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Sample records for dna modifications driving

  1. DNA modification by alkylating compounds

    Energy Technology Data Exchange (ETDEWEB)

    Kruglyakova, E.E.

    1985-09-01

    Results are given for research on the physico-chemical properties of alkylating compounds - nitroso alkyl ureas (NAU) which possess a broad spectrum of biological activity, such as mutagenic, carcinogenic, and anti-tumor action that is due to the alkylation and carbamoylation of DNA as well as other cellular components. Identified chemical products of NAU interaction with DNA and its components are cited. Structural conversions of a DNA macromolecule resulting from its chemical modification are examined. NAU are used to discuss possible biological consequences of DNA modification. 148 references.

  2. Drug Addiction and DNA Modifications.

    Science.gov (United States)

    Brown, Amber N; Feng, Jian

    2017-01-01

    Drug addiction is a complex disorder which can be influenced by both genetic and environmental factors. Research has shown that epigenetic modifications can translate environmental signals into changes in gene expression, suggesting that epigenetic changes may underlie the causes and possibly treatment of substance use disorders. This chapter will focus on epigenetic modifications to DNA, which include DNA methylation and several recently defined additional DNA epigenetic changes. We will discuss the functions of DNA modifications and methods for detecting them, followed by a description of the research investigating the function and consequences of drug-induced changes in DNA methylation patterns. Understanding these epigenetic changes may provide us translational tools for the diagnosis and treatment of addiction in the future.

  3. Chemical modifications and reactions in DNA nanostructures

    DEFF Research Database (Denmark)

    Gothelf, Kurt Vesterager

    2017-01-01

    such as hydrocarbons or steroids have been introduced to change the surface properties of DNA origami structures, either to protect the DNA nanostructure or to dock it into membranes and other hydrophobic surfaces. DNA nanostructures have also been used to control covalent chemical reactions. This article provides......DNA nanotechnology has the power to form self-assembled and well-defined nanostructures, such as DNA origami, where the relative positions of each atom are known with subnanometer precision. Our ability to synthesize oligonucleotides with chemical modifications in almost any desired position...... provides rich opportunity to incorporate molecules, biomolecules, and a variety of nanomaterials in specific positions on DNA nanostructures. Several standard modifications for oligonucleotides are available commercially, such as dyes, biotin, and chemical handles, and such modified oligonucleotides can...

  4. Histone modifications in response to DNA damage

    International Nuclear Information System (INIS)

    Altaf, Mohammed; Saksouk, Nehme; Cote, Jacques

    2007-01-01

    The packaging of the eukaryotic genome into highly condensed chromatin makes it inaccessible to the factors required for gene transcription, DNA replication, recombination and repair. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by chromatin. Histone modifying enzymes and ATP-dependent chromatin remodeling complexes play key roles here as they regulate many nuclear processes by altering the chromatin structure. Significantly, these activities are integral to the process of DNA repair where histone modifications act as signals and landing platforms for various repair proteins. This review summarizes the recent developments in our understanding of histone modifications and their role in the maintenance of genome integrity

  5. Mapping Base Modifications in DNA by Transverse-Current Sequencing

    Science.gov (United States)

    Alvarez, Jose R.; Skachkov, Dmitry; Massey, Steven E.; Kalitsov, Alan; Velev, Julian P.

    2018-02-01

    Sequencing DNA modifications and lesions, such as methylation of cytosine and oxidation of guanine, is even more important and challenging than sequencing the genome itself. The traditional methods for detecting DNA modifications are either insensitive to these modifications or require additional processing steps to identify a particular type of modification. Transverse-current sequencing in nanopores can potentially identify the canonical bases and base modifications in the same run. In this work, we demonstrate that the most common DNA epigenetic modifications and lesions can be detected with any predefined accuracy based on their tunneling current signature. Our results are based on simulations of the nanopore tunneling current through DNA molecules, calculated using nonequilibrium electron-transport methodology within an effective multiorbital model derived from first-principles calculations, followed by a base-calling algorithm accounting for neighbor current-current correlations. This methodology can be integrated with existing experimental techniques to improve base-calling fidelity.

  6. C-5 Propynyl Modifications Enhance the Mechanical Stability of DNA.

    Science.gov (United States)

    Aschenbrenner, Daniela; Baumann, Fabian; Milles, Lukas F; Pippig, Diana A; Gaub, Hermann E

    2015-07-20

    Increased thermal or mechanical stability of DNA duplexes is desired for many applications in nanotechnology or -medicine where DNA is used as a programmable building block. Modifications of pyrimidine bases are known to enhance thermal stability and have the advantage of standard base-pairing and easy integration during chemical DNA synthesis. Through single-molecule force spectroscopy experiments with atomic force microscopy and the molecular force assay we investigated the effect of pyrimidines harboring C-5 propynyl modifications on the mechanical stability of double-stranded DNA. Utilizing these complementary techniques, we show that propynyl bases significantly increase the mechanical stability if the DNA is annealed at high temperature. In contrast, modified DNA complexes formed at room temperature and short incubation times display the same stability as non-modified DNA duplexes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Analysis of epigenetic modifications of DNA in human cells

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Treppendahl, Marianne Bach; Grønbæk, Kirsten

    2013-01-01

    Epigenetics, the study of somatically heritable changes in gene expression not related to changes in the DNA sequence, is a rapidly expanding research field that plays important roles in healthy as well as in diseased cells. DNA methylation and hydroxymethylation are epigenetic modifications found...

  8. Chromatin modifications and the DNA damage response to ionizing radiation

    International Nuclear Information System (INIS)

    Kumar, Rakesh; Horikoshi, Nobuo; Singh, Mayank; Gupta, Arun; Misra, Hari S.; Albuquerque, Kevin; Hunt, Clayton R.; Pandita, Tej K.

    2013-01-01

    In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double-strand breaks (DSBs), that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: (1) non-homologous end joining, which re-ligates the broken ends of the DNA and (2) homologous recombination, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but post-translational modification of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modifications by the respective chromatin modifying factors that occur during the DNA damage response.

  9. Mapping DNA cleavage by the Type ISP restriction-modification enzymes following long-range communication between DNA sites in different orientations

    OpenAIRE

    van Aelst, Kara; Saikrishnan, Kayarat; Szczelkun, Mark D

    2015-01-01

    The prokaryotic Type ISP restriction-modification enzymes are single-chain proteins comprising an Mrr-family nuclease, a superfamily 2 helicase-like ATPase, a coupler domain, a methyltransferase, and a DNA-recognition domain. Upon recognising an unmodified DNA target site, the helicase-like domain hydrolyzes ATP to cause site release (remodeling activity) and to then drive downstream translocation consuming 1-2 ATP per base pair (motor activity). On an invading foreign DNA, double-strand brea...

  10. Drama Drives a DNA Fingerprinting Lab Exercise.

    Science.gov (United States)

    Rubenstein, Elaine C.; And Others

    1996-01-01

    Presents a laboratory exercise for an intermediate cell and molecular biology course that uses a murder-mystery play. Provokes students to think critically about important issues in scientific methodology in general and DNA analysis in particular. (JRH)

  11. Principles of ubiquitin and SUMO modifications in DNA repair

    NARCIS (Netherlands)

    Bergink, Steven; Jentsch, Stefan

    2009-01-01

    With the discovery in the late 1980s that the DNA-repair gene RAD6 encodes a ubiquitin-conjugating enzyme, it became clear that protein modification by ubiquitin conjugation has a much broader significance than had previously been assumed. Now, two decades later, ubiquitin and its cousin SUMO are

  12. Oxidative DNA base modifications as factors in carcinogenesis

    International Nuclear Information System (INIS)

    Olinski, R.; Jaruga, P.; Zastawny, T.H.

    1998-01-01

    Reactive oxygen species can cause extensive DNA modifications including modified bases. Some of the DNA base damage has been found to possess premutagenic properties. Therefore, if not repaired, it can contribute to carcinogenesis. We have found elevated amounts of modified bases in cancerous and precancerous tissues as compared with normal tissues. Most of the agents used in anticancer therapy are paradoxically responsible for induction of secondary malignancies and some of them may generate free radicals. The results of our experiments provide evidence that exposure of cancer patients to therapeutic doses of ionizing radiation and anticancer drugs cause base modifications in genomic DNA of lymphocytes. Some of these base damages could lead to mutagenesis in critical genes and ultimately to secondary cancers such as leukemias. This may point to an important role of oxidative base damage in cancer initiation. Alternatively, the increased level of the modified base products may contribute to genetic instability and metastatic potential of tumor cells. (author)

  13. 5-Hydroxymethylcytosine is a predominantly stable DNA modification

    Science.gov (United States)

    Bachman, Martin; Uribe-Lewis, Santiago; Yang, Xiaoping; Williams, Michael; Murrell, Adele; Balasubramanian, Shankar

    2014-12-01

    5-Hydroxymethylcytosine (hmC) is an oxidation product of 5-methylcytosine which is present in the deoxyribonucleic acid (DNA) of most mammalian cells. Reduction of hmC levels in DNA is a hallmark of cancers. Elucidating the dynamics of this oxidation reaction and the lifetime of hmC in DNA is fundamental to understanding hmC function. Using stable isotope labelling of cytosine derivatives in the DNA of mammalian cells and ultrasensitive tandem liquid-chromatography mass spectrometry, we show that the majority of hmC is a stable modification, as opposed to a transient intermediate. In contrast with DNA methylation, which occurs immediately during replication, hmC forms slowly during the first 30 hours following DNA synthesis. Isotopic labelling of DNA in mouse tissues confirmed the stability of hmC in vivo and demonstrated a relationship between global levels of hmC and cell proliferation. These insights have important implications for understanding the states of chemically modified DNA bases in health and disease.

  14. DNA methylation modifications associated with chronic fatigue syndrome.

    Directory of Open Access Journals (Sweden)

    Wilfred C de Vega

    Full Text Available Chronic Fatigue Syndrome (CFS, also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Gene ontology (GO and network analysis of differentially methylated genes was performed to determine potential biological pathways showing changes in DNA methylation in CFS. We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS. These data are consistent with evidence of multisystem dysregulation in CFS and implicate the involvement of DNA modifications in CFS pathology.

  15. Modifications of DNA clamps and their role in DNA damage management

    NARCIS (Netherlands)

    Wit, N.

    2013-01-01

    We show that proliferating cell nuclear antigen (PCNA) modification plays an important role in the efficient regulation of mammalian translesion DNA synthesis (TLS), but, as opposed to lower eukaryotes such as yeast, TLS polymerases can also be activated without ubiquitinated PCNA (PCNA-Ub). Future

  16. The role of DNA methylation and histone modifications in neurodegenerative diseases: A systematic review

    NARCIS (Netherlands)

    K.-X. Wen (Ke-Xin); J. Milic (Jelena); El-Khodor, B. (Bassem); K. Dhana (Klodian); J. Nano (Jana); Pulido, T. (Tammy); B. Kraja (Bledar); A. Zaciragic (Asija); W.M. Bramer (Wichor); J. Troup; R. Chowdhury (Rajiv); Arfam Ikram, M.; A. Dehghan (Abbas); T. Muka (Taulant); O.H. Franco (Oscar)

    2016-01-01

    textabstractImportance Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). Objective To systematically review studies

  17. Modification of DNA radiolysis by DNA-binding proteins: Structural aspects

    International Nuclear Information System (INIS)

    Davidkova, M.; Stisova, V.; Goffinont, S.; Gillard, N.; Castaing, B.; Spotheim-Maurizot, M.

    2006-01-01

    Formation of specific complexes between proteins and their cognate DNA modulates the yields and the location of radiation damage on both partners of the complex. The radiolysis of DNA-protein complexes is studied for: (1) the Escherichia coli lactose operator-repressor complex, (2) the complex between DNA bearing an analogue of an abasic site and the repair protein Fpg of Lactococcus lactis. Experimental patterns of DNA damages are presented and compared to predicted damage distribution obtained using an improved version of the stochastic model RADACK. The same method is used for predicting the location of damages on the proteins. At doses lower than a threshold that depends on the system, proteins protect their specific binding site on DNA while at high doses, the studied complexes are disrupted mainly through protein damage. The loss of binding ability is the functional consequence of the amino-acids modification by OH . radicals. Many of the most probably damaged amino acids are essential for the DNA-protein interaction and within a complex are protected by DNA. (authors)

  18. Simple surface modification of poly(dimethylsiloxane) for DNA hybridization

    Science.gov (United States)

    Zhou, Jinwen; Voelcker, Nicolas H.; Ellis, Amanda V.

    2010-01-01

    Here, we present a simple chemical modification of poly(dimethylsiloxane) (PDMS) by curing a mixture of 2 wt% undecylenic acid (UDA) in PDMS prepolymer on a gold-coated glass slide. This gold slide had been previously pretreated with a self-assembled hydrophilic monolayer of 3-mercaptopropionic acid (MPA). During curing of the UDA∕PDMS prepolymer, the hydrophilic UDA carboxyl moieties diffuses toward the hydrophilic MPA carboxyl moieties on the gold surface. This diffusion of the UDA within the PDMS prepolymer to the surface is a direct result of surface energy minimization. Once completely cured, the PDMS is peeled off the gold substrate, thereby exposing the interfacial carboxyl groups. These groups are then available for subsequent attachment of 5′-amino terminated DNA oligonucleotides via amide linkages. Our results show that the covalently tethered oligonucleotides can successfully capture fluorescein-labeled complementary oligonucleotides via hybridization, which are visualized using fluorescence microscopy. PMID:21264061

  19. Noncovalent DNA Binding Drives DNA Alkylation by Leinamycin. Evidence That the Z,E-5-(Thiazol-4-yl)-penta-2,4-dienone Moiety of the Natural Product Serves As An Atypical DNA Intercalator

    Science.gov (United States)

    Fekry, Mostafa I.; Szekely, Jozsef; Dutta, Sanjay; Breydo, Leonid; Zang, Hong; Gates, Kent S.

    2012-01-01

    Molecular recognition and chemical modification of DNA are important in medicinal chemistry, toxicology, and biotechnology. Historically, natural products have revealed many interesting and unexpected mechanisms for noncovalent DNA binding and covalent DNA modification. The studies reported here characterize the molecular mechanisms underlying the efficient alkylation of duplex DNA by the Streptomyces-derived natural product leinamycin. Previous studies suggested that alkylation of duplex DNA by activated leinamycin (2) is driven by noncovalent association of the natural product with the double helix. This is striking because leinamycin does not contain a classical noncovalent DNA-binding motif such as an intercalating unit, a groove binder, or a polycation. The experiments described here provide evidence that leinamycin is an atypical DNA-intercalating agent. A competition binding assay involving daunomycin-mediated inhibition of DNA alkylation by leinamycin provided evidence that activated leinamycin binds to duplex DNA with an apparent binding constant of approximately 4.3 ± 0.4 × 103 M−1. Activated leinamycin caused duplex unwinding and hydrodynamic changes in DNA-containing solutions that are indicative of DNA intercalation. Characterization of the reaction of activated leinamycin with palindromic duplexes containing 5'-CG and 5'-GC target sites, bulge-containing duplexes, and 5-methylcytosine-containing duplexes provided evidence regarding the orientation of leinamycin with respect to target guanine residues. The data allows construction of a model for the leinamycin-DNA complex suggesting how a modest DNA-binding constant combines with proper positioning of the natural product to drive efficient alkylation of guanine residues in the major groove of duplex DNA. PMID:21954957

  20. A proposal of a novel DNA modification mechanism induced by irradiation

    International Nuclear Information System (INIS)

    Oka, Toshitaka

    2016-01-01

    This article depicts a proposal of a novel DNA modification mechanism induced by irradiation, and is written as an award work from Japanese Society of Radiation Chemistry. The mechanism of DNA modification induced by K-shell photoabsorption of nitrogen and oxygen atoms was investigated by electron paramagnetic resonance and x-ray absorption near edge structure measurements of calf thymus DNA film. The EPR intensities for DNA film were twofold times larger than those estimated based on the photoabsorption cross section. This suggests that the DNA film itself forms unpaired electron species through the excitation of enhanced electron recapturing, known as the postcollision interaction process. (author)

  1. DNA modification by sulfur mustards and nitrosoureas and repair of these lesions

    International Nuclear Information System (INIS)

    Ludlum, D.B.; Papirmeister, B.; Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD)

    1986-01-01

    The nature and significance of DNA modifications caused by chloroethyl ethyl sulfide (CEES) is compared with those produced by chloroethyl cyclohexyl nitrosourea (CCNU). This comparison illustrates the differences in the kind of biological response which can arise from DNA modification by different agents and the role of DNA repair in determining this response. In particular, the ability of tumor cells to become resistant to therapeutic agents has some important implications for the ability of cells in general to tolerate environmental mutagens. DNA modification by CEES and CCNU can be viewed in the context of DNA modification caused by compounds which naturally react with DNA. For example, cycasin and S-adenosylmethionine both methylate DNA. Not surprisingly, a variety of repair mechanisms has evolved which serve to maintain the integrity of DNA in the presence of such naturally-occurring DNA modifiers. The ability of these enzymes to repair other DNA lesions is currently under active investigation as described here. 19 refs., 4 figs., 3 tabs

  2. Determining the Location of DNA Modification and Mutation Caused by UVB Light in Skin Cancer

    Science.gov (United States)

    2015-09-01

    Award Number: W81XWH-12-1-0333 TITLE: Determining the Location of DNA Modification and Mutation Caused by UVB Light in Skin Cancer PRINCIPAL...COVERED 15 Aug 2012 – 14 Aug 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0333 Determining the Location of DNA Modification and Mutation ...sequencing libraries generated for both yeast and human cells show pyrimidine bias on the 5’ end, indicating that we are sequencing the dimers

  3. A probabilistic generative model for quantification of DNA modifications enables analysis of demethylation pathways.

    Science.gov (United States)

    Äijö, Tarmo; Huang, Yun; Mannerström, Henrik; Chavez, Lukas; Tsagaratou, Ageliki; Rao, Anjana; Lähdesmäki, Harri

    2016-03-14

    We present a generative model, Lux, to quantify DNA methylation modifications from any combination of bisulfite sequencing approaches, including reduced, oxidative, TET-assisted, chemical-modification assisted, and methylase-assisted bisulfite sequencing data. Lux models all cytosine modifications (C, 5mC, 5hmC, 5fC, and 5caC) simultaneously together with experimental parameters, including bisulfite conversion and oxidation efficiencies, as well as various chemical labeling and protection steps. We show that Lux improves the quantification and comparison of cytosine modification levels and that Lux can process any oxidized methylcytosine sequencing data sets to quantify all cytosine modifications. Analysis of targeted data from Tet2-knockdown embryonic stem cells and T cells during development demonstrates DNA modification quantification at unprecedented detail, quantifies active demethylation pathways and reveals 5hmC localization in putative regulatory regions.

  4. When gene medication is also genetic modification--regulating DNA treatment.

    Science.gov (United States)

    Foss, Grethe S; Rogne, Sissel

    2007-07-26

    The molecular methods used in DNA vaccination and gene therapy resemble in many ways the methods applied in genetic modification of organisms. In some regulatory regimes, this creates an overlap between 'gene medication' and genetic modification. In Norway, an animal injected with plasmid DNA, in the form of DNA vaccine or gene therapy, currently is viewed as being genetically modified for as long as the added DNA is present in the animal. However, regulating a DNA-vaccinated animal as genetically modified creates both regulatory and practical challenges. It is also counter-intuitive to many biologists. Since immune responses can be elicited also to alter traits, the borderline between vaccination and the modification of properties is no longer distinct. In this paper, we discuss the background for the Norwegian interpretation and ways in which the regulatory challenge can be handled.

  5. Toward efficient modification of large gold nanoparticles with DNA

    NARCIS (Netherlands)

    Gill, R.; Göeken, Kristian L; Subramaniam, V.

    2014-01-01

    DNA-coated gold nanoparticles are one of the most researched nano-bio hybrid systems. Traditionally their synthesis has been a long and tedious process, involving slow salt addition and long incubation steps. This stems from the fact that both DNA and gold particles are negatively charged, therefore

  6. Biophysical and biochemical studies of modification of damage to DNA

    International Nuclear Information System (INIS)

    Myers, L.S. Jr.; Warnick, A.

    1976-01-01

    Progress is reported on the following research projects: tests of a proposed chemical mechanism by which incorporated 5-bromouracil may sensitize DNA to ionizing radiation; a serologic determination of uridine in irradiatd BU-substituted DNA; and reactivity of aminothiol radioprotectants with hydrated electrons and hydroxyl radicals

  7. Modification of radiation-induced DNA lesions by oxygen

    International Nuclear Information System (INIS)

    Meyn, R.E.; Jenkins, W.T.

    1984-01-01

    The efficiency of DNA strand break production by radiation under aerated and hypoxic conditions was determined in CHO cells using the technique of alkaline elution. The resulting oxygen enhancement ratio was surprisingly high, 7.8. When the pH of the elution was increased from 12.1, the normally used pH, to 12.8, a substantial increase in the strand breaks produced in the hypoxic cells was observed, resulting in an OER of 4.8. This difference in susceptibility of DNA strand break detection as a function of pH suggested a difference in the type of lesions produced in DNA when irradiated under aerated and hypoxic conditions. Further experiments to examine the DNA-protein crosslinks produced by radiation suggested that the apparent lower level of strand breaks in hypoxic cells may be due to a higher level of DNA-protein crosslinks produced under hypoxic conditions. Thus, oxygen may not only act by modifying the quantity of radiation-induced DNA lesions but may also cause qualitative changes. If the different types of DNA lesions have different contributions to lethality, the OER for cell survival may represent a complex composite of these changes at the molecular level

  8. Chromosomal instability drives metastasis through a cytosolic DNA response.

    Science.gov (United States)

    Bakhoum, Samuel F; Ngo, Bryan; Laughney, Ashley M; Cavallo, Julie-Ann; Murphy, Charles J; Ly, Peter; Shah, Pragya; Sriram, Roshan K; Watkins, Thomas B K; Taunk, Neil K; Duran, Mercedes; Pauli, Chantal; Shaw, Christine; Chadalavada, Kalyani; Rajasekhar, Vinagolu K; Genovese, Giulio; Venkatesan, Subramanian; Birkbak, Nicolai J; McGranahan, Nicholas; Lundquist, Mark; LaPlant, Quincey; Healey, John H; Elemento, Olivier; Chung, Christine H; Lee, Nancy Y; Imielenski, Marcin; Nanjangud, Gouri; Pe'er, Dana; Cleveland, Don W; Powell, Simon N; Lammerding, Jan; Swanton, Charles; Cantley, Lewis C

    2018-01-25

    Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.

  9. RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications

    Science.gov (United States)

    Xu, Liang; Wang, Wei; Chong, Jenny; Shin, Ji Hyun; Xu, Jun; Wang, Dong

    2016-01-01

    Accurate genetic information transfer is essential for life. As a key enzyme involved in the first step of gene expression, RNA polymerase II (Pol II) must maintain high transcriptional fidelity while it reads along DNA template and synthesizes RNA transcript in a stepwise manner during transcription elongation. DNA lesions or modifications may lead to significant changes in transcriptional fidelity or transcription elongation dynamics. In this review, we will summarize recent progress towards understanding the molecular basis of RNA Pol II transcriptional fidelity control and impacts of DNA lesions and modifications on Pol II transcription elongation. PMID:26392149

  10. Mapping DNA cleavage by the Type ISP restriction-modification enzymes following long-range communication between DNA sites in different orientations

    Science.gov (United States)

    van Aelst, Kara; Saikrishnan, Kayarat; Szczelkun, Mark D.

    2015-01-01

    The prokaryotic Type ISP restriction-modification enzymes are single-chain proteins comprising an Mrr-family nuclease, a superfamily 2 helicase-like ATPase, a coupler domain, a methyltransferase, and a DNA-recognition domain. Upon recognising an unmodified DNA target site, the helicase-like domain hydrolyzes ATP to cause site release (remodeling activity) and to then drive downstream translocation consuming 1–2 ATP per base pair (motor activity). On an invading foreign DNA, double-strand breaks are introduced at random wherever two translocating enzymes form a so-called collision complex following long-range communication between a pair of target sites in inverted (head-to-head) repeat. Paradoxically, structural models for collision suggest that the nuclease domains are too far apart (>30 bp) to dimerise and produce a double-strand DNA break using just two strand-cleavage events. Here, we examined the organisation of different collision complexes and how these lead to nuclease activation. We mapped DNA cleavage when a translocating enzyme collides with a static enzyme bound to its site. By following communication between sites in both head-to-head and head-to-tail orientations, we could show that motor activity leads to activation of the nuclease domains via distant interactions of the helicase or MTase-TRD. Direct nuclease dimerization is not required. To help explain the observed cleavage patterns, we also used exonuclease footprinting to demonstrate that individual Type ISP domains can swing off the DNA. This study lends further support to a model where DNA breaks are generated by multiple random nicks due to mobility of a collision complex with an overall DNA-binding footprint of ∼30 bp. PMID:26507855

  11. Conflict RNA modification, host-parasite co-evolution, and the origins of DNA and DNA-binding proteins1.

    Science.gov (United States)

    McLaughlin, Paul J; Keegan, Liam P

    2014-08-01

    Nearly 150 different enzymatically modified forms of the four canonical residues in RNA have been identified. For instance, enzymes of the ADAR (adenosine deaminase acting on RNA) family convert adenosine residues into inosine in cellular dsRNAs. Recent findings show that DNA endonuclease V enzymes have undergone an evolutionary transition from cleaving 3' to deoxyinosine in DNA and ssDNA to cleaving 3' to inosine in dsRNA and ssRNA in humans. Recent work on dsRNA-binding domains of ADARs and other proteins also shows that a degree of sequence specificity is achieved by direct readout in the minor groove. However, the level of sequence specificity observed is much less than that of DNA major groove-binding helix-turn-helix proteins. We suggest that the evolution of DNA-binding proteins following the RNA to DNA genome transition represents the major advantage that DNA genomes have over RNA genomes. We propose that a hypothetical RNA modification, a RRAR (ribose reductase acting on genomic dsRNA) produced the first stretches of DNA in RNA genomes. We discuss why this is the most satisfactory explanation for the origin of DNA. The evolution of this RNA modification and later steps to DNA genomes are likely to have been driven by cellular genome co-evolution with viruses and intragenomic parasites. RNA modifications continue to be involved in host-virus conflicts; in vertebrates, edited cellular dsRNAs with inosine-uracil base pairs appear to be recognized as self RNA and to suppress activation of innate immune sensors that detect viral dsRNA.

  12. RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response.

    Science.gov (United States)

    Maréchal, Alexandre; Zou, Lee

    2015-01-01

    The Replication Protein A (RPA) complex is an essential regulator of eukaryotic DNA metabolism. RPA avidly binds to single-stranded DNA (ssDNA) through multiple oligonucleotide/oligosaccharide-binding folds and coordinates the recruitment and exchange of genome maintenance factors to regulate DNA replication, recombination and repair. The RPA-ssDNA platform also constitutes a key physiological signal which activates the master ATR kinase to protect and repair stalled or collapsed replication forks during replication stress. In recent years, the RPA complex has emerged as a key target and an important regulator of post-translational modifications in response to DNA damage, which is critical for its genome guardian functions. Phosphorylation and SUMOylation of the RPA complex, and more recently RPA-regulated ubiquitination, have all been shown to control specific aspects of DNA damage signaling and repair by modulating the interactions between RPA and its partners. Here, we review our current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications.

  13. Histone modification alteration coordinated with acquisition of promoter DNA methylation during Epstein-Barr virus infection.

    Science.gov (United States)

    Funata, Sayaka; Matsusaka, Keisuke; Yamanaka, Ryota; Yamamoto, Shogo; Okabe, Atsushi; Fukuyo, Masaki; Aburatani, Hiroyuki; Fukayama, Masashi; Kaneda, Atsushi

    2017-08-15

    Aberrant DNA hypermethylation is a major epigenetic mechanism to inactivate tumor suppressor genes in cancer. Epstein-Barr virus positive gastric cancer is the most frequently hypermethylated tumor among human malignancies. Herein, we performed comprehensive analysis of epigenomic alteration during EBV infection, by Infinium HumanMethylation 450K BeadChip for DNA methylation and ChIP-sequencing for histone modification alteration during EBV infection into gastric cancer cell line MKN7. Among 7,775 genes with increased DNA methylation in promoter regions, roughly half were "DNA methylation-sensitive" genes, which acquired DNA methylation in the whole promoter regions and thus were repressed. These included anti-oncogenic genes, e.g. CDKN2A . The other half were "DNA methylation-resistant" genes, where DNA methylation is acquired in the surrounding of promoter regions, but unmethylated status is protected in the vicinity of transcription start site. These genes thereby retained gene expression, and included DNA repair genes. Histone modification was altered dynamically and coordinately with DNA methylation alteration. DNA methylation-sensitive genes significantly correlated with loss of H3K27me3 pre-marks or decrease of active histone marks, H3K4me3 and H3K27ac. Apoptosis-related genes were significantly enriched in these epigenetically repressed genes. Gain of active histone marks significantly correlated with DNA methylation-resistant genes. Genes related to mitotic cell cycle and DNA repair were significantly enriched in these epigenetically activated genes. Our data show that orchestrated epigenetic alterations are important in gene regulation during EBV infection, and histone modification status in promoter regions significantly associated with acquisition of de novo DNA methylation or protection of unmethylated status at transcription start site.

  14. Modifications of alkaline microgel electrophoresis for sensitive detection of DNA damage

    International Nuclear Information System (INIS)

    Singh, N.P.; Stephens, R.E.; Schneider, E.L.

    1994-01-01

    The alkaline microgel electrophoresis technique was modified to achieve a substantial increase in sensitivity for the detection of radiation-induced DNA damage in human lymphocytes. This increased sensitivity was achieved through: (1) the addition of free radical scavengers to the electrophoresis solution to reduce DNA damage generated during alkaline unwinding and electrophoresis; (2) the modification of the electrophoresis unit to achieve a more uniform electric field; (3) the use of YOYO-1, a DNA dye, producing fluorescence 500-fold more intense than ethidium bromide; and (4) the introduction of an image analysis system for the quantitation of DNA migration. In human lymphocytes, these modifications have resulted in an increased sensitivity of several fold, allowing the detection of DNA damage in the range of 50 mGy. (author)

  15. BuD, a helix–loop–helix DNA-binding domain for genome modification

    Energy Technology Data Exchange (ETDEWEB)

    Stella, Stefano [Spanish National Cancer Research Centre (CNIO), Calle de Melchor Fernández Almagro 3, 28029 Madrid (Spain); University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen (Denmark); Molina, Rafael; López-Méndez, Blanca [Spanish National Cancer Research Centre (CNIO), Calle de Melchor Fernández Almagro 3, 28029 Madrid (Spain); Juillerat, Alexandre; Bertonati, Claudia; Daboussi, Fayza [Cellectis, 8 Rue de la Croix Jarry, 75013 Paris (France); Campos-Olivas, Ramon [Spanish National Cancer Research Centre (CNIO), Calle de Melchor Fernández Almagro 3, 28029 Madrid (Spain); Duchateau, Phillippe [Cellectis, 8 Rue de la Croix Jarry, 75013 Paris (France); Montoya, Guillermo, E-mail: guillermo.montoya@cpr.ku.dk [Spanish National Cancer Research Centre (CNIO), Calle de Melchor Fernández Almagro 3, 28029 Madrid (Spain); University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen (Denmark)

    2014-07-01

    Crystal structures of BurrH and the BurrH–DNA complex are reported. DNA editing offers new possibilities in synthetic biology and biomedicine for modulation or modification of cellular functions to organisms. However, inaccuracy in this process may lead to genome damage. To address this important problem, a strategy allowing specific gene modification has been achieved through the addition, removal or exchange of DNA sequences using customized proteins and the endogenous DNA-repair machinery. Therefore, the engineering of specific protein–DNA interactions in protein scaffolds is key to providing ‘toolkits’ for precise genome modification or regulation of gene expression. In a search for putative DNA-binding domains, BurrH, a protein that recognizes a 19 bp DNA target, was identified. Here, its apo and DNA-bound crystal structures are reported, revealing a central region containing 19 repeats of a helix–loop–helix modular domain (BurrH domain; BuD), which identifies the DNA target by a single residue-to-nucleotide code, thus facilitating its redesign for gene targeting. New DNA-binding specificities have been engineered in this template, showing that BuD-derived nucleases (BuDNs) induce high levels of gene targeting in a locus of the human haemoglobin β (HBB) gene close to mutations responsible for sickle-cell anaemia. Hence, the unique combination of high efficiency and specificity of the BuD arrays can push forward diverse genome-modification approaches for cell or organism redesign, opening new avenues for gene editing.

  16. Chemical modification of DNA: Molecular specificity studied by tandem mass spectrometry and liquid chromatography

    International Nuclear Information System (INIS)

    Chang, Ching-jer; Cooks, R.G.; Chae, Whi-Gun; Wood, J.M.

    1989-01-01

    Chemical modifications of DNA in vitro could be directly studied by C-13 NMR and P-31 NMR, which eliminated all degradation and separation processes. The prospects of utilized the NMR method in the in vitro experiments are limited because of the inherent low sensitivity of NMR and low level of DNA modification. We have developed a reverse-phase ion-paired HPLC method to study DNA modifications by methylating agents. The structural specificity of HPLC is significantly enhanced by conjunction with the specificity of enzymic transformations. The HPLC studies have also revealed the limitation of HPLC method for simultaneous determination of many minor modified nucleosides. This problem has been overcome by tandem mass spectrometry. In conjunction with the resolving power of HPLC in separating isomers, desorption chemical ionization tandem mass spectrometry has been utilized in the determination of the modified nucleosides at the picomole level using stable-isotope labeled compounds as internal references

  17. Asymmetric epigenetic modification and elimination of rDNA sequences by polyploidization in wheat.

    Science.gov (United States)

    Guo, Xiang; Han, Fangpu

    2014-11-01

    rRNA genes consist of long tandem repeats clustered on chromosomes, and their products are important functional components of the ribosome. In common wheat (Triticum aestivum), rDNA loci from the A and D genomes were largely lost during the evolutionary process. This biased DNA elimination may be related to asymmetric transcription and epigenetic modifications caused by the polyploid formation. Here, we observed both sets of parental nucleolus organizing regions (NORs) were expressed after hybridization, but asymmetric silencing of one parental NOR was immediately induced by chromosome doubling, and reversing the ploidy status could not reactivate silenced NORs. Furthermore, increased CHG and CHH DNA methylation on promoters was accompanied by asymmetric silencing of NORs. Enrichment of H3K27me3 and H3K9me2 modifications was also observed to be a direct response to increased DNA methylation and transcriptional inactivation of NOR loci. Both A and D genome NOR loci with these modifications started to disappear in the S4 generation and were completely eliminated by the S7 generation in synthetic tetraploid wheat. Our results indicated that asymmetric epigenetic modification and elimination of rDNA sequences between different donor genomes may lead to stable allopolyploid wheat with increased differentiation and diversity. © 2014 American Society of Plant Biologists. All rights reserved.

  18. Nucleobase modification as redox DNA labelling for electrochemical detection

    Czech Academy of Sciences Publication Activity Database

    Hocek, Michal; Fojta, Miroslav

    2011-01-01

    Roč. 40, č. 12 (2011), s. 5802-5814 ISSN 0306-0012 R&D Projects: GA MŠk(CZ) LC06035; GA MŠk LC512; GA AV ČR(CZ) IAA400040901; GA ČR GA203/09/0317 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : nucleotides * oligonucleotides * DNA * electrochemistry * redox labeling Subject RIV: CC - Organic Chemistry Impact factor: 28.760, year: 2011

  19. Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.

    Directory of Open Access Journals (Sweden)

    Shunsuke Suzuki

    2007-04-01

    Full Text Available Among mammals, only eutherians and marsupials are viviparous and have genomic imprinting that leads to parent-of-origin-specific differential gene expression. We used comparative analysis to investigate the origin of genomic imprinting in mammals. PEG10 (paternally expressed 10 is a retrotransposon-derived imprinted gene that has an essential role for the formation of the placenta of the mouse. Here, we show that an orthologue of PEG10 exists in another therian mammal, the marsupial tammar wallaby (Macropus eugenii, but not in a prototherian mammal, the egg-laying platypus (Ornithorhynchus anatinus, suggesting its close relationship to the origin of placentation in therian mammals. We have discovered a hitherto missing link of the imprinting mechanism between eutherians and marsupials because tammar PEG10 is the first example of a differentially methylated region (DMR associated with genomic imprinting in marsupials. Surprisingly, the marsupial DMR was strictly limited to the 5' region of PEG10, unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the adjacent imprinted gene SGCE. These results not only demonstrate a common origin of the DMR-associated imprinting mechanism in therian mammals but provide the first demonstration that DMR-associated genomic imprinting in eutherians can originate from the repression of exogenous DNA sequences and/or retrotransposons by DNA methylation.

  20. Determining the Location of DNA Modification and Mutation Caused by UVB Light in Skin Cancer

    Science.gov (United States)

    2013-09-01

    reads were then processed to determine the dinucleotide composition on the 5’ end by separating the Watson and Crick strands, and the dinucleotide...AD_________________ Award Number: W81XWH-12-1-0333 TITLE: Determining the Location of DNA ...COVERED 15 August 2012 – 14 August 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Determining the Location of DNA Modification and Mutation Caused

  1. A new MCM modification cycle regulates DNA replication initiation.

    Science.gov (United States)

    Wei, Lei; Zhao, Xiaolan

    2016-03-01

    The MCM DNA helicase is a central regulatory target during genome replication. MCM is kept inactive during G1, and it initiates replication after being activated in S phase. During this transition, the only known chemical change to MCM is the gain of multisite phosphorylation that promotes cofactor recruitment. Because replication initiation is intimately linked to multiple biological cues, additional changes to MCM can provide further regulatory points. Here, we describe a yeast MCM SUMOylation cycle that regulates replication. MCM subunits undergo SUMOylation upon loading at origins in G1 before MCM phosphorylation. MCM SUMOylation levels then decline as MCM phosphorylation levels rise, thus suggesting an inhibitory role of MCM SUMOylation during replication. Indeed, increasing MCM SUMOylation impairs replication initiation, partly through promoting the recruitment of a phosphatase that decreases MCM phosphorylation and activation. We propose that MCM SUMOylation counterbalances kinase-based regulation, thus ensuring accurate control of replication initiation.

  2. Selective sweeps of mitochondrial DNA can drive the evolution of uniparental inheritance.

    Science.gov (United States)

    Christie, Joshua R; Beekman, Madeleine

    2017-08-01

    Although the uniparental (or maternal) inheritance of mitochondrial DNA (mtDNA) is widespread, the reasons for its evolution remain unclear. Two main hypotheses have been proposed: selection against individuals containing different mtDNAs (heteroplasmy) and selection against "selfish" mtDNA mutations. Recently, uniparental inheritance was shown to promote adaptive evolution in mtDNA, potentially providing a third hypothesis for its evolution. Here, we explore this hypothesis theoretically and ask if the accumulation of beneficial mutations provides a sufficient fitness advantage for uniparental inheritance to invade a population in which mtDNA is inherited biparentally. In a deterministic model, uniparental inheritance increases in frequency but cannot replace biparental inheritance if only a single beneficial mtDNA mutation sweeps through the population. When we allow successive selective sweeps of mtDNA, however, uniparental inheritance can replace biparental inheritance. Using a stochastic model, we show that a combination of selection and drift facilitates the fixation of uniparental inheritance (compared to a neutral trait) when there is only a single selective mtDNA sweep. When we consider multiple mtDNA sweeps in a stochastic model, uniparental inheritance becomes even more likely to replace biparental inheritance. Our findings thus suggest that selective sweeps of beneficial mtDNA haplotypes can drive the evolution of uniparental inheritance. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  3. DNA Polymerases Drive DNA Sequencing-by-Synthesis Technologies: Both Past and Present

    Directory of Open Access Journals (Sweden)

    Cheng-Yao eChen

    2014-06-01

    Full Text Available Next-generation sequencing (NGS technologies have revolutionized modern biological and biomedical research. The engines responsible for this innovation are DNA polymerases; they catalyze the biochemical reaction for deriving template sequence information. In fact, DNA polymerase has been a cornerstone of DNA sequencing from the very beginning. E. coli DNA polymerase I proteolytic (Klenow fragment was originally utilized in Sanger's dideoxy chain terminating DNA sequencing chemistry. From these humble beginnings followed an explosion of organism-specific, genome sequence information accessible via public database. Family A/B DNA polymerases from mesophilic/thermophilic bacteria/archaea were modified and tested in today's standard capillary electrophoresis (CE and NGS sequencing platforms. These enzymes were selected for their efficient incorporation of bulky dye-terminator and reversible dye-terminator nucleotides respectively. Third generation, real-time single molecule sequencing platform requires slightly different enzyme properties. Enterobacterial phage ⱷ29 DNA polymerase copies long stretches of DNA and possesses a unique capability to efficiently incorporate terminal phosphate-labeled nucleoside polyphosphates. Furthermore, ⱷ29 enzyme has also been utilized in emerging DNA sequencing technologies including nanopore-, and protein-transistor-based sequencing. DNA polymerase is, and will continue to be, a crucial component of sequencing technologies.

  4. DNA Phosphorothioate Modification Plays a Role in Peroxides Resistance in Streptomyces lividans

    Directory of Open Access Journals (Sweden)

    Daofeng Dai

    2016-08-01

    Full Text Available DNA phosphorothioation, conferred by dnd genes, was originally discovered in the soil-dwelling bacterium Streptomyces lividans, and thereafter found to exist in various bacterial genera. However, the physiological significance of this sulfur modification of the DNA backbone remains unknown in S. lividans. Our studies indicate that DNA phosphorothioation has a major role in resistance to oxidative stress in the strain. Although Streptomyces species express multiple catalase/peroxidase and organic hydroperoxide resistance genes to protect them against peroxide damage, a wild type strain of S. lividans exhibited two-fold to 10-fold higher survival, compared to a dnd- mutant, following treatment with peroxides. RNA-seq experiments revealed that, catalase and organic hydroperoxide resistance gene expression were not up-regulated in the wild type strain, suggesting that the resistance to oxidative stress was not due to the up-regulation of these genes by DNA phosphorothioation. Quantitative RT-PCR analysis was conducted to trace the expression of the catalase and the organic hydroperoxide resistance genes after peroxides treatments. A bunch of these genes were activated in the dnd- mutant rather than the wild type strain in response to peroxides. Moreover, the organic hydroperoxide peracetic acid was scavenged more rapidly in the presence than in the absence of phosphorothioate modification, both in vivo and in vitro. The dnd gene cluster can be up-regulated by the disulfide stressor diamide. Overall, our observations suggest that DNA phosphorothioate modification functions as a peroxide resistance system in S. lividans.

  5. When we should worry more: using cognitive bias modification to drive adaptive health behaviour.

    Science.gov (United States)

    Notebaert, Lies; Chrystal, Jessica; Clarke, Patrick J F; Holmes, Emily A; MacLeod, Colin

    2014-01-01

    A lack of behavioural engagement in health promotion or disease prevention is a problem across many health domains. In these cases where people face a genuine danger, a reduced focus on threat and low levels of anxiety or worry are maladaptive in terms of promoting protection or prevention behaviour. Therefore, it is possible that increasing the processing of threat will increase worry and thereby enhance engagement in adaptive behaviour. Laboratory studies have shown that cognitive bias modification (CBM) can increase or decrease anxiety and worry when increased versus decreased processing of threat is encouraged. In the current study, CBM for interpretation (CBM-I) is used to target engagement in sun protection behaviour. The goal was to investigate whether inducing a negative rather than a positive interpretation bias for physical threat information can enhance worry elicited when viewing a health campaign video (warning against melanoma skin cancer), and consequently lead to more adaptive behaviour (sun protection). Participants were successfully trained to either adopt a positive or negative interpretation bias using physical threat scenarios. However, contrary to expectations results showed that participants in the positive training condition reported higher levels of worry elicited by the melanoma video than participants in the negative training condition. Video elicited worry was, however, positively correlated with a measure of engagement in sun protection behaviour, suggesting that higher levels of worry do promote adaptive behaviour. These findings imply that more research is needed to determine under which conditions increased versus decreased processing of threat can drive adaptive worry. Various potential explanations for the current findings and suggestions for future research are discussed.

  6. To spread or not to spread - chromatin modifications in response to DNA damage

    DEFF Research Database (Denmark)

    Altmeyer, M.; Lukas, J.

    2013-01-01

    Chromatin modifications in response to DNA damage are vital for genome integrity. Multiple proteins and pathways required to generate specialized chromatin domains around DNA lesions have been identified and the increasing amount of information calls for unifying concepts that would allow us...... to grasp the ever-increasing complexity. This review aims at contributing to this trend by focusing on feed-forward and feedback mechanisms, which in mammalian cells determine the extent of chromatin modifications after DNA damage. We highlight the emerging notion that the nodal points of these highly...... dynamic pathways operate in a rate-limiting mode, whose deregulation can disrupt physiological boundaries between damaged and undamaged chromatin, dictate repair pathway choice, and determine the fate of cells exposed to genotoxic stress....

  7. [Comet assay of DNA fragmentation: modification of silver staining for obtaining permanent preparations].

    Science.gov (United States)

    Kamins'kyĭ, V O; Lutsyk, M D; Stoĭka, R S

    2005-01-01

    Modification of comet analysis is proposed for obtaining permanent preparations by DNA staining with silver compounds. The sensitivity of staining is similar to that observed at the treatment by ethidium bromide and other fluorochromes. The advantages of the method are stability of slides and possibility of their reinvestigation by light microscopy. The method does not need expensive fluorescent microscope and lacks contacting with carcinogenic compounds and UV light irradiation.

  8. New Insights into 5hmC DNA Modification: Generation, Distribution and Function

    Directory of Open Access Journals (Sweden)

    Dong-Qiao Shi

    2017-07-01

    Full Text Available Dynamic DNA modifications, such as methylation/demethylation on cytosine, are major epigenetic mechanisms to modulate gene expression in both eukaryotes and prokaryotes. In addition to the common methylation on the 5th position of the pyrimidine ring of cytosine (5mC, other types of modifications at the same position, such as 5-hydroxymethyl (5hmC, 5-formyl (5fC, and 5-carboxyl (5caC, are also important. Recently, 5hmC, a product of 5mC demethylation by the Ten-Eleven Translocation family proteins, was shown to regulate many cellular and developmental processes, including the pluripotency of embryonic stem cells, neuron development, and tumorigenesis in mammals. Here, we review recent advances on the generation, distribution, and function of 5hmC modification in mammals and discuss its potential roles in plants.

  9. DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.

    Science.gov (United States)

    Oh, Gabriel; Wang, Sun-Chong; Pal, Mrinal; Chen, Zheng Fei; Khare, Tarang; Tochigi, Mamoru; Ng, Catherine; Yang, Yeqing A; Kwan, Andrew; Kaminsky, Zachary A; Mill, Jonathan; Gunasinghe, Cerisse; Tackett, Jennifer L; Gottesman, Irving I; Willemsen, Gonneke; de Geus, Eco J C; Vink, Jacqueline M; Slagboom, P Eline; Wray, Naomi R; Heath, Andrew C; Montgomery, Grant W; Turecki, Gustavo; Martin, Nicholas G; Boomsma, Dorret I; McGuffin, Peter; Kustra, Rafal; Petronis, Art

    2015-02-01

    Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations. Copyright © 2015 Society of Biological Psychiatry. All rights reserved.

  10. DNA modifications by platinum antitumor drugs and its recognition by DNA-binding proteins

    Czech Academy of Sciences Publication Activity Database

    Brabec, Viktor

    2004-01-01

    Roč. 271, Suppl. 1 (2004), s. 90 ISSN 0014-2956. [Meeting of the Federation of the European Biochemical Societies /29./. 26.06.2004-01.07.2004, Warsaw] R&D Projects: GA ČR GA305/02/1552 Keywords : platinum drugs * DNA-protein interaction * NF-kappaB Subject RIV: BO - Biophysics

  11. Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification.

    Science.gov (United States)

    Scharf, Brian; Clement, Cristina C; Yodmuang, Supansa; Urbanska, Aleksandra M; Suadicani, Sylvia O; Aphkhazava, David; Thi, Mia M; Perino, Giorgio; Hardin, John A; Cobelli, Neil; Vunjak-Novakovic, Gordana; Santambrogio, Laura

    2013-07-25

    Aging-related oxidative stress has been linked to degenerative modifications in different organs and tissues. Using redox proteomic analysis and illustrative tandem mass spectrometry mapping, we demonstrate oxidative posttranslational modifications in structural proteins of intervertebral discs (IVDs) isolated from aging mice. Increased protein carbonylation was associated with protein fragmentation and aggregation. Complementing these findings, a significant loss of elasticity and increased stiffness was measured in fibrocartilage from aging mice. Studies using circular dichroism and intrinsic tryptophan fluorescence revealed a significant loss of secondary and tertiary structures of purified collagens following oxidation. Collagen unfolding and oxidation promoted both nonenzymatic and enzymatic degradation. Importantly, induction of oxidative modification in healthy fibrocartilage recapitulated the biochemical and biophysical modifications observed in the aging IVD. Together, these results suggest that protein carbonylation, glycation, and lipoxidation could be early events in promoting IVD degenerative changes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Role of methionine on epigenetic modification of DNA methylation and gene expression in animals

    Directory of Open Access Journals (Sweden)

    Naifeng Zhang

    2018-03-01

    Full Text Available DNA methylation is one of the main epigenetic phenomena affecting gene expression. It is an important mechanism for the development of embryo, growth and health of animals. As a key nutritional factor limiting the synthesis of protein, methionine serves as the precursor of S-adenosylmethionine (SAM in the hepatic one-carbon metabolism. The dietary fluctuation of methionine content can alter the levels of metabolic substrates in one-carbon metabolism, e.g., the SAM, S-adenosylhomocysteine (SAH, and change the expression of genes related to the growth and health of animals by DNA methylation reactions. The ratio of SAM to SAH is called ‘methylation index’ but it should be carefully explained because the complexity of methylation reaction. Alterations of methylation in a specific cytosine-guanine (CpG site, rather than the whole promoter region, might be enough to change gene expression. Aberrant methionine cycle may provoke molecular changes of one-carbon metabolism that results in deregulation of cellular hemostasis and health problems. The importance of DNA methylation has been underscored but the mechanisms of methionine affecting DNA methylation are poorly understood. Nutritional epigenomics provides a promising insight into the targeting epigenetic changes in animals from a nutritional standpoint, which will deepen and expand our understanding of genes, molecules, tissues, and animals in which methionine alteration influences DNA methylation and gene expression. Keywords: Epigenetics, Methionine, DNA methylation, Gene expression, Epigenetic modification

  13. Influence of major-groove chemical modifications of DNA on transcription by bacterial RNA polymerases.

    Science.gov (United States)

    Raindlová, Veronika; Janoušková, Martina; Slavíčková, Michaela; Perlíková, Pavla; Boháčová, Soňa; Milisavljevič, Nemanja; Šanderová, Hana; Benda, Martin; Barvík, Ivan; Krásný, Libor; Hocek, Michal

    2016-04-20

    DNA templates containing a set of base modifications in the major groove (5-substituted pyrimidines or 7-substituted 7-deazapurines bearing H, methyl, vinyl, ethynyl or phenyl groups) were prepared by PCR using the corresponding base-modified 2'-deoxyribonucleoside triphosphates (dNTPs). The modified templates were used in an in vitro transcription assay using RNA polymerase from Bacillus subtilis and Escherichia coli Some modified nucleobases bearing smaller modifications (H, Me in 7-deazapurines) were perfectly tolerated by both enzymes, whereas bulky modifications (Ph at any nucleobase) and, surprisingly, uracil blocked transcription. Some middle-sized modifications (vinyl or ethynyl) were partly tolerated mostly by the E. colienzyme. In all cases where the transcription proceeded, full length RNA product with correct sequence was obtained indicating that the modifications of the template are not mutagenic and the inhibition is probably at the stage of initiation. The results are promising for the development of bioorthogonal reactions for artificial chemical switching of the transcription. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Modification of DNA radiolysis by DNA-binding proteins: Structural aspects

    Czech Academy of Sciences Publication Activity Database

    Davídková, Marie; Štísová, Viktorie; Goffinont, S.; Gillard, N.; Castaing, B.; Maurizot, M. S.

    2007-01-01

    Roč. 122, 1-4 (2007), s. 100-105 ISSN 0144-8420. [Symposium on Microdosimetry /14./. Venezia, 13.11.2005-18.11.2005] R&D Projects: GA MŠk 1P05OC085 Grant - others:GA MŠk(CS1) Barrande 2005-6-018-1 Institutional research plan: CEZ:AV0Z10480505 Keywords : specific DNA-protein complexes * radiolysis * ionizing radiation Subject RIV: BO - Biophysics Impact factor: 0.528, year: 2007

  15. Ultrasensitive Direct Quantification of Nucleobase Modifications in DNA by Surface-Enhanced Raman Scattering: The Case of Cytosine.

    Science.gov (United States)

    Morla-Folch, Judit; Xie, Hai-nan; Gisbert-Quilis, Patricia; Gómez-de Pedro, Sara; Pazos-Perez, Nicolas; Alvarez-Puebla, Ramon A; Guerrini, Luca

    2015-11-09

    Recognition of chemical modifications in canonical nucleobases of nucleic acids is of key importance since such modified variants act as different genetic encoders, introducing variability in the biological information contained in DNA. Herein, we demonstrate the feasibility of direct SERS in combination with chemometrics and microfluidics for the identification and relative quantification of 4 different cytosine modifications in both single- and double-stranded DNA. The minute amount of DNA required per measurement, in the sub-nanogram regime, removes the necessity of pre-amplification or enrichment steps (which are also potential sources of artificial DNA damages). These findings show great potentials for the development of fast, low-cost and high-throughput screening analytical devices capable of detecting known and unknown modifications in nucleic acids (DNA and RNA) opening new windows of activity in several fields such as biology, medicine and forensic sciences. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. The multi-domain protein Np95 connects DNA methylation and histone modification

    Science.gov (United States)

    Rottach, Andrea; Frauer, Carina; Pichler, Garwin; Bonapace, Ian Marc; Spada, Fabio; Leonhardt, Heinrich

    2010-01-01

    DNA methylation and histone modifications play a central role in the epigenetic regulation of gene expression and cell differentiation. Recently, Np95 (also known as UHRF1 or ICBP90) has been found to interact with Dnmt1 and to bind hemimethylated DNA, indicating together with genetic studies a central role in the maintenance of DNA methylation. Using in vitro binding assays we observed a weak preference of Np95 and its SRA (SET- and Ring-associated) domain for hemimethylated CpG sites. However, the binding kinetics of Np95 in living cells was not affected by the complete loss of genomic methylation. Investigating further links with heterochromatin, we could show that Np95 preferentially binds histone H3 N-terminal tails with trimethylated (H3K9me3) but not acetylated lysine 9 via a tandem Tudor domain. This domain contains three highly conserved aromatic amino acids that form an aromatic cage similar to the one binding H3K9me3 in the chromodomain of HP1ß. Mutations targeting the aromatic cage of the Np95 tandem Tudor domain (Y188A and Y191A) abolished specific H3 histone tail binding. These multiple interactions of the multi-domain protein Np95 with hemimethylated DNA and repressive histone marks as well as with DNA and histone methyltransferases integrate the two major epigenetic silencing pathways. PMID:20026581

  17. The multi-domain protein Np95 connects DNA methylation and histone modification.

    Science.gov (United States)

    Rottach, Andrea; Frauer, Carina; Pichler, Garwin; Bonapace, Ian Marc; Spada, Fabio; Leonhardt, Heinrich

    2010-04-01

    DNA methylation and histone modifications play a central role in the epigenetic regulation of gene expression and cell differentiation. Recently, Np95 (also known as UHRF1 or ICBP90) has been found to interact with Dnmt1 and to bind hemimethylated DNA, indicating together with genetic studies a central role in the maintenance of DNA methylation. Using in vitro binding assays we observed a weak preference of Np95 and its SRA (SET- and Ring-associated) domain for hemimethylated CpG sites. However, the binding kinetics of Np95 in living cells was not affected by the complete loss of genomic methylation. Investigating further links with heterochromatin, we could show that Np95 preferentially binds histone H3 N-terminal tails with trimethylated (H3K9me3) but not acetylated lysine 9 via a tandem Tudor domain. This domain contains three highly conserved aromatic amino acids that form an aromatic cage similar to the one binding H3K9me3 in the chromodomain of HP1ss. Mutations targeting the aromatic cage of the Np95 tandem Tudor domain (Y188A and Y191A) abolished specific H3 histone tail binding. These multiple interactions of the multi-domain protein Np95 with hemimethylated DNA and repressive histone marks as well as with DNA and histone methyltransferases integrate the two major epigenetic silencing pathways.

  18. SMRT Sequencing Revealed Mitogenome Characteristics and Mitogenome-Wide DNA Modification Pattern in Ophiocordyceps sinensis.

    Science.gov (United States)

    Kang, Xincong; Hu, Liqin; Shen, Pengyuan; Li, Rui; Liu, Dongbo

    2017-01-01

    Single molecule, real-time (SMRT) sequencing was used to characterize mitochondrial (mt) genome of Ophiocordyceps sinensis and to analyze the mt genome-wide pattern of epigenetic DNA modification. The complete mt genome of O. sinensis , with a size of 157,539 bp, is the fourth largest Ascomycota mt genome sequenced to date. It contained 14 conserved protein-coding genes (PCGs), 1 intronic protein rps3 , 27 tRNAs and 2 rRNA subunits, which are common characteristics of the known mt genomes in Hypocreales. A phylogenetic tree inferred from 14 PCGs in Pezizomycotina fungi supports O. sinensis as most closely related to Hirsutella rhossiliensis in Ophiocordycipitaceae. A total of 36 sequence sites in rps3 were under positive selection, with dN/dS >1 in the 20 compared fungi. Among them, 16 sites were statistically significant. In addition, the mt genome-wide base modification pattern of O. sinensis was determined in this study, especially DNA methylation. The methylations were located in coding and uncoding regions of mt PCGs in O. sinensis , and might be closely related to the expression of PCGs or the binding affinity of transcription factor A to mtDNA. Consequently, these methylations may affect the enzymatic activity of oxidative phosphorylation and then the mt respiratory rate; or they may influence mt biogenesis. Therefore, methylations in the mitogenome of O. sinensis might be a genetic feature to adapt to the cold and low PO 2 environment at high altitude, where O. sinensis is endemic. This is the first report on epigenetic modifications in a fungal mt genome.

  19. Magnetoresistive sensors for measurements of DNA hybridization kinetics - effect of TINA modifications

    DEFF Research Database (Denmark)

    Rizzi, Giovanni; Dufva, Martin; Hansen, Mikkel Fougt

    2017-01-01

    We present the use of magnetoresistive sensors integrated in a microfluidic system for real-time studies of the hybridization kinetics of DNA labeled with magnetic nanoparticles to an array of surface-tethered probes. The nanoparticles were magnetized by the magnetic field from the sensor current....... A local negative reference ensured that only the specific binding signal was measured. Analysis of the real-time hybridization using a two-compartment model yielded both the association and dissociation constants kon, and koff. The effect of probe modifications with ortho-Twisted Intercalating Nucleic...

  20. 5' modification of duplex DNA with a ruthenium electron donor-acceptor pair using solid-phase DNA synthesis

    Science.gov (United States)

    Frank, Natia L.; Meade, Thomas J.

    2003-01-01

    Incorporation of metalated nucleosides into DNA through covalent modification is crucial to measurement of thermal electron-transfer rates and the dependence of these rates with structure, distance, and position. Here, we report the first synthesis of an electron donor-acceptor pair of 5' metallonucleosides and their subsequent incorporation into oligonucleotides using solid-phase DNA synthesis techniques. Large-scale syntheses of metal-containing oligonucleotides are achieved using 5' modified phosporamidites containing [Ru(acac)(2)(IMPy)](2+) (acac is acetylacetonato; IMPy is 2'-iminomethylpyridyl-2'-deoxyuridine) (3) and [Ru(bpy)(2)(IMPy)](2+) (bpy is 2,2'-bipyridine; IMPy is 2'-iminomethylpyridyl-2'-deoxyuridine) (4). Duplexes formed with the metal-containing oligonucleotides exhibit thermal stability comparable to the corresponding unmetalated duplexes (T(m) of modified duplex = 49 degrees C vs T(m) of unmodified duplex = 47 degrees C). Electrochemical (3, E(1/2) = -0.04 V vs NHE; 4, E(1/2) = 1.12 V vs NHE), absorption (3, lambda(max) = 568, 369 nm; 4, lambda(max) = 480 nm), and emission (4, lambda(max) = 720 nm, tau = 55 ns, Phi = 1.2 x 10(-)(4)) data for the ruthenium-modified nucleosides and oligonucleotides indicate that incorporation into an oligonucleotide does not perturb the electronic properties of the ruthenium complex or the DNA significantly. In addition, the absence of any change in the emission properties upon metalated duplex formation suggests that the [Ru(bpy)(2)(IMPy)](2+)[Ru(acac)(2)(IMPy)](2+) pair will provide a valuable probe for DNA-mediated electron-transfer studies.

  1. Production bias: A proposed modification of the driving force for void swelling under cascade damage conditions

    International Nuclear Information System (INIS)

    Woo, C.H.; Garner, F.A.

    1991-11-01

    A new concept of point-defect production as the main driving force for void swelling under cascade damage conditions is proposed. This concept takes into account the recombination and formation of immobile clusters and loops of vacancies and interstitials in the cascade region. The life times of the clusters and loops due to desolution are strong functions of the temperature, as well as their vacancy and interstitial nature. The resulting biased production of free point defects from the internal sources is shown to be a strong driving force for void swelling. The characteristics of void swelling due to production bias are described and compared with experimental results. We conclude that the production bias concept provides a good description of void swelling under cascade damage conditions

  2. Production bias: A proposed modification of the driving force for void swelling under cascade damage conditions

    International Nuclear Information System (INIS)

    Woo, C.H.; Singh, B.N.; Garner, F.A.

    1992-01-01

    A new concept of point defect production as the main driving force for void swelling under cascade damage conditions is proposed. This concept takes into account the recombination and formation of immobile clusters and loops of vacancies and interstitials in the cascade region. The lifetimes of the clusters and loops due to desolution are strong functions of the temperature, as well as their vacancy and interstitial nature. The resulting biased production of free point defects from the internal sources is shown to be a strong driving force for void swelling. The characteristics of void swelling due to production bias are described and compared with experimental results. We conclude that the production bias concept provides a good description of void swelling under cascade damage conditions. (orig.)

  3. DndEi Exhibits Helicase Activity Essential for DNA Phosphorothioate Modification and ATPase Activity Strongly Stimulated by DNA Substrate with a GAAC/GTTC Motif.

    Science.gov (United States)

    Zheng, Tao; Jiang, Pan; Cao, Bo; Cheng, Qiuxiang; Kong, Lingxin; Zheng, Xiaoqing; Hu, Qinghai; You, Delin

    2016-01-15

    Phosphorothioate (PT) modification of DNA, in which the non-bridging oxygen of the backbone phosphate group is replaced by sulfur, is governed by the DndA-E proteins in prokaryotes. To better understand the biochemical mechanism of PT modification, functional analysis of the recently found PT-modifying enzyme DndEi, which has an additional domain compared with canonical DndE, from Riemerella anatipestifer is performed in this study. The additional domain is identified as a DNA helicase, and functional deletion of this domain in vivo leads to PT modification deficiency, indicating an essential role of helicase activity in PT modification. Subsequent analysis reveals that the additional domain has an ATPase activity. Intriguingly, the ATPase activity is strongly stimulated by DNA substrate containing a GAAC/GTTC motif (i.e. the motif at which PT modifications occur in R. anatipestifer) when the additional domain and the other domain (homologous to canonical DndE) are co-expressed as a full-length DndEi. These results reveal that PT modification is a biochemical process with DNA strand separation and intense ATP hydrolysis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. DNA methylation-histone modification relationships across the desmin locus in human primary cells

    Directory of Open Access Journals (Sweden)

    Clelland Gayle K

    2009-05-01

    Full Text Available Abstract Background We present here an extensive epigenetic analysis of a 500 kb region, which encompasses the human desmin gene (DES and its 5' locus control region (LCR, the only muscle-specific transcriptional regulatory element of this type described to date. These data complement and extend Encyclopaedia of DNA Elements (ENCODE studies on region ENr133. We analysed histone modifications and underlying DNA methylation patterns in physiologically relevant DES expressing (myoblast/myotube and non-expressing (peripheral blood mononuclear primary human cells. Results We found that in expressing myoblast/myotube but not peripheral blood mononuclear cell (PBMC cultures, histone H4 acetylation displays a broadly distributed enrichment across a gene rich 200 kb region whereas H3 acetylation localizes at the transcriptional start site (TSS of genes. We show that the DES LCR and TSS of DES are enriched with hyperacetylated domains of acetylated histone H3, with H3 lysine 4 di- and tri-methylation (H3K4me2 and me3 exhibiting a different distribution pattern across this locus. The CpG island that extends into the first intron of DES is methylation-free regardless of the gene's expression status and in non-expressing PBMCs is marked with histone H3 lysine 27 tri-methylation (H3K27me3. Conclusion Overall, our results constitute the first study correlating patterns of histone modifications and underlying DNA methylation of a muscle-specific LCR and its associated downstream gene region whilst additionally placing this within a much broader genomic context. Our results clearly show that there are distinct patterns of histone H3 and H4 acetylation and H3 methylation at the DES LCR, promoter and intragenic region. In addition, the presence of H3K27me3 at the DES methylation-free CpG only in non-expressing PBMCs may serve to silence this gene in non-muscle tissues. Generally, our work demonstrates the importance of using multiple, physiologically relevant

  5. Zebrafish embryos as a screen for DNA methylation modifications after compound exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bouwmeester, Manon C.; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M. [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Brandhof, Evert-Jan van den [Center for Environmental Quality, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Pennings, Jeroen L.A. [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Kamstra, Jorke H. [Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Jelinek, Jaroslav [Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA (United States); Issa, Jean-Pierre J. [Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA (United States); Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Legler, Juliette [Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Ven, Leo T.M. van der, E-mail: leo.van.der.ven@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands)

    2016-01-15

    Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. - Highlights: • Compound induced effects on DNA methylation in zebrafish embryos • Global methylation not an informative biomarker • Minimal genome

  6. Zebrafish embryos as a screen for DNA methylation modifications after compound exposure

    International Nuclear Information System (INIS)

    Bouwmeester, Manon C.; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M.; Brandhof, Evert-Jan van den; Pennings, Jeroen L.A.; Kamstra, Jorke H.; Jelinek, Jaroslav; Issa, Jean-Pierre J.; Legler, Juliette; Ven, Leo T.M. van der

    2016-01-01

    Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. - Highlights: • Compound induced effects on DNA methylation in zebrafish embryos • Global methylation not an informative biomarker • Minimal genome

  7. Lower-hybrid counter current drive for edge current density modification in DIII-D

    International Nuclear Information System (INIS)

    Fenstermacher, M.E.; Nevins, W.M.; Porkolab, M.; Bonoli, P.T.; Harvey, R.W.

    1994-01-01

    Each of the Advanced Tokamak operating modes in DIII-D is thought to have a distinctive current density profile. So far these modes have only been achieved transiently through experiments which ramp the plasma current and shape. Extension of these modes to steady state requires non-inductive current profile control, e.g., with lower hybrid current drive (LHCD). Calculations of LHCD have been done for DIII-D using the ACCOME and CQL3D codes, showing that counter driven current at the plasma edge can cancel some of the undesirable edge bootstrap current and potentially extend the VH-mode. Results will be presented for scenarios using 2.45 GHz LH waves launched from both the midplane and off-axis ports. The sensitivity of the results to injected power, n e and T e , and launched wave spectrum will also be shown

  8. Determination of the level of DNA modification with cisplatin by catalytic hydrogen evolution at mercury-based electrodes.

    Science.gov (United States)

    Horáková, Petra; Tesnohlídková, Lucie; Havran, Ludek; Vidláková, Pavlína; Pivonková, Hana; Fojta, Miroslav

    2010-04-01

    Electrochemical methods proved useful as simple and inexpensive tools for the analysis of natural as well as chemically modified nucleic acids. In particular, covalently attached metal-containing groups usually render the DNA well-pronounced electrochemical activity related to redox processes of the metal moieties, which can in some cases be coupled to catalytic hydrogen evolution at mercury or some types of amalgam electrodes. In this paper we used voltammetry at the mercury-based electrodes for the monitoring of DNA modification with cis-diamminedichloroplatinum (cisplatin), a representative of metallodrugs used in the treatment of various types of cancer or being developed for such purpose. In cyclic voltammetry at the mercury electrode, the cisplatin-modified DNA yielded catalytic currents the intensity of which reflected DNA modification extent. In square-wave voltammetry, during anodic polarization after prereduction of the cisplatinated DNA, a well-developed, symmetrical signal (peak P) was obtained. Intensity of the peak P linearly responded to the extent of DNA modification at levels relevant for biochemical studies (rb = 0.01-0.10, where rb is the number of platinum atoms bound per DNA nucleotide). We demonstrate a correlation between the peak P intensity and a loss of sequence-specific DNA binding by tumor suppressor protein p53, as well as blockage of DNA digestion by a restriction endonuclease Msp I (both caused by the DNA cisplatination). Application of the electrochemical technique in studies of DNA reactivity with various anticancer platinum compounds, as well as for an easy determination of the extent of DNA platination in studies of its biochemical effects, is discussed.

  9. The role of DNA restriction-modification systems in the biology of Bacillus anthracis

    Directory of Open Access Journals (Sweden)

    Ramakrishnan eSitaraman

    2016-01-01

    Full Text Available Restriction-modification (R-M systems are widespread among prokaryotes and, depending on their type, may be viewed as selfish genetic elements that persist as toxin-antitoxin modules or as cellular defense systems against phage infection. Studies in the last decade have made it amply clear that these two options do not exhaust the list of possible biological roles for R-M systems. Their presence in a cell may also have a bearing on other processes such as horizontal gene transfer and gene regulation. From genome sequencing and experimental data, we know that Bacillus anthracis encodes at least three methylation-dependent (typeIV restriction endonucleases, and an orphan DNA methyltransferase. In this article, we first present an outline of our current knowledge of R-M systems in Bacillus anthracis. Based on available DNA sequence data, and on our current understanding of the functions of similar genes in other systems, we conclude with hypotheses on the possible roles of the three restriction endonucleases and the orphan DNA methyltransferase.

  10. Identification of a DNA restriction-modification system in Pectobacterium carotovorum strains isolated from Poland.

    Science.gov (United States)

    Waleron, K; Waleron, M; Osipiuk, J; Podhajska, A J; Lojkowska, E

    2006-02-01

    Polish isolates of pectinolytic bacteria from the species Pectobacterium carotovorum were screened for the presence of a DNA restriction-modification (R-M) system. Eighty-nine strains of P. carotovorum were isolated from infected potato plants. Sixty-six strains belonged to P. carotovorum ssp. atrosepticum and 23 to P. carotovorum ssp. carotovorum. The presence of restriction enzyme Pca17AI, which is an isoschizomer of EcoRII endonuclease, was observed in all isolates of P. c. atrosepticum but not in P. c. carotovorum. The biochemical properties, PCR amplification, and sequences of the Pca17AI restriction endonuclease and methyltransferase genes were compared with the prototype EcoRII R-M system genes. Only when DNA isolated from cells of P. c. atrosepticum was used as a template, amplification of a 680 bp homologous to the gene coding EcoRII endonuclease. Endonuclease Pca17AI, having a relatively low temperature optimum, was identified. PCR amplification revealed that the nucleotide sequence of genes for EcoRII and Pca17AI R-M are different. Dcm methylation was observed in all strains of Pectobacterium and other Erwinia species tested. The sequence of a DNA fragment coding Dcm methylase in P. carotovorum was different from that of Escherichia coli. Pca17AI is the first psychrophilic isoschizomer of EcoRII endonuclease. The presence of specific Dcm methylation in chromosomal DNA isolated from P. carotovorum is described for the first time. A 680 bp PCR product, unique for P. c. atrosepticum strains, could serve as a molecular marker for detection of these bacteria in environmental samples.

  11. Fusion of GFP to the M.EcoKI DNA methyltransferase produces a new probe of Type I DNA restriction and modification enzymes

    International Nuclear Information System (INIS)

    Chen, Kai; Roberts, Gareth A.; Stephanou, Augoustinos S.; Cooper, Laurie P.; White, John H.; Dryden, David T.F.

    2010-01-01

    Research highlights: → Successful fusion of GFP to M.EcoKI DNA methyltransferase. → GFP located at C-terminal of sequence specificity subunit does not later enzyme activity. → FRET confirms structural model of M.EcoKI bound to DNA. -- Abstract: We describe the fusion of enhanced green fluorescent protein to the C-terminus of the HsdS DNA sequence-specificity subunit of the Type I DNA modification methyltransferase M.EcoKI. The fusion expresses well in vivo and assembles with the two HsdM modification subunits. The fusion protein functions as a sequence-specific DNA methyltransferase protecting DNA against digestion by the EcoKI restriction endonuclease. The purified enzyme shows Foerster resonance energy transfer to fluorescently-labelled DNA duplexes containing the target sequence and to fluorescently-labelled ocr protein, a DNA mimic that binds to the M.EcoKI enzyme. Distances determined from the energy transfer experiments corroborate the structural model of M.EcoKI.

  12. Lower hybrid current drive for edge current density modification in DIII-D: Final status report

    International Nuclear Information System (INIS)

    Fenstermacher, M.E.; Porkolab, M.

    1993-01-01

    Application of Lower Hybrid (LH) Current Drive (CD) in the DIII-D tokamak has been studied at LLNL, off and on, for several years. The latest effort began in February 1992 in response to a letter from ASDEX indicating that the 2.45 GHz, 3 MW system there was available to be used on another device. An initial assessment of the possible uses for such a system on DIII-D was made and documented in September 1992. Multiple meetings with GA personnel and members of the LH community nationwide have occurred since that time. The work continued through the submission of the 1995 Field Work Proposals in March 1993 and was then put on hold due to budget limitations. The purpose of this document is to record the status of the work in such a way that it could fairly easily be restarted at a future date. This document will take the form of a collection of Appendices giving both background and the latest results from the FY 1993 work, connected by brief descriptive text. Section 2 will describe the final workshop on LHCD in DIII-D held at GA in February 1993. This was an open meeting with attendees from GA, LLNL, MIT and PPPL. Summary documents from the meeting and subsequent papers describing the results will be included in Appendices. Section 3 will describe the status of work on the use of low frequency (2.45 GHZ) LH power and Parametric Decay Instabilities (PDI) for the special case of high dielectric in the edge regions of the DIII-D plasma. This was one of the critical issues identified at the workshop. Other potential issues for LHCD in the DIII-D scenarios are: (1) damping of the waves on fast ions from neutral beam injection, (2) runaway electrons in the low density edge plasma, (3) the validity of the WKB approximation used in the ray-tracing models in the steep edge density gradients

  13. The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Ke-Xin Wen

    Full Text Available Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND such as Alzheimer's disease (AD and Parkinson's disease (PD.To systematically review studies investigating epigenetic marks in AD or PD.Eleven bibliographic databases (Embase.com, Medline (Ovid, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost, Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form.Of 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes. There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD.Many studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.

  14. Dissociation from DNA of Type III Restriction–Modification enzymes during helicase-dependent motion and following endonuclease activity

    Science.gov (United States)

    Tóth, Júlia; van Aelst, Kara; Salmons, Hannah; Szczelkun, Mark D.

    2012-01-01

    DNA cleavage by the Type III Restriction–Modification (RM) enzymes requires the binding of a pair of RM enzymes at two distant, inversely orientated recognition sequences followed by helicase-catalysed ATP hydrolysis and long-range communication. Here we addressed the dissociation from DNA of these enzymes at two stages: during long-range communication and following DNA cleavage. First, we demonstrated that a communicating species can be trapped in a DNA domain without a recognition site, with a non-specific DNA association lifetime of ∼200 s. If free DNA ends were present the lifetime became too short to measure, confirming that ends accelerate dissociation. Secondly, we observed that Type III RM enzymes can dissociate upon DNA cleavage and go on to cleave further DNA molecules (they can ‘turnover’, albeit inefficiently). The relationship between the observed cleavage rate and enzyme concentration indicated independent binding of each site and a requirement for simultaneous interaction of at least two enzymes per DNA to achieve cleavage. In light of various mechanisms for helicase-driven motion on DNA, we suggest these results are most consistent with a thermally driven random 1D search model (i.e. ‘DNA sliding’). PMID:22523084

  15. Restriction-modification mediated barriers to exogenous DNA uptake and incorporation employed by Prevotella intermedia.

    Science.gov (United States)

    Johnston, Christopher D; Skeete, Chelsey A; Fomenkov, Alexey; Roberts, Richard J; Rittling, Susan R

    2017-01-01

    Prevotella intermedia, a major periodontal pathogen, is increasingly implicated in human respiratory tract and cystic fibrosis lung infections. Nevertheless, the specific mechanisms employed by this pathogen remain only partially characterized and poorly understood, largely due to its total lack of genetic accessibility. Here, using Single Molecule, Real-Time (SMRT) genome and methylome sequencing, bisulfite sequencing, in addition to cloning and restriction analysis, we define the specific genetic barriers to exogenous DNA present in two of the most widespread laboratory strains, P. intermedia ATCC 25611 and P. intermedia Strain 17. We identified and characterized multiple restriction-modification (R-M) systems, some of which are considerably divergent between the two strains. We propose that these R-M systems are the root cause of the P. intermedia transformation barrier. Additionally, we note the presence of conserved Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) systems in both strains, which could provide a further barrier to exogenous DNA uptake and incorporation. This work will provide a valuable resource during the development of a genetic system for P. intermedia, which will be required for fundamental investigation of this organism's physiology, metabolism, and pathogenesis in human disease.

  16. Endogenously generated DNA nucleobase modifications source, and significance as possible biomarkers of malignant transformation risk, and role in anticancer therapy.

    Science.gov (United States)

    Olinski, Ryszard; Gackowski, Daniel; Cooke, Marcus S

    2018-01-01

    The DNA of all living cells undergoes continuous structural and chemical alteration, which may be derived from exogenous sources, or endogenous, metabolic pathways, such as cellular respiration, replication and DNA demethylation. It has been estimated that approximately 70,000 DNA lesions may be generated per day in a single cell, and this has been linked to a wide variety of diseases, including cancer. However, it is puzzling why potentially mutagenic DNA modifications, occurring at a similar level in different organs/tissue, may lead to organ/tissue specific cancers, or indeed non-malignant disease - what is the basis for this differential response? We suggest that it is perhaps the precise location of damage, within the genome, that is a key factor. Finally, we draw attention to the requirement for reliable methods for identification and quantification of DNA adducts/modifications, and stress the need for these assays to be fully validated. Once these prerequisites are satisfied, measurement of DNA modifications may be helpful as a clinical parameter for treatment monitoring, risk group identification and development of prevention strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Modification of DNA bases in mammalian chromatin by radiation-generated free radicals

    International Nuclear Information System (INIS)

    Gajewski, E.; Rao, G.; Nackerdien, Z.; Dizdaroglu, M.

    1990-01-01

    Modification of DNA bases in mammalian chromatin in aqueous suspension by ionizing radiation generated free radicals was investigated. Argon, air, N2O, and N2O/O2 were used for saturation of the aqueous system in order to provide different radical environments. Radiation doses ranging from 20 to 200 Gy (J.kg-1) were used. Thirteen products resulting from radical interactions with pyrimidines and purines in chromatin were identified and quantitated by using the technique of gas chromatography/mass spectrometry with selected-ion monitoring after acidic hydrolysis and trimethylsilylation of chromatin. The methodology used permitted analysis of the modified bases directly in chromatin without the necessity of isolation of DNA from chromatin first. The results indicate that the radical environment provided by the presence of different gases in the system had a substantial effect on the types of products and their quantities. Some products were produced only in the presence of oxygen, whereas other products were detected only in the absence of oxygen. Products produced under all four gaseous conditions were also observed. Generally, the presence of oxygen in the system increased the yields of the products with the exception of formamidopyrimidines. Superoxide radical formed in the presence of air, and to a lesser extent in the presence of N2O/O2, had no effect on product formation. The presence of oxygen dramatically increased the yields of 8-hydroxypurines, whereas the yields of formamidopyrimidines were not affected by oxygen, although these products result from respective oxidation and reduction of the same hydroxyl-adduct radicals of purines. The yields of the products were much lower than those observed previously with DNA

  18. PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

    Science.gov (United States)

    Maréchal, Alexandre; Li, Ju-Mei; Ji, Xiao Ye; Wu, Ching-Shyi; Yazinski, Stephanie A; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E; Jin, Jianping; Zou, Lee

    2014-01-23

    PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Ball with hair: modular functionalization of highly stable G-quadruplex DNA nano-scaffolds through N2-guanine modification.

    Science.gov (United States)

    Lech, Christopher Jacques; Phan, Anh Tuân

    2017-06-20

    Functionalized nanoparticles have seen valuable applications, particularly in the delivery of therapeutic and diagnostic agents in biological systems. However, the manufacturing of such nano-scale systems with the consistency required for biological application can be challenging, as variation in size and shape have large influences in nanoparticle behavior in vivo. We report on the development of a versatile nano-scaffold based on the modular functionalization of a DNA G-quadruplex. DNA sequences are functionalized in a modular fashion using well-established phosphoramidite chemical synthesis with nucleotides containing modification of the amino (N2) position of the guanine base. In physiological conditions, these sequences fold into well-defined G-quadruplex structures. The resulting DNA nano-scaffolds are thermally stable, consistent in size, and functionalized in a manner that allows for control over the density and relative orientation of functional chemistries on the nano-scaffold surface. Various chemistries including small modifications (N2-methyl-guanine), bulky aromatic modifications (N2-benzyl-guanine), and long chain-like modifications (N2-6-amino-hexyl-guanine) are tested and are found to be generally compatible with G-quadruplex formation. Furthermore, these modifications stabilize the G-quadruplex scaffold by 2.0-13.3 °C per modification in the melting temperature, with concurrent modifications producing extremely stable nano-scaffolds. We demonstrate the potential of this approach by functionalizing nano-scaffolds for use within the biotin-avidin conjugation approach. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. DNA alkylation lesions and their repair in human cells: modification of the comet assay with 3-methyladenine DNA glycosylase (AlkD).

    Science.gov (United States)

    Hašplová, Katarína; Hudecová, Alexandra; Magdolénová, Zuzana; Bjøras, Magnar; Gálová, Eliška; Miadoková, Eva; Dušinská, Mária

    2012-01-05

    3-methyladenine DNA glycosylase (AlkD) belongs to a new family of DNA glycosylases; it initiates repair of cytotoxic and promutagenic alkylated bases (its main substrates being 3-methyladenine and 7-methylguanine). The modification of the comet assay (single cell gel electrophoresis) using AlkD enzyme thus allows assessment of specific DNA alkylation lesions. The resulting baseless sugars are alkali-labile, and under the conditions of the alkaline comet assay they appear as DNA strand breaks. The alkylating agent methyl methanesulfonate (MMS) was used to induce alkylation lesions and to optimize conditions for the modified comet assay method with AlkD on human lymphoblastoid (TK6) cells. We also studied cellular and in vitro DNA repair of alkylated bases in DNA in TK6 cells after treatment with MMS. Results from cellular repair indicate that 50% of DNA alkylation is repaired in the first 60 min. The in vitro repair assay shows that while AlkD recognises most alkylation lesions after 60 min, a cell extract from TK6 cells recognises most of the MMS-induced DNA adducts already in the first 15 min of incubation, with maximum detection of lesions after 60 min' incubation. Additionally, we tested the in vitro repair capacity of human lymphocyte extracts from 5 individuals and found them to be able to incise DNA alkylations in the same range as AlkD. The modification of the comet assay with AlkD can be useful for in vitro and in vivo genotoxicity studies to detect alkylation damage and repair and also for human biomonitoring and molecular epidemiology studies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Cytosine modifications after gamma irradiation in aerated aqueous solution of Escherichia coli DNA

    International Nuclear Information System (INIS)

    Polverelli, M.

    1983-04-01

    After gamma irradiation of cytosine in aerated aqueous solution and utilization of various spectrometric methods (mass spectrometry, proton nuclear magnetic resonance and infrared spectrometry) about ten new radiolysis products were identified. The formation of N-glycolylbiuret in H 2 18 O aqueous solution of irradiated cytosine at pH 4,5 indicated that the preferred 18 OH hydroxyl radical attack was at C-5. The formation of trans 1-carbamoyl-4,5 dihydroxyimidazolidin-2 oxo which is the major product after cytosine pyrimidine ring rearrangement took place preferentially at neutral pH, while N-glycolylbiuret predominated at pH 4,5. The deamination pathway was predominant when cytosine was irradiated at acidic pH values (pH 2 ) or in copper complexes. The development of a new acid hydrolysis method using fluorhydric acid stabilized in pyridine made easier the evaluation of cytosine modifications after gamma irradiation in aerated aqueous solution of E. Coli DNA- 14 C-2 cytosine. This hydrolytic agent removed the modified bases from the polynucleotidic chain. A difference was found between the proportion of radiolytic products removed by acid hydrolysis and by irradiation of the free base in solution [fr

  2. Modification of radiation induced genetic damage and impaired DNA synthesis by thiourea treatment in Solanum incanum L

    International Nuclear Information System (INIS)

    Kumar, Girish

    1991-01-01

    Modification of induced genetic damage after exposure to LD 50 and LD 90 doses of 60 Co gamma-irradiation on dormant seeds of Solanum incanum L. by pre- and post-treatments of thiourea was investigated. Thiourea pre-treatment reduced cellular lesions, growth injury and the death of seedlings, while post-treatment increased lethality. Incorporation of 3 H-tymidine into DNA fraction gradually increased with 10 -4 to 10 -2 M thiourea treatment when applied before irradiation. Post-treatment of the thiourea, on the other hand, not only showed poor labelling of DNA but also delayed its synthesis. (author)

  3. Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation

    Science.gov (United States)

    Tropberger, Philipp; Mercier, Alexandre; Robinson, Margaret; Zhong, Weidong; Ganem, Don E.; Holdorf, Meghan

    2015-01-01

    Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and is a major risk factor for liver failure and hepatocellular carcinoma. Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is not curative because it does not directly affect nuclear HBV closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target cccDNA regulation would therefore be highly desirable. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq approach, we report, to our knowledge, the first genome-wide maps of PTMs in cccDNA-containing chromatin from de novo infected HepG2 cells, primary human hepatocytes, and from HBV-infected liver tissue. We find high levels of PTMs associated with active transcription enriched at specific sites within the HBV genome and, surprisingly, very low levels of PTMs linked to transcriptional repression even at silent HBV promoters. We show that transcription and active PTMs in HBV chromatin are reduced by the activation of an innate immunity pathway, and that this effect can be recapitulated with a small molecule epigenetic modifying agent, opening the possibility that chromatin-based regulation of cccDNA transcription could be a new therapeutic approach to chronic HBV infection. PMID:26438841

  4. Microarray-based analysis of plasma cirDNA epigenetic modification profiling in xenografted mice exposed to intermittent hypoxia

    Directory of Open Access Journals (Sweden)

    Rene Cortese

    2015-09-01

    Full Text Available Intermittent hypoxia (IH during sleep is one of the major abnormalities occurring in patients suffering from obstructive sleep apnea (OSA, a highly prevalent disorder affecting 6–15% of the general population, particularly among obese people. IH has been proposed as a major determinant of oncogenetically-related processes such as tumor growth, invasion and metastasis. During the growth and expansion of tumors, fragmented DNA is released into the bloodstream and enters the circulation. Circulating tumor DNA (cirDNA conserves the genetic and epigenetic profiles from the tumor of origin and can be isolated from the plasma fraction. Here we report a microarray-based epigenetic profiling of cirDNA isolated from blood samples of mice engrafted with TC1 epithelial lung cancer cells and controls, which were exposed to IH during sleep (XenoIH group, n = 3 or control conditions, (i.e., room air (RA; XenoRA group, n = 3 conditions. To prepare the targets for microarray hybridization, we applied a previously developed method that enriches the modified fraction of the cirDNA without amplification of genomic DNA. Regions of differential cirDNA modification between the two groups were identified by hybridizing the enriched fractions for each sample to Affymetrix GeneChip Human Promoter Arrays 1.0R. Microarray raw and processed data were deposited in NCBI's Gene Expression Omnibus (GEO database (accession number: GSE61070.

  5. Specific modifications of histone tails, but not DNA methylation, mirror the temporal variation of mammalian recombination hotspots.

    Science.gov (United States)

    Zeng, Jia; Yi, Soojin V

    2014-10-16

    Recombination clusters nonuniformly across mammalian genomes at discrete genomic loci referred to as recombination hotspots. Despite their ubiquitous presence, individual hotspots rapidly lose their activities, and the molecular and evolutionary mechanisms underlying such frequent hotspot turnovers (the so-called "recombination hotspot paradox") remain unresolved. Even though some sequence motifs are significantly associated with hotspots, multiple lines of evidence indicate that factors other than underlying sequences, such as epigenetic modifications, may affect the evolution of recombination hotspots. Thus, identifying epigenetic factors that covary with recombination at fine-scale is a promising step for this important research area. It was previously reported that recombination rates correlate with indirect measures of DNA methylation in the human genome. Here, we analyze experimentally determined DNA methylation and histone modification of human sperms, and show that the correlation between DNA methylation and recombination in long-range windows does not hold with respect to the spatial and temporal variation of recombination at hotspots. On the other hand, two histone modifications (H3K4me3 and H3K27me3) overlap extensively with recombination hotspots. Similar trends were observed in mice. These results indicate that specific histone modifications rather than DNA methylation are associated with the rapid evolution of recombination hotspots. Furthermore, many human recombination hotspots occupy "bivalent" chromatin regions that harbor both active (H3K4me3) and repressive (H3K27me3) marks. This may explain why human recombination hotspots tend to occur in nongenic regions, in contrast to yeast and Arabidopsis hotspots that are characterized by generally active chromatins. Our results highlight the dynamic epigenetic underpinnings of recombination hotspot evolution. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for

  6. Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation.

    Science.gov (United States)

    Ngo, Huu B; Lovely, Geoffrey A; Phillips, Rob; Chan, David C

    2014-01-01

    TFAM (transcription factor A, mitochondrial) is a DNA-binding protein that activates transcription at the two major promoters of mitochondrial DNA (mtDNA)--the light strand promoter (LSP) and the heavy strand promoter 1 (HSP1). Equally important, it coats and packages the mitochondrial genome. TFAM has been shown to impose a U-turn on LSP DNA; however, whether this distortion is relevant at other sites is unknown. Here we present crystal structures of TFAM bound to HSP1 and to nonspecific DNA. In both, TFAM similarly distorts the DNA into a U-turn. Yet, TFAM binds to HSP1 in the opposite orientation from LSP explaining why transcription from LSP requires DNA bending, whereas transcription at HSP1 does not. Moreover, the crystal structures reveal dimerization of DNA-bound TFAM. This dimerization is dispensable for DNA bending and transcriptional activation but is important in DNA compaction. We propose that TFAM dimerization enhances mitochondrial DNA compaction by promoting looping of the DNA.

  7. The dynamic changes of DNA methylation and histone modifications of salt responsive transcription factor genes in soybean.

    Directory of Open Access Journals (Sweden)

    Yuguang Song

    Full Text Available Epigenetic modification contributes to the regulation of gene expression and plant development under salinity stress. Here we describe the identification of 49 soybean transcription factors by microarray analysis as being inducible by salinity stress. A semi-quantitative RT-PCR-based expression assay confirmed the salinity stress inducibility of 45 of these 49 transcription factors, and showed that ten of them were up-regulated when seedlings were exposed to the demethylation agent 5-aza-2-deoxycytidine. Salinity stress was shown to affect the methylation status of four of these ten transcription factors (one MYB, one b-ZIP and two AP2/DREB family members using a combination of bisulfite sequencing and DNA methylation-sensitive DNA gel blot analysis. ChIP analysis indicated that the activation of three of the four DNA methylated transcription factors was correlated with an increased level of histone H3K4 trimethylation and H3K9 acetylation, and/or a reduced level of H3K9 demethylation in various parts of the promoter or coding regions. Our results suggest a critical role for some transcription factors' activation/repression by DNA methylation and/or histone modifications in soybean tolerance to salinity stress.

  8. Histone Modification Associated with Initiation of DNA Replication | Center for Cancer Research

    Science.gov (United States)

    Before cells are able to divide, they must first duplicate their chromosomes accurately. DNA replication and packaging of DNA into chromosomes by histone proteins need to be coordinated by the cell to ensure proper transmission of genetic and epigenetic information to the next generation. Mammalian DNA replication begins at specific chromosomal sites, called replication

  9. C-terminal region of DNA ligase IV drives XRCC4/DNA ligase IV complex to chromatin

    International Nuclear Information System (INIS)

    Liu, Sicheng; Liu, Xunyue; Kamdar, Radhika Pankaj; Wanotayan, Rujira; Sharma, Mukesh Kumar; Adachi, Noritaka; Matsumoto, Yoshihisa

    2013-01-01

    Highlights: •Chromatin binding of XRCC4 is dependent on the presence of DNA ligase IV. •C-terminal region of DNA ligase IV alone can recruit itself and XRCC4 to chromatin. •Two BRCT domains of DNA ligase IV are essential for the chromatin binding of XRCC4. -- Abstract: DNA ligase IV (LIG4) and XRCC4 form a complex to ligate two DNA ends at the final step of DNA double-strand break (DSB) repair through non-homologous end-joining (NHEJ). It is not fully understood how these proteins are recruited to DSBs. We recently demonstrated radiation-induced chromatin binding of XRCC4 by biochemical fractionation using detergent Nonidet P-40. In the present study, we examined the role of LIG4 in the recruitment of XRCC4/LIG4 complex to chromatin. The chromatin binding of XRCC4 was dependent on the presence of LIG4. The mutations in two BRCT domains (W725R and W893R, respectively) of LIG4 reduced the chromatin binding of LIG4 and XRCC4. The C-terminal fragment of LIG4 (LIG4-CT) without N-terminal catalytic domains could bind to chromatin with XRCC4. LIG4-CT with W725R or W893R mutation could bind to chromatin but could not support the chromatin binding of XRCC4. The ability of C-terminal region of LIG4 to interact with chromatin might provide us with an insight into the mechanisms of DSB repair through NHEJ

  10. LuxGLM: a probabilistic covariate model for quantification of DNA methylation modifications with complex experimental designs.

    Science.gov (United States)

    Äijö, Tarmo; Yue, Xiaojing; Rao, Anjana; Lähdesmäki, Harri

    2016-09-01

    5-methylcytosine (5mC) is a widely studied epigenetic modification of DNA. The ten-eleven translocation (TET) dioxygenases oxidize 5mC into oxidized methylcytosines (oxi-mCs): 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). DNA methylation modifications have multiple functions. For example, 5mC is shown to be associated with diseases and oxi-mC species are reported to have a role in active DNA demethylation through 5mC oxidation and DNA repair, among others, but the detailed mechanisms are poorly understood. Bisulphite sequencing and its various derivatives can be used to gain information about all methylation modifications at single nucleotide resolution. Analysis of bisulphite based sequencing data is complicated due to the convoluted read-outs and experiment-specific variation in biochemistry. Moreover, statistical analysis is often complicated by various confounding effects. How to analyse 5mC and oxi-mC data sets with arbitrary and complex experimental designs is an open and important problem. We propose the first method to quantify oxi-mC species with arbitrary covariate structures from bisulphite based sequencing data. Our probabilistic modeling framework combines a previously proposed hierarchical generative model for oxi-mC-seq data and a general linear model component to account for confounding effects. We show that our method provides accurate methylation level estimates and accurate detection of differential methylation when compared with existing methods. Analysis of novel and published data gave insights into to the demethylation of the forkhead box P3 (Foxp3) locus during the induced T regulatory cell differentiation. We also demonstrate how our covariate model accurately predicts methylation levels of the Foxp3 locus. Collectively, LuxGLM method improves the analysis of DNA methylation modifications, particularly for oxi-mC species. An implementation of the proposed method is available under MIT license at https

  11. Detection of irradiation induced modifications in foodstuff DNA using 32p post-labelling

    International Nuclear Information System (INIS)

    Hoey, B.M.; Swallow, A.J.; Margison, G.P.

    1991-01-01

    DNA post-labelling has been used successfully to detect damage to DNA caused by a range of damaging agents. The assay results in a fingerprint of changes induced in DNA which might, in principle, be useful as a test for the detection of the irradiation of foods. The authors present their DNA extraction and 32 p post-labelling methods from chicken or cooked prawn samples and their analysis method (High Performance liquid chromatography). It's hoped that these results could form the basis of a test to detect if foods have been irradiated

  12. Histone Modification Is Involved in Okadaic Acid (OA Induced DNA Damage Response and G2-M Transition Arrest in Maize.

    Directory of Open Access Journals (Sweden)

    Hao Zhang

    Full Text Available Histone modifications are involved in regulation of chromatin structure. To investigate the relationship between chromatin modification and cell cycle regulation during plant cell proliferation, Okadaic acid (OA, a specific inhibitor of serine/threonine protein phosphatase, was applied in this study. The results showed that OA caused the cell cycle arrest at preprophase, leading to seedling growth inhibition. Western blotting assay revealed that the spatial distribution of phosphorylation of Ser10 histone H3 tails (H3S10ph signals was altered under OA treatment. Reactive oxygen species (ROS was found to be at higher levels and TdT-mediated dUTP nick end labeling (TUNEL assay displayed DNA breaks happened at the chromatin after treatment with OA, companied with an increase in the acetylation of histone H4 at lysine 5 (H4K5ac level. From these observations, we speculated that the alteration of the spatial distribution of H3S10ph and the level of H4K5ac was involved in the procedure that OA induced DNA breaks and G2-M arrested by the accumulation of ROS, and that the histone H3S10ph and H4K5ac might facilitate DNA repair by their association with the chromatin decondensation.

  13. Non coding RNA: sequence-specific guide for chromatin modification and DNA damage signaling

    Directory of Open Access Journals (Sweden)

    Sofia eFrancia

    2015-11-01

    Full Text Available Chromatin conformation shapes the environment in which our genome is transcribed into RNA. Transcription is a source of DNA damage, thus it often occurs concomitantly to DNA damage signaling. Growing amounts of evidence suggest that different types of RNAs can, independently from their protein-coding properties, directly affect chromatin conformation, transcription and splicing, as well as promote the activation of the DNA damage response (DDR and DNA repair. Therefore, transcription paradoxically functions to both threaten and safeguard genome integrity. On the other hand, DNA damage signaling is known to modulate chromatin to suppress transcription of the surrounding genetic unit. It is thus intriguing to understand how transcription can modulate DDR signaling while, in turn, DDR signaling represses transcription of chromatin around the DNA lesion. An unexpected player in this field is the RNA interference (RNAi machinery, which play roles in transcription, splicing and chromatin modulation in several organisms. Non-coding RNAs (ncRNAs and several protein factors involved in the RNAi pathway are well known master regulators of chromatin while only recent reports suggest that ncRNAs are involved in DDR signaling and homology-mediated DNA repair. Here, we discuss the experimental evidence supporting the idea that ncRNAs act at the genomic loci from which they are transcribed to modulate chromatin, DDR signaling and DNA repair.

  14. DNA Mapping Made Simple: An Intellectual Activity about the Genetic Modification of Organisms

    Science.gov (United States)

    Marques, Miguel; Arrabaca, Joao; Chagas, Isabel

    2004-01-01

    Since the discovery of the DNA double helix (in 1953 by Watson and Crick), technologies have been developed that allow scientists to manipulate the genome of bacteria to produce human hormones, as well as the genome of crop plants to achieve high yield and enhanced flavor. The universality of the genetic code has allowed DNA isolated from a…

  15. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available Accumulation of DNA damage leading to stem cell exhaustion has been proposed to be a principal mechanism of aging. Using 53BP1-foci as a marker for DNA double-strand breaks (DSBs, hair follicle stem cells (HFSCs in mouse epidermis were analyzed for age-related DNA damage response (DDR. We observed increasing amounts of 53BP1-foci during the natural aging process independent of telomere shortening and after protracted low-dose radiation, suggesting substantial accumulation of DSBs in HFSCs. Electron microscopy combined with immunogold-labeling showed multiple small 53BP1 clusters diffusely distributed throughout the highly compacted heterochromatin of aged HFSCs, but single large 53BP1 clusters in irradiated HFSCs. These remaining 53BP1 clusters did not colocalize with core components of non-homologous end-joining, but with heterochromatic histone modifications. Based on these results we hypothesize that these lesions were not persistently unrepaired DSBs, but may reflect chromatin rearrangements caused by the repair or misrepair of DSBs. Flow cytometry showed increased activation of repair proteins and damage-induced chromatin modifications, triggering apoptosis and cellular senescence in irradiated, but not in aged HFSCs. These results suggest that accumulation of DNA damage-induced chromatin alterations, whose structural dimensions reflect the complexity of the initial genotoxic insult, may lead to different DDR events, ultimately determining the biological outcome of HFSCs. Collectively, our findings support the hypothesis that aging might be largely the remit of structural changes to chromatin potentially leading to epigenetically induced transcriptional deregulation.

  16. Defined-size DNA triple crossover construct for molecular electronics: modification, positioning and conductance properties.

    Science.gov (United States)

    Linko, Veikko; Leppiniemi, Jenni; Paasonen, Seppo-Tapio; Hytönen, Vesa P; Toppari, J Jussi

    2011-07-08

    We present a novel, defined-size, small and rigid DNA template, a so-called B-A-B complex, based on DNA triple crossover motifs (TX tiles), which can be utilized in molecular scale patterning for nanoelectronics, plasmonics and sensing applications. The feasibility of the designed construct is demonstrated by functionalizing the TX tiles with one biotin-triethylene glycol (TEG) and efficiently decorating them with streptavidin, and furthermore by positioning and anchoring single thiol-modified B-A-B complexes to certain locations on a chip via dielectrophoretic trapping. Finally, we characterize the conductance properties of the non-functionalized construct, first by measuring DC conductivity and second by utilizing AC impedance spectroscopy in order to describe the conductivity mechanism of a single B-A-B complex using a detailed equivalent circuit model. This analysis also reveals further information about the conductivity of DNA structures in general.

  17. Protozoan ALKBH8 Oxygenases Display both DNA Repair and tRNA Modification Activities

    DEFF Research Database (Denmark)

    Zdżalik, Daria; Vågbø, Cathrine B; Kirpekar, Finn

    2014-01-01

    The ALKBH family of Fe(II) and 2-oxoglutarate dependent oxygenases comprises enzymes that display sequence homology to AlkB from E. coli, a DNA repair enzyme that uses an oxidative mechanism to dealkylate methyl and etheno adducts on the nucleobases. Humans have nine different ALKBH proteins, ALKBH......1-8 and FTO. Mammalian and plant ALKBH8 are tRNA hydroxylases targeting 5-methoxycarbonylmethyl-modified uridine (mcm5U) at the wobble position of tRNAGly(UCC). In contrast, the genomes of some bacteria encode a protein with strong sequence homology to ALKBH8, and robust DNA repair activity...... was previously demonstrated for one such protein. To further explore this apparent functional duality of the ALKBH8 proteins, we have here enzymatically characterized a panel of such proteins, originating from bacteria, protozoa and mimivirus. All the enzymes showed DNA repair activity in vitro, but...

  18. Organization of the BcgI restriction-modification protein for the cleavage of eight phosphodiester bonds in DNA

    Science.gov (United States)

    Smith, Rachel M.; Marshall, Jacqueline J. T.; Jacklin, Alistair J.; Retter, Susan E.; Halford, Stephen E.; Sobott, Frank

    2013-01-01

    Type IIB restriction-modification systems, such as BcgI, feature a single protein with both endonuclease and methyltransferase activities. Type IIB nucleases require two recognition sites and cut both strands on both sides of their unmodified sites. BcgI cuts all eight target phosphodiester bonds before dissociation. The BcgI protein contains A and B polypeptides in a 2:1 ratio: A has one catalytic centre for each activity; B recognizes the DNA. We show here that BcgI is organized as A2B protomers, with B at its centre, but that these protomers self-associate to assemblies containing several A2B units. Moreover, like the well known FokI nuclease, BcgI bound to its site has to recruit additional protomers before it can cut DNA. DNA-bound BcgI can alternatively be activated by excess A subunits, much like the activation of FokI by its catalytic domain. Eight A subunits, each with one centre for nuclease activity, are presumably needed to cut the eight bonds cleaved by BcgI. Its nuclease reaction may thus involve two A2B units, each bound to a recognition site, with two more A2B units bridging the complexes by protein–protein interactions between the nuclease domains. PMID:23147005

  19. Modification of lymphocyte DNA damage by carotenoid supplementation in postmenopausal women.

    Science.gov (United States)

    Zhao, Xianfeng; Aldini, Giancarlo; Johnson, Elizabeth J; Rasmussen, Helen; Kraemer, Klaus; Woolf, Herb; Musaeus, Nina; Krinsky, Norman I; Russell, Robert M; Yeum, Kyung-Jin

    2006-01-01

    Oxidative stress has been implicated in the pathogenesis of chronic diseases related to aging such as cancer and cardiovascular disease. Carotenoids could be a part of a protective strategy to minimize oxidative damage in vulnerable populations, such as the elderly. Our aim was to determine the protective effect of carotenoids against DNA damage. A randomized, double-blind, placebo-controlled intervention study was conducted. Thirty-seven healthy, nonsmoking postmenopausal women aged 50-70 y were randomly assigned to 1 of 5 groups and were instructed to consume a daily dose of mixed carotenoids (beta-carotene, lutein, and lycopene; 4 mg each), 12 mg of a single carotenoid (beta-carotene, lutein, or lycopene), or placebo for 56 d. Plasma carotenoid concentrations were analyzed by using HPLC, and lymphocyte DNA damage was measured by using a single-cell gel electrophoresis (comet) assay. At day 57, all carotenoid-supplemented groups showed significantly lower endogenous DNA damage than at baseline (P lutein, beta-carotene, and lycopene), an intake that can be achieved by diet, or a larger dose (12 mg) of individual carotenoids exerts protection against DNA damage.

  20. DNA modifications by antitumor platinum and ruthenium compounds: Their recognition and repair

    Czech Academy of Sciences Publication Activity Database

    Brabec, Viktor

    2002-01-01

    Roč. 71, - (2002), s. 1-68 ISSN 0079-6603 R&D Projects: GA AV ČR IAA5004101 Institutional research plan: CEZ:AV0Z5004920 Keywords : interstrand cross-link * cisplatin -demaged DNA * anticancer drug cisplatin Subject RIV: BO - Biophysics Impact factor: 4.839, year: 2002

  1. Suberoylanilide Hydroxyamic Acid Modification of Chromatin Architecture Affects DNA Break Formation and Repair

    International Nuclear Information System (INIS)

    Singh, Sheetal; Le Hongan; Shih, S.-J.; Ho, Bay; Vaughan, Andrew T.

    2010-01-01

    Purpose: Chromatin-modifying compounds that inhibit the activity of histone deacetylases have shown potency as radiosensitizers, but the action of these drugs at a molecular level is not clear. Here we investigated the effect of suberoylanilide hydroxyamic acid (SAHA) on DNA breaks and their repair and induction of rearrangements. Methods and Materials: The effect of SAHA on both clonogenic survival and repair was assessed using cell lines SCC-25, MCF7, and TK6. In order to study unique DNA double-strand breaks, anti-CD95 antibody was employed to introduce a DNA double-strand break at a known location within the 11q23 region. The effects of SAHA on DNA cleavage and rearrangements were analyzed by ligation-mediated PCR and inverse PCR, respectively. Results: SAHA acts as radiosensitizer at 1 μM, with dose enhancement factors (DEFs) at 10% survival of: SCC-25 - 1.24 ± 0.05; MCF7 - 1.16 ± 0.09 and TK6 - 1.17 ± 0.05, and it reduced the capacity of SCC-25 cells to repair radiation induced lesions. Additionally, SAHA treatment diffused site-specific fragmentation over at least 1 kbp in TK6 cells. Chromosomal rearrangements produced in TK6 cells exposed to SAHA showed a reduction in microhomology at the breakpoint between 11q23 and partner chromosomes. Conclusions: SAHA shows efficacy as a radiosensitizer at clinically obtainable levels. In its presence, targeted DNA strand breaks occur over an expanded region, indicating increased chromatin access. The rejoining of such breaks is degraded by SAHA when measured as rearrangements at the molecular level and rejoining that contributes to cell survival.

  2. Complementarily addressed modification and cleavage of a single-stranded fragment of DNA with the aid of alkylating derivatives of oligonucleotides

    International Nuclear Information System (INIS)

    Brosalina, E.B.; Vlasov, V.V.; Kutyavin, I.V.; Mamaev, S.V.; Pletnev, A.G.; Podyminogin, M.A.

    1986-01-01

    The chemical modification of a 303-nucleotide single-stranded fragment of DNA by alkylating oligonucleotide derivatives bearing 4-[N-methyl-N-(2-chloroethyl)amino]benzyl groups in the 5'-terminal phosphate of the 3'-terminal ribose residue has been investigated. It has been shown that under the conditions of the formation of a complex with the DNA fragment both types of derivatives specifically alkylate nucleotides of the DNA fragments that are located directly adjacent to the sections complementary to the oligonucleotides bearing the reactive groups. Alkylation takes place with a high efficiency, and the DNA fragment can be cleaved specifically at the position of the alkylated nucleotides

  3. Modification of the Current Profile in DIII-D by Off-Axis Electron Cyclotron Current Drive

    International Nuclear Information System (INIS)

    Luce, T.C.; Lin-Liu, Y.R.; Harvey, R.W.; Giruzzi, G.; Lohr, J.M.; Petty, C.C.; Politzer, P.A.; Prater; Rice, B.W.

    1999-01-01

    Localized non-inductive currents due to electron cyclotron wave absorption have been measured on the DIII-D tokamak. Clear evidence of the non-inductive currents is seen on the internal magnetic field measurements by motional Stark effect spectroscopy. The magnitude and location of the non-inductive current is evaluated by comparing the total and Ohmic current profiles of discharges with and without electron cyclotron wave power. The measured current agrees with Fokker-Planck calculations near the magnetic axis, but exceeds the predicted value as the location of the current drive is moved to the half radius

  4. Modification by diazepam or thioridazine of the psychomotor skills related to driving: a subacute trial in neurotic out-patients.

    Science.gov (United States)

    Saario, I; Linnoila, M; Mattila, M J

    1976-01-01

    Forty-five out-patients with clinically manifested anxiety were tested in order to study the effects of 2 weeks' treatment with placebo, diazepam (5-10 mg three times daily) or thioridazine (25-50 mg three times daily) on their psychomotor skills related to driving. When compared with placebo, diazepam increased the number of mistakes in reaction and co-ordination tests and also decreased ability to discriminate the fusion of flickering light. When compared to other groups, reactive and co-ordinative skills were more impaired in patients treated with thioridazine which also impaired divided attention. Aubjectively thioridazine was not experienced as effective an anxiolytic as diazepam. PMID:973981

  5. Effects of a piperidine ligand on DNA modification by antitumor cisplatin analogues

    Czech Academy of Sciences Publication Activity Database

    Kašpárková, Jana; Nováková, Olga; Najajreh, Y.; Gibson, D.; Perez, J.M.; Brabec, Viktor

    2003-01-01

    Roč. 16, č. 11 (2003), s. 1424-1432 ISSN 0893-228X R&D Projects: GA ČR GA305/02/1552; GA AV ČR KJB5004301; GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : DNA * piperidine ligand * antitumor cisplatin analogues Subject RIV: BO - Biophysics Impact factor: 3.332, year: 2003

  6. Molecular dipole-driven electronic structure modifications of DNA/RNA nucleobases on graphene

    Czech Academy of Sciences Publication Activity Database

    Yin, Y.; Červenka, Jiří; Medhekar, N.

    2017-01-01

    Roč. 8, č. 13 (2017), s. 3087-3094 ISSN 1948-7185 R&D Projects: GA ČR GA14-15357S Grant - others:AV ČR(CZ) Fellowship J. E. Purkyně Institutional support: RVO:68378271 Keywords : graphene * DNA * nucleobase * DFT Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 9.353, year: 2016

  7. Modification of radiation damage in mouse lung by DNA-binding radioprotectors

    International Nuclear Information System (INIS)

    Budd, R.; D'Abrew, S.; Coultas, P.; Martin, R.F.

    1996-01-01

    Full text: The limited diffusion of Hoechst 33342 through cell layers, which has been exploited in mapping the location of cells in multi-cellular spheroids, and in vivo, reflects a general characteristic of DNA-ligands. This property may confer special advantages on DNA-binding radioprotectors in the context of radiotherapy, where it is important to minimise delivery of the radioprotector to the tumour. For example, one might expect limited diffusion to capillaries and systemic uptake following topical application to epithelial cells, which can be dose-limiting tissues in radiotherapy. These potential applications will require delivery of sufficient concentrations of the DNA-binding radioprotectors to cells in vivo. In this context, the findings of Young and Hill, who could not detect any radioprotective effect in an in vivo setting, is of concern. We have re-examined this question by investigating radioprotection in the mouse lung model. A single intravenous injection of Hoechst 33342 (80mg/kg) given 30min prior to the lung irradiation, extends the radiation dose required for death in 50% of mice at 16 weeks post irradiation, from 19Gy to 23Gy (ie: a DMF of 1.2). This is similar to the extent of radioprotection reported by Travis et al for WR2721 (300 mg/kg) in this model. These results auger well for the potential of the more potent radioprotectors, and indeed preliminary experiments with methylproamine in the mouse lung model suggests a DMF of 1.35

  8. Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.

    Science.gov (United States)

    Stützer, Alexandra; Liokatis, Stamatios; Kiesel, Anja; Schwarzer, Dirk; Sprangers, Remco; Söding, Johannes; Selenko, Philipp; Fischle, Wolfgang

    2016-01-21

    Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended 'male sex drive' hypothesis.

    Science.gov (United States)

    Chatterjee, Aniruddha; Lagisz, Malgorzata; Rodger, Euan J; Zhen, Li; Stockwell, Peter A; Duncan, Elizabeth J; Horsfield, Julia A; Jeyakani, Justin; Mathavan, Sinnakaruppan; Ozaki, Yuichi; Nakagawa, Shinichi

    2016-09-30

    The sex drive hypothesis predicts that stronger selection on male traits has resulted in masculinization of the genome. Here we test whether such masculinizing effects can be detected at the level of the transcriptome and methylome in the adult zebrafish brain. Although methylation is globally similar, we identified 914 specific differentially methylated CpGs (DMCs) between males and females (435 were hypermethylated and 479 were hypomethylated in males compared to females). These DMCs were prevalent in gene body, intergenic regions and CpG island shores. We also discovered 15 distinct CpG clusters with striking sex-specific DNA methylation differences. In contrast, at transcriptome level, more female-biased genes than male-biased genes were expressed, giving little support for the male sex drive hypothesis. Our study provides genome-wide methylome and transcriptome assessment and sheds light on sex-specific epigenetic patterns and in zebrafish for the first time. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. The Landscape of mtDNA Modifications in Cancer: A Tale of Two Cities.

    Science.gov (United States)

    Hertweck, Kate L; Dasgupta, Santanu

    2017-01-01

    Mitochondria from normal and cancerous cells represent a tale of two cities, wherein both execute similar processes but with different cellular and molecular effects. Given the number of reviews currently available which describe the functional implications of mitochondrial mutations in cancer, this article focuses on documenting current knowledge in the abundance and distribution of somatic mitochondrial mutations, followed by elucidation of processes which affect the fate of mutations in cancer cells. The conclusion includes an overview of translational implications for mtDNA mutations, as well as recommendations for future research uniting mitochondrial variants and tumorigenesis.

  11. Biochemical studies of the thermal effects on DNA modifications by the antitumor cisplatin and their repair

    Czech Academy of Sciences Publication Activity Database

    Halámiková, Anna; Vrána, Oldřich; Kašpárková, Jana; Brabec, Viktor

    2007-01-01

    Roč. 8, č. 16 (2007), s. 2008-2015 ISSN 1439-4227 R&D Projects: GA ČR(CZ) GA305/05/2030; GA ČR(CZ) GD204/03/H016; GA ČR(CZ) GA203/05/2032; GA MZd(CZ) NR8562; GA MŠk(CZ) LC06030; GA AV ČR(CZ) 1QS500040581; GA AV ČR(CZ) KAN200200651 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : DNA * ruthenium * cancer Subject RIV: BO - Biophysics Impact factor: 3.446, year: 2007

  12. Polymicrobial infection and bacterium-mediated epigenetic modification of DNA tumor viruses contribute to pathogenesis.

    Science.gov (United States)

    Doolittle, J M; Webster-Cyriaque, J

    2014-04-29

    ABSTRACT The human body plays host to a wide variety of microbes, commensal and pathogenic. In addition to interacting with their host, different microbes, such as bacteria and viruses, interact with each other, sometimes in ways that exacerbate disease. In particular, gene expression of a number of viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV), is known to be regulated by epigenetic modifications induced by bacteria. These viruses establish latent infection in their host cells and can be reactivated by bacterial products. Viral reactivation has been suggested to contribute to periodontal disease and AIDS. In addition, bacterium-virus interactions may play a role in cancers, such as Kaposi's sarcoma, gastric cancer, and head and neck cancer. It is important to consider the effects of coexisting bacterial infections when studying viral diseases in vivo.

  13. Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility.

    Science.gov (United States)

    Lio, Chan-Wang; Zhang, Jiayuan; González-Avalos, Edahí; Hogan, Patrick G; Chang, Xing; Rao, Anjana

    2016-11-21

    Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igκ locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igκ 3' and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igκ enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igκ enhancer function by modulating the modification status of DNA.

  14. Detection of neuronal tissue in meat using tissue specific DNA modifications

    Directory of Open Access Journals (Sweden)

    Harris N.

    2004-01-01

    Full Text Available A method has been developed to differentiate between non-muscle tissues such as liver, kidney and heart and that of muscle in meat samples using tissue specific DNA detection. Only muscle tissue is considered meat from the point of view of labelling (Food Labelling [Amendment] (England Regulations 2003 and Quantitative Ingredient Declaration (QUID, and also certain parts of the carcass are prohibited to be used in raw meat products (Meat Products [England] Regulations 2003. Included in the prohibited offal are brain and spinal cord. The described methodology has therefore been developed primarily to enforce labelling rules but also to contribute to the enforcement of BSE legislation on the detection of Central Nervous System (CNS tissue. The latter requires the removal of Specified Risk Material (SRM, such as bovine and ovine brain and spinal cord, from the food chain. Current methodologies for detection of CNS tissue include histological examination, analysis of cholesterol content and immunodetection. These can potentially be time consuming, less applicable to processed samples and may not be readily adapted to high throughput sample analysis. The objective of this work was therefore to develop a DNAbased detection assay that exploits the sensitivity and specificity of PCR and is potentially applicable to more highly processed food samples. For neuronal tissue, the DNA target selected was the promoter for Glial Fibrillary Acidic Protein (GFAP, a gene whose expression is restricted to astroglial cells within CNS tissue. The promoter fragments from both cattle and sheep have been isolated and key differences in the methylation patterns of certain CpG dinucleotides in the sequences from bovine and sheep brain and spinal cord and the corresponding skeletal muscle identified. These have been used to design a PCR assay exploiting Methylation Specific PCR (MSP to specifically amplify the neuronal tissue derived sequence and therefore identify the

  15. Optimal lipofection reagent varies with the molecular modifications of the DNA.

    Science.gov (United States)

    Conrad, A H; Behlke, M A; Jaffredo, T; Conrad, G W

    1998-10-01

    Cationic lipid reagents differ in their cytofection efficacy with different cell types. No evidence has addressed whether the same lipid reagent is best for different DNAs in a single cell line. Immortalized avian embryonic cardiomyocytes cultured in vitro were tested with 15 cationic lipid reagents using (A) a beta-gal expression plasmid, (B) a fluorescein-tagged, phosphorothioate-modified ODN B, (C) a fluorescein-tagged, ethoxy-modified ODN C with the same nucleotide sequence as ODN B, and (D) a fluorescein-tagged, phosphorothioate-modified ODN D with a different nucleotide sequence from ODNs B and C. Cytofection was scored as percent of cells expressing beta-gal activity or showing diffuse cellular fluorescence. The best lipid reagents for the phosphorothioate-modified ODNs were ODN-specific and markedly different from the best lipid reagents for the expression plasmid or for the ethoxy-modified ODN. These results suggest that the best cationic lipid reagent for a particular cell type varies with the physical and chemical form of the DNA being transfected into the cells.

  16. Modification of gDNA extraction from soil for PCR designed for the routine examination of soil samples contaminated with Toxocara spp. eggs.

    Science.gov (United States)

    Borecka, A; Gawor, J

    2008-06-01

    A modification of gDNA extraction was developed for the polymerase chain reaction (PCR) technique, intended for the detection and differentiation of Toxocara spp. eggs in soil or sediments. Sand samples from sandpits confirmed as being contaminated with Toxocara spp. eggs by the flotation technique were analysed by PCR. The use of proteinase K made it possible to obtain genomic DNA from the sample without needing to isolate eggs using flotation or to inactivate PCR inhibitors present in the sand. Specific primers in the PCR reaction allowed discrimination between T. canis and T. cati eggs. The modification simplified the procedure, thanks to eliminating the step of gDNA isolation from eggs, which is both laborious and difficult.

  17. Comparative Genomics Reveals the Diversity of Restriction-Modification Systems and DNA Methylation Sites in Listeria monocytogenes.

    Science.gov (United States)

    Chen, Poyin; den Bakker, Henk C; Korlach, Jonas; Kong, Nguyet; Storey, Dylan B; Paxinos, Ellen E; Ashby, Meredith; Clark, Tyson; Luong, Khai; Wiedmann, Martin; Weimer, Bart C

    2017-02-01

    Listeria monocytogenes is a bacterial pathogen that is found in a wide variety of anthropogenic and natural environments. Genome sequencing technologies are rapidly becoming a powerful tool in facilitating our understanding of how genotype, classification phenotypes, and virulence phenotypes interact to predict the health risks of individual bacterial isolates. Currently, 57 closed L. monocytogenes genomes are publicly available, representing three of the four phylogenetic lineages, and they suggest that L. monocytogenes has high genomic synteny. This study contributes an additional 15 closed L. monocytogenes genomes that were used to determine the associations between the genome and methylome with host invasion magnitude. In contrast to previous findings, large chromosomal inversions and rearrangements were detected in five isolates at the chromosome terminus and within rRNA genes, including a previously undescribed inversion within rRNA-encoding regions. Each isolate's epigenome contained highly diverse methyltransferase recognition sites, even within the same serotype and methylation pattern. Eleven strains contained a single chromosomally encoded methyltransferase, one strain contained two methylation systems (one system on a plasmid), and three strains exhibited no methylation, despite the occurrence of methyltransferase genes. In three isolates a new, unknown DNA modification was observed in addition to diverse methylation patterns, accompanied by a novel methylation system. Neither chromosome rearrangement nor strain-specific patterns of epigenome modification observed within virulence genes were correlated with serotype designation, clonal complex, or in vitro infectivity. These data suggest that genome diversity is larger than previously considered in L. monocytogenes and that as more genomes are sequenced, additional structure and methylation novelty will be observed in this organism. Listeria monocytogenes is the causative agent of listeriosis, a disease

  18. Detection of endonuclease III- and 8-oxoguanine glycosylase-sensitive base modifications in γ-irradiated DNA and cells by the aldehyde reactive probe (ARP) assay

    International Nuclear Information System (INIS)

    Mohsin Ali, M.; Kurisu, Satofumi; Yoshioka, Yoshihiro; Terato, Hiroaki; Ohyama, Yoshihiko; Ide Hiroshi; Kubo, Kihei

    2004-01-01

    Ionizing radiation generates diverse DNA lesions that differentially induce cell death and mutations. In the present study, calf thymus DNA (400 μg/ml) and HeLa cells were irradiated by 60 Co γ-rays, and abasic (AP) sites and endonuclease (Endo) III- and 8-oxoguanine glycosylase (hOGG1)-sensitive base modifications in DNA were quantitated by the aldehyde reactive probe (ARP) assay. The irradiation of calf thymus DNA in phosphate buffer generated 91 Endo III- and 100 hOGG1-sensitive base modifications and 110 AP sites per 10 6 base pairs (bp) per Gy. The yield of the lesions in Tris buffer was 41- to 91-fold lower than that in phosphate, demonstrating a radioprotective effect of Tris. The HeLa cell chromosomal DNA contained 12 Endo III- and 3.8 hOGG1-sensitive base modifications and less than 1 AP sites per 10 6 bp as endogenous damage, and their level was increased by irradiation. The yields of the damage at 1 Gy (roughly equivalent to the lethal dose of HeLa cells [1.6-1.8 Gy]) were 0.13 Endo III, 0.091 hOGG1, and 0.065 AP sites per 10 6 bp, showing that irradiation with a lethal dose brought about only a marginal increase in base damage relative to an endogenous one. A comparison of the present data with those reported for DNA strand breaks supports the primary importance of double-strand breaks and clustered lesions as lethal damages formed by ionizing radiation. (author)

  19. Surface modification of amorphous nanosilica particles suppresses nanosilica-induced cytotoxicity, ROS generation, and DNA damage in various mammalian cells

    International Nuclear Information System (INIS)

    Yoshida, Tokuyuki; Yoshioka, Yasuo; Matsuyama, Keigo; Nakazato, Yasutaro; Tochigi, Saeko; Hirai, Toshiro; Kondoh, Sayuri; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

    2012-01-01

    Highlights: ► There is increasing concern regarding the potential health risks of nanomaterials. ► We evaluated the effect of surface properties of nanomaterials on cellular responses. ► We showed that the surface properties play an important in determining its safety. ► These data provide useful information for producing safer nanomaterials. -- Abstract: Recently, nanomaterials have been utilized in various fields. In particular, amorphous nanosilica particles are increasingly being used in a range of applications, including cosmetics, food technology, and medical diagnostics. However, there is concern that the unique characteristics of nanomaterials might induce undesirable effects. The roles played by the physical characteristics of nanomaterials in cellular responses have not yet been elucidated precisely. Here, by using nanosilica particles (nSPs) with a diameter of 70 nm whose surface was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C), we examined the relationship between the surface properties of nSPs and cellular responses such as cytotoxicity, reactive oxygen species (ROS) generation, and DNA damage. To compare the cytotoxicity of nSP70, nSP70-N, or nSP70-C, we examined in vitro cell viability after nSP treatment. Although the susceptibility of each cell line to the nSPs was different, nSP70-C and nSP70-N showed lower cytotoxicity than nSP70 in all cell lines. Furthermore, the generation of ROS and induction of DNA damage in nSP70-C- and nSP70-N-treated cells were lower than those in nSP70-treated cells. These results suggest that the surface properties of nSP70 play an important role in determining its safety, and surface modification of nSP70 with amine or carboxyl groups may be useful for the development of safer nSPs. We hope that our results will contribute to the development of safer nanomaterials.

  20. KDM2A integrates DNA and histone modification signals through a CXXC/PHD module and direct interaction with HP1

    Science.gov (United States)

    Borgel, Julie; Tyl, Marek; Schiller, Karin; Pusztai, Zsofia; Dooley, Christopher M.; Deng, Wen; Wooding, Carol; White, Richard J.; Warnecke, Tobias; Leonhardt, Heinrich; Busch-Nentwich, Elisabeth M.

    2017-01-01

    Abstract Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromatin recognition by the lysine demethylase KDM2A. Using biochemical approaches we identify a nucleosome interaction module within KDM2A consisting of a CXXC type zinc finger, a PHD domain and a newly identified Heterochromatin Protein 1 (HP1) interaction motif that mediates direct binding between KDM2A and HP1. This nucleosome interaction module enables KDM2A to decode nucleosomal H3K9me3 modification in addition to CpG methylation signals. The multivalent engagement with DNA and HP1 results in a nucleosome binding circuit in which KDM2A can be recruited to H3K9me3-modified chromatin through HP1, and HP1 can be recruited to unmodified chromatin by KDM2A. A KDM2A mutant deficient in HP1-binding is inactive in an in vivo overexpression assay in zebrafish embryos demonstrating that the HP1 interaction is essential for KDM2A function. Our results reveal a complex regulation of chromatin binding for both KDM2A and HP1 that is modulated by DNA- and H3K9-methylation, and suggest a direct role for KDM2A in chromatin silencing. PMID:28180290

  1. A comparative approach for the investigation of biological information processing: An examination of the structure and function of computer hard drives and DNA

    Science.gov (United States)

    2010-01-01

    Background The robust storage, updating and utilization of information are necessary for the maintenance and perpetuation of dynamic systems. These systems can exist as constructs of metal-oxide semiconductors and silicon, as in a digital computer, or in the "wetware" of organic compounds, proteins and nucleic acids that make up biological organisms. We propose that there are essential functional properties of centralized information-processing systems; for digital computers these properties reside in the computer's hard drive, and for eukaryotic cells they are manifest in the DNA and associated structures. Methods Presented herein is a descriptive framework that compares DNA and its associated proteins and sub-nuclear structure with the structure and function of the computer hard drive. We identify four essential properties of information for a centralized storage and processing system: (1) orthogonal uniqueness, (2) low level formatting, (3) high level formatting and (4) translation of stored to usable form. The corresponding aspects of the DNA complex and a computer hard drive are categorized using this classification. This is intended to demonstrate a functional equivalence between the components of the two systems, and thus the systems themselves. Results Both the DNA complex and the computer hard drive contain components that fulfill the essential properties of a centralized information storage and processing system. The functional equivalence of these components provides insight into both the design process of engineered systems and the evolved solutions addressing similar system requirements. However, there are points where the comparison breaks down, particularly when there are externally imposed information-organizing structures on the computer hard drive. A specific example of this is the imposition of the File Allocation Table (FAT) during high level formatting of the computer hard drive and the subsequent loading of an operating system (OS). Biological

  2. A comparative approach for the investigation of biological information processing: an examination of the structure and function of computer hard drives and DNA.

    Science.gov (United States)

    D'Onofrio, David J; An, Gary

    2010-01-21

    The robust storage, updating and utilization of information are necessary for the maintenance and perpetuation of dynamic systems. These systems can exist as constructs of metal-oxide semiconductors and silicon, as in a digital computer, or in the "wetware" of organic compounds, proteins and nucleic acids that make up biological organisms. We propose that there are essential functional properties of centralized information-processing systems; for digital computers these properties reside in the computer's hard drive, and for eukaryotic cells they are manifest in the DNA and associated structures. Presented herein is a descriptive framework that compares DNA and its associated proteins and sub-nuclear structure with the structure and function of the computer hard drive. We identify four essential properties of information for a centralized storage and processing system: (1) orthogonal uniqueness, (2) low level formatting, (3) high level formatting and (4) translation of stored to usable form. The corresponding aspects of the DNA complex and a computer hard drive are categorized using this classification. This is intended to demonstrate a functional equivalence between the components of the two systems, and thus the systems themselves. Both the DNA complex and the computer hard drive contain components that fulfill the essential properties of a centralized information storage and processing system. The functional equivalence of these components provides insight into both the design process of engineered systems and the evolved solutions addressing similar system requirements. However, there are points where the comparison breaks down, particularly when there are externally imposed information-organizing structures on the computer hard drive. A specific example of this is the imposition of the File Allocation Table (FAT) during high level formatting of the computer hard drive and the subsequent loading of an operating system (OS). Biological systems do not have an

  3. A comparative approach for the investigation of biological information processing: An examination of the structure and function of computer hard drives and DNA

    Directory of Open Access Journals (Sweden)

    D'Onofrio David J

    2010-01-01

    Full Text Available Abstract Background The robust storage, updating and utilization of information are necessary for the maintenance and perpetuation of dynamic systems. These systems can exist as constructs of metal-oxide semiconductors and silicon, as in a digital computer, or in the "wetware" of organic compounds, proteins and nucleic acids that make up biological organisms. We propose that there are essential functional properties of centralized information-processing systems; for digital computers these properties reside in the computer's hard drive, and for eukaryotic cells they are manifest in the DNA and associated structures. Methods Presented herein is a descriptive framework that compares DNA and its associated proteins and sub-nuclear structure with the structure and function of the computer hard drive. We identify four essential properties of information for a centralized storage and processing system: (1 orthogonal uniqueness, (2 low level formatting, (3 high level formatting and (4 translation of stored to usable form. The corresponding aspects of the DNA complex and a computer hard drive are categorized using this classification. This is intended to demonstrate a functional equivalence between the components of the two systems, and thus the systems themselves. Results Both the DNA complex and the computer hard drive contain components that fulfill the essential properties of a centralized information storage and processing system. The functional equivalence of these components provides insight into both the design process of engineered systems and the evolved solutions addressing similar system requirements. However, there are points where the comparison breaks down, particularly when there are externally imposed information-organizing structures on the computer hard drive. A specific example of this is the imposition of the File Allocation Table (FAT during high level formatting of the computer hard drive and the subsequent loading of an operating

  4. Comparison of gamma- and beta radiation stress responses on anti-oxidative defense system and DNA modifications in Lemna minor

    Energy Technology Data Exchange (ETDEWEB)

    Van Hoeck, Arne [SCK.CEN, Boeretang 200 2400 Mol (Belgium); University of Antwerp, Groenenborgerlaan 171, 2020 Antwerpen (Belgium); Horemans, Nele; Van Hees, May; Nauts, Robin; Vandenhove, Hildegarde [SCK.CEN, Boeretang 200 2400 Mol (Belgium); Knapen, Dries; Blust, Ronny [University of Antwerp, Groenenborgerlaan 171, 2020 Antwerpen (Belgium)

    2014-07-01

    frond have been implemented in a dosimetric model derived from ERICA tool. This enabled a reliable comparison of dose-dependent endpoints between gamma- and beta radiation. Dose rates varied from 15 and 1500 mGy/hr, and 19 from 19000 μGy/hr for gamma- and beta radiation respectively. The classic growth related endpoints, like biomass and frond area, were measured and compared with biochemical and molecular endpoints. Therefore, DNA modifications were analyzed to evaluate biological DNA damage and ROS accumulation in plants together with activities of anti-oxidative enzymes to evaluate oxidative stress response. A dose-response curve with 60 percent growth inhibition was determined for gamma radiation and morphological growth effects in root system were observed for beta radiation. Preliminary results showed similar responses in peroxidase activities between both radiation types. These results and ongoing investigations will help to unravel the differences and similarities in response mechanisms for various radiation types in plant systems. As multiple levels in biological organisation of the organism were considered, and also different dose rates taken into account, this approach allows a better understanding the toxic mode of action of radiation stress in higher plants. This research was supported by the European Commission Contract Fission-2010-3.5.1-269672 to Strategy for Allied Radioecology (www.star-radioecology.org) and a project of the Fund for Scientific Research (FWO-Vlaanderen, G.A040.11N) (authors)

  5. Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Yadav Sapkota

    Full Text Available Genome-wide association studies (GWASs have identified low-penetrance common variants (i.e., single nucleotide polymorphisms, SNPs associated with breast cancer susceptibility. Although GWASs are primarily focused on single-locus effects, gene-gene interactions (i.e., epistasis are also assumed to contribute to the genetic risks for complex diseases including breast cancer. While it has been hypothesized that moderately ranked (P value based weak single-locus effects in GWASs could potentially harbor valuable information for evaluating epistasis, we lack systematic efforts to investigate SNPs showing consistent associations with weak statistical significance across independent discovery and replication stages. The objectives of this study were i to select SNPs showing single-locus effects with weak statistical significance for breast cancer in a GWAS and/or candidate-gene studies; ii to replicate these SNPs in an independent set of breast cancer cases and controls; and iii to explore their potential SNP-SNP interactions contributing to breast cancer susceptibility. A total of 17 SNPs related to DNA repair, modification and metabolism pathway genes were selected since these pathways offer a priori knowledge for potential epistatic interactions and an overall role in breast carcinogenesis. The study design included predominantly Caucasian women (2,795 cases and 4,505 controls from Alberta, Canada. We observed two two-way SNP-SNP interactions (APEX1-rs1130409 and RPAP1-rs2297381; MLH1-rs1799977 and MDM2-rs769412 in logistic regression that conferred elevated risks for breast cancer (P(interaction<7.3 × 10(-3. Logic regression identified an interaction involving four SNPs (MBD2-rs4041245, MLH1-rs1799977, MDM2-rs769412, BRCA2-rs1799943 (P(permutation = 2.4 × 10(-3. SNPs involved in SNP-SNP interactions also showed single-locus effects with weak statistical significance, while BRCA2-rs1799943 showed stronger statistical significance (P

  6. Active-site modification of mammalian DNA polymerase β with pyridoxal 5'-phosphate: Mechanism of inhibition and identification of lysine 71 in the deoxynucleoside triphosphate binding pocket

    International Nuclear Information System (INIS)

    Basu, A.; Kedar, P.; Wilson, S.H.; Modak, M.J.

    1989-01-01

    Pyridoxal 5'-phosphate is a potent inhibitor of the DNA polymerase activity of recombinant rat DNA polymerase β. Kinetic studies indicate that the mechanism of PLP inhibition is complex. In a lower range of PLP concentration, inhibition is competitive with respect to substrate dNTP, whereas at higher levels of PLP several forms of enzyme combine with PLP and are involved in the overall inhibition, and a possible model for these interactions during the catalytic process is suggested. Reduction of the PLP-treated enzyme with sodium [ 3 H]borohydride results in covalent incorporation of about 4 mol of PLP/mol of enzyme, and the modified enzyme is not capable of DNA polymerase activity. The presence of dNTP during the modification reaction blocks incorporation of 1 mol of PLP/mol of enzyme, and the enzyme so modified is almost fully active. This protective effect is not observed in the absence of template-primer. Tryptic peptide mapping of the PLP-modified enzyme reveals four major sites of modification. Of these four sites, only one is protected by dNTP from pyridoxylation. Sequence analysis of the tryptic peptide corresponding to the protected site reveals that it spans residues 68-80 in the amino acid sequence of the enzyme, with Lys 71 as the site of pyridoxylation. These results indicate that Lys 71 is at or near the binding pocket for the dNTP substrate

  7. MotifMark: Finding Regulatory Motifs in DNA Sequences

    OpenAIRE

    Hassanzadeh, Hamid Reza; Kolhe, Pushkar; Isbell, Charles L.; Wang, May D.

    2017-01-01

    The interaction between proteins and DNA is a key driving force in a significant number of biological processes such as transcriptional regulation, repair, recombination, splicing, and DNA modification. The identification of DNA-binding sites and the specificity of target proteins in binding to these regions are two important steps in understanding the mechanisms of these biological activities. A number of high-throughput technologies have recently emerged that try to quantify the affinity be...

  8. Novel structural features drive DNA binding properties of Cmr, a CRP family protein in TB complex mycobacteria.

    Science.gov (United States)

    Ranganathan, Sridevi; Cheung, Jonah; Cassidy, Michael; Ginter, Christopher; Pata, Janice D; McDonough, Kathleen A

    2018-01-09

    Mycobacterium tuberculosis (Mtb) encodes two CRP/FNR family transcription factors (TF) that contribute to virulence, Cmr (Rv1675c) and CRPMt (Rv3676). Prior studies identified distinct chromosomal binding profiles for each TF despite their recognizing overlapping DNA motifs. The present study shows that Cmr binding specificity is determined by discriminator nucleotides at motif positions 4 and 13. X-ray crystallography and targeted mutational analyses identified an arginine-rich loop that expands Cmr's DNA interactions beyond the classical helix-turn-helix contacts common to all CRP/FNR family members and facilitates binding to imperfect DNA sequences. Cmr binding to DNA results in a pronounced asymmetric bending of the DNA and its high level of cooperativity is consistent with DNA-facilitated dimerization. A unique N-terminal extension inserts between the DNA binding and dimerization domains, partially occluding the site where the canonical cAMP binding pocket is found. However, an unstructured region of this N-terminus may help modulate Cmr activity in response to cellular signals. Cmr's multiple levels of DNA interaction likely enhance its ability to integrate diverse gene regulatory signals, while its novel structural features establish Cmr as an atypical CRP/FNR family member. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Azide photochemistry for facile modification of graphitic surfaces: preparation of DNA-coated carbon nanotubes for biosensing

    International Nuclear Information System (INIS)

    Moghaddam, Minoo J; Yang Wenrong; Bojarski, Barbara; Gengenbach, Thomas R; Gao Mei; Zareie, Hadi; McCall, Maxine J

    2012-01-01

    A facile, two-step method for chemically attaching single-stranded DNA to graphitic surfaces, represented here by carbon nanotubes, is reported. In the first step, an azide-containing compound, N-5-azido-nitrobenzoyloxy succinimide (ANB-NOS), is used to form photo-adducts on the graphitic surfaces in a solid-state photochemical reaction, resulting in active ester groups being oriented for the subsequent reactions. In the second step, pre-synthesized DNA strands bearing a terminal amine group are coupled in an aqueous solution with the active esters on the photo-adducts. The versatility of the method is demonstrated by attaching pre-synthesized DNA to surfaces of carbon nanotubes in two platforms—as vertically-aligned multi-walled carbon nanotubes on a solid support and as tangled single-walled carbon nanotubes in mats. The reaction products at various stages were characterized by x-ray photoelectron spectroscopy. Two different assays were used to check that the DNA strands attached to the carbon nanotubes were able to bind their partner strands with complementary base sequences. The first assay, using partner DNA strands tethered to gold nanoparticles, enabled the sites of DNA attachment to the carbon nanotubes to be identified in TEM images. The second assay, using radioactively labelled partner DNA strands, quantified the density of functional DNA strands attached to the carbon nanotubes. The diversity of potential applications for these DNA-modified carbon-nanotube platforms is exemplified here by the successful use of a DNA-modified single-walled carbon-nanotube mat as an electrode for the specific detection of metal ions. (paper)

  10. Pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA or histone modification H3K9Me3

    DEFF Research Database (Denmark)

    Rasmussen, Louise; Herzog, Marielle; Rømer, Eva

    2016-01-01

    Aim: To evaluate pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA (5mC) or histone modification H3K9Me3 (H3K9Me3). Materials and methods: Six studies were designed to assess the possible influence of pre-analytical variables. Study 1: influence of stasis...... significantly lower levels of 5mC or H3K9Me3 compared to levels in healthy individuals. Conclusion: Levels of 5mC or H3K9Me3 appear stable in most pre-analytical settings if blood samples are stored at room temperature until centrifugation....

  11. Temperature and Magnetic Field Driven Modifications in the I-V Features of Gold-DNA-Gold Structure

    Directory of Open Access Journals (Sweden)

    Nadia Mahmoudi Khatir

    2014-10-01

    Full Text Available The fabrication of Metal-DNA-Metal (MDM structure-based high sensitivity sensors from DNA micro-and nanoarray strands is a key issue in their development. The tunable semiconducting response of DNA in the presence of external electromagnetic and thermal fields is a gift for molecular electronics. The impact of temperatures (25–55 °C and magnetic fields (0–1200 mT on the current-voltage (I-V features of Au-DNA-Au (GDG structures with an optimum gap of 10 μm is reported. The I-V characteristics acquired in the presence and absence of magnetic fields demonstrated the semiconducting diode nature of DNA in GDG structures with high temperature sensitivity. The saturation current in the absence of magnetic field was found to increase sharply with the increase of temperature up to 45 °C and decrease rapidly thereafter. This increase was attributed to the temperature-assisted conversion of double bonds into single bond in DNA structures. Furthermore, the potential barrier height and Richardson constant for all the structures increased steadily with the increase of external magnetic field irrespective of temperature variations. Our observation on magnetic field and temperature sensitivity of I-V response in GDG sandwiches may contribute towards the development of DNA-based magnetic sensors.

  12. Molecular dynamics simulations shed light on the enthalpic and entropic driving forces that govern the sequence specific recognition between netropsin and DNA.

    Science.gov (United States)

    Dolenc, Jozica; Gerster, Sarah; van Gunsteren, Wilfred F

    2010-09-02

    With the aim to gain a better understanding of the various driving forces that govern sequence specific DNA minor groove binding, we performed a thermodynamic analysis of netropsin binding to an AT-containing and to a set of six mixed AT/GC-containing binding sequences in the DNA minor groove. The relative binding free energies obtained using molecular dynamics simulations and free energy calculations show significant variations with the binding sequence. While the introduction of a GC base pair in the middle or close to the middle of the binding site is unfavorable for netropsin binding, a GC base pair at the end of the binding site appears to have no negative influence on the binding. The results of the structural and energetic analyses of the netropsin-DNA complexes reveal that the differences in the calculated binding affinities cannot be explained solely in terms of netropsin-DNA hydrogen-bonding or interaction energies. In addition, solvation effects and entropic contributions to the relative binding free energy provide a more complete picture of the various factors determining binding. Analysis of the relative binding entropy indicates that its magnitude is highly sequence-dependent, with the ratio |TDeltaDeltaS|/|DeltaDeltaH| ranging from 0.07 for the AAAGA to 1.7 for the AAGAG binding sequence, respectively.

  13. Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells.

    Science.gov (United States)

    Gao, Yunfeng; Foo, Yong Hwee; Winardhi, Ricksen S; Tang, Qingnan; Yan, Jie; Kenney, Linda J

    2017-11-21

    Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in single cells. We discovered a role for the unstructured linker region connecting the N-terminal oligomerization and C-terminal DNA binding domains. In the present work we demonstrate that linker amino acids promote engagement with DNA. In the absence of linker contacts, H-NS binding is significantly reduced, although no change in chromosome compaction is observed. H-NS is not localized to two distinct foci; rather, it is scattered all around the nucleoid. The linker makes DNA contacts that are required for gene silencing, while chromosome compaction does not appear to be an important H-NS function.

  14. Neutralized ion beam modification of cellulose membranes for study of ion charge effect on ion-beam-induced DNA transfer

    Science.gov (United States)

    Prakrajang, K.; Sangwijit, K.; Anuntalabhochai, S.; Wanichapichart, P.; Yu, L. D.

    2012-02-01

    Low-energy ion beam biotechnology (IBBT) has recently been rapidly developed worldwide. Ion-beam-induced DNA transfer is one of the important applications of IBBT. However, mechanisms involved in this application are not yet well understood. In this study plasma-neutralized ion beam was applied to investigate ion charge effect on induction of DNA transfer. Argon ion beam at 7.5 keV was neutralized by RF-driven plasma in the beam path and then bombarded cellulose membranes which were used as the mimetic plant cell envelope. Electrical properties such as impedance and capacitance of the membranes were measured after the bombardment. An in vitro experiment on plasmid DNA transfer through the cellulose membrane was followed up. The results showed that the ion charge input played an important role in the impedance and capacitance changes which would affect DNA transfer. Generally speaking, neutral particle beam bombardment of biologic cells was more effective in inducing DNA transfer than charged ion beam bombardment.

  15. Synthesis of high specific activity tritium-labelled chloroethylcyclohexylnitrosourea and its application to the study of DNA modification

    Energy Technology Data Exchange (ETDEWEB)

    Siew, E.L. (State Univ. of New York, Albany, NY (USA). Dept. of Chemistry); Habraken, Yvette; Ludlum, D.B. (Massachusetts Univ., Worcester, MA (USA). Medical School)

    1991-02-01

    A small-scale synthesis of high specific activity, N-(2-chloro-2-{sup 3}H-ethyl)-N'-cyclohexyl-N-nitrosourea ({sup 3}H-CCNU) has been accomplished from tritium-labelled ethanolamine. The product is pure by TLC and HPLC analysis and has been used successfully to modify DNA. The overall yield on radioactivity including losses in HPLC purification is approximately 4 percent. The availability of this tritium-labelled compound makes studies of DNA repair and of cellular resistance to N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea possible. (author).

  16. Synthesis of high specific activity tritium-labelled chloroethylcyclohexylnitrosourea and its application to the study of DNA modification

    International Nuclear Information System (INIS)

    Siew, E.L.; Habraken, Yvette; Ludlum, D.B.

    1991-01-01

    A small-scale synthesis of high specific activity, N-(2-chloro-2-[ 3 H-ethyl)-N'-cyclohexyl-N-nitrosourea ([ 3 H]-CCNU) has been accomplished from tritium-labelled ethanolamine. The product is pure by TLC and HPLC analysis and has been used successfully to modify DNA. The overall yield on radioactivity including losses in HPLC purification is approximately 4 percent. The availability of this tritium-labelled compound makes studies of DNA repair and of cellular resistance to N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea possible. (author)

  17. Temperature and electrolyte optimization of the α-hemolysin latch sensing zone for detection of base modification in double-stranded DNA.

    Science.gov (United States)

    Johnson, Robert P; Fleming, Aaron M; Jin, Qian; Burrows, Cynthia J; White, Henry S

    2014-08-19

    The latch region of the wild-type protein pore α-hemolysin (α-HL) constitutes a sensing zone for individual abasic sites (and furan analogs) in double-stranded DNA (dsDNA). The presence of an abasic site or furan within a DNA duplex, electrophoretically captured in the α-HL vestibule and positioned at the latch region, can be detected based on the current blockage prior to duplex unzipping. We investigated variations in blockage current as a function of temperature (12-35°C) and KCl concentration (0.15-1.0 M) to understand the origin of the current signature and to optimize conditions for identifying the base modification. In 1 M KCl solution, substitution of a furan for a cytosine base in the latch region results in an ∼ 8 kJ mol(-1) decrease in the activation energy for ion transport through the protein pore. This corresponds to a readily measured ∼ 2 pA increase in current at room temperature. Optimal resolution for detecting the presence of a furan in the latch region is achieved at lower KCl concentrations, where the noise in the measured blockage current is significantly lower. The noise associated with the blockage current also depends on the stability of the duplex (as measured from the melting temperature), where a greater noise in the measured blockage current is observed for less stable duplexes. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Roth, Tania L; Zoladz, Phillip R; Sweatt, J David; Diamond, David M

    2011-07-01

    Epigenetic alterations of the brain-derived neurotrophic factor (Bdnf) gene have been linked with memory, stress, and neuropsychiatric disorders. Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. Adult male Sprague-Dawley rats were given psychosocial stress composed of two acute cat exposures in conjunction with 31 days of daily social instability. These manipulations have been shown previously to produce physiological and behavioral sequelae in rats that are comparable to symptoms observed in traumatized people with PTSD. We then assessed Bdnf DNA methylation patterns (at exon IV) and gene expression. We have found here that the psychosocial stress regimen significantly increased Bdnf DNA methylation in the dorsal hippocampus, with the most robust hypermethylation detected in the dorsal CA1 subregion. Conversely, the psychosocial stress regimen significantly decreased methylation in the ventral hippocampus (CA3). No changes in Bdnf DNA methylation were detected in the medial prefrontal cortex or basolateral amygdala. In addition, there were decreased levels of Bdnf mRNA in both the dorsal and ventral CA1. These results provide evidence that traumatic stress occurring in adulthood can induce CNS gene methylation, and specifically, support the hypothesis that epigenetic marking of the Bdnf gene may underlie hippocampal dysfunction in response to traumatic stress. Furthermore, this work provides support for the speculative notion that altered hippocampal Bdnf DNA methylation is a cellular mechanism underlying the persistent cognitive deficits which are prominent features of the pathophysiology of PTSD. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Determination of DNA methylation associated with Acer rubrum (red maple) adaptation to metals: analysis of global DNA modifications and methylation-sensitive amplified polymorphism.

    Science.gov (United States)

    Kim, Nam-Soo; Im, Min-Ji; Nkongolo, Kabwe

    2016-08-01

    Red maple (Acer rubum), a common deciduous tree species in Northern Ontario, has shown resistance to soil metal contamination. Previous reports have indicated that this plant does not accumulate metals in its tissue. However, low level of nickel and copper corresponding to the bioavailable levels in contaminated soils in Northern Ontario causes severe physiological damages. No differentiation between metal-contaminated and uncontaminated populations has been reported based on genetic analyses. The main objective of this study was to assess whether DNA methylation is involved in A. rubrum adaptation to soil metal contamination. Global cytosine and methylation-sensitive amplified polymorphism (MSAP) analyses were carried out in A. rubrum populations from metal-contaminated and uncontaminated sites. The global modified cytosine ratios in genomic DNA revealed a significant decrease in cytosine methylation in genotypes from a metal-contaminated site compared to uncontaminated populations. Other genotypes from a different metal-contaminated site within the same region appear to be recalcitrant to metal-induced DNA alterations even ≥30 years of tree life exposure to nickel and copper. MSAP analysis showed a high level of polymorphisms in both uncontaminated (77%) and metal-contaminated (72%) populations. Overall, 205 CCGG loci were identified in which 127 were methylated in either outer or inner cytosine. No differentiation among populations was established based on several genetic parameters tested. The variations for nonmethylated and methylated loci were compared by analysis of molecular variance (AMOVA). For methylated loci, molecular variance among and within populations was 1.5% and 13.2%, respectively. These values were low (0.6% for among populations and 5.8% for within populations) for unmethylated loci. Metal contamination is seen to affect methylation of cytosine residues in CCGG motifs in the A. rubrum populations that were analyzed.

  20. Expression of 5 S rRNA genes linked to 35 S rDNA in plants, their epigenetic modification and regulatory element divergence

    Directory of Open Access Journals (Sweden)

    Garcia Sònia

    2012-06-01

    Full Text Available Abstract Background In plants, the 5 S rRNA genes usually occur as separate tandems (S-type arrangement or, less commonly, linked to 35 S rDNA units (L-type. The activity of linked genes remains unknown so far. We studied the homogeneity and expression of 5 S genes in several species from family Asteraceae known to contain linked 35 S-5 S units. Additionally, their methylation status was determined using bisulfite sequencing. Fluorescence in situ hybridization was applied to reveal the sub-nuclear positions of rDNA arrays. Results We found that homogenization of L-type units went to completion in most (4/6 but not all species. Two species contained major L-type and minor S-type units (termed Ls-type. The linked genes dominate 5 S rDNA expression while the separate tandems do not seem to be expressed. Members of tribe Anthemideae evolved functional variants of the polymerase III promoter in which a residing C-box element differs from the canonical angiosperm motif by as much as 30%. On this basis, a more relaxed consensus sequence of a plant C-box: (5’-RGSWTGGGTG-3’ is proposed. The 5 S paralogs display heavy DNA methylation similarly as to their unlinked counterparts. FISH revealed the close association of 35 S-5 S arrays with nucleolar periphery indicating that transcription of 5 S genes may occur in this territory. Conclusions We show that the unusual linked arrangement of 5 S genes, occurring in several plant species, is fully compatible with their expression and functionality. This extraordinary 5 S gene dynamics is manifested at different levels, such as variation in intrachromosomal positions, unit structure, epigenetic modification and considerable divergence of regulatory motifs.

  1. The Helicobacter pylori HpyAXII restriction–modification system limits exogenous DNA uptake by targeting GTAC sites but shows asymmetric conservation of the DNA methyltransferase and restriction endonuclease components

    Science.gov (United States)

    Humbert, Olivier; Salama, Nina R.

    2008-01-01

    The naturally competent organism Helicobacter pylori encodes a large number of restriction–modification (R–M) systems that consist of a restriction endonuclease and a DNA methyltransferase. R–M systems are not only believed to limit DNA exchange among bacteria but may also have other cellular functions. We report a previously uncharacterized H. pylori type II R–M system, M.HpyAXII/R.HpyAXII. We show that this system targets GTAC sites, which are rare in the H. pylori chromosome but numerous in ribosomal RNA genes. As predicted, this type II R–M system showed attributes of a selfish element. Deletion of the methyltransferase M.HpyAXII is lethal when associated with an active endonuclease R.HpyAXII unless compensated by adaptive mutation or gene amplification. R.HpyAXII effectively restricted both unmethylated plasmid and chromosomal DNA during natural transformation and was predicted to belong to the novel ‘half pipe’ structural family of endonucleases. Analysis of a panel of clinical isolates revealed that R.HpyAXII was functional in a small number of H. pylori strains (18.9%, n = 37), whereas the activity of M.HpyAXII was highly conserved (92%, n = 50), suggesting that GTAC methylation confers a selective advantage to H. pylori. However, M.HpyAXII activity did not enhance H. pylori fitness during stomach colonization of a mouse infection model. PMID:18978016

  2. Influence of Ni(II) and Fe(III) complexes of 1,2 dihydroxy 9,10 anthraquinone on the modification in calf thymus DNA upon gamma irradiation

    International Nuclear Information System (INIS)

    Das, Saurabh; Mandal, Parikshit C.

    2009-01-01

    Ionizing radiation when allowed to fall upon cells or DNA, the radicals produced modify the base-pair region of the double strands. Radiation-induced double-strand modifications in calf thymus DNA were detected using Ni(II) and Fe(III) complexes of 1,2 dihydroxy 9,10 anthraquinone (DHA). 60 Co was used as the source for γ-radiation and ethidium bromide (EB) as the fluorescent dye for detecting double-strand modifications caused in DNA. Results show that the Fe(III)-DHA complex is more efficient in modifying the base-pair region in double-stranded DNA in comparison to DHA or the Ni(II)-DHA complex

  3. The New Genetics and Natural versus Artificial Genetic Modification

    Directory of Open Access Journals (Sweden)

    Mae-Wan Ho

    2013-11-01

    Full Text Available The original rationale and impetus for artificial genetic modification was the “central dogma” of molecular biology that assumed DNA carries all the instructions for making an organism, which are transmitted via RNA to protein to biological function in linear causal chains. This is contrary to the reality of the “fluid genome” that has emerged since the mid-1970s. In order to survive, the organism needs to engage in natural genetic modification in real time, an exquisitely precise molecular dance of life with RNA and DNA responding to and participating in “downstream” biological functions. Artificial genetic modification, in contrast, is crude, imprecise, and interferes with the natural process. It drives natural systems towards maximum biosemiotic entropy as the perturbations are propagated and amplified through the complex cascades of interactions between subsystems that are essential for health and longevity.

  4. Determination of the level of DNA modification with cisplatin by catalytic hydrogen evolution at mercury-based electrodes

    Czech Academy of Sciences Publication Activity Database

    Horáková Brázdilová, Petra; Těsnohlídková, Lucie; Havran, Luděk; Vidláková, Pavlína; Pivoňková, Hana; Fojta, Miroslav

    2010-01-01

    Roč. 82, č. 7 (2010), s. 2969-2976 ISSN 0003-2700 R&D Projects: GA ČR(CZ) GP204/07/P476; GA AV ČR(CZ) IAA500040701; GA AV ČR(CZ) 1QS500040581; GA MŠk(CZ) LC06035 Grant - others:GA AV ČR(CZ) IAA400040903 Program:IA Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : cisplatin * electrochemical analysis of DNA * mercury electrode Subject RIV: BO - Biophysics Impact factor: 5.874, year: 2010

  5. Lethal modifications of DNA via the transmutation of 32P and 33P incorporated in the genome of the S13 bacteriophage

    International Nuclear Information System (INIS)

    Cols, P.; Apelgot, S.; Guille, E.

    1988-01-01

    When circular single-standard DNA of phage S13 is labelled with 32 P or 33 P, the transmutations very efficiently bring about a loss of phage infectiousness (efficiency = 1 for 32 P and 0.73 for 33 P). For both radionuclides, the lethal efficiencies as well as the lethal events are different. In the case of 32 P, the lethal event is the loss of the circular integrity of the DNA molecule, occurring as a consequence of a systematic single strand-break caused by each 32 P decay (100%). Conversely, in the case of 33 P, the lethal events are either a single strand-break (40%) or a local stereochemical modification (33%). The same primary event, the substitution at each 33 P decay of a phosphate by a sulfate molecule, leads to one of these lethal events in relation to the decay site. Moreover, neither the phage adsorption nor its genome injection into bacteria depends on the physical state of the genome, and thus lethality is revealed at only the genetic level. (orig.)

  6. The dnd operon for DNA phosphorothioation modification system in Escherichia coli is located in diverse genomic islands.

    Science.gov (United States)

    Ho, Wing Sze; Ou, Hong-Yu; Yeo, Chew Chieng; Thong, Kwai Lin

    2015-03-17

    Strains of Escherichia coli that are non-typeable by pulsed-field gel electrophoresis (PFGE) due to in-gel degradation can influence their molecular epidemiological data. The DNA degradation phenotype (Dnd(+)) is mediated by the dnd operon that encode enzymes catalyzing the phosphorothioation of DNA, rendering the modified DNA susceptible to oxidative cleavage during a PFGE run. In this study, a PCR assay was developed to detect the presence of the dnd operon in Dnd(+) E. coli strains and to improve their typeability. Investigations into the genetic environments of the dnd operon in various E. coli strains led to the discovery that the dnd operon is harboured in various diverse genomic islands. The dndBCDE genes (dnd operon) were detected in all Dnd(+) E. coli strains by PCR. The addition of thiourea improved the typeability of Dnd(+) E. coli strains to 100% using PFGE and the Dnd(+) phenotype can be observed in both clonal and genetically diverse E. coli strains. Genomic analysis of 101 dnd operons from genome sequences of Enterobacteriaceae revealed that the dnd operons of the same bacterial species were generally clustered together in the phylogenetic tree. Further analysis of dnd operons of 52 E. coli genomes together with their respective immediate genetic environments revealed a total of 7 types of genetic organizations, all of which were found to be associated with genomic islands designated dnd-encoding GIs. The dnd-encoding GIs displayed mosaic structure and the genomic context of the 7 islands (with 1 representative genome from each type of genetic organization) were also highly variable, suggesting multiple recombination events. This is also the first report where two dnd operons were found within a strain although the biological implication is unknown. Surprisingly, dnd operons were frequently found in pathogenic E. coli although their link with virulence has not been explored. Genomic islands likely play an important role in facilitating the horizontal

  7. Purification, cDNA cloning and modification of a defensin from the coconut rhinoceros beetle, Oryctes rhinoceros.

    Science.gov (United States)

    Ishibashi, J; Saido-Sakanaka, H; Yang, J; Sagisaka, A; Yamakawa, M

    1999-12-01

    A novel member of the insect defensins, a family of antibacterial peptides, was purified from larvae of the coconut rhinoceros beetle, Oryctes rhinoceros, immunized with Escherichia coli. A full-size cDNA was cloned by combining reverse-transcription PCR (RT-PCR), and 5'- and 3'-rapid amplification of cDNA ends (RACE). Analysis of the O. rhinoceros defensin gene expression showed it to be expressed in the fat body and hemocyte, midgut and Malpighian tubules. O. rhinoceros defensin showed strong antibacterial activity against Staphylococcus aureus. A 9-mer peptide amidated at its C-terminus, AHCLAICRK-NH2 (Ala22-Lys30-NH2), was synthesized based on the deduced amino-acid sequence, assumed to be an active site sequence by analogy with the sequence of a defensin isolated from larvae of the beetle Allomyrina dichotoma. This peptide showed antibacterial activity against S. aureus, methicillin-resistant S. aureus, E. coli and Pseudomonas aeruginosa. We further modified this oligopeptide and synthesized five 9-mer peptides, ALRLAIRKR-NH2, ALLLAIRKR-NH2, AWLLAIRKR-NH2, ALYLAIRKR-NH2 and ALWLAIRKR-NH2. These oligopeptides showed strong antibacterial activity against Gram-negative and Gram-positive bacteria. The antibacterial effect of Ala22-Lys30-NH2 analogues was due to its interaction with bacterial membranes, judging from the leakage of liposome-entrapped glucose. These Ala22-Lys30-NH2 analogues did not show haemolytic activity and did not inhibit the growth of murine fibroblast cells or macrophages, except for AWLLAIRKR-NH2.

  8. ETV6/RUNX1 Induces Reactive Oxygen Species and Drives the Accumulation of DNA Damage in B Cells

    Directory of Open Access Journals (Sweden)

    Hans-Peter Kantner

    2013-11-01

    Full Text Available The t(12;21(p13;q22 chromosomal translocation is the most frequent translocation in childhood B cell precursor-acute lymphoblastic leukemia and results in the expression of an ETV6/RUNX1 fusion protein. The frequency of ETV6/RUNX1 fusions in newborns clearly exceeds the leukemia rate revealing that additional events occur in ETV6/RUNX1-positive cells for leukemic transformation. Hitherto, the mechanisms triggering these second hits remain largely elusive. Thus, we generated a novel ETV6/RUNX1 transgenic mouse model where the expression of the fusion protein is restricted to CD19+ B cells. These animals harbor regular B cell development and lack gross abnormalities. We established stable pro-B cell lines carrying the ETV6/RUNX1 transgene that allowed us to investigate whether ETV6/RUNX1 itself favors the acquisition of second hits. Remarkably, these pro-B cell lines as well as primary bone marrow cells derived from ETV6/RUNX1 transgenic animals display elevated levels of reactive oxygen species (ROS as tested with ETV6/RUNX1 transgenic dihydroethidium staining. In line, intracellular phospho-histone H2AX flow cytometry and comet assay revealed increased DNA damage indicating that ETV6/RUNX1 expression enhances ROS. On the basis of our data, we propose the following model: the expression of ETV6/RUNX1 creates a preleukemic clone and leads to increased ROS levels. These elevated ROS favor the accumulation of secondary hits by increasing genetic instability and doublestrand breaks, thus allowing preleukemic clones to develop into fully transformed leukemic cells.

  9. Role of the DNA Mismatch Repair Gene MutS4 in Driving the Evolution of Mycobacterium yongonense Type I via Homologous Recombination.

    Science.gov (United States)

    Kim, Byoung-Jun; Kim, Bo-Ram; Kook, Yoon-Hoh; Kim, Bum-Joon

    2017-01-01

    We recently showed that Mycobacterium yongonense could be divided into two genotypes: Type I, in which the rpoB gene has been transferred from Mycobacterium parascrofulaceum , and Type II, in which the rpoB gene has not been transferred. Comparative genome analysis of three M. yongonense Type I, two M. yongonense Type II and M. parascrofulaceum type strains were performed in this study to gain insight into gene transfer from M. parascrofulaceum into M. yongonense Type I strains. We found two genome regions transferred from M. parascrofulaceum : one contained 3 consecutive genes, including the rpoBC operon, and the other contained 57 consecutive genes that had been transferred into M. yongonense Type I genomes via homologous recombination. Further comparison between the M. yongonense Type I and II genomes revealed that Type I, but not Type II has a distinct DNA mismatch repair gene ( MutS4 subfamily) that was possibly transferred via non-homologous recombination from other actinomycetes. We hypothesized that it could facilitate homologous recombination from the M. parascrofulaceum to the M. yongonense Type I genomes. We therefore generated recombinant Mycobacterium smegmatis containing a MutS4 operon of M. yongonense . We found that the M. tuberculosis rpoB fragment with a rifampin resistance-conferring mutation was more frequently inserted into recombinant M. smegmatis than the wild type, suggesting that MutS4 is a driving force in the gene transfer from M. parascrofulaceum to M. yongonense Type I strains via homologous recombination. In conclusion, our data indicated that MutS4 in M. yongonense Type I genomes may drive gene transfer from M. parascrofulaceum via homologous recombination, resulting in division of M. yongonense into two genotypes, Type I and II.

  10. Role of the DNA Mismatch Repair Gene MutS4 in Driving the Evolution of Mycobacterium yongonense Type I via Homologous Recombination

    Directory of Open Access Journals (Sweden)

    Byoung-Jun Kim

    2017-12-01

    Full Text Available We recently showed that Mycobacterium yongonense could be divided into two genotypes: Type I, in which the rpoB gene has been transferred from Mycobacterium parascrofulaceum, and Type II, in which the rpoB gene has not been transferred. Comparative genome analysis of three M. yongonense Type I, two M. yongonense Type II and M. parascrofulaceum type strains were performed in this study to gain insight into gene transfer from M. parascrofulaceum into M. yongonense Type I strains. We found two genome regions transferred from M. parascrofulaceum: one contained 3 consecutive genes, including the rpoBC operon, and the other contained 57 consecutive genes that had been transferred into M. yongonense Type I genomes via homologous recombination. Further comparison between the M. yongonense Type I and II genomes revealed that Type I, but not Type II has a distinct DNA mismatch repair gene (MutS4 subfamily that was possibly transferred via non-homologous recombination from other actinomycetes. We hypothesized that it could facilitate homologous recombination from the M. parascrofulaceum to the M. yongonense Type I genomes. We therefore generated recombinant Mycobacterium smegmatis containing a MutS4 operon of M. yongonense. We found that the M. tuberculosis rpoB fragment with a rifampin resistance-conferring mutation was more frequently inserted into recombinant M. smegmatis than the wild type, suggesting that MutS4 is a driving force in the gene transfer from M. parascrofulaceum to M. yongonense Type I strains via homologous recombination. In conclusion, our data indicated that MutS4 in M. yongonense Type I genomes may drive gene transfer from M. parascrofulaceum via homologous recombination, resulting in division of M. yongonense into two genotypes, Type I and II.

  11. Drive Stands

    Data.gov (United States)

    Federal Laboratory Consortium — The Electrical Systems Laboratory (ESL)houses numerous electrically driven drive stands. A drive stand consists of an electric motor driving a gearbox and a mounting...

  12. Dementia & Driving

    Science.gov (United States)

    ... have to give up driving. Many people associate driving with self-reliance and freedom; the loss of driving privileges ... familiar roads and avoid long distances. Avoid heavy traffic and heavily traveled roads. Avoid driving at night and in bad weather. Reduce the ...

  13. A comparative study on low-energy ion beam and neutralized beam modifications of naked DNA and biological effect on mutation

    Science.gov (United States)

    Sarapirom, S.; Thongkumkoon, P.; Prakrajang, K.; Anuntalabhochai, S.; Yu, L. D.

    2012-02-01

    DNA conformation change or damage induced by low-energy ion irradiation has been of great interest owing to research developments in ion beam biotechnology and ion beam application in biomedicine. Mechanisms involved in the induction of DNA damage may account for effect from implanting ion charge. In order to check this effect, we used both ion beam and neutralized beam at keV energy to bombard naked DNA. Argon or nitrogen ion beam was generated and extracted from a radiofrequency (RF) ion source and neutralized by microwave-driven plasma in the beam path. Plasmid DNA pGFP samples were irradiated with the ion or neutralized beam in vacuum, followed by gel electrophoresis to observe changes in the DNA conformations. It was revealed that the ion charge played a certain role in inducing DNA conformation change. The subsequent DNA transfer into bacteria Escherichia coli ( E. coli) for mutation analysis indicated that the charged ion beam induced DNA change had high potential in mutation induction while neutralized beam did not. The intrinsic reason was attributed to additional DNA deformation and contortion caused by ion charge exchange effect so that the ion beam induced DNA damage could hardly be completely repaired, whereas the neutralized beam induced DNA change could be more easily recoverable owing to absence of the additional DNA deformation and contortion.

  14. A comparative study on low-energy ion beam and neutralized beam modifications of naked DNA and biological effect on mutation

    International Nuclear Information System (INIS)

    Sarapirom, S.; Thongkumkoon, P.; Prakrajang, K.; Anuntalabhochai, S.; Yu, L.D.

    2012-01-01

    DNA conformation change or damage induced by low-energy ion irradiation has been of great interest owing to research developments in ion beam biotechnology and ion beam application in biomedicine. Mechanisms involved in the induction of DNA damage may account for effect from implanting ion charge. In order to check this effect, we used both ion beam and neutralized beam at keV energy to bombard naked DNA. Argon or nitrogen ion beam was generated and extracted from a radiofrequency (RF) ion source and neutralized by microwave-driven plasma in the beam path. Plasmid DNA pGFP samples were irradiated with the ion or neutralized beam in vacuum, followed by gel electrophoresis to observe changes in the DNA conformations. It was revealed that the ion charge played a certain role in inducing DNA conformation change. The subsequent DNA transfer into bacteria Escherichia coli (E. coli) for mutation analysis indicated that the charged ion beam induced DNA change had high potential in mutation induction while neutralized beam did not. The intrinsic reason was attributed to additional DNA deformation and contortion caused by ion charge exchange effect so that the ion beam induced DNA damage could hardly be completely repaired, whereas the neutralized beam induced DNA change could be more easily recoverable owing to absence of the additional DNA deformation and contortion.

  15. On the recovery of the DNA-synthesis after X-irradiation in the spleen of mice and its modification by the NAD-metabolism

    International Nuclear Information System (INIS)

    Streffer, C.

    1974-01-01

    The incorporation of tritium-labelled thymidine into the DNA of mice spleen cells after whole body irradiation with X-rays was measured in order to study the decrease of DNA synthesis is decreased for several hours after irradiation with low doses. Recovery effects become operative after six hours. The radiation effect on the NAD metabolism, known to be related to DNA synthesis, was also investigated. The rate of NAD synthesis is influenced via the extremely radiosensitive metabolic process in the nucleus. Conversely, inhibition of DNA synthesis by injection of NAD enhances the recovery of DNA synthesis after irradiaton. (G.G.)

  16. Distracted driving

    Science.gov (United States)

    ... including maps) The Dangers of Talking on the Phone While Driving You are four times more likely to get ... of reach. If you are caught using a phone while driving, you may risk a ticket or fine. Most ...

  17. Distracted Driving

    Science.gov (United States)

    ... and increased awareness of distracted driving using radio advertisements, news stories, and similar media. After the projects ... available at www.trafficsafetymarketing.gov . Distracted Driving Enforcement – TV Ads (Paid). For re-tagging, go to: www. ...

  18. Electric drives

    CERN Document Server

    Boldea, Ion

    2005-01-01

    ENERGY CONVERSION IN ELECTRIC DRIVESElectric Drives: A DefinitionApplication Range of Electric DrivesEnergy Savings Pay Off RapidlyGlobal Energy Savings Through PEC DrivesMotor/Mechanical Load MatchMotion/Time Profile MatchLoad Dynamics and StabilityMultiquadrant OperationPerformance IndexesProblemsELECTRIC MOTORS FOR DRIVESElectric Drives: A Typical ConfigurationElectric Motors for DrivesDC Brush MotorsConventional AC MotorsPower Electronic Converter Dependent MotorsEnergy Conversion in Electric Motors/GeneratorsPOWER ELECTRONIC CONVERTERS (PECs) FOR DRIVESPower Electronic Switches (PESs)The

  19. Parkinson's disease and driving ability

    Science.gov (United States)

    Singh, Rajiv; Pentland, Brian; Hunter, John; Provan, Frances

    2007-01-01

    Objectives To explore the driving problems associated with Parkinson's disease (PD) and to ascertain whether any clinical features or tests predict driver safety. Methods The driving ability of 154 individuals with PD referred to a driving assessment centre was determined by a combination of clinical tests, reaction times on a test rig and an in‐car driving test. Results The majority of cases (104, 66%) were able to continue driving although 46 individuals required an automatic transmission and 10 others needed car modifications. Ability to drive was predicted by the severity of physical disease, age, presence of other associated medical conditions, particularly dementia, duration of disease, brake reaction, time on a test rig and score on a driving test (all pautomatic transmission. A combination of clinical tests and in‐car driving assessment will establish safety to drive, and a number of clinical correlates can be shown to predict the likely outcome and may assist in the decision process. This is the largest series of consecutive patients seen at a driving assessment centre reported to date, and the first to devise a scoring system for on‐road driving assessment. PMID:17178820

  20. Systematic evaluation and optimization of modification reactions of oligonucleotides with amines and carboxylic acids for the synthesis of DNA-encoded chemical libraries.

    Science.gov (United States)

    Franzini, Raphael M; Samain, Florent; Abd Elrahman, Maaly; Mikutis, Gediminas; Nauer, Angela; Zimmermann, Mauro; Scheuermann, Jörg; Hall, Jonathan; Neri, Dario

    2014-08-20

    DNA-encoded chemical libraries are collections of small molecules, attached to DNA fragments serving as identification barcodes, which can be screened against multiple protein targets, thus facilitating the drug discovery process. The preparation of large DNA-encoded chemical libraries crucially depends on the availability of robust synthetic methods, which enable the efficient conjugation to oligonucleotides of structurally diverse building blocks, sharing a common reactive group. Reactions of DNA derivatives with amines and/or carboxylic acids are particularly attractive for the synthesis of encoded libraries, in view of the very large number of building blocks that are commercially available. However, systematic studies on these reactions in the presence of DNA have not been reported so far. We first investigated conditions for the coupling of primary amines to oligonucleotides, using either a nucleophilic attack on chloroacetamide derivatives or a reductive amination on aldehyde-modified DNA. While both methods could be used for the production of secondary amines, the reductive amination approach was generally associated with higher yields and better purity. In a second endeavor, we optimized conditions for the coupling of a diverse set of 501 carboxylic acids to DNA derivatives, carrying primary and secondary amine functions. The coupling efficiency was generally higher for primary amines, compared to secondary amine substituents, but varied considerably depending on the structure of the acids and on the synthetic methods used. Optimal reaction conditions could be found for certain sets of compounds (with conversions >80%), but multiple reaction schemes are needed when assembling large libraries with highly diverse building blocks. The reactions and experimental conditions presented in this article should facilitate the synthesis of future DNA-encoded chemical libraries, while outlining the synthetic challenges that remain to be overcome.

  1. Pile Driving

    Science.gov (United States)

    1987-01-01

    Machine-oriented structural engineering firm TERA, Inc. is engaged in a project to evaluate the reliability of offshore pile driving prediction methods to eventually predict the best pile driving technique for each new offshore oil platform. Phase I Pile driving records of 48 offshore platforms including such information as blow counts, soil composition and pertinent construction details were digitized. In Phase II, pile driving records were statistically compared with current methods of prediction. Result was development of modular software, the CRIPS80 Software Design Analyzer System, that companies can use to evaluate other prediction procedures or other data bases.

  2. A Built-In CpG Adjuvant in RSV F Protein DNA Vaccine Drives a Th1 Polarized and Enhanced Protective Immune Response

    Directory of Open Access Journals (Sweden)

    Yao Ma

    2018-01-01

    Full Text Available Human respiratory syncytial virus (RSV is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F glycoprotein on the vaccine-induced immune response. The addition of CpG-C motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c mice immunized with the DNA vaccines. Moreover, mice vaccinated with CpG-modified vaccines, especially with the higher 20 copies, resulted in an enhanced shift toward a Th1-biased antibody and T-cell response, a decrease in pulmonary pathology and virus replication, and a decrease in weight loss after RSV challenge. This study suggests that CpG-C motif, cloned into the backbone of DNA vaccine encoding RSV F glycoprotein, functions as a built-in adjuvant capable of improving the efficacy of DNA vaccine against RSV infection.

  3. Expression of 5 S rRNA genes linked to 35 S rDNA in plants, their epigenetic modification and regulatory element divergence

    Czech Academy of Sciences Publication Activity Database

    Garcia, S.; Crhák Khaitová, Lucie; Kovařík, Aleš

    2012-01-01

    Roč. 12, JUN 20 (2012), ID 95 ISSN 1471-2229 R&D Projects: GA ČR GAP501/10/0208; GA ČR GBP501/12/G090 Institutional support: RVO:68081707 Keywords : ARABIDOPSIS-THALIANA * NUCLEOTIDE-SEQUENCES * DNA METHYLATION * GENUS ARTEMISIA Subject RIV: BO - Biophysics Impact factor: 4.354, year: 2012

  4. Impaired Driving

    Science.gov (United States)

    ... Get the Facts What Works: Strategies to Increase Car Seat and Booster Seat ... narcotics. 3 That’s one percent of the 111 million self-reported episodes of alcohol-impaired driving among U.S. ...

  5. The phytochemical 3,3'-diindolylmethane decreases expression of AR-controlled DNA damage repair genes through repressive chromatin modifications and is associated with DNA damage in prostate cancer cells.

    Science.gov (United States)

    Palomera-Sanchez, Zoraya; Watson, Gregory W; Wong, Carmen P; Beaver, Laura M; Williams, David E; Dashwood, Roderick H; Ho, Emily

    2017-09-01

    Androgen receptor (AR) is a transcription factor involved in normal prostate physiology and prostate cancer (PCa) development. 3,3'-Diindolylmethane (DIM) is a promising phytochemical agent against PCa that affects AR activity and epigenetic regulators in PCa cells. However, whether DIM suppresses PCa via epigenetic regulation of AR target genes is unknown. We assessed epigenetic regulation of AR target genes in LNCaP PCa cells and showed that DIM treatment led to epigenetic suppression of AR target genes involved in DNA repair (PARP1, MRE11, DNA-PK). Decreased expression of these genes was accompanied by an increase in repressive chromatin marks, loss of AR occupancy and EZH2 recruitment to their regulatory regions. Decreased DNA repair gene expression was associated with an increase in DNA damage (γH2Ax) and up-regulation of genomic repeat elements LINE1 and α-satellite. Our results suggest that DIM suppresses AR-dependent gene transcription through epigenetic modulation, leading to DNA damage and genome instability in PCa cells. Published by Elsevier Inc.

  6. Effects of an overload of animal protein on the rat: brain DNA alterations and tissue morphological modifications during fetal and post-natal stage.

    Science.gov (United States)

    Greco, A M; Sticchi, R; Boschi, G; Vetrani, A; Salvatore, G

    1985-01-01

    On account of many literature reports about the definite correlation between high animal protein intake and cardiovascular diseases, we have studied the effect of a hyperproteic purified diet (casein 40%, lactalbumin 20%) on fetal and post-natal (not further than 40th day) stage of the rat, when cell subdivision process is faster and therefore damage by nutritional imbalance is certainly more serious. Litters of rats were grouped according to mother's (either hyperproteic or common basic) and rat's (after lactation) diet. Brain DNA and histology of various organs were studied. Hyperproteic diet during fetal stage and lactation would inhibit brain cell subdivision since overall content of brain DNA would be decreased on autoptic finding. Structural changes were also shown in liver, heart, kidney and adrenal cortex, especially when hyperproteic diet was continued even after lactation.

  7. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

    Science.gov (United States)

    Glinsky, Gennadi V

    2016-09-19

    Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of creation of

  8. Genome-wide screening identifies Plasmodium chabaudi-induced modifications of DNA methylation status of Tlr1 and Tlr6 gene promoters in liver, but not spleen, of female C57BL/6 mice.

    Science.gov (United States)

    Al-Quraishy, Saleh; Dkhil, Mohamed A; Abdel-Baki, Abdel Azeem S; Delic, Denis; Santourlidis, Simeon; Wunderlich, Frank

    2013-11-01

    Epigenetic reprogramming of host genes via DNA methylation is increasingly recognized as critical for the outcome of diverse infectious diseases, but information for malaria is not yet available. Here, we investigate the effect of blood-stage malaria of Plasmodium chabaudi on the DNA methylation status of host gene promoters on a genome-wide scale using methylated DNA immunoprecipitation and Nimblegen microarrays containing 2,000 bp oligonucleotide features that were split into -1,500 to -500 bp Ups promoters and -500 to +500 bp Cor promoters, relative to the transcription site, for evaluation of differential DNA methylation. Gene expression was analyzed by Agilent and Affymetrix microarray technology. Challenging of female C57BL/6 mice with 10(6) P. chabaudi-infected erythrocytes resulted in a self-healing outcome of infections with peak parasitemia on day 8 p.i. These infections induced organ-specific modifications of DNA methylation of gene promoters. Among the 17,354 features on Nimblegen arrays, only seven gene promoters were identified to be hypermethylated in the spleen, whereas the liver exhibited 109 hyper- and 67 hypomethylated promoters at peak parasitemia in comparison with non-infected mice. Among the identified genes with differentially methylated Cor-promoters, only the 7 genes Pigr, Ncf1, Klkb1, Emr1, Ndufb11, and Tlr6 in the liver and Apol6 in the spleen were detected to have significantly changed their expression. Remarkably, the Cor promoter of the toll-like receptor Tlr6 became hypomethylated and Tlr6 expression increased by 3.4-fold during infection. Concomitantly, the Ups promoter of the Tlr1 was hypermethylated, but Tlr1 expression also increased by 11.3-fold. TLR6 and TLR1 are known as auxillary receptors to form heterodimers with TLR2 in plasma membranes of macrophages, which recognize different pathogen-associated molecular patterns (PAMPs), as, e.g., intact 3-acyl and sn-2-lyso-acyl glycosylphosphatidylinositols of P. falciparum

  9. Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Miralem Mrkonjic

    Full Text Available We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734 and microsatellite unstable (MSI-H colorectal cancers (CRCs in two samples. The current study expanded on this finding as we explored the genetic basis of DNA methylation in this region of chromosome 3. We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and consequently to genome-wide microsatellite instability.We first tested our hypothesis in one sample from Ontario (901 cases, 1,097 controls and replicated major findings in two additional samples from Newfoundland and Labrador (479 cases, 336 controls and from Seattle (591 cases, 629 controls. Logistic regression was used to test for association between SNPs in the region of MLH1 and CRC, MSI-H CRC, MLH1 gene expression in CRC, and DNA methylation in CRC. The association between rs1800734 and MSI-H CRCs, previously reported in Ontario and Newfoundland, was replicated in the Seattle sample. Two additional SNPs, in strong linkage disequilibrium with rs1800734, showed strong associations with MLH1 promoter methylation, loss of MLH1 protein, and MSI-H CRC in all three samples. The logistic regression model of MSI-H CRC that included MLH1-promoter-methylation status and MLH1 immunohistochemistry status fit most parsimoniously in all three samples combined. When rs1800734 was added to this model, its effect was not statistically significant (P-value  = 0.72 vs. 2.3×10(-4 when the SNP was examined alone.The observed association of rs1800734 with MSI-H CRC occurs through its effect on the MLH1 promoter methylation, MLH1 IHC deficiency, or both.

  10. Driving things

    DEFF Research Database (Denmark)

    Nevile, Maurice Richard

    2015-01-01

    I explore how participants organise involvement with objects brought into the car, relative to the demands of driving and social activity. Objects in cars commonly include phones or other technologies, food, body care products, texts, clothing, bags and carry items, toys, and even animals...... 2004, Haddington et al. 2012). I focus here especially on how the practical and interactional work of locating, seeing, placing, handling, hearing, and relinquishing, is ordered and accomplished relative to the emerging and contingent demands of both driving and social participation......, such that involvement with objects is constituted as secondary to driving in a multiactivity setting (e.g. Haddington et al. 2014). We see how events with, for, of, and even by objects can occur as predictable, planned and even designed for (e.g. changing glasses, applying body lotion), or might be unexpected...

  11. Base voltammetric characterization of phenylazide modified deoxycytidine - the potential DNA redox label enabling its post-synthetic modifications by "click-reactions"

    Czech Academy of Sciences Publication Activity Database

    Daňhel, Aleš; Trošanová, Zuzana; Balintová, Jana; Havran, Luděk; Hocek, Michal; Fojta, Miroslav

    2013-01-01

    Roč. 9, č. 1 (2013), s. 140-141 ISSN 1336-7242. [Zjazd chemikov /65./. 09.09.2013-13.09.2013, Tatranské Matliare] R&D Projects: GA ČR GBP206/12/G151; GA AV ČR(CZ) IAA400040901 Grant - others:MŠMT(CZ) CZ.1.07/2.3.00/30.0019 Institutional support: RVO:61388963 ; RVO:68081707 Keywords : DNA redox label * click-reaction Subject RIV: CC - Organic Chemistry

  12. Inclusion of methoxy groups inverts the thermodynamic stabilities of DNA-RNA hybrid duplexes: A molecular dynamics simulation study.

    Science.gov (United States)

    Suresh, Gorle; Priyakumar, U Deva

    2015-09-01

    Modified nucleic acids have found profound applications in nucleic acid based technologies such as antisense and antiviral therapies. Previous studies on chemically modified nucleic acids have suggested that modifications incorporated in furanose sugar especially at 2'-position attribute special properties to nucleic acids when compared to other modifications. 2'-O-methyl modification to deoxyribose sugars of DNA-RNA hybrids is one such modification that increases nucleic acid stability and has become an attractive class of compounds for potential antisense applications. It has been reported that modification of DNA strands with 2'-O-methyl group reverses the thermodynamic stability of DNA-RNA hybrid duplexes. Molecular dynamics simulations have been performed on two hybrid duplexes (DR and RD) which differ from each other and 2'-O-methyl modified counterparts to investigate the effect of 2'-O-methyl modification on their duplex stability. The results obtained suggest that the modification drives the conformations of both the hybrid duplexes towards A-RNA like conformation. The modified hybrid duplexes exhibit significantly contrasting dynamics and hydration patterns compared to respective parent duplexes. In line with the experimental results, the relative binding free energies suggest that the introduced modifications stabilize the less stable DR hybrid, but destabilize the more stable RD duplex. Binding free energy calculations suggest that the increased hydrophobicity is primarily responsible for the reversal of thermodynamic stability of hybrid duplexes. Free energy component analysis further provides insights into the stability of modified duplexes. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Modification of radiation dose-rate sparing effects in a human carcinoma of the cervix cell line by inhibitors of DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Kelland, L.R.; Steel, G.G.

    1988-08-01

    The in vitro cell survival of a human cervix carcinoma cell line (HX156c) was assessed using /sup 60/Co ..gamma..-rays administered at 150 cGy/min or 3.2 cGy/min dose rate. Recovery during low dose-rate irradiation was observed; dose reduction factor at 10/sup -2/ cell kill for 150 versus 3.2 cGy/min was around 1.3. Possible underlying mechanisms of this recovery process have been investigated by addition of non-toxic concentrations of various agents thought to inhibit eukaryotic DNA repair. Differential effects among inhibitors were observed; aphidicolin had no effect on cell survival, novobiocin, hydroxyurea and 3-aminobenzamide reduced survival by a similar extent at both dose rates, ..beta..-ara A and caffeine reduced survival to a greater extent during low dose-rate irradiation. ..beta..-ara A and caffeine seemed to effect mainly by increasing the alpha component of the acute survival curve. Since survival curves obtained at dose rates of around 3 cGy/min help define a dominant component of the initial slope of the acute curve the authors claim to demonstrate that ..beta..-ara A and caffeine modify the initial slope, probably by inhibiting DNA repair processes involved in tumour cell sparing during protracted irradiation.

  14. Exposure to 3,3',5-triiodothyronine affects histone and RNA polymerase II modifications, but not DNA methylation status, in the regulatory region of the Xenopus laevis thyroid hormone receptor βΑ gene.

    Science.gov (United States)

    Kasai, Kentaro; Nishiyama, Norihito; Izumi, Yushi; Otsuka, Shunsuke; Ishihara, Akinori; Yamauchi, Kiyoshi

    2015-11-06

    Thyroid hormones (THs) play a critical role in amphibian metamorphosis, during which the TH receptor (TR) gene, thrb, is upregulated in a tissue-specific manner. The Xenopus laevis thrb gene has 3 TH response elements (TREs) in the 5' flanking regulatory region and 1 TRE in the exon b region, around which CpG sites are highly distributed. To clarify whether exposure to 3,3',5-triiodothyronine (T3) affects histone and RNA polymerase II (RNAPII) modifications and the level of DNA methylation in the 5' regulatory region, we conducted reverse transcription-quantitative polymerase chain reaction, bisulfite sequencing and chromatin immunoprecipitation assay using X. laevis cultured cells and premetamorphic tadpoles treated with or without 2 nM T3. Exposure to T3 increased the amount of the thrb transcript, in parallel with enhanced histone H4 acetylation and RNAPII recruitment, and probably phosphorylation of RNAPII at serine 5, in the 5' regulatory and exon b regions. However, the 5' regulatory region remained hypermethylated even with exposure to T3, and there was no significant difference in the methylation status between DNAs from T3-untreated and -treated cultured cells or tadpole tissues. Our results demonstrate that exposure to T3 induced euchromatin-associated epigenetic marks by enhancing histone acetylation and RNAPII recruitment, but not by decreasing the level of DNA methylation, in the 5' regulatory region of the X. laevis thrb gene. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Estrogen Drives Cellular Transformation and Mutagenesis in Cells Expressing the Breast Cancer-Associated R438W DNA Polymerase Lambda Protein.

    Science.gov (United States)

    Nemec, Antonia A; Bush, Korie B; Towle-Weicksel, Jamie B; Taylor, B Frazier; Schulz, Vincent; Weidhaas, Joanne B; Tuck, David P; Sweasy, Joann B

    2016-11-01

    Repair of DNA damage is critical for maintaining the genomic integrity of cells. DNA polymerase lambda (POLL/Pol λ) is suggested to function in base excision repair (BER) and nonhomologous end-joining (NHEJ), and is likely to play a role in damage tolerance at the replication fork. Here, using next-generation sequencing, it was discovered that the POLL rs3730477 single-nucleotide polymorphism (SNP) encoding R438W Pol λ was significantly enriched in the germlines of breast cancer patients. Expression of R438W Pol λ in human breast epithelial cells induces cellular transformation and chromosomal aberrations. The role of estrogen was assessed as it is commonly used in hormone replacement therapies and is a known breast cancer risk factor. Interestingly, the combination of estrogen treatment and the expression of the R438W Pol λ SNP drastically accelerated the rate of transformation. Estrogen exposure produces 8-oxoguanine lesions that persist in cells expressing R438W Pol λ compared with wild-type (WT) Pol λ-expressing cells. Unlike WT Pol λ, which performs error-free bypass of 8-oxoguanine lesions, expression of R438W Pol λ leads to an increase in mutagenesis and replicative stress in cells treated with estrogen. Together, these data suggest that individuals who carry the rs3730477 POLL germline variant have an increased risk of estrogen-associated breast cancer. The Pol λ R438W mutation can serve as a biomarker to predict cancer risk and implicates that treatment with estrogen in individuals with this mutation may further increase their risk of breast cancer. Mol Cancer Res; 14(11); 1068-77. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Structure of DNA toroids and electrostatic attraction of DNA duplexes

    International Nuclear Information System (INIS)

    Cherstvy, A G

    2005-01-01

    DNA-DNA electrostatic attraction is considered as the driving force for the formation of DNA toroids in the presence of DNA condensing cations. This attraction comes from the DNA helical charge distribution and favours hexagonal toroidal cross-sections. The latter is in agreement with recent cryo-electron microscopy studies on DNA condensed with cobalt hexammine. We treat the DNA-DNA interactions within the modern theory of electrostatic interaction between helical macromolecules. The size and thickness of the toroids is calculated within a simple model; other models of stability of DNA toroids are discussed and compared

  17. Transcription-induced DNA supercoiling: New roles of intranucleosomal DNA loops in DNA repair and transcription.

    Science.gov (United States)

    Gerasimova, N S; Pestov, N A; Kulaeva, O I; Clark, D J; Studitsky, V M

    2016-05-26

    RNA polymerase II (Pol II) transcription through chromatin is accompanied by formation of small intranucleosomal DNA loops. Pol II captured within a small loop drives accumulation of DNA supercoiling, facilitating further transcription. DNA breaks relieve supercoiling and induce Pol II arrest, allowing detection of DNA damage hidden in chromatin structure.

  18. Epigenetic Modifications and Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Renu A. Kowluru

    2013-01-01

    Full Text Available Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2 and matrix metalloproteinase-9 (MMP-9 are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1, and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.

  19. All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available It has been documented all-trans retinoic acid (atRA promotes the development of TGF-β-induced CD4(+Foxp3(+ regulatory T cells (iTreg that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs.Addition of atRA to naïve CD4(+CD25(- cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3(+ iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4(+ cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4(+ cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4(+ cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4(+ cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered.We have identified the cellular and molecular mechanism(s by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.

  20. Community Drive

    DEFF Research Database (Denmark)

    Magnussen, Rikke

    2018-01-01

    Schools and educational institutions are challenged by not adequately educating students for independent knowledge collaboration and solving of complex societal challenges (Bundsgaard & Hansen, 2016; Slot et al., 2017). As an alternative strategy to formal learning has Community-driven research...... opportunity to break boundaries between research institutions and surrounding communities through the involvement of new types of actors, knowledge forms and institutions (OECD, 2011). This paper presents the project Community Drive a three year cross disciplinary community-driven game– and data-based project....... In the paper we present how the project Community Drive initiated in May 2018 is based on results from pilot projects conducted from 2014 – 2017. Overall these studies showed that it is a strong motivational factor for students to be given the task to change their living conditions through redesign...

  1. Synthesis and structural characterization of piperazino-modified DNA that favours hybridization towards DNA over RNA

    DEFF Research Database (Denmark)

    Skov, Joan; Bryld, Torsten; Lindegaard, Dorthe

    2011-01-01

    We report the synthesis of two C4'-modified DNA analogues and characterize their structural impact on dsDNA duplexes. The 4'-C-piperazinomethyl modification stabilizes dsDNA by up to 5°C per incorporation. Extension of the modification with a butanoyl-linked pyrene increases the dsDNA stabilizati...

  2. Validation of a modification to Performance-Tested Method 010403: microwell DNA hybridization assay for detection of Listeria spp. in selected foods and selected environmental surfaces.

    Science.gov (United States)

    Alles, Susan; Peng, Linda X; Mozola, Mark A

    2009-01-01

    A modification to Performance-Tested Method 010403, GeneQuence Listeria Test (DNAH method), is described. The modified method uses a new media formulation, LESS enrichment broth, in single-step enrichment protocols for both foods and environmental sponge and swab samples. Food samples are enriched for 27-30 h at 30 degrees C, and environmental samples for 24-48 h at 30 degrees C. Implementation of these abbreviated enrichment procedures allows test results to be obtained on a next-day basis. In testing of 14 food types in internal comparative studies with inoculated samples, there were statistically significant differences in method performance between the DNAH method and reference culture procedures for only 2 foods (pasteurized crab meat and lettuce) at the 27 h enrichment time point and for only a single food (pasteurized crab meat) in one trial at the 30 h enrichment time point. Independent laboratory testing with 3 foods showed statistical equivalence between the methods for all foods, and results support the findings of the internal trials. Overall, considering both internal and independent laboratory trials, sensitivity of the DNAH method relative to the reference culture procedures was 90.5%. Results of testing 5 environmental surfaces inoculated with various strains of Listeria spp. showed that the DNAH method was more productive than the reference U.S. Department of Agriculture-Food Safety and Inspection Service (USDA-FSIS) culture procedure for 3 surfaces (stainless steel, plastic, and cast iron), whereas results were statistically equivalent to the reference method for the other 2 surfaces (ceramic tile and sealed concrete). An independent laboratory trial with ceramic tile inoculated with L. monocytogenes confirmed the effectiveness of the DNAH method at the 24 h time point. Overall, sensitivity of the DNAH method at 24 h relative to that of the USDA-FSIS method was 152%. The DNAH method exhibited extremely high specificity, with only 1% false

  3. Mycobacterium tuberculosis Latent Antigen Rv2029c from the Multistage DNA Vaccine A39 Drives TH1 Responses via TLR-mediated Macrophage Activation

    Directory of Open Access Journals (Sweden)

    Haibo Su

    2017-11-01

    Full Text Available Targeting of Mycobacterium tuberculosis (MTB latent antigens comprises a crucial strategy for the development of alternative tuberculosis (TB vaccine(s that protects against TB reactivation. Here, we generated a multistage DNA vaccine, A39, containing the early antigens Ag85A and Rv3425 as well as the latency-associated protein Rv2029c, which conferred protective immunity in a pre-exposure mouse model. Moreover, administration of the A39 vaccination after MTB exposure inhibited reactivation and resulted in significantly lower bacterial loads in the lungs and spleen of mice, compared to those in the control population. Subsequently, we investigated the effect of Rv2029c on innate immunity and characterized the molecular details of the interaction of this protein with the host via iTRAQ proteomic and biochemical assay analyses. Rv2029c activated macrophages, triggered the production of pro-inflammatory cytokines, and promoted toll-like receptor/mitogen-activated protein kinase (TLR/MAPK-dependent macrophage apoptosis. Furthermore, Rv2029c treatment enhanced the ability of Mycobacterium bovis Bacillus Calmette-Guérin (BCG-infected macrophages to present antigens to CD4+ T cells in vitro, which correlated with an increase in MHC-II expression. Lastly, Rv2029c-treated macrophages activated T cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and IL-2, and specifically expanded a population of CD44highCD62LlowCD4+/CD8+ effector/memory cells, indicating that Rv2029c, as a specific recall antigen, contributes to Th1 polarization in T cell immunity. These results suggest that Rv2029c and A39 comprise promising targets for the development of next-generation clinical TB therapeutic vaccines.

  4. Configuring NIF for direct drive experiments

    International Nuclear Information System (INIS)

    Eimerl, D.; Rothenberg, J.; Key, M.

    1995-01-01

    The National Ignition Facility (NIF) is a proposed 1.8 MJ laser facility for carrying out experiments in inertial confinement fusion, currently designed for indirect drive experiments. The direct drive approach is being pursued at the 30 kJ Omega facility at the University of Rochester. In this paper we discuss the modifications to the NIF laser that would be required for both indirect and direct drive experiments. A primary concern is the additional cost of adding direct drive capability to the facility

  5. Electric drives

    Energy Technology Data Exchange (ETDEWEB)

    1986-10-01

    Several electric vehicles have been tested in long-term tests, i.e. an electric passenger car (maximum speed 115 km/h) and several busses for use in pedestrians' zones, spas, airports, natural reserves, and urban transportation (DUO busses). The ICE high-speed train is discussed in some detail, i.e. its aeroacoustic and aerodynamic design, running gear, computer-controlled drives and brakes, diagnostic systems, and electrical equipment. The Berlin Maglev system is mentioned as well as current inverters in rail vehicles. (HWJ).

  6. Safe driving for teens

    Science.gov (United States)

    Driving and teenagers; Teens and safe driving; Automobile safety - teenage drivers ... months before taking friends as passengers. Teenage-related driving deaths occur more often in certain conditions. OTHER SAFETY TIPS FOR TEENS Reckless driving is still a ...

  7. Epigenetic modifications in prostate cancer.

    Science.gov (United States)

    Ngollo, Marjolaine; Dagdemir, Aslihan; Karsli-Ceppioglu, Seher; Judes, Gaelle; Pajon, Amaury; Penault-Llorca, Frederique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique J

    2014-01-01

    Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

  8. Extreme exercise and oxidative DNA modification

    DEFF Research Database (Denmark)

    Poulsen, H E; Loft, S; Vistisen, K

    1996-01-01

    Extreme exercise increases oxygen uptake with a potential for increased formation of reactive oxygen species. Damage to biomolecules may occur if such an increase exceeds the protective capacity of antioxidant defence mechanisms. Vigorous exercise amounting to approximately 10 h a day for 30 days...

  9. Hostility, driving anger, and dangerous driving: the emerging role of hemispheric preference.

    Science.gov (United States)

    Gidron, Yori; Gaygısız, Esma; Lajunen, Timo

    2014-12-01

    Various studies have implicated psychosocial variables (e.g., hostility) in risk of dangerous driving and traffic accidents. However, whether these variables are related to more basic neurobiological factors, and whether such associations have implications for the modification of psychosocial risk factors in the context of driving, have not been examined in depth. This study examined the relationship between hemispheric preference (HP), hostility and self-reported dangerous driving, and the ability to affect driving anger via hemisphere activating cognitive exercises (HACE). In Study 1, 254 Turkish students completed questionnaires of hostility, HP and driving behavior. In Study 2, we conducted a "proof of concept" experimental study, and tested effects of left, right and neutral HACE on driving anger, by exposing N=650 Turkish students to written scenarios including either logical (left hemisphere), visuo-spatial (right hemisphere) or "mild doses" of both types of contents (control). In Study 1, left-HP was associated with higher hostility and with more dangerous driving, and hostility mediated the relationship between L-HP and reported driving behavior. In Study 2, only right-HACE led to immediate significant reductions in self-reported driving anger. Left-HP is related to hostility and to dangerous driving, and it may be possible to partly reduce driving anger by right-HACE. Future studies must replicate these findings with objective measures, more enduring interventions and longer follow-ups. Copyright © 2014. Published by Elsevier Ltd.

  10. Ancient DNA

    DEFF Research Database (Denmark)

    Willerslev, Eske; Cooper, Alan

    2004-01-01

    ancient DNA, palaeontology, palaeoecology, archaeology, population genetics, DNA damage and repair......ancient DNA, palaeontology, palaeoecology, archaeology, population genetics, DNA damage and repair...

  11. Extended driving impairs nocturnal driving performances.

    Directory of Open Access Journals (Sweden)

    Patricia Sagaspe

    Full Text Available Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3-5 am, 1-5 am and 9 pm-5 am on open highway. Fourteen young healthy men (mean age [+/-SD] = 23.4 [+/-1.7] years participated Inappropriate line crossings (ILC in the last hour of driving of each session, sleep variables, self-perceived fatigue and sleepiness were measured. Compared to the short (3-5 am driving session, the incidence rate ratio of inappropriate line crossings increased by 2.6 (95% CI, 1.1 to 6.0; P<.05 for the intermediate (1-5 am driving session and by 4.0 (CI, 1.7 to 9.4; P<.001 for the long (9 pm-5 am driving session. Compared to the reference session (9-10 pm, the incidence rate ratio of inappropriate line crossings were 6.0 (95% CI, 2.3 to 15.5; P<.001, 15.4 (CI, 4.6 to 51.5; P<.001 and 24.3 (CI, 7.4 to 79.5; P<.001, respectively, for the three different durations of driving. Self-rated fatigue and sleepiness scores were both positively correlated to driving impairment in the intermediate and long duration sessions (P<.05 and increased significantly during the nocturnal driving sessions compared to the reference session (P<.01. At night, extended driving impairs driving performances and therefore should be limited.

  12. Epigenetic Modifications: Therapeutic Potential in Cancer

    Directory of Open Access Journals (Sweden)

    Manisha Sachan

    2015-08-01

    Full Text Available Epigenetic modifications and alterations in chromatin structure and function contribute to the cumulative changes observed as normal cells undergo malignant transformation. These modifications and enzymes (DNA methyltransferases, histone deacetylases, histone methyltransferases, and demethylases related to them have been deeply studied to develop new drugs, epigenome-targeted therapies and new diagnostic tools. Epigenetic modifiers aim to restore normal epigenetic modification patterns through the inhibition of epigenetic modifier enzymes. Four of them (azacitidine, decitabine, vorinostat and romidepsin are approved by the U.S. Food and Drug Administration. This article provides an overview about the known functional roles of epigenetic enzymes in cancer development.

  13. Driving for shorter outages

    International Nuclear Information System (INIS)

    Tritch, S.

    1996-01-01

    Nuclear plant outages are necessary to complete activities that cannot be completed during the operating cycle, such as steam generator inspection and testing, refueling, installing modifications, and performing maintenance tests. The time devoted to performing outages is normally the largest contributor to plant unavailability. Similarly, outage costs are a sizable portion of the total plant budget. The scope and quality of work done during outages directly affects operating reliability and the number of unplanned outages. Improved management and planning of outages enhances the margin of safety during the outage and results in increased plant reliability. The detailed planning and in-depth preparation that has become a necessity for driving shorter outage durations has also produced safer outages and improved post-outage reliability. Short outages require both plant and vendor management to focus on all aspects of the outage. Short outage durations, such as 26 days at South Texas or 29 days at North Anna, require power plant inter-department and intra-department teamwork and communication and vendor participation. In this paper shorter and safer outage at the 3-loop plants in the United States are explained. (J.P.N.)

  14. Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction.

    Science.gov (United States)

    Klaus, Miriam; Prokoph, Nina; Girbig, Mathias; Wang, Xuecong; Huang, Yong-Heng; Srivastava, Yogesh; Hou, Linlin; Narasimhan, Kamesh; Kolatkar, Prasanna R; Francois, Mathias; Jauch, Ralf

    2016-05-05

    The transcription factor (TF) SOX18 drives lymphatic vessel development in both embryogenesis and tumour-induced neo-lymphangiogenesis. Genetic disruption of Sox18 in a mouse model protects from tumour metastasis and established the SOX18 protein as a molecular target. Here, we report the crystal structure of the SOX18 DNA binding high-mobility group (HMG) box bound to a DNA element regulating Prox1 transcription. The crystals diffracted to 1.75Å presenting the highest resolution structure of a SOX/DNA complex presently available revealing water structure, structural adjustments at the DNA contact interface and non-canonical conformations of the DNA backbone. To explore alternatives to challenging small molecule approaches for targeting the DNA-binding activity of SOX18, we designed a set of five decoys based on modified Prox1-DNA. Four decoys potently inhibited DNA binding of SOX18 in vitro and did not interact with non-SOX TFs. Serum stability, nuclease resistance and thermal denaturation assays demonstrated that a decoy circularized with a hexaethylene glycol linker and terminal phosphorothioate modifications is most stable. This SOX decoy also interfered with the expression of a luciferase reporter under control of a SOX18-dependent VCAM1 promoter in COS7 cells. Collectively, we propose SOX decoys as potential strategy for inhibiting SOX18 activity to disrupt tumour-induced neo-lymphangiogenesis. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. HARMONIC DRIVE SELECTION

    Directory of Open Access Journals (Sweden)

    Piotr FOLĘGA

    2014-03-01

    Full Text Available The variety of types and sizes currently in production harmonic drive is a problem in their rational choice. Properly selected harmonic drive must meet certain requirements during operation, and achieve the anticipated service life. The paper discusses the problems associated with the selection of the harmonic drive. It also presents the algorithm correct choice of harmonic drive. The main objective of this study was to develop a computer program that allows the correct choice of harmonic drive by developed algorithm.

  16. DNA damage by reactive species: Mechanisms, mutation and repair

    Indian Academy of Sciences (India)

    DNA is continuously attacked by reactive species that can affect its structure and function severely. Structural modifications to DNA mainly arise from modifications in its bases that primarily occur due to their exposure to different reactive species. Apart from this, DNA strand break, inter- and intra-strand crosslinks and ...

  17. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  18. Electric Vehicle - Economical driving

    DEFF Research Database (Denmark)

    Jensen, VCE, Steen V.; Schøn, Henriette

    1999-01-01

    Instruct the reader in getting most satisfaction out of an EV, especially concerning driving and loading.......Instruct the reader in getting most satisfaction out of an EV, especially concerning driving and loading....

  19. Dementia and driving

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000028.htm Dementia and driving To use the sharing features on ... please enable JavaScript. If your loved one has dementia , deciding when they can no longer drive may ...

  20. The Optimal Design Method and Standardized Mathematical Model of Tooth Profile Modification of Spur Gear

    Directory of Open Access Journals (Sweden)

    Wenjie Mei

    2016-01-01

    Full Text Available The paper reports a tooth profile modification method of spur gear. After establishing a standardized mathematical model for optimized tooth profile and simulating meshing process with ANSYS finite element analysis, we obtained 625 groups of gear models with different modification parameters. The group with minimum transmission errors owns the optimal parameters. Genetic algorithm was adopted in the entire process for the purpose of reducing the variation of transmission errors in meshing process. The arc and parabolic modification were doing the same processing. After comparing the transmission errors fluctuation produced by the meshing process of gear of nonmodification with arc modification and parabolic modification, we found that the best modification effects of arc modification and parabolic modification were both reduced by 90%. The modification method makes the gear drive process more stable and efficient, and it is also promising in general application for gear drive.

  1. Gear bearing drive

    Science.gov (United States)

    Mavroidis, Constantinos (Inventor); Vranish, John M. (Inventor); Weinberg, Brian (Inventor)

    2011-01-01

    A gear bearing drive provides a compact mechanism that operates as an actuator providing torque and as a joint providing support. The drive includes a gear arrangement integrating an external rotor DC motor within a sun gear. Locking surfaces maintain the components of the drive in alignment and provide support for axial loads and moments. The gear bearing drive has a variety of applications, including as a joint in robotic arms and prosthetic limbs.

  2. Behavior Modification in Coaching.

    Science.gov (United States)

    Lynch, Annette Rutt; Stillman, Stephen M.

    1979-01-01

    An example of behavior modification used in athletic coaching is presented. The case study involves a member of a women's basketball team and details the use of behavior modification for both weight reduction and skill improvement. (JMF)

  3. Antihistamines and driving safety.

    Science.gov (United States)

    O'Hanlon, J F

    1988-10-27

    The results of two placebo-controlled driving performance studies confirm laboratory data showing that the nonsedating antihistamine terfenadine does not influence the driving performance of users. The amplitude of vehicle weaving calculated for drivers who received this agent did not differ from control values. Neither terfenadine nor loratadine, another nonsedating antihistamine, potentiated the adverse effects of alcohol on driving performance.

  4. Driving After a Stroke

    Science.gov (United States)

    ... 23,2015 Can I drive after a stroke? Driving is often a major concern after someone has a stroke. It’s not unusual for stroke survivors to want to drive. Being able to get around after a stroke is important. Safety behind the wheel is even more important after ...

  5. Sequential Dependencies in Driving

    Science.gov (United States)

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

    2012-01-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

  6. Simple Driving Techniques

    DEFF Research Database (Denmark)

    Rosendahl, Mads

    2002-01-01

    -like language. Our aim is to extract a simple notion of driving and show that even in this tamed form it has much of the power of more general notions of driving. Our driving technique may be used to simplify functional programs which use function composition and will often be able to remove intermediate data...

  7. Chemical mechanisms of histone lysine and arginine modifications

    OpenAIRE

    Smith, Brian C.; Denu, John M.

    2008-01-01

    Histone lysine and arginine residues are subject to a wide array of post-translational modifications including methylation, citrullination, acetylation, ubiquitination, and sumoylation. The combinatorial action of these modifications regulates critical DNA processes including replication, repair, and transcription. In addition, enzymes that modify histone lysine and arginine residues have been correlated with a variety of human diseases including arthritis, cancer, heart disease, diabetes, an...

  8. miRNAting control of DNA methylation

    Indian Academy of Sciences (India)

    DNA methylation is a type of epigenetic modification where a methyl group is added to the cytosine or adenine residue of a given DNA sequence. It has been observed that DNA methylation is achieved by some collaborative agglomeration of certain proteins and non-coding RNAs. The assembly of IDN2 and its ...

  9. Early life stress interactions with the epigenome: potential mechanisms driving vulnerability towards psychiatric illness

    Science.gov (United States)

    Olive, Michael Foster

    2014-01-01

    Throughout the 20th century a body of literature concerning the long lasting effects of early environment was produced. Adverse experiences in early life, or early life stress (ELS), is associated with a higher risk for developing various psychiatric illnesses. The mechanisms driving the complex interplay between ELS and adult phenotype has baffled many investigators for decades. Over the last decade, the new field of neuroepigenetics has emerged as one possible mechanism by which ELS can have far reaching effects on adult phenotype, behavior, and risk for psychiatric illness. Here we review two commonly investigated epigenetic mechanisms, histone modifications and DNA methylation, and the emerging field of neuroepigenetics as they relate to ELS. We discuss the current animal literature demonstrating ELS induced epigenetic modulation of gene expression that results in altered adult phenotypes. We also briefly discuss other areas in which neuroepigenetics has emerged as a potential mechanism underlying environmental and genetic interactions. PMID:25003947

  10. Early-life stress interactions with the epigenome: potential mechanisms driving vulnerability toward psychiatric illness.

    Science.gov (United States)

    Lewis, Candace R; Olive, M Foster

    2014-09-01

    Throughout the 20th century a body of literature concerning the long-lasting effects of the early environment was produced. Adverse experiences in early life, or early-life stress (ELS), is associated with a higher risk of developing various psychiatric illnesses. The mechanisms driving the complex interplay between ELS and adult phenotype has baffled many investigators for decades. Over the last decade, the new field of neuroepigenetics has emerged as one possible mechanism by which ELS can have far-reaching effects on adult phenotype, behavior, and risk for psychiatric illness. Here we review two commonly investigated epigenetic mechanisms, histone modifications and DNA methylation, and the emerging field of neuroepigenetics as they relate to ELS. We discuss the current animal literature demonstrating ELS-induced epigenetic modulation of gene expression that results in altered adult phenotypes. We also briefly discuss other areas in which neuroepigenetics has emerged as a potential mechanism underlying environmental and genetic interactions.

  11. Digitized molecular diagnostics: reading disk-based bioassays with standard computer drives.

    Science.gov (United States)

    Li, Yunchao; Ou, Lily M L; Yu, Hua-Zhong

    2008-11-01

    We report herein a digital signal readout protocol for screening disk-based bioassays with standard optical drives of ordinary desktop/notebook computers. Three different types of biochemical recognition reactions (biotin-streptavidin binding, DNA hybridization, and protein-protein interaction) were performed directly on a compact disk in a line array format with the help of microfluidic channel plates. Being well-correlated with the optical darkness of the binding sites (after signal enhancement by gold nanoparticle-promoted autometallography), the reading error levels of prerecorded audio files can serve as a quantitative measure of biochemical interaction. This novel readout protocol is about 1 order of magnitude more sensitive than fluorescence labeling/scanning and has the capability of examining multiplex microassays on the same disk. Because no modification to either hardware or software is needed, it promises a platform technology for rapid, low-cost, and high-throughput point-of-care biomedical diagnostics.

  12. Epigenetic modifications and diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Marpadga A. Reddy

    2012-09-01

    Full Text Available Diabetic nephropathy (DN is a major complication associated with both type 1 and type 2 diabetes, and a leading cause of end-stage renal disease. Conventional therapeutic strategies are not fully efficacious in the treatment of DN, suggesting an incomplete understanding of the gene regulation mechanisms involved in its pathogenesis. Furthermore, evidence from clinical trials has demonstrated a “metabolic memory” of prior exposure to hyperglycemia that continues to persist despite subsequent glycemic control. This remains a major challenge in the treatment of DN and other vascular complications. Epigenetic mechanisms such as DNA methylation, nucleosomal histone modifications, and noncoding RNAs control gene expression through regulation of chromatin structure and function and post-transcriptional mechanisms without altering the underlying DNA sequence. Emerging evidence indicates that multiple factors involved in the etiology of diabetes can alter epigenetic mechanisms and regulate the susceptibility to diabetes complications. Recent studies have demonstrated the involvement of histone lysine methylation in the regulation of key fibrotic and inflammatory genes related to diabetes complications including DN. Interestingly, histone lysine methylation persisted in vascular cells even after withdrawal from the diabetic milieu, demonstrating a potential role of epigenetic modifications in metabolic memory. Rapid advances in high-throughput technologies in the fields of genomics and epigenomics can lead to the identification of genome-wide alterations in key epigenetic modifications in vascular and renal cells in diabetes. Altogether, these findings can lead to the identification of potential predictive biomarkers and development of novel epigenetic therapies for diabetes and its associated complications.

  13. Contribution of granule bound starch synthase in kernel modification

    African Journals Online (AJOL)

    ACSS

    ... modification is rated on a scale of 1(completely hard / vitreous) to 5 (soft opaque). ... synthesis. Therefore this study aimed at understanding the role of gbssI in ... strand cDNA synthesis using the ... cDNA were served as templates for semi-.

  14. Screening vector field modifications of general relativity

    International Nuclear Information System (INIS)

    Beltrán Jiménez, Jose; Delvas Fróes, André Luís; Mota, David F.

    2013-01-01

    A screening mechanism for conformal vector–tensor modifications of general relativity is proposed. The conformal factor depends on the norm of the vector field and makes the field to vanish in high dense regions, whereas drives it to a non-null value in low density environments. Such process occurs due to a spontaneous symmetry breaking mechanism and gives rise to both the screening of fifth forces as well as Lorentz violations. The cosmology and local constraints are also computed

  15. MotifMark: Finding regulatory motifs in DNA sequences.

    Science.gov (United States)

    Hassanzadeh, Hamid Reza; Kolhe, Pushkar; Isbell, Charles L; Wang, May D

    2017-07-01

    The interaction between proteins and DNA is a key driving force in a significant number of biological processes such as transcriptional regulation, repair, recombination, splicing, and DNA modification. The identification of DNA-binding sites and the specificity of target proteins in binding to these regions are two important steps in understanding the mechanisms of these biological activities. A number of high-throughput technologies have recently emerged that try to quantify the affinity between proteins and DNA motifs. Despite their success, these technologies have their own limitations and fall short in precise characterization of motifs, and as a result, require further downstream analysis to extract useful and interpretable information from a haystack of noisy and inaccurate data. Here we propose MotifMark, a new algorithm based on graph theory and machine learning, that can find binding sites on candidate probes and rank their specificity in regard to the underlying transcription factor. We developed a pipeline to analyze experimental data derived from compact universal protein binding microarrays and benchmarked it against two of the most accurate motif search methods. Our results indicate that MotifMark can be a viable alternative technique for prediction of motif from protein binding microarrays and possibly other related high-throughput techniques.

  16. Chemical modification of arginine residues in the lactose repressor

    International Nuclear Information System (INIS)

    Whitson, P.A.; Matthews, K.S.

    1987-01-01

    The lactose repressor protein was chemically modified with 2,3-butanedione and phenylglyoxal. Arginine reaction was quantitated by either amino aced analysis or incorporation of 14 C-labeled phenylglyoxal. Inducer binding activity was unaffected by the modification of arginine residues, while both operator and nonspecific DNA binding activities were diminished, although to differing degrees. The correlation of the decrease in DNA binding activities with the modification of ∼ 1-2 equiv of arginine per monomer suggests increased reactivity of a functionally essential residue(s). For both reagents, operator DNA binding activity was protected by the presence of calf thymus DNA, and the extent of reaction with phenylglyoxal was simultaneously diminished. This protection presumably results from steric restriction of reagent access to an arginine(s) that is (are) essential for DNA binding interactions. These experiments suggest that there is (are) an essential reactive arginine(s) critical for repressor binding to DNA

  17. Control rod drive

    International Nuclear Information System (INIS)

    Okutani, Tetsuro.

    1988-01-01

    Purpose: To provide a simple and economical control rod drive using a control circuit requiring no pulse circuit. Constitution: Control rods in a BWR type reactor are driven by hydraulic pressure and inserted or withdrawn in the direction of applying the hydraulic pressure. The direction of the hydraulic pressure is controlled by a direction control valve. Since the driving for the control rod is extremely important in view of the operation, a self diagnosis function is disposed for rapid inspection of possible abnormality. In the present invention, two driving contacts are disposed each by one between the both ends of a solenoid valve of the direction control valve for driving the control rod and the driving power source, and diagnosis is conducted by alternately operating them. Therefore, since it is only necessary that the control circuit issues a driving instruction only to one of the two driving contacts, the pulse circuit is no more required. Further, since the control rod driving is conducted upon alignment of the two driving instructions, the reliability of the control rod drive can be improved. (Horiuchi, T.)

  18. Regulation and function of DNA methylation in plants and animals

    KAUST Repository

    He, Xinjian; Chen, Taiping; Zhu, Jian-Kang

    2011-01-01

    ) pathway. In animals, multiple mechanisms of active DNA demethylation have been proposed, including a deaminase- and DNA glycosylase-initiated BER pathway. New information concerning the effects of various histone modifications on the establishment

  19. Adjustable speed drives improve circulating water system

    International Nuclear Information System (INIS)

    Dent, R.A.; Dicic, Z.

    1994-01-01

    This paper illustrates the integration of electrical and mechanical engineering requirements to produce a solution to past problems and future operating demands. The application of adjustable speed drives in the modifications of the circulating water system at Indian Point No. 3 Nuclear Power Plant provided increased operating flexibility, efficiency and avoided otherwise costly renovations to the plant electrical systems. Rectification of the original inadequate design of the circulating water system, in addition to maximizing plant efficiency consistent with environmental considerations, formed the basis for this modification. This entailed replacement of all six circulating water pumps and motors and physical modifications to the intake system. This paper details the methodology used in this engineering task. The new system was installed successfully and has been operating reliably and economically for the past eight years

  20. Using driving simulators to assess driving safety.

    Science.gov (United States)

    Boyle, Linda Ng; Lee, John D

    2010-05-01

    Changes in drivers, vehicles, and roadways pose substantial challenges to the transportation safety community. Crash records and naturalistic driving data are useful for examining the influence of past or existing technology on drivers, and the associations between risk factors and crashes. However, they are limited because causation cannot be established and technology not yet installed in production vehicles cannot be assessed. Driving simulators have become an increasingly widespread tool to understand evolving and novel technologies. The ability to manipulate independent variables in a randomized, controlled setting also provides the added benefit of identifying causal links. This paper introduces a special issue on simulator-based safety studies. The special issue comprises 25 papers that demonstrate the use of driving simulators to address pressing transportation safety problems and includes topics as diverse as neurological dysfunction, work zone design, and driver distraction. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  1. Chromatin proteins and modifications as drug targets

    DEFF Research Database (Denmark)

    Helin, Kristian; Dhanak, Dashyant

    2013-01-01

    A plethora of groundbreaking studies have demonstrated the importance of chromatin-associated proteins and post-translational modifications of histones, proteins and DNA (so-called epigenetic modifications) for transcriptional control and normal development. Disruption of epigenetic control...... is a frequent event in disease, and the first epigenetic-based therapies for cancer treatment have been approved. A generation of new classes of potent and specific inhibitors for several chromatin-associated proteins have shown promise in preclinical trials. Although the biology of epigenetic regulation...

  2. Superluminal warp drive

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Diaz, Pedro F. [Colina de los Chopos, Centro de Fisica ' Miguel A. Catalan' , Instituto de Matematicas y Fisica Fundamental, Consejo Superior de Investigaciones Cientificas, Serrano 121, 28006 Madrid (Spain)], E-mail: p.gonzalezdiaz@imaff.cfmac.csic.es

    2007-09-20

    In this Letter we consider a warp drive spacetime resulting from that suggested by Alcubierre when the spaceship can only travel faster than light. Restricting to the two dimensions that retains most of the physics, we derive the thermodynamic properties of the warp drive and show that the temperature of the spaceship rises up as its apparent velocity increases. We also find that the warp drive spacetime can be exhibited in a manifestly cosmological form.

  3. Driving the Landscape

    Science.gov (United States)

    Haff, P. K.

    2012-12-01

    Technological modification of the earth's surface (e.g., agriculture, urbanization) is an old story in human history, but what about the future? The future of landscape in an accelerating technological world, beyond a relatively short time horizon, lies hidden behind an impenetrable veil of complexity. Sufficiently complex dynamics generates not only the trajectory of a variable of interest (e.g., vegetation cover) but also the environment in which that variable evolves (e.g., background climate). There is no way to anticipate what variables will define that environment—the dynamics creates its own variables. We are always open to surprise by a change of conditions we thought or assumed were fixed or by the appearance of new phenomena of whose possible existence we had been unaware or thought unlikely. This is especially true under the influence of technology, where novelty is the rule. Lack of direct long-term predictability of landscape change does not, however, mean we cannot say anything about its future. The presence of persistence (finite time scales) in a system means that prediction by a calibrated numerical model should be good for a limited period of time barring bad luck or faulty implementation. Short-term prediction, despite its limitations, provides an option for dealing with the longer-term future. If a computer-controlled car tries to drive itself from New York to Los Angeles, no conceivable (or possible) stand-alone software can be constructed to predict a priori the space-time trajectory of the vehicle. Yet the drive is normally completed easily by most drivers. The trip is successfully completed because each in a series of very short (linear) steps can be "corrected" on the fly by the driver, who takes her cues from the environment to keep the car on the road and headed toward its destination. This metaphor differs in a fundamental way from the usual notion of predicting geomorphic change, because it involves a goal—to reach a desired

  4. Medications and impaired driving.

    Science.gov (United States)

    Hetland, Amanda; Carr, David B

    2014-04-01

    To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on classes of medications associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Only English-language articles that contained findings from observational or interventional designs with ≥ 10 participants were included in this review. Cross-sectional studies, case series, and case reports were excluded. Driving is an important task and activity for the majority of adults. Some commonly prescribed medications have been associated with driving impairment measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, hypnotics, antidepressants, opioid and nonsteroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies of medication impact on sedation, sleep latency, and psychomotor function, as well as the role of alcohol, are also discussed. Psychotropic agents and those with central nervous system side effects were associated with measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific classes of medications, educate their patients, and/or consider safer alternatives.

  5. Universal Drive Train Facility

    Data.gov (United States)

    Federal Laboratory Consortium — This vehicle drive train research facility is capable of evaluating helicopter and ground vehicle power transmission technologies in a system level environment. The...

  6. Radiolysis of DNA-protein complexes

    Energy Technology Data Exchange (ETDEWEB)

    Begusova, Marie [Department of Radiation Dosimetry, Nuclear Physics Institute, Na Truhlarce 39/64, CZ-18086, Prague 8 (Czech Republic)]. E-mail: begusova@ujf.cas.cz; Gillard, Nathalie [Centre de Biophysique Moleculaire, CNRS, rue Charles-Sadron, F-45071 Orleans Cedex 2 (France); Sy, Denise [Centre de Biophysique Moleculaire, CNRS, rue Charles-Sadron, F-45071 Orleans Cedex 2 (France); Castaing, Bertrand [Centre de Biophysique Moleculaire, CNRS, rue Charles-Sadron, F-45071 Orleans Cedex 2 (France); Charlier, Michel [Centre de Biophysique Moleculaire, CNRS, rue Charles-Sadron, F-45071 Orleans Cedex 2 (France); Spotheim-Maurizot, Melanie [Centre de Biophysique Moleculaire, CNRS, rue Charles-Sadron, F-45071 Orleans Cedex 2 (France)

    2005-02-01

    We discuss here modifications of DNA and protein radiolysis due to the interaction of these two partners in specific complexes. Experimental patterns of frank strand breaks (FSB) and alkali revealed breaks (ARB) obtained for DNA lac operator bound to the lac repressor and for a DNA containing an abasic site analog bound to the formamidopyrimidine-DNA glycosylase are reported. Experimental data are compared to predicted damage distribution obtained using the theoretical model RADACK.

  7. Radiolysis of DNA-protein complexes

    International Nuclear Information System (INIS)

    Begusova, Marie; Gillard, Nathalie; Sy, Denise; Castaing, Bertrand; Charlier, Michel; Spotheim-Maurizot, Melanie

    2005-01-01

    We discuss here modifications of DNA and protein radiolysis due to the interaction of these two partners in specific complexes. Experimental patterns of frank strand breaks (FSB) and alkali revealed breaks (ARB) obtained for DNA lac operator bound to the lac repressor and for a DNA containing an abasic site analog bound to the formamidopyrimidine-DNA glycosylase are reported. Experimental data are compared to predicted damage distribution obtained using the theoretical model RADACK

  8. Whole genome DNA methylation: beyond genes silencing

    OpenAIRE

    Tirado-Magallanes, Roberto; Rebbani, Khadija; Lim, Ricky; Pradhan, Sriharsa; Benoukraf, Touati

    2016-01-01

    The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation at near base pair level resolution, far beyond that of the kilobase-long canonical CpG islands that initially revealed the biological relevance of this covalent DNA modification. The latest high-resolution studies have revealed a role for very punctual DNA methylation in chromatin plasticity, gene regulation and splicing. Here, we aim to outline the ...

  9. Rad52 SUMOylation affects the efficiency of the DNA repair

    DEFF Research Database (Denmark)

    Altmannova, Veronika; Eckert-Boulet, Nadine; Arneric, Milica

    2010-01-01

    Homologous recombination (HR) plays a vital role in DNA metabolic processes including meiosis, DNA repair, DNA replication and rDNA homeostasis. HR defects can lead to pathological outcomes, including genetic diseases and cancer. Recent studies suggest that the post-translational modification by ...

  10. A Review of Research on Driving Styles and Road Safety.

    Science.gov (United States)

    Sagberg, Fridulv; Selpi; Piccinini, Giulio Francesco Bianchi; Engström, Johan

    2015-11-01

    The aim of this study was to outline a conceptual framework for understanding driving style and, on this basis, review the state-of-the-art research on driving styles in relation to road safety. Previous research has indicated a relationship between the driving styles adopted by drivers and their crash involvement. However, a comprehensive literature review of driving style research is lacking. A systematic literature search was conducted, including empirical, theoretical, and methodological research, on driving styles related to road safety. A conceptual framework was proposed whereby driving styles are viewed in terms of driving habits established as a result of individual dispositions as well as social norms and cultural values. Moreover, a general scheme for categorizing and operationalizing driving styles was suggested. On this basis, existing literature on driving styles and indicators was reviewed. Links between driving styles and road safety were identified and individual and sociocultural factors influencing driving style were reviewed. Existing studies have addressed a wide variety of driving styles, and there is an acute need for a unifying conceptual framework in order to synthesize these results and make useful generalizations. There is a considerable potential for increasing road safety by means of behavior modification. Naturalistic driving observations represent particularly promising approaches to future research on driving styles. Knowledge about driving styles can be applied in programs for modifying driver behavior and in the context of usage-based insurance. It may also be used as a means for driver identification and for the development of driver assistance systems. © 2015, Human Factors and Ergonomics Society.

  11. Piezoelectric drive circuit

    Science.gov (United States)

    Treu, C.A. Jr.

    1999-08-31

    A piezoelectric motor drive circuit is provided which utilizes the piezoelectric elements as oscillators and a Meacham half-bridge approach to develop feedback from the motor ground circuit to produce a signal to drive amplifiers to power the motor. The circuit automatically compensates for shifts in harmonic frequency of the piezoelectric elements due to pressure and temperature changes. 7 figs.

  12. Wrong-way driving.

    NARCIS (Netherlands)

    2006-01-01

    Wrong-way driving is a phenomenon that mainly happens on motorways. Although the number of wrong-way crashes is relatively limited, their consequences are much more severe than the consequences of other motorway injury crashes. The groups most often causing wrong-way driving accidents are young,

  13. Recognizing driving in haste

    NARCIS (Netherlands)

    Rendón-Vélez, E.

    2014-01-01

    One can often hear people discussing the reasons why a road accident has happened: “She had to pick up her kids in the school before four o’clock and she was driving in haste and careless”, “He was stressed, he wanted to reach the beginning of the football match, tried to drive faster and didn't

  14. Control rod drives

    International Nuclear Information System (INIS)

    Futatsugi, Masao.

    1980-01-01

    Purpose: To secure the reactor operation safety by the provision of a fluid pressure detecting section for control rod driving fluid and a control rod interlock at the midway of the flow pass for supplying driving fluid to the control rod drives. Constitution: Between a driving line and a direction control valve are provided a pressure detecting portion, an alarm generating device, and a control rod inhibition interlock. The driving fluid from a driving fluid source is discharged by way of a pump and a manual valve into the reactor in which the control rods and reactor fuels are contained. In addition, when the direction control valve is switched and the control rods are inserted and extracted by the control rod drives, the pressure in the driving line is always detected by the pressure detection section, whereby if abnormal pressure is resulted, the alarm generating device is actuated to warn the abnormality and the control rod inhibition interlock is actuated to lock the direction control valve thereby secure the safety operation of the reactor. (Seki, T.)

  15. Switched reluctance motor drives

    Indian Academy of Sciences (India)

    Davis RM, Ray WF, Blake RJ 1981 Inverter drive for switched reluctance: circuits and component ratings. Inst. Elec. Eng. Proc. B128: 126-136. Ehsani M. 1991 Position Sensor elimination technique for the switched reluctance motor drive. US Patent No. 5,072,166. Ehsani M, Ramani K R 1993 Direct control strategies based ...

  16. Self-driving carsickness

    NARCIS (Netherlands)

    Diels, C.; Bos, J.E.

    2016-01-01

    This paper discusses the predicted increase in the occurrence and severity of motion sickness in self-driving cars. Self-driving cars have the potential to lead to significant benefits. From the driver's perspective, the direct benefits of this technology are considered increased comfort and

  17. Self-driving carsickness.

    NARCIS (Netherlands)

    Diels, C.; Bos, J.E.

    2016-01-01

    This paper discusses the predicted increase in the occurrence and severity of motion sickness in self-driving cars. Self-driving cars have the potential to lead to significant benefits. From the driver's perspective, the direct benefits of this technology are considered increased comfort and

  18. Fundamentals of electrical drives

    CERN Document Server

    Veltman, André; De Doncker, Rik W

    2007-01-01

    Provides a comprehensive introduction to various aspects of electrical drive systems. This volume provides a presentation of dynamic generic models that cover all major electrical machine types and modulation/control components of a drive as well as dynamic and steady state analysis of transformers and electrical machines.

  19. Electric Vehicle - Economical driving

    DEFF Research Database (Denmark)

    Jensen, VCE, Steen V.; Schøn, Henriette

    1999-01-01

    How do you reduce the energy-wast when driving and loading EV's - or rather: How do I get more km/l out of an EV......How do you reduce the energy-wast when driving and loading EV's - or rather: How do I get more km/l out of an EV...

  20. Fleet DNA (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Walkokwicz, K.; Duran, A.

    2014-06-01

    The Fleet DNA project objectives include capturing and quantifying drive cycle and technology variation for the multitude of medium- and heavy-duty vocations; providing a common data storage warehouse for medium- and heavy-duty vehicle fleet data across DOE activities and laboratories; and integrating existing DOE tools, models, and analyses to provide data-driven decision making capabilities. Fleet DNA advantages include: for Government - providing in-use data for standard drive cycle development, R&D, tech targets, and rule making; for OEMs - real-world usage datasets provide concrete examples of customer use profiles; for fleets - vocational datasets help illustrate how to maximize return on technology investments; for Funding Agencies - ways are revealed to optimize the impact of financial incentive offers; and for researchers -a data source is provided for modeling and simulation.

  1. Control rod drives

    International Nuclear Information System (INIS)

    Nakamura, Akira.

    1984-01-01

    Purpose: To enable to monitor the coupling state between a control rod and a control rod drive. Constitution: After the completion of a control rod withdrawal, a coolant pressure is applied to a control rod drive being adjusted so as to raise only the control rod drive and, in a case where the coupling between the control rod drive and the control rod is detached, the former is elevated till it contacts the control rod and then stopped. The actual stopping position is detected by an actual position detection circuit and compared with a predetermined position stored in a predetermined position detection circuit. If both of the positions are not aligned with each other, it is judged by a judging circuit that the control rod and the control rod drives are not combined. (Sekiya, K.)

  2. Permit application modifications

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils.

  3. The management of modifications

    International Nuclear Information System (INIS)

    Bernard, C.

    1992-01-01

    Description of the management methods of modifications at EDF. To maintain safety standards of the nuclear power station the 'Direction de l'Equipment' and the 'Direction du Parc en Exploitation' have jointly fixed the modalities of management for all modifications and recorded them in a 'Practical Guide'

  4. Permit application modifications

    International Nuclear Information System (INIS)

    1995-11-01

    This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils

  5. Repair-modification of radiodamaged genes

    International Nuclear Information System (INIS)

    Volpe, P.; Institute of Experimental Medicine, Rome; Eremenko, T.

    1995-01-01

    It is proposed that through repair-modification, the modified base 5mC may have facilitated the divergent evolution of coding (hypomethylated exon) and uncoding (hypermethylated promoter and intron) sequences in eukaryotic genes. The radioinduced repair patches appearing in regions lacking 5mC are fully reconstructed by excision-repair, whereas those appearing in regions containing 5mC are incompletely reconstructed by this conventional mechanism. Such a second class of repair patches may, however, become fully reconstructed, in the S phase, by repair-modification. In fact, while DNA polymerase β - which is a key enzyme of excision-repair - is active through the whole interphase. DNA methylase - which is responsible for post-synthetic DNA modification - is essentially active in S. Uncoupling of these two enzyme systems, outside S, might explain why in unsynchronised cells repair patches of non-replicating strands are hypomethylated when compared with specific methylation of replicating strands. In other words, excision-repair would always be able to re-establish the primary ATGC language of both damaged unmethylated and methylated regions, while repair-modification would be able to re-establish the modified ATGC(5mC) language of the damaged methylated regions, only in S, but not in G 1 or G 2 . In these two phases, when DNA methylation is inversely correlated with pre-mRNA transcription (as in the case of many tissue-specific genes), such demethylation might induce a silent transcriptional unit to become active. (Author)

  6. Identification and Interrogation of Combinatorial Histone Modifications

    Directory of Open Access Journals (Sweden)

    Kelly R Karch

    2013-12-01

    Full Text Available Histone proteins are dynamically modified to mediate a variety of cellular processes including gene transcription, DNA damage repair, and apoptosis. Regulation of these processes occurs through the recruitment of non-histone proteins to chromatin by specific combinations of histone post-translational modifications (PTMs. Mass spectrometry has emerged as an essential tool to discover and quantify histone PTMs both within and between samples in an unbiased manner. Developments in mass spectrometry that allow for characterization of large histone peptides or intact protein has made it possible to determine which modifications occur simultaneously on a single histone polypeptide. A variety of techniques from biochemistry, biophysics, and chemical biology have been employed to determine the biological relevance of discovered combinatorial codes. This review first describes advancements in the field of mass spectrometry that have facilitated histone PTM analysis and then covers notable approaches to probe the biological relevance of these modifications in their nucleosomal context.

  7. Electroactive crown ester-Cu2+ complex with in-situ modification at molecular beacon probe serving as a facile electrochemical DNA biosensor for the detection of CaMV 35s.

    Science.gov (United States)

    Zhan, Fengping; Liao, Xiaolei; Gao, Feng; Qiu, Weiwei; Wang, Qingxiang

    2017-06-15

    A novel electrochemical DNA biosensor has been facilely constructed by in-situ assembly of electroactive 4'-aminobenzo-18-crown-6-copper(II) complex (AbC-Cu 2+ ) on the free terminal of the hairpin-structured molecule beacon. The 3'-SH modified molecule beacon probe was first immobilized on the gold electrode (AuE) surface through self-assembly chemistry of Au-S bond. Then the crow ester of AbC was covalently coupled with 5'-COOH on the molecule beacon, and served as a platform to attach the Cu 2+ by coordination with ether bond (-O-) of the crown cycle. Thus, an electroactive molecule beacon-based biosensing interface was constructed. In comparison with conventional methods for preparation of electroactive molecule beacon, the approach presented in this work is much simpler, reagent- and labor-saving. Selectivity study shows that the in-situ fabricated electroactive molecule beacon remains excellent recognition ability of pristine molecule beacon probe to well differentiate various DNA fragments. The target DNA can be quantatively determined over the range from 0.10pM to 0.50nM. The detection limit of 0.060pM was estimated based on signal-to-noise ratio of 3. When the biosensor was applied for the detection cauliflower mosaic virus 35s (CaMV 35s) in soybean extraction samples, satisfactory results are achieved. This work opens a new strategy for facilely fabricating electrochemical sensing interface, which also shows great potential in aptasensor and immurosensor fabrication. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Mitochondrial DNA: A Blind Spot in Neuroepigenetics

    OpenAIRE

    Manev, Hari; Dzitoyeva, Svetlana; Chen, Hu

    2012-01-01

    Neuroepigenetics, which includes nuclear DNA modifications such as 5-methylcytosine and 5-hydoxymethylcytosine and modifications of nuclear proteins such as histones, is emerging as the leading field in molecular neuroscience. Historically, a functional role for epigenetic mechanisms, including in neuroepigenetics, has been sought in the area of the regulation of nuclear transcription. However, one important compartment of mammalian cell DNA, different from nuclear but equally important for p...

  9. Turbulent current drive mechanisms

    Science.gov (United States)

    McDevitt, Christopher J.; Tang, Xian-Zhu; Guo, Zehua

    2017-08-01

    Mechanisms through which plasma microturbulence can drive a mean electron plasma current are derived. The efficiency through which these turbulent contributions can drive deviations from neoclassical predictions of the electron current profile is computed by employing a linearized Coulomb collision operator. It is found that a non-diffusive contribution to the electron momentum flux as well as an anomalous electron-ion momentum exchange term provide the most efficient means through which turbulence can modify the mean electron current for the cases considered. Such turbulent contributions appear as an effective EMF within Ohm's law and hence provide an ideal means for driving deviations from neoclassical predictions.

  10. Fast wave current drive

    International Nuclear Information System (INIS)

    Goree, J.; Ono, M.; Colestock, P.; Horton, R.; McNeill, D.; Park, H.

    1985-07-01

    Fast wave current drive is demonstrated in the Princeton ACT-I toroidal device. The fast Alfven wave, in the range of high ion-cyclotron harmonics, produced 40 A of current from 1 kW of rf power coupled into the plasma by fast wave loop antenna. This wave excites a steady current by damping on the energetic tail of the electron distribution function in the same way as lower-hybrid current drive, except that fast wave current drive is appropriate for higher plasma densities

  11. Identifying Method of Drunk Driving Based on Driving Behavior

    Directory of Open Access Journals (Sweden)

    Xiaohua Zhao

    2011-05-01

    Full Text Available Drunk driving is one of the leading causes contributing to traffic crashes. There are numerous issues that need to be resolved with the current method of identifying drunk driving. Driving behavior, with the characteristic of real-time, was extensively researched to identify impaired driving behaviors. In this paper, the drives with BACs above 0.05% were defined as drunk driving state. A detailed comparison was made between normal driving and drunk driving. The experiment in driving simulator was designed to collect the driving performance data of the groups. According to the characteristics analysis for the effect of alcohol on driving performance, seven significant indicators were extracted and the drunk driving was identified by the Fisher Discriminant Method. The discriminant function demonstrated a high accuracy of classification. The optimal critical score to differentiate normal from drinking state was found to be 0. The evaluation result verifies the accuracy of classification method.

  12. Modifications to POISSON

    International Nuclear Information System (INIS)

    Harwood, L.H.

    1981-01-01

    At MSU we have used the POISSON family of programs extensively for magnetic field calculations. In the presently super-saturated computer situation, reducing the run time for the program is imperative. Thus, a series of modifications have been made to POISSON to speed up convergence. Two of the modifications aim at having the first guess solution as close as possible to the final solution. The other two aim at increasing the convergence rate. In this discussion, a working knowledge of POISSON is assumed. The amount of new code and expected time saving for each modification is discussed

  13. Linear step drive

    International Nuclear Information System (INIS)

    Haniger, L.; Elger, R.; Kocandrle, L.; Zdebor, J.

    1986-01-01

    A linear step drive is described developed in Czechoslovak-Soviet cooperation and intended for driving WWER-1000 control rods. The functional principle is explained of the motor and the mechanical and electrical parts of the drive, power control, and the indicator of position are described. The motor has latches situated in the reactor at a distance of 3 m from magnetic armatures, it has a low structural height above the reactor cover, which suggests its suitability for seismic localities. Its magnetic circuits use counterpoles; the mechanical shocks at the completion of each step are damped using special design features. The position indicator is of a special design and evaluates motor position within ±1% of total travel. A drive diagram and the flow chart of both the control electronics and the position indicator are presented. (author) 4 figs

  14. Fundamentals of electrical drives

    NARCIS (Netherlands)

    Veltman, A.; Pulle, D.W.J.; de Doncker, R.W.

    2016-01-01

    Comprehensive, user-friendly, color illustrated introductory text for electrical drive systems that simplifies the understanding of electrical machine principles Updated edition covers innovations in machine design, power semi-conductors, digital signal processors and simulation software Presents

  15. Science of driving.

    Science.gov (United States)

    2016-08-01

    The Science of Driving project focused on developing a collaborative relationship to develop curriculum units for middle school and high school students to engage them in exciting real-world scenarios. This effort involved faculty, staff, and student...

  16. Drugs and driving

    NARCIS (Netherlands)

    Walsh, J. Michael; De Gier, Johan J.; Christopherson, Asbjørg S.; Verstraete, Alain G.

    The authors present a global overview on the issue of drugs and driving covering four major areas: (1) Epidemiology and Prevalence-which reviews epidemiological research, summarizes available information, discusses the methodological shortcomings of extant studies, and makes recommendations for

  17. Instant Google Drive starter

    CERN Document Server

    Procopio, Mike

    2013-01-01

    This book is a Starter which teaches you how to use Google Drive practically. This book is perfect for people of all skill levels who want to enjoy the benefits of using Google Drive to safely store their files online and in the cloud. It's also great for anyone looking to learn more about cloud computing in general. Readers are expected to have an Internet connection and basic knowledge of using the internet.

  18. Control rod driving mechanism

    International Nuclear Information System (INIS)

    Ooshima, Yoshio.

    1983-01-01

    Purpose: To perform reliable scram operation, even if abnormality should occur in a system instructing scram operation in FBR type reactors. Constitution: An aluminum alloy member to be melt at a predetermined temperature (about 600sup(o)C) is disposed to a connection part between a control rod and a driving mechanism, whereby the control rod is detached from the driving mechanism and gravitationally fallen to the reactor core. (Ikeda, J.)

  19. Modulated Current Drive Measurements

    International Nuclear Information System (INIS)

    Petty, C.C.; Lohr, J.; Luce, T.C.; Prater, R.; Cox, W.A.; Forest, C.B.; Jayakumar, R.J.; Makowski, M.A.

    2005-01-01

    A new measurement approach is presented which directly determines the noninductive current profile from the periodic response of the motional Stark effect (MSE) signals to the slow modulation of the external current drive source. A Fourier transform of the poloidal magnetic flux diffusion equation is used to analyze the MSE data. An example of this measurement technique is shown using modulated electron cyclotron current drive (ECCD) discharges from the DIII-D tokamak

  20. Belt drive construction improvement

    Directory of Open Access Journals (Sweden)

    I.Yu. Khomenko

    2012-08-01

    Full Text Available The possibility of the traction capacity increase of the belt drive TRK is examined. This was done for the purpose of air conditioning system of passenger car with double-generator system energy supplying. Belts XPC (made by the German firm «Continental ContiTech» testing were conducted. The results confirmed the possibility of their usage in order to improve belt drive TRK characteristics.

  1. DNA methylation in obesity

    Directory of Open Access Journals (Sweden)

    Małgorzata Pokrywka

    2014-11-01

    Full Text Available The number of overweight and obese people is increasing at an alarming rate, especially in the developed and developing countries. Obesity is a major risk factor for diabetes, cardiovascular disease, and cancer, and in consequence for premature death. The development of obesity results from the interplay of both genetic and environmental factors, which include sedentary life style and abnormal eating habits. In the past few years a number of events accompanying obesity, affecting expression of genes which are not directly connected with the DNA base sequence (e.g. epigenetic changes, have been described. Epigenetic processes include DNA methylation, histone modifications such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, as well as non-coding micro-RNA (miRNA synthesis. In this review, the known changes in the profile of DNA methylation as a factor affecting obesity and its complications are described.

  2. Introduction to DNA methods

    International Nuclear Information System (INIS)

    Delincee, H.

    1991-01-01

    The purpose of this session is to discuss the various possibilities for detecting modifications in DNA after irradiation and whether these changes can be utilized as an indicator for the irradiation treatment of foods. The requirement to be fulfilled is that the method be able to distinguish irradiated food without the presence of a control sample, thus the measured response after irradiation must be large enough to supersede background levels from other treatments. Much work has been performed on the effects of radiation on DNA, particularly due to its importance in radiation biology. The main lesions of DNA as a result of irradiation are base damage, damage of the sugar moiety, single strand and double strand breaks. Crosslinking between bases also occurs, e.g. production of thymine dimers, or between DNA and protein. A valuable review on how to utilize these DNA changes for detection purposes has already appeared. Tables 1, 2 and 3 list the proposed methods of detecting changes in irradiated DNA, some identified products as examples for a possible irradiation indicator, in the case of immunoassay the substance used as antigen, and some selected literature references. In this short review, it is not intended to provide a complete literature survey

  3. Self-driving carsickness.

    Science.gov (United States)

    Diels, Cyriel; Bos, Jelte E

    2016-03-01

    This paper discusses the predicted increase in the occurrence and severity of motion sickness in self-driving cars. Self-driving cars have the potential to lead to significant benefits. From the driver's perspective, the direct benefits of this technology are considered increased comfort and productivity. However, we here show that the envisaged scenarios all lead to an increased risk of motion sickness. As such, the benefits this technology is assumed to bring may not be capitalised on, in particular by those already susceptible to motion sickness. This can negatively affect user acceptance and uptake and, in turn, limit the potential socioeconomic benefits that this emerging technology may provide. Following a discussion on the causes of motion sickness in the context of self-driving cars, we present guidelines to steer the design and development of automated vehicle technologies. The aim is to limit or avoid the impact of motion sickness and ultimately promote the uptake of self-driving cars. Attention is also given to less well known consequences of motion sickness, in particular negative aftereffects such as postural instability, and detrimental effects on task performance and how this may impact the use and design of self-driving cars. We conclude that basic perceptual mechanisms need to be considered in the design process whereby self-driving cars cannot simply be thought of as living rooms, offices, or entertainment venues on wheels. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  4. Dementia and driving.

    Science.gov (United States)

    O'Neill, D; Neubauer, K; Boyle, M; Gerrard, J; Surmon, D; Wilcock, G K

    1992-04-01

    Many European countries test cars, but not their drivers, as they age. There is evidence to suggest that human factors are more important than vehicular factors as causes of motor crashes. The elderly also are involved in more accidents per distance travelled than middle-aged drivers. As the UK relies on self-certification of health by drivers over the age of 70 years, we examined the driving practices of patients with dementia attending a Memory Clinic. Nearly one-fifth of 329 patients with documented dementia continued to drive after the onset of dementia, and impaired driving ability was noted in two-thirds of these. Their families experienced great difficulty in persuading patients to stop driving, and had to invoke outside help in many cases. Neuropsychological tests did not help to identify those who drove badly while activity of daily living scores were related to driving ability. These findings suggest that many patients with dementia drive in an unsafe fashion after the onset of the illness. The present system of self-certification of health by the elderly for driver-licensing purposes needs to be reassessed.

  5. Accommodating for plant modifications

    International Nuclear Information System (INIS)

    Weirich, P.H.

    1977-01-01

    Modification to a nuclear power plant may have different causes: 1) new instructions by the authorities; 2) changes of the marginal conditions on the construction site; 3) progress in the technological development. - Examples from different plants are supposed to demonstrate how such changes influence the planning or the construction and how they are integrated in the process of preparation. A distinction can be made between modifications before the completion of the submission of the order, during the phase of preparatory planning and during the construction phase. Of great importance are especially modifications made after the beginning of the construction works, since, in general, there is little scope for technical modifications and since consequences for the time schedule are to be expected. (orig.) [de

  6. Structural dynamic modification

    Indian Academy of Sciences (India)

    and stiffness matrices) andaor modal parameters, in order to acquire some ... For the above reasons, another modification approach is presented here ... The data necessary to solve the direct problem are dynamic behaviour of the original.

  7. Pragmatic Graph Rewriting Modifications

    OpenAIRE

    Rodgers, Peter; Vidal, Natalia

    1999-01-01

    We present new pragmatic constructs for easing programming in visual graph rewriting programming languages. The first is a modification to the rewriting process for nodes the host graph, where nodes specified as 'Once Only' in the LHS of a rewrite match at most once with a corresponding node in the host graph. This reduces the previously common use of tags to indicate the progress of matching in the graph. The second modification controls the application of LHS graphs, where those specified a...

  8. Modification of JRR-2

    International Nuclear Information System (INIS)

    Miyasaka, Yasuhiko

    1978-01-01

    This report gives an outline of some of the main modifications carried out around the Reactor Core on the Research Reactor JRR-2, at the Tokai Research Establishment of JAERI. The JRR-2 was shut down in December 1973, to improve it in heavy water leakage from the metal packing between core tank and support ring, corrosion of the lower shielding plug, and fault in the control-rod mechanism. Main modifications were a standing seal weld at the support ring to stop heavy water leakage, replacement of the reactor top shield and improvement of the helium system. The control-rod assemblies and the refueling devices were replaced by the newly designed ones also. In addition to the modification plan, the irradiated air exhaust system was improved to reduce radioactive argon gas release through the stack. Works were completed successfully in September 1975. But a light water leakage occurred at the stand pipe below the light water tank on November 11, 1975, which was repaired in about 4 months. When considering the operation of above 5,000 hours after the modification, however, the quality of the modification work may be said to be quite satisfactory. The present report in which works to the completion are described may be valuable as a record of reactor modification which is a new experience at JAERI. (auth.)

  9. IBM PC based automatic drive system for Bulat setup

    International Nuclear Information System (INIS)

    Luchaninov, A.A.; Tolok, V.T.

    1999-01-01

    Non-expensive computer drive system for Bulat setup is described. System's hardware consists of IBM PC and conjunction block, providing 12 output channels, Software includes the main program, utilities and technology processes database. System may be used at surface modification processes, especially multilayer multicomponent coatings deposition

  10. Human Rights and Behavior Modification

    Science.gov (United States)

    Roos, Philip

    1974-01-01

    Criticisms of behavior modification, which charge that it violates ethical and legal principles, are discussed and reasons are presented to explain behavior modification's susceptibility to attack. (GW)

  11. Interplay of Inflammatory Mediators with Epigenetics and Cartilage Modifications in Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Swarna Raman

    2018-03-01

    Full Text Available Osteoarthritis (OA, a degenerative disease of diarthrodial joints, is influenced by mechanical and inflammatory factors with aging, obesity, chronic injuries, and secondary diseases thought to be major factors driving the process of articular cartilage degeneration. Chondrocytes, the cellular component of cartilage, reside in an avascular environment and normally have limited potential to replicate. However, extrinsic factors such as injury to the joint or intrinsic alterations to the chondrocytes themselves can lead to an altered phenotype and development of OA. Synovial inflammation is also a pivotal element of the osteoarthritic, degenerative process: influx of pro-inflammatory cytokines and production of matrix metalloproteinases accelerate advanced cellular processes such as synovitis and cartilage damage. As well as a genetic input, recent data have highlighted epigenetic factors as contributing to disease. Studies conducted over the last decade have focused on three key aspects in OA; inflammation and the immune response, genome-wide association studies that have identified important genes undergoing epigenetic modifications, and finally how chondrocytes transform in their function during development and disease. Data highlighted here have identified critical inflammatory genes involved in OA and how these factors impact chondrocyte hypertrophy in the disease. This review also addresses key inflammatory factors in synovial inflammation, epigenetics, and chondrocyte fate, and how agents that inhibit epigenetic mechanisms like DNA methylation and histone modifications could aid in development of long-term treatment strategies for the disease.

  12. Control rod drive

    International Nuclear Information System (INIS)

    Hawke, B.C.

    1986-01-01

    A reactor core, one or more control rods, and a control rod drive are described for selectively inserting and withdrawing the one or more control rods into and from the reactor core, which consists of: a support structure secured beneath the reactor core; control rod positioning means supported by the support structure for movably supporting the control rod for movement between a lower position wherein the control rod is located substantially beneath the reactor core and an upper position wherein at least an upper portion of the control rod extends into the reactor core; transmission means; primary drive means connected with the control rod positioning means by the transmission means for positioning the control rod under normal operating conditions; emergency drive means for moving the control rod from the lower position to the upper position under emergency conditions, the emergency drive means including a weight movable between an upper and a lower position, means for movably supporting the weight, and means for transmitting gravitational force exerted on the weight to the control rod positioning means to move the control rod upwardly when the weight is pulled downwardly by gravity; the transmission means connecting the control rod positioning means with the emergency drive means so that the primary drive means effects movement of the weight and the control rod in opposite directions under normal conditions, thus providing counterbalancing to reduce the force required for upward movement of the control rod under normal conditions; and restraint means for restraining the fall of the weight under normal operating conditions and disengaging the primary drive means to release the weight under emergency conditions

  13. Control rod drives

    International Nuclear Information System (INIS)

    Hayakawa, Hiroyasu.

    1979-01-01

    Purpose: To enable rapid control in a simple circuit by providing a motor control device having an electric capacity capable of simultaneously driving all of the control rods rapidly only in the inserting direction as well as a motor controlling device capable of fine control for the insertion and extraction at usual operation. Constitution: The control rod drives comprise a first motor control device capable of finely controlling the control rods both in inserting and extracting directions, a second motor control device capable of rapidly driving the control rods only in the inserting direction, and a first motor switching circuit and a second motor switching circuit switched by switches. Upon issue of a rapid insertion instruction for the control rods, the second motor switching circuit is closed by the switch and the second motor control circuit and driving motors are connected. Thus, each of the control rod driving motors is driven at a high speed in the inserting direction to rapidly insert all of the control rods. (Yoshino, Y.)

  14. Epilepsy and driving

    Directory of Open Access Journals (Sweden)

    Matej Mavrič

    2015-05-01

    Full Text Available Epilepsy poses a risk for all participants in road traffic; therefore people with epilepsy do not meet the criteria for an unlimited driving license. Their driving is affected not only by epileptic seizures causing impaired consciousness and involuntary movements, but also by antiepileptic drugs with their many unwanted affects. The experts have not yet agreed on whether people with epilepsy have an increased risk of experiencing a road traffic accident. However, recent data suggests that the overall risk is lower compared to other medical conditions. Scientific evidence forms the basis of legislation, which by limiting people with epilepsy, enables all participants in road traffic to drive in the safest possible environment. The legislation that governs epilepsy and driving in Slovenia has been recently thoroughly reformed and thus allows a less discriminatory management of people with epilepsy. Although people with epilepsy experience many issues in their daily life, including their personal relationships and employment, they often list the need for driving as a top concern in surveys. General physicians play an important role in managing the issues of people with epilepsy.

  15. Self-rated Driving and Driving Safety in Older Adults

    OpenAIRE

    Ross, Lesley A.; Dodson, Joan; Edwards, Jerri D.; Ackerman, Michelle L.; Ball, Karlene

    2012-01-01

    Many U.S. states rely on older adults to self-regulate their driving and determine when driving is no longer a safe option. However, the relationship of older adults’ self-rated driving in terms of actual driving competency outcomes is unclear. The current study investigates self-rated driving in terms of (1) systematic differences between older adults with high (good/excellent) versus low (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated driving to adverse driving...

  16. Ultrasonic Recovery and Modification of Food Ingredients

    Science.gov (United States)

    Vilkhu, Kamaljit; Manasseh, Richard; Mawson, Raymond; Ashokkumar, Muthupandian

    There are two general classes of effects that sound, and ultrasound in particular, can have on a fluid. First, very significant modifications to the nature of food and food ingredients can be due to the phenomena of bubble acoustics and cavitation. The applied sound oscillates bubbles in the fluid, creating intense forces at microscopic scales thus driving chemical changes. Second, the sound itself can cause the fluid to flow vigorously, both on a large scale and on a microscopic scale; furthermore, the sound can cause particles in the fluid to move relative to the fluid. These streaming phenomena can redistribute materials within food and food ingredients at both microscopic and macroscopic scales.

  17. Management of scientific information with Google Drive.

    Science.gov (United States)

    Kubaszewski, Łukasz; Kaczmarczyk, Jacek; Nowakowski, Andrzej

    2013-09-20

    The amount and diversity of scientific publications requires a modern management system. By "management" we mean the process of gathering interesting information for the purpose of reading and archiving for quick access in future clinical practice and research activity. In the past, such system required physical existence of a library, either institutional or private. Nowadays in an era dominated by electronic information, it is natural to migrate entire systems to a digital form. In the following paper we describe the structure and functions of an individual electronic library system (IELiS) for the management of scientific publications based on the Google Drive service. Architecture of the system. Architecture system consists of a central element and peripheral devices. Central element of the system is virtual Google Drive provided by Google Inc. Physical elements of the system include: tablet with Android operating system and a personal computer, both with internet access. Required software includes a program to view and edit files in PDF format for mobile devices and another to synchronize the files. Functioning of the system. The first step in creating a system is collection of scientific papers in PDF format and their analysis. This step is performed most frequently on a tablet. At this stage, after being read, the papers are cataloged in a system of folders and subfolders, according to individual demands. During this stage, but not exclusively, the PDF files are annotated by the reader. This allows the user to quickly track down interesting information in review or research process. Modification of the document title is performed at this stage, as well. Second element of the system is creation of a mirror database in the Google Drive virtual memory. Modified and cataloged papers are synchronized with Google Drive. At this stage, a fully functional scientific information electronic library becomes available online. The third element of the system is a

  18. The role of DNA methylation in Obesity and Diabetes

    OpenAIRE

    ISHANT KHURANA

    2018-01-01

    A significant proportion of human disease causality remains unexplained. It is increasingly becoming clear that Epigenetics is a key contributor to many diseases, including cardiovascular diseases, atherosclerosis and diabetes. Epigenetics refers to the external modification to DNA that turn genes “ON” and “OFF”. These modifications do not change the DNA sequence, but instead, they effect cells ability to “read” genes. This thesis investigates the role of DNA methylation in Obesity and Diabet...

  19. Discrete gene replication events drive coupling between the cell cycle and circadian clocks.

    Science.gov (United States)

    Paijmans, Joris; Bosman, Mark; Ten Wolde, Pieter Rein; Lubensky, David K

    2016-04-12

    Many organisms possess both a cell cycle to control DNA replication and a circadian clock to anticipate changes between day and night. In some cases, these two rhythmic systems are known to be coupled by specific, cross-regulatory interactions. Here, we use mathematical modeling to show that, additionally, the cell cycle generically influences circadian clocks in a nonspecific fashion: The regular, discrete jumps in gene-copy number arising from DNA replication during the cell cycle cause a periodic driving of the circadian clock, which can dramatically alter its behavior and impair its function. A clock built on negative transcriptional feedback either phase-locks to the cell cycle, so that the clock period tracks the cell division time, or exhibits erratic behavior. We argue that the cyanobacterium Synechococcus elongatus has evolved two features that protect its clock from such disturbances, both of which are needed to fully insulate it from the cell cycle and give it its observed robustness: a phosphorylation-based protein modification oscillator, together with its accompanying push-pull read-out circuit that responds primarily to the ratios of different phosphoform concentrations, makes the clock less susceptible to perturbations in protein synthesis; the presence of multiple, asynchronously replicating copies of the same chromosome diminishes the effect of replicating any single copy of a gene.

  20. Electronic transport in methylated fragments of DNA

    International Nuclear Information System (INIS)

    Almeida, M. L. de; Oliveira, J. I. N.; Lima Neto, J. X.; Gomes, C. E. M.; Fulco, U. L.; Albuquerque, E. L.; Freire, V. N.; Caetano, E. W. S.; Moura, F. A. B. F. de; Lyra, M. L.

    2015-01-01

    We investigate the electronic transport properties of methylated deoxyribonucleic-acid (DNA) strands, a biological system in which methyl groups are added to DNA (a major epigenetic modification in gene expression), sandwiched between two metallic platinum electrodes. Our theoretical simulations apply an effective Hamiltonian based on a tight-binding model to obtain current-voltage curves related to the non-methylated/methylated DNA strands. The results suggest potential applications in the development of novel biosensors for molecular diagnostics

  1. Electronic transport in methylated fragments of DNA

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, M. L. de; Oliveira, J. I. N.; Lima Neto, J. X.; Gomes, C. E. M.; Fulco, U. L., E-mail: umbertofulco@gmail.com; Albuquerque, E. L. [Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, 59072-970 Natal-RN (Brazil); Freire, V. N. [Departamento de Física, Universidade Federal do Ceará, 60455-760 Fortaleza, CE (Brazil); Caetano, E. W. S. [Instituto Federal de Educação, Ciência e Tecnologia do Ceará, 60040-531 Fortaleza, CE (Brazil); Moura, F. A. B. F. de; Lyra, M. L. [Instituto de Física, Universidade Federal de Alagoas, 57072-900 Maceió-AL (Brazil)

    2015-11-16

    We investigate the electronic transport properties of methylated deoxyribonucleic-acid (DNA) strands, a biological system in which methyl groups are added to DNA (a major epigenetic modification in gene expression), sandwiched between two metallic platinum electrodes. Our theoretical simulations apply an effective Hamiltonian based on a tight-binding model to obtain current-voltage curves related to the non-methylated/methylated DNA strands. The results suggest potential applications in the development of novel biosensors for molecular diagnostics.

  2. DNA methylation in metabolic disorders

    DEFF Research Database (Denmark)

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...... have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

  3. Artificial Intelligence, DNA Mimicry, and Human Health.

    Science.gov (United States)

    Stefano, George B; Kream, Richard M

    2017-08-14

    The molecular evolution of genomic DNA across diverse plant and animal phyla involved dynamic registrations of sequence modifications to maintain existential homeostasis to increasingly complex patterns of environmental stressors. As an essential corollary, driver effects of positive evolutionary pressure are hypothesized to effect concerted modifications of genomic DNA sequences to meet expanded platforms of regulatory controls for successful implementation of advanced physiological requirements. It is also clearly apparent that preservation of updated registries of advantageous modifications of genomic DNA sequences requires coordinate expansion of convergent cellular proofreading/error correction mechanisms that are encoded by reciprocally modified genomic DNA. Computational expansion of operationally defined DNA memory extends to coordinate modification of coding and previously under-emphasized noncoding regions that now appear to represent essential reservoirs of untapped genetic information amenable to evolutionary driven recruitment into the realm of biologically active domains. Additionally, expansion of DNA memory potential via chemical modification and activation of noncoding sequences is targeted to vertical augmentation and integration of an expanded cadre of transcriptional and epigenetic regulatory factors affecting linear coding of protein amino acid sequences within open reading frames.

  4. Reproductive cloning combined with genetic modification.

    Science.gov (United States)

    Strong, C

    2005-11-01

    Although there is widespread opposition to reproductive cloning, some have argued that its use by infertile couples to have genetically related children would be ethically justifiable. Others have suggested that lesbian or gay couples might wish to use cloning to have genetically related children. Most of the main objections to human reproductive cloning are based on the child's lack of unique nuclear DNA. In the future, it may be possible safely to create children using cloning combined with genetic modifications, so that they have unique nuclear DNA. The genetic modifications could be aimed at giving such children genetic characteristics of both members of the couple concerned. Thus, cloning combined with genetic modification could be appealing to infertile, lesbian, or gay couples who seek genetically related children who have genetic characteristics of both members. In such scenarios, the various objections to human reproductive cloning that are based on the lack of genetic uniqueness would no longer be applicable. The author argues that it would be ethically justifiable for such couples to create children in this manner, assuming these techniques could be used safely.

  5. Gears and gear drives

    CERN Document Server

    Jelaska, Damir T

    2012-01-01

    Understanding how gears are formed and how they interact or 'mesh' with each other is essential when designing equipment that uses gears or gear trains. The way in which gear teeth are formed and how they mesh is determined by their geometry and kinematics, which is the topic of this book.  Gears and Gear Drives provides the reader with comprehensive coverage of gears and gear drives. Spur, helical, bevel, worm and planetary gears are all covered, with consideration given to their classification, geometry, kinematics, accuracy control, load capacity and manufacturing. Cylindric

  6. Toyota hybrid synergy drive

    Energy Technology Data Exchange (ETDEWEB)

    Gautschi, H.

    2008-07-01

    This presentation made at the Swiss 2008 research conference on traffic by Hannes Gautschi, director of service and training at the Toyota company in Switzerland, takes a look at Toyota's hybrid drive vehicles. The construction of the vehicles and their combined combustion engines and electric generators and drives is presented and the combined operation of these components is described. Braking and energy recovery are discussed. Figures on the performance, fuel consumption and CO{sub 2} output of the hybrid vehicles are compared with those of conventional vehicles.

  7. Molecular mechanisms of DNA photodamage

    Energy Technology Data Exchange (ETDEWEB)

    Starrs, S.M

    2000-05-01

    Photodamage in DNA, caused by ultraviolet (UV) light, can occur by direct excitation of the nucleobases or indirectly via the action of photosensitisers. Such, DNA photodamage can be potentially mutagenic or lethal. Among the methods available for detecting UV-induced DNA damage, gel sequencing protocols, utilising synthetic oligodeoxyribonucleotides as targets for UV radiation, allow photolesions to be mapped at nucleotide resolution. This approach has been applied to investigate both DNA damage mechanisms. Following a general overview of DNA photoreactivity, and a description of the main experimental procedures, Chapter 3 identifies the origin of an anomalous mobility shift observed in purine chemical sequence ladders that can confuse the interpretation of DNA cleavage results; measures to abolish this shift are also described. Chapters 4 and 5 examine the alkali-labile DNA damage photosensitised by representative nonsteroidal antiinflammatory drugs (NSAIDs) and the fluoroquinolone antibiotics. Suprofen was the most photoactive NSAID studied, producing different patterns of guanine-specific damage in single-stranded and duplex DNA. Uniform modification of guanine bases, typifying attack by singlet oxygen, was observed in single-stranded oligodeoxyribonucleotides. In duplex molecules, modification was limited to the 5'-G of GG doublets, which is indicative of an electron transfer. The effect of quenchers and photoproduct analysis substantiated these findings. The quinolone, nalidixic acid, behaves similarly. The random base cleavage photosensitised by the fluoroquinolones, has been attributed to free radicals produced during their photodecomposition. Chapter 6 addresses the photoreactivity of purines within unusual DNA structures formed by the repeat sequences (GGA){sub n} and (GA){sub n}, and a minihairpin. There was no definitive evidence for enhanced purine reactivity caused by direct excitation. Finally, Chapter 7 investigates the mutagenic potential of a

  8. Molecular mechanisms of DNA photodamage

    International Nuclear Information System (INIS)

    Starrs, S.M.

    2000-05-01

    Photodamage in DNA, caused by ultraviolet (UV) light, can occur by direct excitation of the nucleobases or indirectly via the action of photosensitisers. Such, DNA photodamage can be potentially mutagenic or lethal. Among the methods available for detecting UV-induced DNA damage, gel sequencing protocols, utilising synthetic oligodeoxyribonucleotides as targets for UV radiation, allow photolesions to be mapped at nucleotide resolution. This approach has been applied to investigate both DNA damage mechanisms. Following a general overview of DNA photoreactivity, and a description of the main experimental procedures, Chapter 3 identifies the origin of an anomalous mobility shift observed in purine chemical sequence ladders that can confuse the interpretation of DNA cleavage results; measures to abolish this shift are also described. Chapters 4 and 5 examine the alkali-labile DNA damage photosensitised by representative nonsteroidal antiinflammatory drugs (NSAIDs) and the fluoroquinolone antibiotics. Suprofen was the most photoactive NSAID studied, producing different patterns of guanine-specific damage in single-stranded and duplex DNA. Uniform modification of guanine bases, typifying attack by singlet oxygen, was observed in single-stranded oligodeoxyribonucleotides. In duplex molecules, modification was limited to the 5'-G of GG doublets, which is indicative of an electron transfer. The effect of quenchers and photoproduct analysis substantiated these findings. The quinolone, nalidixic acid, behaves similarly. The random base cleavage photosensitised by the fluoroquinolones, has been attributed to free radicals produced during their photodecomposition. Chapter 6 addresses the photoreactivity of purines within unusual DNA structures formed by the repeat sequences (GGA) n and (GA) n , and a minihairpin. There was no definitive evidence for enhanced purine reactivity caused by direct excitation. Finally, Chapter 7 investigates the mutagenic potential of a dimeric

  9. SET oncoprotein accumulation regulates transcription through DNA demethylation and histone hypoacetylation.

    Science.gov (United States)

    Almeida, Luciana O; Neto, Marinaldo P C; Sousa, Lucas O; Tannous, Maryna A; Curti, Carlos; Leopoldino, Andreia M

    2017-04-18

    Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell carcinoma (HNSCC); SET is a member of the INHAT complex that inhibits gene transcription associating with histones and preventing their acetylation. We explored how SET protein accumulation impacts on the regulation of gene expression, focusing on DNA methylation and histone acetylation. DNA methylation profile of 24 tumour suppressors evidenced that SET accumulation decreased DNA methylation in association with loss of 5-methylcytidine, formation of 5-hydroxymethylcytosine and increased TET1 levels, indicating an active DNA demethylation mechanism. However, the expression of some suppressor genes was lowered in cells with high SET levels, suggesting that loss of methylation is not the main mechanism modulating gene expression. SET accumulation also downregulated the expression of 32 genes of a panel of 84 transcription factors, and SET directly interacted with chromatin at the promoter of the downregulated genes, decreasing histone acetylation. Gene expression analysis after cell treatment with 5-aza-2'-deoxycytidine (5-AZA) and Trichostatin A (TSA) revealed that histone acetylation reversed transcription repression promoted by SET. These results suggest a new function for SET in the regulation of chromatin dynamics. In addition, TSA diminished both SET protein levels and SET capability to bind to gene promoter, suggesting that administration of epigenetic modifier agents could be efficient to reverse SET phenotype in cancer.

  10. Comparing Expert and Novice Driving Behavior in a Driving Simulator

    Directory of Open Access Journals (Sweden)

    Hiran B. Ekanayake

    2014-02-01

    Full Text Available This paper presents a study focused on comparing driving behavior of expert and novice drivers in a mid-range driving simulator with the intention of evaluating the validity of driving simulators for driver training. For the investigation, measurements of performance, psychophysiological measurements, and self-reported user experience under different conditions of driving tracks and driving sessions were analyzed. We calculated correlations between quantitative and qualitative measures to enhance the reliability of the findings. The experiment was conducted involving 14 experienced drivers and 17 novice drivers. The results indicate that driving behaviors of expert and novice drivers differ from each other in several ways but it heavily depends on the characteristics of the task. Moreover, our belief is that the analytical framework proposed in this paper can be used as a tool for selecting appropriate driving tasks as well as for evaluating driving performance in driving simulators.

  11. Modeling DNA

    Science.gov (United States)

    Robertson, Carol

    2016-01-01

    Deoxyribonucleic acid (DNA) is life's most amazing molecule. It carries the genetic instructions that almost every organism needs to develop and reproduce. In the human genome alone, there are some three billion DNA base pairs. The most difficult part of teaching DNA structure, however, may be getting students to visualize something as small as a…

  12. Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Tiziana Angrisano

    Full Text Available Bacterial lipopolysaccharide (LPS induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3, methylation (H3K4, H3K9, H3K27 and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene.

  13. Driving skills after whiplash.

    Science.gov (United States)

    Gimse, R; Bjørgen, I A; Straume, A

    1997-09-01

    Previous studies have shown that some persons with longlasting problems after whiplash have changed eye movements. These changes have been related to disturbance of the posture control system. The question raised in the present study is whether such disturbances can influence daily life functions connected with balance, position and external movements, such as car driving. A group of 23 persons with disturbed eye movements due to whiplash injury, was tested in a driving simulator, together with a closely matched control group. The results revealed significant differences between the two groups with respect to response times to the traffic signs presented, identification of type of sign, as well as steering precision while the subjects' attention was directed to the process of identifying the signs. Alternative explanations such as driving experience, pain, medication or malingering are at least partly controlled for, but cannot completely be ruled out. A distorted posture control system leading to disturbance of eye movements seems to be the most likely primary causative factor, but these disturbances are most certainly complexly determined. Reduced attention capacity is considered to be a mediating secondary factor. Registration of eye movements may be a useful diagnostic tool to evaluate driving skill after whiplash.

  14. Gaze-controlled Driving

    DEFF Research Database (Denmark)

    Tall, Martin; Alapetite, Alexandre; San Agustin, Javier

    2009-01-01

    We investigate if the gaze (point of regard) can control a remote vehicle driving on a racing track. Five different input devices (on-screen buttons, mouse-pointing low-cost webcam eye tracker and two commercial eye tracking systems) provide heading and speed control on the scene view transmitted...

  15. Gas turbine drives

    Energy Technology Data Exchange (ETDEWEB)

    1981-01-01

    Developments in gas turbine drives are reviewed, e.g., low weight per unit power and thrust-weight ratio, fast availability of the maximum speed, absolute resistance to cold and to droplet formation vibrationeless run, and low exhaust gas temperatures. Applications in aeronautic engineering (turbofan), power stations, marine propulsion systems, railways and road transportation vehicles are mentioned.

  16. Chaos in drive systems

    Directory of Open Access Journals (Sweden)

    Kratochvíl C.

    2007-10-01

    Full Text Available The purpose of this article is to provide an elementary introduction to the subject of chaos in the electromechanical drive systems. In this article, we explore chaotic solutions of maps and continuous time systems. These solutions are also bounded like equilibrium, periodic and quasiperiodic solutions.

  17. Electric Drive Study

    Science.gov (United States)

    1987-03-01

    compound promises to reduce weight of future permanent magnet motors by 20 to 30 percent; a similar reduction is expected in size (approximately 20...drive systems. The AC permanent magnet (brushless DC motor) is rapidly evolving and will replace most electrically excited machines. Permanent magnet motors using

  18. Electric-Drive Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Septon, Kendall K [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-11

    Electric-drive vehicles use electricity as their primary fuel or to improve the efficiency of conventional vehicle designs. These vehicles can be divided into three categories: Hybrid electric vehicles (HEVs), Plug-in hybrid electric vehicles (PHEVs), All-electric vehicles (EVs). Together, PHEVs and EVs can also be referred to as plug-in electric vehicles (PEVs).

  19. Electric-Drive Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    None

    2017-09-01

    Electric-drive vehicles use electricity as their primary fuel or to improve the efficiency of conventional vehicle designs. These vehicles can be divided into three categories: Hybrid electric vehicles (HEVs), Plug-in hybrid electric vehicles (PHEVs), All-electric vehicles (EVs). Together, PHEVs and EVs can also be referred to as plug-in electric vehicles (PEVs).

  20. Driving While Intoxicated.

    Science.gov (United States)

    Brick, John

    Alcohol intoxication increases the risk of highway accidents, the relative risk of crash probability increasing as a function of blood alcohol content (BAC). Because alcohol use is more prevalent than use of other drugs, more is known about the relationship between alcohol use and driving. Most states presume a BAC of .10% to be evidence of drunk…

  1. Epigenetic modifications: An important mechanism in diabetic disturbances.

    Science.gov (United States)

    Rorbach-Dolata, Anna; Kubis, Adriana; Piwowar, Agnieszka

    2017-11-29

    In the search for explanations of diabetes pathomechanisms, especially the development of its vascular complications (micro- and macrovascular ), although current, good metabolic control of diabetes, attention was drawn to the role of epigenetic inheritance associated with epigenetic modifications of histone proteins and DNA in hyperglycemia conditions. This study showed the significant role of DNA methylation and histone epigenetic modifications (a different nature and a different degree) in the transmission of information that is not connected with gene inheritance but concerns the persistent changes induced by hyperglycemia..Attention was paid to the role of DNA methylation of pancreatic cells in the pathogenesis of type 1 diabetes, but also type 2. The important role of DNA methylation changes in a so-called intrauterine growth restriction (IUGR) as reason of subsequent development of diabetes was particularly emphasized. In the pathogenesis of type 2 diabetes and its complications, especially microvascular complications, the greatest share and importance of epigenetic modifications on mitochondrial DNA metylation are the most important. The multidirectionality Complicaand complexity of epigenetic modifications of histone proteins indicate their importance in the development of diabetic disturbances. An especially important role is attributed to methylation and acetylation of histone proteins, in particular on arginine and lysine, whose changes occur most frequently. Moreover, epigenetic modifications of the enzymes, especially methylases, responsible for these processes are the underlying. It has been indicated that the identification of epigenetic differences within the DNA or histone proteins may be a useful prognostic biomarker of susceptibility to the disease development in the future. Moreover, they may become a potential target for future therapeutic interventions for clinical disorders in diabetes.

  2. EM modeling of RF drive in DTL tank 4

    International Nuclear Information System (INIS)

    Kurennoy, Sergey S.

    2012-01-01

    A 3-D MicroWave Studio model for the RF drive in the LANSCE DTL tank 4 has been built. Both eigensolver and time-domain modeling are used to evaluate maximal fields in the drive module and RF coupling. The LANSCE DTL tank 4 has recently been experiencing RF problems, which may or may not be related to its replaced RF coupler. This situation stimulated a request by Dan Rees to provide EM modeling of the RF drive in the DTL tank 4 (T4). Jim O'Hara provided a CAD model that was imported into the CST Microwave Studio (MWS) and after some modifications became a part of a simplified MWS model of the T4 RF drive. This technical note describes the model and presents simulation results.

  3. Rod drive and latching mechanism

    International Nuclear Information System (INIS)

    Veronesi, L.; Sherwood, D.G.

    1982-01-01

    Hydraulic drive and latching mechanisms for driving reactivity control mechanisms in nuclear reactors are described. Preferably, the pressurized reactor coolant is utilized to raise the drive rod into contact with and to pivot the latching mechanism so as to allow the drive rod to pass the latching mechanism. The pressure in the housing may then be equalized which allows the drive rod to move downwardly into contact with the latching mechanism but to hold the shaft in a raised position with respect to the reactor core. Once again, the reactor coolant pressure may be utilized to raise the drive rod and thus pivot the latching mechanism so that the drive rod passes above the latching mechanism. Again, the mechanism pressure can be equalized which allows the drive rod to fall and pass by the latching mechanism so that the drive rod approaches the reactor core. (author)

  4. Role of Oxidative Stress in Epigenetic Modification in Endometriosis.

    Science.gov (United States)

    Ito, Fuminori; Yamada, Yuki; Shigemitsu, Aiko; Akinishi, Mika; Kaniwa, Hiroko; Miyake, Ryuta; Yamanaka, Shoichiro; Kobayashi, Hiroshi

    2017-11-01

    Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis. Oxidative stress, secondary to the influx of hemoglobin, heme, and iron during retrograde menstruation, is involved in the expression of CpG demethylases, ten-eleven translocation, and jumonji (JMJ). Ten-eleven translocation and JMJ recognize a wide range of endogenous DNA methyltransferases (DNMTs). The increased expression levels of DNMTs may be involved in the subsequent downregulation of the decidualization-related genes. This review supports the hypothesis that there are at least 2 distinct phases of epigenetic modification in endometriosis: the initial wave of iron-induced oxidative stress would be followed by the second big wave of epigenetic modulation of endometriosis susceptibility genes. We summarize the recent advances in our understanding of the underlying epigenetic mechanisms focusing on oxidative stress in endometriosis.

  5. RNA modifications by oxidation

    DEFF Research Database (Denmark)

    Poulsen, Henrik E; Specht, Elisabeth; Broedbaek, Kasper

    2012-01-01

    to encompass various classes of novel regulatory RNAs, including, e.g., microRNAs. It is well known that DNA is constantly oxidized and repaired by complex genome maintenance mechanisms. Analogously, RNA also undergoes significant oxidation, and there are now convincing data suggesting that oxidation......The past decade has provided exciting insights into a novel class of central (small) RNA molecules intimately involved in gene regulation. Only a small percentage of our DNA is translated into proteins by mRNA, yet 80% or more of the DNA is transcribed into RNA, and this RNA has been found......, and the consequent loss of integrity of RNA, is a mechanism for disease development. Oxidized RNA is found in a large variety of diseases, and interest has been especially devoted to degenerative brain diseases such as Alzheimer disease, in which up to 50-70% of specific mRNA molecules are reported oxidized, whereas...

  6. Posttranslational modifications of Forkhead box O transcription factors

    NARCIS (Netherlands)

    Horst, Aart Arno van der

    2006-01-01

    FOXO transcription factors play an important role in essential biological processes such as differentiation, proliferation, apoptosis, DNA repair, metabolism and stress resistance. Phosphorylation is the modification that was first found on FOXOs and much of the subsequent studies focused on this

  7. Electrical drives for direct drive renewable energy systems

    CERN Document Server

    Mueller, Markus

    2013-01-01

    Wind turbine gearboxes present major reliability issues, leading to great interest in the current development of gearless direct-drive wind energy systems. Offering high reliability, high efficiency and low maintenance, developments in these direct-drive systems point the way to the next generation of wind power, and Electrical drives for direct drive renewable energy systems is an authoritative guide to their design, development and operation. Part one outlines electrical drive technology, beginning with an overview of electrical generators for direct drive systems. Principles of electrical design for permanent magnet generators are discussed, followed by electrical, thermal and structural generator design and systems integration. A review of power electronic converter technology and power electronic converter systems for direct drive renewable energy applications is then conducted. Part two then focuses on wind and marine applications, beginning with a commercial overview of wind turbine drive systems and a...

  8. Driving towards ecotechnologies.

    Science.gov (United States)

    Najjar, Devora A; Normandin, Avery M; Strait, Elizabeth A; Esvelt, Kevin M

    2017-12-01

    The prospect of using genetic methods to target vector, parasite, and reservoir species offers tremendous potential benefits to public health, but the use of genome editing to alter the shared environment will require special attention to public perception and community governance in order to benefit the world. Public skepticism combined with the media scrutiny of gene drive systems could easily derail unpopular projects entirely, especially given the potential for trade barriers to be raised against countries that employ self-propagating gene drives. Hence, open and community-guided development of thoughtfully chosen applications is not only the most ethical approach, but also the most likely to overcome the economic, social, and diplomatic barriers. Here we review current and past attempts to alter ecosystems using biological methods, identify key determinants of social acceptance, and chart a stepwise path for developers towards safe and widely supported use.

  9. Control rod drives

    International Nuclear Information System (INIS)

    Asano, Hiromitsu.

    1979-01-01

    Purpose: To drive control rods at an optimum safety speed corresponding to the reactor core output. Constitution: The reactor power is detected by a neutron detector and the output signal is applied to a process computer. The process computer issues a signal representing the reactor core output, which is converted through a function generator into a signal representing the safety speed of control rods. The converted signal is further supplied to a V/F converter and converted into a pulse signal. The pulse signal is inputted to a step motor driving circuit, which actuates a step motor to operate the control rods always at a safety speed corresponding to the reactor core power. (Furukawa, Y.)

  10. Drive-by-Downloads

    Energy Technology Data Exchange (ETDEWEB)

    Narvaez, Julia; Endicott-Popovsky, Barbara E.; Seifert, Christian; Aval, Chiraag U.; Frincke, Deborah A.

    2010-02-01

    Abstract: Drive-by-downloads are malware that push, and then execute, malicious code on a client system without the user's consent. The purpose of this paper is to introduce a discussion of the usefulness of antivirus software for detecting the installation of such malware, providing groundwork for future studies. Client honeypots collected drive-by malware which was then evaluated using common antivirus products. Initial analysis showed that most of such antivirus products identified less than 70% of these highly polymorphic malware programs. Also, it was observed that the antivirus products tested, even when successfully detecting this malware, often failed to classify it, leading to the conclusion that further work could involve not only developing new behavioral detection technologies, but also empirical studies that improve general understanding of these threats. Toward that end, one example of malicious code was analyzed behaviorally to provide insight into next steps for the future direction of this research.

  11. Safety rod driving device

    International Nuclear Information System (INIS)

    Murakami, Kiyonobu; Kurosaki, Akira.

    1988-01-01

    Purpose: To rapidly insert safety rods for a criticality experiment device into a reactor core container to stop the criticality reaction thereby prevent reactivity accidents. Constitution: A cylinder device having a safety rod as a cylinder rod attached with a piston at one end is constituted. The piston is elevated by pressurized air and attracted and fixed by an electromagnet which is a stationary device disposed at the upper portion of the cylinder. If the current supply to the electromagnet is disconnected, the safety rod constituting the cylinder rod is fallen together with the piston to the lower portion of the cylinder. Since the cylinder rod driving device has neither electrical motor nor driving screw as in the conventional device, necessary space can be reduced and the weight is decreased. In addition, since the inside of the nuclear reactor can easily be shielded completely from the external atmosphere, leakage of radioactive materials can be prevented. (Horiuchi, T.)

  12. Control rod drive mechanism

    International Nuclear Information System (INIS)

    Futatsugi, Masao; Goto, Mikihiko.

    1976-01-01

    Purpose: To provide a control rod drive mechanism using water as an operating source, which prevents a phenomenon for forming two-layers of water in the neighbourhood of a return nozzle in a reactor to limit formation of excessive thermal stress to improve a safety. Constitution: In the control rod drive mechanism of the present invention, a heating device is installed in the neighbourhood of a pressure container for a reactor. This heating device is provided to heat return water in the reactor to a level equal to the temperature of reactor water thereby preventing a phenomenon for forming two-layers of water in the reactor. This limits formation of thermal stress in the return nozzle in the reactor. Accordingly, it is possible to minimize damages in the return nozzle portion and yet a possibility of failure in reactor water. (Kawakami, Y.)

  13. A rotary drive

    International Nuclear Information System (INIS)

    Causer, R.

    1983-01-01

    A rotary drive for a manipulator or teleoperator comprises a ring member freely rotatable about an eccentric boss extending from an input driver shaft. The ring member has a tapered rim portion wedged between two resiliently biassed friction rings of larger diameter than the ring member and coaxial with the driver shaft, and the ring member is rotatably connected to an output driven shaft. The rotary drive provides a considerable velocity ratio, and also provides a safety feature in that friction between the rim portion and the friction rings only causes rotation of the driven shaft if the load on the driven shaft is less than a certain limiting value. This limiting value may be varied by adjusting the resilient bias on the friction rings. (author)

  14. Driving and engine cycles

    CERN Document Server

    Giakoumis, Evangelos G

    2017-01-01

    This book presents in detail the most important driving and engine cycles used for the certification and testing of new vehicles and engines around the world. It covers chassis and engine-dynamometer cycles for passenger cars, light-duty vans, heavy-duty engines, non-road engines and motorcycles, offering detailed historical information and critical review. The book also provides detailed examples from SI and diesel engines and vehicles operating during various cycles, with a focus on how the engine behaves during transients and how this is reflected in emitted pollutants, CO2 and after-treatment systems operation. It describes the measurement methods for the testing of new vehicles and essential information on the procedure for creating a driving cycle. Lastly, it presents detailed technical specifications on the most important chassis-dynamometer cycles around the world, together with a direct comparison of those cycles.

  15. Driving electrostatic transducers

    DEFF Research Database (Denmark)

    Nielsen, Dennis; Knott, Arnold; Andersen, Michael A. E.

    2013-01-01

    Electrostatic transducers represent a very interesting alternative to the traditional inefficient electrodynamic transducers. In order to establish the full potential of these transducers, power amplifiers which fulfill the strict requirements imposed by such loads (high impedance, frequency...... depended, nonlinear and high bias voltage for linearization) must be developed. This paper analyzes power stages and bias configurations suitable for driving an electrostatic transducer. Measurement results of a 300 V prototype amplifier are shown. Measuring THD across a high impedance source is discussed...

  16. Control rod drive mechanism

    International Nuclear Information System (INIS)

    Mizuno, Katsuyuki.

    1976-01-01

    Object: To restrict the reduction in performance due to stress corrosion cracks by making use of condensate produced in a turbine steam condenser. Structure: Water produced in a turbine steam condenser is forced into a condensed water desalting unit by low pressure condensate pump. The condensate is purified and then forced by a high pressure condensate pump into a feedwater heater for heating before it is returned to the reactor by a feedwater pump. Part of the condensate issuing from the condensate desalting unit is branched from the remaining portion at a point upstream the pump and is withdrawn into a control rod drive water pump after passing through a motordriven bypass valve, an orifice and a condenser water level control valve, is pressurized in the control rod drive water desalting unit and supplied to a control rod drive water pressure system. The control rod is vertically moved by the valve operation of the water pressure system. Since water of high oxygen concentration does not enter during normal operation, it is possible to prevent the stress cracking of the stainless steel apparatus. (Nakamura, S.)

  17. Motor car driving; Kraftfahrzeugfuehrung

    Energy Technology Data Exchange (ETDEWEB)

    Juergensohn, T. [Technische Univ. Berlin (Germany). ISS-Fahrzeugtechnik; Timpe, K.P. (eds.) [Technische Univ. Berlin (DE). Zentrum Mensch-Maschine-Systeme (ZMMS)

    2001-07-01

    This is the first comprehensive book on motor car driving, i.e. all aspects of motor car technology that cannot be looked at separately from the needs, characteristics and limitations of the human driver. This includes ergonomics as well as the design of the driver interface in consideration of the findings of cognitive science, problems of driving simulation in the context of simulation of technical systems, problems relating to optimal car automation up to traffic psychology. The book is in honour of Prof. Dr. Willumeit who died in summer 2000. Prof. Willumeit was one of the few scientists in Germany who had been an expert on all aspects of motor car driving for many years. [German] Erstmalig wird das Thema der Fahrzeugfuehrung geschlossen dargestellt. Die Thematik der 'Kraftfahrzeugfuehrung' umfasst in diesem Zusammenhang alle Aspekte der Kraftfahrzeugtechnik, die nicht isoliert von den Erfordernissen, Eigenschaften und Grenzen des menschlichen Fahrers betrachtet werden koennen. Dies beinhaltet u.a. Probleme der Ergonomie, aber auch Fragen nach einer kognitionswissenschaftlich unterstuetzten Schnittstellengestaltung, Fragen der Simulation des Fahrverhalten im Kontext der Simulation technischer Systeme oder Fragen einer optimalen Fahrzeugautomatisierung bis hin zu verkehrspsychologischen Aspekten. Das Buch ist als Gedenkband fuer Prof. Dr. Willumeit konzipiert, der im Sommer 2000 verstarb. Prof. Willumeit war einer der wenigen Wissenschaftler in Deutschland, der ueber viele Jahre diese Thematik der Kraftfahrzeugfuehrung in ihrer vollen Breite verfolgte. (orig.)

  18. Control rod drive

    International Nuclear Information System (INIS)

    Watando, Kosaku; Tanaka, Yuzo; Mizumura, Yasuhiro; Hosono, Kazuya.

    1975-01-01

    Object: To provide a simple and compact construction of an apparatus for driving a drive shaft inside with a magnetic force from the outside of the primary system water side. Structure: The weight of a plunger provided with an attraction plate is supported by a plunger lift spring means so as to provide a buffer action at the time of momentary movement while also permitting the load on lift coil to be constituted solely by the load on the drive shaft. In addition, by arranging the attraction plate and lift coil so that they face each other with a small gap there-between, it is made possible to reduce the size and permit efficient utilization of the attracting force. Because of the small size, cooling can be simply carried out. Further, since there is no mechanical penetration portion, there is no possibility of leakage of the primary system water. Furthermore, concentration of load on a latch pin is prevented by arranging so that with a structure the load of the control rod to be directly beared through the scrum latch. (Kamimura, M.)

  19. Enzymatic modification of starch

    DEFF Research Database (Denmark)

    Jensen, Susanne Langgård

    In the food industry approaches for using bioengineering are investigated as alternatives to conventional chemical and physical starch modification techniques in development of starches with specific properties. Enzyme-assisted post-harvest modification is an interesting approach to this, since...... it is considered a clean and energy saving technology. This thesis aimed to investigate the effect of using reaction conditions, simulating an industrial process, for enzymatic treatment of starch with branching enzyme (BE) from Rhodothermus obamensis. Thus treatements were conducted at 70°C using very high...... substrate concentration (30-40% dry matter (DM)) and high enzyme activity (750-2250 BE units (BEU)/g sample). Starches from various botanical sources, representing a broad range of properties, were used as substrates. The effects of the used conditions on the BE-reaction were evaluated by characterization...

  20. Self-rated driving and driving safety in older adults.

    Science.gov (United States)

    Ross, Lesley A; Dodson, Joan E; Edwards, Jerri D; Ackerman, Michelle L; Ball, Karlene

    2012-09-01

    Many U.S. states rely on older adults to self-regulate their driving and determine when driving is no longer a safe option. However, the relationship of older adults' self-rated driving in terms of actual driving competency outcomes is unclear. The current study investigates self-rated driving in terms of (1) systematic differences between older adults with high (good/excellent) versus low (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated driving to adverse driving outcomes in older adults (n=350; mean age 73.9, SD=5.25, range 65-91). Adverse driving outcomes included self-reported incidences of (1) being pulled over by the police, (2) receiving a citation, (3) receiving a recommendation to cease or limit driving, (4) crashes, and (5) state-reported crashes. Results found that older drivers with low self-ratings reported more medical conditions, less driving frequency, and had been given more suggestions to stop/limit their driving; there were no other significant differences between low and high self-raters. Logistic regression revealed older drivers were more likely to have a state-reported crash and receive a suggestion to stop or limit driving. Men were more likely to report all adverse driving outcomes except for receiving a suggestion to stop or limit driving. Regarding self-rated driving, older adults with high ratings were 66% less likely (OR=0.34, 95% CI=0.14-0.85) to have received suggestions to limit or stop driving after accounting for demographics, health and driving frequency. Self-ratings were not predictive of other driving outcomes (being pulled over by the police, receiving a citation, self-reported crashes, or state-reported crashes, ps>0.05). Most older drivers (85.14%) rated themselves as either good or excellent drivers regardless of their actual previous citation or crash rates. Self-rated driving is likely not related to actual driving proficiency as indicated by previous crash involvement in older adults

  1. Geometrically Consistent Mesh Modification

    KAUST Repository

    Bonito, A.

    2010-01-01

    A new paradigm of adaptivity is to execute refinement, coarsening, and smoothing of meshes on manifolds with incomplete information about their geometry and yet preserve position and curvature accuracy. We refer to this collectively as geometrically consistent (GC) mesh modification. We discuss the concept of discrete GC, show the failure of naive approaches, and propose and analyze a simple algorithm that is GC and accuracy preserving. © 2010 Society for Industrial and Applied Mathematics.

  2. Radiation modification of materials

    International Nuclear Information System (INIS)

    Pikaev, A.K.

    1987-01-01

    Industrial and radiation chemical processes of material modification based on cross-linking of polymers as a result of radiation are considered. Among them are production of cables and rods with irradiated modified insulation, production of hardened and thermo-shrinkaging polymer products (films, tubes, fashioned products), production of radiation cross-linked polyethylene foam, technology of radiation vulcanization of elastomers. Attention is paid to radiation plants on the basis of γ-sources and electron acceleratos as well as to radiation conditions

  3. Low Sex Drive in Women

    Science.gov (United States)

    Low sex drive in women Overview Women's sexual desires naturally fluctuate over the years. Highs and lows commonly coincide ... used for mood disorders also can cause low sex drive in women. If your lack of interest ...

  4. Marijuana and actual driving performance

    Science.gov (United States)

    1993-11-01

    This report concerns the effects of marijuana smoking on actual driving performance. It presents the results of one pilot and three actual driving studies. The pilot study's major purpose was to establish the THC dose current marijuana users smoke to...

  5. Distracted Driving Raises Crash Risk

    Science.gov (United States)

    ... this issue Health Capsule Distracted Driving Raises Crash Risk En español Send us your comments Video technology ... distracted driving, especially among new drivers, raises the risk for car crashes and near crashes. The study ...

  6. DNA Camouflage

    Science.gov (United States)

    2016-01-08

    1 DNA Camouflage Supplementary Information Bijan Zakeri1,2*, Timothy K. Lu1,2*, Peter A. Carr2,3* 1Department of Electrical Engineering and...ll.mit.edu). Distribution A: Public Release   2 Supplementary Figure 1 DNA camouflage with the 2-state device. (a) In the presence of Cre, DSD-2[α...10 1 + Cre 1 500 1,000 length (bp) chromatogram alignment template − Cre   4 Supplementary Figure 3 DNA camouflage with a switchable

  7. DNA as a component of ER materials

    International Nuclear Information System (INIS)

    Minagawa, K; Aoki, Y; Berber, M R; Mori, T; Tanaka, M

    2009-01-01

    Deoxyribonucleic acid (DNA), which is known as a typical biopolymer, has been utilized for a few types of ER materials. Suspensions were prepared with the particles of DNA, DNA/lipid complexes, and LDH (layered double hydroxide)/DNA composites. The purified DNA showed larger ER effect than the others, but this particle tended to absorb water, which caused less stability. Preliminary experiments of preparing composite with LDH indicated that this inorganic material would be useful for hydrophobic modification of DNA particles, although further optimization of composite preparation is needed. In addition, the LDH/DNA suspensions showed interesting behaviours under some conditions, which indicated possibility for controlling ER property in a wide range.

  8. DNA as a component of ER materials

    Energy Technology Data Exchange (ETDEWEB)

    Minagawa, K; Aoki, Y; Berber, M R [Institute of Technology and Science, University of Tokushima, Tokushima 770-8506 (Japan); Mori, T [Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka 819-0395 (Japan); Tanaka, M [Faculty of Pharmaceutical Science, Tokushima Bunri University, Tokushima 770-8514 (Japan)], E-mail: minagawa@chem.tokushima-u.ac.jp

    2009-02-01

    Deoxyribonucleic acid (DNA), which is known as a typical biopolymer, has been utilized for a few types of ER materials. Suspensions were prepared with the particles of DNA, DNA/lipid complexes, and LDH (layered double hydroxide)/DNA composites. The purified DNA showed larger ER effect than the others, but this particle tended to absorb water, which caused less stability. Preliminary experiments of preparing composite with LDH indicated that this inorganic material would be useful for hydrophobic modification of DNA particles, although further optimization of composite preparation is needed. In addition, the LDH/DNA suspensions showed interesting behaviours under some conditions, which indicated possibility for controlling ER property in a wide range.

  9. Mechanisms of bacterial DNA replication restart

    Science.gov (United States)

    Windgassen, Tricia A; Wessel, Sarah R; Bhattacharyya, Basudeb

    2018-01-01

    Abstract Multi-protein DNA replication complexes called replisomes perform the essential process of copying cellular genetic information prior to cell division. Under ideal conditions, replisomes dissociate only after the entire genome has been duplicated. However, DNA replication rarely occurs without interruptions that can dislodge replisomes from DNA. Such events produce incompletely replicated chromosomes that, if left unrepaired, prevent the segregation of full genomes to daughter cells. To mitigate this threat, cells have evolved ‘DNA replication restart’ pathways that have been best defined in bacteria. Replication restart requires recognition and remodeling of abandoned replication forks by DNA replication restart proteins followed by reloading of the replicative DNA helicase, which subsequently directs assembly of the remaining replisome subunits. This review summarizes our current understanding of the mechanisms underlying replication restart and the proteins that drive the process in Escherichia coli (PriA, PriB, PriC and DnaT). PMID:29202195

  10. Behavior Modification in the Classroom

    Science.gov (United States)

    Whitman, Mryon; Whitman, Joan

    1971-01-01

    This article presents the theoretical rationale for behavior modification, principally through its comparison with traditional psychotherapies, and suggests some behavior modification techniques for the classroom management of maladaptive behavior. (Author)

  11. Nuclear refueling platform drive system

    International Nuclear Information System (INIS)

    Busch, F.R.; Faulstich, D.L.

    1992-01-01

    This patent describes a drive system. It comprises: a gantry including a bridge having longitudinal and transverse axes and supported by spaced first and second end frames joined to fist and second end frames joined to first and second drive trucks for moving the bridge along the transverse axis; first means for driving the first drive truck; second means for driving the second drive truck being independent from the first driving means; and means for controlling the first and second driving means for reducing differential transverse travel between the first and second drive trucks, due to a skewing torque acting on the bridge, to less than a predetermined maximum, the controlling means being in the form of an electrical central processing unit and including: a closed-loop first velocity control means for controlling velocity of the first drive truck by providing a first command signal to the first driver means; a close loop second velocity control means for controlling velocity of the second drive truck by providing a second command signal to the second driving means; and an auxiliary closed-loop travel control means

  12. Tumor‐associated DNA mutation detection in individuals undergoing colonoscopy

    OpenAIRE

    Fleshner, Phillip; Braunstein, Glenn D.; Ovsepyan, Gayane; Tonozzi, Theresa R.; Kammesheidt, Anja

    2017-01-01

    Abstract The majority of colorectal cancers (CRC) harbor somatic mutations and epigenetic modifications in the tumor tissue, and some of these mutations can be detected in plasma as circulating tumor DNA (ctDNA). Precancerous colorectal lesions also contain many of these same mutations. This study examined plasma for ctDNA from patients undergoing a screening or diagnostic colonoscopy to determine the sensitivity and specificity of the ctDNA panel for detecting CRC and precancerous lesions. T...

  13. Biomaterials modification by ion beam

    International Nuclear Information System (INIS)

    Zhang Tonghe; Yi Zhongzhen; Zhang Xu; Wu Yuguang

    2001-01-01

    Ion beam technology is one of best ways for the modification of biomaterials. The results of ion beam modification of biomaterials are given. The method and results of improved biocompatibility are indicated by ion beam technology. The future development of ion beam modification of biomaterials is discussed

  14. The Development of Vocational Vehicle Drive Cycles and Segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Duran, Adam W. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Phillips, Caleb T. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Konan, Arnaud M. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kelly, Kenneth J. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-09-28

    Under a collaborative interagency agreement between the U.S. Environmental Protection Agency and the U.S Department of Energy (DOE), the National Renewable Energy Laboratory (NREL) performed a series of in-depth analyses to characterize the on-road driving behavior including distributions of vehicle speed, idle time, accelerations and decelerations, and other driving metrics of medium- and heavy-duty vocational vehicles operating within the United States. As part of this effort, NREL researchers segmented U.S. medium- and heavy-duty vocational vehicle driving characteristics into three distinct operating groups or clusters using real world drive cycle data collected at 1 Hz and stored in NREL's Fleet DNA database. The Fleet DNA database contains millions of miles of historical real-world drive cycle data captured from medium- and heavy vehicles operating across the United States. The data encompass data from existing DOE activities as well as contributions from valued industry stakeholder participants. For this project, data captured from 913 unique vehicles comprising 16,250 days of operation were drawn from the Fleet DNA database and examined. The Fleet DNA data used as a source for this analysis has been collected from a total of 30 unique fleets/data providers operating across 22 unique geographic locations spread across the United States. This includes locations with topology ranging from the foothills of Denver, Colorado, to the flats of Miami, Florida. The range of fleets, geographic locations, and total number of vehicles analyzed ensures results that include the influence of these factors. While no analysis will be perfect without unlimited resources and data, it is the researchers understanding that the Fleet DNA database is the largest and most thorough publicly accessible vocational vehicle usage database currently in operation. This report includes an introduction to the Fleet DNA database and the data contained within, a presentation of the

  15. Offset Compound Gear Drive

    Science.gov (United States)

    Stevens, Mark A.; Handschuh, Robert F.; Lewicki, David G.

    2010-01-01

    The Offset Compound Gear Drive is an in-line, discrete, two-speed device utilizing a special offset compound gear that has both an internal tooth configuration on the input end and external tooth configuration on the output end, thus allowing it to mesh in series, simultaneously, with both a smaller external tooth input gear and a larger internal tooth output gear. This unique geometry and offset axis permits the compound gear to mesh with the smaller diameter input gear and the larger diameter output gear, both of which are on the same central, or primary, centerline. This configuration results in a compact in-line reduction gear set consisting of fewer gears and bearings than a conventional planetary gear train. Switching between the two output ratios is accomplished through a main control clutch and sprag. Power flow to the above is transmitted through concentric power paths. Low-speed operation is accomplished in two meshes. For the purpose of illustrating the low-speed output operation, the following example pitch diameters are given. A 5.0 pitch diameter (PD) input gear to 7.50 PD (internal tooth) intermediate gear (0.667 reduction mesh), and a 7.50 PD (external tooth) intermediate gear to a 10.00 PD output gear (0.750 reduction mesh). Note that it is not required that the intermediate gears on the offset axis be of the same diameter. For this example, the resultant low-speed ratio is 2:1 (output speed = 0.500; product of stage one 0.667 reduction and stage two 0.750 stage reduction). The design is not restricted to the example pitch diameters, or output ratio. From the output gear, power is transmitted through a hollow drive shaft, which, in turn, drives a sprag during which time the main clutch is disengaged.

  16. Electrical machines and drives

    CERN Document Server

    Hindmarsh, John

    2002-01-01

    Recent years have brought substantial developments in electrical drive technology, with the appearance of highly rated, very-high-speed power-electronic switches, combined with microcomputer control systems.This popular textbook has been thoroughly revised and updated in the light of these changes. It retains its successful formula of teaching through worked examples, which are put in context with concise explanations of theory, revision of equations and discussion of the engineering implications. Numerous problems are also provided, with answers supplied.The third edition in

  17. Electrical machines & drives

    CERN Document Server

    Hammond, P

    1985-01-01

    Containing approximately 200 problems (100 worked), the text covers a wide range of topics concerning electrical machines, placing particular emphasis upon electrical-machine drive applications. The theory is concisely reviewed and focuses on features common to all machine types. The problems are arranged in order of increasing levels of complexity and discussions of the solutions are included where appropriate to illustrate the engineering implications. This second edition includes an important new chapter on mathematical and computer simulation of machine systems and revised discussions o

  18. Measurement of Driving Terms

    CERN Document Server

    Schmidt, F; Faus-Golfe, A

    2001-01-01

    In 2000 a series of MDs has been performed at the SPS to measure resonance driving terms. Theory predicts that these terms can be determined by harmonic analysis of BPM data recorded after applying single kicks at various amplitudes. Strong sextupoles were introduced to create a sizeable amount of nonlinearities. Experiments at injection energy (26 GeV) with single bunch as well as one experiment at 120 GeV with 84 bunches were carried out. The expected nonlinear content is compared to the experimenteal observation.

  19. DNA glue

    DEFF Research Database (Denmark)

    Filichev, Vyacheslav V; Astakhova, Irina V.; Malakhov, Andrei D.

    2008-01-01

    Significant alterations in thermal stability of parallel DNA triplexes and antiparallel duplexes were observed upon changing the attachment of ethynylpyrenes from para to ortho in the structure of phenylmethylglycerol inserted as a bulge into DNA (TINA). Insertions of two ortho-TINAs as a pseudo...

  20. Hyperstretching DNA

    NARCIS (Netherlands)

    Schakenraad, Koen; Biebricher, Andreas S.; Sebregts, Maarten; Ten Bensel, Brian; Peterman, Erwin J.G.; Wuite, Gijs J L; Heller, Iddo; Storm, Cornelis; Van Der Schoot, Paul

    2017-01-01

    The three-dimensional structure of DNA is highly susceptible to changes by mechanical and biochemical cues in vivo and in vitro. In particular, large increases in base pair spacing compared to regular B-DNA are effected by mechanical (over)stretching and by intercalation of compounds that are widely

  1. Cognitive impairment and driving safety.

    Science.gov (United States)

    Eby, David W; Molnar, Lisa J

    2012-11-01

    As the populations of many countries continue to age, cognitive impairment will likely become more common. Individuals with cognitive impairment pose special challenges for families, health professionals, driving safety professionals, and the larger community, particularly if these older adults depend on driving as their primary means of community mobility. It is vital that we continue to extend our knowledge about the driving behavior of individuals' with cognitive impairment, as well as try to develop effective means of screening and assessing these individuals for fitness to drive and help facilitate their transition to non-driving when appropriate. This special issue is intended to provide researchers and practitioners an opportunity to present the most recent research findings on driving-related issues among older adults with cognitive impairment. The issue contains 11 original contributions from seven countries. The topics covered by these papers are: crash risks; screening, assessment, and fitness to drive; driving performance using a driving simulator; and driving behaviors and driving-related decisions of people with cognitive impairments. Copyright © 2012. Published by Elsevier Ltd.

  2. Genetic modification and genetic determinism

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  3. Glaucoma and Driving: On-Road Driving Characteristics

    Science.gov (United States)

    Wood, Joanne M.; Black, Alex A.; Mallon, Kerry; Thomas, Ravi; Owsley, Cynthia

    2016-01-01

    Purpose To comprehensively investigate the types of driving errors and locations that are most problematic for older drivers with glaucoma compared to those without glaucoma using a standardized on-road assessment. Methods Participants included 75 drivers with glaucoma (mean = 73.2±6.0 years) with mild to moderate field loss (better-eye MD = -1.21 dB; worse-eye MD = -7.75 dB) and 70 age-matched controls without glaucoma (mean = 72.6 ± 5.0 years). On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist using a standardized scoring system which assessed the types of driving errors and the locations where they were made and the number of critical errors that required an instructor intervention. Driving safety was rated on a 10-point scale. Self-reported driving ability and difficulties were recorded using the Driving Habits Questionnaire. Results Drivers with glaucoma were rated as significantly less safe, made more driving errors, and had almost double the rate of critical errors than those without glaucoma. Driving errors involved lane positioning and planning/approach, and were significantly more likely to occur at traffic lights and yield/give-way intersections. There were few between group differences in self-reported driving ability. Conclusions Older drivers with glaucoma with even mild to moderate field loss exhibit impairments in driving ability, particularly during complex driving situations that involve tactical problems with lane-position, planning ahead and observation. These results, together with the fact that these drivers self-report their driving to be relatively good, reinforce the need for evidence-based on-road assessments for evaluating driving fitness. PMID:27472221

  4. A qualitative exploration of driving stress and driving discourtesy.

    Science.gov (United States)

    Scott-Parker, B; Jones, C M; Rune, K; Tucker, J

    2018-05-31

    Driving courtesy, and conversely driving discourtesy, recently has been of great interest in the public domain. In addition, there has been increasing recognition of the negative impact of stress upon the individual's health and wellbeing, with a plethora of interventions aimed at minimising stress more generally. The research literature regarding driving dis/courtesy, in comparison, is scant, with a handful of studies examining the dis/courteous driving behaviour of road users, and the relationship between driving discourtesy and driving stress. To examine courteous and discourteous driving experiences, and to explore the impact of stress associated with such driving experiences. Thirty-eight drivers (20 females) from the Sunshine Coast region volunteered to participate in one of four 1-1.5 h focus groups. Content analysis used the verbatim utterances captured via an Mp3 device. Three themes pertaining to stressful and discourteous interactions were identified. Theme one pertained to the driving context: road infrastructure (eg, roundabouts, roadwork), vehicles (eg, features), location (eg, country vs city, unfamiliar areas), and temporal aspects (eg, holidays). Theme two pertained to other road users: their behaviour (eg, tailgating, merging), and unknown factors (eg, illicit and licit drug use). Theme three pertained to the self as road user: their own behaviours (eg, deliberate intimidation), and their emotions (eg, angry reaction to other drivers, being in control). Driving dis/courtesy and driving stress is a complex phenomenon, suggesting complex intervention efforts are required. Driving discourtesy was reported as being highly stressful, therefore intervention efforts which encourage driving courtesy and which foster emotional capacity to cope with stressful circumstances appear warranted. Copyright © 2018. Published by Elsevier Ltd.

  5. Glaucoma and Driving: On-Road Driving Characteristics.

    Directory of Open Access Journals (Sweden)

    Joanne M Wood

    Full Text Available To comprehensively investigate the types of driving errors and locations that are most problematic for older drivers with glaucoma compared to those without glaucoma using a standardized on-road assessment.Participants included 75 drivers with glaucoma (mean = 73.2±6.0 years with mild to moderate field loss (better-eye MD = -1.21 dB; worse-eye MD = -7.75 dB and 70 age-matched controls without glaucoma (mean = 72.6 ± 5.0 years. On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist using a standardized scoring system which assessed the types of driving errors and the locations where they were made and the number of critical errors that required an instructor intervention. Driving safety was rated on a 10-point scale. Self-reported driving ability and difficulties were recorded using the Driving Habits Questionnaire.Drivers with glaucoma were rated as significantly less safe, made more driving errors, and had almost double the rate of critical errors than those without glaucoma. Driving errors involved lane positioning and planning/approach, and were significantly more likely to occur at traffic lights and yield/give-way intersections. There were few between group differences in self-reported driving ability.Older drivers with glaucoma with even mild to moderate field loss exhibit impairments in driving ability, particularly during complex driving situations that involve tactical problems with lane-position, planning ahead and observation. These results, together with the fact that these drivers self-report their driving to be relatively good, reinforce the need for evidence-based on-road assessments for evaluating driving fitness.

  6. Glaucoma and Driving: On-Road Driving Characteristics.

    Science.gov (United States)

    Wood, Joanne M; Black, Alex A; Mallon, Kerry; Thomas, Ravi; Owsley, Cynthia

    2016-01-01

    To comprehensively investigate the types of driving errors and locations that are most problematic for older drivers with glaucoma compared to those without glaucoma using a standardized on-road assessment. Participants included 75 drivers with glaucoma (mean = 73.2±6.0 years) with mild to moderate field loss (better-eye MD = -1.21 dB; worse-eye MD = -7.75 dB) and 70 age-matched controls without glaucoma (mean = 72.6 ± 5.0 years). On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist using a standardized scoring system which assessed the types of driving errors and the locations where they were made and the number of critical errors that required an instructor intervention. Driving safety was rated on a 10-point scale. Self-reported driving ability and difficulties were recorded using the Driving Habits Questionnaire. Drivers with glaucoma were rated as significantly less safe, made more driving errors, and had almost double the rate of critical errors than those without glaucoma. Driving errors involved lane positioning and planning/approach, and were significantly more likely to occur at traffic lights and yield/give-way intersections. There were few between group differences in self-reported driving ability. Older drivers with glaucoma with even mild to moderate field loss exhibit impairments in driving ability, particularly during complex driving situations that involve tactical problems with lane-position, planning ahead and observation. These results, together with the fact that these drivers self-report their driving to be relatively good, reinforce the need for evidence-based on-road assessments for evaluating driving fitness.

  7. Control rod drives

    International Nuclear Information System (INIS)

    Hayakawa, Hiroyasu; Kawamura, Atsuo.

    1979-01-01

    Purpose: To reduce pellet-clad mechanical interactions, as well as improve the fuel safety. Constitution: In the rod drive of a bwr type reactor, an electric motor operated upon intermittent input such as of pulse signals is connected to a control rod. A resolver for converting the rotational angle of the motor to electric signals is connected to the rotational shaft of the motor and the phase difference between the output signal from the resolver and a reference signal is adapted to detect by a comparator. Based on the detection result, the controller is actuated to control a motor for control rod drive so that fine control for the movement of the control rod is made possible. This can reduce the moving distance of the control rod, decrease the thermal stress applied to the control rod and decrease the pellet clad mechanical interaction failures due to thermal expansion between the cladding tube and the pellets caused by abrupt changes in the generated power. (Furukawa, Y.)

  8. Control rod drives

    International Nuclear Information System (INIS)

    Oonuki, Koji.

    1981-01-01

    Purpose: To increase the driving speed of control rods at rapid insertion with an elongate control rod and an extension pipe while ensuring sufficient buffering performance in a short buffering distance, by providing a plurality of buffers to an extension pipe between a control rod drive source and a control rod in LMFBR type reactor. Constitution: First, second and third buffers are respectively provided to an acceleration piston, an extension pipe and a control rod respectively and the insertion positions for each of the buffers are displaced orderly from above to below. Upon disconnection of energizing current for an electromagnet, the acceleration piston, the extension pipe and the control rod are rapidly inserted in one body. The first, second and third buffers are respectively actuated at each of their falling strokes upon rapid insertion respectively, and the acceleration piston, the extension pipe and the control rod receive the deceleration effect in the order correspondingly. Although the compression force is applied to the control rod only near the stroke end, it does not cause deformation. (Kawakami, Y.)

  9. Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference series)

    OpenAIRE

    Loscalzo, Joseph; Handy, Diane E.

    2014-01-01

    Abstract Epigenetics refers to heritable traits that are not a consequence of DNA sequence. Three classes of epigenetic regulation exist: DNA methylation, histone modification, and noncoding RNA action. In the cardiovascular system, epigenetic regulation affects development, differentiation, and disease propensity or expression. Defining the determinants of epigenetic regulation offers opportunities for novel strategies for disease prevention and treatment.

  10. Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference series).

    Science.gov (United States)

    Loscalzo, Joseph; Handy, Diane E

    2014-06-01

    Epigenetics refers to heritable traits that are not a consequence of DNA sequence. Three classes of epigenetic regulation exist: DNA methylation, histone modification, and noncoding RNA action. In the cardiovascular system, epigenetic regulation affects development, differentiation, and disease propensity or expression. Defining the determinants of epigenetic regulation offers opportunities for novel strategies for disease prevention and treatment.

  11. Chromatin remodelling: the industrial revolution of DNA around histones.

    Science.gov (United States)

    Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

    2006-06-01

    Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

  12. Ligation bias in Illumina next-generation DNA libraries

    DEFF Research Database (Denmark)

    Seguin-Orlando, Andaine; Schubert, Mikkel; Clary, Joel

    2013-01-01

    Ancient DNA extracts consist of a mixture of endogenous molecules and contaminant DNA templates, often originating from environmental microbes. These two populations of templates exhibit different chemical characteristics, with the former showing depurination and cytosine deamination by-products,...... for authenticating ancient sequence data. Consequently, we show that models adequate for estimating post-mortem DNA damage levels must be robust to the molecular tools used for building ancient DNA libraries.......Ancient DNA extracts consist of a mixture of endogenous molecules and contaminant DNA templates, often originating from environmental microbes. These two populations of templates exhibit different chemical characteristics, with the former showing depurination and cytosine deamination by......-products, resulting from post-mortem DNA damage. Such chemical modifications can interfere with the molecular tools used for building second-generation DNA libraries, and limit our ability to fully characterize the true complexity of ancient DNA extracts. In this study, we first use fresh DNA extracts to demonstrate...

  13. Genetic Control of the Secondary Modification of Deoxyribonucleic Acid in Escherichia coli1

    Science.gov (United States)

    Mamelak, Linda; Boyer, Herbert W.

    1970-01-01

    The wild-type restriction and modification alleles of Escherichia coli K-12 and B were found to have no measurable effect on the patterns of methylated bases in the deoxyribonucleic acid (DNA) of these strains. The genetic region controlling the methylation of cytosine in E. coli K-12 was mapped close to his, and the presence or absence of this gene in E. coli B or E. coli K had no effect on the restriction and modification properties of these strains. Thus, only a few of the methylated bases in the DNA of these strains are involved in host modification, and the biological role of the remainder remains obscure. PMID:4919756

  14. Epigenetic silencing of the DNA mismatch repair gene, MLH1, induced by hypoxic stress in a pathway dependent on the histone demethylase, LSD1

    Science.gov (United States)

    Lu, Yuhong; Wajapeyee, Narendra; Turker, Mitchell S.; Glazer, Peter M.

    2014-01-01

    SUMMARY Silencing of the MLH1 gene is frequently seen in sporadic cancers. We report that hypoxia causes decreased H3K4 methylation at the MLH1 promoter via the H3K4 demethylases, LSD1 and PLU-1, and promotes long-term silencing of the promoter in a pathway that requires LSD1. Knockdown of LSD1 or its co-repressor, CoREST, also prevents the re-silencing (and cytosine DNA methylation) of the endogenous MLH1 promoter in RKO colon cancer cells following transient reactivation by the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC). The results demonstrate that hypoxia is a critical driving force for silencing of MLH1 through chromatin modification and indicate that the LSD1/CoREST complex is essential for MLH1 silencing. PMID:25043185

  15. DNA probes

    International Nuclear Information System (INIS)

    Castelino, J.

    1992-01-01

    The creation of DNA probes for detection of specific nucleotide segments differs from ligand detection in that it is a chemical rather than an immunological reaction. Complementary DNA or RNA is used in place of the antibody and is labelled with 32 P. So far, DNA probes have been successfully employed in the diagnosis of inherited disorders, infectious diseases, and for identification of human oncogenes. The latest approach to the diagnosis of communicable and parasitic infections is based on the use of deoxyribonucleic acid (DNA) probes. The genetic information of all cells is encoded by DNA and DNA probe approach to identification of pathogens is unique because the focus of the method is the nucleic acid content of the organism rather than the products that the nucleic acid encodes. Since every properly classified species has some unique nucleotide sequences that distinguish it from every other species, each organism's genetic composition is in essence a finger print that can be used for its identification. In addition to this specificity, DNA probes offer other advantages in that pathogens may be identified directly in clinical specimens

  16. DNA probes

    Energy Technology Data Exchange (ETDEWEB)

    Castelino, J

    1993-12-31

    The creation of DNA probes for detection of specific nucleotide segments differs from ligand detection in that it is a chemical rather than an immunological reaction. Complementary DNA or RNA is used in place of the antibody and is labelled with {sup 32}P. So far, DNA probes have been successfully employed in the diagnosis of inherited disorders, infectious diseases, and for identification of human oncogenes. The latest approach to the diagnosis of communicable and parasitic infections is based on the use of deoxyribonucleic acid (DNA) probes. The genetic information of all cells is encoded by DNA and DNA probe approach to identification of pathogens is unique because the focus of the method is the nucleic acid content of the organism rather than the products that the nucleic acid encodes. Since every properly classified species has some unique nucleotide sequences that distinguish it from every other species, each organism`s genetic composition is in essence a finger print that can be used for its identification. In addition to this specificity, DNA probes offer other advantages in that pathogens may be identified directly in clinical specimens 10 figs, 2 tabs

  17. Raman spectroscopic study of plasma-treated salmon DNA

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Geon Joon; Kim, Yong Hee; Choi, Eun Ha [Plasma Bioscience Research Center, Kwangwoon University, Seoul 139-701 (Korea, Republic of); Kwon, Young-Wan [Department of Chemistry, Korea University, Seoul 136-701 (Korea, Republic of)

    2013-01-14

    In this research, we studied the effect of plasma treatment on the optical/structural properties of the deoxyribonucleic acid (DNA) extracted from salmon sperm. DNA-cetyltrimethylammonium (CTMA) films were obtained by complexation of DNA with CTMA. Circular dichroism (CD) and Raman spectra indicated that DNA retained its double helical structure in the solid film. The Raman spectra exhibited several vibration modes corresponding to the nuclear bases and the deoxyribose-phosphate backbones of the DNA, as well as the alkylchains of CTMA. Dielectric-barrier-discharge (DBD) plasma treatment induced structural modification and damage to the DNA, as observed by changes in the ultraviolet-visible absorption, CD, and Raman spectra. The optical emission spectra of the DBD plasma confirmed that DNA modification was induced by plasma ions such as reactive oxygen species and reactive nitrogen species.

  18. Implication of Posttranslational Histone Modifications in Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    Shisheng Li

    2012-09-01

    Full Text Available Histones are highly alkaline proteins that package and order the DNA into chromatin in eukaryotic cells. Nucleotide excision repair (NER is a conserved multistep reaction that removes a wide range of generally bulky and/or helix-distorting DNA lesions. Although the core biochemical mechanism of NER is relatively well known, how cells detect and repair lesions in diverse chromatin environments is still under intensive research. As with all DNA-related processes, the NER machinery must deal with the presence of organized chromatin and the physical obstacles it presents. A huge catalogue of posttranslational histone modifications has been documented. Although a comprehensive understanding of most of these modifications is still lacking, they are believed to be important regulatory elements for many biological processes, including DNA replication and repair, transcription and cell cycle control. Some of these modifications, including acetylation, methylation, phosphorylation and ubiquitination on the four core histones (H2A, H2B, H3 and H4 or the histone H2A variant H2AX, have been found to be implicated in different stages of the NER process. This review will summarize our recent understanding in this area.

  19. Dimensions of driving anger and their relationships with aberrant driving.

    Science.gov (United States)

    Zhang, Tingru; Chan, Alan H S; Zhang, Wei

    2015-08-01

    The purpose of this study was to investigate the relationship between driving anger and aberrant driving behaviours. An internet-based questionnaire survey was administered to a sample of Chinese drivers, with driving anger measured by a 14-item short Driving Anger Scale (DAS) and the aberrant driving behaviours measured by a 23-item Driver Behaviour Questionnaire (DBQ). The results of Confirmatory Factor Analysis demonstrated that the three-factor model (hostile gesture, arrival-blocking and safety-blocking) of the DAS fitted the driving anger data well. The Exploratory Factor Analysis on DBQ data differentiated four types of aberrant driving, viz. emotional violation, error, deliberate violation and maintaining progress violation. For the anger-aberration relation, it was found that only "arrival-blocking" anger was a significant positive predictor for all four types of aberrant driving behaviours. The "safety-blocking" anger revealed a negative impact on deliberate violations, a finding different from previously established positive anger-aberration relation. These results suggest that drivers with different patterns of driving anger would show different behavioural tendencies and as a result intervention strategies may be differentially effective for drivers of different profiles. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Trophic interaction modifications: an empirical and theoretical framework.

    Science.gov (United States)

    Terry, J Christopher D; Morris, Rebecca J; Bonsall, Michael B

    2017-10-01

    Consumer-resource interactions are often influenced by other species in the community. At present these 'trophic interaction modifications' are rarely included in ecological models despite demonstrations that they can drive system dynamics. Here, we advocate and extend an approach that has the potential to unite and represent this key group of non-trophic interactions by emphasising the change to trophic interactions induced by modifying species. We highlight the opportunities this approach brings in comparison to frameworks that coerce trophic interaction modifications into pairwise relationships. To establish common frames of reference and explore the value of the approach, we set out a range of metrics for the 'strength' of an interaction modification which incorporate increasing levels of contextual information about the system. Through demonstrations in three-species model systems, we establish that these metrics capture complimentary aspects of interaction modifications. We show how the approach can be used in a range of empirical contexts; we identify as specific gaps in current understanding experiments with multiple levels of modifier species and the distributions of modifications in networks. The trophic interaction modification approach we propose can motivate and unite empirical and theoretical studies of system dynamics, providing a route to confront ecological complexity. © 2017 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

  1. Control rod drive mechanism

    International Nuclear Information System (INIS)

    Nakamura, Akira.

    1981-01-01

    Purpose: To ensure the scram operation of a control rod by the reliable detection for the position of control rods. Constitution: A permanent magnet is provided to the lower portion of a connecting rod in engagement with a control rod and a tube having a plurality of lead switches arranged axially therein in a predetermined pitch is disposed outside of the control rod drives. When the control rod moves upwardly in the scram operation, the lead switches are closed successively upon passage of the permanent magnet to operate the electrical circuit provided by way of each of the lead switches. Thus, the position for the control rod during the scram can reliably be determined and the scram characteristic of the control rod can be recognized. (Furukawa, Y.)

  2. [Epilepsy and driving].

    Science.gov (United States)

    Matsuura, Masato

    2014-05-01

    In Japan, the Road Traffic Act was amended in June 2013, including new penalty to false statement in a disease condition declaration form, and new voluntary notification system for a doctor who is aware that a person is at high risk for traffic accident and in possession of a driver license. Moreover, New Criminal Law Act was established in November 2013, including a prison sentence of up to 15 years for persons, who under the influence of specific drugs or diseases, causing death or injury to other persons by driving a motor vehicle. Both laws are supposed to be enforced during 2014, after additional resolutions including the review of the laws after five years, considerations so as not to create discrimination due to diseases, etc are examined.

  3. Control rod drives

    International Nuclear Information System (INIS)

    Furumitsu, Yutaka.

    1981-01-01

    Purpose: To improve the reliability of a device for driving an LMFBR type reactor control rod by providing a buffer unit having a stationary electromagnetic coil and a movable electromagnetic coil in the device to thereby avord impact stress at scram time and to simplify the structure of the buffer unit. Constitution: A non-contact type buffer unit is constructed with a stationary electromagnetic coil, a cable for the stationary coil, a movable electromagnetic coil, a spring cable for the movable coil, and a backup coil spring or the like. Force produced at scram time is delivered without impact by the attracting or repelling force between the stationary coil and the movable coil of the buffer unit. Accordingly, since the buffer unit is of a non-contact type, there is no mechanical impact and thus no large impact stress, and as it has simple configuration, the reliability is improved and the maintenance can be conducted more easily. (Yoshihara, H.)

  4. Control rod drives

    International Nuclear Information System (INIS)

    Yamanaka, Toshikatsu.

    1979-01-01

    Purpose: To protect bellows against failures due to negative pressure to prevent the loss of pressure balance caused by the expansion of the bellows upon scram. Constitution: An expansion pipe connected to the control rod drive is driven along a guide pipe to insert a control rod into the reactor core. Expansible bellows are provided at the step between the expansion pipe and the guide pipe. Further, a plurality of bore holes or slits are formed on the side wall of the guide pipe corresponding to the expansion portion of the bellows. In such an arrangement, when the expansion pipe falls rapidly and the bellows are expanded upon scram, the volume between each of the pipes of the bellows and the guide pipe is increased to produce a negative pressure, but the effect of the negative pressure on the bellows can be eliminated by the flowing-in of coolants corresponding to that pressure through the bore holes or the slits. (Furukawa, Y.)

  5. PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination.

    Science.gov (United States)

    Baker, Christopher L; Kajita, Shimpei; Walker, Michael; Saxl, Ruth L; Raghupathy, Narayanan; Choi, Kwangbom; Petkov, Petko M; Paigen, Kenneth

    2015-01-01

    Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced experimentally. Comparing these two strains, we find that haplotype differences at hotspots lead to qualitative and quantitative changes in PRDM9 binding and activity. Using Mus spretus as an outlier, we found most variants affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing hotspot activity. Furthermore, M.m. castaneus×M.m. domesticus F1 hybrids exhibit novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin modification. These novel hotspots represent sites of historic evolutionary erosion that become activated in hybrids due to crosstalk between one parent's Prdm9 allele and the opposite parent's chromosome. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion.

  6. Do emotions drive psychosis?

    Directory of Open Access Journals (Sweden)

    João G. Ribeiro

    2012-12-01

    Full Text Available Introduction: How important is the emotional life of persons who manifest psychotic symptoms? Aims: The aim of this paper is to review evidence on a causal role for emotions in psychotic processes. Methods: Selective review of literature on affective symptoms in psychoses, on emotions in the production of psychotic symptoms and on dopaminergic models of psychosis. Results: Affective symptoms are relevant across psychoses. Persons with schizophrenia have high levels of emotional reactivity and the intensification of negative affects not only is associated with but also precedes the intensification of psychotic symptoms, which is evidence that negative emotions drive the course of psychotic symptoms. Negative self‑representations are central in psychotic processes and can be the link between negative emotions and psychosis. Evidence favours the notion that persecutory delusions are consistent with negative affects and self‑representations, while grandiose delusions are consistent with a defensive amplification of positive affects and self‑representations. Shame has been proposed as the core emotional experience of psychosis, one in which the self becomes vulnerable to the external world, which is consistent with persecutory experiences. Assaults on the self, under the form of hostility in the family environment and society, are strong predictors of relapse and development of schizophrenia. Assaults on the self which induce social defeat are also strong stimulants of mesolimbic dopaminergic pathways, whose hyperactivity is associated with acute psychotic episodes and the experience of “aberrant salience”, put forward as a dopaminergic model of psychosis. Conclusions: The “defeat of the self” emerges as a central link that binds the experience of negative emotions to the expression of psychotic symptoms and its psychological and neurobiological correlates. The hypothesis gains support that the emotions related to that defeat control

  7. Enzymatic Modification of Sphingomyelin

    DEFF Research Database (Denmark)

    Due to its major role in maintaining the water-retaining properties of the epidermis, ceramide is of great commercial potential in cosmetic and pharmaceuticals such as hair and skin care products. Currently, chemical synthesis of ceramide is a costly process, and developments of alternative cost......-efficient, high yield production methods are of great interest. In the present study, the potential of producing ceramide through the enzymatic hydrolysis of sphingomyelin have been studied. sphingomyelin is a ubiquitous membrane-lipid and rich in dairy products or by-products. It has been verified...... that sphingomyelin modification gives a feasible approach to the potential production of ceramide. The reaction system has been improved through system evaluation and the optimization of several important factors, and phospholipase C from Clostridium perfringens shows higher activity towards the hydrolysis reaction...

  8. CLIC Drive Beam Phase Stabilisation

    CERN Document Server

    Gerbershagen, Alexander; Schulte, Daniel

    The thesis presents phase stability studies for the Compact Linear Collider (CLIC) and focuses in particular on CLIC Drive Beam longitudinal phase stabilisation. This topic constitutes one of the main feasibility challenges for CLIC construction and is an essential component of the current CLIC stabilisation campaign. The studies are divided into two large interrelated sections: the simulation studies for the CLIC Drive Beam stability, and measurements, data analysis and simulations of the CLIC Test Facility (CTF3) Drive Beam phase errors. A dedicated software tool has been developed for a step-by-step analysis of the error propagation through the CLIC Drive Beam. It uses realistic RF potential and beam loading amplitude functions for the Drive and Main Beam accelerating structures, complete models of the recombination scheme and compressor chicane as well as of further CLIC Drive Beam modules. The tool has been tested extensively and its functionality has been verified. The phase error propagation at CLIC h...

  9. H1 antihistamines and driving.

    Science.gov (United States)

    Popescu, Florin Dan

    2008-01-01

    Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion. Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one.

  10. Targeting post-translational modifications of histones for cancer therapy.

    Science.gov (United States)

    Hsu, Y-C; Hsieh, Y-H; Liao, C-C; Chong, L-W; Lee, C-Y; Yu, Y-L; Chou, R-H

    2015-10-30

    Post-translational modifications (PTMs) on histones including acetylation, methylation, phosphorylation, citrullination, ubiquitination, ADP ribosylation, and sumoylation, play important roles in different biological events including chromatin dynamics, DNA replication, and transcriptional regulation. Aberrant histones PTMs leads to abnormal gene expression and uncontrolled cell proliferation, followed by development of cancers. Therefore, targeting the enzymes required for specific histone PTMs holds a lot of potential for cancer treatment. In this review article, we retrospect the latest studies in the regulations of acetylation, methylation, and phosphorylation of histones. We also summarize inhibitors/drugs that target these modifications for cancer treatment.

  11. DNA methylation

    DEFF Research Database (Denmark)

    Williams, Kristine; Christensen, Jesper; Helin, Kristian

    2012-01-01

    DNA methylation is involved in key cellular processes, including X-chromosome inactivation, imprinting and transcriptional silencing of specific genes and repetitive elements. DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. The recent...... discovery that the three members of the TET protein family can convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) has provided a potential mechanism leading to DNA demethylation. Moreover, the demonstration that TET2 is frequently mutated in haematopoietic tumours suggests that the TET...... proteins are important regulators of cellular identity. Here, we review the current knowledge regarding the function of the TET proteins, and discuss various mechanisms by which they contribute to transcriptional control. We propose that the TET proteins have an important role in regulating DNA methylation...

  12. DNA data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Raw DNA chromatogram data produced by the ABI 373, 377, 3130 and 3730 automated sequencing machines in ABI format. These are from fish (primarily Sebastes spp.,...

  13. DNA nanotechnology

    Science.gov (United States)

    Seeman, Nadrian C.; Sleiman, Hanadi F.

    2018-01-01

    DNA is the molecule that stores and transmits genetic information in biological systems. The field of DNA nanotechnology takes this molecule out of its biological context and uses its information to assemble structural motifs and then to connect them together. This field has had a remarkable impact on nanoscience and nanotechnology, and has been revolutionary in our ability to control molecular self-assembly. In this Review, we summarize the approaches used to assemble DNA nanostructures and examine their emerging applications in areas such as biophysics, diagnostics, nanoparticle and protein assembly, biomolecule structure determination, drug delivery and synthetic biology. The introduction of orthogonal interactions into DNA nanostructures is discussed, and finally, a perspective on the future directions of this field is presented.

  14. Failure Prediction for Autonomous Driving

    OpenAIRE

    Hecker, Simon; Dai, Dengxin; Van Gool, Luc

    2018-01-01

    The primary focus of autonomous driving research is to improve driving accuracy. While great progress has been made, state-of-the-art algorithms still fail at times. Such failures may have catastrophic consequences. It therefore is important that automated cars foresee problems ahead as early as possible. This is also of paramount importance if the driver will be asked to take over. We conjecture that failures do not occur randomly. For instance, driving models may fail more likely at places ...

  15. The Drive-Wise Project: Driving Simulator Training increases real driving performance in healthy older drivers

    Directory of Open Access Journals (Sweden)

    Gianclaudio eCasutt

    2014-05-01

    Full Text Available Background: Age-related cognitive decline is often associated with unsafe driving behavior. We hypothesized that 10 active training sessions in a driving simulator increase cognitive and on-road driving performance. In addition, driving simulator training should outperform cognitive training.Methods: Ninety-one healthy active drivers (62 – 87 years were randomly assigned to either (1 a driving simulator training group, (2 an attention training group (vigilance and selective attention, or (3 a control group. The main outcome variables were on-road driving and cognitive performance. Seventy-seven participants (85% completed the training and were included in the analyses. Training gains were analyzed using a multiple regression analysis with planned comparisons.Results: The driving simulator training group showed an improvement in on-road driving performance compared to the attention training group. In addition, both training groups increased cognitive performance compared to the control group. Conclusion: Driving simulator training offers the potential to enhance driving skills in older drivers. Compared to the attention training, the simulator training seems to be a more powerful program for increasing older drivers’ safety on the road.

  16. DNA expressions - A formal notation for DNA

    NARCIS (Netherlands)

    Vliet, Rudy van

    2015-01-01

    We describe a formal notation for DNA molecules that may contain nicks and gaps. The resulting DNA expressions denote formal DNA molecules. Different DNA expressions may denote the same molecule. Such DNA expressions are called equivalent. We examine which DNA expressions are minimal, which

  17. Noninductive current drive in tokamaks

    International Nuclear Information System (INIS)

    Uckan, N.A.

    1985-01-01

    Various current drive mechanisms may be grouped into four classes: (1) injection of energetic particle beams; (2) launching of rf waves; (3) hybrid schemes, which are combinations of various rf schemes (rf plus beams, rf and/or beam plus ohmic heating, etc.); and (4) other schemes, some of which are specific to reactor plasma conditions requiring the presence of alpha particle or intense synchrotron radiation. Particle injection schemes include current drive by neutral beams and relativistic electron beams. The rf schemes include current drive by the lower hybrid (LH) waves, the electron waves, the waves in the ion cyclotron range of frequencies, etc. Only a few of these approaches, however, have been tested experimentally, with the broadest data base available for LH waves. Included in this report are (1) efficiency criteria for current drive, (2) current drive by neutral beam injection, (3) LH current drive, (4) electron cyclotron current drive, (5) current drive by ion cyclotron waves - minority species heating, and (6) current drive by other schemes (such as hybrids and low frequency waves)

  18. Electric motor drive unit, especially adjustment drive for vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Litterst, P

    1980-05-29

    An electric motor drive unit, particularly an adjustment drive for vehicles with at least two parallel drive shafts is described, which is compact and saves space, and whose manufacturing costs are low compared with those of well-known drive units of this type. The drive unit contains a suitable number of magnet systems, preferably permanent magnet systems, whose pole axes are spaced and run parallel. The two pole magnet systems have diametrically opposite shell-shaped segments, to which the poles are fixed. In at least one magnet system the two segments are connected by diametrically opposite flat walls parallel to the pole axes to form a single magnetic circuit pole housing. The segments of at least one other magnet system are arranged on this pole housing so that one of these flat walls is a magnetically conducting, connecting component of the magnetic circuit of the other magnet system.

  19. What Is Mitochondrial DNA?

    Science.gov (United States)

    ... DNA What is mitochondrial DNA? What is mitochondrial DNA? Although most DNA is packaged in chromosomes within ... proteins. For more information about mitochondria and mitochondrial DNA: Molecular Expressions, a web site from the Florida ...

  20. Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1.

    Science.gov (United States)

    Harrison, Joseph S; Cornett, Evan M; Goldfarb, Dennis; DaRosa, Paul A; Li, Zimeng M; Yan, Feng; Dickson, Bradley M; Guo, Angela H; Cantu, Daniel V; Kaustov, Lilia; Brown, Peter J; Arrowsmith, Cheryl H; Erie, Dorothy A; Major, Michael B; Klevit, Rachel E; Krajewski, Krzysztof; Kuhlman, Brian; Strahl, Brian D; Rothbart, Scott B

    2016-09-06

    The epigenetic inheritance of DNA methylation requires UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that recruits DNMT1 to sites of newly replicated DNA through ubiquitylation of histone H3. UHRF1 binds DNA with selectivity towards hemi-methylated CpGs (HeDNA); however, the contribution of HeDNA sensing to UHRF1 function remains elusive. Here, we reveal that the interaction of UHRF1 with HeDNA is required for DNA methylation but is dispensable for chromatin interaction, which is governed by reciprocal positive cooperativity between the UHRF1 histone- and DNA-binding domains. HeDNA recognition activates UHRF1 ubiquitylation towards multiple lysines on the H3 tail adjacent to the UHRF1 histone-binding site. Collectively, our studies are the first demonstrations of a DNA-protein interaction and an epigenetic modification directly regulating E3 ubiquitin ligase activity. They also define an orchestrated epigenetic control mechanism involving modifications both to histones and DNA that facilitate UHRF1 chromatin targeting, H3 ubiquitylation, and DNA methylation inheritance.

  1. Control rod drives

    International Nuclear Information System (INIS)

    Ikakura, Hiroaki.

    1986-01-01

    Purpose: To enable to direct disconnection of control rods upon abnormal temperature rise in the reactor thereby improve the reliability for the disconnecting operation in control rod drives for FBR type reactors upon emergency. Constitution: A diaphragm is disposed to the upper opening of a sealing vessel inserted to the hollow portion of an electromagnet and a rod is secured to the central position of the upper surface. A spring contacts are attached by way of an insulator to the inner surface at the lower portion of an extension pipe and connected with cables for supplying electric power sources respectively to a magnet. If the temperature in the reactor abnormally rises, liquid metals in the sealing vessel are expanded tending to extend the bellows downwardly. However, since they are attracted by the electromagnet, the thermal expansion of the liquid metals exert on the diaphragm prior to the bellows. Thus, the switch between the spring contacts is made open to attain the deenergized state to thereby disconnect the control rod and shutdown the neclear reactor. (Horiuchi, T.)

  2. Control rod drive

    International Nuclear Information System (INIS)

    Kojima, Akira.

    1989-01-01

    In the control rod drive for a BWR type reactor, etc., according to this invention, the lower limit flow rate is set so as to keep the restriction for stability upon spectral shift operation. The setting condition for keeping the restriction is the lowest pump speed and the lower limit for the automatic control of the flow rate, which are considered to be important in view of the stablility from the actual power state. In view of the above, it is possible to keep the reactor core stably even in a case where such a transient phenomenon occurs that the recycling flow rate has to be run back to the lowest pump speed during spectral shift opeeration or in a case where the load demand is reduced and the flow rate is decreased by an automatic mode as in night operation. Accordingly, in the case of conducting the spectral shift operation according to this invention, the operation region capable of keeping the reactor core state stably during operation can be extended. (I.S.)

  3. Implication des modifications épigénétiques dans les cancers : développement de nouvelles approches thérapeutiques

    Directory of Open Access Journals (Sweden)

    Willems L.

    2008-01-01

    Full Text Available Involvement of epigenetic modifications in cancers: development of new therapeutic approaches. Since cancer is the second cause of death after cardiovascular diseases in industrialized countries, it is urgent to elaborate new therapeutic approaches. Besides DNA mutations of essential genes, expansion of a cancer cell is frequently associated with epigenetic modifications i.e. not directly coded by the DNA sequence. Amongst epigenetic modifications, histones acetylation and DNA methylation are known to play important roles. In this context, a very promising anticancer therapy would be to correct epigenetic errors using compounds modulating histone acetylation and DNA methylation alone or in combination with other chemotherapeutic agents.

  4. Cas9-triggered chain ablation of cas9 as a gene drive brake

    OpenAIRE

    Wu, Bing; Luo, Liqun; Gao, Xiaojing J.

    2016-01-01

    With the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) technology, researchers can construct gene drives that can bias the inheritance of edited alleles to alter entire populations. As demonstrated with the mutagenic chain reaction in Drosophila4, the CRISPR-Cas9 system can propagate genomic modification together with the genome-editing machinery itself. Although gene drives might have the potential to control insect-borne di...

  5. Control rod drive shaft latch

    International Nuclear Information System (INIS)

    Thorp, A.G. II.

    1976-01-01

    A latch mechanism is operated by differential pressure on a piston to engage the drive shaft for a control rod in a nuclear reactor, thereby preventing the control rod from being ejected from the reactor in case of failure of the control rod drive mechanism housing which is subjected to the internal pressure in the reactor vessel. 6 claims, 4 drawing figures

  6. ECO-DRIVING MODELING ENVIRONMENT

    Science.gov (United States)

    2015-11-01

    This research project aims to examine the eco-driving modeling capabilities of different traffic modeling tools available and to develop a driver-simulator-based eco-driving modeling tool to evaluate driver behavior and to reliably estimate or measur...

  7. Real-world driving behaviour

    NARCIS (Netherlands)

    Rijkeboer, R.C.; Hendriksen, P.; Gense, N.L.J.

    2001-01-01

    With increasing complexity of engine management system there is a tendency for traditional driving cyles to become further and further removed from reality. So for a sensible evaluation of emissions and fuel consumption of road vehicles in the field there is an urgent need for 'real-world' driving

  8. H1 antihistamines and driving

    OpenAIRE

    Florin-Dan, Popescu

    2008-01-01

    Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion, Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and...

  9. Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage

    Directory of Open Access Journals (Sweden)

    Robert L. Eoff

    2010-01-01

    Full Text Available DNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and disease in multi-cellular organisms. Investigations into the chemical and biological aspects of DNA damage have identified multi-tiered and overlapping cellular systems that have evolved as a means of stabilizing the genome. One of these pathways supports DNA replication events by in a sense adopting the mantra that one must “make the best of a bad situation” and tolerating covalent modification to DNA through less accurate copying of the damaged region. Part of this so-called DNA damage tolerance pathway involves the recruitment of specialized DNA polymerases to sites of stalled or collapsed replication forks. These enzymes have unique structural and functional attributes that often allow bypass of adducted template DNA and successful completion of genomic replication. What follows is a selective description of the salient structural features and bypass properties of specialized DNA polymerases with an emphasis on Y-family members.

  10. Regulation and function of DNA methylation in plants and animals

    KAUST Repository

    He, Xinjian

    2011-02-15

    DNA methylation is an important epigenetic mark involved in diverse biological processes. In plants, DNA methylation can be established through the RNA-directed DNA methylation pathway, an RNA interference pathway for transcriptional gene silencing (TGS), which requires 24-nt small interfering RNAs. In mammals, de novo DNA methylation occurs primarily at two developmental stages: during early embryogenesis and during gametogenesis. While it is not clear whether establishment of DNA methylation patterns in mammals involves RNA interference in general, de novo DNA methylation and suppression of transposons in germ cells require 24-32-nt piwi-interacting small RNAs. DNA methylation status is dynamically regulated by DNA methylation and demethylation reactions. In plants, active DNA demethylation relies on the repressor of silencing 1 family of bifunctional DNA glycosylases, which remove the 5-methylcytosine base and then cleave the DNA backbone at the abasic site, initiating a base excision repair (BER) pathway. In animals, multiple mechanisms of active DNA demethylation have been proposed, including a deaminase- and DNA glycosylase-initiated BER pathway. New information concerning the effects of various histone modifications on the establishment and maintenance of DNA methylation has broadened our understanding of the regulation of DNA methylation. The function of DNA methylation in plants and animals is also discussed in this review. © 2011 IBCB, SIBS, CAS All rights reserved.

  11. [Driving and health at work].

    Science.gov (United States)

    Giorgio, Marie-Thérèse

    2015-09-01

    The role of the occupational physician is to prevent occupational accidents and diseases. Therefore, he is the one to decide if a worker is fit to drive in the context of his professional activity, including in cases where no specific driving license is required (e.g. forklift truck, mobile crane). This decision is an important one, as two thirds of fatal occupational accidents occur on the road. The decision is made on the basis of both a medical examination and the regulation, which indicates all contraindications to driving. The physician's responsibility is involved, as is the employer's, as he must ensure that his employee is fit to drive and possesses a valid driving license at all times. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Epigenetics: Making your mark on DNA

    Science.gov (United States)

    Harada, Bryan T.; He, Chuan

    2017-11-01

    Understanding the biological roles of modifications to DNA, RNA and proteins is critical to revealing how cells regulate gene expression in development and disease. Two papers now present a combination of new tools and discoveries that could enable biologists and chemical biologists to better study epigenetic regulation in mammals.

  13. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  14. Epigenetic Modifications of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Kathleen Saavedra

    2016-08-01

    Full Text Available Major depressive disorder (MDD is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders.

  15. Modification of radiation effect by sodium fluoride in Tradescantia

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.; Guminska, M.; Huczkowski, J.; Kuternozinska, W.

    1988-01-01

    Frequency of somatic mutations in the Tradescantia stamen hairs served as a measure of biological effect of gamma irradiation with single and split doses and of modifications caused by sodium fluoride. It was found that treatment of plants with fluoride before irradiation affects considerably radiation-induced mutations. The changed peak mutation frequency in plants treated with fluoride suggests that it vitally influences the repair processes of DNA and possibly modifies the mutation spectrum. 14 refs., 3 figs. (author)

  16. Personal Computer Based Controller For Switched Reluctance Motor Drives

    Science.gov (United States)

    Mang, X.; Krishnan, R.; Adkar, S.; Chandramouli, G.

    1987-10-01

    Th9, switched reluctance motor (SRM) has recently gained considerable attention in the variable speed drive market. Two important factors that have contributed to this are, the simplicity of construction and the possibility of developing low cost con-trollers with minimum number of switching devices in the drive circuits. This is mainly due to the state-of-art of the present digital circuits technology and the low cost of switching devices. The control of this motor drive is under research. Optimized performance of the SRM motor drive is very dependent on the integration of the controller, converter and the motor. This research on system integration involves considerable changes in the control algorithms and their implementation. A Personal computer (PC) based controller is very appropriate for this purpose. Accordingly, the present paper is concerned with the design of a PC based controller for a SRM. The PC allows for real-time microprocessor control with the possibility of on-line system parameter modifications. Software reconfiguration of this controller is easier than a hardware based controller. User friendliness is a natural consequence of such a system. Considering the low cost of PCs, this controller will offer an excellent cost-effective means of studying the control strategies for the SRM drive intop greater detail than in the past.

  17. An integrated epigenetic and genetic analysis of DNA methyltransferase genes (DNMTs) in tumor resistant and susceptible chicken lines

    Science.gov (United States)

    Both epigenetic alterations and genetic variations play essential roles in tumorigenesis. The epigenetic modification of DNA methylation is catalyzed and maintained by the DNA methyltransferases (DNMT3a, DNMT3b and DNMT1). DNA mutations and DNA methylation profiles of DNMTs themselves and their rela...

  18. DNA damage in plant herbarium tissue.

    Science.gov (United States)

    Staats, Martijn; Cuenca, Argelia; Richardson, James E; Vrielink-van Ginkel, Ria; Petersen, Gitte; Seberg, Ole; Bakker, Freek T

    2011-01-01

    Dried plant herbarium specimens are potentially a valuable source of DNA. Efforts to obtain genetic information from this source are often hindered by an inability to obtain amplifiable DNA as herbarium DNA is typically highly degraded. DNA post-mortem damage may not only reduce the number of amplifiable template molecules, but may also lead to the generation of erroneous sequence information. A qualitative and quantitative assessment of DNA post-mortem damage is essential to determine the accuracy of molecular data from herbarium specimens. In this study we present an assessment of DNA damage as miscoding lesions in herbarium specimens using 454-sequencing of amplicons derived from plastid, mitochondrial, and nuclear DNA. In addition, we assess DNA degradation as a result of strand breaks and other types of polymerase non-bypassable damage by quantitative real-time PCR. Comparing four pairs of fresh and herbarium specimens of the same individuals we quantitatively assess post-mortem DNA damage, directly after specimen preparation, as well as after long-term herbarium storage. After specimen preparation we estimate the proportion of gene copy numbers of plastid, mitochondrial, and nuclear DNA to be 2.4-3.8% of fresh control DNA and 1.0-1.3% after long-term herbarium storage, indicating that nearly all DNA damage occurs on specimen preparation. In addition, there is no evidence of preferential degradation of organelle versus nuclear genomes. Increased levels of C→T/G→A transitions were observed in old herbarium plastid DNA, representing 21.8% of observed miscoding lesions. We interpret this type of post-mortem DNA damage-derived modification to have arisen from the hydrolytic deamination of cytosine during long-term herbarium storage. Our results suggest that reliable sequence data can be obtained from herbarium specimens.

  19. Mitochondrial DNA: A Blind Spot in Neuroepigenetics.

    Science.gov (United States)

    Manev, Hari; Dzitoyeva, Svetlana; Chen, Hu

    2012-04-01

    Neuroepigenetics, which includes nuclear DNA modifications such as 5-methylcytosine and 5-hydoxymethylcytosine and modifications of nuclear proteins such as histones, is emerging as the leading field in molecular neuroscience. Historically, a functional role for epigenetic mechanisms, including in neuroepigenetics, has been sought in the area of the regulation of nuclear transcription. However, one important compartment of mammalian cell DNA, different from nuclear but equally important for physiological and pathological processes (including in the brain), mitochondrial DNA has for the most part not had a systematic epigenetic characterization. The importance of mitochondria and mitochondrial DNA (particularly its mutations) in central nervous system physiology and pathology has long been recognized. Only recently have mechanisms of mitochondrial DNA methylation and hydroxymethylation, including the discovery of mitochondrial DNA-methyltransferases and the presence and the functionality of 5-methylcytosine and 5-hydroxymethylcytosine in mitochondrial DNA (e.g., in modifying the transcription of mitochondrial genome), been unequivocally recognized as a part of mammalian mitochondrial physiology. Here we summarize for the first time evidence supporting the existence of these mechanisms and we propose the term "mitochondrial epigenetics" to be used when referring to them. Currently, neuroepigenetics does not include mitochondrial epigenetics - a gap that we expect to close in the near future.

  20. Signatures of DNA target selectivity by ETS transcription factors.

    Science.gov (United States)

    Poon, Gregory M K; Kim, Hye Mi

    2017-05-27

    The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation.

  1. DNA-nuclear matrix interactions and ionizing radiation sensitivity

    International Nuclear Information System (INIS)

    Schwartz, J.L.; Chicago Univ., IL; Vaughan, A.T.M.

    1993-01-01

    The association between inherent ionizing radiation sensitivity and DNA supercoil unwinding in mammalian cells suggests that the DNA-nuclear matrix attachment region (MAR) plays an important role in radiation response. In radioresistant cells, the MAR structure may exist in a more stable, open configuration, limiting DNA unwinding following strand break induction and maintaining DNA ends in close proximity for more rapid and accurate rejoining. In addition, the open configuration at these matrix attachment sites may serve to facilitate rapid DNA processing of breaks by providing (1) sites for repair proteins to collect and (2) energy to drive enzymatic reactions

  2. Histone H2AX in DNA repair

    International Nuclear Information System (INIS)

    Lewandowska, H.; Szumiel, I.

    2002-01-01

    The paper reviews the recent reports on the role of the phosphorylated histone H2AX (γ-H2AX). The modification of this histone is an important part of the cellular response to the induction of DNA double strand brakes (DSB) by ionising radiation and other DSB-generating factors. In irradiated cells the modification is carried out mainly by ATM (ataxia-telangiectasia mutated) kinase, the enzyme that starts the alarm signalling upon induction of DSB.γ-H2AX molecules are formed within 1-3 min after irradiation and form foci at the sites of DSB. This seems to be necessary for the recruitment of repair factors that are later present in foci of damaged nuclei. Modification of a constant percentage of H2AX molecules per DSB takes place, corresponding to chromatin domains of megabase of DNA. (author)

  3. Radiation damage to DNA in DNA-protein complexes.

    Science.gov (United States)

    Spotheim-Maurizot, M; Davídková, M

    2011-06-03

    The most aggressive product of water radiolysis, the hydroxyl (OH) radical, is responsible for the indirect effect of ionizing radiations on DNA in solution and aerobic conditions. According to radiolytic footprinting experiments, the resulting strand breaks and base modifications are inhomogeneously distributed along the DNA molecule irradiated free or bound to ligands (polyamines, thiols, proteins). A Monte-Carlo based model of simulation of the reaction of OH radicals with the macromolecules, called RADACK, allows calculating the relative probability of damage of each nucleotide of DNA irradiated alone or in complexes with proteins. RADACK calculations require the knowledge of the three dimensional structure of DNA and its complexes (determined by X-ray crystallography, NMR spectroscopy or molecular modeling). The confrontation of the calculated values with the results of the radiolytic footprinting experiments together with molecular modeling calculations show that: (1) the extent and location of the lesions are strongly dependent on the structure of DNA, which in turns is modulated by the base sequence and by the binding of proteins and (2) the regions in contact with the protein can be protected against the attack by the hydroxyl radicals via masking of the binding site and by scavenging of the radicals. 2011 Elsevier B.V. All rights reserved.

  4. MODELING CONTROLLED ASYNCHRONOUS ELECTRIC DRIVES WITH MATCHING REDUCERS AND TRANSFORMERS

    Directory of Open Access Journals (Sweden)

    V. S. Petrushin

    2015-04-01

    Full Text Available Purpose. Working out of mathematical models of the speed-controlled induction electric drives ensuring joint consideration of transformers, motors and loadings, and also matching reducers and transformers, both in static, and in dynamic regimes for the analysis of their operating characteristics. Methodology. At mathematical modelling are considered functional, mass, dimensional and cost indexes of reducers and transformers that allows observing engineering and economic aspects of speed-controlled induction electric drives. The mathematical models used for examination of the transitive electromagnetic and electromechanical processes, are grounded on systems of nonlinear differential equations with nonlinear coefficients (parameters of equivalent circuits of motors, varying in each operating point, including owing to appearances of saturation of magnetic system and current displacement in a winding of a rotor of an induction motor. For the purpose of raise of level of adequacy of models a magnetic circuit iron, additional and mechanical losses are considered. Results. Modelling of the several speed-controlled induction electric drives, different by components, but working on a loading equal on character, magnitude and a demanded control range is executed. At use of characteristic families including mechanical, at various parameters of regulating on which performances of the load mechanism are superimposed, the adjusting characteristics representing dependences of a modification of electrical, energy and thermal magnitudes from an angular speed of motors are gained. Originality. The offered complex models of speed-controlled induction electric drives with matching reducers and transformers, give the chance to realize well-founded sampling of components of drives. They also can be used as the design models by working out of speed-controlled induction motors. Practical value. Operating characteristics of various speed-controlled induction electric

  5. Automated driving safer and more efficient future driving

    CERN Document Server

    Horn, Martin

    2017-01-01

    The main topics of this book include advanced control, cognitive data processing, high performance computing, functional safety, and comprehensive validation. These topics are seen as technological bricks to drive forward automated driving. The current state of the art of automated vehicle research, development and innovation is given. The book also addresses industry-driven roadmaps for major new technology advances as well as collaborative European initiatives supporting the evolvement of automated driving. Various examples highlight the state of development of automated driving as well as the way forward. The book will be of interest to academics and researchers within engineering, graduate students, automotive engineers at OEMs and suppliers, ICT and software engineers, managers, and other decision-makers.

  6. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    Science.gov (United States)

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

  7. Extraction of genomic DNA from Melipona quadrifasciata (Hymenoptera: Apidae, Meliponinae)

    OpenAIRE

    Waldschmidt, Ana Maria; Salomão, Tânia Maria Fernandes; Barros, Everaldo Gonçalves de; Campos, Lúcio de Antônio Oliveira

    1997-01-01

    The objective of the present study was to test three different procedures for DNA extraction of Melipona quadrifasciata based on existing methods for DNA extraction of Apis, plants and fungi. These methods differ in the concentrations of specific substances in the extraction buffer. The results demonstrate that the method used for Apis is not adequate for DNA extraction from M. quadrifasciata. On the other hand, with minor modifications this method and the methods for plants and fungi were ad...

  8. Allele-Specific DNA Methylation Detection by Pyrosequencing®

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Johansen, Jens Vilstrup; Grønbæk, Kirsten

    2015-01-01

    DNA methylation is an epigenetic modification that plays important roles in healthy as well as diseased cells, by influencing the transcription of genes. In spite the fact that human somatic cells are diploid, most of the currently available methods for the study of DNA methylation do not provide......-effective protocol for allele-specific DNA methylation detection based on Pyrosequencing(®) of methylation-specific PCR (MSP) products including a single nucleotide polymorphism (SNP) within the amplicon....

  9. Induced Polarization Influences the Fundamental Forces in DNA Base Flipping

    OpenAIRE

    Lemkul, Justin A.; Savelyev, Alexey; MacKerell, Alexander D.

    2014-01-01

    Base flipping in DNA is an important process involved in genomic repair and epigenetic control of gene expression. The driving forces for these processes are not fully understood, especially in the context of the underlying dynamics of the DNA and solvent effects. We studied double-stranded DNA oligomers that have been previously characterized by imino proton exchange NMR using both additive and polarizable force fields. Our results highlight the importance of induced polarization on the base...

  10. DNA Vaccines

    Indian Academy of Sciences (India)

    diseases. Keywords. DNA vaccine, immune response, antibodies, infectious diseases. GENERAL .... tein vaccines require expensive virus/protein purification tech- niques as ... sphere continue to remain major health hazards in developing nations. ... significance since it can be produced at a very low cost and can be stored ...

  11. DNA Investigations.

    Science.gov (United States)

    Mayo, Ellen S.; Bertino, Anthony J.

    1991-01-01

    Presents a simulation activity that allow students to work through the exercise of DNA profiling and to grapple with some analytical and ethical questions involving a couple arranging with a surrogate mother to have a baby. Can be used to teach the principles of restriction enzyme digestion, gel electrophoresis, and probe hybridization. (MDH)

  12. THE IMPACT OF TEXT DRIVING ON DRIVING SAFETY

    OpenAIRE

    Sanaz Motamedi; Jyh-Hone Wang

    2016-01-01

    In an increasingly mobile era, the wide availability of technology for texting and the prevalence of hands-free form have introduced a new safety concern for drivers. To assess this concern, a questionnaire was first deployed online to gain an understanding of drivers’ text driving experiences as well as their demographic information. The results from 232 people revealed that the majority of drivers are aware of the associated risks with texting while driving. However, more than one-fourth of...

  13. DNA fingerprinting, DNA barcoding, and next generation sequencing technology in plants.

    Science.gov (United States)

    Sucher, Nikolaus J; Hennell, James R; Carles, Maria C

    2012-01-01

    DNA fingerprinting of plants has become an invaluable tool in forensic, scientific, and industrial laboratories all over the world. PCR has become part of virtually every variation of the plethora of approaches used for DNA fingerprinting today. DNA sequencing is increasingly used either in combination with or as a replacement for traditional DNA fingerprinting techniques. A prime example is the use of short, standardized regions of the genome as taxon barcodes for biological identification of plants. Rapid advances in "next generation sequencing" (NGS) technology are driving down the cost of sequencing and bringing large-scale sequencing projects into the reach of individual investigators. We present an overview of recent publications that demonstrate the use of "NGS" technology for DNA fingerprinting and DNA barcoding applications.

  14. The assessment of cold atmospheric plasma treatment of DNA in synthetic models of tissue fluid, tissue and cells

    Science.gov (United States)

    Szili, Endre J.; Gaur, Nishtha; Hong, Sung-Ha; Kurita, Hirofumi; Oh, Jun-Seok; Ito, Masafumi; Mizuno, Akira; Hatta, Akimitsu; Cowin, Allison J.; Graves, David B.; Short, Robert D.

    2017-07-01

    There is a growing literature database that demonstrates the therapeutic potential of cold atmospheric plasma (herein referred to as plasma). Given the breadth of proposed applications (e.g. from teeth whitening to cancer therapy) and vast gamut of plasma devices being researched, it is timely to consider plasma interactions with specific components of the cell in more detail. Plasma can produce highly reactive oxygen and nitrogen species (RONS) such as the hydroxyl radical (OH•), peroxynitrite (ONOO-) and superoxide (\\text{O}2- ) that would readily modify essential biomolecules such as DNA. These modifications could in principle drive a wide range of biological processes. Against this possibility, the reported therapeutic action of plasmas are not underpinned by a particularly deep knowledge of the potential plasma-tissue, -cell or -biomolecule interactions. In this study, we aim to partly address this issue by developing simple models to study plasma interactions with DNA, in the form of DNA-strand breaks. This is carried out using synthetic models of tissue fluid, tissue and cells. We argue that this approach makes experimentation simpler, more cost-effective and faster than compared to working with real biological materials and cells. Herein, a helium plasma jet source was utilised for these experiments. We show that the plasma jet readily induced DNA-strand breaks in the tissue fluid model and in the cell model, surprisingly without any significant poration or rupture of the phospholipid membrane. In the plasma jet treatment of the tissue model, DNA-strand breaks were detected in the tissue mass after pro-longed treatment (on the time-scale of minutes) with no DNA-strand breaks being detected in the tissue fluid model underneath the tissue model. These data are discussed in the context of the therapeutic potential of plasma.

  15. Semiclassical instability of warp drives

    Energy Technology Data Exchange (ETDEWEB)

    Barcelo, C [Instituto de Astrofisica de Andalucia, IAA-CSIC, Glorieta de la Astronomia s/n, 18008 Granada (Spain); Finazzi, S; Liberati, S, E-mail: carlos@iaa.e, E-mail: finazzi@sissa.i, E-mail: liberati@sissa.i

    2010-05-01

    Warp drives, at least theoretically, provide a way to travel at superluminal speeds. However, even if one succeeded in providing the necessary exotic matter to construct them, it would still be necessary to check whether they would survive to the switching on of quantum effects. In this contribution we will report on the behaviour of the Renormalized Stress-Energy Tensor (RSET) in the spacetimes associated with superluminal warp drives. We find that the RSET will exponentially grow in time close to the front wall of the superluminal bubble, hence strongly supporting the conclusion that the warp-drive geometries are unstable against semiclassical back-reaction.

  16. Driving Safety and Fitness to Drive in Sleep Disorders.

    Science.gov (United States)

    Tippin, Jon; Dyken, Mark Eric

    2017-08-01

    Driving an automobile while sleepy increases the risk of crash-related injury and death. Neurologists see patients with sleepiness due to obstructive sleep apnea, narcolepsy, and a wide variety of neurologic disorders. When addressing fitness to drive, the physician must weigh patient and societal health risks and regional legal mandates. The Driver Fitness Medical Guidelines published by the National Highway Traffic Safety Administration (NHTSA) and the American Association of Motor Vehicle Administrators (AAMVA) provide assistance to clinicians. Drivers with obstructive sleep apnea may continue to drive if they have no excessive daytime sleepiness and their apnea-hypopnea index is less than 20 per hour. Those with excessive daytime sleepiness or an apnea-hypopnea index of 20 per hour or more may not drive until their condition is effectively treated. Drivers with sleep disorders amenable to pharmaceutical treatment (eg, narcolepsy) may resume driving as long as the therapy has eliminated excessive daytime sleepiness. Following these guidelines, documenting compliance to recommended therapy, and using the Epworth Sleepiness Scale to assess subjective sleepiness can be helpful in determining patients' fitness to drive.

  17. Restriction-modification systems in Mycoplasma spp

    Directory of Open Access Journals (Sweden)

    Marcelo Brocchi

    2007-01-01

    Full Text Available Restriction and Modification (R-M systems are present in all Mycoplasma species sequenced so far. The presence of these genes poses barriers to gene transfer and could protect the cell against phage infections. The number and types of R-M genes between different Mycoplasma species are variable, which is characteristic of a polymorphism. The majority of the CDSs code for Type III R-M systems and particularly for methyltransferase enzymes, which suggests that functions other than the protection against the invasion of heterologous DNA may exist. A possible function of these enzymes could be the protection against the invasion of other but similar R-M systems. In Mycoplasma hyopneumoniae strain J, three of the putative methyltransferase genes were clustered in a region forming a genomic island. Many R-M CDSs were mapped in the vicinity of transposable elements suggesting an association between these genes and reinforcing the idea of R-M systems as mobile selfish DNA. Also, many R-M genes present repeats within their coding sequences, indicating that their expression is under the control of phase variation mechanisms. Altogether, these data suggest that R-M systems are a remarkable characteristic of Mycoplasma species and are probably involved in the adaptation of these bacteria to different environmental conditions.

  18. Novel concepts in modification of radiation sensitivity

    International Nuclear Information System (INIS)

    Bump, E.A.; Palayoor, S.T.; Lai, L.L.; Cerce, B.A.; Langley, R.E.; Coleman, C.N.; Braunhut, S.J.

    1994-01-01

    The purpose of this study was to determine whether biological effects of radiation, such as apoptosis, that differ from classical clonogenic cell killing, can be modified with agents that would not be expected to modify classical clonogenic cell killing. This would expand the range of potential modifiers of radiation therapy. EL4 murine lymphoma cell apoptosis was determined by electrophoretic analysis of deoxyribonucleic acid (DNA) fragmentation. DNA was extracted 24 h after irradiation or addition of inducing agents. Modifiers of radiation-induced apoptosis were added immediately after irradiation. The effects of radiation on wounded endothelial monolayers were studied by scraping a line across the monolayer 30 min after irradiation. Cell detachment was used as an endpoint to determine the protective effect of prolonged exposure to retinol prior to irradiation. EL4 cell apoptosis can be induced by tert-butyl hydroperoxide or the glutathione oxidant SR-4077. Radiation-induced EL4 cell apoptosis can be inhibited with 3-aminobenzamide, an agent that sensitizes cells to classical clonogenic cell killing. Radiation-induced endothelial cell detachment from confluent monolayers can be modified by pretreatment with retinol. These results raise the possibility that radiation could induce apoptosis by an oxidative stress mechanism that is different from that involved in classical clonogenic cell killing. These and other recent findings encourage the notion that differential modification of classical clonogenic cell killing and other important endpoints of radiation action may be possible. 47 refs., 3 figs

  19. Single-molecule chemical reactions on DNA origami

    DEFF Research Database (Denmark)

    Voigt, Niels Vinther; Tørring, Thomas; Rotaru, Alexandru

    2010-01-01

    as templates for building materials with new functional properties. Relatively large nanocomponents such as nanoparticles and biomolecules can also be integrated into DNA nanostructures and imaged. Here, we show that chemical reactions with single molecules can be performed and imaged at a local position...... on a DNA origami scaffold by atomic force microscopy. The high yields and chemoselectivities of successive cleavage and bond-forming reactions observed in these experiments demonstrate the feasibility of post-assembly chemical modification of DNA nanostructures and their potential use as locally......DNA nanotechnology and particularly DNA origami, in which long, single-stranded DNA molecules are folded into predetermined shapes, can be used to form complex self-assembled nanostructures. Although DNA itself has limited chemical, optical or electronic functionality, DNA nanostructures can serve...

  20. The Role of the Transcriptional Response to DNA Replication Stress.

    Science.gov (United States)

    Herlihy, Anna E; de Bruin, Robertus A M

    2017-03-02

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage.

  1. The Role of the Transcriptional Response to DNA Replication Stress

    Science.gov (United States)

    Herlihy, Anna E.; de Bruin, Robertus A.M.

    2017-01-01

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage. PMID:28257104

  2. Quantum effects in warp drives

    Directory of Open Access Journals (Sweden)

    Finazzi Stefano

    2013-09-01

    Full Text Available Warp drives are interesting configurations that, at least theoretically, provide a way to travel at superluminal speed. Unfortunately, several issues seem to forbid their realization. First, a huge amount of exotic matter is required to build them. Second, the presence of quantum fields propagating in superluminal warp-drive geometries makes them semiclassically unstable. Indeed, a Hawking-like high-temperature flux of particles is generated inside the warp-drive bubble, which causes an exponential growth of the energy density measured at the front wall of the bubble by freely falling observers. Moreover, superluminal warp drives remain unstable even if the Lorentz symmetry is broken by the introduction of regulating higher order terms in the Lagrangian of the quantum field. If the dispersion relation of the quantum field is subluminal, a black-hole laser phenomenon yields an exponential amplification of the emitted flux. If it is superluminal, infrared effects cause a linear growth of this flux.

  3. Multidisciplinary design of electrical drives

    Energy Technology Data Exchange (ETDEWEB)

    Blaabjerg, F.; Rasmussen, P.O.; Pedersen, J.K.

    1999-07-01

    Traditionally, simulation tools for drives can simulate electrical parameters, torque and different loads. Those parameters are in many cases appropriate. However, power electronics in drives will also influence on torque ripple, temperature, vibration and acoustical noise from the motor and it is necessary to include those phenomena in the next generation of simulation tools for electrical drives. This paper describes a new design program where acoustic noise of electromagnetic origin can be simulated and even be heard by the motor and drives designer. The design program is based on a simple vibrational/acoustic model where the parameters can be calculated based on the geometry of the motor. Examples of vibrational/acoustical modelling are included and verified in both time and frequency domain. Special emphasis is on the switched reluctance motor. (au)

  4. Clinical Action against Drunk Driving.

    Directory of Open Access Journals (Sweden)

    Donald A Redelmeier

    2017-02-01

    Full Text Available In advance of a safety campaign on 17 March 2017, Donald Redelmeier and Allan Detsky call on physicians and clinical colleagues to reduce the chances that patients will drive drunk.

  5. Biotechnological mass production of DNA origami

    Science.gov (United States)

    Praetorius, Florian; Kick, Benjamin; Behler, Karl L.; Honemann, Maximilian N.; Weuster-Botz, Dirk; Dietz, Hendrik

    2017-12-01

    DNA nanotechnology, in particular DNA origami, enables the bottom-up self-assembly of micrometre-scale, three-dimensional structures with nanometre-precise features. These structures are customizable in that they can be site-specifically functionalized or constructed to exhibit machine-like or logic-gating behaviour. Their use has been limited to applications that require only small amounts of material (of the order of micrograms), owing to the limitations of current production methods. But many proposed applications, for example as therapeutic agents or in complex materials, could be realized if more material could be used. In DNA origami, a nanostructure is assembled from a very long single-stranded scaffold molecule held in place by many short single-stranded staple oligonucleotides. Only the bacteriophage-derived scaffold molecules are amenable to scalable and efficient mass production; the shorter staple strands are obtained through costly solid-phase synthesis or enzymatic processes. Here we show that single strands of DNA of virtually arbitrary length and with virtually arbitrary sequences can be produced in a scalable and cost-efficient manner by using bacteriophages to generate single-stranded precursor DNA that contains target strand sequences interleaved with self-excising ‘cassettes’, with each cassette comprising two Zn2+-dependent DNA-cleaving DNA enzymes. We produce all of the necessary single strands of DNA for several DNA origami using shaker-flask cultures, and demonstrate end-to-end production of macroscopic amounts of a DNA origami nanorod in a litre-scale stirred-tank bioreactor. Our method is compatible with existing DNA origami design frameworks and retains the modularity and addressability of DNA origami objects that are necessary for implementing custom modifications using functional groups. With all of the production and purification steps amenable to scaling, we expect that our method will expand the scope of DNA nanotechnology in

  6. Acetylation regulates WRN catalytic activities and affects base excision DNA repair

    DEFF Research Database (Denmark)

    Muftuoglu, Meltem; Kusumoto, Rika; Speina, Elzbieta

    2008-01-01

    The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone...... acetyltransferases is of key interest because of its potential importance in aging, DNA repair and transcription....

  7. Modes of DNA repair and replication

    International Nuclear Information System (INIS)

    Hanawalt, P.; Kondo, S.

    1979-01-01

    Modes of DNA repair and replication require close coordination as well as some overlap of enzyme functions. Some classes of recovery deficient mutants may have defects in replication rather than repair modes. Lesions such as the pyrimidine dimers produced by ultraviolet light irradiation are the blocks to normal DNA replication in vivo and in vitro. The DNA synthesis by the DNA polymerase 1 of E. coli is blocked at one nucleotide away from the dimerized pyrimidines in template strands. Thus, some DNA polymerases seem to be unable to incorporate nucleotides opposite to the non-pairing lesions in template DNA strands. The lesions in template DNA strands may block the sequential addition of nucleotides in the synthesis of daughter strands. Normal replication utilizes a constitutive ''error-free'' mode that copies DNA templates with high fidelity, but which may be totally blocked at a lesion that obscures the appropriate base pairing specificity. It might be expected that modified replication system exhibits generally high error frequency. The error rate of DNA polymerases may be controlled by the degree of phosphorylation of the enzyme. Inducible SOS system is controlled by recA genes that also control the pathways for recombination. It is possible that SOS system involves some process other than the modification of a blocked replication apparatus to permit error-prone transdimer synthesis. (Yamashita, S.)

  8. Driving safety in Parkinson's disease.

    Science.gov (United States)

    Zesiewicz, T A; Cimino, C R; Malek, A R; Gardner, N; Leaverton, P L; Dunne, P B; Hauser, R A

    2002-12-10

    In this study, 39 patients with PD and 25 control subjects without neurologic disease completed testing in a driving simulator. PD patients had more total collisions on the driving simulator than control subjects (t = -3.7, p < 0.01). In PD patients, collisions were associated with Hoehn and Yahr stage (chi(2) = 12.4, p = 0.006) and correlated with Unified Parkinson's Disease Rating Scale score (r = 0.5, p < 0.01).

  9. Warp drive with zero expansion

    Energy Technology Data Exchange (ETDEWEB)

    Natario, Jose [Department of Mathematics, Instituto Superior Tecnico (Portugal)

    2002-03-21

    It is commonly believed that Alcubierre's warp drive works by contracting space in front of the warp bubble and expanding the space behind it. We show that this contraction/expansion is but a marginal consequence of the choice made by Alcubierre and explicitly construct a similar spacetime where no contraction/expansion occurs. Global and optical properties of warp-drive spacetimes are also discussed.

  10. Selective Perception for Robot Driving

    Science.gov (United States)

    1992-05-01

    models are theories of human cognitive activity during driving. Van der Molen and Botticher recently reviewed several of these models [ van der Molen 871...how to represent driving knowledge, how to perceive traffic situations, or how to process information to obtain actions. Van der Molen and Botticher...attempted to compare the operations of various models objectively on the same task [Rothengatter 88, van der Molen 87], but the models could be

  11. Structural dynamic modifications via models

    Indian Academy of Sciences (India)

    The study shows that as many as half of the matrix ... the dynamicist's analytical modelling skill which would appear both in the numerator as. Figure 2. ..... Brandon J A 1990 Strategies for structural dynamic modification (New York: John Wiley).

  12. Modifications to Replacement Costs System

    International Nuclear Information System (INIS)

    Godec, M.

    1989-01-01

    The purpose of this memorandum is to document the improvements and modifications made to the Replacement Costs of Crude Oil (REPCO) Supply Analysis System. While some of this work was performed under our previous support contract to DOE/ASFE, we are presenting all modifications and improvements are presented here for completeness. The memo primarily documents revisions made to the Lower-48 Onshore Model. Revisions and modifications made to other components and models in the REPCO system which are documented elsewhere are only highlighted in this memo. Generally, the modifications made to the Lower-48 Onshore Model reflect changes that have occurred in domestic drilling, oil field costs, and reserves since 1982, the date of the most recent available data used for the original Replacement Costs report, published in 1985

  13. PREFACE Surface Modifications of Diamond and Related Materials (Session D, E-MRS Spring Meeting)

    Science.gov (United States)

    Nebel, Christoph E.

    2010-11-01

    This special issue contains selected papers which were presented at the E-MRS Symposium BIOMATERIALS, SENSORS & SURFACES, D: 'Surface modifications of diamond and related materials' which was held on 7-9 June 2010 in Strasbourg (France). With about 54 oral and poster presentations given from teams all over the world it was a very interesting, dense and lively meeting. The symposium focused on chemical modifications applied to graft surfaces of diamond, nano-diamond particles, diamond-like carbon, graphene, graphite and carbon nano-tubes with linker molecular layers for realization of bio-sensors, bio-markers, separation techniques, and switchable chemical links. Presented techniques span spontaneous bonding to photo-chemical attachment, electrochemical modifications, to Suzuki-coupling of aryl molecules. Special attention was drawn to mechanisms driving bonding kinetics such as electron transfer reactions, hydrogen cleavage reactions by nucleophilic molecules and growths schemas which vary from correlated two-dimensional chain reactions to three-dimensional cross polymerization. Hydrogen terminations, surface defects, surface roughness and atomic arrangements of surface carbon atoms were of interest to elucidate bonding mechanisms. In addition, bonding stability, either of linker molecules or of complex functionalized surfaces with DNA, proteins and enzymes was discussed by several speakers as well as details of the electronic interfaces between solid transducers and bio-layers. Here the characterization of surface and interface defect densities, of Fermi level pinning and of electron transfer rates was a major topic. Miniaturization of sensor area and application of new detection schemas was discussed. Diamond nano-particles which are increasingly used as biomarkers in drug delivery experiments also attracted attention. The organizers express our gratitude to the international members of the scientific committee who actively contributed to ensure an attractive

  14. Low backlash direct drive actuator

    Science.gov (United States)

    Kuklo, Thomas C.

    1994-01-01

    A low backlash direct drive actuator is described which comprises a motor such as a stepper motor having at least 200 steps per revolution; a two part hub assembly comprising a drive hub coaxially attached to the shaft of the motor and having a plurality of drive pins; a driven hub having a plurality of bores in one end thereof in alignment with the drive pins in the drive hub and a threaded shaft coaxially mounted in an opposite end of the driven hub; and a housing having a central bore therein into which are fitted the drive hub and driven hub, the housing having a motor mount on one end thereof to which is mounted the stepper motor, and a closed end portion with a threaded opening therein coaxial with the central bore in the housing and receiving therein the threaded shaft attached to the driven hub. Limit switches mounted to the housing cooperate with an enlarged lip on the driven hub to limit the lateral travel of the driven hub in the housing, which also acts to limit the lateral travel of the threaded shaft which functions as a lead screw.

  15. Standard approach to plant modifications

    International Nuclear Information System (INIS)

    Mecredy, R.C.

    1988-01-01

    Organizational and management approaches to the design, installation, and turnover of nuclear plant modifications have changed dramatically in the last 10 to 15 yr. In response to these changes, organizational and individual responsibilities have been defined and management systems have been established at Rochester Gas and Electric (RG and E) Corporation to ensure that high-quality plant modifications are installed in a timely manner that satisfies user needs at minimal cost

  16. Cellular modifications produced by D2O in yeast culture

    International Nuclear Information System (INIS)

    Mihancea, I.; Mircea, R.Al.

    1996-01-01

    The cellular cycle of the Saccharomyces Cerevisiae, chosen as experimental object, is unmodified by the presence in the culture medium of D 2 O at different concentrations. An increased concentration of D 2 O in the culture medium leads to a decrease of the number of budded cells, to metabolic alterations, to DNA structure modification as well as to enzymatic changes produced by blocking. Other anomalies appear, as a function of the cell defence capacity and of the influence of the factors from the nutrient substrate or exterior medium. Due to D 2 O, the medium's pH changes and modifications at the enzyme level and of the cell microstructure and morphology occur. The enzymatic reactions take place in D 2 O slower than in H 2 O. Three-dimensional modifications appear in the organic components of the live cell which, in turn, produce profound modifications in the cell growth and division. Due to the kinetic and isotopic effects, modifications of the biochemical reactions affecting the cell integrity happen

  17. Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans

    DEFF Research Database (Denmark)

    Larsen, Emil List; Cejvanovic, Vanja; Kjaer, Laura Kofoed

    2017-01-01

    , phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation.......7% (95% CI: 5.8–37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde. Conclusion Clarithromycin significantly increases oxidative nucleic acid...... modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications....

  18. DNA repair

    International Nuclear Information System (INIS)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals

  19. High-power converters and AC drives

    CERN Document Server

    Wu, Bin

    2017-01-01

    This new edition reflects the recent technological advancements in the MV drive industry, such as advanced multilevel converters and drive configurations. It includes three new chapters, Control of Synchronous Motor Drives, Transformerless MV Drives, and Matrix Converter Fed Drives. In addition, there are extensively revised chapters on Multilevel Voltage Source Inverters and Voltage Source Inverter-Fed Drives. This book includes a systematic analysis on a variety of high-power multilevel converters, illustrates important concepts with simulations and experiments, introduces various megawatt drives produced by world leading drive manufacturers, and addresses practical problems and their mitigations methods.

  20. Efficient Driving of Piezoelectric Transducers Using a Biaxial Driving Technique.

    Directory of Open Access Journals (Sweden)

    Samuel Pichardo

    Full Text Available Efficient driving of piezoelectric materials is desirable when operating transducers for biomedical applications such as high intensity focused ultrasound (HIFU or ultrasound imaging. More efficient operation reduces the electric power required to produce the desired bioeffect or contrast. Our preliminary work [Cole et al. Journal of Physics: Condensed Matter. 2014;26(13:135901.] suggested that driving transducers by applying orthogonal electric fields can significantly reduce the coercivity that opposes ferroelectric switching. We present here the experimental validation of this biaxial driving technique using piezoelectric ceramics typically used in HIFU. A set of narrow-band transducers was fabricated with two sets of electrodes placed in an orthogonal configuration (following the propagation and the lateral mode. The geometry of the ceramic was chosen to have a resonance frequency similar for the propagation and the lateral mode. The average (± s.d. resonance frequency of the samples was 465.1 (± 1.5 kHz. Experiments were conducted in which each pair of electrodes was driven independently and measurements of effective acoustic power were obtained using the radiation force method. The efficiency (acoustic/electric power of the biaxial driving method was compared to the results obtained when driving the ceramic using electrodes placed only in the pole direction. Our results indicate that the biaxial method increases efficiency from 50% to 125% relative to the using a single electric field.

  1. Mitochondrial DNA mutation load in a family with the m.8344A>G point mutation and lipomas

    DEFF Research Database (Denmark)

    Jeppesen, Tina Dysgaard; Al-Hashimi, Noor; Duno, Morten

    2017-01-01

    Studies have shown that difference in mtDNA mutation load among tissues is a result of postnatal modification. We present five family members with the m.8344A>G with variable phenotypes but uniform intrapersonal distribution of mutation load, indicating that there is no postnatal modification of mt......DNA mutation load in this genotype....

  2. i3Drive, a 3D interactive driving simulator.

    Science.gov (United States)

    Ambroz, Miha; Prebil, Ivan

    2010-01-01

    i3Drive, a wheeled-vehicle simulator, can accurately simulate vehicles of various configurations with up to eight wheels in real time on a desktop PC. It presents the vehicle dynamics as an interactive animation in a virtual 3D environment. The application is fully GUI-controlled, giving users an easy overview of the simulation parameters and letting them adjust those parameters interactively. It models all relevant vehicle systems, including the mechanical models of the suspension, power train, and braking and steering systems. The simulation results generally correspond well with actual measurements, making the system useful for studying vehicle performance in various driving scenarios. i3Drive is thus a worthy complement to other, more complex tools for vehicle-dynamics simulation and analysis.

  3. Alfven-wave current drive and magnetic field stochasticity

    International Nuclear Information System (INIS)

    Litwin, C.; Hegna, C.C.

    1993-01-01

    Propagating Alfven waves can generate parallel current through an alpha effect. In resistive MHD however, the dynamo field is proportional to resistivity and as such cannot drive significant currents for realistic parameters. In the search for an enhancement of this effect the authors investigate the role of magnetic field stochasticity. They show that the presence of a stochastic magnetic field, either spontaneously generated by instabilities or induced externally, can enhance the alpha effect of the wave. This enhancement is caused by an increased wave dissipation due to both current diffusion and filamentation. For the range of parameters of current drive experiments at Phaedrus-T tokamak, a moderate field stochasticity leads to significant modifications in the loop voltage

  4. Driving performance at lateral system limits during partially automated driving.

    Science.gov (United States)

    Naujoks, Frederik; Purucker, Christian; Wiedemann, Katharina; Neukum, Alexandra; Wolter, Stefan; Steiger, Reid

    2017-11-01

    This study investigated driver performance during system limits of partially automated driving. Using a motion-based driving simulator, drivers encountered different situations in which a partially automated vehicle could no longer safely keep the lateral guidance. Drivers were distracted by a non-driving related task on a touch display or driving without an additional secondary task. While driving in partially automated mode drivers could either take their hands off the steering wheel for only a short period of time (10s, so-called 'Hands-on' variant) or for an extended period of time (120s, so-called 'Hands-off' variant). When the system limit was reached (e.g., when entering a work zone with temporary lines), the lateral vehicle control by the automation was suddenly discontinued and a take-over request was issued to the drivers. Regardless of the hands-off interval and the availability of a secondary task, all drivers managed the transition to manual driving safely. No lane exceedances were observed and the situations were rated as 'harmless' by the drivers. The lack of difference between the hands-off intervals can be partly attributed to the fact that most of the drivers kept contact to the steering wheel, even in the hands-off condition. Although all drivers were able to control the system limits, most of them could not explain why exactly the take-over request was issued. The average helpfulness of the take-over request was rated on an intermediate level. Consequently, providing drivers with information about the reason for a system limit can be recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. DNA Polymerases λ and β: The Double-Edged Swords of DNA Repair

    Directory of Open Access Journals (Sweden)

    Elisa Mentegari

    2016-08-01

    Full Text Available DNA is constantly exposed to both endogenous and exogenous damages. More than 10,000 DNA modifications are induced every day in each cell’s genome. Maintenance of the integrity of the genome is accomplished by several DNA repair systems. The core enzymes for these pathways are the DNA polymerases. Out of 17 DNA polymerases present in a mammalian cell, at least 13 are specifically devoted to DNA repair and are often acting in different pathways. DNA polymerases β and λ are involved in base excision repair of modified DNA bases and translesion synthesis past DNA lesions. Polymerase λ also participates in non-homologous end joining of DNA double-strand breaks. However, recent data have revealed that, depending on their relative levels, the cell cycle phase, the ratio between deoxy- and ribo-nucleotide pools and the interaction with particular auxiliary proteins, the repair reactions carried out by these enzymes can be an important source of genetic instability, owing to repair mistakes. This review summarizes the most recent results on the ambivalent properties of these enzymes in limiting or promoting genetic instability in mammalian cells, as well as their potential use as targets for anticancer chemotherapy.

  6. DNA Polymerases λ and β: The Double-Edged Swords of DNA Repair.

    Science.gov (United States)

    Mentegari, Elisa; Kissova, Miroslava; Bavagnoli, Laura; Maga, Giovanni; Crespan, Emmanuele

    2016-08-31

    DNA is constantly exposed to both endogenous and exogenous damages. More than 10,000 DNA modifications are induced every day in each cell's genome. Maintenance of the integrity of the genome is accomplished by several DNA repair systems. The core enzymes for these pathways are the DNA polymerases. Out of 17 DNA polymerases present in a mammalian cell, at least 13 are specifically devoted to DNA repair and are often acting in different pathways. DNA polymerases β and λ are involved in base excision repair of modified DNA bases and translesion synthesis past DNA lesions. Polymerase λ also participates in non-homologous end joining of DNA double-strand breaks. However, recent data have revealed that, depending on their relative levels, the cell cycle phase, the ratio between deoxy- and ribo-nucleotide pools and the interaction with particular auxiliary proteins, the repair reactions carried out by these enzymes can be an important source of genetic instability, owing to repair mistakes. This review summarizes the most recent results on the ambivalent properties of these enzymes in limiting or promoting genetic instability in mammalian cells, as well as their potential use as targets for anticancer chemotherapy.

  7. Exploring Forensic Implications of the Fusion Drive

    Directory of Open Access Journals (Sweden)

    Shruti Gupta

    2014-09-01

    Full Text Available This paper explores the forensic implications of Apple's Fusion Drive. The Fusion Drive is an example of auto-tiered storage. It uses a combination of a flash drive and a magnetic drive. Data is moved between the drives automatically to maximize system performance. This is different from traditional caches because data is moved and not simply copied. The research included understanding the drive structure, populating the drive, and then accessing data in a controlled setting to observe data migration strategies. It was observed that all the data is first written to the flash drive with 4 GB of free space always maintained. If data on the magnetic drive is frequently accessed, it is promoted to the flash drive while demoting other information. Data is moved at a block-level and not a file-level. The Fusion Drive didn't alter the timestamps of files with data migration.

  8. Biochemical systems approaches for the analysis of histone modification readout.

    Science.gov (United States)

    Soldi, Monica; Bremang, Michael; Bonaldi, Tiziana

    2014-08-01

    Chromatin is the macromolecular nucleoprotein complex that governs the organization of genetic material in the nucleus of eukaryotic cells. In chromatin, DNA is packed with histone proteins into nucleosomes. Core histones are prototypes of hyper-modified proteins, being decorated by a large number of site-specific reversible and irreversible post-translational modifications (PTMs), which contribute to the maintenance and modulation of chromatin plasticity, gene activation, and a variety of other biological processes and disease states. The observations of the variety, frequency and co-occurrence of histone modifications in distinct patterns at specific genomic loci have led to the idea that hPTMs can create a molecular barcode, read by effector proteins that translate it into a specific transcriptional state, or process, on the underlying DNA. However, despite the fact that this histone-code hypothesis was proposed more than 10 years ago, the molecular details of its working mechanisms are only partially characterized. In particular, two questions deserve specific investigation: how the different modifications associate and synergize into patterns and how these PTM configurations are read and translated by multi-protein complexes into a specific functional outcome on the genome. Mass spectrometry (MS) has emerged as a versatile tool to investigate chromatin biology, useful for both identifying and validating hPTMs, and to dissect the molecular determinants of histone modification readout systems. We review here the MS techniques and the proteomics methods that have been developed to address these fundamental questions in epigenetics research, emphasizing approaches based on the proteomic dissection of distinct native chromatin regions, with a critical evaluation of their present challenges and future potential. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. DNA repair

    International Nuclear Information System (INIS)

    Van Zeeland, A.A.

    1984-01-01

    In this chapter a series of DNA repair pathways are discussed which are available to the cell to cope with the problem of DNA damaged by chemical or physical agents. In the case of microorganisms our knowledge about the precise mechanism of each DNA repair pathway and the regulation of it has been improved considerably when mutants deficient in these repair mechanisms became available. In the case of mammalian cells in culture, until recently there were very little repair deficient mutants available, because in almost all mammalian cells in culture at least the diploid number of chromosomes is present. Therefore the frequency of repair deficient mutants in such populations is very low. Nevertheless because replica plating techniques are improving some mutants from Chinese hamsters ovary cells and L5178Y mouse lymphoma cells are now available. In the case of human cells, cultures obtained from patients with certain genetic diseases are available. A number of cells appear to be sensitive to some chemical or physical mutagens. These include cells from patients suffering from xeroderma pigmentosum, Ataxia telangiectasia, Fanconi's anemia, Cockayne's syndrome. However, only in the case of xeroderma pigmentosum cells, has the sensitivity to ultraviolet light been clearly correlated with a deficiency in excision repair of pyrimidine dimers. Furthermore the work with strains obtained from biopsies from man is difficult because these cells generally have low cloning efficiencies and also have a limited lifespan in vitro. It is therefore very important that more repair deficient mutants will become available from established cell lines from human or animal origin

  10. The surface modification of polystyrene

    International Nuclear Information System (INIS)

    Tremlett, C.

    2000-03-01

    Polymers have ideal bulk properties for many applications. However, adhesion to many polymers is poor without surface pretreatment. This can result, for example, in peeling paint and printing, adhesive joint failure and bio-incompatibility. In applications such as painting, printing, adhesive bonding and biocompatibility, various cleaning or surface chemical modifications may be employed. A commodity polymer where pretreatment is sometimes needed is polystyrene. This project investigated, in detail, the effects of a novel method of modification namely mediated electrochemical oxidation (MEO), as a mode of surface modification on polystyrene and a comparison was made with other polymers. The resulting modification was investigated using a range of surface analysis techniques to obtain complementary information. These included, X-ray photoelectron spectroscopy, contact angles, static secondary ion mass spectrometry, atomic force microscopy, chemical derivatization, scanning electron microscopy, attenuated total reflection Fourier Transform infrared spectroscopy and composite lap shear joint testing. It has been shown that MEO modifies the surface of polystyrene introduced oxygen mainly as hydroxyl groups, and a small number of carbonyl groups, that are positioned only on the backbone hydrocarbon chain. This modification improved adhesion, was stable and samples could be stored in aqueous media. The resulting hydroxylation was further derivatized using an amino acid to provide a specialised surface. This was very different from the multiple oxygen functionalities introduced in the comparison studies by UV/ozone and plasma treatments. (author)

  11. Driving safety in elderly individuals.

    Science.gov (United States)

    Marottoli, R A

    1993-05-01

    Driving safety in elderly individuals is becoming an increasingly important issue in geriatrics and in medical practice. The number of elderly drivers is increasing as the population ages, and especially as current generations of female drivers age. Concern is raised about their safe operation of motor vehicles because of the increasing likelihood with advancing age of developing conditions that may adversely affect the visual, cognitive, and motor abilities integral to driving. But this issue is not only a medical one, since there are social and political components as well. This discussion will describe the background of this issue, focus on the changes that may occur with aging and their potential relationship to driving ability, and, finally, will outline an approach that physicians may employ in their practice.

  12. Drive: Theory and Construct Validation.

    Science.gov (United States)

    Siegling, Alex B; Petrides, K V

    2016-01-01

    This article explicates the theory of drive and describes the development and validation of two measures. A representative set of drive facets was derived from an extensive corpus of human attributes (Study 1). Operationalised using an International Personality Item Pool version (the Drive:IPIP), a three-factor model was extracted from the facets in two samples and confirmed on a third sample (Study 2). The multi-item IPIP measure showed congruence with a short form, based on single-item ratings of the facets, and both demonstrated cross-informant reliability. Evidence also supported the measures' convergent, discriminant, concurrent, and incremental validity (Study 3). Based on very promising findings, the authors hope to initiate a stream of research in what is argued to be a rather neglected niche of individual differences and non-cognitive assessment.

  13. CLIC Drive Beam Position Monitor

    CERN Document Server

    Smith, S; Gudkov, D; Soby, L; Syratchev, I

    2011-01-01

    CLIC, an electron-positron linear collider proposed to probe the TeV energy scale, is based on a two-beam scheme where RF power to accelerate a high energy luminosity beam is extracted from a high current drive beam. The drive beam is efficiently generated in a long train at modest frequency and current then compressed in length and multiplied in frequency via bunch interleaving. The drive beam decelerator requires >40000 quadrupoles, each holding a beam position monitor (BPM). Though resolution requirements are modest (2 microns) these BPMs face several challenges. They must be compact and inexpensive. They must operate below waveguide cutoff to insure locality of position signals, ruling out processing at the natural 12 GHz bunch spacing frequency. Wakefields must be kept low. We find compact conventional stripline BPM with signals processed below 40 MHz can meet requirements. Choices of mechanical design, operating frequency, bandwidth, calibration and processing algorithm are presented. Calculations of wa...

  14. Glare disability and driving safety.

    Science.gov (United States)

    Babizhayev, M A

    2003-01-01

    Increasing investigation of the visual elements of safe driving environments may be of great benefit to society. Visual disability appears to be only one of many visual factors related to traffic accidents. The purpose of this article was to examine the type of visual impairment mediated by the increased glare sensitivity in adult drivers using the original halometer glare test. In this article, the visual sensory, cognitive and motor functions relevant to driving, their measurement, the epidemiology and prevention of age-associated functional impairments and the relationship of functional impairments to both self-reported driving and the imposition of legal restrictions are reviewed. The problem of night and tunnel driving is the most urgent in relation to the effects of glare from vehicle headlights on motion perception of drivers. The reduced mesopic vision and increased sensitivity to glare are accompanied by an increased risk of nighttime accidents. Elderly drivers and patients with beginning cataract cannot sufficiently fulfill the criteria for night driving ability because of contrast and glare sensitivity. It is indispensable for the parameters mentioned to be carefully measured and for drivers to be informed that night driving ability may be impaired, even if visual acuity is sufficient. It would be advisable for traffic safety if simple tests for contrast and glare sensitivity were implemented for vehicles and/or were regularly added to the requirements for a driver's licence, at least for older drivers. The age, functional status and test result limits should be defined to avoid a risk factor in traffic. Copyright 2003 S. Karger AG, Basel

  15. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    International Nuclear Information System (INIS)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A.

    2014-01-01

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting

  16. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: sarah.martin@qmul.ac.uk [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)

    2014-08-05

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.

  17. DNA immunoprecipitation semiconductor sequencing (DIP-SC-seq) as a rapid method to generate genome wide epigenetic signatures

    OpenAIRE

    Thomson, John P.; Fawkes, Angie; Ottaviano, Raffaele; Hunter, Jennifer M.; Shukla, Ruchi; Mjoseng, Heidi K.; Clark, Richard; Coutts, Audrey; Murphy, Lee; Meehan, Richard R.

    2015-01-01

    Modification of DNA resulting in 5-methylcytosine (5 mC) or 5-hydroxymethylcytosine (5hmC) has been shown to influence the local chromatin environment and affect transcription. Although recent advances in next generation sequencing technology allow researchers to map epigenetic modifications across the genome, such experiments are often time-consuming and cost prohibitive. Here we present a rapid and cost effective method of generating genome wide DNA modification maps utilising commercially ...

  18. Influence of roadside infrastructure on driving behavior: driving simulator study

    NARCIS (Netherlands)

    Horst, A.R.A. van der; Ridder, S. de

    2007-01-01

    This paper describes the results of a driving simulator study that focused on the influence of roadside infrastructure on speed choice and lateral placement of car drivers. A review of the RISER detailed accident database revealed that lateral positioning and speed of the vehicle were two of the

  19. Driving and Age-Related Macular Degeneration

    OpenAIRE

    Owsley, Cynthia; McGwin, Gerald

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety, and considers directions for future research.

  20. Digital control of electric drives

    CERN Document Server

    Koziol, R; Szklarski, L

    1992-01-01

    The electromechanical systems employed in different branches of industry are utilized most often as drives of working machines which must be fed with electric energy in a continuous, periodic or even discrete way. Some of these machines operate at constant speed, others require wide and varying energy control. In many designs the synchronous cooperation of several electric drives is required in addition to the desired dynamic properties. For these reasons the control of the cooperation and dynamics of electromechanical systems requires the use of computers.This book adopts an unusual approach

  1. Control-rod driving mechanism

    International Nuclear Information System (INIS)

    Jodoi, Takashi.

    1976-01-01

    Purpose: To prevent falling of control rods due to malfunction. Constitution: The device of the present invention has a scram function in particular, and uses principally a fluid pressure as a scram accelerating means. The control rod is held by upper and lower holding devices, which are connected by a connecting mechanism. This connecting mechanism is designed to be detachable only at the lower limit of driving stroke of the control rod so that there occurs no erroneous scram resulting from careless disconnection of the connecting mechanism. Further, scramming operation due to own weight of the scram operating portion such as control rod driving shaft may be effected to increase freedom. (Kamimura, M.)

  2. Minimal modification to tribimaximal mixing

    International Nuclear Information System (INIS)

    He Xiaogang; Zee, A.

    2011-01-01

    We explore some ways of minimally modifying the neutrino mixing matrix from tribimaximal, characterized by introducing at most one mixing angle and a CP violating phase thus extending our earlier work. One minimal modification, motivated to some extent by group theoretic considerations, is a simple case with the elements V α2 of the second column in the mixing matrix equal to 1/√(3). Modifications by keeping one of the columns or one of the rows unchanged from tribimaximal mixing all belong to the class of minimal modification. Some of the cases have interesting experimentally testable consequences. In particular, the T2K and MINOS collaborations have recently reported indications of a nonzero θ 13 . For the cases we consider, the new data sharply constrain the CP violating phase angle δ, with δ close to 0 (in some cases) and π disfavored.

  3. DNA Damage Response and Immune Defence: Links and Mechanisms

    Directory of Open Access Journals (Sweden)

    Björn Schumacher

    2016-08-01

    Full Text Available DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i which molecular and cellular pathways of DDR activate immune signalling, (ii how DNA damage drives chronic inflammation, and (iii how chronic inflammation causes DNA damage and pathology in humans.

  4. Structural analysis of DNA–protein complexes regulating the restriction–modification system Esp1396I

    International Nuclear Information System (INIS)

    Martin, Richard N. A.; McGeehan, John E.; Ball, Neil J.; Streeter, Simon D.; Thresh, Sarah-Jane; Kneale, G. G.

    2013-01-01

    Comparison of bound and unbound DNA in protein–DNA co-crystal complexes reveals insights into controller-protein binding and DNA distortion in transcriptional regulation. The controller protein of the type II restriction–modification (RM) system Esp1396I binds to three distinct DNA operator sequences upstream of the methyltransferase and endonuclease genes in order to regulate their expression. Previous biophysical and crystallographic studies have shown molecular details of how the controller protein binds to the operator sites with very different affinities. Here, two protein–DNA co-crystal structures containing portions of unbound DNA from native operator sites are reported. The DNA in both complexes shows significant distortion in the region between the conserved symmetric sequences, similar to that of a DNA duplex when bound by the controller protein (C-protein), indicating that the naked DNA has an intrinsic tendency to bend when not bound to the C-protein. Moreover, the width of the major groove of the DNA adjacent to a bound C-protein dimer is observed to be significantly increased, supporting the idea that this DNA distortion contributes to the substantial cooperativity found when a second C-protein dimer binds to the operator to form the tetrameric repression complex

  5. DNA origami as a nanoscale template for protein assembly

    Energy Technology Data Exchange (ETDEWEB)

    Kuzyk, Anton; Laitinen, Kimmo T [Nanoscience Center, Department of Physics, University of Jyvaeskylae, PO Box 35, FIN-40014 (Finland); Toermae, Paeivi [Department of Applied Physics, Helsinki University of Technology, PO Box 5100, FIN-02015 (Finland)], E-mail: paivi.torma@hut.fi

    2009-06-10

    We describe two general approaches to the utilization of DNA origami structures for the assembly of materials. In one approach, DNA origami is used as a prefabricated template for subsequent assembly of materials. In the other, materials are assembled simultaneously with the DNA origami, i.e. the DNA origami technique is used to drive the assembly of materials. Fabrication of complex protein structures is demonstrated by these two approaches. The latter approach has the potential to be extended to the assembly of multiple materials with single attachment chemistry.

  6. DNA origami as a nanoscale template for protein assembly

    International Nuclear Information System (INIS)

    Kuzyk, Anton; Laitinen, Kimmo T; Toermae, Paeivi

    2009-01-01

    We describe two general approaches to the utilization of DNA origami structures for the assembly of materials. In one approach, DNA origami is used as a prefabricated template for subsequent assembly of materials. In the other, materials are assembled simultaneously with the DNA origami, i.e. the DNA origami technique is used to drive the assembly of materials. Fabrication of complex protein structures is demonstrated by these two approaches. The latter approach has the potential to be extended to the assembly of multiple materials with single attachment chemistry.

  7. Corrosion principles and surface modification

    International Nuclear Information System (INIS)

    Kruger, J.

    1982-01-01

    This chapter examines the important strategies provided by the newer ideas of corrosion science and engineering that surface modification techniques must utilize to help prevent corrosion, especially the most damaging kind of aqueous corrosion, localized corrosion. Provides a brief introduction to the principles underlying the phenomenon of corrosion in order to use them to discuss surface modification strategies to combat corrosion. Discusses the electrochemistry of corrosion; the thermodynamics of corrosion; the kinetics of corrosion; thermodynamic strategies; and kinetic strategies (formation of more protective passive films; resistance to breakdown; ductility; repassivation)

  8. Electrohydraulic drive system with planetary superposed gears

    Energy Technology Data Exchange (ETDEWEB)

    Graetz, A.; Klimek, K.H.; Welz, H.

    1989-01-01

    To prevent drive problems in ploughs the drives must be designed in such a way as to compensate for asymmetries. If electromechanical drives are replaced by an electrohydraulic drive system with superposed planetary gears and hydrostatic torque reaction supports the following advantages occur: load-free acceleration, load equalisation between main and auxiliary drive, overload protection, and reduction of systems vibrations. 2 figs., 2 tabs.

  9. Altered DNA methylation associated with a translocation linked to major mental illness

    OpenAIRE

    McCartney, Daniel L; Walker, Rosie M; Morris, Stewart W; Anderson, Susan M; Duff, Barbara J; Marioni, Riccardo E; Millar, J Kirsty; McCarthy, Shane E; Ryan, Niamh M; Lawrie, Stephen M; Watson, Andrew R; Blackwood, Douglas H R; Thomson, Pippa A; McIntosh, Andrew M; McCombie, W Richard

    2018-01-01

    Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumin...

  10. FOREIGN DRIVING LICENCES IN SWITZERLAND

    CERN Document Server

    Relatiopns with the Host States Service

    2001-01-01

    1. PERSONS RESIDING IN SWITZERLAND 1.1 Holders of a B, C, D or E-type carte de légitimation For holders of B, C, D or E-type cartes de légitimation issued by the Swiss Federal Department for Foreign Affairs (Département fédéral suisse des Affaires étrangères, hereinafter called DFAE), current non-Swiss national driving licences are valid in Switzerland. Should they so wish, holders of such driving licences may apply to the relevant roads authority in the canton where they live (Service des Automobiles et de la Navigation ; for Geneva call 022/343 02 00, website: http://www.geneve.ch/san/welcome.html, for Vaud call 021/316 82 10, website: http://www.dse.vd.ch/auto/index.html) in order to exchange their driving licence for an equivalent Swiss licence. However, exchanges are not permitted if the driving licence was issued in a foreign country during a stay there of less than six months' duration while the person concerned was officially...

  11. Drive-By-Wire Technology

    Science.gov (United States)

    2001-05-29

    Symposium Intelligent Systems for the Objective Fleet uTransmission controls uSteering (both on-transmission and under-carriage) uBraking (service and...parking) uTransmission select uThrottle uOther Electromechanical Opportunities uTurret drives (elevation, traverse) uAutomatic propellant handling systems

  12. Foreign driving licences in Switzerland

    CERN Multimedia

    DG Unit

    2009-01-01

    1. Persons residing in Switzerland 1.1 Holders of a B, C, D, E or P-type "carte de légitimation" For holders of a B, C, D, E or P-type "carte de légitimation" issued by the Swiss Federal Department for Foreign Affairs (DFAE), current non-Swiss national driving licences are valid in Switzerland. If they so wish, holders of such driving licences may apply to the relevant road licensing authority in the canton where they live (Service des Automobiles et de la Navigation; for Geneva call + 41 22 388 30 30, website http://www.geneve.ch/san; for Vaud call + 41 21 316 82 10, website http://www.san.vd.ch/index.html) to exchange their driving licence for an equivalent Swiss licence (they must pass a test if they are not citizens of countries with which Switzerland has concluded an agreement on this matter, e.g. Member States of the European Union, the United States and Japan). However, such an exchange is not possible if the driving licence was issued in a foreign country during a...

  13. Synergy in RF Current Drive

    International Nuclear Information System (INIS)

    Dumont, R.J.; Giruzzi, G.

    2005-01-01

    Auxiliary methods for efficient non-inductive current drive in tokamaks generally involve the interaction of externally driven waves with superthermal electrons. Among the possible schemes, Lower Hybrid (LH) and Electron Cyclotron (EC) current drive have been so far the most successful. An interesting aspect of their combined use is the fact that since they involve possibly overlapping domains in velocity and configuration spaces, a synergy between them is expected for appropriate parameters. The signature of this effect, significant improvement of the EC current drive efficiency, results from a favorable interplay of the quasilinear diffusions induced by both waves. Recently, improvements of the EC current drive efficiency in the range of 2-4 have been measured in fully non-inductive discharges in the Tore Supra tokamak, providing the first clear evidence of this effect in steady-state conditions. We present here the experimental aspects of these discharges. The associated kinetic modeling and current state of understanding of the LH-EC synergy phenomenon are also discussed. (authors)

  14. Synergy in RF Current Drive

    International Nuclear Information System (INIS)

    Dumont, R.J.; Giruzzi, G.

    2005-01-01

    Auxiliary methods for efficient non-inductive current drive in tokamaks generally involve the interaction of externally driven waves with superthermal electrons. Among the possible schemes, Lower Hybrid (LH) and Electron Cyclotron (EC) current drive have been so far the most successful. An interesting aspect of their combined use is the fact that since they involve possibly overlapping domains in velocity and configuration spaces, a synergy between them is expected for appropriate parameters. The signature of this effect, significant improvement of the EC current drive efficiency, results from a favorable interplay of the quasilinear diffusions induced by both waves. Recently, improvements of the EC current drive efficiency in the range of 2-4 have been measured in fully non-inductive discharges in the Tore Supra tokamak, providing the first clear evidence of this effect in steady-state conditions. We present here the experimental aspects of these discharges. The associated kinetic modeling and current state of understanding of the LH-EC synergy phenomenon are also discussed

  15. Safe Driving After Propofol Sedation.

    Science.gov (United States)

    Summerlin-Grady, Lee; Austin, Paul N; Gabaldon, Dion A

    2017-10-01

    Propofol is a short-acting medication with fast cognitive and psychomotor recovery. However, patients are usually instructed not to drive a motor vehicle for 24 hours after receiving propofol. The purpose of this article was to review the evidence examining when it is safe to drive after receiving propofol for sedation for diagnostic and surgical procedures. This is a systematic review of the literature. A search of the literature was conducted using Google Scholar, PubMed, and the Cochrane Library for the time period 1990 to 2015. Two randomized controlled trials and two observational studies met the inclusion criteria. Using a simulator, investigators examined driving ability of subjects who received modest doses (about 100 mg) of propofol for endoscopic procedures and surveyed subjects who drove immediately after discharge. There were methodological concerns with the studies such as small sample sizes, modest doses of propofol, and three of the four studies were done in Japan by the same group of investigators limiting generalizability. This limited research suggests that it may be safe for patients to drive sooner than 24 hours after receiving propofol. However, large multicenter trials using heterogenous samples using a range of propofol doses are needed to support an evidence-based revision to the current discharge guidelines for patients receiving propofol. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  16. Driving When You Have Cataracts

    Science.gov (United States)

    ... asp Wear your safety belt Always wear your safety belt when you are driving or riding in a car. Make sure that every person who is riding with you also is buckled up. Wear your safety belt even if your car has air bags. ...

  17. Current drive for rotamak plasmas

    Indian Academy of Sciences (India)

    Abstract. Experiments which have been undertaken over a number of years have shown that a rotating magnetic field can drive a significant non-linear Hall current in a plasma. Successful experiments of this concept have been made with a device called rotamak. In its original configuration this device was a field reversed ...

  18. Control rod driving hydraulic device

    International Nuclear Information System (INIS)

    Sugano, Hiroshi.

    1993-01-01

    In a control rod driving hydraulic device for an improved BWR type reactor, a bypass pipeline is disposed being branched from a scram pipeline, and a control orifice and a throttle valve are interposed to the bypass pipeline for restricting pressure. Upon occurrence of scram, about 1/2 of water quantity flowing from an accumulator of a hydraulic control unit to the lower surface of a piston of control rod drives by way of a scram pipeline is controlled by the restricting orifice and the throttle valve, by which the water is discharged to a pump suction pipeline or other pipelines by way of the bypass pipeline. With such procedures, a function capable of simultaneously conducting scram for two control rod drives can be attained by one hydraulic control unit. Further, an excessive peak pressure generated by a water hammer phenomenon in the scram pipeline or the control rod drives upon occurrence of scram can be reduced. Deformation and failure due to the excessive peak pressure can be prevented, as well as vibrations and degradation of performance of relevant portions can be prevented. (N.H.)

  19. Virtual Rewards for Driving Green

    Science.gov (United States)

    Pritchard, Josh

    2010-01-01

    Carbon dioxide from automobiles is a major contributor to global climate change. In "Virtual Rewards for Driving Green," Josh Pritchard proposes a computer application that will enable fuel-efficient drivers to earn "green" dollars with which to buy digital merchandise on the Web. Can getting items that exist only in cyberspace actually change a…

  20. Older drivers with cognitive impairment: Perceived changes in driving skills, driving-related discomfort and self-regulation of driving

    DEFF Research Database (Denmark)

    Meng, A.; Siren, A.; Teasdale, Thomas William

    2013-01-01

    The results of a previous study indicate that in general, older drivers who recognise cognitive problems show realistic self-assessment of changes in their driving skills and that driving-related discomfort may function as an indirect monitoring of driving ability, contributing to their safe...... drivers may recognise cognitive problems, they tend not to recognise changes to their driving, which may reflect reluctance to acknowledge the impact of cognitive impairment on their driving. Furthermore, the results suggest that driving-related discomfort plays an important role in the self......-regulation of driving among cognitively impaired older drivers. However, it is less clear what triggers driving-related discomfort among cognitively impaired older drivers indicating that it may be a less reliable aspect of their self-monitoring of driving ability....

  1. Detecting differential DNA methylation from sequencing of bisulfite converted DNA of diverse species.

    Science.gov (United States)

    Huh, Iksoo; Wu, Xin; Park, Taesung; Yi, Soojin V

    2017-07-21

    DNA methylation is one of the most extensively studied epigenetic modifications of genomic DNA. In recent years, sequencing of bisulfite-converted DNA, particularly via next-generation sequencing technologies, has become a widely popular method to study DNA methylation. This method can be readily applied to a variety of species, dramatically expanding the scope of DNA methylation studies beyond the traditionally studied human and mouse systems. In parallel to the increasing wealth of genomic methylation profiles, many statistical tools have been developed to detect differentially methylated loci (DMLs) or differentially methylated regions (DMRs) between biological conditions. We discuss and summarize several key properties of currently available tools to detect DMLs and DMRs from sequencing of bisulfite-converted DNA. However, the majority of the statistical tools developed for DML/DMR analyses have been validated using only mammalian data sets, and less priority has been placed on the analyses of invertebrate or plant DNA methylation data. We demonstrate that genomic methylation profiles of non-mammalian species are often highly distinct from those of mammalian species using examples of honey bees and humans. We then discuss how such differences in data properties may affect statistical analyses. Based on these differences, we provide three specific recommendations to improve the power and accuracy of DML and DMR analyses of invertebrate data when using currently available statistical tools. These considerations should facilitate systematic and robust analyses of DNA methylation from diverse species, thus advancing our understanding of DNA methylation. © The Author 2017. Published by Oxford University Press.

  2. Current challenges in autonomous driving

    Science.gov (United States)

    Barabás, I.; Todoruţ, A.; Cordoş, N.; Molea, A.

    2017-10-01

    Nowadays the automotive industry makes a quantum shift to a future, where the driver will have smaller and smaller role in driving his or her vehicle ending up being totally excluded. In this paper, we have investigated the different levels of driving automatization, the prospective effects of these new technologies on the environment and traffic safety, the importance of regulations and their current state, the moral aspects of introducing these technologies and the possible scenarios of deploying the autonomous vehicles. We have found that the self-driving technologies are facing many challenges: a) They must make decisions faster in very diverse conditions which can include many moral dilemmas as well; b) They have an important potential in reducing the environmental pollution by optimizing their routes, driving styles by communicating with other vehicles, infrastructures and their environment; c) There is a considerable gap between the self-drive technology level and the current regulations; fortunately, this gap shows a continuously decreasing trend; d) In case of many types of imminent accidents management there are many concerns about the ability of making the right decision. Considering that this field has an extraordinary speed of development, our study is up to date at the submission deadline. Self-driving technologies become increasingly sophisticated and technically accessible, and in some cases, they can be deployed for commercial vehicles as well. According to the current stage of research and development, it is still unclear how the self-driving technologies will be able to handle extreme and unexpected events including their moral aspects. Since most of the traffic accidents are caused by human error or omission, it is expected that the emergence of the autonomous technologies will reduce these accidents in their number and gravity, but the very few currently available test results have not been able to scientifically underpin this issue yet. The

  3. Driver headway choice : A comparison between driving simulator and real-road driving

    NARCIS (Netherlands)

    Risto, M.; Martens, M.H.

    2014-01-01

    Driving simulators have become an established tool in driver behaviour research by offering a controllable, safe and cost-effective alternative to real world driving. A challenge for using driving simulators as a research tool has been to elicit driving behaviour that equals real world driving. With

  4. Driver headway choice: a comparison between driving simulator and real-road driving

    NARCIS (Netherlands)

    Risto, Malte; Martens, Marieke Hendrikje

    2014-01-01

    Driving simulators have become an established tool in driver behaviour research by offering a controllable, safe and cost-effective alternative to real world driving. A challenge for using driving simulators as a research tool has been to elicit driving behaviour that equals real world driving. With

  5. Analysis of DNA Hydroxymethylation Using Colorimetric Assay.

    Science.gov (United States)

    Golubov, Andrey; Kovalchuk, Igor

    2017-01-01

    Hydroxymethylcytosine (hmC or 5-hmC) is a nitrogen base occurring as a result of cytosine methylation followed by replacing a methyl group with a hydroxyl group through active oxidation. 5-hmC is considered to be one of the forms of epigenetic modification and is suggested as an intermediate step in a semi-active loss of DNA methylation mark. 5-hmC plays an important role in the epigenetic regulation of gene expression in animals, although its role in plants remains controversial. Here, we present a colorimetric method of quantification of 5-hmC using Brassica rapa DNA.

  6. Cannabis effects on driving skills.

    Science.gov (United States)

    Hartman, Rebecca L; Huestis, Marilyn A

    2013-03-01

    Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ(9)-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. We review and evaluate the current literature on cannabis' effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and

  7. Cannabis Effects on Driving Skills

    Science.gov (United States)

    Hartman, Rebecca L.; Huestis, Marilyn A.

    2013-01-01

    BACKGROUND Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ9-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. CONTENT We review and evaluate the current literature on cannabis’ effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. SUMMARY Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2–5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention

  8. Superhydrophobic cotton by fluorosilane modification

    CSIR Research Space (South Africa)

    Erasmus, E

    2009-12-01

    Full Text Available the treatment with fluorinated or silicon compounds)1-4 and by enhancing the surface roughness with a fractal structure5-8. Cotton, a cellulose-based material, that is greatly hydrophilic, is more benefited when made hydrophobic. Modification of cotton...

  9. Close encounters for the first time: Helicase interactions with DNA damage.

    Science.gov (United States)

    Khan, Irfan; Sommers, Joshua A; Brosh, Robert M

    2015-09-01

    DNA helicases are molecular motors that harness the energy of nucleoside triphosphate hydrolysis to unwinding structured DNA molecules that must be resolved during cellular replication, DNA repair, recombination, and transcription. In vivo, DNA helicases are expected to encounter a wide spectrum of covalent DNA modifications to the sugar phosphate backbone or the nitrogenous bases; these modifications can be induced by endogenous biochemical processes or exposure to environmental agents. The frequency of lesion abundance can vary depending on the lesion type. Certain adducts such as oxidative base modifications can be quite numerous, and their effects can be helix-distorting or subtle perturbations to DNA structure. Helicase encounters with specific DNA lesions and more novel forms of DNA damage will be discussed. We will also review the battery of assays that have been used to characterize helicase-catalyzed unwinding of damaged DNA substrates. Characterization of the effects of specific DNA adducts on unwinding by various DNA repair and replication helicases has proven to be insightful for understanding mechanistic and biological aspects of helicase function in cellular DNA metabolism. Published by Elsevier B.V.

  10. Selective Gene Delivery for Integrating Exogenous DNA into Plastid and Mitochondrial Genomes Using Peptide-DNA Complexes.

    Science.gov (United States)

    Yoshizumi, Takeshi; Oikawa, Kazusato; Chuah, Jo-Ann; Kodama, Yutaka; Numata, Keiji

    2018-05-14

    Selective gene delivery into organellar genomes (mitochondrial and plastid genomes) has been limited because of a lack of appropriate platform technology, even though these organelles are essential for metabolite and energy production. Techniques for selective organellar modification are needed to functionally improve organelles and produce transplastomic/transmitochondrial plants. However, no method for mitochondrial genome modification has yet been established for multicellular organisms including plants. Likewise, modification of plastid genomes has been limited to a few plant species and algae. In the present study, we developed ionic complexes of fusion peptides containing organellar targeting signal and plasmid DNA for selective delivery of exogenous DNA into the plastid and mitochondrial genomes of intact plants. This is the first report of exogenous DNA being integrated into the mitochondrial genomes of not only plants, but also multicellular organisms in general. This fusion peptide-mediated gene delivery system is a breakthrough platform for both plant organellar biotechnology and gene therapy for mitochondrial diseases in animals.

  11. Pharmacogenomic study using bio- and nanobioelectrochemistry: Drug-DNA interaction.

    Science.gov (United States)

    Hasanzadeh, Mohammad; Shadjou, Nasrin

    2016-04-01

    Small molecules that bind genomic DNA have proven that they can be effective anticancer, antibiotic and antiviral therapeutic agents that affect the well-being of millions of people worldwide. Drug-DNA interaction affects DNA replication and division; causes strand breaks, and mutations. Therefore, the investigation of drug-DNA interaction is needed to understand the mechanism of drug action as well as in designing DNA-targeted drugs. On the other hand, the interaction between DNA and drugs can cause chemical and conformational modifications and, thus, variation of the electrochemical properties of nucleobases. For this purpose, electrochemical methods/biosensors can be used toward detection of drug-DNA interactions. The present paper reviews the drug-DNA interactions, their types and applications of electrochemical techniques used to study interactions between DNA and drugs or small ligand molecules that are potentially of pharmaceutical interest. The results are used to determine drug binding sites and sequence preference, as well as conformational changes due to drug-DNA interactions. Also, the intention of this review is to give an overview of the present state of the drug-DNA interaction cognition. The applications of electrochemical techniques for investigation of drug-DNA interaction were reviewed and we have discussed the type of qualitative or quantitative information that can be obtained from the use of each technique. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Heavy ion induced DNA transfer in biological cells

    International Nuclear Information System (INIS)

    Vilaithong, T.; Yu, L.D.; Apavatjrut, P.; Phanchaisri, B.; Sangyuenyongpipat, S.; Anuntalabhochai, S.; Brown, I.G.

    2004-01-01

    Low-energy ion beam bombardment of biological materials for genetic modification purposes has experienced rapid growth in the last decade, particularly for the direct DNA transfer into living organisms including both plants and bacteria. Attempts have been made to understand the mechanisms involved in ion-bombardment-induced direct gene transfer into biological cells. Here we summarize the present status of the application of low-energy ions for genetic modification of living sample materials

  13. Nanomechanical DNA Origami pH Sensors

    Directory of Open Access Journals (Sweden)

    Akinori Kuzuya

    2014-10-01

    Full Text Available Single-molecule pH sensors have been developed by utilizing molecular imaging of pH-responsive shape transition of nanomechanical DNA origami devices with atomic force microscopy (AFM. Short DNA fragments that can form i-motifs were introduced to nanomechanical DNA origami devices with pliers-like shape (DNA Origami Pliers, which consist of two levers of 170-nm long and 20-nm wide connected at a Holliday-junction fulcrum. DNA Origami Pliers can be observed as in three distinct forms; cross, antiparallel and parallel forms, and cross form is the dominant species when no additional interaction is introduced to DNA Origami Pliers. Introduction of nine pairs of 12-mer sequence (5'-AACCCCAACCCC-3', which dimerize into i-motif quadruplexes upon protonation of cytosine, drives transition of DNA Origami Pliers from open cross form into closed parallel form under acidic conditions. Such pH-dependent transition was clearly imaged on mica in molecular resolution by AFM, showing potential application of the system to single-molecular pH sensors.

  14. Nanomechanical DNA origami pH sensors.

    Science.gov (United States)

    Kuzuya, Akinori; Watanabe, Ryosuke; Yamanaka, Yusei; Tamaki, Takuya; Kaino, Masafumi; Ohya, Yuichi

    2014-10-16

    Single-molecule pH sensors have been developed by utilizing molecular imaging of pH-responsive shape transition of nanomechanical DNA origami devices with atomic force microscopy (AFM). Short DNA fragments that can form i-motifs were introduced to nanomechanical DNA origami devices with pliers-like shape (DNA Origami Pliers), which consist of two levers of 170-nm long and 20-nm wide connected at a Holliday-junction fulcrum. DNA Origami Pliers can be observed as in three distinct forms; cross, antiparallel and parallel forms, and cross form is the dominant species when no additional interaction is introduced to DNA Origami Pliers. Introduction of nine pairs of 12-mer sequence (5'-AACCCCAACCCC-3'), which dimerize into i-motif quadruplexes upon protonation of cytosine, drives transition of DNA Origami Pliers from open cross form into closed parallel form under acidic conditions. Such pH-dependent transition was clearly imaged on mica in molecular resolution by AFM, showing potential application of the system to single-molecular pH sensors.

  15. Habitat modification drives benthic trophic diversity in an intertidal soft-bottom ecosystem

    NARCIS (Netherlands)

    van der Zee, E.M.; Tielens, E.; Holthuijsen, S.; Donadi, S.; Eriksson, B.K.; van der Veer, H.W.; Piersma, T.; Olff, H.; van der Heide, T.

    2015-01-01

    In intertidal soft-bottom ecosystems, ecosystem engineers such as reef-building bivalves, can strongly affect the associated benthic community by providing structure and stabilizing the sediment. Although several engineering species have declined dramatically in the past centuries, the consequences

  16. Genetic Mutations and Epigenetic Modifications: Driving Cancer and Informing Precision Medicine

    Science.gov (United States)

    Coyle, Krysta Mila; Boudreau, Jeanette E.

    2017-01-01

    Cancer treatment is undergoing a significant revolution from “one-size-fits-all” cytotoxic therapies to tailored approaches that precisely target molecular alterations. Precision strategies for drug development and patient stratification, based on the molecular features of tumors, are the next logical step in a long history of approaches to cancer therapy. In this review, we discuss the history of cancer treatment from generic natural extracts and radical surgical procedures to site-specific and combinatorial treatment regimens, which have incrementally improved patient outcomes. We discuss the related contributions of genetics and epigenetics to cancer progression and the response to targeted therapies and identify challenges and opportunities for the success of precision medicine. The identification of patients who will benefit from targeted therapies is more complex than simply identifying patients whose tumors harbour the targeted aberration, and intratumoral heterogeneity makes it difficult to determine if a precision therapy is successful during treatment. This heterogeneity enables tumors to develop resistance to targeted approaches; therefore, the rational combination of therapeutic agents will limit the threat of acquired resistance to therapeutic success. By incorporating the view of malignant transformation modulated by networks of genetic and epigenetic interactions, molecular strategies will enable precision medicine for effective treatment across cancer subtypes. PMID:28685150

  17. Multi-scale habitat modification by coexisting ecosystem engineers drives spatial separation of macrobenthic functional groups

    NARCIS (Netherlands)

    Donadi, S.; van der Heide, T.; Piersma, T.; van der Zee, E.M.; Weerman, E.J.; van de Koppel, J.; Olff, H.; Devine, C.; Hernawan, U. E.; Boers, M.; Planthof, L.; Eriksson, B.K.

    2015-01-01

    By changing habitat conditions, ecosystem engineers increase niche diversity and have profound effects on the distribution and abundances of other organisms. Although many ecosystems contain several engineering species, it is still unclear how the coexistence of multiple engineers affects the

  18. Design and specificity of long ssDNA donors for CRISPR-based knock-in

    OpenAIRE

    Leonetti, Manuel; Li, Han; Beckman, Kyle; Pessino, Veronica; Huang, Bo; Weissman, Jonathan

    2017-01-01

    CRISPR/Cas technologies have transformed our ability to manipulate genomes for research and gene-based therapy. In particular, homology-directed repair after genomic cleavage allows for precise modification of genes using exogenous donor sequences as templates. While both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) forms of donors have been used as repair templates, a systematic comparison of the performance and specificity of repair using ssDNA versus dsDNA donors is still la...

  19. SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair

    DEFF Research Database (Denmark)

    Van Cuijk, Loes; Van Belle, Gijsbert J.; Turkyilmaz, Yasemin

    2015-01-01

    XPC recognizes UV-induced DNA lesions and initiates their removal by nucleotide excision repair (NER). Damage recognition in NER is tightly controlled by ubiquitin and SUMO modifications. Recent studies have shown that the SUMO-targeted ubiquitin ligase RNF111 promotes K63-linked ubiquitylation o...

  20. DNA Repair Systems

    Indian Academy of Sciences (India)

    DNA molecule which makes it ideal for storage and propagation of genetic information. ... of these errors are broadly referred to as DNA repair. DNA can ... changes occur in the human genome per day. ..... nails, frequent physical and mental.