugs have nonetheless laid the foundations for entire classes of drug candidates to follow. This review will examine further advances in chemistry that are earlier in the pipeline of oligonucleotide drug candidates. Finally, we consider the possible effect of delivery systems that may provide extra footholds to improve the potency and specificity of oligonucleotide drugs. Our overview focuses on strategies to imbue antisense oligonucleotides with more drug-like properties and their applicability to other nucleic acid therapeutics.

  17. 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

  18. 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...

  19. 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...

  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. Alignment fixture

    Science.gov (United States)

    Bell, Grover C.; Gibson, O. Theodore

    1980-01-01

    A part alignment fixture is provided which may be used for precise variable lateral and tilt alignment relative to the fixture base of various shaped parts. The fixture may be used as a part holder for machining or inspection of parts or alignment of parts during assembly and the like. The fixture includes a precisely machined diameter disc-shaped hub adapted to receive the part to be aligned. The hub is nested in a guide plate which is adapted to carry two oppositely disposed pairs of positioning wedges so that the wedges may be reciprocatively positioned by means of respective micrometer screws. The sloping faces of the wedges contact the hub at respective quadrants of the hub periphery. The lateral position of the hub relative to the guide plate is adjusted by positioning the wedges with the associated micrometer screws. The tilt of the part is adjusted relative to a base plate, to which the guide plate is pivotally connected by means of a holding plate. Two pairs of oppositely disposed wedges are mounted for reciprocative lateral positioning by means of separate micrometer screws between flanges of the guide plate and the base plate. Once the wedges are positioned to achieve the proper tilt of the part or hub on which the part is mounted relative to the base plate, the fixture may be bolted to a machining, inspection, or assembly device.

  2. Kinetic effects on signal normalization in oligonucleotide microchips with labeled immobilized probes.

    Science.gov (United States)

    Pan'kov, S V; Chechetkin, V R; Somova, O G; Antonova, O V; Moiseeva, O V; Prokopenko, D V; Yurasov, R A; Gryadunov, D A; Chudinov, A V

    2009-10-01

    Among various factors affecting operation of oligonucleotide microchips, the variations in concentration and in homogeneous distribution of immobilized probes over the cells are one of the most important. The labeling of immobilized probes ensures the complete current monitoring on the probe distribution and is reliable and convenient. Using hydrogel-based oligonucleotide microchips, the applicability of Cy3-labeled immobilized probes for quality control and signal normalization after hybridization with Cy5-labeled target DNA was investigated. This study showed that proper signal normalization should be different in thermodynamic conditions and in transient regime with hybridization far from saturation. This kinetic effect holds for both hydrogel-based and surface oligonucleotide microchips. Besides proving basic features, the technique was assessed on a sampling batch of 50 microchips developed for identifying mutations responsible for rifampicin and isoniazid resistance of Mycobacterium tuberculosis.

  3. 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

  4. 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

  5. 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)

  6. 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...

  7. Chemosensitization by antisense oligonucleotides targeting MDM2.

    Science.gov (United States)

    Bianco, Roberto; Ciardiello, Fortunato; Tortora, Giampaolo

    2005-02-01

    The MDM2 oncogene is overexpressed in many human cancers, including sarcomas, certain hematologic malignancies, and breast, colon and prostate cancers. The p53-MDM2 interaction pathway has been suggested as a novel target for cancer therapy. To that end, several strategies have been explored, including the use of small polypeptides targeted to the MDM2-p53 binding domain, anti-MDM2 antisense oligonucleotides, and natural agents. Different generations of anti-human-MDM2 oligonucleotides have been tested in in vitro and in vivo human cancer models, revealing specific inhibition of MDM2 expression and significant antitumor activity. Use of antisense oligos potentiated the effects of growth inhibition, p53 activation and p21 induction by several chemotherapeutic agents. Increased therapeutic effectiveness of chemotherapeutic drugs in human cancer cell lines carrying p53 mutations or deletions have shown the ability of MDM2 inhibitors to act as chemosensitizers in various types of tumors through both p53-dependent and p53-independent mechanisms. Inhibiting MDM2 appears to also have a role in radiation therapy for human cancer, regardless of p53 status, providing a rationale for the development of a new class of radiosensitizers. Moreover, MDM2 antisense oligonucleotides potentiate the effect of epidermal growth factor receptor (EGFR) inhibitors by affecting in vitro and in vivo proliferation, apoptosis and protein expression in hormone-refractory and hormone-dependent human prostate cancer cells. These data support the development, among other MDM2 inhibitors, of anti-MDM2 antisense oligonucleotides as a novel class of anticancer agents, and suggest a potentially relevant role for the oligonucleotides when integrated with conventional treatments and/or other signaling inhibitors in novel therapeutic strategies.

  8. Electrochemical study of hepta–oligonucleotides

    Directory of Open Access Journals (Sweden)

    Zdenka Balcarova

    2010-12-01

    Full Text Available The study deals with the description and characterization of twohepta–oligonucleotides (DNA and RNA forming special structures.We studied their electrochemical behaviour by means of cyclicvoltammetry (CV and elimination voltammetry with linear scan(EVLS in combination with adsorptive stripping (AdS technique.Differences in electrochemical behaviour of hepta–deoxyribonucleotide and its RNA analog were discussed with regardto their different structures in solutions and their melting points.

  9. 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 indexing the reference sequence in the main memory. We tested it on the whole human genome and found that this new algorithm reduced memory usage from 14.7 to 5.4 GB and improved alignment speed by 20-30 times. SOAP2 is compatible with both single- and paired-end reads. Additionally, this tool now supports...... multiple text and compressed file formats. A consensus builder has also been developed for consensus assembly and SNP detection from alignment of short reads on a reference genome. AVAILABILITY: http://soap.genomics.org.cn....

  10. 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

  11. 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

  12. 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

  13. Investigations of oligonucleotide usage variance within and between prokaryotes

    DEFF Research Database (Denmark)

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

    2008-01-01

    of 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...

  14. 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.

  15. Predicting oligonucleotide-directed mutagenesis failures in protein engineering.

    Science.gov (United States)

    Wassman, Christopher D; Tam, Phillip Y; Lathrop, Richard H; Weiss, Gregory A

    2004-01-01

    Protein engineering uses oligonucleotide-directed mutagenesis to modify DNA sequences through a two-step process of hybridization and enzymatic synthesis. Inefficient reactions confound attempts to introduce mutations, especially for the construction of vast combinatorial protein libraries. This paper applied computational approaches to the problem of inefficient mutagenesis. Several results implicated oligonucleotide annealing to non-target sites, termed 'cross-hybridization', as a significant contributor to mutagenesis reaction failures. Test oligonucleotides demonstrated control over reaction outcomes. A novel cross-hybridization score, quickly computable for any plasmid and oligonucleotide mixture, directly correlated with yields of deleterious mutagenesis side products. Cross-hybridization was confirmed conclusively by partial incorporation of an oligonucleotide at a predicted cross-hybridization site, and by modification of putative template secondary structure to control cross-hybridization. Even in low concentrations, cross-hybridizing species in mixtures poisoned reactions. These results provide a basis for improved mutagenesis efficiencies and increased diversities of cognate protein libraries.

  16. 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...

  17. 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 ...

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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.

  3. 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

  4. 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/.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  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. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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 ...

  18. 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...

  19. 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)

  20. Brain Basics

    Medline Plus

    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 ...

  1. 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 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 ...

  2. Potent Antiscrapie Activities of Degenerate Phosphorothioate Oligonucleotides

    Science.gov (United States)

    Kocisko, David A.; Vaillant, Andrew; Lee, Kil Sun; Arnold, Kevin M.; Bertholet, Nadine; Race, Richard E.; Olsen, Emily A.; Juteau, Jean-Marc; Caughey, Byron

    2006-01-01

    Although transmissible spongiform encephalopathies (TSEs) are incurable, a key therapeutic approach is prevention of conversion of the normal, protease-sensitive form of prion protein (PrP-sen) to the disease-specific protease-resistant form of prion protein (PrP-res). Here degenerate phosphorothioate oligonucleotides (PS-ONs) are introduced as low-nM PrP-res conversion inhibitors with strong antiscrapie activities in vivo. Comparisons of various PS-ON analogs indicated that hydrophobicity and size were important, while base composition was only minimally influential. PS-ONs bound avidly to PrP-sen but could be displaced by sulfated glycan PrP-res inhibitors, indicating the presence of overlapping binding sites. Labeled PS-ONs also bound to PrP-sen on live cells and were internalized. This binding likely accounts for the antiscrapie activity. Prophylactic PS-ON treatments more than tripled scrapie survival periods in mice. Survival times also increased when PS-ONs were mixed with scrapie brain inoculum. With these antiscrapie activities and their much lower anticoagulant activities than that of pentosan polysulfate, degenerate PS-ONs are attractive new compounds for the treatment of TSEs. PMID:16495266

  3. 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.

  4. 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

  5. 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

  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. Silver and Cyanine Staining of Oligonucleotides in Polyacrylamide Gel.

    Directory of Open Access Journals (Sweden)

    Weizhong Tang

    Full Text Available 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 of an oligonucleotide containing base T could be partially or completely inhibited by base T. The inhibition of silver staining by base T was a competitive inhibition which could be affected by the amounts of the argyrophil nucleobase and base T, the cis-distance between the argyrophil nucleobase and base T, and the gel concentration. The changes of the intensity of an oligonucleotide band caused by the changes of DNA base composition were diverse and interesting. The intensity of some oligonucleotide bands would significantly change when the changes of DNA base composition accumulated to a certain extent (usually ≥ 4 nt. The sensitivity of cyanine staining of ≤ 11-nt long oligonucleotides could be enhanced about 250-fold by fixing the gels with methanol fixing solution.

  8. 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.

  9. 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...

  10. Carboranyl oligonucleotides. 3. Biochemical properties of oligonucleotides containing 5-(o-carboranyl-l-yl)-2{prime}-deoxyuridine

    Energy Technology Data Exchange (ETDEWEB)

    Lesnikowski, Z.J.; Fulcrand, G.; Lloyd, R.M. Jr. [Veterans Affairs Medical Center and Georgia Research Center for AIDS and HIV Infections, Decatur, GA (United States)]|[Emory Univ. School of Medicine, Atlanta, GA (United States)

    1996-05-07

    Boronated oligonucleotides are potential candidates for boron neutron capture therapy, antisense technology, and as tools in molecular biology. The biological properties of dodecathymidylic acids containing one or more 5-(o-carboran-l-yl)-2{prime}-deoxyuridine residues at different locations within the oligonucleotide chain were studied. 5-(o-carboran-l-yl)-2{prime}-deoxyuridine containing oligonucleotides manifested marked increased lipophilicity and resistance to 3{prime}- or 5{prime}-phosphodiesterases compared to the corresponding unmodified oligomer. They were substrates for T4 polynucleotide kinase and primers for Escherichia coli polymerase I and human immunodeficiency virus type 1 reverse transcriptase but not for human DNA polymerase {alpha} and {beta}. They also formed heteroduplexes that were substrates for E. coli RNase H, an essential property for antisense technology. These studies indicate that the carboranyl-containing oligonucleotides have desirable properties that need to be exploited further in the design of novel biopharmaceuticals. 33 refs., 2 figs., 1 tab.

  11. 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

  12. 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...

  13. 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 ...

  14. 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...

  15. Basic hydraulics

    CERN Document Server

    Smith, P D

    1982-01-01

    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;

  16. Brain Basics

    Medline Plus

    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 ...

  17. Brain Basics

    Medline Plus

    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 ...

  18. Brain Basics

    Medline Plus

    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 ...

  19. Brain Basics

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    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 ...

  20. 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, ...

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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.

  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

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    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 ...

  7. 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 ...

  8. 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. ...

  9. 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 ...

  10. Brain Basics

    Medline Plus

    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 ...

  11. 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 ...

  12. 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 ...

  13. Brain Basics

    Medline Plus

    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. ...

  14. 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

  15. 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 ...

  16. 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...

  17. 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...

  18. 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

  19. 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

  20. 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.

  1. 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...

  2. 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...... of each member to the residual dipolar coupling signals. We find that molecular fluctuations can affect the alignment and discover a resulting emphasis of certain conformations. However, the internal fluctuations are largely uncorrelated with those of the alignment, implying that proteins have liquidlike...

  3. 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

  4. 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

  5. Galaxy Alignments: An Overview

    Science.gov (United States)

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

    2015-11-01

    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.

  6. 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.

  7. Discriminative Shape Alignment

    DEFF Research Database (Denmark)

    Loog, M.; de Bruijne, M.

    2009-01-01

    The alignment of shape data to a common mean before its subsequent processing is an ubiquitous step within the area shape analysis. Current approaches to shape analysis or, as more specifically considered in this work, shape classification perform the alignment in a fully unsupervised way......, not 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...

  8. 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…

  9. 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 ...

  10. 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 ...

  11. 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.

  12. 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)

  13. Oligonucleotide Tagging for Copper-Free Click Conjugation

    Directory of Open Access Journals (Sweden)

    Alan Rowan

    2013-06-01

    Full Text Available Copper-free click chemistry between cyclooctynes and azide is a mild, fast and selective technology for conjugation of oligonucleotides. However, technology for site-specific introduction of the requisite probes by automated protocols is scarce, while the reported cyclooctynes are large and hydrophobic. In this work, it is demonstrated that the introduction of bicyclo[6.1.0]nonyne (BCN into synthetic oligonucleotides is feasible by standard solid-phase phosphoramidite chemistry. A range of phosphoramidite building blocks is presented for incoporation of BCN or azide, either on-support or in solution. The usefulness of the approach is demonstrated by the straightforward and high-yielding conjugation of the resulting oligonucleotides, including biotinylation, fluorescent labeling, dimerization and attachment to polymer.

  14. 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.

  15. Rapid and accurate synthesis of TALE genes from synthetic oligonucleotides.

    Science.gov (United States)

    Wang, Fenghua; Zhang, Hefei; Gao, Jingxia; Chen, Fengjiao; Chen, Sijie; Zhang, Cuizhen; Peng, Gang

    2016-01-01

    Custom synthesis of transcription activator-like effector (TALE) genes has relied upon plasmid libraries of pre-fabricated TALE-repeat monomers or oligomers. Here we describe a novel synthesis method that directly incorporates annealed synthetic oligonucleotides into the TALE-repeat units. Our approach utilizes iterative sets of oligonucleotides and a translational frame check strategy to ensure the high efficiency and accuracy of TALE-gene synthesis. TALE arrays of more than 20 repeats can be constructed, and the majority of the synthesized constructs have perfect sequences. In addition, this novel oligonucleotide-based method can readily accommodate design changes to the TALE repeats. We demonstrated an increased gene targeting efficiency against a genomic site containing a potentially methylated cytosine by incorporating non-conventional repeat variable di-residue (RVD) sequences.

  16. 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 ...

  17. 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...

  18. A novel catechol-based universal support for oligonucleotide synthesis.

    Science.gov (United States)

    Anderson, Keith M; Jaquinod, Laurent; Jensen, Michael A; Ngo, Nam; Davis, Ronald W

    2007-12-21

    A novel universal support for deoxyribo- and ribonucleic acid synthesis has been developed. The support, constructed from 1,4-dimethoxycatechol, represents an improvement over existing universal supports because of its ability to cleave and deprotect under mild conditions in standard reagents. Because no nonvolatile additives are required for cleavage and deprotection, the synthesized oligonucleotides do not require purification prior to use in biochemical assays. Using reverse phase HPLC and electrospray mass spectroscopy, it was determined that oligonucleotides synthesized on the universal support (UL1) 3'-dephosphorylate quickly (9 h in 28-30% ammonium hydroxide (NH4OH) at 55 degrees C, 2 h in 28-30% NH4OH at 80 degrees C, or <1 h in ammonium hydroxide/methylamine (1:1) (AMA) at 80 degrees C). Oligonucleotides used as primers for the polymerase chain reaction (PCR) assay were found to perform identically to control primers, demonstrating full biological compatibility. In addition, a method was developed for sintering the universal support directly into a filter plug which can be pressure fit into the synthesis column of a commercial synthesizer. The universal support plugs allow the synthesis of high-quality oligonucleotides at least 120 nucleotides in length, with purity comparable to non-universal commercial supports and approximately 50% lower reagent consumption. The universal support plugs are routinely used to synthesize deoxyribo-, ribo-, 3'-modified, 5'-modified, and thioated oligonucleotides. The flexibility of the universal support and the efficiency of 3'-dephosphorylation are expected to increase the use of universal supports in oligonucleotide synthesis.

  19. 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?

  20. 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 ...

  1. 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...

  2. 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...

  3. Incremental Alignment Manifold Learning

    Institute of Scientific and Technical Information of China (English)

    Zhi Han; De-Yu Meng; Zong-Sen Xu; Nan-Nan Gu

    2011-01-01

    A new manifold learning method, called incremental alignment method (IAM), is proposed for nonlinear dimensionality reduction of high dimensional data with intrinsic low dimensionality. The main idea is to incrementally align low-dimensional coordinates of input data patch-by-patch to iteratively generate the representation of the entire dataset. The method consists of two major steps, the incremental step and the alignment step. The incremental step incrementally searches neighborhood patch to be aligned in the next step, and the alignment step iteratively aligns the low-dimensional coordinates of the neighborhood patch searched to generate the embeddings of the entire dataset. Compared with the existing manifold learning methods, the proposed method dominates in several aspects: high efficiency, easy out-of-sample extension, well metric-preserving, and averting of the local minima issue. All these properties are supported by a series of experiments performed on the synthetic and real-life datasets. In addition, the computational complexity of the proposed method is analyzed, and its efficiency is theoretically argued and experimentally demonstrated.

  4. Wavelet basics

    CERN Document Server

    Chan, Y T

    1995-01-01

    Since the study of wavelets is a relatively new area, much of the research coming from mathematicians, most of the literature uses terminology, concepts and proofs that may, at times, be difficult and intimidating for the engineer. Wavelet Basics has therefore been written as an introductory book for scientists and engineers. The mathematical presentation has been kept simple, the concepts being presented in elaborate detail in a terminology that engineers will find familiar. Difficult ideas are illustrated with examples which will also aid in the development of an intuitive insight. Chapter 1 reviews the basics of signal transformation and discusses the concepts of duals and frames. Chapter 2 introduces the wavelet transform, contrasts it with the short-time Fourier transform and clarifies the names of the different types of wavelet transforms. Chapter 3 links multiresolution analysis, orthonormal wavelets and the design of digital filters. Chapter 4 gives a tour d'horizon of topics of current interest: wave...

  5. 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…

  6. 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...

  7. MaxAlign: maximizing usable data in an alignment

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...

  8. 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.

  9. 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

  10. Oligonucleotides with 1,4-dioxane-based nucleotide monomers

    DEFF Research Database (Denmark)

    Madsen, Andreas S; Wengel, Jesper

    2012-01-01

    An epimeric mixture of H-phosphonates 5R and 5S has been synthesized in three steps from known secouridine 1. Separation of the epimers has been accomplished by RP-HPLC, allowing full characterization and incorporation of monomers X and Y into 9-mer oligonucleotides using H-phosphonates building ...

  11. LNA 5'-phosphoramidites for 5'→3'-oligonucleotide synthesis

    DEFF Research Database (Denmark)

    Madsen, Andreas Stahl; Kumar, Santhosh T.; Wengel, Jesper

    2010-01-01

    Hereby we report an efficient synthesis of LNA thymine and LNA 5-methylcytosine 5′-phosphoramidites, allowing incorporation of LNA thymine and LNA 5-methylcytosine into oligonucleotides synthesized in the 5′→3′ direction. Key steps include regioselective enzymatic benzoylation of the 5′-hydroxy...

  12. 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.

  13. 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

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. RNA Structural Alignments, Part I

    DEFF Research Database (Denmark)

    Havgaard, Jakob Hull; Gorodkin, Jan

    2014-01-01

    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...

  19. 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:

  20. 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

  1. 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)

  2. Magnetically aligned supramolecular hydrogels.

    Science.gov (United States)

    Wallace, Matthew; Cardoso, Andre Zamith; Frith, William J; Iggo, Jonathan A; Adams, Dave J

    2014-12-01

    The magnetic-field-induced alignment of the fibrillar structures present in an aqueous solution of a dipeptide gelator, and the subsequent retention of this alignment upon transformation to a hydrogel upon the addition of CaCl2 or upon a reduction in solution pH is reported. Utilising the switchable nature of the magnetic field coupled with the slow diffusion of CaCl2 , it is possible to precisely control the extent of anisotropy across a hydrogel, something that is generally very difficult to do using alternative methods. The approach is readily extended to other compounds that form viscous solutions at high pH. It is expected that this work will greatly expand the utility of such low-molecular-weight gelators (LMWG) in areas where alignment is key. PMID:25345918

  3. 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

  4. 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...

  5. Orientation and Alignment Echoes

    CERN Document Server

    Karras, G; Billard, F; Lavorel, B; Hartmann, J -M; Faucher, O; Gershnabel, E; Prior, Y; Averbukh, I Sh

    2015-01-01

    We present what is probably the simplest classical system featuring the echo phenomenon - a collection of randomly oriented free rotors with dispersed rotational velocities. Following excitation by a pair of time-delayed impulsive kicks, the mean orientation/alignment of the ensemble exhibits multiple echoes and fractional echoes. We elucidate the mechanism of the echo formation by kick-induced filamentation of phase space, and provide the first experimental demonstration of classical alignment echoes in a thermal gas of CO_2 molecules excited by a pair of femtosecond laser pulses.

  6. 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...... on the application of the BMG to publicly available datasets, the Leuven natural concept database [3] representing semantic structures of domain knowledge possessed by individual subjects [3]. Results indicate that the BMG is potentially a model applicable to simulating the alignment of domain knowledge from...

  7. PILOT optical alignment

    Science.gov (United States)

    Longval, Y.; Mot, B.; Ade, P.; André, Y.; Aumont, J.; Baustista, L.; Bernard, J.-Ph.; Bray, N.; de Bernardis, P.; Boulade, O.; Bousquet, F.; Bouzit, M.; Buttice, V.; Caillat, A.; Charra, M.; Chaigneau, M.; Crane, B.; Crussaire, J.-P.; Douchin, F.; Doumayrou, E.; Dubois, J.-P.; Engel, C.; Etcheto, P.; Gélot, P.; Griffin, M.; Foenard, G.; Grabarnik, S.; Hargrave, P..; Hughes, A.; Laureijs, R.; Lepennec, Y.; Leriche, B.; Maestre, S.; Maffei, B.; Martignac, J.; Marty, C.; Marty, W.; Masi, S.; Mirc, F.; Misawa, R.; Montel, J.; Montier, L.; Narbonne, J.; Nicot, J.-M.; Pajot, F.; Parot, G.; Pérot, E.; Pimentao, J.; Pisano, G.; Ponthieu, N.; Ristorcelli, I.; Rodriguez, L.; Roudil, G.; Salatino, M.; Savini, G.; Simonella, O.; Saccoccio, M.; Tapie, P.; Tauber, J.; Torre, J.-P.; Tucker, C.

    2016-07-01

    PILOT is a balloon-borne astronomy experiment designed to study the polarization of dust emission in the diffuse interstellar medium in our Galaxy at wavelengths 240 μm with an angular resolution about two arcminutes. Pilot optics is composed an off-axis Gregorian type telescope and a refractive re-imager system. All optical elements, except the primary mirror, are in a cryostat cooled to 3K. We combined the optical, 3D dimensional measurement methods and thermo-elastic modeling to perform the optical alignment. The talk describes the system analysis, the alignment procedure, and finally the performances obtained during the first flight in September 2015.

  8. 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...

  9. 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.

  10. Parameters for accurate genome alignment

    Directory of Open Access Journals (Sweden)

    Hamada Michiaki

    2010-02-01

    Full Text Available Abstract Background Genome sequence alignments form the basis of much research. Genome alignment depends on various mundane but critical choices, such as how to mask repeats and which score parameters to use. Surprisingly, there has been no large-scale assessment of these choices using real genomic data. Moreover, rigorous procedures to control the rate of spurious alignment have not been employed. Results We have assessed 495 combinations of score parameters for alignment of animal, plant, and fungal genomes. As our gold-standard of accuracy, we used genome alignments implied by multiple alignments of proteins and of structural RNAs. We found the HOXD scoring schemes underlying alignments in the UCSC genome database to be far from optimal, and suggest better parameters. Higher values of the X-drop parameter are not always better. E-values accurately indicate the rate of spurious alignment, but only if tandem repeats are masked in a non-standard way. Finally, we show that γ-centroid (probabilistic alignment can find highly reliable subsets of aligned bases. Conclusions These results enable more accurate genome alignment, with reliability measures for local alignments and for individual aligned bases. This study was made possible by our new software, LAST, which can align vertebrate genomes in a few hours http://last.cbrc.jp/.

  11. Inflation Basics

    Energy Technology Data Exchange (ETDEWEB)

    Green, Dan [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2014-03-01

    inflation since metrical fluctuations, both scalar and tensor, are also produced in inflationary models. Thus, the time appears to be appropriate for a very basic and simple exposition of the inflationary model written from a particle physics perspective. Only the simplest scalar model will be explored because it is easy to understand and contains all the basic elements of the inflationary model.

  12. 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.

  13. 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.

  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. MUSE alignment onto VLT

    Science.gov (United States)

    Laurent, Florence; Renault, Edgard; Boudon, Didier; Caillier, Patrick; Daguisé, Eric; Dupuy, Christophe; Jarno, Aurélien; Lizon, Jean-Louis; Migniau, Jean-Emmanuel; Nicklas, Harald; Piqueras, Laure

    2014-07-01

    MUSE (Multi Unit Spectroscopic Explorer) is a second generation Very Large Telescope (VLT) integral field spectrograph developed for the European Southern Observatory (ESO). It combines a 1' x 1' field of view sampled at 0.2 arcsec for its Wide Field Mode (WFM) and a 7.5"x7.5" field of view for its Narrow Field Mode (NFM). Both modes will operate with the improved spatial resolution provided by GALACSI (Ground Atmospheric Layer Adaptive Optics for Spectroscopic Imaging), that will use the VLT deformable secondary mirror and 4 Laser Guide Stars (LGS) foreseen in 2015. MUSE operates in the visible wavelength range (0.465-0.93 μm). A consortium of seven institutes is currently commissioning MUSE in the Very Large Telescope for the Preliminary Acceptance in Chile, scheduled for September, 2014. 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 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 2012 and 2013, all MUSE subsystems were integrated, aligned and tested to the P.I. institute at Lyon. After successful PAE in September 2013, MUSE instrument was shipped to the Very Large Telescope in Chile where that was aligned and tested in ESO integration hall at Paranal. After, MUSE was directly transported, fully aligned and without any optomechanical dismounting, onto VLT telescope where the first light was overcame the 7th of February, 2014. This paper describes the alignment procedure of the whole MUSE instrument with respect to the Very Large Telescope (VLT). It describes how 6 tons could be move with accuracy better than 0.025mm and less than 0.25 arcmin in order to reach alignment requirements. The success

  16. Palladium-Catalyzed Modification of Unprotected Nucleosides, Nucleotides, and Oligonucleotides

    Directory of Open Access Journals (Sweden)

    Kevin H. Shaughnessy

    2015-05-01

    Full Text Available Synthetic modification of nucleoside structures provides access to molecules of interest as pharmaceuticals, biochemical probes, and models to study diseases. Covalent modification of the purine and pyrimidine bases is an important strategy for the synthesis of these adducts. Palladium-catalyzed cross-coupling is a powerful method to attach groups to the base heterocycles through the formation of new carbon-carbon and carbon-heteroatom bonds. In this review, approaches to palladium-catalyzed modification of unprotected nucleosides, nucleotides, and oligonucleotides are reviewed. Polar reaction media, such as water or polar aprotic solvents, allow reactions to be performed directly on the hydrophilic nucleosides and nucleotides without the need to use protecting groups. Homogeneous aqueous-phase coupling reactions catalyzed by palladium complexes of water-soluble ligands provide a general approach to the synthesis of modified nucleosides, nucleotides, and oligonucleotides.

  17. Typing of enteroviruses by use of microwell oligonucleotide arrays.

    Science.gov (United States)

    Susi, P; Hattara, L; Waris, M; Luoma-Aho, T; Siitari, H; Hyypiä, T; Saviranta, P

    2009-06-01

    We have developed a straightforward assay for the rapid typing of enteroviruses using oligonucleotide arrays in microtiter wells. The viral nucleic acids are concomitantly amplified and labeled during reverse transcription-PCR, and unpurified PCR products are used for hybridization. DNA strands are separated by alkaline denaturation, and hybridization is started by neutralization. The microarray hybridization reactions and the subsequent washes are performed in standard 96-well microtiter plates, which makes the method easily adaptable to high-throughput analysis. We describe here the assay principle and its potential in clinical laboratory use by correctly identifying 10 different enterovirus reference strains. Furthermore, we explore the detection of unknown sequence variants using serotype consensus oligonucleotide probes. With just two consensus probes for the coxsackievirus A9 (CVA9) serotype, we detected 23 out of 25 highly diverse CVA9 isolates. Overall, the assay involves several features aiming at ease of performance, robustness, and applicability to large-scale studies.

  18. 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.

  19. 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.

  20. 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.

  1. Block Copolymer Nanocomposites in Electric Fields: Kinetics of Alignment

    Energy Technology Data Exchange (ETDEWEB)

    Liedel, Clemens [RWTH Aachen University; Pester, Christian [RWTH Aachen University; Ruppel, Markus A [ORNL; Lewin, Christian [RWTH Aachen University; Pavan, Mariela J. [Hebrew University of Jerusalem; Urban, Volker S [ORNL; Shenhar, Roy [Hebrew University of Jerusalem; Bosecke, Peter [European Synchrotron Radiation Facility (ESRF); Boker, Alexander [RWTH Aachen University

    2013-01-01

    We investigate the kinetics of block copolymer/nanoparticle composite alignment in an electric field using in situ transmission small-angle X-ray scattering. As a model system, we employ a lamellae forming polystyrene-block-poly(2-vinyl pyridine) block copolymer with different contents of gold nanoparticles in thick films under solvent vapor annealing. While the alignment improves with increasing nanoparticle fraction, the kinetics slows down. This is explained by changes in the degree of phase separation and viscosity. Our findings provide extended insights into the basics of nanocomposite alignment.

  2. Time Interference Alignment via Delay Offset for Long Delay Networks

    CERN Document Server

    Blasco, Francisco Lazaro; Bauch, Gerhard

    2011-01-01

    Time Interference Alignment is a flavor of Interference Alignment that increases the network capacity by suitably staggering the transmission delays of the senders. In this work the analysis of the existing literature is generalized and the focus is on the computation of the dof for networks with randomly placed users in a n-dimensional Euclidean space. In the basic case without coordination among the transmitters analytical expressions of the sum dof can be derived. If the transmit delays are coordinated, in 20% of the cases time Interference Alignment yields additional dof with respect to orthogonal access schemes. The potential capacity improvements for satellite networks are also investigated.

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

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Lund, Ole

    2007-01-01

    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...... benchmark data set, and SMM-align prediction method (NetMHCII) are made publicly available....

  4. Formatt: Correcting protein multiple structural alignments by incorporating sequence alignment

    Directory of Open Access Journals (Sweden)

    Daniels Noah M

    2012-10-01

    Full Text Available Abstract Background The quality of multiple protein structure alignments are usually computed and assessed based on geometric functions of the coordinates of the backbone atoms from the protein chains. These purely geometric methods do not utilize directly protein sequence similarity, and in fact, determining the proper way to incorporate sequence similarity measures into the construction and assessment of protein multiple structure alignments has proved surprisingly difficult. Results We present Formatt, a multiple structure alignment based on the Matt purely geometric multiple structure alignment program, that also takes into account sequence similarity when constructing alignments. We show that Formatt outperforms Matt and other popular structure alignment programs on the popular HOMSTRAD benchmark. For the SABMark twilight zone benchmark set that captures more remote homology, Formatt and Matt outperform other programs; depending on choice of embedded sequence aligner, Formatt produces either better sequence and structural alignments with a smaller core size than Matt, or similarly sized alignments with better sequence similarity, for a small cost in average RMSD. Conclusions Considering sequence information as well as purely geometric information seems to improve quality of multiple structure alignments, though defining what constitutes the best alignment when sequence and structural measures would suggest different alignments remains a difficult open question.

  5. 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...

  6. 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 ...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. Characterization of self-assembled DNA concatemers from synthetic oligonucleotides

    Directory of Open Access Journals (Sweden)

    Lu Sun

    2014-08-01

    Full Text Available Studies of DNA–ligand interaction on a single molecule level provide opportunities to understand individual behavior of molecules. Construction of DNA molecules with repetitive copies of the same segments of sequences linked in series could be helpful for enhancing the interaction possibility for sequence-specific binding ligand to DNA. Here we report on the use of synthetic oligonucleotides to self-assembly into duplex DNA concatemeric molecules. Two strands of synthetic oligonucleotides used here were designed with 50-mer in length and the sequences are semi-complimentary so to hybridize spontaneously into concatemers of double stranded DNA. In order to optimize the length of the concatemers the oligonucleotides were incubated at different oligomer concentrations, ionic strengths and temperatures for different durations. Increasing the salt concentration to 200 mM NaCl was found to be the major optimizing factor because at this enhanced ionic strength the concatemers formed most quickly and the other parameters had no detectable effect. The size and shape of formed DNA concatemers were studied by gel electrophoresis in agarose, polyacrylamide gels and by AFM. Our results show that linear DNA constructs up to several hundred base pairs were formed and could be separated from a substantial fraction of non-linear constructs.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Orbit IMU alignment: Error analysis

    Science.gov (United States)

    Corson, R. W.

    1980-01-01

    A comprehensive accuracy analysis of orbit inertial measurement unit (IMU) alignments using the shuttle star trackers was completed and the results are presented. Monte Carlo techniques were used in a computer simulation of the IMU alignment hardware and software systems to: (1) determine the expected Space Transportation System 1 Flight (STS-1) manual mode IMU alignment accuracy; (2) investigate the accuracy of alignments in later shuttle flights when the automatic mode of star acquisition may be used; and (3) verify that an analytical model previously used for estimating the alignment error is a valid model. The analysis results do not differ significantly from expectations. The standard deviation in the IMU alignment error for STS-1 alignments was determined to the 68 arc seconds per axis. This corresponds to a 99.7% probability that the magnitude of the total alignment error is less than 258 arc seconds.

  2. 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.

  3. Alignment of concerns

    DEFF Research Database (Denmark)

    Andersen, Tariq Osman; Bansler, Jørgen P.; Kensing, Finn;

    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’....

  4. Alignment reference device

    Science.gov (United States)

    Patton, Gail Y.; Torgerson, Darrel D.

    1987-01-01

    An alignment reference device provides a collimated laser beam that minimizes angular deviations therein. A laser beam source outputs the beam into a single mode optical fiber. The output end of the optical fiber acts as a source of radiant energy and is positioned at the focal point of a lens system where the focal point is positioned within the lens. The output beam reflects off a mirror back to the lens that produces a collimated beam.

  5. 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...

  6. 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…

  7. Alignment Pins for Assembling and Disassembling Structures

    Science.gov (United States)

    Campbell, Oliver C.

    2008-01-01

    Simple, easy-to-use, highly effective tooling has been devised for maintaining alignment of bolt holes in mating structures during assembly and disassembly of the structures. The tooling was originally used during removal of a body flap from the space shuttle Atlantis, in which misalignments during removal of the last few bolts could cause the bolts to bind in their holes. By suitably modifying the dimensions of the tooling components, the basic design of the tooling can readily be adapted to other structures that must be maintained in alignment. The tooling includes tapered, internally threaded alignment pins designed to fit in the bolt holes in one of the mating structures, plus a draw bolt and a cup that are used to install or remove each alignment pin. In preparation for disassembly of two mating structures, external supports are provided to prevent unintended movement of the structures. During disassembly of the structures, as each bolt that joins the structures is removed, an alignment pin is installed in its place. Once all the bolts have been removed and replaced with pins, the pins maintain alignment as the structures are gently pushed or pulled apart on the supports. In assembling the two structures, one reverses the procedure described above: pins are installed in the bolt holes, the structures are pulled or pushed together on the supports, then the pins are removed and replaced with bolts. The figure depicts the tooling and its use. To install an alignment pin in a bolt hole in a structural panel, the tapered end of the pin is inserted from one side of the panel, the cup is placed over the pin on the opposite side of the panel, the draw bolt is inserted through the cup and threaded into the pin, the draw bolt is tightened to pull the pin until the pin is seated firmly in the hole, then the draw bolt and cup are removed, leaving the pin in place. To remove an alignment pin, the cup is placed over the pin on the first-mentioned side of the panel, the draw

  8. 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.

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

    Science.gov (United States)

    Cao, Boyang; Liu, Xiangqian; Yu, Xiang; Chen, Min; Feng, Lu; Wang, Lei

    2014-01-01

    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. PMID:25469776

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. CELT optics Alignment Procedure

    Science.gov (United States)

    Mast, Terry S.; Nelson, Jerry E.; Chanan, Gary A.; Noethe, Lothar

    2003-01-01

    The California Extremely Large Telescope (CELT) is a project to build a 30-meter diameter telescope for research in astronomy at visible and infrared wavelengths. The current optical design calls for a primary, secondary, and tertiary mirror with Ritchey-Chretién foci at two Nasmyth platforms. The primary mirror is a mosaic of 1080 actively-stabilized hexagonal segments. This paper summarizes a CELT report that describes a step-by-step procedure for aligning the many degrees of freedom of the CELT optics.

  16. Alignment of concerns

    DEFF Research Database (Denmark)

    Andersen, Tariq Osman; Bansler, Jørgen P.; Kensing, Finn;

    2014-01-01

    The emergence of patient-centered eHealth systems introduces new challenges, where patients come to play an increasingly important role. Realizing the promises requires an in-depth understanding of not only the technology, but also the needs of both clinicians and patients. However, insights from...... medical phenomenology bring forth how physicians and patients focus on different aspects of illness and that they often have starkly divergent concerns. This has important implications for the design of eHealth systems that seek to engage patients as active participants. We emphasize the crucial...... as a design rationale for successful eHealth, termed 'alignment of concerns'....

  17. 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

  18. ATLAS Inner Detector Alignment

    CERN Document Server

    Bocci, A

    2008-01-01

    The ATLAS experiment is a multi-purpose particle detector that will study high-energy particle collisions produced by the Large Hadron Collider at CERN. In order to achieve its physics goals, the ATLAS tracking requires that the positions of the silicon detector elements have to be known to a precision better than 10 μm. Several track-based alignment algorithms have been developed for the Inner Detector. An extensive validation has been performed with simulated events and real data coming from the ATLAS. Results from such validation are reported in this paper.

  19. TSGC and JSC Alignment

    Science.gov (United States)

    Sanchez, Humberto

    2013-01-01

    NASA and the SGCs are, by design, intended to work closely together and have synergistic Vision, Mission, and Goals. The TSGC affiliates and JSC have been working together, but not always in a concise, coordinated, nor strategic manner. Today we have a couple of simple ideas to present about how TSGC and JSC have started to work together in a more concise, coordinated, and strategic manner, and how JSC and non-TSG Jurisdiction members have started to collaborate: Idea I: TSGC and JSC Technical Alignment Idea II: Concept of Clusters.

  20. Hemopoiesis-stimulating activity of immobilized oligonucleotides and hyaluronidase during cytostatic-induced myelosuppression.

    Science.gov (United States)

    Dygai, A M; Skurikhin, E G; Pershina, O V; Zhdanov, V V; Khmelevskaya, A M; Andreeva, T V; Poponina, A M; Zjuzkov, G N; Udut, E V; Khrichkova, T Ju; Simanina, E V; Miroshnichenko, L A; Stavrova, L A; Tchaikovsky, A S; Markova, T S; Gurto, R V; Brjushinina, O S; Slepichev, V A

    2011-03-01

    The hemopoiesis-stimulating effect of combined treatment with immobilized oligonucleotides and hyaluronidase preparations was studied during cytostatic-induced myelosuppression caused by cyclophosphamide administration. Immobilized hyaluronidase was shown to increase the efficiency of correction of changes in the erythroid and granulocytic hemopoietic stems with immobilized oligonucleotides. This potentiation of the effect of immobilized oligonucleotides by immobilized hyaluronidase was related to an increase in functional activity of committed hemopoietic precursors.

  1. 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...

  2. 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...

  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. 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...

  6. Efficient assessment of modified nucleoside stability under conditions of automated oligonucleotide synthesis: characterization of the oxidation and oxidative desulfurization of 2-thiouridine.

    Science.gov (United States)

    Sochacka, E

    2001-01-01

    In order to efficiently assess the chemical stability of modified nucleosides to the reagents and conditions of automated oligonucleotide synthesis, we designed, developed and tested a scheme in which the modified nucleoside, directly attached to a solid support, is exposed to the cyclic chemistry of the instrument. Stability of 2-thiouridine against different oxidizers was investigated. Tertbutyl hydroperoxide (1 M) in anhydrous acetonitrile was a more effective oxidizer for the incorporation of 2-thiouridine into oligonucleotide chains than the same oxidizer in methylene chloride. Carbon tetrachloride/water in the presence of a basic catalyst was superior in maintaining the thiocarbonyl function, but its utility for RNA synthesis has yet to be fully tested, whereas 2-phenylsulfonyloxaziridine was a very efficient reagent for oxidative desulfurization of 2-thiouridine. PMID:11720000

  7. 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...

  8. 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...

  9. 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

  10. Overcoming low-alignment signal contrast induced alignment failure by alignment signal enhancement

    Science.gov (United States)

    Lee, Byeong Soo; Kim, Young Ha; Hwang, Hyunwoo; Lee, Jeongjin; Kong, Jeong Heung; Kang, Young Seog; Paarhuis, Bart; Kok, Haico; de Graaf, Roelof; Weichselbaum, Stefan; Droste, Richard; Mason, Christopher; Aarts, Igor; de Boeij, Wim P.

    2016-03-01

    Overlay is one of the key factors which enables optical lithography extension to 1X node DRAM manufacturing. It is natural that accurate wafer alignment is a prerequisite for good device overlay. However, alignment failures or misalignments are commonly observed in a fab. There are many factors which could induce alignment problems. Low alignment signal contrast is one of the main issues. Alignment signal contrast can be degraded by opaque stack materials or by alignment mark degradation due to processes like CMP. This issue can be compounded by mark sub-segmentation from design rules in combination with double or quadruple spacer process. Alignment signal contrast can be improved by applying new material or process optimization, which sometimes lead to the addition of another process-step with higher costs. If we can amplify the signal components containing the position information and reduce other unwanted signal and background contributions then we can improve alignment performance without process change. In this paper we use ASML's new alignment sensor (as was introduced and released on the NXT:1980Di) and sample wafers with special stacks which can induce poor alignment signal to demonstrate alignment and overlay improvement.

  11. Pareto optimal pairwise sequence alignment.

    Science.gov (United States)

    DeRonne, Kevin W; Karypis, George

    2013-01-01

    Sequence alignment using evolutionary profiles is a commonly employed tool when investigating a protein. Many profile-profile scoring functions have been developed for use in such alignments, but there has not yet been a comprehensive study of Pareto optimal pairwise alignments for combining multiple such functions. We show that the problem of generating Pareto optimal pairwise alignments has an optimal substructure property, and develop an efficient algorithm for generating Pareto optimal frontiers of pairwise alignments. All possible sets of two, three, and four profile scoring functions are used from a pool of 11 functions and applied to 588 pairs of proteins in the ce_ref data set. The performance of the best objective combinations on ce_ref is also evaluated on an independent set of 913 protein pairs extracted from the BAliBASE RV11 data set. Our dynamic-programming-based heuristic approach produces approximated Pareto optimal frontiers of pairwise alignments that contain comparable alignments to those on the exact frontier, but on average in less than 1/58th the time in the case of four objectives. Our results show that the Pareto frontiers contain alignments whose quality is better than the alignments obtained by single objectives. However, the task of identifying a single high-quality alignment among those in the Pareto frontier remains challenging.

  12. 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.

  13. Chemically modified oligonucleotides with efficient RNase H response

    DEFF Research Database (Denmark)

    Vester, Birte; Boel, Anne Marie; Lobedanz, Sune;

    2008-01-01

    Ten different chemically modified nucleosides were incorporated into short DNA strands (chimeric oligonucleotides ON3-ON12 and ON15-ON24) and then tested for their capacity to mediate RNAse H cleavage of the complementary RNA strand. The modifications were placed at two central positions directly...... in the RNase H cleaving region. The RNA strand of duplexes with ON3, ON5 and ON12 were cleaved more efficiently than the RNA strand of the DNA:RNA control duplex. There seems to be no correlation between the thermal stability between the duplexes and RNase H cleavage....

  14. 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

  15. 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.

  16. 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.

  17. 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...

  18. Onorbit IMU alignment error budget

    Science.gov (United States)

    Corson, R. W.

    1980-01-01

    The Star Tracker, Crew Optical Alignment Sight (COAS), and Inertial Measurement Unit (IMU) from a complex navigation system with a multitude of error sources were combined. A complete list of the system errors is presented. The errors were combined in a rational way to yield an estimate of the IMU alignment accuracy for STS-1. The expected standard deviation in the IMU alignment error for STS-1 type alignments was determined to be 72 arc seconds per axis for star tracker alignments and 188 arc seconds per axis for COAS alignments. These estimates are based on current knowledge of the star tracker, COAS, IMU, and navigation base error specifications, and were partially verified by preliminary Monte Carlo analysis.

  19. 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.

  20. 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.

  1. 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.

  2. The alignment strategy of HADES

    Energy Technology Data Exchange (ETDEWEB)

    Pechenova, O., E-mail: O.Pechenova@gsi.de [Institut für Kernphysik, Johann Wolfgang Goethe-Universität, 60438 Frankfurt (Germany); Pechenov, V. [GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt (Germany); Galatyuk, T. [GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt (Germany); Technische Universität Darmstadt, D-64289 Darmstadt (Germany); Hennino, T. [Institut de Physique Nucléaire (UMR 8608), CNRS/IN2P3 – Université Paris Sud, F-91406 Orsay Cedex (France); Holzmann, R. [GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt (Germany); Kornakov, G. [Departamento de Física de Partículas, Univ. de Santiago de Compostela, 15706 Santiago de Compostela (Spain); Technische Universität Darmstadt, D-64289 Darmstadt (Germany); Markert, J.; Müntz, C. [Institut für Kernphysik, Johann Wolfgang Goethe-Universität, 60438 Frankfurt (Germany); Salabura, P. [Smoluchowski Institute of Physics, Jagiellonian University of Kraków, 30-059 Kraków (Poland); Schmah, A. [Lawrence Berkeley National Laboratory, Berkeley (United States); Schwab, E. [GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt (Germany); Stroth, J. [Institut für Kernphysik, Johann Wolfgang Goethe-Universität, 60438 Frankfurt (Germany); GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt (Germany)

    2015-06-11

    The global as well as intrinsic alignment of any spectrometer impacts directly on its performance and the quality of the achievable physics results. An overview of the current alignment procedure of the DiElectron Spectrometer HADES is presented with an emphasis on its main features and its accuracy. The sequence of all steps and procedures is given, including details on photogrammetric and track-based alignment.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Affinity hydrogels for controlled protein release using nucleic acid aptamers and complementary oligonucleotides.

    Science.gov (United States)

    Soontornworajit, Boonchoy; Zhou, Jing; Snipes, Matthew P; Battig, Mark R; Wang, Yong

    2011-10-01

    Biomaterials for the precise control of protein release are important to the development of new strategies for treating human diseases. This study aimed to fundamentally understand aptamer--protein dissociation triggered by complementary oligonucleotides, and to apply this understanding to develop affinity hydrogels for controlled protein release. The results showed that the oligonucleotide tails of the aptamers played a critical role in inducing intermolecular hybridization and triggering aptamer--protein dissociation. In addition, the attachment of the oligonucleotide tails to the aptamers and the increase of hybridizing length could produce a synergistic effect on the dissociation of bound proteins from their aptamers. More importantly, pegylated complementary oligonucleotides could successfully trigger protein release from the aptamer-functionalized hydrogels at multiple time points. Based on these results, it is believed that aptamer-functionalized hydrogels and complementary oligonucleotides hold great potential of controlling the release of protein drugs to treat human diseases.

  11. 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/....

  12. Vacuum Alignment with more Flavors

    DEFF Research Database (Denmark)

    Ryttov, Thomas

    2014-01-01

    We study the alignment of the vacuum in gauge theories with $N_f$ Dirac fermions transforming according to a complex representation of the gauge group. The alignment of the vacuum is produced by adding a small mass perturbation to the theory. We study in detail the $N_f=2,3$ and $4$ case. For $N...

  13. CATO: The Clone Alignment Tool.

    Directory of Open Access Journals (Sweden)

    Peter V Henstock

    Full Text Available High-throughput cloning efforts produce large numbers of sequences that need to be aligned, edited, compared with reference sequences, and organized as files and selected clones. Different pieces of software are typically required to perform each of these tasks. We have designed a single piece of software, CATO, the Clone Alignment Tool, that allows a user to align, evaluate, edit, and select clone sequences based on comparisons to reference sequences. The input and output are designed to be compatible with standard data formats, and thus suitable for integration into a clone processing pipeline. CATO provides both sequence alignment and visualizations to facilitate the analysis of cloning experiments. The alignment algorithm matches each of the relevant candidate sequences against each reference sequence. The visualization portion displays three levels of matching: 1 a top-level summary of the top candidate sequences aligned to each reference sequence, 2 a focused alignment view with the nucleotides of matched sequences displayed against one reference sequence, and 3 a pair-wise alignment of a single reference and candidate sequence pair. Users can select the minimum matching criteria for valid clones, edit or swap reference sequences, and export the results to a summary file as part of the high-throughput cloning workflow.

  14. 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.

  15. Alignment of flexible protein structures.

    Science.gov (United States)

    Shatsky, M; Fligelman, Z Y; Nussinov, R; Wolfson, H J

    2000-01-01

    We present two algorithms which align flexible protein structures. Both apply efficient structural pattern detection and graph theoretic techniques. The FlexProt algorithm simultaneously detects the hinge regions and aligns the rigid subparts of the molecules. It does it by efficiently detecting maximal congruent rigid fragments in both molecules and calculating their optimal arrangement which does not violate the protein sequence order. The FlexMol algorithm is sequence order independent, yet requires as input the hypothesized hinge positions. Due its sequence order independence it can also be applied to protein-protein interface matching and drug molecule alignment. It aligns the rigid parts of the molecule using the Geometric Hashing method and calculates optimal connectivity among these parts by graph-theoretic techniques. Both algorithms are highly efficient even compared with rigid structure alignment algorithms. Typical running times on a standard desktop PC (400 MHz) are about 7 seconds for FlexProt and about 1 minute for FlexMol.

  16. 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.

  17. 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.

  18. Space Mirror Alignment System

    Science.gov (United States)

    Jau, Bruno M.; McKinney, Colin; Smythe, Robert F.; Palmer, Dean L.

    2011-01-01

    An optical alignment mirror mechanism (AMM) has been developed with angular positioning accuracy of +/-0.2 arcsec. This requires the mirror s linear positioning actuators to have positioning resolutions of +/-112 nm to enable the mirror to meet the angular tip/tilt accuracy requirement. Demonstrated capabilities are 0.1 arc-sec angular mirror positioning accuracy, which translates into linear positioning resolutions at the actuator of 50 nm. The mechanism consists of a structure with sets of cross-directional flexures that enable the mirror s tip and tilt motion, a mirror with its kinematic mount, and two linear actuators. An actuator comprises a brushless DC motor, a linear ball screw, and a piezoelectric brake that holds the mirror s position while the unit is unpowered. An interferometric linear position sensor senses the actuator s position. The AMMs were developed for an Astrometric Beam Combiner (ABC) optical bench, which is part of an interferometer development. Custom electronics were also developed to accommodate the presence of multiple AMMs within the ABC and provide a compact, all-in-one solution to power and control the AMMs.

  19. Magnetic alignment and the Poisson alignment reference system

    Science.gov (United States)

    Griffith, L. V.; Schenz, R. F.; Sommargren, G. E.

    1990-08-01

    Three distinct metrological operations are necessary to align a free-electron laser (FEL): the magnetic axis must be located, a straight line reference (SLR) must be generated, and the magnetic axis must be related to the SLR. This article begins with a review of the motivation for developing an alignment system that will assure better than 100-μm accuracy in the alignment of the magnetic axis throughout an FEL. The 100-μm accuracy is an error circle about an ideal axis for 300 m or more. The article describes techniques for identifying the magnetic axes of solenoids, quadrupoles, and wiggler poles. Propagation of a laser beam is described to the extent of revealing sources of nonlinearity in the beam. Development of a straight-line reference based on the Poisson line, a diffraction effect, is described in detail. Spheres in a large-diameter laser beam create Poisson lines and thus provide a necessary mechanism for gauging between the magnetic axis and the SLR. Procedures for installing FEL components and calibrating alignment fiducials to the magnetic axes of the components are also described. The Poisson alignment reference system should be accurate to 25 μm over 300 m, which is believed to be a factor-of-4 improvement over earlier techniques. An error budget shows that only 25% of the total budgeted tolerance is used for the alignment reference system, so the remaining tolerances should fall within the allowable range for FEL alignment.

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. Enhanced gene repair mediated by methyl-CpG-modified single-stranded oligonucleotides

    Science.gov (United States)

    Bertoni, Carmen; Rustagi, Arjun; Rando, Thomas A.

    2009-01-01

    Gene editing mediated by oligonucleotides has been shown to induce stable single base alterations in genomic DNA in both prokaryotic and eukaryotic organisms. However, the low frequencies of gene repair have limited its applicability for both basic manipulation of genomic sequences and for the development of therapeutic approaches for genetic disorders. Here, we show that single-stranded oligodeoxynucleotides (ssODNs) containing a methyl-CpG modification and capable of binding to the methyl-CpG binding domain protein 4 (MBD4) are able to induce >10-fold higher levels of gene correction than ssODNs lacking the specific modification. Correction was stably inherited through cell division and was confirmed at the protein, transcript and genomic levels. Downregulation of MBD4 expression using RNAi prevented the enhancement of gene correction efficacy obtained using the methyl-CpG-modified ssODN, demonstrating the specificity of the repair mechanism being recruited. Our data demonstrate that efficient manipulation of genomic targets can be achieved and controlled by the type of ssODN used and by modulation of the repair mechanism involved in the correction process. This new generation of ssODNs represents an important technological advance that is likely to have an impact on multiple applications, especially for gene therapy where permanent correction of the genetic defect has clear advantages over viral and other nonviral approaches currently being tested. PMID:19854937

  5. A review of statistical methods for preprocessing oligonucleotide microarrays.

    Science.gov (United States)

    Wu, Zhijin

    2009-12-01

    Microarrays have become an indispensable tool in biomedical research. This powerful technology not only makes it possible to quantify a large number of nucleic acid molecules simultaneously, but also produces data with many sources of noise. A number of preprocessing steps are therefore necessary to convert the raw data, usually in the form of hybridisation images, to measures of biological meaning that can be used in further statistical analysis. Preprocessing of oligonucleotide arrays includes image processing, background adjustment, data normalisation/transformation and sometimes summarisation when multiple probes are used to target one genomic unit. In this article, we review the issues encountered in each preprocessing step and introduce the statistical models and methods in preprocessing.

  6. 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

  7. 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.

  8. 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

  9. Polymerase-endonuclease amplification reaction (PEAR for large-scale enzymatic production of antisense oligonucleotides.

    Directory of Open Access Journals (Sweden)

    Xiaolong Wang

    Full Text Available Antisense oligonucleotides targeting microRNAs or their mRNA targets prove to be powerful tools for molecular biology research and may eventually emerge as new therapeutic agents. Synthetic oligonucleotides are often contaminated with highly homologous failure sequences. Synthesis of a certain oligonucleotide is difficult to scale up because it requires expensive equipment, hazardous chemicals and a tedious purification process. Here we report a novel thermocyclic reaction, polymerase-endonuclease amplification reaction (PEAR, for the amplification of oligonucleotides. A target oligonucleotide and a tandem repeated antisense probe are subjected to repeated cycles of denaturing, annealing, elongation and cleaving, in which thermostable DNA polymerase elongation and strand slipping generate duplex tandem repeats, and thermostable endonuclease (PspGI cleavage releases monomeric duplex oligonucleotides. Each round of PEAR achieves over 100-fold amplification. The product can be used in one more round of PEAR directly, and the process can be further repeated. In addition to avoiding dangerous materials and improved product purity, this reaction is easy to scale up and amenable to full automation. PEAR has the potential to be a useful tool for large-scale production of antisense oligonucleotide drugs.

  10. Magnetic axis alignment and the Poisson alignment reference system

    Science.gov (United States)

    Griffith, Lee V.; Schenz, Richard F.; Sommargren, Gary E.

    1989-01-01

    Three distinct metrological operations are necessary to align a free-electron laser (FEL): the magnetic axis must be located, a straight line reference (SLR) must be generated, and the magnetic axis must be related to the SLR. This paper begins with a review of the motivation for developing an alignment system that will assure better than 100 micrometer accuracy in the alignment of the magnetic axis throughout an FEL. The paper describes techniques for identifying the magnetic axis of solenoids, quadrupoles, and wiggler poles. Propagation of a laser beam is described to the extent of revealing sources of nonlinearity in the beam. Development and use of the Poisson line, a diffraction effect, is described in detail. Spheres in a large-diameter laser beam create Poisson lines and thus provide a necessary mechanism for gauging between the magnetic axis and the SLR. Procedures for installing FEL components and calibrating alignment fiducials to the magnetic axes of the components are also described. An error budget shows that the Poisson alignment reference system will make it possible to meet the alignment tolerances for an FEL.

  11. 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...

  12. 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

  13. 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.

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

    DEFF Research Database (Denmark)

    1997-01-01

    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), PROXYL (N......, to a method for preparing a labelled oligonucleotide, and to the use of the labelled oligonucleotide as hybridisation probe, in polymerase chain reactions (PCR), in nucleic acid sequencing, in cloning recombinant DNA and $i(in vitro) mutagenesis....

  15. 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.

  16. 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...

  17. 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

  18. 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

  19. MAGSAT: Vector magnetometer absolute sensor alignment determination

    Science.gov (United States)

    Acuna, M. H.

    1981-01-01

    A procedure is described for accurately determining the absolute alignment of the magnetic axes of a triaxial magnetometer sensor with respect to an external, fixed, reference coordinate system. The method does not require that the magnetic field vector orientation, as generated by a triaxial calibration coil system, be known to better than a few degrees from its true position, and minimizes the number of positions through which a sensor assembly must be rotated to obtain a solution. Computer simulations show that accuracies of better than 0.4 seconds of arc can be achieved under typical test conditions associated with existing magnetic test facilities. The basic approach is similar in nature to that presented by McPherron and Snare (1978) except that only three sensor positions are required and the system of equations to be solved is considerably simplified. Applications of the method to the case of the MAGSAT Vector Magnetometer are presented and the problems encountered discussed.

  20. 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.

  1. Sensing Characteristics of A Precision Aligner Using Moire Gratings for Precision Alignment System

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lizhong; Hideo Furuhashi; Yoshiyuki Uchida

    2001-01-01

    Sensing characteristics of a precision aligner using moire gratings for precision alignment sysem has been investigated. A differential moire alignment system and a modified alignment system were used. The influence of the setting accuracy of the gap length and inclination of gratings on the alignment accuracy has been studied experimentally and theoretically. Setting accuracy of the gap length less than 2.5μm is required in modified moire alignment. There is no influence of the gap length on the alignment accuracy in the differential alignment system. The inclination affects alignment accuracies in both differential and modified moire alignment systems.

  2. 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

  3. Nucleoside, nucleotide and oligonucleotide based amphiphiles: a successful marriage of nucleic acids with lipids.

    Science.gov (United States)

    Gissot, Arnaud; Camplo, Michel; Grinstaff, Mark W; Barthélémy, Philippe

    2008-04-21

    Amphiphilic molecules based on nucleosides, nucleotides and oligonucleotides are finding more and more biotechnological applications. This Perspective highlights their synthesis, supramolecular organization as well as their applications in the field of biotechnology.

  4. Sheath liquid effects in capillary high-performance liquid chromatography-electrospray mass spectrometry of oligonucleotides.

    Science.gov (United States)

    Huber, C G; Krajete, A

    2000-02-18

    Fused-silica capillary columns of 200 microm inner diameter were packed with micropellicular, octadecylated, 2.3 microm poly(styrene-divinylbenzene) particles and applied to the separation of oligonucleotides by ion-pair reversed-phase high-performance liquid chromatography. Oligonucleotides were eluted at 50 degrees C with gradients of 3-13% acetonitrile in 50 mM triethylammonium bicarbonate. Addition of sheath liquid to the column effluent allowed the detection of oligonucleotides by electrospray ionization mass spectrometry using full-scan data acquisition with a detectability comparable to that obtained with UV detection. The signal-to-noise ratios with different sheath liquids increased in the order isopropanololigonucleotides longer than 20 nucleotide units whereas no significant effect was observed with shorter oligonucleotides. Organic acids and bases in the sheath liquid generally deteriorated the signal-to-noise ratios in the chromatograms and mass spectra mainly because of increased background noise. Only a few charge states were observed in the mass spectra of oligonucleotides because of charge state reduction due to the presence of carbonic acid in the eluent. With triethylammonium hydrogencarbonate as chromatographic eluent and acetonitrile as sheath liquid, very few cation adducts of oligonucleotides were observed in the mass spectra. However, the presence of small amounts of monopotassium adducts enabled the calculation of the charge state of multiply charged ions. With acetonitrile as sheath liquid, 710 amol of a 16-mer oligonucleotide were detected using selected ion monitoring data acquisition with a signal-to-noise ratio of 3:1. Finally, capillary ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry was

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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 ...

  11. 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...

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  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. Effect of oligonucleotide primers in determining viral variability within hosts

    Directory of Open Access Journals (Sweden)

    Moya Andrés

    2004-12-01

    Full Text Available Abstract Background Genetic variability in viral populations is usually estimated by means of polymerase chain reaction (PCR based methods in which the relative abundance of each amplicon is assumed to be proportional to the frequency of the corresponding template in the initial sample. Although bias in template-to-product ratios has been described before, its relevance in describing viral genetic variability at the intrapatient level has not been fully assessed yet. Results To investigate the role of oligonucleotide design in estimating viral variability within hosts, genetic diversity in hepatitis C virus (HCV populations from eight infected patients was characterised by two parallel PCR amplifications performed with two slightly different sets of primers, followed by cloning and sequencing (mean = 89 cloned sequences per patient. Population genetics analyses of viral populations recovered by pairs of amplifications revealed that in seven patients statistically significant differences were detected between populations sampled with different set of primers. Conclusions Genetic variability analyses demonstrates that PCR selection due to the choice of primers, differing in their degeneracy degree at some nucleotide positions, can eclipse totally or partially viral variants, hence yielding significant different estimates of viral variability within a single patient and therefore eventually producing quite different qualitative and quantitative descriptions of viral populations within each host.

  5. 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.

  6. 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...

  7. 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 ...

  8. 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 ...

  9. DIDA: Distributed Indexing Dispatched Alignment.

    Directory of Open Access Journals (Sweden)

    Hamid Mohamadi

    Full Text Available One essential application in bioinformatics that is affected by the high-throughput sequencing data deluge is the sequence alignment problem, where nucleotide or amino acid sequences are queried against targets to find regions of close similarity. When queries are too many and/or targets are too large, the alignment process becomes computationally challenging. This is usually addressed by preprocessing techniques, where the queries and/or targets are indexed for easy access while searching for matches. When the target is static, such as in an established reference genome, the cost of indexing is amortized by reusing the generated index. However, when the targets are non-static, such as contigs in the intermediate steps of a de novo assembly process, a new index must be computed for each run. To address such scalability problems, we present DIDA, a novel framework that distributes the indexing and alignment tasks into smaller subtasks over a cluster of compute nodes. It provides a workflow beyond the common practice of embarrassingly parallel implementations. DIDA is a cost-effective, scalable and modular framework for the sequence alignment problem in terms of memory usage and runtime. It can be employed in large-scale alignments to draft genomes and intermediate stages of de novo assembly runs. The DIDA source code, sample files and user manual are available through http://www.bcgsc.ca/platform/bioinfo/software/dida. The software is released under the British Columbia Cancer Agency License (BCCA, and is free for academic use.

  10. Porous silicon-cell penetrating peptide hybrid nanocarrier for intracellular delivery of oligonucleotides.

    Science.gov (United States)

    Rytkönen, Jussi; Arukuusk, Piret; Xu, Wujun; Kurrikoff, Kaido; Langel, Ulo; Lehto, Vesa-Pekka; Närvänen, Ale

    2014-02-01

    The largest obstacle to the use of oligonucleotides as therapeutic agents is the delivery of these large and negatively charged biomolecules through cell membranes into intracellular space. Mesoporous silicon (PSi) is widely recognized as a potential material for drug delivery purposes due to its several beneficial features like large surface area and pore volume, high loading capacity, biocompatibility, and biodegradability. In the present study, PSi nanoparticles stabilized by thermal oxidation or thermal carbonization and subsequently modified by grafting aminosilanes on the surface are utilized as an oligonucleotide carrier. Splice correcting oligonucleotides (SCOs), a model oligonucleotide drug, were loaded into the positively charged PSi nanoparticles with a loading degree as high as 14.3% (w/w). Rapid loading was achieved by electrostatic interactions, with the loading efficiencies reaching 100% within 5 min. The nanoparticles were shown to deliver and release SCOs, in its biologically active form, inside cells when formulated together with cell penetrating peptides (CPP). The biological effect was monitored with splice correction assay and confocal microscopy utilizing HeLa pLuc 705 cells. Furthermore, the use of PSi carrier platform in oligonucleotide delivery did not reduce the cell viability. Additionally, the SCO-CPP complexes formed in the pores of the carrier were stabilized against proteolytic digestion. The advantageous properties of protecting and releasing the cargo and the possibility to further functionalize the carrier surface make the hybrid nanoparticles a potential system for oligonucleotide delivery.

  11. Oligonucleotide chip, real-time PCR and sequencing for genotyping of hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Yong-Zhong Wang; Guo-Xiang Wu; Li-Bo Luo; Min Chen; Li-Hua Ruan

    2007-01-01

    AIM: To compare the oligonucleotide chip, real-time PCR and sequencing for genotyping of hepatitis B virus in Chinese patients with chronic hepatitis B.METHODS: Mixture of samples with different genotypes and clinical serum samples from 126 chronic hepatitis B patients was tested for hepatitis B virus genotypes by oligonucleotide chip, real-time PCR and sequencing of PCR products, respectively. Clinical performances, time required and costs of the three assays were evaluated.RESULTS: Oligonucleotide chips and real-time PCR detected 1% and 0.1% genotypes, respectively, in mixed samples. Of the 126 clinical samples from patients with chronic hepatitis B, genotype B was detected in 41(33%), 41 (33%) and 45 (36%) samples, and genotype C in 76 (60%), 76 (60%) and 81 (64%) samples, by oligonucleotide chip, real-time PCR and sequencing,respectively. Oligonucleotide chip and real-time PCR detected mixed genotypes B and C in 9 samples. Realtime PCR was the rapidest and cheapest among the three assays.CONCLUSION: Oligonucleotide chip and real-time PCR are able to detect mixed genotypes, while sequencing only detects the dominant genotype in clinical samples.

  12. Improving signal intensities for genes with low-expression on oligonucleotide microarrays

    Directory of Open Access Journals (Sweden)

    Hu Limei

    2004-06-01

    Full Text Available Abstract Background DNA microarrays using long oligonucleotide probes are widely used to evaluate gene expression in biological samples. These oligonucleotides are pre-synthesized and sequence-optimized to represent specific genes with minimal cross-hybridization to homologous genes. Probe length and concentration are critical factors for signal sensitivity, particularly when genes with various expression levels are being tested. We evaluated the effects of oligonucleotide probe length and concentration on signal intensity measurements of the expression levels of genes in a target sample. Results Selected genes of various expression levels in a single cell line were hybridized to oligonucleotide arrays of four lengths and four concentrations of probes to determine how these critical parameters affected the intensity of the signal representing their expression. We found that oligonucleotides of longer length significantly increased the signals of genes with low-expression in the target. High-expressing gene signals were also boosted but to a lesser degree. Increasing the probe concentration, however, did not linearly increase the signal intensity for either low- or high-expressing genes. Conclusions We conclude that the longer the oligonuclotide probe the better the signal intensities of low expressing genes on oligonucleotide arrays.

  13. 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

  14. Intracerebroventricular Administration of Mineralocorticoid Receptor Antisense Oligonucleotides Attenuates Salt Appetite in the Rat.

    Science.gov (United States)

    Ma; Itharat; Fluharty; Sakai

    1997-10-01

    The anterior ventral third ventricle (AV3V) region of the brain contains high concentrations of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) that are important in the maintenance of body fluid and electrolyte balance as well as other physiological processes. Daily intracerebroventricular pulse injections of MR antisense oligonucleotides significantly suppressed deoxycorticosterone acetate (DOCA) induced salt appetite in a dose-related manner. Similar administration of GR antisense or scrambled/sense oligonucleotide into the third ventricle failed to inhibit salt appetite. Salt appetite aroused after adrenalectomy was not suppressed by MR antisense oligonucleotide treatments but was suppressed by an antisense oligonucleotide directed against the angiotensin II AT1 receptor subtype. Receptor binding analysis demonstrated that MR and GR oligonucleotide treatments each reduced their respective receptor subtypes. Finally, although GR antisense oligonucleotide treatment was ineffective in suppressing DOCA-induced salt appetite, this treatment did increase stress induced corticosterone release as well as delayed the recovery of corticosterone to basal levels after stress. PMID:9787254

  15. 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.

  16. 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

  17. Photosensitive Polymers for Liquid Crystal Alignment

    Science.gov (United States)

    Mahilny, U. V.; Stankevich, A. I.; Trofimova, A. V.; Muravsky, A. A.; Murauski, A. A.

    The peculiarities of alignment of liquid crystal (LC) materials by the layers of photocrosslinkable polymers with side benzaldehyde groups are considered. The investigation of mechanism of photostimulated alignment by rubbed benzaldehyde layer is performed. The methods of creation of multidomain aligning layers on the basis of photostimulated rubbing alignment are described.

  18. 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 ...

  19. 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);…

  20. Alignment method for parabolic trough solar concentrators

    Science.gov (United States)

    Diver, Richard B.

    2010-02-23

    A Theoretical Overlay Photographic (TOP) alignment method uses the overlay of a theoretical projected image of a perfectly aligned concentrator on a photographic image of the concentrator to align the mirror facets of a parabolic trough solar concentrator. The alignment method is practical and straightforward, and inherently aligns the mirror facets to the receiver. When integrated with clinometer measurements for which gravity and mechanical drag effects have been accounted for and which are made in a manner and location consistent with the alignment method, all of the mirrors on a common drive can be aligned and optimized for any concentrator orientation.

  1. Strategic Alignment and New Product Development

    DEFF Research Database (Denmark)

    Acur, Nuran; Kandemir, Destan; Boer, Harry

    2012-01-01

    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......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...... 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. Furthermore...

  2. 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.

  3. 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

  4. 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...

  5. 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.

  6. 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.

  7. Position list word aligned hybrid

    DEFF Research Database (Denmark)

    Deliege, Francois; Pedersen, Torben Bach

    2010-01-01

    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......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...

  8. 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.

  9. Correction of a Cystic Fibrosis Splicing Mutation by Antisense Oligonucleotides.

    Science.gov (United States)

    Igreja, Susana; Clarke, Luka A; Botelho, Hugo M; Marques, Luís; Amaral, Margarida D

    2016-02-01

    Cystic fibrosis (CF), the most common life-threatening genetic disease in Caucasians, is caused by ∼2,000 different mutations in the CF transmembrane conductance regulator (CFTR) gene. A significant fraction of these (∼13%) affect pre-mRNA splicing for which novel therapies have been somewhat neglected. We have previously described the effect of the CFTR splicing mutation c.2657+5G>A in IVS16, showing that it originates transcripts lacking exon 16 as well as wild-type transcripts. Here, we tested an RNA-based antisense oligonucleotide (AON) strategy to correct the aberrant splicing caused by this mutation. Two AONs (AON1/2) complementary to the pre-mRNA IVS16 mutant region were designed and their effect on splicing was assessed at the RNA and protein levels, on intracellular protein localization and function. To this end, we used the 2657+5G>A mutant CFTR minigene stably expressed in HEK293 Flp-In cells that express a single copy of the transgene. RNA data from AON1-treated mutant cells show that exon 16 inclusion was almost completely restored (to 95%), also resulting in increased levels of correctly localized CFTR protein at the plasma membrane (PM) and with increased function. A novel two-color CFTR splicing reporter minigene developed here allowed the quantitative monitoring of splicing by automated microscopy localization of CFTR at the PM. The AON strategy is thus a promising therapeutic approach for the specific correction of alternative splicing.

  10. 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

  11. Molecular Cloning of MAPK Gene Family Using Synthetic Oligonucleotide Probe.

    Science.gov (United States)

    Zhou, Song; Wang, Qin; Chen, Jing; Chen, Jiang-Ye

    1999-01-01

    MAPK(mitogen activated protein kinase) is a kind of Ser/Thr protein kinase. The MAPKs play an important role in several different signal transduction pathways. The MAPKs may also have a role in morphorgenesis of Candida albicans. An oligonucleotide probe was used to screen novel MAPKs in C. albicans. All MAPKs shared high homogeneity in their eleven kinase subdomains, especially subdoman VII and VIII. In subdomain VII, nearly all MAPKs have the same KIDFGLAR sequence, and the two known MAPKs in C. albicans CEK1 and MKC1 have only one different nucleotide in that DNA sequence. This probe was hybridized with C. albicans genomic DNA. Under stringent conditions, the probe could only hybridize with CEK1 and MKC1 gene fragment. But when hybridized at 40 degrees in non-SDS solution, two novel bands appeared. This condition was used to screen SC5314 DNA library, and many positive clones with different hybridization density were obtained. The strongest hybridization clones were identified to contain CEK1 and MKC1 gene. From the stronger positive hybridization clones, two novel genes were identified. The first gene, named CRK1(CDC2-related protein kinase 1), shared high homogeneity to MAPKs, but was not of them. It is closest to SGV1 from S. cerevisiae (with homology 47%) and PITALRE from human (with homology 41%), both of which are CDC2-related protein kinases. The second gene called CEK2(Candida albicans extracelluar signal-regulated kinase 2) is a novel MAPK of Candida albicans, which shares the highest identity with CEK1 and its S. cerevisiae homologs, FUS3 and KSS1, two redundant MAPKs in yeast pheromone response and morphogenesis. PMID:12114967

  12. 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.

  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. Laser-Beam-Alignment Controller

    Science.gov (United States)

    Krasowski, M. J.; Dickens, D. E.

    1995-01-01

    In laser-beam-alignment controller, images from video camera compared to reference patterns by fuzzy-logic pattern comparator. Results processed by fuzzy-logic microcontroller, which sends control signals to motor driver adjusting lens and pinhole in spatial filter.

  15. 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.

  16. 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.

  17. 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.

  18. Self crimped and aligned fibers

    Directory of Open Access Journals (Sweden)

    Thinakaran Senthilram

    2011-05-01

    Full Text Available Electrospinning is one of the most successful means of producing nanofibers with enormous application potential. New methods of producing nanofibers without high voltages are presently being explored by researchers around the globe. In the present work, a facile method of producing aligned and crimped fibers with polycaprolactone by rotating the needle assembly is described.

  19. 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...

  20. 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...

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide

    Directory of Open Access Journals (Sweden)

    Roh C

    2012-05-01

    Full Text Available Changhyun RohDivision of Biotechnology, Advanced Radiation Technology Institute (ARTI, Korea Atomic Energy Research Institute (KAERI, Jeongeup, Republic of KoreaAbstract: Hundreds of million people worldwide have been infected with severe acute respiratory syndrome (SARS, and the rate of global death from SARS has remarkably increased. Hence, the development of efficient drug treatments for the biological effects of SARS is highly needed. We have previously shown that quantum dots (QDs-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV nucleocapsid (N protein. In this study, we found that a designed biochip could analyze inhibitors of the SARS-CoV N protein using nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, (--catechin gallate and (--gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. (--catechin gallate and (--gallocatechin gallate attenuated the binding affinity in a concentrated manner as evidenced by QDs-conjugated RNA oligonucleotide on a designed biochip. At a concentration of 0.05 µg mL–1, (--catechin gallate and (--gallocatechin gallate showed more than 40% inhibition activity on a nanoparticle-based RNA oligonucleotide biochip system.Keywords: SARS, RNA oligonucleotide, quantum dots, inhibitor, screening

  7. Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents.

    Science.gov (United States)

    Stein, C A; Hansen, J Bo; Lai, Johnathan; Wu, SiJian; Voskresenskiy, Anatoliy; Høg, Anja; Worm, Jesper; Hedtjärn, Maj; Souleimanian, Naira; Miller, Paul; Soifer, Harris S; Castanotto, Daniella; Benimetskaya, Luba; Ørum, Henrik; Koch, Troels

    2010-01-01

    For the past 15-20 years, the intracellular delivery and silencing activity of oligodeoxynucleotides have been essentially completely dependent on the use of a delivery technology (e.g. lipofection). We have developed a method (called 'gymnosis') that does not require the use of any transfection reagent or any additives to serum whatsoever, but rather takes advantage of the normal growth properties of cells in tissue culture in order to promote productive oligonucleotide uptake. This robust method permits the sequence-specific silencing of multiple targets in a large number of cell types in tissue culture, both at the protein and mRNA level, at concentrations in the low micromolar range. Optimum results were obtained with locked nucleic acid (LNA) phosphorothioate gap-mers. By appropriate manipulation of oligonucleotide dosing, this silencing can be continuously maintained with little or no toxicity for >240 days. High levels of oligonucleotide in the cell nucleus are not a requirement for gene silencing, contrary to long accepted dogma. In addition, gymnotic delivery can efficiently deliver oligonucleotides to suspension cells that are known to be very difficult to transfect. Finally, the pattern of gene silencing of in vitro gymnotically delivered oligonucleotides correlates particularly well with in vivo silencing. The establishment of this link is of particular significance to those in the academic research and drug discovery and development communities.

  8. 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

  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. 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.

  11. Combined in vitro transcription and reverse transcription to amplify and label complex synthetic oligonucleotide probe libraries.

    Science.gov (United States)

    Murgha, Yusuf; Beliveau, Brian; Semrau, Kassandra; Schwartz, Donald; Wu, Chao-Ting; Gulari, Erdogan; Rouillard, Jean-Marie

    2015-06-01

    Oligonucleotide microarrays allow the production of complex custom oligonucleotide libraries for nucleic acid detection-based applications such as fluorescence in situ hybridization (FISH). We have developed a PCR-free method to make single-stranded DNA (ssDNA) fluorescent probes through an intermediate RNA library. A double-stranded oligonucleotide library is amplified by transcription to create an RNA library. Next, dye- or hapten-conjugate primers are used to reverse transcribe the RNA to produce a dye-labeled cDNA library. Finally the RNA is hydrolyzed under alkaline conditions to obtain the single-stranded fluorescent probes library. Starting from unique oligonucleotide library constructs, we present two methods to produce single-stranded probe libraries. The two methods differ in the type of reverse transcription (RT) primer, the incorporation of fluorescent dye, and the purification of fluorescent probes. The first method employs dye-labeled reverse transcription primers to produce multiple differentially single-labeled probe subsets from one microarray library. The fluorescent probes are purified from excess primers by oligonucleotide-bead capture. The second method uses an RNA:DNA chimeric primer and amino-modified nucleotides to produce amino-allyl probes. The excess primers and RNA are hydrolyzed under alkaline conditions, followed by probe purification and labeling with amino-reactive dyes. The fluorescent probes created by the combination of transcription and reverse transcription can be used for FISH and to detect any RNA and DNA targets via hybridization.

  12. 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

  13. Delivery of antisense oligonucleotide to the cornea by iontophoresis.

    Science.gov (United States)

    Berdugo, M; Valamanesh, F; Andrieu, C; Klein, C; Benezra, D; Courtois, Y; Behar-Cohen, F

    2003-04-01

    We wished to evaluate the potential of iontophoresis to promote the delivery of antisense oligonucleotides (ODN) directed at the vascular endothelial growth factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally administered to rat eyes, and their fate within the anterior segment was studied. Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM) were delivered by iontophoresis (300 microA for 5 minutes) using a specially designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM) were delivered using the same applicator, but no electrical current was applied. In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior to the application of ODNs (20 microM), and iontophoresis electrical current was delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM) iontophoresis application (300 microA for 5 minutes) and were used for ODN integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours after a single ODN application and studied. Topically applied ODNs using the same iontophoresis applicator but without current do not penetrate the cornea and remain confined to the superficial epithelial layer. ODNs delivered with transcorneoscleral iontophoresis penetrate into all corneal layers and are also detected in the iris. In corneas with neovascularization, ODNs were particularly localized within the vascular endothelial cells of the stroma. ODNs extracted from eye tissues 24 hours after iontophoresis remained unaltered. The iontophoresis current did not cause any detectable ocular damage under these conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF-R2 may be used for the

  14. Basic Science Training Program.

    Science.gov (United States)

    Brummel, Clete

    These six learning modules were developed for Lake Michigan College's Basic Science Training Program, a workshop to develop good study skills while reviewing basic science. The first module, which was designed to provide students with the necessary skills to study efficiently, covers the following topics: time management; an overview of a study…

  15. 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.

  16. 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…

  17. 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…

  18. Shuttle onboard IMU alignment methods

    Science.gov (United States)

    Henderson, D. M.

    1976-01-01

    The current approach to the shuttle IMU alignment is based solely on the Apollo Deterministic Method. This method is simple, fast, reliable and provides an accurate estimate for the present cluster to mean of 1,950 transformation matrix. If four or more star sightings are available, the application of least squares analysis can be utilized. The least squares method offers the next level of sophistication to the IMU alignment solution. The least squares method studied shows that a more accurate estimate for the misalignment angles is computed, and the IMU drift rates are a free by-product of the analysis. Core storage requirements are considerably more; estimated 20 to 30 times the core required for the Apollo Deterministic Method. The least squares method offers an intermediate solution utilizing as much data that is available without a complete statistical analysis as in Kalman filtering.

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. Alignment of the James Webb Space Telescope optical telescope element

    Science.gov (United States)

    Glassman, Tiffany; Levi, Joshua; Liepmann, Till; Hahn, Walter; Bisson, Gary; Porpora, Dan; Hadjimichael, Theo

    2016-07-01

    The optical telescope element (OTE) of the James Webb Space Telescope has now been integrated and aligned. The OTE comprises the flight mirrors and the structure that supports them - 18 primary mirror segments, the secondary mirror, and the tertiary and fine steering mirrors (both housed in the aft optics subsystem). The primary mirror segments and the secondary mirror have actuators to actively control their positions during operations. This allows the requirements for aligning the OTE subsystems to be in the range of microns rather than nanometers. During OTE integration, the alignment of the major subsystems of the OTE structure and optics were controlled to ensure that, when the telescope is on orbit and at cryogenic temperatures, the active mirrors will be within the adjustment range of the actuators. Though the alignment of this flagship mission was complex and intricate, the key to a successful integration process turned out to be very basic: a clear, concise series of steps employing advanced planning, backup measurements, and cross checks that this multi-organizational team executed with a careful and methodical approach. This approach was not only critical to our own success but has implications for future space observatories.

  4. Automated alignment method for coherence-controlled holographic microscope

    Science.gov (United States)

    Dostal, Zbynek; Slaby, Tomas; Kvasnica, Lukas; Lostak, Martin; Krizova, Aneta; Chmelik, Radim

    2015-11-01

    A coherence-controlled holographic microscope (CCHM) was developed particularly for quantitative phase imaging and measurement of live cell dynamics, which is the proper subject of digital holographic microscopy (DHM). CCHM in low-coherence mode extends DHM in the study of living cells. However, this advantage is compensated by sensitivity of the system to easily become misaligned, which is a serious hindrance to wanted performance. Therefore, it became clear that introduction of a self-correcting system is inevitable. Accordingly, we had to devise a theory of a suitable control and design an automated alignment system for CCHM. The modulus of the reconstructed holographic signal was identified as a significant variable for guiding the alignment procedures. From this, we derived the original basic realignment three-dimensional algorithm, which encompasses a unique set of procedures for automated alignment that contains processes for initial and advanced alignment as well as long-term maintenance of microscope tuning. All of these procedures were applied to a functioning microscope and the tested processes were successfully validated. Finally, in such a way, CCHM is enabled to substantially contribute to study of biology, particularly of cancer cells in vitro.

  5. 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.

  6. 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...

  7. 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...

  8. 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

  9. Cellular uptake of antisense oligonucleotides after complexing or conjugation with cell-penetrating model peptides.

    Science.gov (United States)

    Oehlke, J; Birth, P; Klauschenz, E; Wiesner, B; Beyermann, M; Oksche, A; Bienert, M

    2002-08-01

    The uptake by mammalian cells of phosphorothioate oligonucleotides was compared with that of their respective complexes or conjugates with cationic, cell-penetrating model peptides of varying helix-forming propensity and amphipathicity. An HPLC-based protocol for the synthesis and purification of disulfide bridged conjugates in the 10-100 nmol range was developed. Confocal laser scanning microscopy (CLSM) in combination with gel-capillary electrophoresis and laser induced fluorescence detection (GCE-LIF) revealed cytoplasmic and nuclear accumulationin all cases. The uptake differences between naked oligonucleotides and their respective peptide complexes or conjugates were generally confined to one order of magnitude. No significant influence of the structural properties of the peptide components upon cellular uptake was found. Our results question the common belief that the increased biological activity of oligonucleotides after derivatization with membrane permeable peptides may be primarily due to improved membrane translocation.

  10. 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)

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Dynamics of human telomerase RNA structure revealed by antisense oligonucleotide technique.

    Science.gov (United States)

    Vasilkova, Daria V; Azhibek, Dulat M; Zatsepin, Timofei S; Naraikina, Yulia V; Prassolov, Vladimir S; Prokofjeva, Maria M; Zvereva, Maria I; Rubtsova, Maria P

    2013-12-01

    Telomeres are the nucleoprotein complexes that cap the linear chromosome ends. Telomerase is a ribonucleoprotein that maintains telomere length in stem, embryonic and cancer cells. Somatic cells don't contain active telomerase and telomere function as mitotic clock and telomere length determines the number of cell divisions. Telomerase RNA (TER) contains the template for telomere synthesis and serves as a structural scaffold for holoenzyme assembly. We compared different oligonucleotide based methods for telomerase RNA inhibition, such as antisense oligonucleotides, knockdown by transient siRNA transfection and silencing by miRNA derived from short expressed RNA hairpin in HEK293 cells. All of these methods were applied to different TER regions. Our results revealed that CR2/CR3 domain of TER is accessible in vitro and in vivo and could serve as an optimal site for oligonucleotide-based telomerase silencing.

  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. 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...

  18. A highly sensitive and selective viral protein detection method based on RNA oligonucleotide nanoparticle

    Science.gov (United States)

    Roh, Changhyun; Lee, Ho-Young; Kim, Sang-Eun; Jo, Sung-Kee

    2010-01-01

    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 ProLinker™ 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. PMID:20517476

  19. 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

  20. 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.

  1. 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.)

  2. 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.

  3. Alignment of lower-limb prostheses.

    Science.gov (United States)

    Zahedi, M S; Spence, W D; Solomonidis, S E; Paul, J P

    1986-04-01

    Alignment of a prosthesis is defined as the position of the socket relative to the other prosthetic components of the limb. During dynamic alignment the prosthetist, using subjective judgment and feedback from the patient, aims to achieve the most suitable limb geometry for best function and comfort. Until recently it was generally believed that a patient could only be satisfied with a unique "optimum alignment." The purpose of this systematic study of lower-limb alignment parameters was to gain an understanding of the factors that make a limb configuration or optimum alignment, acceptable to the patient, and to obtain a measure of the variation of this alignment that would be acceptable to the amputee. In this paper, the acceptable range of alignments for 10 below- and 10 above-knee amputees are established. Three prosthetists were involved in the majority of the 183 below-knee and 100 above-knee fittings, although several other prosthetists were also involved. The effects of each different prosthetist on the established range of alignment for each patient are reported to be significant. It is now established that an amputee can tolerate several alignments ranging in some parameters by as much as 148 mm in shifts and 17 degrees in tilts. This paper describes the method of defining and measuring the alignment of lower-limb prostheses. It presents quantitatively established values for bench alignment position and the range of adjustment required for incorporation into the design of new alignment units.

  4. Hardware Acceleration of Bioinformatics Sequence Alignment Applications

    NARCIS (Netherlands)

    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 pr

  5. Shift dynamics of capillary self-alignment

    NARCIS (Netherlands)

    Arutinov, G.; Mastrangeli, M.; Smits, E.C.P.; Heck, G.V.; Schoo, H.F.M.; Toonder, J.J.M. den; Dietzel, A.H.

    2014-01-01

    This paper describes the dynamics of capillary self-alignment of components with initial shift offsets from matching receptor sites. The analysis of the full uniaxial self-alignment dynamics of foil-based mesoscopic dies from pre-alignment to final settling evidenced three distinct, sequential regim

  6. Inferring comprehensible business/ICT alignment rules

    NARCIS (Netherlands)

    B. Cumps; D. Martens; M. De Backer; R. Haesen; S. Viaene; G. Dedene; B. Baesens; M. Snoeck

    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 reputati

  7. 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...

  8. Customized oligonucleotide microchips that convert multiple genetic information to simple patterns, are portable and reusable

    Science.gov (United States)

    Mirzabekov, Andrei; Guschin, Dmitry Y.; Chik, Valentine; Drobyshev, Aleksei; Fotin, Alexander; Yershov, Gennadiy; Lysov, Yuri

    2002-01-01

    This invention relates to using customized oligonucleotide microchips as biosensors for the detection and identification of nucleic acids specific for different genes, organisms and/or individuals in the environment, in food and in biological samples. The microchips are designed to convert multiple bits of genetic information into simpler patterns of signals that are interpreted as a unit. Because of an improved method of hybridizing oligonucleotides from samples to microchips, microchips are reusable and transportable. For field study, portable laser or bar code scanners are suitable.

  9. 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...

  10. Sequence selective naked-eye detection of DNA harnessing extension of oligonucleotide-modified nucleotides.

    Science.gov (United States)

    Verga, Daniela; Welter, Moritz; Marx, Andreas

    2016-02-01

    DNA polymerases can efficiently and sequence selectively incorporate oligonucleotide (ODN)-modified nucleotides and the incorporated oligonucleotide strand can be employed as primer in rolling circle amplification (RCA). The effective amplification of the DNA primer by Φ29 DNA polymerase allows the sequence-selective hybridisation of the amplified strand with a G-quadruplex DNA sequence that has horse radish peroxidase-like activity. Based on these findings we develop a system that allows DNA detection with single-base resolution by naked eye.

  11. 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)

  12. 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.

  13. 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

  14. Basic stress analysis

    CERN Document Server

    Iremonger, M J

    1982-01-01

    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

  15. Multiple structural alignment and core detection by geometric hashing.

    Science.gov (United States)

    Leibowitz, N; Fligelman, Z Y; Nussinov, R; Wolfson, H J

    1999-01-01

    A Multiple Structural Alignment algorithm is presented. The algorithm accepts an ensemble of protein structures and finds the largest substructure (core) of C alpha atoms whose geometric configuration appear in all the molecules of the ensemble (core). Both the detection of this core and the resulting structural alignment are done simultaneously. Other large enough multistructural superimpositions are detected as well. Our method is based on the Geometric Hashing paradigm and a superimposition clustering technique which represents superimpositions by sets of matching atoms. The algorithm proved to be efficient on real data in a series of experiments. The same method can be applied to any ensemble of molecules (not necessarily proteins) since our basic technique is sequence order independent.

  16. Local graph alignment and motif search in biological networks

    Science.gov (United States)

    Berg, Johannes; Lässig, Michael

    2004-10-01

    Interaction networks are of central importance in postgenomic molecular biology, with increasing amounts of data becoming available by high-throughput methods. Examples are gene regulatory networks or protein interaction maps. The main challenge in the analysis of these data is to read off biological functions from the topology of the network. Topological motifs, i.e., patterns occurring repeatedly at different positions in the network, have recently been identified as basic modules of molecular information processing. In this article, we discuss motifs derived from families of mutually similar but not necessarily identical patterns. We establish a statistical model for the occurrence of such motifs, from which we derive a scoring function for their statistical significance. Based on this scoring function, we develop a search algorithm for topological motifs called graph alignment, a procedure with some analogies to sequence alignment. The algorithm is applied to the gene regulation network of Escherichia coli.

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

    Institute of Scientific and Technical Information of China (English)

    TianXiaobing; ZhangLihe; MinJimei

    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.

  18. FLUORESCENT OLIGONUCLEOTIDES CONTAINING A NOVEL PERYLENE 2 '-AMINO-alpha-L-LNA MONOMER: SYNTHESIS AND ANALYTICAL POTENTIAL

    DEFF Research Database (Denmark)

    Astakhova, I. V.; Kumar, T. S.; Wengel, J.

    2011-01-01

    efficiency of the resulting perylene-2'-amino-alpha-L-LNA monomer (T*) into synthetic oligonucleotides was significantly improved by replacement of the typically used 1H-tetrazole activator with pyridine hydrochloride. Generally, oligonucleotides containing monomer T* showed high binding affinity towards...

  19. The Effect of Organic Modifiers on Electrospray Ionization Charge-State Distribution and Desorption Efficiency for Oligonucleotides

    Science.gov (United States)

    Chen, Buyun; Mason, Sadie F.; Bartlett, Michael G.

    2013-02-01

    The chemical composition of the solution has a critical impact on the electrospray desorption efficiency of oligonucleotides. Several physiochemical properties of various organic modifiers were investigated with respect to their role in the desorption process of oligonucleotides. The Henry's Law Constant, which reflects the volatility of alkylamines, was found to have a prominent effect on both the electrospray charge state distribution and desorption efficiency of oligonucleotides. Alkylamines with higher k_{H,cc}( {aq/gas} ) values such as hexylamine, piperidine, and imidazole reduced the charge state distribution by forming complexes with the oligonucleotide and dissociating from it in the gas phase, while alkylamines with extremely low k_{H,cc}( {aq/gas} ) values reduced the electrospray charge state distribution by facilitating ion emission at an earlier stage of the electrospray desorption process. Ion-pairing agents with moderate k_{H,cc}( {aq/gas} ) values do not alter the electrospray charge state distribution of oligonucleotides and their ability to enhance oligonucleotide ionization followed the order of decreasing k_{H,cc}( {aq/gas} ) values. The Henry's Law Constant also correlated to the impact of the acidic modifiers on oligonucleotide ionization efficiency. Ionization enhancement effects were observed with hexafluoroisopropanol, and this effect was attributed to its low k_{H,cc}( {aq/gas} ) and moderate acidity. The comprehensive effects of both alkylamine and hexafluoroisoproapnol on the electrospray ionization desorption of oligonucleotides were also evaluated, and acid-base equilibrium was found to play a critical role in determining these effects.

  20. 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

  1. RevTrans: multiple alignment of coding DNA from aligned amino acid sequences

    DEFF Research Database (Denmark)

    Wernersson, Rasmus; Pedersen, Anders Gorm

    2003-01-01

    proteins. It is therefore preferable to align coding DNA at the amino acid level and it is for this purpose we have constructed the program RevTrans. RevTrans constructs a multiple DNA alignment by: (i) translating the DNA; (ii) aligning the resulting peptide sequences; and (iii) building a multiple DNA...... alignment by 'reverse translation' of the aligned protein sequences. In the resulting DNA alignment, gaps occur in groups of three corresponding to entire codons, and analogous codon positions are therefore always lined up. These features are useful when constructing multiple DNA alignments for phylogenetic...

  2. 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....

  3. 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- ...

  4. 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 ...

  5. 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 ...

  6. 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 ...

  7. 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 ...

  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. 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 ...

  10. 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.

  11. 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...

  12. 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...

  13. 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....

  14. Galaxy alignments: Theory, modelling and simulations

    CERN Document Server

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

    2015-01-01

    The shapes of galaxies are not randomly oriented on the sky. During the galaxy formation and evolution process, environment has a strong influence, as tidal gravitational fields in large-scale structure tend to align the shapes and angular momenta of nearby galaxies. Additionally, events such as galaxy mergers affect the relative alignments of galaxies throughout their history. These "intrinsic galaxy alignments" are known to exist, but are still poorly understood. This review will offer a pedagogical introduction to the current theories that describe intrinsic galaxy alignments, including the apparent difference in intrinsic alignment between early- and late-type galaxies and the latest efforts to model them analytically. It will then describe the ongoing efforts to simulate intrinsic alignments using both $N$-body and hydrodynamic simulations. Due to the relative youth of this field, there is still much to be done to understand intrinsic galaxy alignments and this review summarises the current state of the ...

  15. Aligning Sequences by Minimum Description Length

    Directory of Open Access Journals (Sweden)

    John S. Conery

    2008-01-01

    Full Text Available This paper presents a new information theoretic framework for aligning sequences in bioinformatics. A transmitter compresses a set of sequences by constructing a regular expression that describes the regions of similarity in the sequences. To retrieve the original set of sequences, a receiver generates all strings that match the expression. An alignment algorithm uses minimum description length to encode and explore alternative expressions; the expression with the shortest encoding provides the best overall alignment. When two substrings contain letters that are similar according to a substitution matrix, a code length function based on conditional probabilities defined by the matrix will encode the substrings with fewer bits. In one experiment, alignments produced with this new method were found to be comparable to alignments from CLUSTALW. A second experiment measured the accuracy of the new method on pairwise alignments of sequences from the BAliBASE alignment benchmark.

  16. Alignment method for solar collector arrays

    Science.gov (United States)

    Driver, Jr., Richard B

    2012-10-23

    The present invention is directed to an improved method for establishing camera fixture location for aligning mirrors on a solar collector array (SCA) comprising multiple mirror modules. The method aligns the mirrors on a module by comparing the location of the receiver image in photographs with the predicted theoretical receiver image location. To accurately align an entire SCA, a common reference is used for all of the individual module images within the SCA. The improved method can use relative pixel location information in digital photographs along with alignment fixture inclinometer data to calculate relative locations of the fixture between modules. The absolute locations are determined by minimizing alignment asymmetry for the SCA. The method inherently aligns all of the mirrors in an SCA to the receiver, even with receiver position and module-to-module alignment errors.

  17. 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

  18. 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.

  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. 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.

  3. Phosphorothioate anti-sense oligonucleotides: the kinetics and mechanism of the generation of the sulfurising agent from phenylacetyl disulfide (PADS).

    Science.gov (United States)

    Scotson, James L; Andrews, Benjamin I; Laws, Andrew P; Page, Michael I

    2016-09-21

    The synthesis of phosphorothioate oligonucleotides is often accomplished in the pharmaceutical industry by the sulfurisation of the nucleotide-phosphite using phenylacetyl disulfide (PADS) which has an optimal combination of properties. This is best achieved by an initial 'ageing' of PADS for 48 h in acetonitrile with 3-picoline to generate polysulfides. The initial base-catalysed degradation of PADS occurs by an E1cB-type elimination to generate a ketene and acyldisulfide anion. Proton abstraction to reversibly generate a carbanion is demonstrated by H/D exchange, the rate of which is greatly increased by electron-withdrawing substituents in the aromatic ring of PADS. The ketene can be trapped intramolecularly by an o-allyl group. The disulfide anion generated subsequently attacks unreacted PADS on sulfur to give polysulfides, the active sulfurising agent. The rate of degradation of PADS is decreased by less basic substituted pyridines and is only first order in PADS indicating that the rate-limiting step is formation of the disulfide anion from the carbanion. PMID:27531007

  4. Sequence determination of rRNA genes of pathogenic Vibrio species and whole-cell identification of Vibrio vulnificus with rRNA-targeted oligonucleotide probes.

    Science.gov (United States)

    Aznar, R; Ludwig, W; Amann, R I; Schleifer, K H

    1994-04-01

    A comparative analysis of seven new 16S rRNA gene sequences of pathogenic Vibrio species with previously published vibrio sequences confirmed that Vibrio vulnificus represents a group that is not closely related to the core organisms of the genus Vibrio. In addition, we found that V. vulnificus, Listonella (Vibrio) anguillarum and Vibrio diazotrophicus branch off separately from the core group. A comparison of the 16S rRNA gene sequences of V. vulnificus strains belonging to biotypes 1 and 2 revealed that the sequences of all but four biotype 1 strains were identical to each other but slightly different (17 bases) from the sequences of the rest of the V. vulnificus strains investigated. In addition, the sequences of variable regions of the 23S rRNA genes of Vibrio fluvialis, Vibrio furnissii, Vibrio harveyi, Vibrio cholerae, and V. vulnificus C7184 and TW1 were determined, aligned, and compared with all available bacterial 23S rRNA sequences in order to search for specific target sites. As a result, four oligonucleotide probes specific for V. vulnificus were synthesized, and the specificities of these probes were evaluated by dot blot hybridization to membrane-bound RNAs from 21 V. vulnificus strains, 13 strains belonging to other Vibrio species, 61 strains belonging to species that are members of the alpha, beta, and gamma subclasses of the Proteobacteria, and 3 eucaryotic microorganisms. Two probes hybridized with all of the V. vulnificus strains tested, and the other two probes distinguished V. vulnificus biotype 1 strains from all other organisms. In situ identification of V. vulnificus by using tetramethylrhodamine- or fluorescein-labelled oligonucleotides is now possible.

  5. High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases

    DEFF Research Database (Denmark)

    Chen, Fuqiang; Pruett-Miller, Shondra M; Huang, Yuping;

    2011-01-01

    Zinc-finger nucleases (ZFNs) have enabled highly efficient gene targeting in multiple cell types and organisms. Here we describe methods for using simple ssDNA oligonucleotides in tandem with ZFNs to efficiently produce human cell lines with three distinct genetic outcomes: (i) targeted point...

  6. 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

  7. Refinement of antisense oligonucleotide mediated exon skipping as therapy for Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Heemskerk, Johannes Antonius

    2011-01-01

    In recent years, modulation of mRNA has emerged as a promising therapeutic tool. For instance, in the field of neuromuscular disorders therapeutic strategies are being developed for several diseases, including antisense oligonucleotide (AON) mediated exon skipping for Duchenne Muscular Dystrophy (DM

  8. Optimization of single-base-pair mismatch discrimination in oligonucleotide microarrays

    NARCIS (Netherlands)

    Urakawa, H.; Fantroussi, El S.; Smidt, H.; Smoot, J.C.; Tribou, E.H.; Kelly, J.J.; Noble, P.A.; Stahl, D.A.

    2003-01-01

    The discrimination between perfect-match and single-base-pair-mismatched nucleic acid duplexes was investigated by using oligonucleotide DNA microarrays and nonequilibrium dissociation rates (melting profiles). DNA and RNA versions of two synthetic targets corresponding to the 16S rRNA sequences of

  9. 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

  10. 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

  11. 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

  12. An oral oligonucleotide delivery system based on a thiolated polymer: Development and in vitro evaluation.

    Science.gov (United States)

    Martien, Ronny; Hoyer, Herbert; Perera, Glen; Schnürch, Andreas Bernkop

    2011-08-01

    The purpose of this study was to develop and evaluate an oral oligonucleotide delivery system based on a thiolated polymer/reduced glutathione (GSH) system providing a protective effect toward nucleases and permeation enhancement. A polycarbophil-cysteine conjugate (PCP-Cys) was synthesized. Enzymatic degradation of a model oligonucleotide by DNase I and within freshly collected intestinal fluid was investigated in the absence and presence of PCP-Cys. Permeation studies with PCP-Cys/GSH versus control were performed in vitro on Caco-2 cell monolayers and ex vivo on rat intestinal mucosa. PCP-Cys displayed 223 ± 13.8 μmol thiol groups per gram polymer. After 4h, 61% of the free oligonucleotides were degraded by DNase I and 80% within intestinal fluid. In contrast, less than 41% (DNase I) and 60% (intestinal fluid) were degraded in the presence of 0.02% (m/v) PCP-Cys. Permeation studies revealed an 8-fold (Caco-2) and 10-fold (intestinal mucosa) increase in apparent permeability compared to buffer control. Hence, this PCP-Cys/GSH system might be a promising tool for the oral administration of oligonucleotides as it allows a significant protection toward degrading enzymes and facilitates their transport across intestinal membranes.

  13. Pd0-Catalyzed Methyl Transfer on Nucleosides and Oligonucleotides, Envisaged as a PET Tracer

    Directory of Open Access Journals (Sweden)

    Eric Fouquet

    2013-11-01

    Full Text Available The methyl transfer reaction from activated monomethyltin, via a modified Stille coupling reaction, was studied under “ligandless” conditions on fully deprotected 5'-modified nucleosides and one dinucleotide. The reaction was optimized to proceed in a few minutes and quantitative yield, even under dilute conditions, thus affording a rapid and efficient new method for oligonucleotide labelling with carbon-11.

  14. 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

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

    DEFF Research Database (Denmark)

    Behrens, Carsten; Petersen, Kenneth H.; Egholm, Michael;

    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...

  16. Stable gene targeting in human cells using single-strand oligonucleotides with modified bases.

    Directory of Open Access Journals (Sweden)

    Xavier Rios

    Full Text Available Recent advances allow multiplexed genome engineering in E. coli, employing easily designed oligonucleotides to edit multiple loci simultaneously. A similar technology in human cells would greatly expedite functional genomics, both by enhancing our ability to test how individual variants such as single nucleotide polymorphisms (SNPs are related to specific phenotypes, and potentially allowing simultaneous mutation of multiple loci. However, oligo-mediated targeting of human cells is currently limited by low targeting efficiencies and low survival of modified cells. Using a HeLa-based EGFP-rescue reporter system we show that use of modified base analogs can increase targeting efficiency, in part by avoiding the mismatch repair machinery. We investigate the effects of oligonucleotide toxicity and find a strong correlation between the number of phosphorothioate bonds and toxicity. Stably EGFP-corrected cells were generated at a frequency of ~0.05% with an optimized oligonucleotide design combining modified bases and reduced number of phosphorothioate bonds. We provide evidence from comparative RNA-seq analysis suggesting cellular immunity induced by the oligonucleotides might contribute to the low viability of oligo-corrected cells. Further optimization of this method should allow rapid and scalable genome engineering in human cells.

  17. Precise construction of oligonucleotide-Fab fragment conjugate for homogeneous immunoassay using HaloTag technology.

    Science.gov (United States)

    Päkkilä, Henna; Peltomaa, Riikka; Lamminmäki, Urpo; Soukka, Tero

    2015-03-01

    The use of oligonucleotide-protein conjugates enables the development of novel types of bioanalytical assays. However, convenient methods for producing covalent and stoichiometric oligonucleotide-protein conjugates are still rare. Here we demonstrate, for the first time, covalent conjugation of DNA oligonucleotide to Fab fragments with a 1:1 ratio using HaloTag self-labeling technology. The oligonucleotide coupling was carried out while the Fab was attached to protein G matrix, thereby enabling straightforward production of covalent conjugates. Furthermore, it allowed convenient purification of the product because the unreacted components were easily removed before the elution of the high-purity conjugate. The prepared conjugate was employed in a homogeneous immunoassay where prostate-specific antigen was used as a model analyte. Switchable lanthanide luminescence was used for detection, and the obtained limit of detection was 0.27 ng/ml. In the future, the developed method for covalent conjugation and successive purification in protein G column could also be applied for introducing other kinds of modifications to Fab fragments in a simple and site-specific manner.

  18. Effects of antisense oligonucleotides on the expression of macrophage migration inhibitory factor on macrophages

    Institute of Scientific and Technical Information of China (English)

    WEIYINGCHEN; GUANGRANLI; XUEQINGYU; XIAOYANLI; XIAOYANG

    2005-01-01

    To investigate the effects of antisense oligonucleotides on the expression of macrophage migration inhibitory factor (MIF) on macrophages, the mouse phosphorothioate oligonucleotides were designed and synthesized with the sequences of antisense, 5'-TACGGATACAAGTAGCAC-3';Sense, 5'-ATGC-CTATGTTCATCGTG-3';Missense, 5'-CTCTCAGACTCGATCTGT-3'. These phosphorothioate oligonucleotides were then transfected into cultured macrophages (RAW264.7) by luciferase vector, and the transfected macrophages were incubated with Lipopolysaccharide (LPS) (1 ng/ml) for various periods of times and collected afterwards. The content of MIF protein in the cultural supernatants was determined by ELISA, cellular RNA extracted and the expression of MIF mRNA was examined by RT-PCR analysis.The experimental results showed that LPS could induce a time-dependent specific expression of MIF on macrophages, in which the MIF mRNA in cells and the MIF protein in cultural supernatants appeared after 3 h and reached their highest concentration at 9-12 h after LPS stimulation. The levels of mRNA and proteins in the macrophages treated with antisense olignucleotides were decreased significantly after stimulation with LPS in comparison with that of stimulation with LPS alone or with that with LPS plus sense or missense oligonucleotides.There were no differences among those without LPS stimulation. It is concluded that macrophages stimulated with LPS express MIF, and the antisense olignucleotides of MIF inhibitthe expression of MIF mRNA as well as the secretion of MIF proteins in macrophages.

  19. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates.

    Science.gov (United States)

    Lindholm, Marie W; Elmén, Joacim; Fisker, Niels; Hansen, Henrik F; Persson, Robert; Møller, Marianne R; Rosenbohm, Christoph; Ørum, Henrik; Straarup, Ellen M; Koch, Troels

    2012-02-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for the reduction of low-density lipoprotein cholesterol (LDL-C). PCSK9 increases the degradation of the LDL receptor, resulting in high LDL-C in individuals with high PCSK9 activity. Here, we show that two 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% reduction in circulating LDL-C. Serum total cholesterol (TC) levels were reduced to the same extent as LDL-C with no reduction in high-density lipoprotein levels, demonstrating a specific pharmacological effect on LDL-C. The reduction in hepatic PCSK9 mRNA correlated with liver LNA oligonucleotide content. This verified that anti-PCSK9 LNA oligonucleotides regulated LDL-C through an antisense mechanism. The compounds were well tolerated with no observed effects on toxicological parameters (liver and kidney histology, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine). The pharmacologic evidence and initial safety profile of the compounds used in this study indicate that LNA antisense oligonucleotides targeting PCSK9 provide a viable therapeutic strategy and are potential complements to statins in managing high LDL-C.

  20. Oligonucleotide array outperforms SNP array on formalin-fixed paraffin-embedded clinical samples.

    Science.gov (United States)

    Nasri, Soroush; Anjomshoaa, Ahmad; Song, Sarah; Guilford, Parry; McNoe, Les; Black, Michael; Phillips, Vicky; Reeve, Anthony; Humar, Bostjan

    2010-04-01

    Compromised quality of formalin-fixed paraffin-embedded (FFPE)-derived DNA has compounded the use of archival specimens for array-based genomic studies. Recent technological advances have led to first successes in this field; however, there is currently no general agreement on the most suitable platform for the array-based analysis of FFPE DNA. In this study, FFPE and matched fresh-frozen (FF) specimens were separately analyzed with Affymetrix single nucleotide polymorphism (SNP) 6.0 and Agilent 4x44K oligonucleotide arrays to compare the genomic profiles from the two tissue sources and to assess the relative performance of the two platforms on FFPE material. Genomic DNA was extracted from matched FFPE-FF pairs of normal intestinal epithelium from four patients and were applied to the SNP and oligonucleotide platforms according to the manufacturer-recommended protocols. On the Affymetrix platform, a substantial increase in apparent copy number alterations was observed in all FFPE tissues relative to their matched FF counterparts. In contrast, FFPE and matched FF genomic profiles obtained via the Agilent platform were very similar. Both the SNP and the oligonucleotide platform performed comparably on FF material. This study demonstrates that Agilent oligonucleotide array comparative genomic hybridization generates reliable results from FFPE extracted DNA, whereas the Affymetrix SNP-based array seems less suitable for the analysis of FFPE material.

  1. Tetrahedron-structured DNA and functional oligonucleotide for construction of an electrochemical DNA-based biosensor.

    Science.gov (United States)

    Bu, Nan-Nan; Tang, Chun-Xia; He, Xi-Wen; Yin, Xue-Bo

    2011-07-21

    Tetrahedron-structured DNA (ts-DNA) in combination with a functionalized oligonucleotide was used to develop a "turn-on" biosensor for Hg(2+) ions. The ts-DNA provided an improved sensitivity and was used to block the active sites.

  2. In situ entry of oligonucleotides into brain cells can occur through a nucleic acid channel

    NARCIS (Netherlands)

    Shi, Fuxin; Gounko, Natasha V.; Wang, Xiaoqin; Ronken, Eric; Hoekstra, Dick

    2007-01-01

    Brain tissue has become a challenging therapeutic target, in part because of failure of conventional treatments of brain tumors and a gradually increasing number of neurodegenerative diseases. Because antisense oligonucleotides are readily internalized by neuronal cells in culture, these compounds c

  3. Obstructive Effects of Ultrasonic Microbubble Intensifier on CHG-5 Cell with Survivin Antisense Oligonucleotides Transfection

    Institute of Scientific and Technical Information of China (English)

    CAO Hong-ying; CAO You-de; WANG Zhi-gang; LI Pan

    2008-01-01

    Objective:To study the effects on human glioma cell line CHG-5 by ultrasonic microbubble intensifier with survivin antisense oligonucleotides (ASODN)transfection. Methods: Antisense oligonucleotides targeting survivin mRNA was designed and synthesized.Four regimen groups were designed,group A:survivin antisense oligonucleotides transfected with ultrasonic microbubble intensifier combined with ultrasound irradiation,group B: survivin antisense oligonucleotides transfected with lipofectamine combined with ultrasound irradiation,group C:survivin antisense oligonucelotides with lipofectamine transfection.group D:blank control.The expression changes of surviving protein were measured by immunohistochemical staining and Western blotting,and MTr assay was used to measure the changes of proliferation.Results:Survivin protein expression in group A was decreased significantly in human glioma cell line CHG-5 than other groups(P<0.05),and the proliferating rate of CHG-5 in group A was also significantly inhibited(P<0.05).Conclusion:Ultrasonic microbubble intensifier transfection combined with ultrasound irradiation is a promising method in gene transfection effectively and noninvasively.

  4. 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

  5. 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.

  6. Galaxy alignment on large and small scales

    Science.gov (United States)

    Kang, X.; Lin, W. P.; Dong, X.; Wang, Y. O.; Dutton, A.; Macciò, A.

    2016-10-01

    Galaxies are not randomly distributed across the universe but showing different kinds of alignment on different scales. On small scales satellite galaxies have a tendency to distribute along the major axis of the central galaxy, with dependence on galaxy properties that both red satellites and centrals have stronger alignment than their blue counterparts. On large scales, it is found that the major axes of Luminous Red Galaxies (LRGs) have correlation up to 30Mpc/h. Using hydro-dynamical simulation with star formation, we investigate the origin of galaxy alignment on different scales. It is found that most red satellite galaxies stay in the inner region of dark matter halo inside which the shape of central galaxy is well aligned with the dark matter distribution. Red centrals have stronger alignment than blue ones as they live in massive haloes and the central galaxy-halo alignment increases with halo mass. On large scales, the alignment of LRGs is also from the galaxy-halo shape correlation, but with some extent of mis-alignment. The massive haloes have stronger alignment than haloes in filament which connect massive haloes. This is contrary to the naive expectation that cosmic filament is the cause of halo alignment.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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...

  16. Decontamination: back to basics.

    Science.gov (United States)

    Meredith, Susan J; Sjorgen, Geoff

    2008-07-01

    My invitation from this Journal's Editor, Felicia Cox, to provide a paper for this themed issue, included the sentence 'I was wondering if you or a colleague would like to contribute a back to basics article on the relevant standards and guidelines for decontamination, including what is compliance?'. The reason it is so interesting to me is that the term 'back to basics' implies reverting to a simpler time in life - when by just sticking to the rules, life became easier. However, with decontamination this is not actually true.

  17. 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

  18. 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

  19. 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''.

  20. Dynamic interferometer alignment and its utility in UV Fourier transform spectrometer systems

    Science.gov (United States)

    Dorval, Rick K.; Engel, James R.; Wyntjes, Geert J.

    1993-01-01

    Dynamic alignment has been demonstrated as a practical approach to alignment maintenance for systems in the infrared region of the spectrum. On the basis of work done by OPTRA, this technique was introduced in commercial Fourier transform spectrometer systems in 1982 and in various forms is now available from a number of manufacturers. This paper reports on work by OPTRA to extend the basic technique to systems operating in the ultraviolet. In addition, this paper reports the preliminary results of the development of an alignment system using a laser diode in place of a gas laser normally found in dynamic alignment systems. A unique optical system and spatial heterodyne technique allows for achievement of a metrology system with characteristics that fully satisfy the requirements of an ultraviolet spectrometer system.

  1. 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.

  2. 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...

  3. Comparative genomics beyond sequence-based alignments

    DEFF Research Database (Denmark)

    Þórarinsson, Elfar; Yao, Zizhen; Wiklund, Eric D.;

    2008-01-01

    Recent computational scans for non-coding RNAs (ncRNAs) in multiple organisms have relied on existing multiple sequence alignments. However, as sequence similarity drops, a key signal of RNA structure--frequent compensating base changes--is increasingly likely to cause sequence-based alignment...... methods to misalign, or even refuse to align, homologous ncRNAs, consequently obscuring that structural signal. We have used CMfinder, a structure-oriented local alignment tool, to search the ENCODE regions of vertebrate multiple alignments. In agreement with other studies, we find a large number...... of potential RNA structures in the ENCODE regions. We report 6587 candidate regions with an estimated false-positive rate of 50%. More intriguingly, many of these candidates may be better represented by alignments taking the RNA secondary structure into account than those based on primary sequence alone, often...

  4. Scintillation counter: photomultiplier tube alignment

    International Nuclear Information System (INIS)

    A scintillation counter, particularly for counting gamma ray photons, includes a massive lead radiation shield surrounding a sample-receiving zone. The shield is disassembleable into a plurality of segments to allow facile installation and removal of a photomultiplier tube assembly, the segments being so constructed as to prevent straight-line access of external radiation through the shield into the sample receiving zone. Provisions are made for accurately aligning the photomultiplier tube with respect to one or more sample-transmitting bores extending through the shield to the sample receiving zone. A sample elevator, used in transporting samples into the zone, is designed to provide a maximum gamma-receiving aspect to maximize the gamma detecting efficiency. (auth)

  5. Recursions for Statistical Multiple Alignment

    DEFF Research Database (Denmark)

    Hein, Jotun; Pedersen, Christian Nørgaard Storm; Jensen, Jens Ledet

    2002-01-01

    Algorithms are presented that allow the calculation of the probability of a set of sequences related by a binary tree that have evolved according to the Thorne–Kishino–Felsenstein model for a fixed set of parameters. The algorithms are based on a Markov chain generating sequences and their alignm...... but probabilistically different. The running time of the algorithms is , where Li is the length of the ith observed sequences and d is the number of sequences. An alternative recursion is also formulated that uses only a Markov chain involving the inner nodes of a tree....... and their alignment at nodes in a tree. Depending on whether the complete realization of this Markov chain is decomposed into the first transition and the rest of the realization or the last transition and the first part of the realization, two kinds of recursions are obtained that are computationally similar...

  6. Fiscal State-Citizen Alignment

    DEFF Research Database (Denmark)

    Celik, Tim Holst

    2016-01-01

    to the 2008 crisis and the larger post-1970s politico-economic constellation. The crisis can be perceived as a particular articulation of an age-old state-household dynamic—a dialectical alignment of the mode of fiscal state-crafting with the ethos of the state-citizen nexus—characterized by a heightened......The 2008 crisis ended the growth bubble of the 2000s, which Organisation for Economic Co-operation and Development (OECD) governments facilitated through the normative/political-regulatory promotion of household indebtedness. Historically contextualizing this state-citizen relationship......, this article maps out four episodes of sovereign fiscalism, namely, debt-taking in the Italian city-states, the making of the absolutist tax/fiscal state, the eighteenth/nineteenth century elaboration of the economic citizen, and the postwar era of managed capitalism. Finally, it applies this framework...

  7. 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

  8. Using Student Reflections to Explore Curriculum Alignment

    OpenAIRE

    Marina Harvey; Chris Baumann

    2012-01-01

    The concept of curriculum alignment is held as a guiding principle of good curriculum design in higher education. Curriculum alignment can be mapped using a variety of strategies and tools. This paper reports on a project that expands the horizons of curriculum review by applying a novel methodology, word clouds, to investigate the use of student reflections for exploring curriculum alignment.Students, from Australia and Denmark, engaged in written reflections about their learning in a Busine...

  9. Measurement of alignment between standards and assessment

    OpenAIRE

    Näsström, Gunilla

    2008-01-01

    Many educational systems of today are standards-based and aim at for alignment, i.e. consistency, among the components of the educational system: standards, teaching and assessment. To conclude whether the alignment is sufficiently high, analyses with a useful model are needed. This thesis investigates the usefulness of models for analyzing alignment between standards and assessments, with emphasis on one method: Bloom’s revised taxonomy. The thesis comprises an introduction and five articles...

  10. FUSE: Multiple Network Alignment via Data Fusion

    OpenAIRE

    Gligorijević, Vladimir; Malod-Dognin, Noël; Pržulj, Nataša

    2014-01-01

    Discovering patterns in networks of protein-protein interactions (PPIs) is a central problem in systems biology. Alignments between these networks aid functional understanding as they uncover important information, such as evolutionary conserved pathways, protein complexes and functional orthologs. The objective of a multiple network alignment is to create clusters of nodes that are evolutionarily conserved and functionally consistent across all networks. Unfortunately, the alignment methods ...

  11. Alignment performance monitoring for ASML systems

    Science.gov (United States)

    Chung, Woong-Jae; Temchenko, Vlad; Hauck, Tarja; Schmidt, Sebastian

    2006-03-01

    In today's semiconductor industry downscaling of the IC design puts a stringent requirement on pattern overlay control. Tighter overlay requirements lead to exceedingly higher rework rates, meaning additional costs to manufacturing. Better alignment control became a target of engineering efforts to decrease rework rate for high-end technologies. Overlay performance is influenced by known parameters such as "Shift, Scaling, Rotation, etc", and unknown parameters defined as "Process Induced Variation", which are difficult to control by means of a process automation system. In reality, this process-induced variation leads to a strong wafer to wafer, or lot to lot variation, which are not easy to detect in the mass-production environment which uses sampling overlay measurements for only several wafers in a lot. An engineering task of finding and correcting a root cause for Process Induced Variations of overlay performance will be greatly simplified if the unknown parameters could be tracked for each wafer. This paper introduces an alignment performance monitoring method based on analysis of automatically generated "AWE" files for ASML scanner systems. Because "AWE" files include alignment results for each aligned wafer, it is possible to use them for monitoring, controlling and correcting the causes of "process induced" overlay performance without requiring extra measurement time. Since "AWE" files include alignment information for different alignment marks, it is also possible to select and optimize the best alignment recipe for each alignment strategy. Several case studies provided in our paper will demonstrate how AWE file analysis can be used to assist engineer in interpreting pattern alignment data. Since implementing our alignment data monitoring method, we were able to achieve significant improvement of alignment and overlay performance without additional overlay measurement time. We also noticed that the rework rate coming from alignment went down and

  12. COS to FGS Alignment {NUV}

    Science.gov (United States)

    Hartig, George

    2009-07-01

    DESCRIPTION: In order to determine the location of the COS reference frame with respect to the FGS reference frames, NUV MIRRORA images will be obtained of an astrometric target and field. Astrometric guide stars and targets must be employed for this activity in order to facilitate the alignment wth the FGS. Images will be obtained at the initial pointing and at positions offset in V2 and in V3. Starting with the original blind pointing, obtain MIRRORA image exposures in a 5x5 POS-TARG grid centered on initial pointing; repeat the image sequence at two bracketing focus positions in same visit. Following completion of third pattern, return to nominal focus and perform 5x5 ACQ/SEARCH target acquisition and obtain one TIME-TAG MIRRORA image and one ACCUM verification exposure. Next perform an ACQ/IMAGE target acquisition followed by an ACCUM verification exposure. Also obtain ACCUM verification exposure for each of the two alternate focus positions used previously. Using MIRRORB obtain ACCUM confirmation image at nominal focus and ACCUM images at alternate focus positions and then perform an ACQ/IMAGE and confirming image at nominal focus. Analyze imagery, uplink pointing offset as offset 11469A and adjust nominal focus via patchable constant uplinked with subsequent visit of this program; update aperture locations via modified SIAF file uplinked with subsequent SMS. Use updated focus and offset pointing as input for COS 09 {program 11469 - NUV Optics Alignment and Focus} {note the SIAF update is not a prerequisite for COS 09 to proceed, but the pointing offset and focus update are}.

  13. Basic Drafting: Book Two.

    Science.gov (United States)

    Davis, Ronald; And Others

    The second of a two-book course in drafting, this manual consists of 12 topics in the following units: sketching techniques, geometric constructions, orthographic views, dimensioning procedures, basic tolerancing, auxiliary views, sectional views, inking tools and techniques, axonometrics, oblique, perspective, and computer-aided drafting.…

  14. 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,…

  15. 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...

  16. 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.

  17. 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.

  18. 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)

  19. FULA BASIC COURSE.

    Science.gov (United States)

    SWIFT, LLOYD B.; AND OTHERS

    THIS BEGINNING COURSE IS AN INTRODUCTION TO FULA (KNOWN VARIOUSLY AS FULANI, FUL, PEUL, OR PHEUL), A NIGER-CONGO LANGUAGE SPOKEN THROUGHOUT THE GRASSLAND AREAS OF WEST AFRICA FROM THE ATLANTIC TO CAMEROUN. THE TEXT IS ONE OF A SERIES OF SHORT BASIC COURSES IN SELECTED AFRICAN LANGUAGES BEING PREPARED BY THE FOREIGN SERVICE INSTITUTE. IT IS…

  20. Basic bioreactor design.

    NARCIS (Netherlands)

    Riet, van 't K.; Tramper, J.

    1991-01-01

    Based on a graduate course in biochemical engineering, provides the basic knowledge needed for the efficient design of bioreactors and the relevant principles and data for practical process engineering, with an emphasis on enzyme reactors and aerated reactors for microorganisms. Includes exercises.

  1. 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…

  2. 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…

  3. 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.

  4. Track Based Alignment of Composite Detector Structures

    CERN Document Server

    Karimäki, V; Schilling, F P

    2006-01-01

    An iterative algorithm for track based alignment is presented. The algorithm can be applied to rigid composite detector structures or to individual modules. The iterative process involves track reconstruction and alignment, in which the chi-2 function of the hit residuals of each alignable object is minimized. Six alignment parameters per structure or per module, three for location and three for orientation, can be computed. The method is computationally light and easily parallelizable. The performance of the method is demonstrated with simulated tracks in the CMS pixel detector and tracks reconstructed from experimental data recorded with a test beam setup.

  5. Molecular alignment using circularly polarized laser pulses

    CERN Document Server

    Smeenk, C T L

    2013-01-01

    We show that circularly polarized femtosecond laser pulses produce field-free alignment in linear and planar molecules. We study the rotational wavepacket evolution of O$_2$ and benzene created by circularly polarized light. For benzene, we align the molecular plane to the plane of polarization. For O$_2$, we demonstrate that circular polarization yields a net alignment along the laser propagation axis at certain phases of the evolution. Circular polarization gives us the ability to control alignment of linear molecules outside the plane of polarization, providing new capabilities for molecular imaging.

  6. The twilight zone of cis element alignments.

    Science.gov (United States)

    Sebastian, Alvaro; Contreras-Moreira, Bruno

    2013-02-01

    Sequence alignment of proteins and nucleic acids is a routine task in bioinformatics. Although the comparison of complete peptides, genes or genomes can be undertaken with a great variety of tools, the alignment of short DNA sequences and motifs entails pitfalls that have not been fully addressed yet. Here we confront the structural superposition of transcription factors with the sequence alignment of their recognized cis elements. Our goals are (i) to test TFcompare (http://floresta.eead.csic.es/tfcompare), a structural alignment method for protein-DNA complexes; (ii) to benchmark the pairwise alignment of regulatory elements; (iii) to define the confidence limits and the twilight zone of such alignments and (iv) to evaluate the relevance of these thresholds with elements obtained experimentally. We find that the structure of cis elements and protein-DNA interfaces is significantly more conserved than their sequence and measures how this correlates with alignment errors when only sequence information is considered. Our results confirm that DNA motifs in the form of matrices produce better alignments than individual sequences. Finally, we report that empirical and theoretically derived twilight thresholds are useful for estimating the natural plasticity of regulatory sequences, and hence for filtering out unreliable alignments.

  7. IMAGA: INTRON MULTIPLE ALIGNMENT USING GENETIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    V. AMOUDA,

    2010-11-01

    Full Text Available Multiple sequence alignment (MSA is one of the multi-dimensional problems in biology. This paper describes a new approach to solve MSA, a NP-hard problem using modified Genetic Algorithm with new mutation operator. A web based tool iMAGA (Intron Multiple Alignment using Genetic Algorithm is developed for aligning the intron sequences in order to find the pattern. It has two modules (i iExtractor/ iClassifier which extracts and classifies introns (ii iAligner/ Pattern Finder which aligns the intron sequences and finds the patterns. iAligner, the core module of the tool aligns any type of sequences (DNA, RNA, Protein & Intron. In this module GA is applied in which the chromosome consists of gap positions. On applying conventional mutation operator leads to problems like repetition and increase in number of gap positions. To overcome theseproblems, a newly designed mutation operator X-Shuffler is proposed.To validate the alignment, the sum-of-pairs score is used to compare iMAGA with widely used tools. The data sets chosen from the standard BaliBASE, SMART and OXBENCH benchmark alignment suite. To validate the pattern obtained using iMAGA tool, the similarity percentage of the pattern is compared with MEME, a widely used motif finder. Dataset of Saccharomyces Cerviceae with 254 intron sequences are used to prove this work. The tool is available at www.imaga.bicpu.edu.in.

  8. Triangular Alignment (TAME). A Tensor-based Approach for Higher-order Network Alignment

    Energy Technology Data Exchange (ETDEWEB)

    Mohammadi, Shahin [Purdue Univ., West Lafayette, IN (United States); Gleich, David F. [Purdue Univ., West Lafayette, IN (United States); Kolda, Tamara G. [Sandia National Laboratories (SNL-CA), Livermore, CA (United States); Grama, Ananth [Purdue Univ., West Lafayette, IN (United States)

    2015-11-01

    Network alignment is an important tool with extensive applications in comparative interactomics. Traditional approaches aim to simultaneously maximize the number of conserved edges and the underlying similarity of aligned entities. We propose a novel formulation of the network alignment problem that extends topological similarity to higher-order structures and provide a new objective function that maximizes the number of aligned substructures. This objective function corresponds to an integer programming problem, which is NP-hard. Consequently, we approximate this objective function as a surrogate function whose maximization results in a tensor eigenvalue problem. Based on this formulation, we present an algorithm called Triangular AlignMEnt (TAME), which attempts to maximize the number of aligned triangles across networks. We focus on alignment of triangles because of their enrichment in complex networks; however, our formulation and resulting algorithms can be applied to general motifs. Using a case study on the NAPABench dataset, we show that TAME is capable of producing alignments with up to 99% accuracy in terms of aligned nodes. We further evaluate our method by aligning yeast and human interactomes. Our results indicate that TAME outperforms the state-of-art alignment methods both in terms of biological and topological quality of the alignments.

  9. Amino acids attached to 2'-amino-LNA: Synthesis of DNA mixmer oligonucleotides with increased duplex stability

    DEFF Research Database (Denmark)

    Johannsen, Marie Willaing; Wengel, Jesper; Wamberg, Michael Chr.;

    2010-01-01

    The synthesis of 2'-amino-LNA (locked nucleic acid) opens up exciting possibilities for modification of nucleic acids by conjugation to the 2'-nitrogen. Incorporation of unmodified and N-functionalized 2'-amino-LNA nucleotides improve duplex stability compared to unmodified DNA. 2'-Amino......-LNA nucleosides derivatized with amino acids have been synthesized and incorporated into DNA oligonucleotides. Following oligonucleotide synthesis, peptides have been added using solid phase peptide coupling chem. Modification of oligonucleotides with pos. charged residues greatly improves thermal stability....

  10. Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates

    DEFF Research Database (Denmark)

    Straarup, Ellen Marie; Fisker, Niels; Hedtjärn, Maj;

    2010-01-01

    -life as longer oligonucleotides. Pharmacology studies in both mice and non-human primates were conducted with a 13-mer LNA oligonucleotide against apoB, and the data showed that repeated dosing of the 13-mer at 1-2 mg/kg/week was sufficient to provide a significant and long lasting lowering of non-high-density......The potency and specificity of locked nucleic acid (LNA) antisense oligonucleotides was investigated as a function of length and affinity. The oligonucleotides were designed to target apolipoprotein B (apoB) and were investigated both in vitro and in vivo. The high affinity of LNA enabled...... the design of short antisense oligonucleotides (12- to 13-mers) that possessed high affinity and increased potency both in vitro and in vivo compared to longer oligonucleotides. The short LNA oligonucleotides were more target specific, and they exhibited the same biodistribution and tissue half...

  11. Bayesian coestimation of phylogeny and sequence alignment

    Directory of Open Access Journals (Sweden)

    Jensen Jens

    2005-04-01

    Full Text Available Abstract Background Two central problems in computational biology are the determination of the alignment and phylogeny of a set of biological sequences. The traditional approach to this problem is to first build a multiple alignment of these sequences, followed by a phylogenetic reconstruction step based on this multiple alignment. However, alignment and phylogenetic inference are fundamentally interdependent, and ignoring this fact leads to biased and overconfident estimations. Whether the main interest be in sequence alignment or phylogeny, a major goal of computational biology is the co-estimation of both. Results We developed a fully Bayesian Markov chain Monte Carlo method for coestimating phylogeny and sequence alignment, under the Thorne-Kishino-Felsenstein model of substitution and single nucleotide insertion-deletion (indel events. In our earlier work, we introduced a novel and efficient algorithm, termed the "indel peeling algorithm", which includes indels as phylogenetically informative evolutionary events, and resembles Felsenstein's peeling algorithm for substitutions on a phylogenetic tree. For a fixed alignment, our extension analytically integrates out both substitution and indel events within a proper statistical model, without the need for data augmentation at internal tree nodes, allowing for efficient sampling of tree topologies and edge lengths. To additionally sample multiple alignments, we here introduce an efficient partial Metropolized independence sampler for alignments, and combine these two algorithms into a fully Bayesian co-estimation procedure for the alignment and phylogeny problem. Our approach results in estimates for the posterior distribution of evolutionary rate parameters, for the maximum a-posteriori (MAP phylogenetic tree, and for the posterior decoding alignment. Estimates for the evolutionary tree and multiple alignment are augmented with confidence estimates for each node height and alignment column

  12. Alignments between galaxies, satellite systems and haloes

    Science.gov (United States)

    Shao, Shi; Cautun, Marius; Frenk, Carlos S.; Gao, Liang; Crain, Robert A.; Schaller, Matthieu; Schaye, Joop; Theuns, Tom

    2016-08-01

    The spatial distribution of the satellite populations of the Milky Way and Andromeda are puzzling in that they are nearly perpendicular to the discs of their central galaxies. To understand the origin of such configurations we study the alignment of the central galaxy, satellite system and dark matter halo in the largest of the `Evolution and Assembly of GaLaxies and their Environments' (EAGLE) simulation. We find that centrals and their satellite systems tend to be well aligned with their haloes, with a median misalignment angle of 33° in both cases. While the centrals are better aligned with the inner 10 kpc halo, the satellite systems are better aligned with the entire halo indicating that satellites preferentially trace the outer halo. The central-satellite alignment is weak (median misalignment angle of 52°) and we find that around 20 per cent of systems have a misalignment angle larger than 78°, which is the value for the Milky Way. The central-satellite alignment is a consequence of the tendency of both components to align with the dark matter halo. As a consequence, when the central is parallel to the satellite system, it also tends to be parallel to the halo. In contrast, if the central is perpendicular to the satellite system, as in the case of the Milky Way and Andromeda, then the central-halo alignment is much weaker. Dispersion-dominated (spheroidal) centrals have a stronger alignment with both their halo and their satellites than rotation-dominated (disc) centrals. We also found that the halo, the central galaxy and the satellite system tend to be aligned with the surrounding large-scale distribution of matter, with the halo being the better aligned of the three.

  13. Basics of RF electronics

    CERN Document Server

    Gallo, A

    2011-01-01

    RF electronics deals with the generation, acquisition and manipulation of high-frequency signals. In particle accelerators signals of this kind are abundant, especially in the RF and beam diagnostics systems. In modern machines the complexity of the electronics assemblies dedicated to RF manipulation, beam diagnostics, and feedbacks is continuously increasing, following the demands for improvement of accelerator performance. However, these systems, and in particular their front-ends and back-ends, still rely on well-established basic hardware components and techniques, while down-converted and acquired signals are digitally processed exploiting the rapidly growing computational capability offered by the available technology. This lecture reviews the operational principles of the basic building blocks used for the treatment of high-frequency signals. Devices such as mixers, phase and amplitude detectors, modulators, filters, switches, directional couplers, oscillators, amplifiers, attenuators, and others are d...

  14. 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.

  15. 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:...

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. 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....

  1. 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

  2. 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)

  3. 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.

  4. 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.

  5. Business and IT alignment in context

    NARCIS (Netherlands)

    Silvius, A.J.G.

    2013-01-01

    Already for more than two decades, the necessity and desirability of aligning business needs and information technology (IT) capabilities is considered to be one of the key issues in IT management. However, several studies report quite low scores on business and IT alignment (BIA). The question “Why

  6. Sambamba: fast processing of NGS alignment formats

    NARCIS (Netherlands)

    Tarasov, A.; Vilella, A.J.; Cuppen, E.; Nijman, I.J.; Prins, J.C.P.

    2015-01-01

    Sambamba is a high-performance robust tool and library for working with SAM, BAM and CRAM sequence alignment files; the most common file formats for aligned next generation sequencing data. Sambamba is a faster alternative to samtools that exploits multi-core processing and dramatically reduces proc

  7. Automatic alignment of hieroglyphs and transliteration

    OpenAIRE

    Nederhof, Mark Jan

    2009-01-01

    Automatic alignment has important applications in philology, facilitating study of texts on the basis of electronic resources produced by different scholars. A simple technique is presented to realise such alignment for Ancient Egyptian hieroglyphic texts and transliteration. Preliminary experiments with the technique are reported, and plans for future work are discussed. Postprint

  8. A cross-species alignment tool (CAT)

    DEFF Research Database (Denmark)

    Li, Heng; Guan, Liang; Liu, Tao;

    2007-01-01

    BACKGROUND: The main two sorts of automatic gene annotation frameworks are ab initio and alignment-based, the latter splitting into two sub-groups. The first group is used for intra-species alignments, among which are successful ones with high specificity and speed. The other group contains more...

  9. Aligning the μs-ALEX Setup.

    Science.gov (United States)

    Kapanidis, Achillefs; Majumdar, Devdoot; Heilemann, Mike; Nir, Eyal; Weiss, Shimon

    2015-11-01

    To achieve single-molecule sensitivity and thus have the ability to detect single diffusing fluorophores, careful alignment of the microsecond-alternating laser excitation (μs-Alex) setup is crucial. The following protocol describes routine alignment for 2c-ALEX (532 nm/635 nm) with spectral windows G(550-620)R(650-750). PMID:26527766

  10. Compositions for directed alignment of conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinsang; Kim, Bong-Gi; Jeong, Eun Jeong

    2016-04-19

    Conjugated polymers (CPs) achieve directed alignment along an applied flow field and a dichroic ratio of as high as 16.67 in emission from well-aligned thin films and fully realized anisotropic optoelectronic properties of CPs in field-effect transistor (FET).

  11. Evaluating Alignment between Curriculum, Assessment, and Instruction

    Science.gov (United States)

    Martone, Andrea; Sireci, Stephen G.

    2009-01-01

    The authors (a) discuss the importance of alignment for facilitating proper assessment and instruction, (b) describe the three most common methods for evaluating the alignment between state content standards and assessments, (c) discuss the relative strengths and limitations of these methods, and (d) discuss examples of applications of each…

  12. Instructional Alignment under No Child Left Behind

    Science.gov (United States)

    Polikoff, Morgan S.

    2012-01-01

    The alignment of instruction with the content of standards and assessments is the key mediating variable separating the policy of standards-based reform (SBR) from the outcome of improved student achievement. Few studies have investigated SBR's effects on instructional alignment, and most have serious methodological limitations. This research uses…

  13. Optical packet switching without packet alignment

    DEFF Research Database (Denmark)

    Hansen, Peter Bukhave; Danielsen, Søren Lykke; Stubkjær, Kristian

    1998-01-01

    Operation without packet alignment of an all-optical packet switch is proposed and predicted feasible through a detailed traffic analysis. Packet alignment units are eliminated resulting in a simple switch architecture while optimal traffic performance is maintained through the flexibility provided...

  14. Alignment Nashville. Complementary Learning in Action

    Science.gov (United States)

    Bouffard, Suzanne; Malone, Helen

    2007-01-01

    This profile illustrates how Alignment Nashville brings together diverse community members and organizations to leverage existing resources in support of Nashville's youth and the Metro Nashville Public Schools. In addition to a diversified funding structure, Alignment leaders point to three factors that have helped them get the effort off the…

  15. Sambamba : Fast processing of NGS alignment formats

    NARCIS (Netherlands)

    Tarasov, Artem; Vilella, Albert J.; Cuppen, Edwin; Nijman, Isaac J.; Prins, Pjotr

    2015-01-01

    Summary: Sambamba is a high-performance robust tool and library for working with SAM, BAM and CRAM sequence alignment files; the most common file formats for aligned next generation sequencing data. Sambamba is a faster alternative to samtools that exploits multi-core processing and dramatically red

  16. On comparing two structured RNA multiple alignments.

    Science.gov (United States)

    Patel, Vandanaben; Wang, Jason T L; Setia, Shefali; Verma, Anurag; Warden, Charles D; Zhang, Kaizhong

    2010-12-01

    We present a method, called BlockMatch, for aligning two blocks, where a block is an RNA multiple sequence alignment with the consensus secondary structure of the alignment in Stockholm format. The method employs a quadratic-time dynamic programming algorithm for aligning columns and column pairs of the multiple alignments in the blocks. Unlike many other tools that can perform pairwise alignment of either single sequences or structures only, BlockMatch takes into account the characteristics of all the sequences in the blocks along with their consensus structures during the alignment process, thus being able to achieve a high-quality alignment result. We apply BlockMatch to phylogeny reconstruction on a set of 5S rRNA sequences taken from fifteen bacteria species. Experimental results showed that the phylogenetic tree generated by our method is more accurate than the tree constructed based on the widely used ClustalW tool. The BlockMatch algorithm is implemented into a web server, accessible at http://bioinformatics.njit.edu/blockmatch. A jar file of the program is also available for download from the web server. PMID:21121021

  17. The GEM Detector projective alignment simulation system

    International Nuclear Information System (INIS)

    Precision position knowledge (< 25 microns RMS) of the GEM Detector muon system at the Superconducting Super Collider Laboratory (SSCL) is an important physics requirement necessary to minimize sagitta error in detecting and tracking high energy muons that are deflected by the magnetic field within the GEM Detector. To validate the concept of the sagitta correction function determined by projective alignment of the muon detectors (Cathode Strip Chambers or CSCs), the basis of the proposed GEM alignment scheme, a facility, called the ''Alignment Test Stand'' (ATS), is being constructed. This system simulates the environment that the CSCs and chamber alignment systems are expected to experience in the GEM Detector, albeit without the 0.8 T magnetic field and radiation environment. The ATS experimental program will allow systematic study and characterization of the projective alignment approach, as well as general mechanical engineering of muon chamber mounting concepts, positioning systems and study of the mechanical behavior of the proposed 6 layer CSCs. The ATS will consist of a stable local coordinate system in which mock-ups of muon chambers (i.e., non-working mechanical analogs, representing the three superlayers of a selected barrel and endcap alignment tower) are implemented, together with a sufficient number of alignment monitors to overdetermine the sagitta correction function, providing a self-consistency check. This paper describes the approach to be used for the alignment of the GEM muon system, the design of the ATS, and the experiments to be conducted using the ATS

  18. Achieving Organisational Change through Values Alignment

    Science.gov (United States)

    Branson, Christopher M.

    2008-01-01

    Purpose: The purpose of this paper is to, first, establish the interdependency between the successful achievement of organisational change and the attainment of values alignment within an organisation's culture and then, second, to describe an effective means for attaining such values alignment. Design/methodology/approach: Literature from the…

  19. SOA-Driven Business-Software Alignment

    NARCIS (Netherlands)

    Shishkov, Boris; Sinderen, van Marten; Quartel, Dick

    2006-01-01

    The alignment of business processes and their supporting application software is a major concern during the initial software design phases. This paper proposes a design approach addressing this problem of business-software alignment. The approach takes an initial business model as a basis in derivin

  20. Vacuum alignment with(out) elementary scalars

    CERN Document Server

    Alanne, Tommi; Meroni, Aurora; Sannino, Francesco

    2016-01-01

    We systematically elucidate differences and similarities of the vacuum alignment issue in composite and renormalizable elementary extensions of the Standard Model featuring a pseudo-Goldstone Higgs. We also provide general conditions for the stability of the vacuum in the elementary framework, thereby extending previous studies of the vacuum alignment.