Detection of clonal immunoglobulin heavy chain gene rearrangements by the polymerase chain reaction and capillary gel electrophoresis.

Science.gov (United States)

Fan, Hongxin; Robetorye, Ryan S

2013-01-01

Although well-established diagnostic criteria exist for mature B-cell neoplasms, a definitive diagnosis of a B-cell lymphoproliferative disorder cannot always be obtained using more conventional techniques such as flow cytometric immunophenotyping, conventional cytogenetics, fluorescence in situ hybridization, or immunohistochemistry. However, because B-cell malignancies contain identically rearranged immunoglobulin heavy chain genes, the polymerase chain reaction (PCR) can be a fast, convenient, and dependable option to identify clonal B-cell processes. This chapter describes the use of PCR and capillary electrophoresis to identify clonal immunoglobulin heavy chain (IGH) variable and joining region (VH-JH) gene rearrangements (IGH VH-JH PCR) using a commercially available method employing multiple multiplex PCR tubes that was originally developed as the result of a large European BIOMED-2 collaborative study (Invivoscribe Technologies). The core protocol involves the use of three separate master mix tubes that target the conserved framework (FR1, FR2, and FR3) and joining (J) regions of the IGH gene. Analysis of these three framework regions can detect approximately 88% of clonal IGH gene rearrangements.

EncM, a versatile enterocin biosynthetic enzyme involved in Favorskii oxidative rearrangement, aldol condensation, and heterocycle-forming reactions

Science.gov (United States)

Xiang, Longkuan; Kalaitzis, John A.; Moore, Bradley S.

2004-01-01

The bacteriostatic natural product enterocin from the marine microbe “Streptomyces maritimus” has an unprecedented carbon skeleton that is derived from an aromatic polyketide biosynthetic pathway. Its caged tricyclic, nonaromatic core is derived from a linear poly-β-ketide precursor that formally undergoes a Favorskii-like oxidative rearrangement. In vivo characterization of the gene encM through mutagenesis and heterologous biosynthesis demonstrated that its protein product not only is solely responsible for the oxidative C—C rearrangement, but also facilitates two aldol condensations plus two heterocycle forming reactions. In total, at least five chiral centers and four rings are generated by this multifaceted flavoprotein. Heterologous expression of the enterocin biosynthesis genes encABCDLMN in Streptomyces lividans resulted in the formation of the rearranged metabolite desmethyl-5-deoxyenterocin and the shunt products wailupemycins D-G. Addition of the methyltransferase gene encK, which was previously proposed through mutagenesis to additionally assist EncM in the Favorskii rearrangement, shifted the production to the O-methyl derivative 5-deoxyenterocin. The O-methyltransferase EncK seems to be specific for the pyrone ring of enterocin, because bicyclic polyketides bearing pyrone rings are not methylated in vivo. Expression of encM with different combinations of homologous actinorhodin biosynthesis genes did not result in the production of oxidatively rearranged enterocin-actinorhodin hybrid compounds as anticipated, suggesting that wild-type EncM may be specific for its endogenous type II polyketide synthase or for benzoyl-primed polyketide precursors. PMID:15505225

Efficient assembly of polysubstituted pyrroles via a (3 + 2) cycloaddition/skeletal rearrangement/redox isomerization cascade reaction.

Science.gov (United States)

Yu, Yuanyuan; Wang, Chunyu; He, Xinze; Yao, Xiaotong; Zu, Liansuo

2014-07-03

An unprecedented cascade strategy, used in conjunction with a redox isomerization, for the synthesis of 3-allyl pyrroles is reported. In a single step, readily accessible simple starting materials are transformed into highly substituted pyrroles with high efficiency. The products obtained contain allyl substituents, which can be readily elaborated to other useful functional groups. The reaction proceeds through an unusual (3 + 2) cycloaddition/skeletal rearrangement/redox isomerization pathway.

Density functional computational studies on the glucose and glycine Maillard reaction: Formation of the Amadori rearrangement products

Science.gov (United States)

Jalbout, Abraham F.; Roy, Amlan K.; Shipar, Abul Haider; Ahmed, M. Samsuddin

Theoretical energy changes of various intermediates leading to the formation of the Amadori rearrangement products (ARPs) under different mechanistic assumptions have been calculated, by using open chain glucose (O-Glu)/closed chain glucose (A-Glu and B-Glu) and glycine (Gly) as a model for the Maillard reaction. Density functional theory (DFT) computations have been applied on the proposed mechanisms under different pH conditions. Thus, the possibility of the formation of different compounds and electronic energy changes for different steps in the proposed mechanisms has been evaluated. B-Glu has been found to be more efficient than A-Glu, and A-Glu has been found more efficient than O-Glu in the reaction. The reaction under basic condition is the most favorable for the formation of ARPs. Other reaction pathways have been computed and discussed in this work.0

Design and synthesis of polycyclic sulfones via Diels-Alder reaction and ring-rearrangement metathesis as key steps.

Science.gov (United States)

Kotha, Sambasivarao; Gunta, Rama

2015-01-01

Here, we describe a new and simple synthetic strategy to various polycyclic sulfones via Diels-Alder reaction and ring-rearrangement metathesis (RRM) as the key steps. This approach delivers tri- and tetracyclic sulfones with six (n = 1), seven (n = 2) or eight-membered (n = 3) fused-ring systems containing trans-ring junctions unlike the conventional all cis-ring junctions generally obtained during the RRM sequence. Interestingly the starting materials used are simple and commercially available.

Methanetrisulfonic Acid: A Highly Efficient Strongly Acidic Catalyst for Wagner-Meerwein Rearrangement, Friedel-Crafts Alkylation and Acylation Reactions. Examples from Vitamin E Synthesis

Directory of Open Access Journals (Sweden)

Francesco Pace

2009-04-01

Full Text Available Methanetrisulfonic acid had been prepared for the first time over 140 years ago, but it was used only scarcely in chemical transformations. In the course of our activities dealing with key-steps of industrial syntheses of vitamins, e.g. economically important vitamin E (acetate, we found that methanetrisulfonic acid is an extremely effective catalyst in a variety of reactions. Examples of its applications are Wagner-Meerwein rearrangements, Friedel-Crafts alkylations and ring closures, as well as acylation reactions. Use of this catalyst in truly catalytic amounts (0.04-1.0 mol% resulted in highly selective transformations and yields over 95%. (Remark by the authors: We are describing only one example each for the various types of reactions. Therefore, it would be more appropriate to write (here and in the Introduction and in the Conclusion sections: “Wagner-Meerwein rearrangement, Friedel-Crafts alkylation and ring closure, as well as acylation reactions”

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

Directory of Open Access Journals (Sweden)

Stephanie R. Hare

2016-02-01

Full Text Available This review describes unexpected dynamical behaviors of rearranging carbocations and the modern computational methods used to elucidate these aspects of reaction mechanisms. Unique potential energy surface topologies associated with these rearrangements have been discovered in recent years that are not only of fundamental interest, but also provide insight into the way Nature manipulates chemical space to accomplish specific chemical transformations. Cautions for analyzing both experimental and theoretical data on carbocation rearrangements are included throughout.

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

Directory of Open Access Journals (Sweden)

Sebastian Krüger

2014-01-01

Full Text Available This review summarizes the application of the divinylcyclopropane–cycloheptadiene rearrangement in synthetic organic chemistry. A brief overview of the new mechanistic insights concerning the title reaction is provided as well as a condensed account on the biological relevance of the topic. Heteroatom variants of this rearrangement are covered briefly.

Thermal aromatic Claisen rearrangement and Strecker reaction of alkyl(allyl-aryl ethers under green reaction conditions: Efficient and clean preparation of ortho-allyl phenols (naphthols and alkyl(allyloxyarene-based γ-amino nitriles

Directory of Open Access Journals (Sweden)

Kheila N. Silgado-Gómez

2017-11-01

Full Text Available Chemical transformations of 13 diverse allyl(alkyl-aryl ethers, easily prepared using Williamson reaction of different hydroxyarenes and allyl bromide and alkyl (n-butyl, n-octyl bromides, were studied. Thermal aromatic Claisen rearrangement of allyl-aryl ethers to obtain ortho-allyl phenols (naphthols employing propylene carbonate as a nontoxic and biodegradable solvent was described for the first time. The use of this green solvent allowed to enhance notably product yields and reduce significantly the reaction time comparing with the use of 1,2-dichlorobenzene, toxic solvent, which is traditionally employed in this type of Claisen rearrangement. Three-component Strecker reaction of selected alkyl(allyl-aryl ethers with formyl function on aryl fragment and, piperidine and potassium cyanide in the presence of sulfuric acid supported on silica gel (SSA, SiO2-O-SO3H under mild reaction conditions was used in the preparation of new γ-amino nitriles, analogues of alkaloid girgensohnine [2-(4-hydroxyphenyl-2-(piperidin-1-ylacetonitrile], a perspective biological model in the search for new insecticidal agrochemicals against Aedes aegypti. The use of SSA, an inexpensive and reusable solid catalyst, allowed to obtain new series of 2-[4-alkyl(allyloxyphenyl]-2-(piperidin-1-ylacetonitriles in short time at room temperature with good yields.

Generalization of the quark rearrangement model

International Nuclear Information System (INIS)

Fields, T.; Chen, C.K.

1976-01-01

An extension and generalization of the quark rearrangement model of baryon annihilation is described which can be applied to all annihilation reactions and which incorporates some of the features of the highly successful quark parton model. Some p anti-p interactions are discussed

Mechanistic and kinetic insights into the thermally induced rearrangement of alpha-pinene.

Science.gov (United States)

Stolle, Achim; Ondruschka, Bernd; Findeisen, Matthias

2008-11-07

The thermal rearrangement of alpha-pinene (1) is interesting from mechanistic as well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal network of these hydrocarbons. Kinetic analysis of the major reaction steps allows for a deeper insight in the reaction mechanism. Thus it was possible to explain the racemization of 1, the formation of racemic limonene (4), and the absence of the primary pyrolysis product 2 in the reaction mixture resulting from thermal rearrangement of 1. Results supported the conclusion that the reactions starting with 1 involve biradical transition states.

Claisen, Cope and Related Rearrangements in the Synthesis of Flavour and Fragrance Compounds

Directory of Open Access Journals (Sweden)

Janusz Nowicki

2000-08-01

Full Text Available A review of the use of the Claisen, Cope and related [3,3]-sigmatropic rearrangements, sequential ("tandem" sigmatropic rearrangements and the "ene" reaction in the syntheses of flavour and fragrance compounds is presented.

Rapid analysis of rearranged kappa light chain genes of circulating polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the polymerase chain reaction

DEFF Research Database (Denmark)

Hougs, L; Barington, T; Madsen, HO

1993-01-01

reaction (PCR) using in addition a degenerate kappa light chain signal peptide region primer. The PCR product was cloned into the M13mp18 phage. The cloning efficiency was 100-600 clones/ml of blood. Of the 86 clones sequenced, 90% represented rearranged kappa light chain genes from different antibody...... of the B lymphocytes activated in vivo. Here, we present a method for rapid analysis of the rearranged kappa light chain genes used by human circulating antigen-specific B lymphocytes. After vaccination with Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugated with protein, the Hib...

Thermal degradation and isothermal crystalline behavior of poly(trimethylene terephthalate)

Institute of Scientific and Technical Information of China (English)

Jian Liu; Shu Guang Bian; Min Xiao; Shuan Jin Wang; Yue Zhong Meng

2009-01-01

Poly(trimethylene terephthalate)(PTT)is an excellent fiber material.Its thermal degradation and isothermal crystalline behaviors were in this study investigated using thermogravimetric analysis(TGA),thermogravimetric analysis-Fourier transform infrared spectroscopy(TGA-FTIR)analysis,differential scanning calorimetry(DSC)and X-ray diffraction(XRD).The thermal degradation mechanism of PTT follows Mclafferty rearrangement principle.The PTT with intrinsicviscosity(IV)of 0.74 dL/g has a maximum crystallinity of about 55%at 190℃,as demonstrated by DSC and XRD measurements consistently.

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

Directory of Open Access Journals (Sweden)

Valerij A. Nikolaev

2016-08-01

Full Text Available Rh(II-сatalyzed reactions of aroyldiazomethanes, diazoketoesters and diazodiketones with α,β-unsaturated δ-aminoesters, in contrast to reactions of diazomalonates and other diazoesters, give rise to the Wolff rearrangement and/or oxidative cleavage of the initially formed N–H-insertion products. These oxidation processes are mediated by Rh(II catalysts possessing perfluorinated ligands. The formation of pyrrolidine structures, characteristic for catalytic reactions of diazoesters, was not observed in these processes at all.

Selenium-mediated synthesis of biaryls through rearrangement.

Science.gov (United States)

Shahzad, Sohail A; Vivant, Clotilde; Wirth, Thomas

2010-03-19

A new cyclization of beta-keto ester substituted stilbene derivatives using selenium electrophiles in the presence of Lewis acids is described. Substituted naphthols are obtained through cyclization and subsequent 1,2-rearrangement of aryl groups under very mild reaction conditions.

Synthesis of fused tricyclic systems by thermal Cope rearrangement of furan-substituted vinyl cyclopropanes.

Science.gov (United States)

Klaus, Verena; Wittmann, Stéphane; Senn, Hans M; Clark, J Stephen

2018-05-15

A novel method for the stereoselective construction of hexahydroazuleno[4,5-b]furans from simple precursors has been developed. The route involves the use of our recently developed Brønsted acid catalysed cyclisation reaction of acyclic ynenones to prepare fused 1-furanyl-2-alkenylcyclopropanes that undergo highly stereoselective thermal Cope rearrangement to produce fused tricyclic products. Substrates possessing an E-alkene undergo smooth Cope rearrangement at 40 °C, whereas the corresponding Z-isomers do not react at this temperature. Computational studies have been performed to explain the difference in behaviour of the E- and Z-isomers in the Cope rearrangement reaction. The hexahydroazuleno[4,5-b]furans produced by Cope rearrangement have potential as advanced intermediates for the synthesis of members of the guaianolide family of natural products.

Hexose rearrangements upon fragmentation of N-glycopeptides and reductively aminated N-glycans.

Science.gov (United States)

Wuhrer, Manfred; Koeleman, Carolien A M; Deelder, André M

2009-06-01

Tandem mass spectrometry of glycans and glycoconjugates in protonated form is known to result in rearrangement reactions leading to internal residue loss. Here we studied the occurrence of hexose rearrangements in tandem mass spectrometry of N-glycopeptides and reductively aminated N-glycans by MALDI-TOF/TOF-MS/MS and ESI-ion trap-MS/MS. Fragmentation of proton adducts of oligomannosidic N-glycans of ribonuclease B that were labeled with 2-aminobenzamide and 2-aminobenzoic acid resulted in transfer of one to five hexose residues to the fluorescently tagged innermost N-acetylglucosamine. Glycopeptides from various biological sources with oligomannosidic glycans were likewise shown to undergo hexose rearrangement reactions, resulting in chitobiose cleavage products that have acquired one or two hexose moieties. Tryptic immunoglobulin G Fc-glycopeptides with biantennary N-glycans likewise showed hexose rearrangements resulting in hexose transfer to the peptide moiety retaining the innermost N-acetylglucosamine. Thus, as a general phenomenon, tandem mass spectrometry of reductively aminated glycans as well as glycopeptides may result in hexose rearrangements. This characteristic of glycopeptide MS/MS has to be considered when developing tools for de novo glycopeptide structural analysis.

Rearrangement of cluster structure during fission processes

DEFF Research Database (Denmark)

Lyalin, Andrey G.; Obolensky, Oleg I.; Solov'yov, Andrey V.

2004-01-01

Results of molecular dynamics simulations of fission reactions $Na_10^2+ -->Na_7^++ Na_3^+ and Na_18^2+--> 2Na_9^+ are presented. The dependence of the fission barriers on the isomer structure of the parent cluster is analysed. It is demonstrated that the energy necessary for removing homothetic...... groups of atoms from the parent cluster is largely independent of the isomer form of the parent cluster. The importance of rearrangement of the cluster structure during the fission process is elucidated. This rearrangement may include transition to another isomer state of the parent cluster before actual...

Nuclear structure in cold rearrangement processes in fission and fusion

Energy Technology Data Exchange (ETDEWEB)

Armbruster, P.

1998-11-01

In fission and fusion of heavy nuclei large numbers of nucleons are rearranged at a scale of excitation energy very small compared to the binding energy of the nuclei. The energies involved are less than 40 MeV at nuclear temperatures below 1.5 MeV. The shapes of the configurations in the rearrangement of a binary system into a monosystem in fusion, or vice versa in fission, change their elongations by as much as 8 fm, the radius of the monosystem. The dynamics of the reactions macroscopically described by a potential energy surface, inertia parameters, dissipation, and a collision energy is strongly modified by the nuclear structure of the participating nuclei. Experiments showing nuclear structure effects in fusion and fission of the heaviest nuclei are reviewed. The reaction kinematics and the multitude of isotopes involved are investigated by detector techniques and by recoil spectrometers. The advancement of the latter allows to find very small reaction branches in the range of 10{sup -5} to 10{sup -10}. The experiments reveal nuclear structure effects in all stages of the rearrangement processes. These are discussed pointing to analogies in fusion and fission on the microscopic scale, notwithstanding that both processes macroscopically are irreversible. Heavy clusters, as 132Sn, 208Pb, nuclei with closed shell configurations N=82,126, Z=50,82 survive in large parts of the nuclear rearrangement. They determine the asymmetry in the mass distribution of low energy fission, and they allow to synthesise superheavy elements, until now up to element 112. Experiments on the cold rearrangement in fission and fusion are presented. Here, in the range of excitation energies below 12 MeV the phenomena are observed most convincingly. (orig.)

Tandem catalytic allylic amination and [2,3]-Stevens rearrangement of tertiary amines.

Science.gov (United States)

Soheili, Arash; Tambar, Uttam K

2011-08-24

We have developed a catalytic allylic amination involving tertiary aminoesters and allylcarbonates, which is the first example of the use of tertiary amines as intermolecular nucleophiles in metal-catalyzed allylic substitution chemistry. This process is employed in a tandem ammonium ylide generation/[2,3]-rearrangement reaction, which formally represents a palladium-catalyzed Stevens rearrangement. Low catalyst loadings and mild reaction conditions are compatible with an unprecedented substrate scope for the ammonium ylide functionality, and products are generated in high yields and diastereoselectivities. Mechanistic studies suggested the reversible formation of an ammonium intermediate.

Biotransformation and Rearrangement of Laromustine.

Science.gov (United States)

Nassar, Alaa-Eldin F; Wisnewski, Adam V; King, Ivan

2016-08-01

This review highlights the recent research into the biotransformations and rearrangement of the sulfonylhydrazine-alkylating agent laromustine. Incubation of [(14)C]laromustine with rat, dog, monkey, and human liver microsomes produced eight radioactive components (C-1 to C-8). There was little difference in the metabolite profile among the species examined, partly because NADPH was not required for the formation of most components, which instead involved decomposition and/or hydrolysis. The exception was C-7, a hydroxylated metabolite, largely formed by CYP2B6 and CYP3A4/5. Liquid chromatography-multistage mass spectrometry (LC-MS(n)) studies determined that collision-induced dissociation, and not biotransformation or enzyme catalysis, produced the unique mass spectral rearrangement. Accurate mass measurements performed with a Fourier-transform ion cyclotron resonance mass spectrometer (FTICR-MS) significantly aided determination of the elemental compositions of the fragments and in the case of laromustine revealed the possibility of rearrangement. Further, collision-induced dissociation produced the loss of nitrogen (N2) and methylsulfonyl and methyl isocyanate moieties. The rearrangement, metabolite/decomposition products, and conjugation reactions were analyzed utilizing hydrogen-deuterium exchange, exact mass, (13)C-labeled laromustine, nuclear magnetic resonance spectroscopy (NMR), and LC-MS(n) experiments to assist with the assignments of these fragments and possible mechanistic rearrangement. Such techniques produced valuable insights into these functions: 1) Cytochrome P450 is involved in C-7 formation but plays little or no role in the conversion of [(14)C]laromustine to C-1 through C-6 and C-8; 2) the relative abundance of individual degradation/metabolite products was not species-dependent; and 3) laromustine produces several reactive intermediates that may produce the toxicities seen in the clinical trials. Copyright © 2016 by The American Society for

Detection of clonal T-cell receptor beta and gamma chain gene rearrangement by polymerase chain reaction and capillary gel electrophoresis.

Science.gov (United States)

Fan, Hongxin; Robetorye, Ryan S

2013-01-01

Although established diagnostic criteria exist for mature T-cell neoplasms, a definitive diagnosis of a T-cell lymphoproliferative disorder cannot always be obtained using more conventional techniques such as flow cytometric immunophenotyping, conventional cytogenetics, fluorescence in situ hybridization, or immunohistochemistry. However, because T-cell malignancies contain identically rearranged T-cell receptor gamma (TCRG) and/or beta (TCRB) genes, the polymerase chain reaction (PCR) can be a fast, convenient, and dependable option to identify clonal T-cell processes. This chapter describes the use of PCR and capillary electrophoresis to identify clonal TCRB and TCRG gene rearrangements (TCRB and TCRG PCR) using a commercially available method employing multiple multiplex PCR tubes that was originally developed as the result of a large European BIOMED-2 collaborative study (Invivoscribe Technologies). The core protocol for the TCRB assay involves the use of three separate multiplex master mix tubes. Tubes A and B target the framework regions within the variable and joining regions of the TCRB gene, and Tube C targets the diversity and joining regions of the TCRB gene. The core protocol for the TCRG assay utilizes two multiplex master mix tubes (Tubes A and B) that target the variable and joining regions of the TCRG gene. Use of the five BIOMED-2 TCRB and TCRG PCR multiplex tubes in parallel can detect approximately 94% of clonal TCR gene rearrangements.

Heterogeneity of BCR-ABL rearrangement in patients with chronic myeloid leukemia in Pakistan.

Science.gov (United States)

Tabassum, Najia; Saboor, Mohammad; Ghani, Rubina; Moinuddin, Moinuddin

2014-07-01

Breakpoint cluster region-Abelson (BCR-ABL) rearrangement or Philadelphia (Ph) chromosome in Chronic Myeloid Leukemia (CML) is derived from a reciprocal chromosomal translocation between ABL gene on chromosome 9 and BCR gene on chromosome 22. This chimeric protein has various sizes and therefore different clinical behaviour. The purpose of this study was to determine the heterogeneity of BCR-ABL rearrangement in patients with Ph(+)CML in Pakistan. The study was conducted at Civil Hospital and Baqai Institute of Hematology (BIH) Karachi. Blood samples from 25 patients with CML were collected. Multiplex reverse transcription polymerase chain reaction (RT-PCR) was performed to identify various BCR-ABL transcripts. All 25 samples showed BCR-ABL rearrangements. Out of these, 24 (96%) patients expressed p210 BCR-ABL rearrangements i.e. 60% (n=15) had b3a2 and 32% (n=8) had b2a2 rearrangements. Co-expression of b3a2 /b2a2 rearrangement and p190 (e1a3) rearrangement was also identified in two patients. It is apparent that majority of the patients had p210 BCR-ABL rearrangements. Frequency of co-expression and rare fusion transcripts was very low.

Multicomponent Reaction of Z-Chlorooximes, Isocyanides, and Hydroxylamines as Hypernucleophilic Traps. A One-Pot Route to Aminodioximes and Their Transformation into 5-Amino-1,2,4-oxadiazoles by Mitsunobu-Beckmann Rearrangement.

Science.gov (United States)

Mercalli, Valentina; Massarotti, Alberto; Varese, Monica; Giustiniano, Mariateresa; Meneghetti, Fiorella; Novellino, Ettore; Tron, Gian Cesare

2015-10-02

Synthetically useful aminodioximes are prepared via a novel three-component reaction among Z-chlorooximes, isocyanides, and hydroxylamines by exploiting the preferential attack of isocyanides to nitrile N-oxides via a [3 + 1] cycloaddition reaction. The results of quantum mechanical studies of the reaction mechanism are also discussed. Furthermore, the one-pot conversion of aminodioximes to 1,2,3-oxadiazole-5-amines via Mitsunobu-Beckmann rearrangement is reported for the first time.

Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

Directory of Open Access Journals (Sweden)

Neil Spencer

2011-06-01

Full Text Available Isotopic labelling studies were performed to probe a proposed 1,2-aryl shift in the gold-catalysed cycloisomerisation of alkynyl aziridines into 2,4-disubstituted pyrroles. Two isotopomers of the expected skeletal rearrangement product were identified using 13C-labelling and led to a revised mechanism featuring two distinct skeletal rearrangements. The mechanistic proposal has been rationalised against the reaction of a range of 13C- and deuterium-labelled substrates.

A proposal for calculating the importance of exchange effects in rearrangement collisions

International Nuclear Information System (INIS)

Mihailovic, M.V.; Nagarajan, M.A.

1980-02-01

A formalism based on the generator co-ordinate method (GCM) for reactions is derived to test approximations in the most commonly used methods for calculating the rearrangement amplitudes: namely the distorted wave Born approximation (DWBA), the coupled channel Born approximation (CCBA) and the coupled reaction channel (CRC). (author)

Rearrangements in ground and excited states

CERN Document Server

de Mayo, Paul

1980-01-01

Rearrangements in Ground and Excited States, Volume 2 covers essays on the theoretical approach of rearrangements; the rearrangements involving boron; and the molecular rearrangements of organosilicon compounds. The book also includes essays on the polytopal rearrangement at phosphorus; the rearrangement in coordination complexes; and the reversible thermal intramolecular rearrangements of metal carbonyls. Chemists and people involved in the study of rearrangements will find the book invaluable.

Exohedral and skeletal rearrangements in the molecules of fullerene derivatives

Energy Technology Data Exchange (ETDEWEB)

Ignat' eva, Daria V; Ioffe, I N; Troyanov, Sergey I; Sidorov, Lev N [Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow (Russian Federation)

2011-07-31

The data on the migration of monoatomic addends, perfluoroalkyl and more complex organic groups in the molecules of fullerene derivatives published mainly in the last decade are analyzed. Skeletal rearrangements of the carbon cage occurring during chemical reactions are considered.

Rearrangements in ground and excited states

CERN Document Server

de Mayo, Paul

1980-01-01

Rearrangements in Ground and Excited States, Volume 3 presents essays on the chemical generation of excited states; the cis-trans isomerization of olefins; and the photochemical rearrangements in trienes. The book also includes essays on the zimmerman rearrangements; the photochemical rearrangements of enones; the photochemical rearrangements of conjugated cyclic dienones; and the rearrangements of the benzene ring. Essays on the photo rearrangements via biradicals of simple carbonyl compounds; the photochemical rearrangements involving three-membered rings or five-membered ring heterocycles;

Enantioselective catalytic fluorinative aza-semipinacol rearrangement.

Science.gov (United States)

Romanov-Michailidis, Fedor; Pupier, Marion; Besnard, Céline; Bürgi, Thomas; Alexakis, Alexandre

2014-10-03

An efficient and highly stereoselective fluorinative aza-semipinacol rearrangement is described. The catalytic reaction requires use of Selectfluor in combination with the chiral, enantiopure phosphate anion derived from acid L3. Under optimized conditions, cyclopropylamines A were transformed into β-fluoro cyclobutylimines B in good yields and high levels of diastereo- and enantiocontrol. Furthermore, the optically active cyclobutylimines were reduced diastereoselectively with L-Selectride in the corresponding fluorinated amines C, compounds of significant interest in the pharmacological industry.

Aza Cope Rearrangement of Propargyl Enammonium Cations Catalyzed By a Self-Assembled `Nanozyme

Energy Technology Data Exchange (ETDEWEB)

Hastings, Courntey J.; Fiedler, Dorothea; Bergman, Robert G.; Raymond, Kenneth N.

2008-02-27

The tetrahedral [Ga{sub 4}L{sub 6}]{sup 12-} assembly (L = N,N-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) encapsulates a variety of cations, including propargyl enammonium cations capable of undergoing the aza Cope rearrangement. For propargyl enammonium substrates that are encapsulated in the [Ga{sub 4}L{sub 6}]{sup 12-} assembly, rate accelerations of up to 184 are observed when compared to the background reaction. After rearrangement, the product iminium ion is released into solution and hydrolyzed allowing for catalytic turnover. The activation parameters for the catalyzed and uncatalyzed reaction were determined, revealing that a lowered entropy of activation is responsible for the observed rate enhancements. The catalyzed reaction exhibits saturation kinetics; the rate data obey the Michaelis-Menten model of enzyme kinetics, and competitive inhibition using a non-reactive guest has been demonstrated.

Beckmann rearrangement of aldoximes catalyzed by transition metal salts: mechanical aspects

NARCIS (Netherlands)

Leusink, A.J.; Meerbeek, T.G.; Noltes, J.G.

1977-01-01

The Beckmann rearrangement of aldoximes catalyzed by transition metal salts like palladium and nickel acetylacetonates is shown to be a dehydration‐hydration reaction in which the anti‐oxime is converted into nitrile and the nitrile is converted into amide.

Reaction of hypochlorite with amino acids and peptides : EPR evidence for rapid rearrangement and fragmentation of nitrogen-centred radicals

International Nuclear Information System (INIS)

Hawkins, C.L.; Davies, M.J.

1998-01-01

Various amino acid side chains have been shown to be particularly susceptible to attack and modification by hypochlorite (HOCl). It is known that tyrosine is readily chlorinated by HOCl to give 3-chlorotyrosine and this product has been employed as a marker of HOCl-mediated damage to proteins. Cysteine and methionine react rapidly with HOCl to give oxy acids and cystine (from cysteine) and sulphoxides (from methionine). Lysine and amino acids which lack the above functional groups also react with HOCl via the free amino group which results in the generation of unstable chloramine intermediates; subsequent decomposition of these species gives NH 3 , CO 2 and aldehydes. While the products of reaction of HOCl with amino acids and peptides are reasonably well characterised, the mechanism(s) by which these products arise is less well understood. Electron paramagnetic resonance (EPR) spectroscopy with spin trapping and UV/visible spectroscopy has been employed to examine the reaction of HOCl with amino acids and some small peptides. Reaction of HOCl with N-acetyl amino acids or small peptides gives radicals predominantly at α-carbon sites via reaction at N-terminal free amino groups or amide (peptide) bonds. It is proposed that these carbon-centred radicals are produced as a result of the rearrangement of initial nitrogen-centred radicals formed on cleavage of the N-CI bond of the chloramine/chloramide species by a 1,2-shift reaction

Fries rearrangement of naphthyl benzoates; Ansoku kosan naphthyl no fries ten`i

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, J.; Haraguchi, Y.; Iwaki, T.; Yamana, Sasaki, H. [Tottori University, Tottori (Japan). Faculty of Engineering

1996-10-10

When 1-naphthyl benzoate (1{alpha}) was boiled with anhydrous aluminum chloride (AlCl3) in chlorobenzene, 2-benzoyl-l-naphthol(2) and 4-benzoyl-l-naphthol(3) were obtained as the rearrangement products. A product 1-benzoyl-2-naphthol (4) was given from 2-naphthyl benzoate (1{beta}) under the same reaction conditions. It seems that 2 and 3 are formed via intramolecular pathway from 1{alpha}. Other ester 1{beta} may proceed via both inter- and intramolecular pathways to give 4. Retro-Fries rearrangement of 2 and 3 to 1{alpha} took place in the presence of AlCl3 in boiling chlorobenzene. The compound 4 `however` was almost recovered the reaction of 4 with AlCl3 in chlorobenzene at refluxed temperature. 25 refs., 3 figs., 1 tab.

Ring Expansion and Rearrangements of Rhodium(II) Azavinyl Carbenes

Science.gov (United States)

Selander, Nicklas; Worrell, Brady T.

2013-01-01

An efficient, regioselective and convergent method for the ring expansion and rearrangement of 1-sulfonyl-1,2,3-triazoles under rhodium(II)-catalyzed conditions is described. These denitrogenative reactions form substituted enaminone and olefin-based products, which in the former case can be further functionalized to unique products rendering the sulfonyl triazole traceless. PMID:23161725

The photochemical reaction of 1,1-dicyano-3-phenylbut-1-ene. Simultaneous occurrence of p-methane and di-p-methane rearrangements

Directory of Open Access Journals (Sweden)

Silva Francisco A. da

1999-01-01

Full Text Available The direct photolysis of 1,1-dicyano-3-phenylbut-1-ene (3-MDCN was investigated at room temperature in solvents of different polarities (hexane, dichloromethane and acetonitrile. Cyclopropanes arising from both the di-pi-methane and pi-methane (1,2-H migration processes were obtained as photoproducts. The structures of the products were elucidated by ¹H-NMR, GC/MS, IR and chromatography. Relative quantum yield determination and GC analysis of sequential irradiations gave evidence that: i no secondary reactions occur, even at high conversions; ii the di-pi-methane rearrangement is significantly more affected by the solvent variation than the pi-methane reaction. Photosensitization with acetophenone or acetone did not yield any observable products. The existence of the simultaneous mechanisms and the observed effects were considered as evidence of a possible differentiation between localized and delocalized excitation on the excited state surface.

Fragmentation pathways and structural characterization of organophosphorus compounds related to the Chemical Weapons Convention by electron ionization and electrospray ionization tandem mass spectrometry.

Science.gov (United States)

Hosseini, Seyed Esmaeil; Saeidian, Hamid; Amozadeh, Ali; Naseri, Mohammad Taghi; Babri, Mehran

2016-12-30

For unambiguous identification of Chemical Weapons Convention (CWC)-related chemicals in environmental samples, the availability of mass spectra, interpretation skills and rapid microsynthesis of suspected chemicals are essential requirements. For the first time, the electron ionization single quadrupole and electrospray ionization tandem mass spectra of a series of O-alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates (Scheme 1, cpd 4) were studied for CWC verification purposes. O-Alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates were prepared through a microsynthetic method and were analyzed using electron ionization and electrospray ionization mass spectrometry with gas and liquid chromatography, respectively, as MS-inlet systems. General EI and ESI fragmentation pathways were proposed and discussed, and collision-induced dissociation studies of the protonated derivatives of these compounds were performed to confirm proposed fragment ion structures by analyzing mass spectra of deuterated analogs. Mass spectrometric studies revealed some interesting fragmentation pathways during the ionization process, such as McLafferty rearrangement, hydrogen rearrangement and a previously unknown intramolecular electrophilic aromatic substitution reaction. The EI and ESI fragmentation routes of the synthesized compounds 4 were investigated with the aim of detecting and identifying CWC-related chemicals during on-site inspection and/or off-site analysis and toxic chemical destruction monitoring. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Mutations and Rearrangements in the Genome of Sulfolobus solfataricus P2

DEFF Research Database (Denmark)

Redder, P.; Garrett, R. A.

2006-01-01

The genome of Sulfolobus solfataricus P2 carries a larger number of transposable elements than any other sequenced genome from an archaeon or bacterium and, as a consequence, may be particularly susceptible to rearrangement and change. In order to gain more insight into the natures and frequencies...... of different types of mutation and possible rearrangements that can occur in the genome, the pyrEF locus was examined for mutations that were isolated after selection with 5-fluoroorotic acid. About two-thirds of the 130 mutations resulted from insertions of mobile elements, including insertion sequence (IS...... deletions, insertions, and a duplication, were observed, and about one-fifth of the mutations occurred elsewhere in the genome, possibly in an orotate transporter gene. One mutant exhibited a 5-kb genomic rearrangement at the pyrEF locus involving a two-step IS element-dependent reaction, and its boundaries...

Catalytic synthesis of amides via aldoximes rearrangement.

Science.gov (United States)

Crochet, Pascale; Cadierno, Victorio

2015-02-14

Amide bond formation reactions are among the most important transformations in organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method to generate secondary amides from ketoximes. However, under the acidic conditions commonly employed, aldoximes RHC=NOH rarely rearrange into the corresponding primary amides RC(=O)NH2. In recent years, it was demonstrated that this atom-economical transformation can be carried out efficiently and selectively with the help of metal catalysts. Several homogeneous and heterogenous systems have been described. In addition, protocols offering the option to generate the aldoximes in situ from the corresponding aldehydes and hydroxylamine, or even from alcohols, have also been developed, as well as a series of tandem processes allowing the access to N-substituted amide products. In this Feature article a comprehensive overview of the advances achieved in this particular research area is presented.

Optimal control of a Cope rearrangement by coupling the reaction path to a dissipative bath or a second active mode

International Nuclear Information System (INIS)

Chenel, A.; Meier, C.; Dive, G.; Desouter-Lecomte, M.

2015-01-01

We compare the strategy found by the optimal control theory in a complex molecular system according to the active subspace coupled to the field. The model is the isomerization during a Cope rearrangement of Thiele’s ester that is the most stable dimer obtained by the dimerization of methyl-cyclopentadienenylcarboxylate. The crudest partitioning consists in retaining in the active space only the reaction coordinate, coupled to a dissipative bath of harmonic oscillators which are not coupled to the field. The control then fights against dissipation by accelerating the passage across the transition region which is very wide and flat in a Cope reaction. This mechanism has been observed in our previous simulations [Chenel et al., J. Phys. Chem. A 116, 11273 (2012)]. We compare here, the response of the control field when the reaction path is coupled to a second active mode. Constraints on the integrated intensity and on the maximum amplitude of the fields are imposed limiting the control landscape. Then, optimum field from one-dimensional simulation cannot provide a very high yield. Better guess fields based on the two-dimensional model allow the control to exploit different mechanisms providing a high control yield. By coupling the reaction surface to a bath, we confirm the link between the robustness of the field against dissipation and the time spent in the delocalized states above the transition barrier

Nitrile anion cyclization with epoxysilanes followed by Brook rearrangement/ring-opening of cyclopropane nitriles/alkylation.

Science.gov (United States)

Okugawa, Seigo; Masu, Hyuma; Yamaguchi, Kentaro; Takeda, Kei

2005-12-09

[reactions: see text] The reaction of delta-silyl-gamma,delta-epoxypentanenitrile derivatives 9-12 with a base and an alkylating agent affords (Z)-delta-siloxy-gamma,delta-unsaturated pentanenitrile derivatives via a tandem process that involves the formation of a cyclopropane derivative by epoxy nitrile cyclization followed by Brook rearrangement and an anion-induced cleavage of the cyclopropane ring. Exclusive formation of a (Z)-derivative from trans-epoxides is explained by the reaction pathway that involves a backside displacement of the epoxide by the alpha-nitrile carbanion and the O-Si bond formation followed by concerted processes involving Brook rearrangement and the anti-mode of eliminative ring fission of the cyclopropane from the rotamer 19. The fact that (E)-isomers are exclusively obtained from cis-epoxides and alpha-cyclopropyl-alpha-silylcarbinol derivative 26 provides experimental support for the proposed pathway.

Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

Directory of Open Access Journals (Sweden)

Jungho Jun

2013-08-01

Full Text Available Gold-catalyzed intermolecular couplings of sulfonylacetylenes with allyl ethers are reported. A cooperative polarization of alkynes both by a gold catalyst and a sulfonyl substituent resulted in an efficient intermolecular tandem carboalkoxylation. Reactions of linear allyl ethers are consistent with the [3,3]-sigmatropic rearrangement mechanism, while those of branched allyl ethers provided [3,3]- and [1,3]-rearrangement products through the formation of a tight ion–dipole pair.

Study of the rearrangement of N-alkylanilines to P-aminoalkylbencene. III. N-n-propil-l-14C aniline

International Nuclear Information System (INIS)

Molera, J. M.; Gamboa, J. M.; Val del Cob, M.; Ortin, N.

1964-01-01

The rearrangement of N-n-propyl aniline to p-amino propylbenzene has been studied at 250 degree centigrade using several catalysts: CoCl 2 , ZnCl 2 and HBr. N-propyl-1-14 C -aniline has been synthesized from sodium propionate-1-14 C through conversion to n-propyl-1-14 C -iodide and further reaction with aniline. After the rearrangement and among the reaction products both p-aminopropylbenzene and p-aminoisopropylbencene were found. To determine the 14 C position in both the starting aniline and reaction products two degradation schemes are followed. In the light of experimental evidence a mechanism is set forth based on the assumption of an organic cation as intermediate. (Author) 13 refs

Mapping of 5q35 chromosomal rearrangements within a genomically unstable region

DEFF Research Database (Denmark)

Buysse, Karen; Crepel, An; Menten, Björn

2008-01-01

these rearrangements. METHODS: We analysed a series of patients with breakpoints clustering within chromosome band 5q35. Using high density arrays and subsequent quantitative polymerase chain reaction (qPCR), we characterised the breakpoints of four interstitial deletions (including one associated with an unbalanced...

Recent Developments in the Reformatsky-Claisen Rearrangement

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Susumi Hatakeyama

2012-11-01

Full Text Available The rearrangement of allyl a-bromoacetates with Zn dust is known as the Reformatsky-Claisen rearrangement. Whereas the Ireland-Claisen rearrangement has been widely used in the synthesis of a diverse range of natural products, the Zn-mediated Reformatsky-Claisen rearrangement has not been utilized so often. In this article, we will provide an overview of recent advances in the Reformatsky-Claisen rearrangement field, including the In-mediated Reformatsky-Claisen rearrangement we have recently developed.

Study of the rearrangement of N-alkylaniline to p-aminoalkylbencene. I. N-ethyl-l-14C-aniline

International Nuclear Information System (INIS)

Molera, M. J.; Gamboa, J. M.; Val Cob, M. del

1961-01-01

The rearrangement of N-ethylaniline to p-aminoethylbenzene has been studied over the temperature range 200-300 degree centigrade using different catalysts: Cl 2 Co, Cl 2 Zn, Cl 2 Ni, Cl 3 Al, Cl 2 Cd and Br H.N-ethyl-1- 1 4C-aniline has been synthesized from ethyl-1- 1 4C-iodide and aniline and its rearrangement to p-aminoethyl-benzene proves that the ethyl group does not rearrange itself during the reaction. A scheme for the degradation of both the N-ethyl-1- 1 4C aniline and the p-aminoethylbenzene produces is described. (Author) 14 refs

Electron beam-induced Fries rearrangement of arylsulfonamides and arylsulfonates in the crystalline state

International Nuclear Information System (INIS)

Kato, Jun; Yuasa, Kanako; Yamashita, Takashi; Maekawa, Yasunari; Yoshida, Masaru

2003-01-01

Electron beam (EB)-induced reactions of organic crystals containing a carbonyl or a sulfonyl group have been investigated. The EB irradiation of benzenesulfonanilide (BSA) in the crystalline state induced the Fries rearrangement to yield o- and p-aminodiphenylsulfones as the major and minor products, respectively. Several BSA derivatives also had the same reactivity, while benzanilide as the corresponding carbonyl compound did not rearrange under the same conditions. These results showed that the S-N bond could be cleaved selectively by EB irradiation but the C-N bond couldn't, which could take place only by the use of EB. The EB irradiation of phenyl p-toluenesulfonate (PTS) crystals gave not only Fries-type products but also the oxidation product. By comparing with the reactivity of liquid phenyl benzenesulfonate, the EB-induced Fries rearrangement was suggested to proceed under crystalline lattice restrictions. The G-values of arylsulfonamides and arylsulfonates were in the range of ca. 1-2 molecules per 100 eV of absorbed energy. This is the first Fries rearrangement via direct excitation by EB irradiation. (author)

Oxidoreduction reactions involving the electrostatic and the covalent complex of cytochrome c and plastocyanin: Importance of the protein rearrangement for the intracomplex electron-transfer reaction

International Nuclear Information System (INIS)

Peerey, L.M.; Kostic, N.M.

1989-01-01

Horse heart cytochrome c and French bean plastocyanin are cross-linked one-to-one by a carbodiimide in the same general orientation in which they associate electrostatically. The reduction potentials of the Fe and Cu atoms in the covalent diprotein complex are respectively 245 and 385 mV vs NHE; the EPR spectra of the two metals are not perturbed by cross-linking. For isomers of the covalent diprotein complex, which probably differ slightly from one another in the manner of cross-linking, are separated efficiently by cation-exchange chromatography. Stopped-flow spectrophotometric experiments with the covalent diprotein complex show that the presence of plastocyanin somewhat inhibits oxidation of ferrocytochrome c by [Fe(CN) 6 ] 3- and somewhat promotes oxidation of this protein by [Fe(C 5 H 5 ) 2 ] + . These changes in reactivity are explained in terms of electrostatic and steric effects. Pulse-radiolysis experiments with the electrostatic diprotein complex yield association constants of ≥5 x 10 6 and 1 x 10 5 M -1 at ionic strengths of 1 and 40 mM, respectively, and the rate constant of 1.05 x 10 3 s -1 , regardless of the ionic strength, for the intracomplex electron-transfer reaction. Analogous pulse-radiolysis experiments with each of the four isomers of the covalent diprotein complex, at ionic strengths of both 2 and 200 mM, show an absence of the intracomplex electron-transfer reaction. A rearrangement of the proteins for this reaction seems to be possible (or unnecessary) in the electrostatic complex but impossible in the covalent complex

Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange

DEFF Research Database (Denmark)

Hansen, Tina Østergaard; Lange, Anders Blaabjerg; Barington, Torben

2015-01-01

Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B...... frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus....

Gold(I)-assisted catalysis - a comprehensive view on the [3,3]-sigmatropic rearrangement of allyl acetate

Science.gov (United States)

Freindorf, Marek; Cremer, Dieter; Kraka, Elfi

2018-03-01

The unified reaction valley approach (URVA) combined with the local mode, ring puckering and electron density analysis is applied to elucidate the mechanistic differences of the non-catalysed and the Au[I]-N-heterocyclic carbene (NHC)-catalysed [3,3]-sigmatropic rearrangement of allyl acetate. Using a dual-level approach (DFT and DLPNO-CCSD(T)), the influence of solvation, counter-ions, bulky and electron withdrawing/donating substituents as well as the exchange of the Au[I]-NHC with a Au[I]-phosphine catalyst is investigated. The catalyst breaks up the rearrangement into two steps by switching between Au[I]-π and Au[I]-σ complexation, thus avoiding the energy-consuming CO cleavage in the first step. Based on local stretching force constants ka(C=C), we derive for the first time a quantitative measure of the π-acidity of the Au[I] catalyst; in all catalysed reactions, the bond order n(C=C) drops from 2 to 1.65. The ring puckering analysis clarifies that all reactions start and end via a six-membered ring with a boat form. All Au[I]-σ-complex intermediates show a considerable admixture of the chair form. The non-catalysed [3,3]-sigmatropic rearrangement goes through a maximum of charge separation between the allyl and acetate units at the transition state, while all catalysed reactions proceed via a minimum of charge separation reached in the region of the Au[I]-σ-complex.

Transverse momentum in the multiple production processes and urbaryon rearrangement model

International Nuclear Information System (INIS)

Igarashi, Yuji; Matsuoka, Takeo; Sawada, Shoji

1977-01-01

Several characteristic features of p sub(T) distribution are studied on the basis of the multibody amplitude of urbaryon rearrangement model which is a generalization of the all-angle formula for two-body hadronic reactions at high energies. Several characteristic structures of amplitudes of the model are compared with other models. The seagull behaviour observed in the longitudinal momentum dependence of the average p sub(T) of pion is explained as a result of long range correlation among the hadrons linked with each other by rearranged urbaryons. It is also shown that the increase of average p sub(T) with particle mass and the dependence on unitary spins such as strangeness and charm are well reproduced by the model amplitudes. (auth.)

Catalytic Asymmetric Piancatelli Rearrangement: Brønsted Acid Catalyzed 4π Electrocyclization for the Synthesis of Multisubstituted Cyclopentenones

KAUST Repository

Cai, Yunfei

2016-10-13

The first catalytic asymmetric Piancatelli reaction is reported. Catalyzed by a chiral Brønsted acid, the rearrangement of a wide range of furylcarbinols with a series of aniline derivatives provides valuable aminocyclopentenones in high yields as well as excellent enantioselectivities and diastereoselectivities. The high value of the aza-Piancatelli rearrangement was demonstrated by the synthesis of a cyclopentane-based hNK1 antagonist analogue.

ON THE PECULIARITIES OF THE RING CONTRACTION REACTIONS OF HOMODRIMANES VIA ACID MEDIATED EPOXIDE REARRANGEMENT

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Veaceslav Kulciţki

2011-06-01

Full Text Available A selective rearrangement of a epoxy-homodrimanic substrate is described. Using fluorosulfonic acid at low temperature leads by ring contraction to a perhydrindanic structure. On the contrary, using boron trifluoride-diethyl ether at r.t. selectively brings about angular methyl migration.

Regioselective 1-N-Alkylation and Rearrangement of Adenosine Derivatives.

Science.gov (United States)

Oslovsky, Vladimir E; Drenichev, Mikhail S; Mikhailov, Sergey N

2015-01-01

Several methods for the preparation of some N(6)-substituted adenosines based on selective 1-N-alkylation with subsequent Dimroth rearrangement were developed. The proposed methods seem to be effective for the preparation of natural N(6)-isopentenyl- and N(6)-benzyladenosines, which are known to possess pronounced biological activities. Direct 1-N-alkylation of 2',3',5'-tri-O-acetyladenosine and 3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides in N,N-dimethylformamide (DMF) in the presence of BaCO3 and KI gave 1-N-substituted derivatives with quantitative yields, whereas 1-N-alkylation of adenosine was accompanied by significant O-alkylation. Moreover, the reaction of trimethylsilyl derivatives of N(6)-acetyl-2',3',5'-tri-O-acetyladenosine and N(6)-acetyl-3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides leads to the formation of the stable 1-N-substituted adenosines. Dimroth rearrangement of 1-N-substituted adenosines in aqueous ammonia yields pure N(6)-substituted adenosines.

Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

Directory of Open Access Journals (Sweden)

Hyun-Kyoung Kim

Full Text Available BACKGROUND: The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs, which are abundant in solid tumors, can be utilized for identification of rearranged ends. METHOD: As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP microarray method entailing CNB-region refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9% were identified, and two polymerase chain reaction (PCR-amplifiable rearrangements were obtained in six cases (66.7%. And significantly, TNGS-CNB, with its high positive identification rate (82.6% of PCR-amplifiable rearrangements at candidate sites (19/23, just from filtering of aligned sequences, requires little effort for validation. CONCLUSION: Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

Science.gov (United States)

Kim, Hyun-Kyoung; Park, Won Cheol; Lee, Kwang Man; Hwang, Hai-Li; Park, Seong-Yeol; Sorn, Sungbin; Chandra, Vishal; Kim, Kwang Gi; Yoon, Woong-Bae; Bae, Joon Seol; Shin, Hyoung Doo; Shin, Jong-Yeon; Seoh, Ju-Young; Kim, Jong-Il; Hong, Kyeong-Man

2014-01-01

The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends. As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA. Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation. Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

Application of microwave irradiation to organic liquid phase reactions

International Nuclear Information System (INIS)

Huang Kun; Liu Hua; Ji Xuelin

1994-01-01

Microwave irradiation has been used in organic liquid phase reactions to significantly reduce the reaction time and improve the yield. The proposed mechanism, the development of techniques and reactions, such as Diels-Alder, ene, rearrangement reactions etc., are discussed

Claisen thermally rearranged (CTR) polymers

Science.gov (United States)

Tena, Alberto; Rangou, Sofia; Shishatskiy, Sergey; Filiz, Volkan; Abetz, Volker

2016-01-01

Thermally rearranged (TR) polymers, which are considered the next-generation of membrane materials because of their excellent transport properties and high thermal and chemical stability, are proven to have significant drawbacks because of the high temperature required for the rearrangement and low degree of conversion during this process. We demonstrate that using a [3,3]-sigmatropic rearrangement, the temperature required for the rearrangement of a solid glassy polymer was reduced by 200°C. Conversions of functionalized polyimide to polybenzoxazole of more than 97% were achieved. These highly mechanically stable polymers were almost five times more permeable and had more than two times higher degrees of conversion than the reference polymer treated under the same conditions. Properties of these second-generation TR polymers provide the possibility of preparing efficient polymer membranes in a form of, for example, thin-film composite membranes for various gas and liquid membrane separation applications. PMID:27482538

Excited- and Ground-State Versions of the Tri-.pi.-methane Rearrangement: Mechanistic and Exploratory Organic Photochemistry

Czech Academy of Sciences Publication Activity Database

Zimmerman, H. E.; Církva, Vladimír

2001-01-01

Roč. 66, č. 5 (2001), s. 1839-1851 ISSN 0022-3263 Grant - others:NSF(US) CHE-9709005 Keywords : Tri-.pi.-methane rearrangement * molecular systems * reaction Subject RIV: CH - Nuclear ; Quantum Chemistry Impact factor: 3.280, year: 2001

Detection of PAX8/PPARG and RET/PTC Rearrangements Is Feasible in Routine Air-Dried Fine Needle Aspiration Smears

DEFF Research Database (Denmark)

Ferraz, Carolina; Rehfeld, Christian; Krogdahl, Annelise

2012-01-01

Background: The diagnostic limitations of fine needle aspiration (FNA), like the indeterminate category, can be partially overcome by molecular analysis. As PAX8/PPARG and RET/PTC rearrangements have been detected in follicular thyroid carcinomas (FTCs) and papillary thyroid carcinomas (PTCs......), their detection in FNA smears could improve the FNA diagnosis. To date, these rearrangements have never been analyzed in routine air-dried FNA smears, but only in frozen tissue, formalin-fixed paraffin-embedded (FFPE) tissue, and in fresh FNA material. Fixed routine air-dried FNA samples have hitherto been judged...... as generally not suitable for testing these rearrangements in a clinical setting. Therefore, the objective of the present study was to investigate the feasibility of extracting RNA from routine air-dried FNA smears for the detection of these rearrangements with real-time polymerase chain reaction (RT...

Acid- and base-catalysis in the mononuclear rearrangement of some (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole in toluene: effect of substituents on the course of reaction.

Science.gov (United States)

D'Anna, Francesca; Frenna, Vincenzo; Ghelfi, Franco; Marullo, Salvatore; Spinelli, Domenico

2011-04-15

The reaction rates for the rearrangement of eleven (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole 3a-k into the relevant (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas 4a-k in the presence of trichloroacetic acid or of piperidine have been determined in toluene at 313.1 K. The results have been related to the effect of the aryl substituent by using Hammett and/or Ingold-Yukawa-Tsuno correlations and have been compared with those previously collected in a protic polar solvent (dioxane/water) as well as with those on the analogous rearrangement of the corresponding (Z)-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole 1a-k in benzene. Some light can thus be shed on the general differences of chemical reactivity between protic polar (or dipolar aprotic) and apolar solvents.

T-cell acute lymphoblastic leukemia associated with complex karyotype and SET-NUP214 rearrangement: a case study and review of the literature.

Science.gov (United States)

Lee, Sang-Guk; Park, Tae Sung; Cho, Sun Young; Lim, Gayoung; Park, Gwang Jin; Oh, Seung Hwan; Cho, Eun Hae; Chong, So Young; Huh, Ji Young

2011-01-01

SET-NUP214 rearrangements have been rarely reported in T-cell acute lymphoblastic leukemia (T-ALL), acute undifferentiated leukemia, and acute myeloid leukemia, and most documented cases have been associated with normal karyotypes in conventional cytogenetic analyses. Here, we describe a novel case of T-ALL associated with a mediastinal mass and a SET-NUP214 rearrangement, which was masked by a complex karyotype at the time of initial diagnosis. Using multiplex reverse transcriptase-polymerase chain reaction analysis, we detected a cryptic SET-NUP214 rearrangement in our patient. As only 11 cases (including the present study) of T-ALL with SET-NUP214 rearrangement have been reported, the clinical features and treatment outcomes have not been fully determined. Further studies are necessary to evaluate the incidence of SET-NUP214 rearrangement in T-ALL patients and the treatment responses as well as prognosis of these patients.

Reactions of the ionized enol tautomer of acetanilide: elimination of HNCO via a novel rearrangement.

Science.gov (United States)

Heydorn, Lisa N; Carter, Lynn M; Bowen, Richard D; Terlouw, Johan K

2003-01-01

The reactions of ionised acetanilide, C(6)H(5)NH(=O)CH(3)(.+), and its enol, C(6)H(5)NH(OH)=CH(2)(.+), have been studied by a combination of tandem mass spectrometric and computational methods. These two isomeric radical cations have distinct chemistries at low internal energies. The keto tautomer eliminates exclusively CH(2)=C=O to give ionised aniline. In contrast, the enol tautomer loses H-N=C=O, via an unusual skeletal rearrangement, to form predominantly ionised methylene cyclohexadiene. Hydrogen atom loss also occurs from the enol tautomer, with the formation of protonated oxindole. The mechanisms for H-N=C=O and hydrogen atom loss both involve cyclisation; the former proceeds via a spiro transition state formed by attachment of the methylene group to the ipso position, whereas the latter entails the formation of a five-membered ring by attachment to the ortho position. The behaviour of labelled analogues reveals that these two processes have different site selectivities. Hydrogen atom loss involves a reverse critical energy and is subject to an isotope effect. Surprisingly, attempts to promote the enolisation of ionised acetanilide by proton-transport catalysis were unsuccessful. In a reversal of the usual situation for ionised carbonyl compounds, ionised acetanilide is actually more stable than its enol tautomer. The enol tautomer was resistant to proton-transport catalysed ketonisation to ionised acetanilide, possibly because the favoured geometry of the encounter complex with the base molecule is inappropriate for facilitating tautomerisation.

Circumambulatory rearrangements of cyclopolyenes containing element-centred migrants

International Nuclear Information System (INIS)

Minkin, Vladimir I; Mikhailov, Igor E; Dushenko, Galina A; Zschunke, Adolf

2003-01-01

Data on circumambulatory rearrangements caused by rapid migrations of substituents formed by Group 13-17 elements around three- to nine-membered cyclopolyenes are generalised and systematised. Depending on the ring size, the nature of the migrating group, substituents in the ring and the medium, the rate constants of circumambulatory rearrangements vary over a wide range from 10 6 to 10 -8 s -1 at room temperature. Particular attention is given to analysis of the mechanisms of these rearrangements ([1, j]-, [2,3]- and [3,3]-sigmatropic shifts, haptotropic rearrangements and ionisation-recombination) and to the correlation of these mechanisms with the structural characteristics of the compounds that undergo rearrangements.

Chemical reaction due to stronger Ramachandran interaction

Indian Academy of Sciences (India)

actions between two polarized atoms are responsible for initiating a chemical reaction, either before or after ... Chemical reaction; Ramachandran interaction; anisotropic and asymmetric polarization; ionization ..... man sequence exactly, including the generalized mech- ..... We now move on and rearrange Eq. (8) to arrive at.

The Chapman-type rearrangement in pseudosaccharins: The case of 3-(methoxy)-1,2-benzisothiazole 1,1-dioxide

Science.gov (United States)

Kaczor, A.; Proniewicz, L. M.; Almeida, R.; Gómez-Zavaglia, A.; Cristiano, M. L. S.; Matos Beja, A. M.; Ramos Silva, M.; Fausto, R.

2008-12-01

The thermal Chapman-type rearrangement of the pseudosaccharin 3-(methoxy)-1,2-benzisothiazole 1,1-dioxide (MBID) into 2-methyl-1,2-benzisothiazol-3(2 H)-one 1,1-dioxide (MBIOD) was investigated on the basis of computational models and knowledge of the structure of the reactant and product in the isolated and solid phases. X-ray diffraction was used to obtain the structure of the substrate in the crystalline phase, providing fundamental structural data for the development of the theoretical models used to investigate the reaction mechanism in the condensed phase. The intra- and different intermolecular mechanisms were compared on energetic grounds, based on the various developed theoretical models of the rearrangement reactions. The energetic preference ( ca. 3.2 kJ mol -1, B3LYP/6-31+G(d,p)) of inter- over intramolecular transfer of the methyl group is predicted for the " quasi-simultaneous" transfer of the methyl groups model, explaining the potential of MBID towards [1,3']-isomerization to MBIOD in the condensed phases. The predicted lower energy of MBIOD relative to MBID ( ca. 60 kJ mol -1), due to the lower steric hindrance in the MBIOD molecule, acts as a molecular motor for the observed thermal rearrangement.

A Wittig-olefination-Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis.

Science.gov (United States)

Kulkarni, Mukund G; Desai, Mayur P; Birhade, Deekshaputra R; Shaikh, Yunus B; Dhatrak, Ajit N; Gannimani, Ramesh

2012-01-01

Efficient syntheses are described for the synthetically important 3-methylquinoline-4-carbaldehydes 6a-h from o-nitrobenzaldehydes 1a-h employing a Wittig-olefination-Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a-h, which on heating under reflux in xylene underwent Claisen rearrangement to give 4-pentenals 3a-h. Protection of the aldehyde group of the 4-pentenals as acetals 4a-h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a-h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4-carbaldehydes 6a-h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure.

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

Directory of Open Access Journals (Sweden)

Mukund G. Kulkarni

2012-10-01

Full Text Available Efficient syntheses are described for the synthetically important 3-methylquinoline-4-carbaldehydes 6a–h from o-nitrobenzaldehydes 1a–h employing a Wittig-olefination–Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a–h, which on heating under reflux in xylene underwent Claisen rearrangement to give 4-pentenals 3a–h. Protection of the aldehyde group of the 4-pentenals as acetals 4a–h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a–h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4-carbaldehydes 6a–h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure.

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

Science.gov (United States)

Desai, Mayur P; Birhade, Deekshaputra R; Shaikh, Yunus B; Dhatrak, Ajit N; Gannimani, Ramesh

2012-01-01

Summary Efficient syntheses are described for the synthetically important 3-methylquinoline-4-carbaldehydes 6a–h from o-nitrobenzaldehydes 1a–h employing a Wittig-olefination–Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a–h, which on heating under reflux in xylene underwent Claisen rearrangement to give 4-pentenals 3a–h. Protection of the aldehyde group of the 4-pentenals as acetals 4a–h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a–h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4-carbaldehydes 6a–h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure. PMID:23209506

Mixed Lichenoid and Follicular T- and B-Cell Lymphoid Reaction to Red Tattoos With Monoclonal T Cells.

Science.gov (United States)

Zaaroura, Hiba; Bergman, Reuven

2017-09-28

Pseudolymphomatous reactions have been described to occur in tattoos. Most cases have exhibited T-cell predominance and polyclonal T-cell receptor gene rearrangements. One case with monoclonal IgH gene rearrangements progressed into B-cell lymphoma. Lichenoid infiltrates are commonly described but lymphoid follicles much less frequently. We report a case with mixed lichenoid and follicular T- and B-cell reaction to red tattoos. The histopathology and the immunohistochemical studies were constant with a mixed T- and B-cell pseudolymphoma, the IgH gene rearrangement study was polyclonal, but the T-cell receptor gene rearrangement study was monoclonal. The patient who responded to intralesional corticosteroid injections remains under close scrutiny.

Radical Smiles Rearrangement: An Update

Directory of Open Access Journals (Sweden)

Ingrid Allart-Simon

2016-07-01

Full Text Available Over the decades the Smiles rearrangement and its variants have become essential synthetic tools in modern synthetic organic chemistry. In this mini-review we summarized some very recent results of the radical version of these rearrangements. The selected examples illustrate the synthetic power of this approach, especially if it is incorporated into a domino process, for the preparation of polyfunctionalized complex molecules.

Catalytic Asymmetric Piancatelli Rearrangement: Brønsted Acid Catalyzed 4π Electrocyclization for the Synthesis of Multisubstituted Cyclopentenones

KAUST Repository

Cai, Yunfei; Tang, Yurong; Atodiresei, Iuliana; Rueping, Magnus

2016-01-01

The first catalytic asymmetric Piancatelli reaction is reported. Catalyzed by a chiral Brønsted acid, the rearrangement of a wide range of furylcarbinols with a series of aniline derivatives provides valuable aminocyclopentenones in high yields

Gas chromatography-mass spectrometric studies of O-alkyl O-2-(N,N-dialkylamino) ethyl alkylphosphonites(phosphonates) for chemical weapons convention verification.

Science.gov (United States)

Saeidian, Hamid; Babri, Mehran; Ramezani, Atefeh; Ashrafi, Davood; Sarabadani, Mansour; Naseri, Mohammad Taghi

2013-01-01

The electron ionization (EI) mass spectra of a series of O-alkyl O-2-(N,N-dialkylaminolethyl alkylphosphonites(phosphonates), which are precursors of nerve agents, were studied for Chemical Weapons Convention (CWC) verification. General El fragmentation pathways were constructed and discussed. Proposed fragment structures were confirmed through analyzing fragment ions of deuterated analogs and density functional theory (DFT) calculations. The observed fragment ions are due to different fragmentation pathways such as hydrogen and McLafferty+1 rearrangements, alkene, amine and alkoxy elimination by alpha- or beta-cleavage process. Fragment ions distinctly allow unequivocal identification of the interested compounds including those of isomeric compounds. The presence and abundance of fragment ions were found to depend on the size and structure of the alkyl group attached to nitrogen, phosphorus and oxygen atoms.

The von Auwers reaction - history and synthetic applications.

Science.gov (United States)

Dumeunier, Raphaël; Jaeckh, Simon

2014-01-01

Dienones obtained from the facile dearomatization of phenols, can be further transformed to semi-benzenes prone to rearomatize in clean, but sometimes unexpected, fashion. Over a hundred years ago, K. von Auwers found that adding Grignards on dienones would lead spontaneously to subsequent dehydration and a novel aromatizing rearrangement. This reaction was ignored for 50 years before Melvin Newman re-investigated these findings, studied the mechanism, and developed variations on the same theme. Since then, despite the tremendous potential of the reactions, those studies were only rarely mentioned, before finally falling into oblivion. This review aims to provide the reader with a detailed history and comprehensive bibliography of the von Auwers rearrangement, some of its synthetic applications, and new unpublished material in the hope to open new perspectives on this forgotten reaction.

Nitrosation of amides involves a pseudopericyclic 1,3-sigmatropic rearrangement.

Science.gov (United States)

Birney, David M

2004-03-04

Two possible pathways for the nitrosation of formamide and N-methyl formamide by nitrosonium ion (NO(+)) have been investigated at the B3LYP/6-31G(d,p) level. The key steps are pseudopericyclic 1,3-sigmatropic rearrangements to give the observed N-nitrosamides. The transition structures (8a and 8b) are close to planar on the amide moiety and have remarkably low barriers of only 6.6 and 4.8 kcal/mol from the lowest energy conformations of 6a and 6b, respectively. [reaction: see text

Genomic regulatory landscapes and chromosomal rearrangements

DEFF Research Database (Denmark)

Ladegaard, Elisabete L Engenheiro

2008-01-01

The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes is that they ......The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes...... the complex spatio-temporal expression of the associated trans-dev gene. Rare chromosomal breakpoints that disrupt the integrity of these regulatory landscapes may be used as a tool, not only to make genotype-phenotype associations, but also to link the associated phenotype with the position and tissue...... specificity of the individual CNEs. In this PhD study I have studied several chromosomal rearrangements with breakpoints in the vicinity of trans-dev genes. This included chromosomal rearrangements compatible with known phenotype-genotype associations (Rieger syndrome-PITX2, Mowat-Wilson syndrome-ZEB2...

The unified theory of nuclear reactions

International Nuclear Information System (INIS)

Tobocman, W.

A unified nuclear reaction theory is a formalism for the scattering reactions of many-body nuclear systems which is capable of describing both direct interaction and compound nucleus formation processes. The Feshbach projection operator formalism is the original unified nuclear reaction theory. An alternative unified nuclear reaction theory called the X-matrix formalism is described. The X-matrix formalism is a generalization of the Brown-de Dominicis formalism. It does not require projection operators and is readly applied to rearrangement collisions

Evaporation rates and surface profiles on heterogeneous surfaces with mass transfer and surface reaction

Energy Technology Data Exchange (ETDEWEB)

Flytzani-Stephanopoulos, M; Schmidt, L D

1979-01-01

Simple models incorporating surface reaction and diffusion of volatile products through a boundary layer are developed to calculate effective rates of evaporation and local surface profiles on surfaces having active and inactive regions. The coupling between surface heterogeneities with respect to a particular reaction and external mass transfer may provide a mechanism for the surface rearrangement and metal loss encountered in several catalytic systems of practical interest. Calculated transport rates for the volatilization of platinum in oxidizing environments and the rearrangement of this metal during the ammonia oxidation reaction agree well with published experimental data.

Synthesis of enyne and aryl vinyl sulfoxides: functionalization via Pummerer rearrangement.

Science.gov (United States)

Souza, Frederico B; Shamim, Anwar; Argomedo, Luiz M Z; Pimenta, Daniel C; Stefani, Hélio A

2015-11-01

An efficient methodology for the synthesis of aryl-substituted vinyl sulfoxides through direct substitution of aryl-substituted alkynyl grignard reagents on menthyl-p-toluenesulfinate followed by Suzuki-Miyaura cross-coupling reaction has been developed. It has also been described that the reaction of alkyl-substituted and cycloalkyl-substituted alkynyl grignard reagents with menthyl-p-toluenesulfinate led to two products, i.e., alkynyl sulfoxide derivatives, as a result of substitution, and enyne sulfoxide derivatives, which resulted from substitution followed by Michael type addition. It was possible to selectively synthesize the enyne sulfoxide derivatives by changing the concentration of the grignard reagent. These alkenyl sulfoxides were transformed into the corresponding [Formula: see text]-thio aldehydes in high yields via additive Pummerer rearrangement.

Novel Reagents for Multi-Component Reactions

Science.gov (United States)

Wang, Yanguang; Basso, Andrea; Nenajdenko, Valentine G.; Gulevich, Anton V.; Krasavin, Mikhail; Bushkova, Ekaterina; Parchinsky, Vladislav; Banfi, Luca; Basso, Andrea; Cerulli, Valentina; Guanti, Giuseppe; Riva, Renata; Rozentsveig, Igor B.; Rozentsveig, Gulnur N.; Popov, Aleksandr V.; Serykh, Valeriy J.; Levkovskaya, Galina G.; Cao, Song; Shen, Li; Liu, Nianjin; Wu, Jingjing; Li, Lina; Qian, Xuhong; Chen, Xiaopeng; Wang, Hongbo; Feng, Jinwu; Wang, Yanguang; Lu, Ping; Heravi, Majid M.; Sadjadi, Samaheh; Kazemizadeh, Ali Reza; Ramazani, Ali; Kudyakova, Yulia S.; Goryaeva, Marina V.; Burgart, Yanina V.; Saloutin, Victor I.; Mossetti, Riccardo; Pirali, Tracey; Tron, Gian Cesare; Rozhkova, Yulia S.; Mayorova, Olga A.; Shklyaev, Yuriy V.; Zhdanko, Alexander G.; Nenajdenko, Valentine G.; Stryapunina, Olga G.; Plekhanova, Irina V.; Glushkov, Vladimir A.; Shklyaev, Yurii V.

Ketenimines are a class of versatile and highly reactive intermediates that can participate in a variety of organic reactions, such as nucleophilic additions, radical additions, [2 + 2] and [2 + 4] cycloadditions, and sigmatropic rearrangements. In this presentation, we report on a series of multi-component reactions that involve a ketenimine intermediate. These reactions could furnish diverse heterocyclic compounds, including functionalized iminocoumarin, iminodihydroqunolines, iminothiochromens, pyrrolines, isoquinolines, pyridines, β-lactams, imino-1,2-dihydrocoumarins, and benzimidazoles.

Chromosomal rearrangements in Tourette syndrome

DEFF Research Database (Denmark)

Bertelsen, Birgitte; Debes, Nanette Mol; Hjermind, Lena E

2013-01-01

, and identification of susceptibility genes through linkage and association studies has been complicated due to inherent difficulties such as no clear mode of inheritance, genetic heterogeneity, and apparently incomplete penetrance. Positional cloning through mapping of disease-related chromosome rearrangements has...... been an efficient tool for the cloning of disease genes in several Mendelian disorders and in a number of complex disorders. Through cytogenetic investigation of 205 TS patients, we identified three possibly disease-associated chromosome rearrangements rendering this approach relevant in chasing TS...

Synthesis of rearranged unsaturated drimane derivatives

Directory of Open Access Journals (Sweden)

Miranda Domingos S. de

2001-01-01

Full Text Available A full account to the preparation and application of three appropriately substituted vinylcyclohexenes (2,2-dimethyl-3-vinylcyclohex-3-en-1-ol, 2,2-dimethyl-3-vinylcyclohex-3-en-1-one and 3,3-dimethyl-2-vinylcyclohexene in thermal Diels-Alder reactions with alpha,beta-unsaturated esters (methyl tiglate and methyl angelate is given. This approach delivered the racemic synthesis of ten octalin derivatives bearing a rearranged drimane skeleton (4 diastereomers of 1-methoxycarbonyl-6-hydroxy-1,2,5,5-tetramethyl-1,2,3,5,6,7, 8,8a-octahydronaphthalene; 1-methoxycarbonyl-6-oxo-1,2,5,5-tetramethyl-1,2,3,4,5,6,7,8-octahydronaphthalene; 2-methoxycarbonyl-6-oxo-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene; 3 diastereomers of 1-methoxycarbonyl-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene and 2-methoxycarbonyl-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene . Central synthetic features included preparation of enoltriflates by Stang's protocol and the successful palladium-catalyzed cross-coupling reaction (Stille reaction of the triflate with the tri-n-butylvinylstannane. The octalins relative stereochemistry was unequivocally ascertained by spectroscopic methods and/or X-ray crystallography and these data now stand as useful tools to support the correct assignment of related natural products usually isolated in minute amounts.

Detection of clonal B cells in microdissected reactive lymphoproliferations: possible diagnostic pitfalls in PCR analysis of immunoglobulin heavy chain gene rearrangement

DEFF Research Database (Denmark)

Zhou, X.G.; Sandvej, K.; Gregersen, Niels

1999-01-01

Aims-To evaluate the specificity of standard and fluorescence based (GENESCAN) polymerase chain reaction (PCR) immunoglobulin heavy chain (IgH) gene rearrangement analysis in complete and microdissected paraffin wax embedded sections from lymphoid proliferations. Methods-PCR IgH gene rearrangement...... because of preferential priming or detection of local B cell clones. Data from clonal analysis of small, microdissected or lymphocyte poor samples must be evaluated critically. It is recommended that analyses should be run in parallel on at least two tissue specimens. Only reproducible bands present...

Sorting permutations by prefix and suffix rearrangements.

Science.gov (United States)

Lintzmayer, Carla Negri; Fertin, Guillaume; Dias, Zanoni

2017-02-01

Some interesting combinatorial problems have been motivated by genome rearrangements, which are mutations that affect large portions of a genome. When we represent genomes as permutations, the goal is to transform a given permutation into the identity permutation with the minimum number of rearrangements. When they affect segments from the beginning (respectively end) of the permutation, they are called prefix (respectively suffix) rearrangements. This paper presents results for rearrangement problems that involve prefix and suffix versions of reversals and transpositions considering unsigned and signed permutations. We give 2-approximation and ([Formula: see text])-approximation algorithms for these problems, where [Formula: see text] is a constant divided by the number of breakpoints (pairs of consecutive elements that should not be consecutive in the identity permutation) in the input permutation. We also give bounds for the diameters concerning these problems and provide ways of improving the practical results of our algorithms.

Quantum control of the photoinduced Wolff rearrangement of diazonaphthoquinone in the condensed phase

Energy Technology Data Exchange (ETDEWEB)

Wolpert, Daniel; Gerber, Gustav; Brixner, Tobias [Physikalisches Institut, Universitaet Wuerzburg, Am Hubland, 97074 Wuerzburg (Germany); Schade, Marco; Langhojer, Florian [Institut fuer Physikalische Chemie, Universitaet Wuerzburg, Am Hubland, 97074 Wuerzburg (Germany)], E-mail: brixner@phys-chemie.uni-wuerzburg.de

2008-04-14

A shaped UV pump-MIR probe setup is employed for quantum control of the photoinduced Wolff rearrangement reaction of diazonaphthoquinone (DNQ) dissolved in methanol, yielding a ketene photoproduct. Time-resolved vibrational spectroscopy is a well-suited tool to monitor a photoreaction in the liquid phase as the narrow vibrational lines allow the observation of structural changes. Especially in the mid-infrared region, marker modes originating from different photoproducts can be identified unambiguously providing suitable feedback signals for open-loop or closed-loop control schemes. We report an experiment where the initiation of a complicated structural change of a molecule, involving bond cleavage and rearrangement, in the liquid phase can be controlled and mechanistic insight is obtained. Single-parameter scans show that the molecule is sensitive to intrapulse dumping during the excitation. Adaptive optimizations lead to pulse structures which can be understood consistently with this dumping mechanism.

System for the detection of chromosomal rearrangements using Sordaria macrospora

Energy Technology Data Exchange (ETDEWEB)

Arnaise, S.; Leblon, G.; Lares, L. (Paris-11 Univ., 91 - Orsay (France). Lab. de Biologie Cellulaire et Genetique)

1984-01-01

A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine.

Radical S-adenosylmethionine (SAM) enzymes in cofactor biosynthesis: a treasure trove of complex organic radical rearrangement reactions.

Science.gov (United States)

Mehta, Angad P; Abdelwahed, Sameh H; Mahanta, Nilkamal; Fedoseyenko, Dmytro; Philmus, Benjamin; Cooper, Lisa E; Liu, Yiquan; Jhulki, Isita; Ealick, Steven E; Begley, Tadhg P

2015-02-13

In this minireview, we describe the radical S-adenosylmethionine enzymes involved in the biosynthesis of thiamin, menaquinone, molybdopterin, coenzyme F420, and heme. Our focus is on the remarkably complex organic rearrangements involved, many of which have no precedent in organic or biological chemistry. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Investigation of organometallic reaction mechanisms with one and two dimensional vibrational spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Cahoon, James Francis [Univ. of California, Berkeley, CA (United States)

2008-12-01

One and two dimensional time-resolved vibrational spectroscopy has been used to investigate the elementary reactions of several prototypical organometallic complexes in room temperature solution. The electron transfer and ligand substitution reactions of photogenerated 17-electron organometallic radicals CpW(CO)₃ and CpFe(CO)₂ have been examined with one dimensional spectroscopy on the picosecond through microsecond time-scales, revealing the importance of caging effects and odd-electron intermediates in these reactions. Similarly, an investigation of the photophysics of the simple Fischer carbene complex Cr(CO)₅[CMe(OMe)] showed that this class of molecule undergoes an unusual molecular rearrangement on the picosecond time-scale, briefly forming a metal-ketene complex. Although time-resolved spectroscopy has long been used for these types of photoinitiated reactions, the advent of two dimensional vibrational spectroscopy (2D-IR) opens the possibility to examine the ultrafast dynamics of molecules under thermal equilibrium conditions. Using this method, the picosecond fluxional rearrangements of the model metal carbonyl Fe(CO)₅ have been examined, revealing the mechanism, time-scale, and transition state of the fluxional reaction. The success of this experiment demonstrates that 2D-IR is a powerful technique to examine the thermally-driven, ultrafast rearrangements of organometallic molecules in solution.

Polymethylated [Fe(η6-arene)2]2+ dications: methyl-group rearrangements and application of the EINS mechanism.

Science.gov (United States)

Štíbr, Bohumil; Bakardjiev, Mario; Hájková, Zuzana; Holub, Josef; Padělková, Zdenka; Růžička, Aleš; Kennedy, John D

2011-06-14

Reactions between the methylated arenes ArMe(n) [where ArMe(n) = C(6)Me(n)H((6-n)), and n = 1-6] and FeCl(2) in heptane at 90 °C in the presence of anhydrous AlCl(3) give, for the arenes with n = 1-5, extensive isomerisations and disproportionations involving the methyl groups on the arene rings, and the formation of mixtures of [Fe(ArMe(n))(2)](2+) dications that defy separation into pure species. GC-MS studies of AlCl(3)/mesitylene and AlCl(3)/durene reactions in the absence of FeCl(2) (90 °C, 2 h) allow quantitative assessments of the rearrangements, and the EINS mechanism (electrophile-induced nucleophilic substitution) is applied to rationalise the phenomena. By contrast, ArMe(n) / FeCl(2) /AlCl(3) reactions in heptane for 24-36 h at room-temperature proceed with no rearrangements, allowing the synthesis of the complete series of pure [Fe(ArMen)](2+) cations in yields of 48-71%. The pure compounds are characterised by (1)H NMR spectroscopy and electrospray-ionization mass-spectrometry (ESI-MS), and the structures of [Fe(m-xylene)(2)][PF(6)](2) and [Fe(durene)(2)][PF(6)](2) are established by single-crystal X-ray diffraction analyses.

A mechanistic investigation on the formation and rearrangement of silaspiropentane: A theoretical study.

Science.gov (United States)

Yildiz, Cem Burak; Azizoglu, Akin

2016-07-01

The formation of silaspiropentane from addition of singlet silacyclopropylidene 1 and silacyclopropylidenoid 8 to ethylene has been investigated separately at the B3LYP, X3LYP, WB97XD, and M05-2X theories using the 6-31+G(d,p) basis set. The silacycloproylidenoid addition follows a stepwise route. In contrast, a concerted mechanism occurs for silacyclopropylidene addition. Moreover, the intramolecular rearrangements of silaspiropentane 9 to methylenesilacyclobutane 11 and 2-silaallene + ethylene 12 have been studied extensively. The required energy barrier for the isomerization of 9 to 10 was determined to be 44.0 kcal mol(-1) at the B3LYP/6-31+G(d,p) level. After formation of 10, the rearrangement to methylenesilacyclobutane 12 is highly exergonic by -15.9 kcal mol(-1), which makes this reaction promising. However, the conversion of 9 to 11 is calculated to be quite endergonic, by 26.5 kcal mol(-1).

Mechanism of chimera formation during the Multiple Displacement Amplification reaction

Directory of Open Access Journals (Sweden)

Stockwell Timothy B

2007-04-01

Full Text Available Abstract Background Multiple Displacement Amplification (MDA is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Results Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2–21 nucleotides (nts in the new templates. Conclusion Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.

Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer

Science.gov (United States)

2016-05-01

COVERED 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer 5b. GRANT NUMBER W81XWH...that result from gene rearrangements given their high frequency relative to somatic point mutations. Gene rearrangements can yield novel chimeric

SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis

Science.gov (United States)

Ohashi, Masao; Liu, Fang; Hai, Yang; Chen, Mengbin; Tang, Man-Cheng; Yang, Zhongyue; Sato, Michio; Watanabe, Kenji; Houk, K. N.; Tang, Yi

2017-09-01

Pericyclic reactions—which proceed in a concerted fashion through a cyclic transition state—are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-L-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme ‘toolboxes’. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.

Exploiting the CNC side chain in heterocyclic rearrangements: synthesis of 4(5)-acylamino-imidazoles.

Science.gov (United States)

Piccionello, Antonio Palumbo; Buscemi, Silvestre; Vivona, Nicolò; Pace, Andrea

2010-08-06

A new variation on the Boulton-Katritzky reaction is reported, namely, involving use of a CNC side chain. A novel Montmorillonite-K10 catalyzed nonreductive transamination of a 3-benzoyl-1,2,4-oxadiazole afforded a 3-(alpha-aminobenzyl)-1,2,4-oxadiazole, which was condensed with benzaldehydes to afford the corresponding imines. In the presence of strong base, these imines underwent Boulton-Katritzky-type rearrangement to afford novel 4(5)-acylaminoimidazoles.

UV-rearranged PIM-1 polymeric membranes for advanced hydrogen purification and production

Energy Technology Data Exchange (ETDEWEB)

Li, Fu Yun; Ong, Yee Kang; Chung, Tai-Shung [Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore (Singapore); Xiao, Youchang [Suzhou Faith and Hope Membrane Technology Co. Ltd., Jiangsu Province (China)

2012-12-15

Polymers of intrinsic microporosity (PIM-1) have been known for their super high permeability but average selectivity for medium-size gas pairs. They have unimpressive selectivity for H{sub 2} and CO{sub 2} separation (i.e., {alpha} (H{sub 2}/CO{sub 2}) = 0.6). For the first time, we have discovered that ultraviolet (UV)-rearranged polymers of PIM-1 membranes can be used for H{sub 2}/CO{sub 2} separation with far superior separation performance to others in literatures. The PIM-1 membrane after UV radiation for 4 hours shows H{sub 2} permeability of 452 barrer with H{sub 2}/CO{sub 2} selectivity of 7.3. Experimental data and molecular simulation reveal that the polymer chains of PIM-1 undergo 1,2-migration reaction and transform to close-to-planar like rearranged structure after UV radiation. As a result, the UV-irradiated PIM-1 membrane shows considerable drops in both fractional free volume (FFV) and size of micro-pores. Positron annihilation lifetime (PAL) results have confirmed the chemical and structural changes, suggesting the FFV and pore size drops are mainly ascribed to the destructed spiro-carbon centre during UV radiation. Sorption and x-ray diffractor (XRD) analyses indicate that the impressive H{sub 2}/CO{sub 2} selectivity arises from the significantly enhanced diffusivity selectivity induced by UV radiation, followed by molecular rearrangement, conformation change and chain packing. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Structure and Reactivity of the Glutathione Radical Cation: Radical Rearrangement from the Cysteine Sulfur to the Glutamic Acid alpha-Carbon Atom

NARCIS (Netherlands)

Osburn, S.; Berden, G.; Oomens, J.; Gulyuz, K.; Polfer, N.C.; O'Hair, R.A.J.; Ryzhov, V.

2013-01-01

A gas-phase radical rearrangement through intramolecular hydrogen-atom transfer (HAT) was studied in the glutathione radical cation, [-ECG](+.), which was generated by a homolytic cleavage of the protonated S-nitrosoglutathione. Ion-molecule reactions suggested that the radical migrates from the

Genome organization influences partner selection for chromosomal rearrangements

NARCIS (Netherlands)

Wijchers, P.J.; de Laat, W.

2010-01-01

Chromosomal rearrangements occur as a consequence of the erroneous repair of DNA double-stranded breaks, and often underlie disease. The recurrent detection of specific tumorigenic rearrangements suggests that there is a mechanism behind chromosomal partner selection involving the shape of the

Progress in microscopic direct reaction modeling of nucleon induced reactions

Energy Technology Data Exchange (ETDEWEB)

Dupuis, M.; Bauge, E.; Hilaire, S.; Lechaftois, F.; Peru, S.; Pillet, N.; Robin, C. [CEA, DAM, DIF, Arpajon (France)

2015-12-15

A microscopic nuclear reaction model is applied to neutron elastic and direct inelastic scatterings, and pre-equilibrium reaction. The JLM folding model is used with nuclear structure information calculated within the quasi-particle random phase approximation implemented with the Gogny D1S interaction. The folding model for direct inelastic scattering is extended to include rearrangement corrections stemming from both isoscalar and isovector density variations occurring during a transition. The quality of the predicted (n,n), (n,n{sup '}), (n,xn) and (n,n{sup '}γ) cross sections, as well as the generality of the present microscopic approach, shows that it is a powerful tool that can help improving nuclear reactions data quality. Short- and long-term perspectives are drawn to extend the present approach to more systems, to include missing reactions mechanisms, and to consistently treat both structure and reaction problems. (orig.)

Rearrangement moves on rooted phylogenetic networks.

Science.gov (United States)

Gambette, Philippe; van Iersel, Leo; Jones, Mark; Lafond, Manuel; Pardi, Fabio; Scornavacca, Celine

2017-08-01

Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide a solid basis for

Rearrangement moves on rooted phylogenetic networks.

Directory of Open Access Journals (Sweden)

Philippe Gambette

2017-08-01

Full Text Available Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide

A system for the detection of chromosomal rearrangements using Sordaria macrospora

International Nuclear Information System (INIS)

Arnaise, S.; Leblon, G.; Lares, L.

1984-01-01

A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine. (orig.)

A system for the detection of chromosomal rearrangements using Sordaria macrospora.

Science.gov (United States)

Arnaise, S; Leblon, G; Lares, L

1984-01-01

A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine.

Detection of an ylide intermediate in the electrochemically-induced Stevens rearrangement of an ammonium salt by in situ UV–vis spectroelectrochemistry

International Nuclear Information System (INIS)

Capobianco, Amedeo; Caruso, Tonino; Palombi, Laura; Peluso, Andrea

2013-01-01

Highlights: ► Mechanistic insights of the electro-induced Stevens rearrangement are provided. ► The reduction of PhCOCH 2 N + (CH 3 ) 2 CH 2 Ph is ascribed to a one-electron transfer process. ► An electrogenerated ammonium ylide has been detected by UV-spectroelectrochemistry. -- Abstract: The electrochemically-induced Stevens rearrangement of 2-(benzyldimethyl)ammonium acetophenone has been investigated by in situ UV–vis spectroelectrochemistry. Voltammetric analysis and absorption spectra recorded during the potentiostatic reduction indicate that the reaction proceeds via a one-electron transfer with a Platinum cathode and generation of an ammonium ylide intermediate

Ethynamine - Ketenimine - Acetonitrile - Rearrangements: A computational Study of Flash Vacuum Pyrolysis Processes

OpenAIRE

Wentrup, Curt; Begue, Didier; Leung-Toung, Regis

2017-01-01

The rearrangements of ethynamine 3 (H-CºC-NH2) to ketenimine 4 (CH2=C=NH) and acetonitrile 5 (CH3CN) were investigated computationally up to the MP4(SDTQ)/6-31G*//MP2(FU)/6-31G* level. The calculated barrier for a concerted reaction 3 -> 4 is very high, 74 kcal/mol, the structure of the transition state very unusual, and this path is discredited. A lower barrier of about 60 kcal/mol via aminovinylidene 2 and imidoylcarbene 15 has been found. The calculated barrier for ...

Frequency of p190 and p210 BCR-ABL rearrangements and survival in Brazilian adult patients with acute lymphoblastic leukemia

Directory of Open Access Journals (Sweden)

Ilana de França Azevedo

2014-10-01

Full Text Available Objective: This study investigated the occurrence of the p190 and p210 break point clusterregion-Abelson (BCR-ABL rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival. Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR using specific primers was employed to identify molecular rearrangements. Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%. The most common immunophenotype was B lineage (76%. BCR-ABL rearrangements was detected in 14 (34% patients with the following distribution: p190 (28%, p210 (50% and double positive (22%. Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44% and positive BCR-ABL (28%. Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia.

Scope and Mechanism of a True Organocatalytic Beckmann Rearrangement with a Boronic Acid/Perfluoropinacol System under Ambient Conditions.

Science.gov (United States)

Mo, Xiaobin; Morgan, Timothy D R; Ang, Hwee Ting; Hall, Dennis G

2018-04-18

Catalytic activation of hydroxyl functionalities is of great interest for the production of pharmaceuticals and commodity chemicals. Here, 2-alkoxycarbonyl- and 2-phenoxycarbonyl-phenylboronic acid were identified as efficient catalysts for the direct and chemoselective activation of oxime N-OH bonds in the Beckmann rearrangement. This classical organic reaction provides a unique approach to prepare functionalized amide products that may be difficult to access using traditional amide coupling between carboxylic acids and amines. Using only 5 mol % of boronic acid catalyst and perfluoropinacol as an additive in a polar solvent mixture, the operationally simple protocol features mild conditions, a broad substrate scope, and a high functional group tolerance. A wide variety of diaryl, aryl-alkyl, heteroaryl-alkyl, and dialkyl oximes react under ambient conditions to afford high yields of amide products. Free alcohols, amides, carboxyesters, and many other functionalities are compatible with the reaction conditions. Investigations of the catalytic cycle revealed a novel boron-induced oxime transesterification providing an acyl oxime intermediate involved in a fully catalytic nonself-propagating Beckmann rearrangement mechanism. The acyl oxime intermediate was prepared independently and was subjected to the reaction conditions. It was found to be self-sufficient; it reacts rapidly, unimolecularly without the need for free oxime. A series of control experiments and 18 O labeling studies support a true catalytic pathway involving an ionic transition structure with an active and essential role for the boronyl moiety in both steps of transesterification and rearrangement. According to 11 B NMR spectroscopic studies, the additive perfluoropinacol provides a transient, electrophilic boronic ester that is thought to serve as an internal Lewis acid to activate the ortho-carboxyester and accelerate the initial, rate-limiting step of transesterification between the precatalyst

Combining the [2,3] Sigmatropic Rearrangement and Ring-Closing Metathesis Strategies for the Synthesis of Spirocyclic Alkaloids. A Short and Efficient Route to (+/-)-Perhydrohistrionicotoxin

DEFF Research Database (Denmark)

Tanner, David Ackland; Hagberg, Lars; Poulsen, Anders

1999-01-01

This paper describes the use of selenium-based [2,3] sigmatropic rearrangement in combination with ruthenium-catalyzed ring-closing metathesis (RCM) for the synthesis of azaspiro ring systems, as exemplified by the reactions of model substrates 5 and 6. The methodology has been applied to a short...... is potentially enantioselective, and key steps were the [2,3] sigmatropic rearrangement of 11 to 12 via the corresponding allylic selenide (86% yield) and ruthenium-catalyzed RCM of 13 to 14 (80%). (C) 1999 Elsevier Science Ltd. All rights reserved....

Quantum concept of the rearrangement of a crystal lattice

International Nuclear Information System (INIS)

Gureev, M.D.; Mednikov, S.I.

1995-01-01

Using quantum considerations based on the concept of lattice rearrangement waves, we carried out an analysis of processes of rearrangement of a crystal lattice occurring on a moving front (interface) of crystal rearrangement. For the introduction and quantization of these waves we use the method of acoustomechanical analogy and the Sommerfeld quantum conditions. We calculate the energies and the propagation velocities of the lattice rearrangement waves. Along with quanta having a certain momentum, quanta that have a certain angular momentum are introduced into consideration. On the basis of the concepts developed, we suggest a new expression for calculating the probability of thermofluctuational processes in a crystal. We perform a numerical analysis of the rate of growth of the γ-phase in iron in the process of α-γ-conversion. Satisfactory agreement with experiment is obtained. We discuss the limitations and prospects of further development of the concept suggested. For direct experimental verification of the concept we propose to investigate the diffraction of electrons and other particles on the lattice rearrangement waves, i.e., in the process of phase conversions or disintegration of crystals

Árni Magnússon's rearrangement of paper manuscripts

DEFF Research Database (Denmark)

Stegmann, Beeke

Árni Magnússon’s rearrangement of paper manuscripts draws attention to the early history of Árni Magnússon’s (1663-1730) manuscript collection. The thesis examines Árni’s extensive rearrangement of paper manuscripts, showing that he repeatedly altered the physical composition of codices in his...

Efficient Nazarov cyclization/Wagner-Meerwein rearrangement terminated by a Cu(II)-promoted oxidation: synthesis of 4-alkylidene cyclopentenones.

Science.gov (United States)

Lebœuf, David; Theiste, Eric; Gandon, Vincent; Daifuku, Stephanie L; Neidig, Michael L; Frontier, Alison J

2013-04-08

The discovery and elucidation of a new Nazarov cyclization/Wagner-Meerwein rearrangement/oxidation sequence is described that constitutes an efficient strategy for the synthesis of 4-alkylidene cyclopentenones. DFT computations and EPR experiments were conducted to gain further mechanistic insight into the reaction pathways. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of Methylenebicyclo[3.2.1]octanol by a Sm(II)-Induced 1,2-Rearrangement Reaction with Ring Expansion of Methylenebicyclo[4.2.0]octanone.

Science.gov (United States)

Takatori, Kazuhiko; Ota, Shoya; Tendo, Kenta; Matsunaga, Kazuma; Nagasawa, Kokoro; Watanabe, Shinya; Kishida, Atsushi; Kogen, Hiroshi; Nagaoka, Hiroto

2017-07-21

Direct conversion of methylenebicyclo[4.2.0]octanone to methylenebicyclo[3.2.1]octanol by a Sm(II)-induced 1,2-rearrangement with ring expansion of the methylenecyclobutane is described. Three conditions were optimized to allow the adaptation of this approach to various substrates. A rearrangement mechanism is proposed involving the generation of a ketyl radical and cyclopentanation by ketyl-olefin cyclization, followed by radical fragmentation and subsequent protonation.

Explore the reaction mechanism of the Maillard reaction: a density functional theory study.

Science.gov (United States)

Ren, Ge-Rui; Zhao, Li-Jiang; Sun, Qiang; Xie, Hu-Jun; Lei, Qun-Fang; Fang, Wen-Jun

2015-05-01

The mechanism of Maillard reaction has been investigated by means of density functional theory calculations in the gaseous phase and aqueous solution. The Maillard reaction is a cascade of consecutive and parallel reaction. In the present model system study, glucose and glycine were taken as the initial reactants. On the basis of previous experimental results, the mechanisms of Maillard reaction have been proposed, and the possibility for the formation of different compounds have been evaluated through calculating the relative energy changes for different steps of reaction under different pH conditions. Our calculations reveal that the TS3 in Amadori rearrangement reaction is the rate-determining step of Maillard reaction with the activation barriers of about 66.7 and 68.8 kcal mol(-1) in the gaseous phase and aqueous solution, respectively. The calculation results are in good agreement with previous studies and could provide insights into the reaction mechanism of Maillard reaction, since experimental evaluation of the role of intermediates in the Maillard reaction is quite complicated.

Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

Science.gov (United States)

Bekker-Méndez, Vilma Carolina; Miranda-Peralta, Enrique; Núñez-Enríquez, Juan Carlos; Olarte-Carrillo, Irma; Guerra-Castillo, Francisco Xavier; Pompa-Mera, Ericka Nelly; Ocaña-Mondragón, Alicia; Bernáldez-Ríos, Roberto; Medina-Sanson, Aurora; Jiménez-Hernández, Elva; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; de Diego Flores-Chapa, José; Fajardo-Gutiérrez, Arturo; Flores-Lujano, Janet; Rodríguez-Zepeda, María del Carmen; Dorantes-Acosta, Elisa María; Bolea-Murga, Victoria; Núñez-Villegas, Nancy; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, Cesar; Mejía-Aranguré, Juan Manuel

2014-01-01

Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children. PMID:25692130

Synthesis of cationic dibenzosemibullvalene-based phase-transfer catalysts by di-π-methane rearrangements of pyrrolinium-annelated dibenzobarrelene derivatives

Directory of Open Access Journals (Sweden)

Jia Luo

2011-01-01

Full Text Available Dibenzobarrelene derivatives, that are annelated with a pyrrolinium unit [N,N-dialkyl-3,4-(9',10'-dihydro-9',10'-anthraceno-3-pyrrolinium derivatives], undergo a photo-induced di-π-methane rearrangement upon triplet sensitization to give the corresponding cationic dibenzosemibullvalene derivatives [N,N-dialkyl-3,4-{8c,8e-(4b,8b-dihydrodibenzo[a,f]cyclopropa[cd]pentaleno}pyrrolidinium derivatives]. Whereas the covalent attachment of a benzophenone functionality to the pyrrolinium nitrogen atom did not result in an internal triplet sensitization, the introduction of a benzophenone unit as part of the counter ion enables the di-π-methane rearrangement of the dibenzobarrelene derivative in the solid-state. Preliminary experiments indicate that a cationic pyrrolidinium-annelated dibenzosemibullvalene may act as phase-transfer catalyst in alkylation reactions.

Computational Prediction of Excited-State Carbon Tunneling in the Two Steps of Triplet Zimmerman Di-π-Methane Rearrangement.

Science.gov (United States)

Li, Xin; Liao, Tao; Chung, Lung Wa

2017-11-22

The photoinduced Zimmerman di-π-methane (DPM) rearrangement of polycyclic molecules to form synthetically useful cyclopropane derivatives was found experimentally to proceed in a triplet excited state. We have applied state-of-the-art quantum mechanical methods, including M06-2X, DLPNO-CCSD(T) and variational transition-state theory with multidimensional tunneling corrections, to an investigation of the reaction rates of the two steps in the triplet DPM rearrangement of dibenzobarrelene, benzobarrelene and barrelene. This study predicts a high probability of carbon tunneling in regions around the two consecutive transition states at 200-300 K, and an enhancement in the rates by 104-276/35-67% with carbon tunneling at 200/300 K. The Arrhenius plots of the rate constants were found to be curved at low temperatures. Moreover, the computed 12 C/ 13 C kinetic isotope effects were affected significantly by carbon tunneling and temperature. Our predictions of electronically excited-state carbon tunneling and two consecutive carbon tunneling are unprecedented. Heavy-atom tunneling in some photoinduced reactions with reactive intermediates and narrow barriers can be potentially observed at relatively low temperature in experiments.

Genome rearrangements and phylogeny reconstruction in Yersinia pestis.

Science.gov (United States)

Bochkareva, Olga O; Dranenko, Natalia O; Ocheredko, Elena S; Kanevsky, German M; Lozinsky, Yaroslav N; Khalaycheva, Vera A; Artamonova, Irena I; Gelfand, Mikhail S

2018-01-01

Genome rearrangements have played an important role in the evolution of Yersinia pestis from its progenitor Yersinia pseudotuberculosis . Traditional phylogenetic trees for Y. pestis based on sequence comparison have short internal branches and low bootstrap supports as only a small number of nucleotide substitutions have occurred. On the other hand, even a small number of genome rearrangements may resolve topological ambiguities in a phylogenetic tree. We reconstructed phylogenetic trees based on genome rearrangements using several popular approaches such as Maximum likelihood for Gene Order and the Bayesian model of genome rearrangements by inversions. We also reconciled phylogenetic trees for each of the three CRISPR loci to obtain an integrated scenario of the CRISPR cassette evolution. Analysis of contradictions between the obtained evolutionary trees yielded numerous parallel inversions and gain/loss events. Our data indicate that an integrated analysis of sequence-based and inversion-based trees enhances the resolution of phylogenetic reconstruction. In contrast, reconstructions of strain relationships based on solely CRISPR loci may not be reliable, as the history is obscured by large deletions, obliterating the order of spacer gains. Similarly, numerous parallel gene losses preclude reconstruction of phylogeny based on gene content.

Molecular screening of pituitary adenomas for gene mutations and rearrangements

Energy Technology Data Exchange (ETDEWEB)

Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

1993-07-01

Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.

Sintering with a chemical reaction as applied to uranium monocarbide; Frittage-reaction dans le cas du monocarbure d'uranium

Energy Technology Data Exchange (ETDEWEB)

Accary, A; Caillat, R [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1960-07-01

The present paper provides a survey of different investigations whose aim was the preparation and fabrication of uranium monocarbide for nuclear use. If a chemical reaction takes place in the sample during the sintering operation, it may be expected that the atom rearrangements involved in this reaction should favour the sintering process and thereby lower the temperature needed to yield a body of a given density. With this hypothesis in mind, the following methods have been studied: - Sintering of U-C mixtures; - Sintering of UO{sub 2}-C mixtures; - Hot pressing of U-C mixtures; - Extrusion of U-C mixtures. To generalize our result, it could be said that a chemical reaction does not lead to high densification, if one depends on a simple contact between discrete particles. On the contrary, a chemical reaction can help sintering if, as our hot pressing experiments shows, the densification can be achieved prior to the reaction. (author) [French] Le present article resume les etudes faites pour le compte du Commissariat a l'Energie Atomique dans le but de preparer du monocarbure d'uranium pour usage nucleaire. Si, en meme temps que l'on fritte une poudre, celle-ci est le siege d'une reaction chimique, on peut s'attendre a ce que le rearrangement atomique d'une reaction chimique favorise le frittage et, ainsi abaisse la temperature de travail necessaire pour obtenir une densite donnee. Nous avons etudie les methodes suivantes: - frittage des melanges U-C; - frittage des melanges UO{sub 2}-C; - frittage sous charge des melanges U-C; - filage des melanges U-C. Nos resultats montrent qu'une reaction chimique en cours de frittage ne conduit pas a un produit de haute densite si on opere sur un melange de poudres. Par contre, elle permet d'atteindre de hautes densites si la densification peut etre obtenue avant la reaction chimique. (auteur)

Cascade synthesis of dihydrobenzofuran via Claisen rearrangement of allyl aryl ethers using FeCl3/MCM-41 catalyst

Directory of Open Access Journals (Sweden)

Sachin S. Sakate

2018-05-01

Full Text Available Dihydrobenzofuran as one of the active ingredients of the naturally occurring motif is synthesized by using in situ generation of ortho allyl phenols. Aryl allyl ethers on reacting with catalytic amounts of non noble metal iron (III chloride supported on MCM-41 under moderate reaction conditions yield dihydrobenzofuran. First step via Claisen rearrangement gives ortho allyl phenol followed by its in situ cyclization to yield dihydrobenzofuran in very good yields. Both Lewis as well as Brønsted acidity of the catalyst as evidenced by Py-FTIR studies was found to catalyze the cascade synthesis of dihydrobenzofuran. The scope of the present strategy was successfully demonstrated for several substrates with varying electronic effects for the synthesis of corresponding dihydrobenzofuran with high yields in a range of 71–86%. Keywords: Claisen rearrangement, Dihydrobenzofuran, Aryl allyl ether, MCM-41, Ferric chloride

In situ generation of nitrilium from nitrile ylide and the subsequent Mumm rearrangement: copper-catalyzed synthesis of unsymmetrical diacylglycine esters.

Science.gov (United States)

Chen, Jijun; Shao, Ying; Ma, Liang; Ma, Meihua; Wan, Xiaobing

2016-12-07

A novel in situ generation of nitrilium from a nitrile ylide and the subsequent Mumm rearrangement of carboxylic acid, nitrile, and diazo compounds gave various unsymmetrical diacylglycine esters in moderate to high yields. This copper-catalyzed cascade reaction enables one-pot generation of two C-N bonds, one C[double bond, length as m-dash]O bond, and one C-H bond, with nitrogen as the only byproduct. The reaction has a broad functional-group tolerance, is rapid, easily scales up to the 100 mmol scale, and is insensitive to air and moisture.

Dynamics of genome rearrangement in bacterial populations.

Directory of Open Access Journals (Sweden)

Aaron E Darling

2008-07-01

Full Text Available Genome structure variation has profound impacts on phenotype in organisms ranging from microbes to humans, yet little is known about how natural selection acts on genome arrangement. Pathogenic bacteria such as Yersinia pestis, which causes bubonic and pneumonic plague, often exhibit a high degree of genomic rearrangement. The recent availability of several Yersinia genomes offers an unprecedented opportunity to study the evolution of genome structure and arrangement. We introduce a set of statistical methods to study patterns of rearrangement in circular chromosomes and apply them to the Yersinia. We constructed a multiple alignment of eight Yersinia genomes using Mauve software to identify 78 conserved segments that are internally free from genome rearrangement. Based on the alignment, we applied Bayesian statistical methods to infer the phylogenetic inversion history of Yersinia. The sampling of genome arrangement reconstructions contains seven parsimonious tree topologies, each having different histories of 79 inversions. Topologies with a greater number of inversions also exist, but were sampled less frequently. The inversion phylogenies agree with results suggested by SNP patterns. We then analyzed reconstructed inversion histories to identify patterns of rearrangement. We confirm an over-representation of "symmetric inversions"-inversions with endpoints that are equally distant from the origin of chromosomal replication. Ancestral genome arrangements demonstrate moderate preference for replichore balance in Yersinia. We found that all inversions are shorter than expected under a neutral model, whereas inversions acting within a single replichore are much shorter than expected. We also found evidence for a canonical configuration of the origin and terminus of replication. Finally, breakpoint reuse analysis reveals that inversions with endpoints proximal to the origin of DNA replication are nearly three times more frequent. Our findings

Telomerase activation by genomic rearrangements in high-risk neuroblastoma

Science.gov (United States)

Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L.; Sand, Frederik; Heuckmann, Johannes M.; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Glöckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R.; Savelyeva, Larissa; Watkins, Simon C.; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H.; Herrmann, Carl; O’Sullivan, Roderick J.; Westermann, Frank; Thomas, Roman K.; Fischer, Matthias

2016-01-01

Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system1. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2–4. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type1,2,5. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

An Intramolecular Heck reaction that Prefers a 5-endo- to a 6-exo-trig Cyclization Pathway

DEFF Research Database (Denmark)

Vital, Paulo; Norrby, Per-Ola; Tanner, David Ackland

2006-01-01

A regioselective aromatic Claisen rearrangement was used to prepare 17a, the precursor of triflate 17e. The intramolecular Heck reaction of 17e is promoted only by bidentate phosphine ligands, giving exclusively and in excellent yield 20, the product of a 5-endo-trig cyclization, despite the poss......A regioselective aromatic Claisen rearrangement was used to prepare 17a, the precursor of triflate 17e. The intramolecular Heck reaction of 17e is promoted only by bidentate phosphine ligands, giving exclusively and in excellent yield 20, the product of a 5-endo-trig cyclization, despite...

Combinatorial aspects of genome rearrangements and haplotype networks

OpenAIRE

Labarre , Anthony

2008-01-01

The dissertation covers two problems motivated by computational biology: genome rearrangements, and haplotype networks. Genome rearrangement problems are a particular case of edit distance problems, where one seeks to transform two given objects into one another using as few operations as possible, with the additional constraint that the set of allowed operations is fixed beforehand; we are also interested in computing the corresponding distances between those objects, i.e. merely computing t...

Rearrangement of beta,gamma-unsaturated esters with thallium trinitrate: synthesis of indans bearing a beta-keto ester moiety

Directory of Open Access Journals (Sweden)

Silva Jr. Luiz F.

2006-01-01

Full Text Available The rearrangement of beta,gamma-unsaturated esters, such as 2-(3,4-dihydronaphthalen-1-yl-propionic acid ethyl ester, with thallium trinitrate (TTN in acetic acid leads to 3-indan-1-yl-2-methyl-3-oxo-propionic acid ethyl ester in good yield, through a ring contraction reaction. The new indans thus obtained feature a beta-keto ester moiety, which would be useful for further functionalization.

The hardness of train rearrangements

NARCIS (Netherlands)

Eggermont, C.E.J.; Hurkens, C.A.J.; Modelski, M.S.; Woeginger, G.J.

2009-01-01

We derive several results on the computational complexity of train rearrangement problems in railway optimization. Our main result states that arranging a departing train in a depot is NP-complete, even if each track in the depot contains only two cars.

Optimal control of the initiation of a pericyclic reaction in the ...

Indian Academy of Sciences (India)

Abstract. Pericyclic reactions in the electronic ground state may be initiated by down-chirped pump-dump ... Figure 1. Cope rearrangement of semibullvalene, with pincer-motion-type ... investigations which have centred attention on the simp-.

Initiation of MLL-rearranged AML is dependent on C/EBPα

DEFF Research Database (Denmark)

Ohlsson, Ewa; Hasemann, Marie Sigurd; Willer, Anton

2014-01-01

have compared gene expression profiles from human MLL-rearranged AML to normal progenitors and identified the myeloid tumor suppressor C/EBPα as a putative collaborator in MLL-rearranged AML. Interestingly, we find that deletion of Cebpa rendered murine hematopoietic progenitors completely resistant...

Tandem mass spectrometric analysis of cyclophosphamide, ifosfamide and their metabolites.

Science.gov (United States)

Liu, Zhongfa; Chan, Kenneth K; Wang, Jeffrey J

2005-01-01

A detailed multi-stage (MSn) fragmentation study of cyclophosphamide (CP), ifosfamide (IF) and their major metabolites, using an ion-trap mass spectrometer and a Q-TOF mass spectrometer, was performed with the aid of specifically deuterium-labeled analogs. The analytes showed good responses in positive-ion electrospray mass spectrometry as [MH]+ ions. Tandem mass spectra revealed a wealth of structurally specific ions, allowing characterization of the fragmentation pathways of these analytes. The major fragmentation pathways of the protonated CP and IF are elimination of ethylene from C5 and C6 of 1,3,2-oxazaphosphorine-2-oxide via a McLafferty rearrangement, and cleavage of the P-N bond. However, their activated 4-OOH and 4-OH metabolites primarily underwent hydrogen peroxide elimination and dehydration, respectively, followed by fragmentation pathways similar to those of CP and IF. These results should prove useful in structural elucidation of future analogs of CP and IF, and/or of their metabolites. Copyright (c) 2005 John Wiley & Sons, Ltd.

1,2-Fluorine Radical Rearrangements: Isomerization Events in Perfluorinated Radicals.

Science.gov (United States)

Van Hoomissen, Daniel J; Vyas, Shubham

2017-11-16

Devising effective degradation technologies for perfluoroalkyl substances (PFASs) is an active area of research, where the molecular mechanisms involving both oxidative and reductive pathways are still elusive. One commonly neglected pathway in PFAS degradation is fluorine atom migration in perfluoroalkyl radicals, which was largely assumed to be implausible because of the high C-F bond strength. Using density functional theory calculations, it was demonstrated that 1,2-F atom migrations are thermodynamically favored when the fluorine atom migrated from a less branched carbon center to a more branched carbon center. Activation barriers for these rearrangements were within 19-29 kcal/mol, which are possible to easily overcome at elevated temperatures or in photochemically activated species in the gas or aqueous phase. It was also found that the activation barriers for the 1,2-F atom migration are lowered as much as by 10 kcal/mol when common oxidative degradation products such as HF assisted the rearrangements or if the resulting radical center was stabilized by vicinal π-bonds. Natural bond orbital analyses showed that fluorine moves as a radical in a noncharge-separated state. These findings add an important reaction to the existing knowledge of mechanisms for PFAS degradation and highlights the fact that 1,2-F atom shifts may be a small channel for isomerization of these compounds, but upon availability of mineralization products, this isomerization process could become more prominent.

Vibronic coupling in ionized organic molecules. Structural distortions and chemical reactions

International Nuclear Information System (INIS)

Williams, F.

2002-01-01

Complete text of publication follows. Ionized organic molecules (radical cations, RC) are prone to undergo vibronic coupling whenever there is a relatively small energy gap ( 2v point group of the neutral parent molecule by twisting at the olefinic π bond to the lower C 2 symmetry in the RC (Chem. Eur. J. 2002, 8, 1074). These experiments clearly revealed a double minimum in the potential energy surface along the a 2 torsional mode. This is in accord with the coupling of the 2 B 1 and 2 B 2 Born-Oppenheimer states in C 2v symmetry, this mixing of the 2 B 1 π-ionized ground state and the 2 B 2 δ-ionized excited state being facilitated by the low (∼ 1.0 eV) gap between these states, as estimated from photoelectron spectroscopy. Turning to the second class of RC where unimolecular rearrangement reactions are promoted by vibronic interaction, several cases have emerged where the rearrangement would not be expected if it were based only on the ground-state properties of the RC. It was found (Chem. Phy. Lett. 1988, 143, 521) that the ethylene oxide RC undergoes C-C ring opening to the oxallyl species despite the fact that the ground state corresponds to ionization from the nonbonding oxygen π lone-pair orbital. The reaction develops excited-state character as a result of the vibronic mixing so that the activation barrier to ring opening is lowered. We will discuss the unusual rearrangements of the bicyclo[1.1.1.]pentane and [1.1.1]propellane RC from a similar perspective, emphasis being placed on the decisive role of symmetry in predicting the course of these rearrangements. We illustrate how this approach can reconcile conflicting considerations on some of the 'unexpected' reaction pathways followed by highly strained organic RC

Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG-Rearrangements in Prostate Cancer.

Science.gov (United States)

Catelain, Cyril; Pailler, Emma; Oulhen, Marianne; Faugeroux, Vincent; Pommier, Anne-Laure; Farace, Françoise

2017-01-01

Circulating tumor cells (CTCs) hold promise as biomarkers to aid in patient treatment stratification and disease monitoring. Because the number of cells is a critical parameter for exploiting CTCs for predictive biomarker's detection, we developed a FISH (fluorescent in situ hybridization) method for CTCs enriched on filters (filter-adapted FISH [FA-FISH]) that was optimized for high cell recovery. To increase the feasibility and reliability of the analyses, we combined fluorescent staining and FA-FISH and developed a semi-automated microscopy method for optimal FISH signal identification in filtration-enriched CTCs . Here we present these methods and their use for the detection and characterization of ALK-, ROS1-, RET-rearrangement in CTCs from non-small-cell lung cancer and ERG-rearrangements in CTCs from prostate cancer patients.

Comparing genomes with rearrangements and segmental duplications.

Science.gov (United States)

Shao, Mingfu; Moret, Bernard M E

2015-06-15

Large-scale evolutionary events such as genomic rearrange.ments and segmental duplications form an important part of the evolution of genomes and are widely studied from both biological and computational perspectives. A basic computational problem is to infer these events in the evolutionary history for given modern genomes, a task for which many algorithms have been proposed under various constraints. Algorithms that can handle both rearrangements and content-modifying events such as duplications and losses remain few and limited in their applicability. We study the comparison of two genomes under a model including general rearrangements (through double-cut-and-join) and segmental duplications. We formulate the comparison as an optimization problem and describe an exact algorithm to solve it by using an integer linear program. We also devise a sufficient condition and an efficient algorithm to identify optimal substructures, which can simplify the problem while preserving optimality. Using the optimal substructures with the integer linear program (ILP) formulation yields a practical and exact algorithm to solve the problem. We then apply our algorithm to assign in-paralogs and orthologs (a necessary step in handling duplications) and compare its performance with that of the state-of-the-art method MSOAR, using both simulations and real data. On simulated datasets, our method outperforms MSOAR by a significant margin, and on five well-annotated species, MSOAR achieves high accuracy, yet our method performs slightly better on each of the 10 pairwise comparisons. http://lcbb.epfl.ch/softwares/coser. © The Author 2015. Published by Oxford University Press.

A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production.

Science.gov (United States)

Srour, Nivine; Chemin, Guillaume; Tinguely, Aurélien; Ashi, Mohamad Omar; Oruc, Zéliha; Péron, Sophie; Sirac, Christophe; Cogné, Michel; Delpy, Laurent

2016-01-11

Aberrantly rearranged immunoglobulin (Ig) alleles are frequent. They are usually considered sterile and innocuous as a result of nonsense-mediated mRNA decay. However, alternative splicing can yield internally deleted proteins from such nonproductively V(D)J-rearranged loci. We show that nonsense codons from variable (V) Igκ exons promote exon-skipping and synthesis of V domain-less κ light chains (ΔV-κLCs). Unexpectedly, such ΔV-κLCs inhibit plasma cell (PC) differentiation. Accordingly, in wild-type mice, rearrangements encoding ΔV-κLCs are rare in PCs, but frequent in B cells. Likewise, enforcing expression of ΔV-κLCs impaired PC differentiation and antibody responses without disturbing germinal center reactions. In addition, PCs expressing ΔV-κLCs synthesize low levels of Ig and are mostly found among short-lived plasmablasts. ΔV-κLCs have intrinsic toxic effects in PCs unrelated to Ig assembly, but mediated by ER stress-associated apoptosis, making PCs producing ΔV-κLCs highly sensitive to proteasome inhibitors. Altogether, these findings demonstrate a quality control checkpoint blunting terminal PC differentiation by eliminating those cells expressing nonfunctionally rearranged Igκ alleles. This truncated Ig exclusion (TIE) checkpoint ablates PC clones with ΔV-κLCs production and exacerbated ER stress response. The TIE checkpoint thus mediates selection of long-lived PCs with limited ER stress supporting high Ig secretion, but with a cost in terms of antigen-independent narrowing of the repertoire. © 2016 Srour et al.

Modeling the reactions catalyzed by coenzyme B12-dependent enzymes.

Science.gov (United States)

Sandala, Gregory M; Smith, David M; Radom, Leo

2010-05-18

Enzymes accelerate chemical reactions with an exceptional selectivity that makes life itself possible. Understanding the factors responsible for this efficient catalysis is of utmost importance in our quest to harness the tremendous power of enzymes. Computational chemistry has emerged as an important adjunct to experimental chemistry and biochemistry in this regard, because it provides detailed insights into the relationship between structure and function in a systematic and straightforward manner. In this Account, we highlight our recent high-level theoretical investigations toward this end in studying the radical-based reactions catalyzed by enzymes dependent on coenzyme B(12) (or adenosylcobalamin, AdoCbl). In addition to their fundamental position in biology, the AdoCbl-dependent enzymes represent a valuable framework within which to understand Nature's method of efficiently handling high-energy species to execute very specific reactions. The AdoCbl-mediated reactions are characterized by the interchange of a hydrogen atom and a functional group on adjacent carbon atoms. Our calculations are consistent with the conclusion that the main role of AdoCbl is to provide a source of radicals, thus moving the 1,2-rearrangements onto the radical potential energy surface. Our studies also show that the radical rearrangement step is facilitated by partial proton transfer involving the substrate. Specifically, we observe that the energy requirements for radical rearrangement are reduced dramatically with appropriate partial protonation or partial deprotonation or sometimes (synergistically) both. Such interactions are particularly relevant to enzyme catalysis, because it is likely that the local amino acid environment in the active site of an enzyme can function in this capacity through hydrogen bonding. Finally, our calculations indicate that the intervention of a very stable radical along the reaction pathway may inactivate the enzyme, demonstrating that sustained

Stress-induced rearrangement of Fusarium retrotransposon sequences.

Science.gov (United States)

Anaya, N; Roncero, M I

1996-11-27

Rearrangement of fusarium oxysporum retrotransposon skippy was induced by growth in the presence of potassium chlorate. Three fungal strains, one sensitive to chlorate (Co60) and two resistant to chlorate and deficient for nitrate reductase (Co65 and Co94), were studied by Southern analysis of their genomic DNA. Polymorphism was detected in their hybridization banding pattern, relative to the wild type grown in the absence of chlorate, using various enzymes with or without restriction sites within the retrotransposon. Results were consistent with the assumption that three different events had occurred in strain Co60: genomic amplification of skippy yielding tandem arrays of the element, generation of new skippy sequences, and deletion of skippy sequences. Amplification of Co60 genomic DNA using the polymerase chain reaction and divergent primers derived from the retrotransposon generated a new band, corresponding to one long terminal repeat plus flanking sequences, that was not present in the wild-type strain. Molecular analysis of nitrate reductase-deficient mutants showed that generation and deletion of skippy sequences, but not genomic amplification in tandem repeats, had occurred in their genomes.

Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

Science.gov (United States)

Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

2012-06-28

Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Study of the rearrangement of N-alkylanilines to P-aminoalkylbencene. III. N-n-propil-l-14{sup C} aniline; Estudio de la transposicion de N-Alquilanilinas a p-Aminoalquibenceno mediante 14{sup C}. III. N-n Propilanilina

Energy Technology Data Exchange (ETDEWEB)

Molera, J M; Gamboa, J M; Val del Cob, M; Ortin, N

1964-07-01

The rearrangement of N-n-propyl aniline to p-amino propylbenzene has been studied at 250 degree centigrade using several catalysts: CoCl{sub 2}, ZnCl{sub 2} and HBr. N-propyl-1-14{sup C}-aniline has been synthesized from sodium propionate-1-14{sup C} through conversion to n-propyl-1-14{sup C}-iodide and further reaction with aniline. After the rearrangement and among the reaction products both p-aminopropylbenzene and p-aminoisopropylbencene were found. To determine the 14{sup C} position in both the starting aniline and reaction products two degradation schemes are followed. In the light of experimental evidence a mechanism is set forth based on the assumption of an organic cation as intermediate. (Author) 13 refs.

Detection of SYT and EWS gene rearrangements by dual-color break-apart CISH in liquid-based cytology samples of synovial sarcoma and Ewing sarcoma/primitive neuroectodermal tumor.

Science.gov (United States)

Kumagai, Arisa; Motoi, Toru; Tsuji, Kaori; Imamura, Tetsuo; Fukusato, Toshio

2010-08-01

To improve cytologic diagnostic accuracy for translocation-associated sarcomas, we explored dual-color break-apart (dc) chromogenic in situ hybridization (CISH) on liquid-based cytology (LBC) samples of 2 prototypic sarcomas: synovial sarcoma (SS) and Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET). LBC samples of 10 cases of SS and 9 cases of ES/PNET were subjected to dc-CISH using probes for the specifically rearranged genes in each tumor entity: SYT in SS and EWS in ES/PNET. Rearranged SYT was successfully detected in all SSs but not in any ES/PNETs. In contrast, EWS rearrangement was identified in all ES/PNETs but not in any SSs. These results were validated by dc-fluorescence in situ hybridization and reverse transcription-polymerase chain reaction. dc-CISH on LBC samples is a reliable modality to detect gene rearrangements in sarcomas. This system has a clear advantage over other methods, enabling simultaneous visualization of the genetic abnormality and well-preserved, nonoverlapping cytomorphologic features with clear background under bright-field microscope.

Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer

Directory of Open Access Journals (Sweden)

Kyung Park

2010-07-01

Full Text Available TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC and fluorescence in situ hybridization (FISH analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role. Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5% of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.

Study of the rearrangement of N-alkylaniline to p-aminoalkylbencene. I. N-ethyl-l-{sup 1}4C-aniline; Estudio de la transposicion de N-alquilanilinas A p-Aminoalquilbenceno mediante {sup 1}4C

Energy Technology Data Exchange (ETDEWEB)

Molera, M J; Gamboa, J M; Val Cob, M del

1961-07-01

The rearrangement of N-ethylaniline to p-aminoethylbenzene has been studied over the temperature range 200-300 degree centigrade using different catalysts: Cl{sub 2}Co, Cl{sub 2}Zn, Cl{sub 2}Ni, Cl{sub 3}Al, Cl{sub 2}Cd and Br H.N-ethyl-1-{sup 1}4C-aniline has been synthesized from ethyl-1-{sup 1}4C-iodide and aniline and its rearrangement to p-aminoethyl-benzene proves that the ethyl group does not rearrange itself during the reaction. A scheme for the degradation of both the N-ethyl-1-{sup 1}4C aniline and the p-aminoethylbenzene produces is described. (Author) 14 refs.

Synthesis of the naturally occurring prenylated coumarins balsamiferone and cedrelopsin by domino reactions

Digital Repository Service at National Institute of Oceanography (India)

Patre, R.E.; Parameswaran, P.S.; Tilve, S.G.

Regioselective one step synthesis of naturally occurring prenyl coumarin balsamiferone is described using domino Wittig reaction, 3,3-sigmatropic rearrangements and deprenylation, while regioselective synthesis of cedrelopsin is described via domino...

Gene activation by induced DNA rearrangements

International Nuclear Information System (INIS)

Schnipper, L.E.; Chan, V.; Sedivy, J.; Jat, P.; Sharp, P.A.

1989-01-01

A murine cell line (EN/NIH) containing the retroviral vector ZIPNeoSV(x)1 that was modified by deletion of the enhancer elements in the viral long terminal repeats has been used as an assay system to detect induced DNA rearrangements that result in activation of a transcriptionally silent reporter gene encoded by the viral genome. The spontaneous frequency of G418 resistance is less than 10(-7), whereas exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the combination of UV irradiation plus TPA resulted in the emergence of drug resistant cell lines at a frequency of 5 per 10(6) and 67 per 10(6) cells, respectively. In several of the cell lines that were analyzed a low level of amplification of one of the two parental retroviral integrants was observed, whereas in others no alteration in the region of the viral genome was detected. To determine the effect of the SV40 large T antigen on induced DNA rearrangements, EN/NIH cells were transfected with a temperature sensitive (ts) mutant of SV40 T. Transfectants were maintained at the permissive temperature (33 degrees C) for varying periods of time (1-5 days) in order to vary SV40 T antigen exposure, after which they were shifted to 39.5 degrees C for selection in G418. The frequency of emergence of drug resistant cell clones increased with duration of exposure to large T antigen (9-52 per 10(6) cells over 1-5 days, respectively), and all cell lines analyzed demonstrated DNA rearrangements in the region of the neo gene. A novel 18-kilobase pair XbaI fragment was cloned from one cell line which revealed the presence of a 2.0-kilobase pair EcoRI segment containing an inverted duplication which hybridized to neo sequences. It is likely that the observed rearrangement was initiated by the specific binding of large T antigen to the SV40 origin of replication encoded within the viral genome

Comparison of detection methods and follow-up study on the tyrosine kinase inhibitors therapy in non-small cell lung cancer patients with ROS1 fusion rearrangement

International Nuclear Information System (INIS)

Wu, Jieyu; Lin, Yunen; He, Xinming; Yang, Haihong; He, Ping; Fu, Xinge; Li, Guangqiu; Gu, Xia

2016-01-01

The screening of ROS proto-oncogene 1, receptor tyrosine kinase(ROS1) fusion rearrangement might be potentially beneficial for an effective therapy against non-small cell lung cancer (NSCLC). However, the three main ROS1 rearrangement detection methods have limitations, and no routine protocol for the detection of ROS1 rearrangement in NSCLC is available. In this study, our aims were to compare immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in their ability to detect ROS1 rearrangement in NSCLC, and discuss the clinical characteristics and histopathology of the patients with ROS1 rearrangement. Moreover, the effects of tyrosine kinase inhibitors (TKIs) therapy on the patients with ROS1 rearrangement and advanced stage disease (III b–IV) were investigated. Patients with a previously diagnosed NSCLC were recruited in this study from November 2013 to October 2015. IHC was performed using the D4D6 monoclonal antibody (mAb) in an automatic IHC instrument, while FISH and qRT-PCR were carried out to confirm the IHC results. FISH and qRT-PCR positive cases underwent direct sequencing. After detection, patients with advanced ROS1 rearranged NSCLC had received TKI therapy. Two hundred and thirty-eight patients were included in this study. ROS1 rearrangement was detected in 10 patients. The concordant rate of FISH and qRT-PCR results was 100 %, while in the FISH and IHC results high congruence was present when IHC showed a diffusely (≥60 % tumor cells) 2–3+ cytoplasmic reactivity pattern. Patients harboring ROS1 rearrangement were mostly young (8/10), females (7/10) and non-smokers (7/10) with adenocarcinoma (10/10) and acinar pattern. Most of their tumor were in intermediate grade (6/8). Among these 10 patients, three of them in stage IV with ROS1 rearrangement gained benefits from ROS1 TKI therapy. IHC, FISH and qRT-PCR can reliably detect ROS1 rearrangement in NSCLC, while IHC can be

Contribution of canonical nonhomologous end joining to chromosomal rearrangements is enhanced by ATM kinase deficiency.

Science.gov (United States)

Bhargava, Ragini; Carson, Caree R; Lee, Gabriella; Stark, Jeremy M

2017-01-24

A likely mechanism of chromosomal rearrangement formation involves joining the ends from two different chromosomal double-strand breaks (DSBs). These events could potentially be mediated by either of two end-joining (EJ) repair pathways [canonical nonhomologous end joining (C-NHEJ) or alternative end joining (ALT-EJ)], which cause distinct rearrangement junction patterns. The relative role of these EJ pathways during rearrangement formation has remained controversial. Along these lines, we have tested whether the DNA damage response mediated by the Ataxia Telangiectasia Mutated (ATM) kinase may affect the relative influence of C-NHEJ vs. ALT-EJ on rearrangement formation. We developed a reporter in mouse cells for a 0.4-Mbp deletion rearrangement that is formed by EJ between two DSBs induced by the Cas9 endonuclease. We found that disruption of the ATM kinase causes an increase in the frequency of the rearrangement as well as a shift toward rearrangement junctions that show hallmarks of C-NHEJ. Furthermore, ATM suppresses rearrangement formation in an experimental condition, in which C-NHEJ is the predominant EJ repair event (i.e., expression of the 3' exonuclease Trex2). Finally, several C-NHEJ factors are required for the increase in rearrangement frequency caused by inhibition of the ATM kinase. We also examined ATM effectors and found that H2AX shows a similar influence as ATM, whereas the influence of ATM on this rearrangement seems independent of 53BP1. We suggest that the contribution of the C-NHEJ pathway to the formation of a 0.4-Mbp deletion rearrangement is enhanced in ATM-deficient cells.

Ionization-induced rearrangement of defects in silicon

International Nuclear Information System (INIS)

Vinetskij, V.L.; Manojlo, M.A.; Matvijchuk, A.S.; Strikha, V.I.; Kholodar', G.A.

1988-01-01

Ionizing factor effect on defect rearrangement in silicon including centers with deep local electron levels in the p-n-transition region is considered. Deep center parameters were determined using non-steady-state capacity spectroscopy of deep levels (NCDLS) method. NCDLS spectrum measurement was performed using source p + -n - diodes and after their irradiation with 15 keV energy electrons or laser pulses. It is ascertained that in silicon samples containing point defect clusters defect rearrangement under ionizing factor effect takes place, i.e. deep level spectra are changed. This mechanism is efficient in case of silicon irradiation with subthreshold energy photons and electrons and can cause degradation of silicon semiconducting structures

DNA rearrangements from γ-irradiated normal human fibroblasts preferentially occur in transcribed regions of the genome

International Nuclear Information System (INIS)

Forrester, H.B.; Radford, I.R.

2003-01-01

Full text: DNA rearrangement events leading to chromosomal aberrations are central to ionizing radiation-induced cell death. Although DNA double-strand breaks are probably the lesion that initiates formation of chromosomal aberrations, little is understood about the molecular mechanisms that generate and modulate DNA rearrangement. Examination of the sequences that flank sites of DNA rearrangement may provide information regarding the processes and enzymes involved in rearrangement events. Accordingly, we developed a method using inverse PCR that allows the detection and sequencing of putative radiation-induced DNA rearrangements in defined regions of the human genome. The method can detect single copies of a rearrangement event that has occurred in a particular region of the genome and, therefore, DNA rearrangement detection does not require survival and continued multiplication of the affected cell. Ionizing radiation-induced DNA rearrangements were detected in several different regions of the genome of human fibroblast cells that were exposed to 30 Gy of γ-irradiation and then incubated for 24 hours at 37 deg C. There was a 3- to 5-fold increase in the number of products amplified from irradiated as compared with control cells in the target regions 5' to the C-MYC, CDKN1A, RB1, and FGFR2 genes. Sequences were examined from 121 DNA rearrangements. Approximately half of the PCR products were derived from possible inter-chromosomal rearrangements and the remainder were from intra-chromosomal events. A high proportion of the sequences that rearranged with target regions were located in genes, suggesting that rearrangements may occur preferentially in transcribed regions. Eighty-four percent of the sequences examined by reverse transcriptase PCR were from transcribed sequences in IMR-90 cells. The distribution of DNA rearrangements within the target regions is non-random and homology occurs between the sequences involved in rearrangements in some cases but is not

Programmed Rearrangement in Ciliates: Paramecium.

Science.gov (United States)

Betermier, Mireille; Duharcourt, Sandra

2014-12-01

Programmed genome rearrangements in the ciliate Paramecium provide a nice illustration of the impact of transposons on genome evolution and plasticity. During the sexual cycle, development of the somatic macronucleus involves elimination of ∼30% of the germline genome, including repeated DNA (e.g., transposons) and ∼45,000 single-copy internal eliminated sequences (IES). IES excision is a precise cut-and-close process, in which double-stranded DNA cleavage at IES ends depends on PiggyMac, a domesticated piggyBac transposase. Genome-wide analysis has revealed that at least a fraction of IESs originate from Tc/mariner transposons unrelated to piggyBac. Moreover, genomic sequences with no transposon origin, such as gene promoters, can be excised reproducibly as IESs, indicating that genome rearrangements contribute to the control of gene expression. How the system has evolved to allow elimination of DNA sequences with no recognizable conserved motif has been the subject of extensive research during the past two decades. Increasing evidence has accumulated for the participation of noncoding RNAs in epigenetic control of elimination for a subset of IESs, and in trans-generational inheritance of alternative rearrangement patterns. This chapter summarizes our current knowledge of the structure of the germline and somatic genomes for the model species Paramecium tetraurelia, and describes the DNA cleavage and repair factors that constitute the IES excision machinery. We present an overview of the role of specialized RNA interference machineries and their associated noncoding RNAs in the control of DNA elimination. Finally, we discuss how RNA-dependent modification and/or remodeling of chromatin may guide PiggyMac to its cognate cleavage sites.

A route to hydroxylfluorenes: TsOH-mediated condensation reactions of 1,3-diketones with propargylic alcohols

KAUST Repository

Yao, Liangfeng

2012-01-01

An efficient method of preparing hydroxylfluorenes by TsOH-mediated tandem alkylation/rearrangements of propargylic alcohols with 1,3-diketones is described. These reactions are accomplished in moderate to good yields under mild conditions to offer a straightforward and convenient one step synthetic route to hydroxylfluorene derivatives through a plausible mechanism involving a sequence of dehydration, addition, rearrangement and aromatization. This journal is © The Royal Society of Chemistry 2012.

Structure and Reaction Mechanism of Pyrrolysine Synthase (PylD)

KAUST Repository

Quitterer, Felix; Beck, Philipp; Bacher, Adelbert; Groll, Michael

2013-01-01

The final step in the biosynthesis of the 22nd genetically encoded amino acid, pyrrolysine, is catalyzed by PylD, a structurally and mechanistically unique dehydrogenase. This catalyzed reaction includes an induced-fit mechanism achieved by major structural rearrangements of the N-terminal helix upon substrate binding. Different steps of the reaction trajectory are visualized by complex structures of PylD with substrate and product. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure and Reaction Mechanism of Pyrrolysine Synthase (PylD)

KAUST Repository

Quitterer, Felix

2013-05-29

The final step in the biosynthesis of the 22nd genetically encoded amino acid, pyrrolysine, is catalyzed by PylD, a structurally and mechanistically unique dehydrogenase. This catalyzed reaction includes an induced-fit mechanism achieved by major structural rearrangements of the N-terminal helix upon substrate binding. Different steps of the reaction trajectory are visualized by complex structures of PylD with substrate and product. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement].

Science.gov (United States)

Caliez, J; Monnet, I; Pujals, A; Rousseau-Bussac, G; Jabot, L; Boudjemaa, A; Leroy, K; Chouaid, C

2017-05-01

Among patients with non-small-cell lung cancer, coexistence of EGFR mutation and ALK rearrangement is rare. We describe the clinical features of two patients with this double anomaly. A 62-year-old Caucasian non-smoking woman was diagnosed with cT4N0M0 lung adenocarcinoma. Initial biopsy showed EGFR mutation and ALK rearrangement. She received cisplatin-gemcitabine, followed by 17 months of gemcitabine. Owing to progression, she received erlotinib for 14 months, then paclitaxel for 6 months and finally crizotinib. A partial response was achieved and maintained for 24 months. A 45-year-old Caucasian woman, light smoker, was diagnosed with cT2N3M0 lung adenocarcinoma. Only EGFR mutation was found on initial analysis. She underwent treatment with cisplatin-gemcitabine and thoracic radiotherapy. Progression occurred after 8 months and afatinbib was started. Eight months later, progression was observed with a neoplasic pleural effusion in which tumor cells expressing ALK rearrangement were found. A new FISH analysis was performed on the initial tumor but did not find this rearrangement. Despite a third line of crizotinib, the patient died one month later. The literature shows 45 other cases of these two abnormalities, observed either from the start or during follow-up. EGFR's TKI were almost always given before ALK's TKI. Therapeutic strategy needs to be clarified in cases of double alteration. With regard to the second patient, appearance of ALK rearrangement may constitute a resistance mechanism to EGFR's TKI. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Aromatic Polyimide and Crosslinked Thermally Rearranged Poly(benzoxazole-co-imide) Membranes for Isopropanol Dehydration via Pervaporation

KAUST Repository

Ming Xu, Yi

2015-10-31

Novel crosslinked thermally rearranged polybenzoxazole (C-TR-PBO) membranes, which show impressive results for isopropanol dehydration, have been obtained via in-situ thermal conversion of hydroxyl-containing polyimide precursors. The polyimide precursors are synthesized by the polycondensation of three monomers; namely, 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA), 3,3′-dihydroxybenzidine diamine (HAB) and 3,5-diaminobenzoic acid (DABA). Due to the incorporation of the carboxylic-group containing diamine DABA into an ortho-hydroxypolyimide precursor, the thermal induced crosslinking reaction can be achieved together with the thermal rearrangement process. Consequently, a synergistic effect of high permeability and high selectivity can be realized in one step. The resultant C-TR-PBO membrane exhibits an unambiguous enhancement in permeation flux compared to their polyimide precursors. Moreover, the newly developed C-TR-PBO membrane displays stable isopropanol dehydration performance at 60 °C throughout the continuous 200 hours. The promising preliminary results achieved in this study may offer useful insights for the selection of membrane materials for pervaporation and new methods to molecularly design next-generation pervaporation membranes.

Aromatic Polyimide and Crosslinked Thermally Rearranged Poly(benzoxazole-co-imide) Membranes for Isopropanol Dehydration via Pervaporation

KAUST Repository

Ming Xu, Yi; Le, Ngoc Lieu; Zuo, Jian; Chung, Neal Tai-Shung

2015-01-01

Novel crosslinked thermally rearranged polybenzoxazole (C-TR-PBO) membranes, which show impressive results for isopropanol dehydration, have been obtained via in-situ thermal conversion of hydroxyl-containing polyimide precursors. The polyimide precursors are synthesized by the polycondensation of three monomers; namely, 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA), 3,3′-dihydroxybenzidine diamine (HAB) and 3,5-diaminobenzoic acid (DABA). Due to the incorporation of the carboxylic-group containing diamine DABA into an ortho-hydroxypolyimide precursor, the thermal induced crosslinking reaction can be achieved together with the thermal rearrangement process. Consequently, a synergistic effect of high permeability and high selectivity can be realized in one step. The resultant C-TR-PBO membrane exhibits an unambiguous enhancement in permeation flux compared to their polyimide precursors. Moreover, the newly developed C-TR-PBO membrane displays stable isopropanol dehydration performance at 60 °C throughout the continuous 200 hours. The promising preliminary results achieved in this study may offer useful insights for the selection of membrane materials for pervaporation and new methods to molecularly design next-generation pervaporation membranes.

Recurrent DNA inversion rearrangements in the human genome

DEFF Research Database (Denmark)

Flores, Margarita; Morales, Lucía; Gonzaga-Jauregui, Claudia

2007-01-01

Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome...... to human genomic variation is discussed........ In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located...

The He+H¯→He p¯+e+ rearrangement

Science.gov (United States)

Todd, Allan C.; Armour, Edward A. G.

2006-06-01

In this paper, we present a summary of our work in progress on calculating cross sections for the He+H¯→He p¯+e+ rearrangement process in He H¯ scattering. This has involved a study of the system He p¯ within the Born-Oppenheimer (BO) approximation using the Rayleigh-Ritz variational method. This work has been reported in [A.C. Todd, E.A.G. Armour, J. Phys. B 38 (2005) 3367] and is summarised here. Similar calculations are in progress for the He+H¯ entrance channel. We intend to use the entrance channel and rearrangement channel wave functions to obtain the cross sections for the rearrangement using the distorted wave Born approximation T-matrix method described elsewhere in these proceedings [E.A.G. Armour, S. Jonsell, Y. Liu, A.C. Todd, these Proceedings, doi:10.1016/j.nimb.2006.01.049].

The He+H-bar → Hep-bar +e+ rearrangement

International Nuclear Information System (INIS)

Todd, Allan C.; Armour, Edward A.G.

2006-01-01

In this paper, we present a summary of our work in progress on calculating cross sections for the He+H-bar ->Hep-bar +e + rearrangement process in HeH-bar scattering. This has involved a study of the system Hep-bar within the Born-Oppenheimer (BO) approximation using the Rayleigh-Ritz variational method. This work has been reported in [A.C. Todd, E.A.G. Armour, J. Phys. B 38 (2005) 3367] and is summarised here. Similar calculations are in progress for the He+H-bar entrance channel. We intend to use the entrance channel and rearrangement channel wave functions to obtain the cross sections for the rearrangement using the distorted wave Born approximation T-matrix method described elsewhere in these proceedings [E.A.G. Armour, S. Jonsell, Y. Liu, A.C. Todd, these Proceedings, doi:10.1016/j.nimb.2006.01.049

Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia

International Nuclear Information System (INIS)

Shen, A.; Humphries, C.; Tucker, P.; Blattner, F.

1987-01-01

The authors have identified a family of human immunoglobulin heavy-chain variable-region (V/sub H/) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged V/sub H/ genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged V/sub H/ genes (V/sub H/TS1 and V/sub H/WS1) that were 90% homologous. The corresponding germ-line gene, V/sub H/251, was found to part of a small (four gene) V/sub H/ gene family, which they term V/sub H/V. The DNA sequence homology to V/sub H/WS1 (95%) and V/sub H/TS1 (88%) and identical restriction sites on the 5' side of V/sub H/ confirm that rearrangement of V/sub H/251 followed by somatic mutation produced the identical V/sub H/ gene rearrangements in the two siblings. V/sub H/TS1 is not a functional V/sub H/ gene; a functional V/sub H/ rearrangement was found on the other chromosome of this patient. The other two siblings had different V/sub H/ gene rearrangements. All used different diversity genes. Mechanisms proposed for nonrandom selection of a single V/sub H/ gene include developmental regulation of this V/sub H/ gene rearrangement or selection of a subpopulation of B cells in which this V/sub H/ has been rearranged

A BAC clone fingerprinting approach to the detection of human genome rearrangements

Science.gov (United States)

Krzywinski, Martin; Bosdet, Ian; Mathewson, Carrie; Wye, Natasja; Brebner, Jay; Chiu, Readman; Corbett, Richard; Field, Matthew; Lee, Darlene; Pugh, Trevor; Volik, Stas; Siddiqui, Asim; Jones, Steven; Schein, Jacquie; Collins, Collin; Marra, Marco

2007-01-01

We present a method, called fingerprint profiling (FPP), that uses restriction digest fingerprints of bacterial artificial chromosome clones to detect and classify rearrangements in the human genome. The approach uses alignment of experimental fingerprint patterns to in silico digests of the sequence assembly and is capable of detecting micro-deletions (1-5 kb) and balanced rearrangements. Our method has compelling potential for use as a whole-genome method for the identification and characterization of human genome rearrangements. PMID:17953769

Triisobutylaluminium (TIBAL Promoted Rearrangement of C-glycosides

Directory of Open Access Journals (Sweden)

P. Sinay

2005-08-01

Full Text Available Triisobutylaluminium-promoted rearrangement of unsaturated glycosides containing electron-donating aglycons, such as C-aryl glycosides, provides direct access to highly functionalised cyclohexane derivatives.

Quantifying stretching and rearrangement in epithelial sheet migration

International Nuclear Information System (INIS)

Lee, Rachel M; Nordstrom, Kerstin N; Losert, Wolfgang; Kelley, Douglas H; Ouellette, Nicholas T

2013-01-01

Although understanding the collective migration of cells, such as that seen in epithelial sheets, is essential for understanding diseases such as metastatic cancer, this motion is not yet as well characterized as individual cell migration. Here we adapt quantitative metrics used to characterize the flow and deformation of soft matter to contrast different types of motion within a migrating sheet of cells. Using a finite-time Lyapunov exponent (FTLE) analysis, we find that—in spite of large fluctuations—the flow field of an epithelial cell sheet is not chaotic. Stretching of a sheet of cells (i.e. positive FTLE) is localized at the leading edge of migration and increases when the cells are more highly stimulated. By decomposing the motion of the cells into affine and non-affine components using the metric D m in 2 , we quantify local plastic rearrangements and describe the motion of a group of cells in a novel way. We find an increase in plastic rearrangements with increasing cell densities, whereas inanimate systems tend to exhibit less non-affine rearrangements with increasing density. (paper)

Reactions of transition metal complexes with cyclic ethers

International Nuclear Information System (INIS)

Milstein, D.

1977-02-01

Three novel reactions of epoxides with homogeneous transition-metal catalysts have been explored: (a) the selective rearrangement of internal epoxides to ketones; (b) the cleavage of C-C bond in epoxides having electron-attracting substituents; (c) the transformation of terminal epoxides into esters. Based on an intensive kinetic study, a general mechanism for the transformations of epoxides is postulated

Input-output rearrangement of isolated converters

DEFF Research Database (Denmark)

Madsen, Mickey Pierre; Kovacevic, Milovan; Mønster, Jakob Døllner

2015-01-01

This paper presents a new way of rearranging the input and output of isolated converters. The new arrangement posses several advantages, as increased voltage range, higher power handling capabilities, reduced voltage stress and improved efficiency, for applications where galvanic isolation...

Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project.

Science.gov (United States)

Higgins, Anne W; Alkuraya, Fowzan S; Bosco, Amy F; Brown, Kerry K; Bruns, Gail A P; Donovan, Diana J; Eisenman, Robert; Fan, Yanli; Farra, Chantal G; Ferguson, Heather L; Gusella, James F; Harris, David J; Herrick, Steven R; Kelly, Chantal; Kim, Hyung-Goo; Kishikawa, Shotaro; Korf, Bruce R; Kulkarni, Shashikant; Lally, Eric; Leach, Natalia T; Lemyre, Emma; Lewis, Janine; Ligon, Azra H; Lu, Weining; Maas, Richard L; MacDonald, Marcy E; Moore, Steven D P; Peters, Roxanna E; Quade, Bradley J; Quintero-Rivera, Fabiola; Saadi, Irfan; Shen, Yiping; Shendure, Jay; Williamson, Robin E; Morton, Cynthia C

2008-03-01

Apparently balanced chromosomal rearrangements in individuals with major congenital anomalies represent natural experiments of gene disruption and dysregulation. These individuals can be studied to identify novel genes critical in human development and to annotate further the function of known genes. Identification and characterization of these genes is the goal of the Developmental Genome Anatomy Project (DGAP). DGAP is a multidisciplinary effort that leverages the recent advances resulting from the Human Genome Project to increase our understanding of birth defects and the process of human development. Clinically significant phenotypes of individuals enrolled in DGAP are varied and, in most cases, involve multiple organ systems. Study of these individuals' chromosomal rearrangements has resulted in the mapping of 77 breakpoints from 40 chromosomal rearrangements by FISH with BACs and fosmids, array CGH, Southern-blot hybridization, MLPA, RT-PCR, and suppression PCR. Eighteen chromosomal breakpoints have been cloned and sequenced. Unsuspected genomic imbalances and cryptic rearrangements were detected, but less frequently than has been reported previously. Chromosomal rearrangements, both balanced and unbalanced, in individuals with multiple congenital anomalies continue to be a valuable resource for gene discovery and annotation.

Kinugasa Reactions in Water: From Green Chemistry to Bioorthogonal Labelling

Directory of Open Access Journals (Sweden)

Mariya Chigrinova

2015-04-01

Full Text Available The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions followed by rearrangement furnishing high yields of β-lactams. The high yields of stable products under aqueous conditions render the modified Kinugasa reaction amenable to metabolic labelling and bioorthogonal applications. Herein, the development of methods for use of the Kinugasa reaction in aqueous media is reviewed, with emphasis on its potential use as a bioorthogonal coupling strategy.

Kinugasa reactions in water: from green chemistry to bioorthogonal labelling.

Science.gov (United States)

Chigrinova, Mariya; MacKenzie, Douglas A; Sherratt, Allison R; Cheung, Lawrence L W; Pezacki, John Paul; Pezacki, Paul

2015-04-16

The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I) acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions followed by rearrangement furnishing high yields of β-lactams. The high yields of stable products under aqueous conditions render the modified Kinugasa reaction amenable to metabolic labelling and bioorthogonal applications. Herein, the development of methods for use of the Kinugasa reaction in aqueous media is reviewed, with emphasis on its potential use as a bioorthogonal coupling strategy.

A 45 X male patient with 7q distal deletion and rearrangement with SRY gene translocation: a case report.

Science.gov (United States)

Bilen, S; Okten, A; Karaguzel, G; Ikbal, M; Aslan, Y

2013-01-01

Here we present a male newborn with multiple congenital anomalies who also has an extremely rare form of testicular disorder of sex development (DSD). His karyotype was 45X, without any mosaicism. SRY gene was positive by polymerase chain reaction (PCR), and rearranged on distal part of the 7th chromosome by fluorescence in situ hybridization (FISH) analysis. SRY, normally located on the Y chromosome, is the most important gene that plays a role in the development of male sex. SRY gen may be translocated onto another chromosome, mostly X chromosome in the XX testicular DSD. On the other hand very few cases of 45 X testicular DSD were published to date. Other clinical manifestations of our patient were compatible with distal 7 q deletion syndrome. To the best of our knowledge this is the first case of 45 X testicular DSD with SRY gene rearranged on the 7th autosomal chromosome.

A Prediction Model for ROS1-Rearranged Lung Adenocarcinomas based on Histologic Features

OpenAIRE

Zhou, Jianya; Zhao, Jing; Zheng, Jing; Kong, Mei; Sun, Ke; Wang, Bo; Chen, Xi; Ding, Wei; Zhou, Jianying

2016-01-01

Aims To identify the clinical and histological characteristics of ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) and build a prediction model to prescreen suitable patients for molecular testing. Methods and Results We identified 27 cases of ROS1-rearranged lung adenocarcinomas in 1165 patients with NSCLCs confirmed by real-time PCR and FISH and performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement and finally developed predi...

Low energy acetoin ions CH3C(=O)C(H)(OH)CH3.+ decompose to CH3CO. and CH3CHOH+ via a remarkable "hidden rearrangement"

Science.gov (United States)

Suh, Dennis; Burgers, Peter C.; Terlouw, Johan K.

1995-06-01

Tandem mass spectrometry based experiments on D and 18O labelled acetoin isotopomers show that the title reaction is not just a simple bond cleavage, but rather involves rearrangement via ion--dipole complexes; the intermediacy of a charge-transfer complex is proposed to account for the observed product ratios.

An efficient synthesis of symmetric and unsymmetric bis-(β-aminoamides) via Ugi multicomponent reaction.

Science.gov (United States)

La Spisa, Fabio; Feo, Alberto; Mossetti, Riccardo; Tron, Gian Cesare

2012-12-07

A library of symmetrical and unsymmetrical bis-(β-aminoamides) has been prepared starting from symmetrical secondary diamines by using a double Ugi four-component reaction. A sacrifical Mumm rearrangement, thanks to the use of 2-hydroxymethyl benzoic acid, is necessary to suppress the competing split-Ugi reaction, increasing the yield and simplifying the purification step. The scope, the reaction conditions, and the role of water in trapping the nitrilium intermediate are also discussed.

Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

Energy Technology Data Exchange (ETDEWEB)

O' Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

2010-08-19

Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding

Magnetic isotope and external magnetic field effects upon the photo-Fries rearrangement of 1-naphthyl acetate

International Nuclear Information System (INIS)

Nakagaki, R.; Hiramatsu, M.; Watanabe, T.; Tanimoto, Y.; Nagakura, S.

1985-01-01

The reaction mechanisms of the photo-Fries rearrangement of 1-naphthyl acetate has been studied by means of steady-state photolysis and laser flash photolysis. A radical pair consisting of the 1-naphthoxyl and acetyl radicals is concluded to be a reaction intermediate. The yield of an in-cage product (2-acetyl-1-naphthol) exhibits a positive external magnetic field effect for the ester labeled by magnetically active 13 C, but no effect for the normal 12 C ester. The magnetic field effect observed for the labeled ester is quantitatively or semiquantitatively explained in terms of the radical-pair mechanism by considering hyperfine coupling between magnetically active nuclei ( 1 H and 13 C) and an unpaired electron in the acetyl radical. The in-cage product is formed through the singlet radical pair. 26 references, 5 figures, 3 tables

Delineating Rearrangements in Single Yeast Artificial Chromosomes by Quantitative DNA Fiber Mapping

Energy Technology Data Exchange (ETDEWEB)

Weier, Heinz-Ulrich G.; Greulich-Bode, Karin M.; Wu, Jenny; Duell, Thomas

2009-09-18

Cloning of large chunks of human genomic DNA in recombinant systems such as yeast or bacterial artificial chromosomes has greatly facilitated the construction of physical maps, the positional cloning of disease genes or the preparation of patient-specific DNA probes for diagnostic purposes. For this process to work efficiently, the DNA cloning process and subsequent clone propagation need to maintain stable inserts that are neither deleted nor otherwise rearranged. Some regions of the human genome; however, appear to have a higher propensity than others to rearrange in any host system. Thus, techniques to detect and accurately characterize such rearrangements need to be developed. We developed a technique termed 'Quantitative DNA Fiber Mapping (QDFM)' that allows accurate tagging of sequence elements of interest with near kilobase accuracy and optimized it for delineation of rearrangements in recombinant DNA clones. This paper demonstrates the power of this microscopic approach by investigating YAC rearrangements. In our examples, high-resolution physical maps for regions within the immunoglobulin lambda variant gene cluster were constructed for three different YAC clones carrying deletions of 95 kb and more. Rearrangements within YACs could be demonstrated unambiguously by pairwise mapping of cosmids along YAC DNA molecules. When coverage by YAC clones was not available, distances between cosmid clones were estimated by hybridization of cosmids onto DNA fibers prepared from human genomic DNA. In addition, the QDFM technology provides essential information about clone stability facilitating closure of the maps of the human genome as well as those of model organisms.

The impact of complex chromosomal rearrangements on the detection of radiosensitivity in cancer patients

International Nuclear Information System (INIS)

Neubauer, Susann; Dunst, Juergen; Gebhart, Erich

1997-01-01

Background and purpose: Lymphocytes of a small fraction of cancer patients responded to in vitro irradiation with an extreme chromosomal reaction. A large portion of the observed chromosome aberrations were complex chromosomal rearrangements (CCR). The present study is an attempt to define the impact of CCR on the predictive detection of an intrinsic clinical radiosensitivity in cancer patients in more detail. Materials and methods: A three-colour 'FISH-painting' technique (chromosome in situ suppression (CISS) hybridization) was used for the detection of chromosomal rearrangements, induced by in vitro irradiation, in 81 samples of peripheral blood lymphocytes from 66 cancer patients. Thirty-three of those were assigned for radiation therapy, the others having just undergone radiation therapy. Seven healthy individuals served as controls. Results: CCRs are a very rare event in non-irradiated cells. Lymphocytes of patients who had just undergone therapeutic irradiation, however, not only exhibited high basic frequencies of CCR but also responded to in vitro irradiation with a more drastic increase of CCR than did the lymphocytes of non-exposed patients. A high inter-individual variability of the reaction to in vitro irradiation could be generally stated. The lymphocytes of patients with clinical signs of an outstanding radiosensitivity responded with an unusually high frequency of CCR. The total number of CCRs detected by CISS was found to be dependent on the interval from a previous radiation therapy and was slightly influenced by previous cytostatic therapy. Irrespective of these influences, patients with clinically defined radiation hypersensitivity were those with the highest radiosensitivity also in cytogenetic terms (including CCR). Conclusion: The successful use of FISH-painting for the detection of CCR, in addition to the general breakage frequency, highlights its suitability in the identification of individual hypersensitivity to ionizing radiation. The

Organocatalyzed Domino [3+2] Cycloaddition/Payne-Type Rearrangement using Carbon Dioxide and Epoxy Alcohols.

Science.gov (United States)

Kleij, Arjan Willem; Sopeña, Sergio; Cozzolino, Mariachiara; Escudero-Adán, Eduardo C; Martínez Belmonte, Marta; Maquilón, Cristina

2018-05-09

An unprecedented organocatalytic approach towards highly substituted cyclic carbonates from tri- and tetra-substituted oxiranes and carbon dioxide has been developed. The protocol involves the use of a simple and cheap superbase under mild, additive- and metal-free conditions towards the initial formation of a less substituted carbonate product that equilibrates to a tri- or even tetra-substituted cyclic carbonate under thermodynamic control. The latter are conveniently trapped in situ providing overall a new domino process for synthetically elusive heterocyclic scaffolds. Control experiments provide a rationale for the observed cascade reactions, which demonstrate high similarity with the well-known Payne rearrangement of epoxy alcohols. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transformation of follicular lymphoma to plasmablastic lymphoma with c-myc gene rearrangement.

Science.gov (United States)

Ouansafi, Ihsane; He, Bing; Fraser, Cory; Nie, Kui; Mathew, Susan; Bhanji, Rumina; Hoda, Rana; Arabadjief, Melissa; Knowles, Daniel; Cerutti, Andrea; Orazi, Attilio; Tam, Wayne

2010-12-01

Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.

Distribution of the various radiation-induced chromosomal rearrangements in relation to the dose and sampling time

International Nuclear Information System (INIS)

Dutrillaux, B.; Viegas-Pequignot, E.; Prod'homme, M.; Sportes, M.

1985-01-01

The quantitative analysis of the chromosome rearrangements detected in 2128 R-banded metaphases, obtained from γ-irradiated human lymphocytes after 48 to 96 h in culture is reported. Depending on the culture time, and possibly on the dose of radiation (from 1 to 3 Gy), the most frequent type of rearrangement was either dicentrics or reciprocal translocations. In first generation mitoses, the frequency of cells without rearrangement ranged from 0.66 to 0.18, and the mean number of rearranged chromosomes per cell from 0.79 to 3.28. The dose-response curve follows a quadratic function for dicentric aberration yields, but not for other rearrangements. (Auth.)

Evaluation of multiplex ligation-dependent probe amplification analysis versus multiplex polymerase chain reaction assays in the detection of dystrophin gene rearrangements in an Iranian population subset

Directory of Open Access Journals (Sweden)

Nayereh Nouri

2014-01-01

Full Text Available Background: The Duchenne muscular dystrophy (DMD gene is located in the short arm of the X chromosome (Xp21. It spans 2.4 Mb of the human genomic DNA and is composed of 79 exons. Mutations in the Dystrophin gene result in DMD and Becker muscular dystrophy. In this study, the efficiency of multiplex ligation-dependent probe amplification (MLPA over multiplex polymerase chain reaction (PCR assays in an Iranian population was investigated. Materials and Methods: Multiplex PCR assays and MLPA analysis were carried out in 74 patients affected with DMD. Results: Multiplex PCR detected deletions in 51% of the patients with DMD. MLPA analysis could determine all the deletions detected by the multiplex PCR. Additionally, MLPA was able to identify one more deletion and duplication in patients without detectable mutations by multiplex PCR. Moreover, MLPA precisely determined the exact size of the deletions. Conclusion: Although MLPA analysis is more sensitive for detection of deletions and duplications in the dystrophin gene, multiplex PCR might be used for the initial analysis of the boys affected with DMD in the Iranian population as it was able to detect 95% of the rearrangements in patients with DMD.

Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement

Science.gov (United States)

Louie, Gordon; Noel, Joseph P.; Baran, Phil S.; Palfey, Bruce; Moore, Bradley S.

2013-01-01

Flavoproteins catalyze a diversity of fundamental redox reactions and are one of the most studied enzyme families1,2. As monooxygenases, they are universally thought to control oxygenation by means of a peroxyflavin species that transfers a single atom of molecular oxygen to an organic substrate1,3,4. Here we report that the bacterial flavoenzyme EncM5,6 catalyzes the peroxyflavin-independent oxygenation-dehydrogenation dual oxidation of a highly reactive poly(β-carbonyl). The crystal structure of EncM with bound substrate mimics coupled with isotope labeling studies reveal previously unknown flavin redox biochemistry. We show that EncM maintains an unanticipated stable flavin oxygenating species, proposed to be a flavin-N5-oxide, to promote substrate oxidation and trigger a rare Favorskii-type rearrangement that is central to the biosynthesis of the antibiotic enterocin. This work provides new insight into the fine-tuning of the flavin cofactor in offsetting the innate reactivity of a polyketide substrate to direct its efficient electrocyclization. PMID:24162851

Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer.

Science.gov (United States)

Pailler, Emma; Adam, Julien; Barthélémy, Amélie; Oulhen, Marianne; Auger, Nathalie; Valent, Alexander; Borget, Isabelle; Planchard, David; Taylor, Melissa; André, Fabrice; Soria, Jean Charles; Vielh, Philippe; Besse, Benjamin; Farace, Françoise

2013-06-20

The diagnostic test for ALK rearrangement in non-small-cell lung cancer (NSCLC) for crizotinib treatment is currently done on tumor biopsies or fine-needle aspirations. We evaluated whether ALK rearrangement diagnosis could be performed by using circulating tumor cells (CTCs). The presence of an ALK rearrangement was examined in CTCs of 18 ALK-positive and 14 ALK-negative patients by using a filtration enrichment technique and filter-adapted fluorescent in situ hybridization (FA-FISH), a FISH method optimized for filters. ALK-rearrangement patterns were determined in CTCs and compared with those present in tumor biopsies. ALK-rearranged CTCs and tumor specimens were characterized for epithelial (cytokeratins, E-cadherin) and mesenchymal (vimentin, N-cadherin) marker expression. ALK-rearranged CTCs were monitored in five patients treated with crizotinib. All ALK-positive patients had four or more ALK-rearranged CTCs per 1 mL of blood (median, nine CTCs per 1 mL; range, four to 34 CTCs per 1 mL). No or only one ALK-rearranged CTC (median, one per 1 mL; range, zero to one per 1 mL) was detected in ALK-negative patients. ALK-rearranged CTCs harbored a unique (3'5') split pattern, and heterogeneous patterns (3'5', only 3') of splits were present in tumors. ALK-rearranged CTCs expressed a mesenchymal phenotype contrasting with heterogeneous epithelial and mesenchymal marker expressions in tumors. Variations in ALK-rearranged CTC levels were detected in patients being treated with crizotinib. ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment. Our results suggest that CTCs harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC.

Chromosome-specific staining to detect genetic rearrangements

Energy Technology Data Exchange (ETDEWEB)

Gray, Joe W.; Pinkel, Daniel; Tkachuk, Douglas; Westbrook, Carol

2013-04-09

Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyzes. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML) and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

Quantitative and Qualitative Changes in V-J α Rearrangements During Mouse Thymocytes Differentiation

Science.gov (United States)

Pasqual, Nicolas; Gallagher, Maighréad; Aude-Garcia, Catherine; Loiodice, Mélanie; Thuderoz, Florence; Demongeot, Jacques; Ceredig, Rod; Marche, Patrice Noël; Jouvin-Marche, Evelyne

2002-01-01

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR α chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR α repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3′ side than 5′ end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR α repertoire size and suggest a scenario for V usage during differentiation. PMID:12417627

Synthesis of cyclopentadiene-fused chromanones via one-pot multicomponent reactions.

Science.gov (United States)

Ghandi, Mehdi; Ghomi, Ali-Tabatabaei; Kubicki, Maciej

2013-03-15

We have developed one-pot method for the synthesis of functionalized novel cyclopentadiene-fused chromanone scaffolds. A variety of 4-oxo-2,4-dihydrocyclopenta[c]chromene-1,2-dicarboxylates were obtained in moderate to good yields via condensation of 2-hydroxybenzaldehydes and ethyl acetoacetate with 1:1 acetylenecarboxylate-isocyanides in toluene. These reactions presumably proceed via reaction of the in situ generated 3-acetyl-2H-chromen-2-ones with acetylenecarboxylate-isocyanide zwitterionic intermediates through Michael addition/intramolecular cyclization and double [1,5] acyl shift rearrangement cascade.

Fine-tiling array CGH to improve diagnostics for alpha- and beta-thalassemia rearrangements

NARCIS (Netherlands)

Phylipsen, M.; Chaibunruang, A.; Vogelaar, I.P.; Balak, J.R.; Schaap, R.A.; Ariyurek, Y.; Fucharoen, S.; den Dunnen, J.T.; Giordano, P.C.; Bakker, E.; Harteveld, C.L.

2012-01-01

Implementation of multiplex ligation-dependent probe amplification (MLPA) for thalassemia causing deletions has lead to the detection of new rearrangements. Knowledge of the exact breakpoint sequences should give more insight into the molecular mechanisms underlying these rearrangements, and would

Classic theory for chromosome rearrangements with spatially restricted volume for broken ends interaction

International Nuclear Information System (INIS)

Omel'yanchuk, L.V.

1997-01-01

D. Lea classic theory for chromosomal rearrangements formation was modified to account for local interaction of broken chromosome ends. This assumption makes it possible to drastically improve coincidence of the theory and experiment in the case of complex rearrangements

High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

Science.gov (United States)

Pailler, E; Auger, N; Lindsay, C R; Vielh, P; Islas-Morris-Hernandez, A; Borget, I; Ngo-Camus, M; Planchard, D; Soria, J-C; Besse, B; Farace, F

2015-07-01

Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene

Reaction of acid esters of methylenebis(phosphonous acid) with carbonyl compounds

International Nuclear Information System (INIS)

Novikova, Z.S.; Odinets, I.L.; Lutsenko, I.F.

1987-01-01

The reaction of methylenebis(phosphonites) containing two hydrophosphoryl groupings with aliphatic and aromatic aldehydes and ketones in the presence of alkali metal fluorides leads to methylenebis(α-hydroxyalkylphosphinates). The reaction of methylenebis(phosphonites) containing one hydrophosphoryl groupings with carbonyl compounds in the presence of alkali metal fluorides proceeds with the formation of a new type of heterocyclic phosphorus compound, viz., 1,2λ 3 ,4λ 5 -oxadiphospholanes. The reaction of acid esters of methylenebis(phosphonous) acid with carbonyl compounds in the presence of alkali metal alkoxides or a tertiary amine is accompanied by phosphinate-phosphonate rearrangement of the intermediately formed α-hydroxylalkylphosphinates

Chromosomal Rearrangements in Post-Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

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Ludwig Hieber

2011-01-01

Full Text Available Structural genomic rearrangements are frequent findings in human cancers. Therefore, papillary thyroid carcinomas (PTCs were investigated for chromosomal aberrations and rearrangements of the RET proto-oncogene. For this purpose, primary cultures from 23 PTC have been established and metaphase preparations were analysed by spectral karyotyping (SKY. In addition, interphase cell preparations of the same cases were investigated by fluorescence in situ hybridisation (FISH for the presence of RET/PTC rearrangements using RET-specific DNA probes. SKY analysis of PTC revealed structural aberrations of chromosome 11 and several numerical aberrations with frequent loss of chromosomes 20, 21, and 22. FISH analysis for RET/PTC rearrangements showed prevalence of this rearrangement in 72% (16 out of 22 of cases. However, only subpopulations of tumour cells exhibited this rearrangement indicating genetic heterogeneity. The comparison of visual and automated scoring of FISH signals revealed concordant results in 19 out of 22 cases (87% indicating reliable scoring results using the optimised scoring parameter for RET/PTC with the automated Metafer4 system. It can be concluded from this study that genomic rearrangements are frequent in PTC and therefore important events in thyroid carcinogenesis.

The unexpected decarbonylation of ionized 2,3-pentanedione and related diketones

Science.gov (United States)

Wang, Xian; Holmes, John L.

2006-03-01

The fragmentation of the 2,3-pentanedione radical cation gives rise to an unexpected composite metastable ion peak, m/z 72, resulting from the isobaric losses of CO and C2H4. These two fragmentation channels are energetically competitive (i.e., the transition states have similar energies). The two processes yield [CH3C(O)CH2CH3]+ and [CH3C(OH)CO]+, respectively. The latter new ion, which is produced by a McLafferty rearrangement, has [Delta]fH° = 604 kJ/mol, obtained from G3 calculations. The four competing processes for metastable [CH3COCOCH2CH3]+, the (intense) losses of CH3CO, CH3CH2CO and the weak losses of C2H4 and CO and their transition states were placed on a potential energy surface computed at the G3 level of theory. The homologous ionized diketone 2,3-butanedione also displays the decarbonylation channel and 3,4-hexanedione loses CO and C2H4.

Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms

NARCIS (Netherlands)

Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

2012-01-01

Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed

PCR-based clonality analysis of B-cell lymphomas in paraffin-embedded tissues: diagnostic value of immunoglobulin kappa and lambda light chain gene rearrangement investigation.

Science.gov (United States)

Amara, Khaled; Trimeche, Mounir; Ziadi, Sonia; Sriha, Badreddine; Mokni, Moncef; Korbi, Sadok

2006-01-01

Polymerase chain reaction (PCR)-based analysis, employed for detecting immunoglobulin heavy chain (IgH) gene rearrangements, has become a diagnostic tool widely used in the investigation of B-cell lymphomas, but the overall sensitivity of these methods does not exceed 80%, notably in germinal center (GC) and post-GC B-cell origin lymphomas. Many PCR strategies devised for detecting immunoglobulin light chain (IgL) gene rearrangements have been developed to enhance the clonality detection rates. However, the feasibility of these methods in routine clinical diagnosis using paraffin-embedded tissues has not yet been investigated sufficiently. We studied a large series of 108 cases of B-cell lymphomas, as well as 20 reactive lymphoid tissues using degenerate primers to amplify immunoglobulin kappa (Igkappa) and lambda (Iglambda) light chain genes. B-cell clonality was further investigated using semi-nested PCR for IgH gene rearrangements. B-cell clonality was detected in 74%, 56.5%, and 43.5% of cases using IgH, Igkappa, and Iglambda PCR, respectively. By combining these methods, the clonality detection rate increased to 93.5%. Only polyclonal patterns were noted in reactive lymphoid samples. We concluded that in addition to the established methods for IgH analysis, a PCR-based approach for IgL gene rearrangements analysis improves the clonality detection rate in over 90% of B-cell lymphoma cases using routine histological specimens with poor preservation of the genomic DNA.

Rearrangement of 5-trimethylsilylthebaine on treatment with L-selectride: an efficient synthesis of (+)-bractazonine.

Science.gov (United States)

Chen, Weibin; Wu, Huifang; Bernard, Denzil; Metcalf, Matthew D; Deschamps, Jeffrey R; Flippen-Anderson, Judith L; MacKerell, Alexander D; Coop, Andrew

2003-03-07

Treatment of 5-trimethylsilylthebaine with L-Selectride gave rise to a rearrangement to 10-trimethylsilylbractazonine through migration of the phenyl group, whereas treatment of thebaine with strong Lewis acids is known to lead to a similar rearrangement through migration of the alkyl bridge to give, after reduction, (+)-neodihydrothebaine. It is suggested that the rearrangement of the alkyl group of thebaine is favored due to the formation of a tertiary benzylic cation. However, for 5-trimethylsilylthebaine, the lithium ion of L-Selectride acts as the Lewis acid and the beta-silyl effect dominates in the stabilization of any positive charge. This rearrangement provides a clear example of the greater relative migratory aptitude of phenyl groups over alkyl groups, and provides an efficient synthesis of (+)-bractazonine from thebaine.

Deciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement

OpenAIRE

Willis, Nicholas A.; Rass, Emilie; Scully, Ralph

2015-01-01

Chromosome rearrangement plays a causal role in tumorigenesis by contributing to the inactivation of tumor suppressor genes, the dysregulated expression or amplification of oncogenes and the generation of novel gene fusions. Chromosome breaks are important intermediates in this process. How, when and where these breaks arise and the specific mechanisms engaged in their repair strongly influence the resulting patterns of chromosome rearrangement. Here, we review recent progress in understandin...

A route to hydroxylfluorenes: TsOH-mediated condensation reactions of 1,3-diketones with propargylic alcohols

KAUST Repository

Yao, Liangfeng; Tan, Davin; Miao, Xiaohe; Huang, Kuo-Wei

2012-01-01

An efficient method of preparing hydroxylfluorenes by TsOH-mediated tandem alkylation/rearrangements of propargylic alcohols with 1,3-diketones is described. These reactions are accomplished in moderate to good yields under mild conditions to offer

A general heuristic for genome rearrangement problems.

Science.gov (United States)

Dias, Ulisses; Galvão, Gustavo Rodrigues; Lintzmayer, Carla Négri; Dias, Zanoni

2014-06-01

In this paper, we present a general heuristic for several problems in the genome rearrangement field. Our heuristic does not solve any problem directly, it is rather used to improve the solutions provided by any non-optimal algorithm that solve them. Therefore, we have implemented several algorithms described in the literature and several algorithms developed by ourselves. As a whole, we implemented 23 algorithms for 9 well known problems in the genome rearrangement field. A total of 13 algorithms were implemented for problems that use the notions of prefix and suffix operations. In addition, we worked on 5 algorithms for the classic problem of sorting by transposition and we conclude the experiments by presenting results for 3 approximation algorithms for the sorting by reversals and transpositions problem and 2 approximation algorithms for the sorting by reversals problem. Another algorithm with better approximation ratio can be found for the last genome rearrangement problem, but it is purely theoretical with no practical implementation. The algorithms we implemented in addition to our heuristic lead to the best practical results in each case. In particular, we were able to improve results on the sorting by transpositions problem, which is a very special case because many efforts have been made to generate algorithms with good results in practice and some of these algorithms provide results that equal the optimum solutions in many cases. Our source codes and benchmarks are freely available upon request from the authors so that it will be easier to compare new approaches against our results.

Internal flow inside droplets within a concentrated emulsion during droplet rearrangement

Science.gov (United States)

Leong, Chia Min; Gai, Ya; Tang, Sindy K. Y.

2018-03-01

Droplet microfluidics, in which each droplet serves as a micro-reactor, has found widespread use in high-throughput biochemical screening applications. These droplets are often concentrated at various steps to form a concentrated emulsion. As part of a serial interrogation and sorting process, such concentrated emulsions are typically injected into a tapered channel leading to a constriction that fits one drop at a time for the probing of droplet content in a serial manner. The flow physics inside the droplets under these flow conditions are not well understood but are critical for predicting and controlling the mixing of reagents inside the droplets as reactors. Here we investigate the flow field inside droplets of a concentrated emulsion flowing through a tapered microchannel using micro-particle image velocimetry. The confining geometry of the channel forces the number of rows of drops to reduce by one at specific and uniformly spaced streamwise locations, which are referred to as droplet rearrangement zones. Within each rearrangement zone, the phase-averaged velocity results show that the motion of the droplets involved in the rearrangement process, also known as a T1 event, creates vortical structures inside themselves and their adjacent droplets. These flow structures increase the circulation inside droplets up to 2.5 times the circulation in droplets at the constriction. The structures weaken outside of the rearrangement zones suggesting that the flow patterns created by the T1 process are transient. The time scale of circulation is approximately the same as the time scale of a T1 event. Outside of the rearrangement zones, flow patterns in the droplets are determined by the relative velocity between the continuous and disperse phases.

Ligand flexibility and framework rearrangement in a new family of porous metal-organic frameworks

DEFF Research Database (Denmark)

Hawxwell, Samuel M; Espallargas, Guillermo Mínguez; Bradshaw, Darren

2007-01-01

Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs.......Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs....

MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression.

Directory of Open Access Journals (Sweden)

Fen Zhu

Full Text Available INTRODUCTION: Primary pulmonary mucoepidermoid carcinoma (PMEC is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19 resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. METHODS: We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC, and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC. The findings were then examined regarding the clinicopathological parameters and patient outcomes. RESULTS: FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001 and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively. Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023 or disease-free survival (p = 0.027 as well as correlation between FLT1 and overall survival (p = 0.009. CONCLUSIONS: MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.

Reciprocity theory of homogeneous reactions

Science.gov (United States)

Agbormbai, Adolf A.

1990-03-01

The reciprocity formalism is applied to the homogeneous gaseous reactions in which the structure of the participating molecules changes upon collision with one another, resulting in a change in the composition of the gas. The approach is applied to various classes of dissociation, recombination, rearrangement, ionizing, and photochemical reactions. It is shown that for the principle of reciprocity to be satisfied it is necessary that all chemical reactions exist in complementary pairs which consist of the forward and backward reactions. The backward reaction may be described by either the reverse or inverse process. The forward and backward processes must satisfy the same reciprocity equation. Because the number of dynamical variables is usually unbalanced on both sides of a chemical equation, it is necessary that this balance be established by including as many of the dynamical variables as needed before the reciprocity equation can be formulated. Statistical transformation models of the reactions are formulated. The models are classified under the titles free exchange, restricted exchange and simplified restricted exchange. The special equations for the forward and backward processes are obtained. The models are consistent with the H theorem and Le Chatelier's principle. The models are also formulated in the context of the direct simulation Monte Carlo method.

Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

International Nuclear Information System (INIS)

Cohen-Gihon, Inbar; Nussinov, Ruth; Sharan, Roded

2011-01-01

During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently

Relationship between mitochondrial gene rearrangements and stability of the origin of light strand replication

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Miguel M. Fonseca

2008-01-01

Full Text Available Mitochondrial gene rearrangements are much more frequent in vertebrates than initially thought. It has been suggested that the origin of light strand replication could have an important role in the process of gene rearrangements, but this hypothesis has never been tested before. We used amphibians to test the correlation between light-strand replication origin thermodynamic stability and the occurrence of gene rearrangements. The two variables were correlated in a non-phylogenetic approach, but when tested in a phylogenetically based comparative method the correlation was not significant, although species with unstable light-strand replication origins were much more likely to have undergone gene rearrangements. This indicates that within amphibians there are stable and unstable phylogenetic groups regarding mitochondrial gene order. The species analyzed showed variability in the thermodynamic stability of the secondary structure, in the length of its stem and loop, and several species did not present the 5’-GCCGG-3’ motif reported to be necessary for efficient mitochondrial DNA replication. Future studies should focus on the role of the light-strand replication origin in mitochondrial DNA replication and gene rearrangements mechanisms.

Solvent effects in the acid-catalysed rearrangements of 1,2-oxazines

International Nuclear Information System (INIS)

Yagoub, A.K.; Ogur, J.A.; Wanekaya, A.K.

2005-12-01

The rates of acid-catalyzed rearrangements of 6-ethoxy-5,6-dihydro-3-phenyl-4H-1,2-oxazines have been investigated in H 2 SO 4 /methanol, MeCN and Me 2 SO by means of spectrophotometric methods. Pseudo first order rate constants were obtained in each case. Results in methanol supported an A1 type mechanism. Also investigated were the correlation of reaction rates with Hammet acidity function (H 0 ) by application of the Bunnet criterion where a slope of -0.67 was obtained. Further, the solvent effect was considered from two points of mechanistic views: the thermodynamic transfer functions of MeOH to MeCN and Me 2 SO where the rate was found fast in MeCN and slow in Me 2 SO and the Kirkwood-Buff preferential solvation with aqueous MeOH, MeCN and Me 2 SO. The techniques supported the proposed transition state structure. (author)

Large Clinically Consequential Imbalances Detected at the Breakpoints of Apparently Balanced and Inherited Chromosome Rearrangements

OpenAIRE

South, Sarah T.; Rector, Lyndsey; Aston, Emily; Rowe, Leslie; Yang, Samuel P.

2010-01-01

When a chromosome abnormality is identified in a child with a developmental delay and/or multiple congenital anomalies and the chromosome rearrangement appears balanced, follow-up studies often examine both parents for this rearrangement. If either clinically unaffected parent has a chromosome abnormality with a banding pattern identical to the affected child's study, then it is assumed that the chromosome rearrangement is balanced and directly inherited from the normal carrier parent. It is ...

Spatially Rearranged Object Parts Can Facilitate Perception of Intact Whole Objects

Directory of Open Access Journals (Sweden)

Laura eCacciamani

2014-05-01

Full Text Available The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively. We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime’s border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

Spatially rearranged object parts can facilitate perception of intact whole objects.

Science.gov (United States)

Cacciamani, Laura; Ayars, Alisabeth A; Peterson, Mary A

2014-01-01

The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively). We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime's border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

Complete nucleotide sequence and gene rearrangement of the ...

Indian Academy of Sciences (India)

3Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People's Republic of China ... of these rearrangements involve tRNA genes, ND5 gene and ... ncbi.nlm.nih.gov/projects/Sequin/download/seq_win_download.

Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria.

Science.gov (United States)

Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

2017-04-01

A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compensate for the genome-destabilizing effect of environmental DNA damage and may be expected to result in a more conserved gene order in radiation-resistant species. However, here we show that rates of genome rearrangements, measured as loss of gene order conservation with time, are higher in radiation-resistant species in multiple, phylogenetically independent groups of bacteria. Comparison of indicators of selection for genome organization between radiation-resistant and phylogenetically matched, nonresistant species argues against tolerance to disruption of genome structure as a strategy for radiation resistance. Interestingly, an important mechanism affecting genome rearrangements in prokaryotes, the symmetrical inversions around the origin of DNA replication, shapes genome structure of both radiation-resistant and nonresistant species. In conclusion, the opposing effects of environmental DNA damage and DNA repair result in elevated rates of genome rearrangements in radiation-resistant bacteria. Copyright © 2017 Repar et al.

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

DEFF Research Database (Denmark)

Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc

2014-01-01

In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using...... with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC...... was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude...

On colour rearrangement in hadronic W+W- events

International Nuclear Information System (INIS)

Sjoestrand, T.; Khoze, V.A.

1994-01-01

We discuss the possibility of colour rearrangement in e + e - →W + W - →q 1 anti q 2 q 3 anti q 4 events, i.e. that the original colour singlets q 1 anti q 2 and q 3 anti q 4 may be transmuted, for instance, into new singlets q 1 anti q 4 and q 3 anti q 2 . The effects on event properties could be quite large if such a rearrangement would occur instantaneously, so that gluon emission would be restricted to each of the new singlets separately. We argue that such a scenario is unlikely for two reasons. Firstly, the W + and W - usually decay at separate times after the W + W - production, which leads to large relative phases for energetic radiation off the two constituents of a rearranged system, and a corresponding dampening of the QCD cascades. Secondly, within the perturbative scenario the colour transmutation appears only in order α s 2 and is colour-suppressed. Colour reconnection at longer time scales is quite feasible, however, and may affect the fragmentation phase. If so, the nature of non-perturbative QCD can be probed in a new way. We formulate several alternative toy models and use these to estimate the colour reconnection probability as a function of the event kinematics. Possible consequences for LEP 2 events are illustrated, with special attention to systematic errors in W mass determinations. (orig.)

Adiabatic Rearrangement of Hollow PV Towers

Directory of Open Access Journals (Sweden)

Eric A Hendricks

2010-10-01

Full Text Available Diabatic heating from deep moist convection in the hurricane eyewall produces a towering annular structure of elevated potential vorticity (PV. This structure has been referred to as a hollow PV tower. The sign reversal of the radial gradient of PV satisfies the Charney-Stern necessary condition for combined barotropic-baroclinic instability. For thin enough annular structures, small perturbations grow exponentially, extract energy from the mean flow, and lead to hollow tower breakdown, with significant vortex structural and intensity change. The three-dimensional adiabatic rearrangements of two prototypical hurricane-like hollow PV towers (one thick and one thin are examined in an idealized framework. For both hollow towers, dynamic instability causes air parcels with high PV to be mixed into the eye preferentially at lower levels, where unstable PV wave growth rates are the largest. Little or no mixing is found to occur at upper levels. The mixing at lower and middle levels is most rapid for the breakdown of the thin hollow tower, consistent with previous barotropic results. For both hollow towers, this advective rearrangement of PV affects the tropical cyclone structure and intensity in a number of ways. First, the minimum central pressure and maximum azimuthal mean velocity simultaneously decrease, consistent with previous barotropic results. Secondly, isosurfaces of absolute angular momentum preferentially shift inward at low levels, implying an adiabatic mechanism by which hurricane eyewall tilt can form. Thirdly, a PV bridge, similar to that previously found in full-physics hurricane simulations, develops as a result of mixing at the isentropic levels where unstable PV waves grow most rapidly. Finally, the balanced mass field resulting from the PV rearrangement is warmer in the eye between 900 and 700 hPa. The location of this warming is consistent with observed warm anomalies in the eye, indicating that in certain instances the hurricane

Experimental study of the rearrangements of valence protons and neutrons amongst single-particle orbits during double-β decay in 100Mo

Science.gov (United States)

Freeman, S. J.; Sharp, D. K.; McAllister, S. A.; Kay, B. P.; Deibel, C. M.; Faestermann, T.; Hertenberger, R.; Mitchell, A. J.; Schiffer, J. P.; Szwec, S. V.; Thomas, J. S.; Wirth, H.-F.

2017-11-01

The rearrangements of protons and neutrons amongst the valence single-particle orbitals during double-β decay of 100Mo have been determined by measuring cross sections in (d ,p ), (p ,d ), (3He,α ), and (3He,d ) reactions on Mo,10098 and Ru,102100 targets. The deduced nucleon occupancies reveal significant discrepancies when compared with theoretical calculations; the same calculations have previously been used to determine the nuclear matrix element associated with the decay probability of double-β decay of the 100Mo system.

A Rare De novo Complex Chromosomal Rearrangement (CCR) Involving Four Chromosomes in An Oligo-asthenosperm Infertile Man.

Science.gov (United States)

Asia, Saba; Vaziri Nasab, Hamed; Sabbaghian, Marjan; Kalantari, Hamid; Zari Moradi, Shabnam; Gourabi, Hamid; Mohseni Meybodi, Anahita

2014-01-01

Complex chromosomal rearrangements (CCRs) are rare events involving more than two chromosomes and over two breakpoints. They are usually associated with infertility or sub fertility in male carriers. Here we report a novel case of a CCR in a 30-year-old oligoasthenosperm man with a history of varicocelectomy, normal testes size and normal endocrinology profile referred for chromosome analysis to the Genetics unit of Royan Reproductive Biomedicine Research Center. Chromosomal analysis was performed using peripheral blood lymphocyte cultures and analyzed by GTG banding. Additional tests such as C-banding and multicolor fluorescence in situ hybridization (FISH) procedure for each of the involved chromosomes were performed to determine the patterns of the segregations. Y chromosome microdeletions in the azoospermia factor (AZF) region were analyzed with multiplex polymerase chain reaction. To identify the history and origin of this CCR, all the family members were analyzed. No micro deletion in Y chromosome was detected. The same de novo reciprocal exchange was also found in his monozygous twin brother. The other siblings and parents were normal. CCRs are associated with male infertility as a result of spermatogenic disruption due to complex meiotic configurations and the production of chromosomally abnormal sperms. These chromosomal rearrangements might have an influence on decreasing the number of sperms.

Hydrogen rearrangement to and from radical z fragments in electron capture dissociation of peptides

DEFF Research Database (Denmark)

Savitski, Mikhail M; Kjeldsen, Frank; Nielsen, Michael L

2007-01-01

Hydrogen rearrangement is an important process in radical chemistry. A high degree of H. rearrangement to and from z. ionic fragments (combined occurrence frequency 47% compared with that of z.) is confirmed in analysis of 15,000 tandem mass spectra of tryptic peptides obtained with electron...

Dienone-phenol Rearrangement of C-9 Oxygenated Decalinic Dienone and Analogs through B-Ring Cleavage

Institute of Scientific and Technical Information of China (English)

无

2003-01-01

Dehydrogenation of 9-hydroxy decalinic enones and analogs with DDQ resulted in a formal dienone-phenol type rearrangement via B-ring cleavage, while the corresponding dienone acetates underwent base-catalyzed formal dienone-phenol type rearrangement analogously.

Analysis of chromosome rearrangements on the basis of synaptonemal complexes in the offspring of mice exposed to γ-rays

International Nuclear Information System (INIS)

Kalikinskaya, E.I.; Bogdanov, Yu.F.; Kolomiets, O.L.; Shevchenko, V.A.

1986-01-01

Electron-microscopic analysis of synaptonemic complexes (SC), spread on the hypophase surface, was conducted to investigate chromosome rearrangements in sterile and semisterile F 1 malemause offsprings, exposed to 5 Gy γ-rays Paralelly Chromosome rearrangement account in diakinesis-metaphase 1 was conducted using light microscope, in the same animals. During SC analysis in pachytene chromosome rearrangements were found in 63% of spermatocytes. Under chromosome analysis in diakinesis-metaphase 1 in the same animals chromosome rearrangements were found only in 32% of cells. SC analysis allows one to reveal chromosome rearrangements, which can not be revealed in diakinesis-metaphase 1

Expedient synthesis of fused azepine derivatives using a sequential rhodium(II)-catalyzed cyclopropanation/1-aza-Cope rearrangement of dienyltriazoles.

Science.gov (United States)

Schultz, Erica E; Lindsay, Vincent N G; Sarpong, Richmond

2014-09-08

A general method for the formation of fused dihydroazepine derivatives from 1-sulfonyl-1,2,3-triazoles bearing a tethered diene is reported. The process involves an intramolecular cyclopropanation of an α-imino rhodium(II) carbenoid, leading to a transient 1-imino-2-vinylcyclopropane intermediate which rapidly undergoes a 1-aza-Cope rearrangement to generate fused dihydroazepine derivatives in moderate to excellent yields. The reaction proceeds with similar efficiency on gram scale. The use of catalyst-free conditions leads to the formation of a novel [4.4.0] bicyclic heterocycle. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Matrix isolation as a tool for studying interstellar chemical reactions

Science.gov (United States)

Ball, David W.; Ortman, Bryan J.; Hauge, Robert H.; Margrave, John L.

1989-01-01

Since the identification of the OH radical as an interstellar species, over 50 molecular species were identified as interstellar denizens. While identification of new species appears straightforward, an explanation for their mechanisms of formation is not. Most astronomers concede that large bodies like interstellar dust grains are necessary for adsorption of molecules and their energies of reactions, but many of the mechanistic steps are unknown and speculative. It is proposed that data from matrix isolation experiments involving the reactions of refractory materials (especially C, Si, and Fe atoms and clusters) with small molecules (mainly H2, H2O, CO, CO2) are particularly applicable to explaining mechanistic details of likely interstellar chemical reactions. In many cases, matrix isolation techniques are the sole method of studying such reactions; also in many cases, complexations and bond rearrangements yield molecules never before observed. The study of these reactions thus provides a logical basis for the mechanisms of interstellar reactions. A list of reactions is presented that would simulate interstellar chemical reactions. These reactions were studied using FTIR-matrix isolation techniques.

Refining borders of genome-rearrangements including repetitions

Directory of Open Access Journals (Sweden)

JA Arjona-Medina

2016-10-01

Full Text Available Abstract Background DNA rearrangement events have been widely studied in comparative genomic for many years. The importance of these events resides not only in the study about relatedness among different species, but also to determine the mechanisms behind evolution. Although there are many methods to identify genome-rearrangements (GR, the refinement of their borders has become a huge challenge. Until now no accepted method exists to achieve accurate fine-tuning: i.e. the notion of breakpoint (BP is still an open issue, and despite repeated regions are vital to understand evolution they are not taken into account in most of the GR detection and refinement methods. Methods and results We propose a method to refine the borders of GR including repeated regions. Instead of removing these repetitions to facilitate computation, we take advantage of them using a consensus alignment sequence of the repeated region in between two blocks. Using the concept of identity vectors for Synteny Blocks (SB and repetitions, a Finite State Machine is designed to detect transition points in the difference between such vectors. The method does not force the BP to be a region or a point but depends on the alignment transitions within the SBs and repetitions. Conclusion The accurate definition of the borders of SB and repeated genomic regions and consequently the detection of BP might help to understand the evolutionary model of species. In this manuscript we present a new proposal for such a refinement. Features of the SBs borders and BPs are different and fit with what is expected. SBs with more diversity in annotations and BPs short and richer in DNA replication and stress response, which are strongly linked with rearrangements.

Precise detection of rearrangement breakpoints in mammalian chromosomes

Directory of Open Access Journals (Sweden)

Gautier Christian

2008-06-01

Full Text Available Abstract Background Genomes undergo large structural changes that alter their organisation. The chromosomal regions affected by these rearrangements are called breakpoints, while those which have not been rearranged are called synteny blocks. We developed a method to precisely delimit rearrangement breakpoints on a genome by comparison with the genome of a related species. Contrary to current methods which search for synteny blocks and simply return what remains in the genome as breakpoints, we propose to go further and to investigate the breakpoints themselves in order to refine them. Results Given some reliable and non overlapping synteny blocks, the core of the method consists in refining the regions that are not contained in them. By aligning each breakpoint sequence against its specific orthologous sequences in the other species, we can look for weak similarities inside the breakpoint, thus extending the synteny blocks and narrowing the breakpoints. The identification of the narrowed breakpoints relies on a segmentation algorithm and is statistically assessed. Since this method requires as input synteny blocks with some properties which, though they appear natural, are not verified by current methods for detecting such blocks, we further give a formal definition and provide an algorithm to compute them. The whole method is applied to delimit breakpoints on the human genome when compared to the mouse and dog genomes. Among the 355 human-mouse and 240 human-dog breakpoints, 168 and 146 respectively span less than 50 Kb. We compared the resulting breakpoints with some publicly available ones and show that we achieve a better resolution. Furthermore, we suggest that breakpoints are rarely reduced to a point, and instead consist in often large regions that can be distinguished from the sequences around in terms of segmental duplications, similarity with related species, and transposable elements. Conclusion Our method leads to smaller

Brueckner Rearrangement Effects in $^5_\\Lambda$He and $^6_{\\Lambda\\Lambda}$He

OpenAIRE

Kohno, M.; Fujiwara, Y.; Akaishi, Y.

2003-01-01

Rearrangement effects in light hypernuclei are investigated in the framework of the Brueckner theory. We can estimate without detailed numerical calculations that the energy of the $\\alpha$-core is reduced by more than 2.5 MeV when the $\\Lambda$ adheres to $^4$He to form $^5_\\Lambda$He. Similar assessment of rearrangement contributions is essential to deduce the strength of $\\Lambda\\Lambda$ interaction from experimentally observed $\\Delta B_{\\Lambda\\Lambda}$. The recently observed experimenta...

Caryophyllene driven diversity in an one-pot rearrangement of oxidation and transanular reactions

Science.gov (United States)

Tang, Hao-Yu; Quan, Lu-Lu; Yu, Jie; Zhang, Qiang; Gao, Jin-Ming

2018-03-01

Diversity oriented synthesis starting from natural products is a newly coming strategy to build diverse skeletons to meet the demands of high throughput screening in drug development. Caryophyllene was being considered as an ideal starting point to build divers natural-like sesquiterpenes due to its rich sources and build-in reactivity. In this paper, six new natural-like products (2-7) were synthesized form the natural cryophyllene oxide via cascade oxidation and transannular reactions in a one-pot procedure. Their structures were elucidated by exhaustive spectra method including 2D NMR and X-ray diffraction. Of the products, compounds 6 and 7 possess very similar skeleton to natural products. Our findings demonstrated that one-pot cascade reactions on macrocyclic natural products is a concise strategy to create diverse natural-like skeletons.

The rearrangement process in a two-stage broadcast switching network

DEFF Research Database (Denmark)

Jacobsen, Søren B.

1988-01-01

The rearrangement process in the two-stage broadcast switching network presented by F.K. Hwang and G.W. Richards (ibid., vol.COM-33, no.10, p.1025-1035, Oct. 1985) is considered. By defining a certain function it is possible to calculate an upper bound on the number of connections to be moved...... during a rearrangement. When each inlet channel appears twice, the maximum number of connections to be moved is found. For a special class of inlet assignment patterns in the case of which each inlet channel appears three times, the maximum number of connections to be moved is also found. In the general...

Deciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement

Science.gov (United States)

Willis, Nicholas A.; Rass, Emilie; Scully, Ralph

2015-01-01

Chromosome rearrangement plays a causal role in tumorigenesis by contributing to the inactivation of tumor suppressor genes, the dysregulated expression or amplification of oncogenes and the generation of novel gene fusions. Chromosome breaks are important intermediates in this process. How, when and where these breaks arise and the specific mechanisms engaged in their repair strongly influence the resulting patterns of chromosome rearrangement. Here, we review recent progress in understanding how certain distinctive features of the cancer genome, including clustered mutagenesis, tandem segmental duplications, complex breakpoints, chromothripsis, chromoplexy and chromoanasynthesis may arise. PMID:26726318

Low frequency of large genomic rearrangements of BRCA1 and BRCA2 in western Denmark

DEFF Research Database (Denmark)

Thomassen, Mads; Gerdes, Anne-Marie; Cruger, Dorthe

2006-01-01

Germline mutations in BRCA1 and BRCA2 predispose female carriers to breast and ovarian cancer. The majority of mutations identified are small deletions or insertions or are nonsense mutations. Large genomic rearrangements in BRCA1 are found with varying frequencies in different populations......, but BRCA2 rearrangements have not been investigated thoroughly. The objective in this study was to determine the frequency of large genomic rearrangements in BRCA1 and BRCA2 in a large group of Danish families with increased risk of breast and ovarian cancer. A total of 617 families previously tested...... negative for mutations involving few bases were screened with multiplex ligation-dependent probe amplification (MLPA). Two deletions in BRCA1 were identified in three families; no large rearrangements were detected in BRCA2. The large deletions constitute 3.8% of the BRCA1 mutations identified, which...

Occupancy statistics arising from weighted particle rearrangements

International Nuclear Information System (INIS)

Huillet, Thierry

2007-01-01

The box-occupancy distributions arising from weighted rearrangements of a particle system are investigated. In the grand-canonical ensemble, they are characterized by determinantal joint probability generating functions. For doubly non-negative weight matrices, fractional occupancy statistics, generalizing Fermi-Dirac and Bose-Einstein statistics, can be defined. A spatially extended version of these balls-in-boxes problems is investigated

Thermal rearrangement of 7-methylbicyclo

Science.gov (United States)

Bender; Leber; Lirio; Smith

2000-08-25

The gas-phase thermal rearrangement of exo-7-methylbicyclo[3.2.0]hept-2-ene yields almost exclusively 5-methylnorbornene products. Inversion (i) of configuration dominates this [1,3] sigmatropic shift although some retention (r) is also observed. Because the [1,3] migration can only occur suprafacially (s) in this geometrically constrained system, the si/sr ratio of 7 observed for the migration of C7 in exo-7-methylbicyclo[3.2.0]hept-2-ene indicates that the orbital symmetry rules are somewhat permissive for the [1,3] sigmatropic migration of carbon.

Reactions of ruthenium and osmium cluster carbonyls with heteroatom-substituted and functionalized alkynes

International Nuclear Information System (INIS)

Koridze, A.A.

2000-01-01

The results of studies of the reactions of ruthenium and osmium cluster carbonyls with metal (M = Re, Mn, Fe) alkynes, silylalkynes, propargyl alcohols and their derivatives, diynes, enynes, and ferrocenylacetylene are summarized. Intramolecular rearrangements in the cluster complexes including migrations of carbonyl, hydride, and hydrocarbon ligands and the metal core reorganization are considered [ru

An Efficient Synthesis of de novo Imidates via Aza-Claisen Rearrangements of N-Allyl Ynamides

Science.gov (United States)

DeKorver, Kyle A.; North, Troy D.; Hsung, Richard P.

2010-01-01

A novel thermal 3-aza-Claisen rearrangement of N-allyl ynamides for the synthesis of α-allyl imidates is described. Also, a sequential aza-Claisen, Pd-catalyzed Overman rearrangement is described for the synthesis of azapine-2-ones. PMID:21278848

Rearrangement of crystallographic domains driven by magnetic field in ferromagnetic Ni2MnGa and antiferromagnetic CoO

International Nuclear Information System (INIS)

Terai, Tomoyuki; Yasui, Motoyoshi; Yamamoto, Masataka; Kakeshita, Tomoyuki

2009-01-01

We have investigated the rearrangement of crystallographic domains (martensite variants) in Ni 2 MnGa ferromagnetic shape memory alloy and CoO antiferromagnetic oxide by applying magnetic field up to 8.0 MA/m. From the result of optical microscope observation of Ni 2 MnGa single crystal, when a magnetic field is applied along [001] p (p represents a parent phase), the rearrangement of crystallographic domains occurs and the single domain state is obtained below T Ms = 202 K. The same rearrangement occurs but partially when a magnetic field is applied along [110] p . On the other hand, when a magnetic field is applied along [111] p , the rearrangement does not occur. In case of the CoO single crystal, when a magnetic field is applied along [001] p below T Ms = 293 K, the rearrangement occurs at 170 K ≤ T ≤ 293 K, but does not occur at T p and [111] p , the rearrangement does not occur below T Ms . In order to explain the rearrangement in the alloy and the oxide, we have evaluated the magnetic shear stress, τ mag , which is derived from the difference in magnetic energy among crystallographic domains and have compared it with the shear stress required for the twinning plane movement, τ req . As a result, we have found that the rearrangement occurs when the value of τ mag is larger than or equal to the value of τ req for the present alloy and oxide.

Genomecmp: computer software to detect genomic rearrangements using markers

Science.gov (United States)

Kulawik, Maciej; Nowak, Robert M.

2017-08-01

Detection of genomics rearrangements is a tough task, because of the size of data to be processed. As genome sequences may consist of hundreds of millions symbols, it is not only practically impossible to compare them by hand, but it is also complex problem for computer software. The way to significantly accelerate the process is to use rearrangement detection algorithm based on unique short sequences called markers. The algorithm described in this paper develops markers using base genome and find the markers positions on other genome. The algorithm has been extended by support for ambiguity symbols. Web application with graphical user interface has been created using three-layer architecture, where users could run the task simultaneously. The accuracy and efficiency of proposed solution has been studied using generated and real data.

Clinical and CT characteristics of surgically resected lung adenocarcinomas harboring ALK rearrangements or EGFR mutations

International Nuclear Information System (INIS)

Wang, Hua; Schabath, Matthew B.; Liu, Ying; Han, Ying; Li, Qi; Gillies, Robert J.; Ye, Zhaoxiang

2016-01-01

Purpose: To determine if clinical and CT characteristics of surgically resected lung adenocarcinomas can distinguish those harboring ALK rearrangements from EGFR mutations. Materials and methods: Patients who had surgical resection and histologically confirmed lung adenocarcinoma were enrolled, including 41 patients with ALK rearrangements and 66 patients with EGFR mutations. Eighteen categorical and six quantitative CT characteristics were used to evaluate the tumors. Differences in clinical and CT characteristics between the two groups were investigated. Results: Age (P = 0.003), histological subtypes (P < 0.001), pathological stage (P = 0.007), and five CT characteristics, including size (P < 0.001), GGO (P = 0.001), bubble-like lucency (P = 0.048), lymphadenopathy (P = 0.001), and tumor shadow disappearance rate (P = 0.005) were significantly different between patients harboring ALK rearrangements compared to patients with EGFR mutations. When we compared histologic components, a solid pattern was more common (P = 0.009) in tumors with ALK rearrangements, and lepidic and acinar patterns were more common (P < 0.001 and P = 0.040, respectively) in those with EGFR mutations. Backward elimination analyses revealed that age (OR = 0.93; 95% CI 0.89–0.98), GGO (OR = 0.14; 95% CI 0.03–0.67), and lymphadenopathy (OR = 4.15; 95% CI 1.49–11.60) were significantly associated with ALK rearrangement status. Conclusion: Our analyses revealed that clinical and CT characteristics of lung adenocarcinomas harboring ALK rearrangements were significantly different, compared with those with EGFR mutations. These differences may be related to the molecular pathology of these diseases.

Clinical and CT characteristics of surgically resected lung adenocarcinomas harboring ALK rearrangements or EGFR mutations

Energy Technology Data Exchange (ETDEWEB)

Wang, Hua [Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Schabath, Matthew B. [Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Liu, Ying [Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Han, Ying [Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Li, Qi [Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Gillies, Robert J. [Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Ye, Zhaoxiang, E-mail: yezhaoxiang@163.com [Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China)

2016-11-15

Purpose: To determine if clinical and CT characteristics of surgically resected lung adenocarcinomas can distinguish those harboring ALK rearrangements from EGFR mutations. Materials and methods: Patients who had surgical resection and histologically confirmed lung adenocarcinoma were enrolled, including 41 patients with ALK rearrangements and 66 patients with EGFR mutations. Eighteen categorical and six quantitative CT characteristics were used to evaluate the tumors. Differences in clinical and CT characteristics between the two groups were investigated. Results: Age (P = 0.003), histological subtypes (P < 0.001), pathological stage (P = 0.007), and five CT characteristics, including size (P < 0.001), GGO (P = 0.001), bubble-like lucency (P = 0.048), lymphadenopathy (P = 0.001), and tumor shadow disappearance rate (P = 0.005) were significantly different between patients harboring ALK rearrangements compared to patients with EGFR mutations. When we compared histologic components, a solid pattern was more common (P = 0.009) in tumors with ALK rearrangements, and lepidic and acinar patterns were more common (P < 0.001 and P = 0.040, respectively) in those with EGFR mutations. Backward elimination analyses revealed that age (OR = 0.93; 95% CI 0.89–0.98), GGO (OR = 0.14; 95% CI 0.03–0.67), and lymphadenopathy (OR = 4.15; 95% CI 1.49–11.60) were significantly associated with ALK rearrangement status. Conclusion: Our analyses revealed that clinical and CT characteristics of lung adenocarcinomas harboring ALK rearrangements were significantly different, compared with those with EGFR mutations. These differences may be related to the molecular pathology of these diseases.

Synthesis of (±)-amathaspiramide F and discovery of an unusual stereocontrolling element for the [2,3]-Stevens rearrangement.

Science.gov (United States)

Soheili, Arash; Tambar, Uttam K

2013-10-04

A formal total synthesis of (±)-amathaspiramide F through a tandem palladium-catalyzed allylic amination/[2,3]-Stevens rearrangement is reported. The unexpected diastereoselectivity of the [2,3]-Stevens rearrangement was controlled by the substitution patterns of an aromatic ring. This discovery represents a new stereocontrolling element for [2,3]-sigmatropic rearrangements in complex molecular settings.

Bootstrapping phylogenies inferred from rearrangement data

Directory of Open Access Journals (Sweden)

Lin Yu

2012-08-01

Full Text Available Abstract Background Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. Results We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Conclusions Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its

Bootstrapping phylogenies inferred from rearrangement data.

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Lin, Yu; Rajan, Vaibhav; Moret, Bernard Me

2012-08-29

Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its support values follow a similar scale and its receiver

Measurement of correlations between low-frequency vibrational modes and particle rearrangements in quasi-two-dimensional colloidal glasses.

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Chen, Ke; Manning, M L; Yunker, Peter J; Ellenbroek, Wouter G; Zhang, Zexin; Liu, Andrea J; Yodh, A G

2011-09-02

We investigate correlations between low-frequency vibrational modes and rearrangements in two-dimensional colloidal glasses composed of thermosensitive microgel particles, which readily permit variation of the sample packing fraction. At each packing fraction, the particle displacement covariance matrix is measured and used to extract the vibrational spectrum of the "shadow" colloidal glass (i.e., the particle network with the same geometry and interactions as the sample colloid but absent damping). Rearrangements are induced by successive, small reductions in the packing fraction. The experimental results suggest that low-frequency quasilocalized phonon modes in colloidal glasses, i.e., modes that present low energy barriers for system rearrangements, are spatially correlated with rearrangements in this thermal system.

REARRANGEMENT IN THE B-GENOME FROM DIPLOID PROGENITOR TO WHEAT ALLOPOLYPOLID

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Salina E.A.

2012-08-01

Full Text Available Three key periods that were accompanied by considerable rearrangements in the B genome of wheat and its progenitor can be considered. The first period covers the period from the divergence of diploid Triticum and Aegilops species from their common progenitor (2.5–6 million years ago to formation of the tetraploid T. diccocoides (about 500 thousand years ago. Significant genomic rearrangements in the diploid progenitor of the B genome, Ae. speltoides (SS genome, involved a considerable amplification of repeated DNA sequences, which led to an increase in the number of heterochromatin blocks on chromosomes relative to other diploid Aegilops and Triticum species. Our analysis has demonstrated that during this period the Spelt1 repeats intensively amplified as well as several mobile elements proliferated, in particular, the genome-specific gypsy LTR-retrotransposon Fatima and CACTA DNA-transposon Caspar. The second period in the B-genome evolution was associated with the emergence of tetraploid (BBAA genome and its subsequent evolution. The third most important event leading to the next rearrangement of the B genome took place relatively recently, 7000–9500 years ago, being associated with the emergence of hexaploid wheat with the genomic formula BBAADD. The evolution of the B/S genome involved intergenomic and intragenomic translocations and chromosome inversions. So far, five rearrangements in the B-genome chromosomes of polyploid wheats has been observed and described; the majority of them took place during the formation and evolution of tetraploid species. The mapping of the S-genome chromosomes and comparison with the B-genome chromosome maps have demonstrated that individual rearrangements pre-existed in Ae. speltoides; moreover, Ae. speltoides is polymorphic for these rearrangements.Chromosome 5B is nearly 870 Mbp (5BL = 580 Mbp and 5BS = 290 Mbp and is known to carry important genes controlling the key aspects of wheat biology, in

Symmetry Breaking in NMR Spectroscopy: The Elucidation of Hidden Molecular Rearrangement Processes

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Michael J. McGlinchey

2014-08-01

Full Text Available Variable-temperature NMR spectroscopy is probably the most convenient and sensitive technique to monitor changes in molecular structure in solution. Rearrangements that are rapid on the NMR time-scale exhibit simplified spectra, whereby non-equivalent nuclear environments yield time-averaged resonances. At lower temperatures, when the rate of exchange is sufficiently reduced, these degeneracies are split and the underlying “static” molecular symmetry, as seen by X-ray crystallography, becomes apparent. Frequently, however, such rearrangement processes are hidden, even when they become slow on the NMR time-scale, because the molecular point group remains unchanged. Judicious symmetry breaking, such as by substitution of a molecular fragment by a similar, but not identical moiety, or by the incorporation of potentially diastereotopic (chemically non-equivalent nuclei, allows the elucidation of the kinetics and energetics of such processes. Examples are chosen that include a wide range of rotations, migrations and other rearrangements in organic, inorganic and organometallic chemistry.

Highly variable rates of genome rearrangements between hemiascomycetous yeast lineages.

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2006-03-01

Full Text Available Hemiascomycete yeasts cover an evolutionary span comparable to that of the entire phylum of chordates. Since this group currently contains the largest number of complete genome sequences it presents unique opportunities to understand the evolution of genome organization in eukaryotes. We inferred rates of genome instability on all branches of a phylogenetic tree for 11 species and calculated species-specific rates of genome rearrangements. We characterized all inversion events that occurred within synteny blocks between six representatives of the different lineages. We show that the rates of macro- and microrearrangements of gene order are correlated within individual lineages but are highly variable across different lineages. The most unstable genomes correspond to the pathogenic yeasts Candida albicans and Candida glabrata. Chromosomal maps have been intensively shuffled by numerous interchromosomal rearrangements, even between species that have retained a very high physical fraction of their genomes within small synteny blocks. Despite this intensive reshuffling of gene positions, essential genes, which cluster in low recombination regions in the genome of Saccharomyces cerevisiae, tend to remain syntenic during evolution. This work reveals that the high plasticity of eukaryotic genomes results from rearrangement rates that vary between lineages but also at different evolutionary times of a given lineage.

The Wolff rearrangement in radical cations

International Nuclear Information System (INIS)

Ohashi, Mamoru; Tsujimoto, Kazuo; Shida, Yasuo; Yamada, Yasuji.

1975-01-01

The mass spectrometric behavior of 1-phenyl-4,5,6,7-tetrahydrobenzotriazole and its seven membered analog is described. The principal fragmentation process of the molecular ions is loss of nitrogen. It was concluded from the results of deuterium labeling and accurate mass measurements that the subsequent fragmentation of the M-N 2 ions proceeds via isomerization to the ring-contracted ketenimine ions by the Wolff rearrangement, in sharp contrast to the case of 1-phenylbenzotriazole. (auth.)

Secondary isotope effects on alpha-cleavage reactions

International Nuclear Information System (INIS)

Ingemann, S.; Hammerum, S.

1980-01-01

Kinetic deuterium isotope effects on mass spectral reactions have in several instances been utilized to provide structural information and to answer mechanistic questions. Typically, the influence of the deuterium label on the rate of one of a number of competing reactions has been studied. Secondary isotope effects have usually been assumed to be relatively insignificant in comparison with the observed kinetic effects, even though various workers have shown that secondary isotope effects may indeed exert a considerable influence on the rates of competing simple cleavages. Recent studies have provided quantitative data to show that the mere presence of deuterium atoms up to six bonds away may influence the rate of a simple cleavage reaction. In relation to an investigation of rearrangements accompanying simple cleavage reactions, a semi-quantitative measure was needed of the variation of the secondary isotope effect with the number of bonds between the deuterium label and the point of rupture. The influence has therefore been examined of the presence of remote deuterium atoms on a typical simple cleavage reaction, the α-cleavage of aliphatic amines. As a model compound, N-methyldipentylamine was chosen, systematically labelled with deuterium. (author)

Carbocyclization cascades of allyl ketenimines via aza-Claisen rearrangements of N-phosphoryl-N-allyl-ynamides.

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DeKorver, Kyle A; Wang, Xiao-Na; Walton, Mary C; Hsung, Richard P

2012-04-06

A series of carbocyclization cascades of allyl ketenimines initiated through a thermal aza-Claisen rearrangement of N-phosphoryl-N-allyl ynamides is described. Interceptions of the cationic intermediate via Meerwein-Wagner rearrangements and polyene-type cyclizations en route to fused bi- and tricyclic frameworks are featured.

Recurrence risk in de novo structural chromosomal rearrangements.

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Röthlisberger, Benno; Kotzot, Dieter

2007-08-01

According to the textbook of Gardner and Sutherland [2004], the standard on genetic counseling for chromosome abnormalities, the recurrence risk of de novo structural or combined structural and numeric chromosome rearrangements is less than 0.5-2% and takes into account recurrence by chance, gonadal mosaicism, and somatic-gonadal mosaicism. However, these figures are roughly estimated and neither any systematic study nor exact or evidence-based risk calculations are available. To address this question, an extensive literature search was performed and surprisingly only 29 case reports of recurrence of de novo structural or combined structural and numeric chromosomal rearrangements were found. Thirteen of them were with a trisomy 21 due to an i(21q) replacing one normal chromosome 21. In eight of them low-level mosaicism in one of the parents was found either in fibroblasts or in blood or in both. As a consequence of the low number of cases and theoretical considerations (clinical consequences, mechanisms of formation, etc.), the recurrence risk should be reduced to less than 1% for a de novo i(21q) and to even less than 0.3% for all other de novo structural or combined structural and numeric chromosomal rearrangements. As the latter is lower than the commonly accepted risk of approximately 0.3% for indicating an invasive prenatal diagnosis and as the risk of abortion of a healthy fetus after chorionic villous sampling or amniocentesis is higher than approximately 0.5%, invasive prenatal investigation in most cases is not indicated and should only be performed if explicitly asked by the parents subsequent to appropriate genetic counseling. (c) 2007 Wiley-Liss, Inc.

Sintering with a chemical reaction as applied to uranium monocarbide

International Nuclear Information System (INIS)

Accary, A.; Caillat, R.

1960-01-01

The present paper provides a survey of different investigations whose aim was the preparation and fabrication of uranium monocarbide for nuclear use. If a chemical reaction takes place in the sample during the sintering operation, it may be expected that the atom rearrangements involved in this reaction should favour the sintering process and thereby lower the temperature needed to yield a body of a given density. With this hypothesis in mind, the following methods have been studied: - Sintering of U-C mixtures; - Sintering of UO 2 -C mixtures; - Hot pressing of U-C mixtures; - Extrusion of U-C mixtures. To generalize our result, it could be said that a chemical reaction does not lead to high densification, if one depends on a simple contact between discrete particles. On the contrary, a chemical reaction can help sintering if, as our hot pressing experiments shows, the densification can be achieved prior to the reaction. (author) [fr

Intergenomic rearrangements after polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae) affected by environmental factors.

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Wang, Qiuxia; Liu, Huitao; Gao, Ainong; Yang, Xinming; Liu, Weihua; Li, Xiuquan; Li, Lihui

2012-01-01

Polyploidization is a major evolutionary process. Approximately 70-75% species of Triticeae (Poaceae) are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng) J.L.Yang et al. (2n = 6x = 42, StStPPYY), collected from different environments, were studied using genome in situ hybridization (GISH). We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15%) and Y (22.22%), in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05). The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01). Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution.

Intergenomic rearrangements after polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae affected by environmental factors.

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Qiuxia Wang

Full Text Available Polyploidization is a major evolutionary process. Approximately 70-75% species of Triticeae (Poaceae are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng J.L.Yang et al. (2n = 6x = 42, StStPPYY, collected from different environments, were studied using genome in situ hybridization (GISH. We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15% and Y (22.22%, in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05. The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01. Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution.

Antibody repertoire development in fetal and neonatal piglets. XXII. Lambda rearrangement precedes kappa rearrangement during B-cell lymphogenesis in swine

Science.gov (United States)

PCR was used to detect VDJ and VJ rearrangement, expression of RAG-1, TdT and VpreB and the presence of signal joint circles (SJC) in an effort to identify sites of B cell lymphogenesis in tissue lysates and sorted leukocytes of fetal and newborn piglets. VDJ, VlambdaJlambda but not VkappaJkappa re...

Region-Specific Involvement of Actin Rearrangement-Related Synaptic Structure Alterations in Conditioned Taste Aversion Memory

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Bi, Ai-Ling; Wang, Yue; Li, Bo-Qin; Wang, Qian-Qian; Ma, Ling; Yu, Hui; Zhao, Ling; Chen, Zhe-Yu

2010-01-01

Actin rearrangement plays an essential role in learning and memory; however, the spatial and temporal regulation of actin dynamics in different phases of associative memory has not been fully understood. Here, using the conditioned taste aversion (CTA) paradigm, we investigated the region-specific involvement of actin rearrangement-related…

Dysregulation of the DNA Damage Response and KMT2A Rearrangement in Fetal Liver Hematopoietic Cells.

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Mai Nanya

Full Text Available Etoposide, a topoisomerase 2 (TOP2 inhibitor, is associated with the development of KMT2A (MLL-rearranged infant leukemia. An epidemiological study suggested that in utero exposure to TOP2 inhibitors may be involved in generation of KMT2A (MLL rearrangement. The present study examined the mechanism underlying the development of KMT2A (MLL-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Fetal liver hematopoietic stem cells were more susceptible to etoposide than maternal bone marrow mononuclear cells. Etoposide-induced Kmt2a breakage was detected in fetal liver hematopoietic stem cells using a newly developed chromatin immunoprecipitation (ChIP assay. Assessment of etoposide-induced chromosomal translocation by next-generation RNA sequencing (RNA-seq identified several chimeric fusion messenger RNAs that were generated by etoposide treatment. However, Kmt2a (Mll-rearranged fusion mRNA was detected in Atm-knockout mice, which are defective in the DNA damage response, but not in wild-type mice. The present findings suggest that in utero exposure to TOP2 inhibitors induces Kmt2a rearrangement when the DNA damage response is defective.

Evolution of the Petasis-Ferrier union/rearrangement tactic: construction of architecturally complex natural products possessing the ubiquitous cis-2,6-substituted tetrahydropyran structural element.

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Smith, Amos B; Fox, Richard J; Razler, Thomas M

2008-05-01

The frequent low abundance of architecturally complex natural products possessing significant bioregulatory properties mandates the development of rapid, efficient, and stereocontrolled synthetic tactics, not only to provide access to the biologically rare target but also to enable elaboration of analogues for the development of new therapeutic agents with improved activities and/or pharmacokinetic properties. In this Account, the genesis and evolution of the Petasis-Ferrier union/rearrangement tactic, in the context of natural product total syntheses, is described. The reaction sequence comprises a powerful tactic for the construction of the 2,6- cis-substituted tetrahydropyran ring system, a ubiquitous structural element often found in complex natural products possessing significant bioactivities. The three-step sequence, developed in our laboratory, extends two independent methods introduced by Ferrier and Petasis and now comprises: condensation between a chiral, nonracemic beta-hydroxy acid and an aldehyde to furnish a dioxanone; carbonyl olefination; and Lewis-acid-induced rearrangement of the resultant enol acetal to generate the 2,6- cis-substituted tetrahydropyranone system in a highly stereocontrolled fashion. To demonstrate the envisioned versatility and robustness of the Petasis-Ferrier union/rearrangement tactic in complex molecule synthesis, we exploited the method as the cornerstone in our now successful total syntheses of (+)-phorboxazole A, (+)-zampanolide, (+)-dactylolide, (+)-spongistatins 1 and 2, (-)-kendomycin, (-)-clavosolide A, and most recently, (-)-okilactomycin. Although each target comprises a number of synthetic challenges, this Account focuses on the motivation, excitement, and frustrations associated with the evolution and implementation of the Petasis-Ferrier union/rearrangement tactic. For example, during our (+)-phorboxazole A endeavor, we recognized and exploited the inherent pseudo symmetry of the 2,6- cis

Computational investigation of rearrangements in huisgen cycloadducts of azolium N-dicyanomethanide 1,3-dipoles with alkynes: a mechanistic panoply.

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Burke, Luke A; Butler, Richard N

2009-08-07

The reaction surfaces leading to rearrangements and ring expansions of azapentalene cycloadducts of imidazolo- and triazolodicyanomethanide 1,3-dipoles with alkynes are studied with the B3LYP DFT method using the 6-31G(d) and 6-311+G(2d,p) basis sets. The surprisingly complex surface involves (1) consecutive but not combined pericyclic steps, a coarctate TS, and pseudopericyclic mechanisms, (2) anchimerically assisted H-atom transfer competing effectively with concerted symmetry-allowed sigmatropic steps, and (3) azolium methanide zwitterions and ketenimines as key intermediates. The azolium methanide is identified as the intermediate detected previously in a variable-temperature NMR experiment that converted the unstable cycloadduct to product imine.

Zinc Finger Nuclease induced DNA double stranded breaks and rearrangements in MLL

International Nuclear Information System (INIS)

Do, To Uyen; Ho, Bay; Shih, Shyh-Jen; Vaughan, Andrew

2012-01-01

Highlights: ► A Zinc Finger Nuclease (ZFN) targeting a leukemogenic hot spot for rearrangement in MLL is created. ► The novel ZFN efficiently cleaves MLL exon 13. ► Despite MLL cleavage and evidence of mis-repair, no leukemogenic translocations were produced. ► MLL cleavage alone is insufficient to generate leukemogenic translocations. - Abstract: Radiation treatment or chemotherapy has been linked with a higher risk of secondary cancers such as therapy related Acute Myeloid Leukemia (tAML). Several of these cancers have been shown to be correlated to the introduction of double stranded breaks (DSB) and rearrangements within the Mixed Lineage Leukemia (MLL) gene. We used Zinc Finger Nucleases (ZFNs) to introduce precise cuts within MLL to examine how a single DNA DSB might lead to chromosomal rearrangements. A ZFN targeting exon 13 within the Breakpoint Cluster Region of MLL was transiently expressed in a human lymphoblast cell line originating from a CML patient. Although FISH analysis showed ZFN DSB at this region increased the rate of MLL fragmentation, we were unable to detect leukemogenic rearrangements or translocations via inverse PCR. Interestingly, gene fragmentation as well as small interstitial deletions, insertions and base substitutions increased with the inhibition of DNA-PK, suggesting repair of this particular DSB is linked to non-homologous end joining (NHEJ). Although mis-repair of DSBs may be necessary for the initiation of leukemogenic translocations, a MLL targeted DNA break alone is insufficient

Radiation-induced genomic instability driven by de novo chromosomal rearrangement hot spots

International Nuclear Information System (INIS)

Grosovsky, A.J.; Allen, R.N.; Moore, S.R.

2003-01-01

Genomic instability has become generally recognized as a critical contributor to tumor progression by generating the necessary number of genetic alterations required for expression of a clinically significant malignancy. Our study of chromosomal instability investigates the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in instability acting predominantly in cis. Here we present an analysis of the karyotypic distribution of instability associated chromosomal rearrangements in TK6 and derivative human lymphoblasts. Karyotypic analysis performed on a total of 455 independent clones included 183 rearrangements distributed among 100 separate unstable clones. The results demonstrate that the breakpoints of chromosomal rearrangements in unstable clones are non-randomly distributed throughout the genome. This pattern is statistically significant, and incompatible with expectations for random breakage associated with loss or alteration of a trans-acting factor. Furthermore, specific chromosomal breakage hot spots associated with instability have been identified; these occur in several independent unstable clones and are often repeatedly broken and rejoined during the outgrowth of an individual clone. In complimentary studies, genomic instability was generated without any exposure to a DNA-damaging agent, but rather by transfection with alpha heterochromatin DNA. In a prospective analysis, human-hamster hybrid AL cells containing a single human chromosome 11 were transfected with heterochromatic alpha DNA repeats and clones were analyzed by chromosome 11 painting. Transfection with alpha DNA was associated with karyotypic heterogeneity in 40% of clones examined; control transfections with plasmid alone did not lead to karyotypic heterogeneity

Zinc Finger Nuclease induced DNA double stranded breaks and rearrangements in MLL

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Do, To Uyen [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Ho, Bay; Shih, Shyh-Jen [Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Vaughan, Andrew, E-mail: Andrew.vaughan@ucdmc.ucdavis.edu [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States)

2012-12-15

Highlights: ► A Zinc Finger Nuclease (ZFN) targeting a leukemogenic hot spot for rearrangement in MLL is created. ► The novel ZFN efficiently cleaves MLL exon 13. ► Despite MLL cleavage and evidence of mis-repair, no leukemogenic translocations were produced. ► MLL cleavage alone is insufficient to generate leukemogenic translocations. - Abstract: Radiation treatment or chemotherapy has been linked with a higher risk of secondary cancers such as therapy related Acute Myeloid Leukemia (tAML). Several of these cancers have been shown to be correlated to the introduction of double stranded breaks (DSB) and rearrangements within the Mixed Lineage Leukemia (MLL) gene. We used Zinc Finger Nucleases (ZFNs) to introduce precise cuts within MLL to examine how a single DNA DSB might lead to chromosomal rearrangements. A ZFN targeting exon 13 within the Breakpoint Cluster Region of MLL was transiently expressed in a human lymphoblast cell line originating from a CML patient. Although FISH analysis showed ZFN DSB at this region increased the rate of MLL fragmentation, we were unable to detect leukemogenic rearrangements or translocations via inverse PCR. Interestingly, gene fragmentation as well as small interstitial deletions, insertions and base substitutions increased with the inhibition of DNA-PK, suggesting repair of this particular DSB is linked to non-homologous end joining (NHEJ). Although mis-repair of DSBs may be necessary for the initiation of leukemogenic translocations, a MLL targeted DNA break alone is insufficient.

Structural rearrangements of chromosomes in the domestic chicken: experimental production by X-irradiation of spermatozoa

International Nuclear Information System (INIS)

Wooster, W.E.; Fechheimer, N.S.; Jaap, R.G.

1977-01-01

In order to produce chicks heterozygous for structural aberrations of chromosomes, 67 hens were inseminated with semen that had been exposed to 1200 R of X-rays. A sample of 204 chicks was hatched and survived. Among these, 18 (8.9%) contained rearrangements comprising 19 translocations and one pericentric inversion. All 10 males and eight females heterozygous for rearrangements were fertile and transmitted these rearrangements to approximately half their hatched progeny. Each of the major chromosomes of the chicken karyotype, except number 6, was involved in one or more of the translocations. The pericentric inversion was of a segment of chromosome number 2. (author)

Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

International Nuclear Information System (INIS)

Ritchie, K.A.

1986-01-01

Transgenic mice were produced by microinjection of the functionally rearranged immunoglobulin kappa gene from the myeloma MOPC-21 into the male pronucleus of fertilized mouse eggs, and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were detected by hybridizing tail DNA dots with radioactively labelled pBR322 plasmid DNA, which detects pBR322 sequences left as a tag on the microinjected DNA. Mice that integrated the injected gene (six males) were mated and the DNA, RNA and serum kappa chains of their offspring were analyzed. A rabbit anti-mouse kappa chain antiserum was also produced for use in detection of mouse kappa chains on protein blots. Hybridomas were produced from the spleen cells of these kappa transgenic mice to immortalize representative B cells and to investigate expression of the transgenic kappa gene, its effect on allelic exclusion, and its effect on the control of light chain gene rearrangement and expression. The results show that the microinjected DNA is integrated as concatamers in unique single or, rarely, two separate sites in the genome. The concatamers are composed of several copies (16 to 64) of injected DNA arranged in a head to tail fashion. The transgene is expressed into protein normally and in a tissue specific fashion. For the first time in these transgenic mice, all tissues contain a functionally rearranged and potentially expressible immunoglobulin gene. The transgene is expressed only in B cells and not in hepatocytes, for example. This indicates that rearrangement of immunoglobulin genes is necessary but not sufficient for the tissue specific expression of these genes by B cells

Semiclassical asymptotic behavior and the rearrangement mechanisms for Coulomb particles

International Nuclear Information System (INIS)

Bogdanov, A.V.; Gevorkyan, A.S.; Dubrovskii, G.V.

1986-01-01

The semiclassical asymptotic behavior of the eikonal amplitude of the resonance rearrangement in a system of three Coulomb particles is studied. It is shown that the general formula for the amplitude correctly describes two classical mechanisms (pickup and knockout) and one nonclassical mechanism (stripping). The classical mechanisms predominate at high energies, while the stripping mechanism predominates at lower energies. In the region of medium energies the dominant mechanism is the pickup (or Thomas) mechanism, which is realized by nonclassical means. For such transitions the classical cross section diverges, and the amplitude must be computed on a complex trajectory. The physical reasons for introducing the approximate complex trajectories are discussed. The contributions of all the mechanisms to the rearrangement cross section are found in their analytic forms

Incremental exposure facilitates adaptation to sensory rearrangement. [vestibular stimulation patterns

Science.gov (United States)

Lackner, J. R.; Lobovits, D. N.

1978-01-01

Visual-target pointing experiments were performed on 24 adult volunteers in order to compare the relative effectiveness of incremental (stepwise) and single-step exposure conditions on adaptation to visual rearrangement. The differences between the preexposure and postexposure scores served as an index of the adaptation elicited during the exposure period. It is found that both single-step and stepwise exposure to visual rearrangement elicit compensatory changes in sensorimotor coordination. However, stepwise exposure, when compared to single-step exposur in terms of the average magnitude of visual displacement over the exposure period, clearly enhances the rate of adaptation. It seems possible that the enhancement of adaptation to unusual patterns of sensory stimulation produced by incremental exposure reflects a general principle of sensorimotor function.

Screening for subtle chromosomal rearrangements in an Egyptian ...

African Journals Online (AJOL)

A descriptive study was carried out to screen for subtle chromosomal rearrangements in a group of Egyptian children with idiopathic mental retardation (IMR) to estimate its frequency if detected. The study enrolled 30 patients with IMR, with the perquisite criteria of being <18 years at referral, their IQ <70, and manifesting at ...

The requirement for pre-TCR during thymic differentiation enforces a developmental pause that is essential for V-DJβ rearrangement.

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Karen S Hathcock

Full Text Available T cell development occurs in the thymus and is critically dependent on productive TCRβ rearrangement and pre-TCR expression in DN3 cells. The requirement for pre-TCR expression results in the arrest of thymocytes at the DN3 stage (β checkpoint, which is uniquely permissive for V-DJβ recombination; only cells expressing pre-TCR survive and develop beyond the DN3 stage. In addition, the requirement for TCRβ rearrangement and pre-TCR expression enforces suppression of TCRβ rearrangement on a second allele, allelic exclusion, thus ensuring that each T cell expresses only a single TCRβ product. However, it is not known whether pre-TCR expression is essential for allelic exclusion or alternatively if allelic exclusion is enforced by developmental changes that can occur in the absence of pre-TCR. We asked if thymocytes that were differentiated without pre-TCR expression, and therefore without pause at the β checkpoint, would suppress all V-DJβ rearrangement. We previously reported that premature CD28 signaling in murine CD4(-CD8(- (DN thymocytes supports differentiation of CD4(+CD8(+ (DP cells in the absence of pre-TCR expression. The present study uses this model to define requirements for TCRβ rearrangement and allelic exclusion. We demonstrate that if cells exit the DN3 developmental stage before TCRβ rearrangement occurs, V-DJβ rearrangement never occurs, even in DP cells that are permissive for D-Jβ and TCRα rearrangement. These results demonstrate that pre-TCR expression is not essential for thymic differentiation to DP cells or for V-DJβ suppression. However, the requirement for pre-TCR signals and the exclusion of alternative stimuli such as CD28 enforce a developmental "pause" in early DN3 cells that is essential for productive TCRβ rearrangement to occur.

Theoretic investigation into polytopic rearrangements mechanism of molecules of sulfurans and their analogs

International Nuclear Information System (INIS)

Minkin, V.I.; Minyaev, R.M.

1975-01-01

The energy characteristics and electron distributions were calculated for the fundamental and transitional states in topomerization of configuration of sulfo-, selenium and tellurium-uranium compounds of the AX 4 type. Also mapping of the potential energies was made for the predominant topomerization mechanisms. The mechanisms were classified into rearrangement types according to exchange-responsible apical and equatorial ligands. The physical mechanisms of the topomerization were determined on the basis of symmetry requirements for transitional configuration with respect to non-interchanging ligands. The lowest activation barrier was characteristic for the Berry mechanism of pseudorotation; however, other mechanism (the lever and pyramidal type) can compete with the Berry mechanisms. The expanded method of Hukkel does not give correct values for the relative energy of the fundamental and transitional configurations for sulfouranium molecules and their analogs for two of the three exchange mechanisms examined. Tunnel ligand-exchange mechanism cannot compete with the kinetic path of psudorotation reaction even at very low temperatures

Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

Energy Technology Data Exchange (ETDEWEB)

Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston MA, 02215 (United States); Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States); Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States)

2017-03-15

Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

International Nuclear Information System (INIS)

Nishino, Mizuki; Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra; Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto; Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin

2017-01-01

Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

[Genome Rearrangements in Azospirillum brasilense Sp7 with the Involvement of the Plasmid pRhico and the Prophage phiAb-Cd].

Science.gov (United States)

Katsy, E I; Petrova, L P

2015-12-01

Alphaproteobacteria of the species Azospirillum brasilense have a multicomponent genome that undergoes frequent spontaneous rearrangements, yielding changes in the plasmid profiles of strains. Specifically, variants (Cd, Sp7.K2, Sp7.1, Sp7.4, Sp7.8, etc.) of the type strainA. brasilense Sp7 that had lost a 115-MDa plasmid were previously selected. In many of them, the molecular weight of a 90-MDa plasmid (p90 or pRhico), which is a kind of "depot" for glycopolymer biosynthesis genes, increased. In this study, a collection of primers was designed to the plasmid pRhico and to the DNA of prophage phiAb-Cd integrated in it. The use ofthese primers in polymerase chain reactions allowed the detection of the probable excision of phiAb-Cd phage from the DNA of A. brasilense variants Sp7.4 and Sp7.8 and other alterations of the pRhico structure in A. brasilense strains Cd, Sp7.K2, and Sp7.8. The developed primers and PCR conditions may be recoin mended for primary analysis of spontaneous plasmid rearrangements in A. brasilense Sp7 and related strains.

Transposon domestication versus mutualism in ciliate genome rearrangements.

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Alexander Vogt

Full Text Available Ciliated protists rearrange their genomes dramatically during nuclear development via chromosome fragmentation and DNA deletion to produce a trimmer and highly reorganized somatic genome. The deleted portion of the genome includes potentially active transposons or transposon-like sequences that reside in the germline. Three independent studies recently showed that transposase proteins of the DDE/DDD superfamily are indispensible for DNA processing in three distantly related ciliates. In the spirotrich Oxytricha trifallax, high copy-number germline-limited transposons mediate their own excision from the somatic genome but also contribute to programmed genome rearrangement through a remarkable transposon mutualism with the host. By contrast, the genomes of two oligohymenophorean ciliates, Tetrahymena thermophila and Paramecium tetraurelia, encode homologous PiggyBac-like transposases as single-copy genes in both their germline and somatic genomes. These domesticated transposases are essential for deletion of thousands of different internal sequences in these species. This review contrasts the events underlying somatic genome reduction in three different ciliates and considers their evolutionary origins and the relationships among their distinct mechanisms for genome remodeling.

Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.

Science.gov (United States)

Demaerel, Wolfram; Hestand, Matthew S; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Morrow, Bernice E; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R

2017-10-05

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders. Copyright © 2017. Published by Elsevier Inc.

Vibronic coupling in ionized organic molecules: structural distortions and chemical reactions

International Nuclear Information System (INIS)

Williams, Ffrancon

2003-01-01

Ionized organic molecules (radical cations) in radiation chemistry are liable to undergo vibronic coupling whenever there is a relatively small energy gap (∼0.5-1.5 eV) between their ground and excited states. As a result of this mixing, the force constant for the symmetry-allowed vibrational mode that couples these states is lowered in the ground state of the radical cation so that deformation can take place more easily along this specific mode. This pseudo-Jahn-Teller effect can then result in a permanent structural distortion of the radical cation relative to the symmetry of the parent neutral molecule. It can also bring about an energetically favored pathway for a facile chemical rearrangement along a reaction coordinate defined by the coupling mode. Examples taken from matrix-isolation studies are used to illustrate these dramatic consequences of vibronic coupling in radical cations. Thus, the bicyclo[2.2.2]oct-2-ene and tetramethylurea radical cations are found to have twisted structures departing from the C 2v symmetry of their parent molecules, while the oxirane and bicyclo[1.1.1]pentane radical cations undergo ring-opening rearrangements along reaction coordinates that correspond to the deformational modes predicted by the pseudo-Jahn-Teller effect

Unexpected rearrangements in the synthesis of an unsymmetrical tridentate dianionic N-heterocyclic carbene

KAUST Repository

Despagnet-Ayoub, Emmanuelle; Miqueu, Karinne; Sotiropoulos, Jean-Marc; Henling, Lawrence M.; Day, Michael W.; Labinger, Jay A.; Bercaw, John E.

2013-01-01

Starting from the same ethylenediamine species, three valuable carbene precursors were synthesized under differing conditions: a tridentate dianionic N-heterocyclic carbene bearing an aniline, a phenol and a central dihydroimidazolium salt, its benzimidazolium isomer by intramolecular rearrangement and a dicationic benzimidazolium-benzoxazolium salt by changing the Brønsted acid from HCl to HBF4. A DFT study was performed to understand the rearrangement pathway. The structure of a bis[(NCO)carbene] zirconium complex was determined. © 2013 The Royal Society of Chemistry.

The Globular State of the Single-Stranded RNA: Effect of the Secondary Structure Rearrangements

Science.gov (United States)

Grigoryan, Zareh A.; Karapetian, Armen T.

2015-01-01

The mutual influence of the slow rearrangements of secondary structure and fast collapse of the long single-stranded RNA (ssRNA) in approximation of coarse-grained model is studied with analytic calculations. It is assumed that the characteristic time of the secondary structure rearrangement is much longer than that for the formation of the tertiary structure. A nonequilibrium phase transition of the 2nd order has been observed. PMID:26345143

The Globular State of the Single-Stranded RNA: Effect of the Secondary Structure Rearrangements

Directory of Open Access Journals (Sweden)

Zareh A. Grigoryan

2015-01-01

Full Text Available The mutual influence of the slow rearrangements of secondary structure and fast collapse of the long single-stranded RNA (ssRNA in approximation of coarse-grained model is studied with analytic calculations. It is assumed that the characteristic time of the secondary structure rearrangement is much longer than that for the formation of the tertiary structure. A nonequilibrium phase transition of the 2nd order has been observed.

Genome-wide signatures of 'rearrangement hotspots' within segmental duplications in humans.

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Mohammed Uddin

Full Text Available The primary objective of this study was to create a genome-wide high resolution map (i.e., >100 bp of 'rearrangement hotspots' which can facilitate the identification of regions capable of mediating de novo deletions or duplications in humans. A hierarchical method was employed to fragment segmental duplications (SDs into multiple smaller SD units. Combining an end space free pairwise alignment algorithm with a 'seed and extend' approach, we have exhaustively searched 409 million alignments to detect complex structural rearrangements within the reference-guided assembly of the NA18507 human genome (18× coverage, including the previously identified novel 4.8 Mb sequence from de novo assembly within this genome. We have identified 1,963 rearrangement hotspots within SDs which encompass 166 genes and display an enrichment of duplicated gene nucleotide variants (DNVs. These regions are correlated with increased non-allelic homologous recombination (NAHR event frequency which presumably represents the origin of copy number variations (CNVs and pathogenic duplications/deletions. Analysis revealed that 20% of the detected hotspots are clustered within the proximal and distal SD breakpoints flanked by the pathogenic deletions/duplications that have been mapped for 24 NAHR-mediated genomic disorders. FISH Validation of selected complex regions revealed 94% concordance with in silico localization of the highly homologous derivatives. Other results from this study indicate that intra-chromosomal recombination is enhanced in genic compared with agenic duplicated regions, and that gene desert regions comprising SDs may represent reservoirs for creation of novel genes. The generation of genome-wide signatures of 'rearrangement hotspots', which likely serve as templates for NAHR, may provide a powerful approach towards understanding the underlying mutational mechanism(s for development of constitutional and acquired diseases.

The Trojan Horse method for nuclear astrophysics: Recent results for direct reactions

International Nuclear Information System (INIS)

Tumino, A.; Gulino, M.; Spitaleri, C.; Cherubini, S.; Romano, S.; Cognata, M. La; Pizzone, R. G.; Rapisarda, G. G.; Lamia, L.

2014-01-01

The Trojan Horse method is a powerful indirect technique to determine the astrophysical factor for binary rearrangement processes A+x→b+B at astrophysical energies by measuring the cross section for the Trojan Horse (TH) reaction A+a→B+b+s in quasi free kinematics. The Trojan Horse Method has been successfully applied to many reactions of astrophysical interest, both direct and resonant. In this paper, we will focus on direct sub-processes. The theory of the THM for direct binary reactions will be shortly presented based on a few-body approach that takes into account the off-energy-shell effects and initial and final state interactions. Examples of recent results will be presented to demonstrate how THM works experimentally

The Trojan Horse method for nuclear astrophysics: Recent results for direct reactions

Energy Technology Data Exchange (ETDEWEB)

Tumino, A.; Gulino, M. [Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare, Catania, Italy and Università degli Studi di Enna Kore, Enna (Italy); Spitaleri, C.; Cherubini, S.; Romano, S. [Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare, Catania, Italy and Dipartimento di Fisica e Astronomia, Università di Catania, Catania (Italy); Cognata, M. La; Pizzone, R. G.; Rapisarda, G. G. [Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare, Catania (Italy); Lamia, L. [Dipartimento di Fisica e Astronomia, Università di Catania, Catania (Italy)

2014-05-09

The Trojan Horse method is a powerful indirect technique to determine the astrophysical factor for binary rearrangement processes A+x→b+B at astrophysical energies by measuring the cross section for the Trojan Horse (TH) reaction A+a→B+b+s in quasi free kinematics. The Trojan Horse Method has been successfully applied to many reactions of astrophysical interest, both direct and resonant. In this paper, we will focus on direct sub-processes. The theory of the THM for direct binary reactions will be shortly presented based on a few-body approach that takes into account the off-energy-shell effects and initial and final state interactions. Examples of recent results will be presented to demonstrate how THM works experimentally.

Exceptional Complex Chromosomal Rearrangements in Three Generations

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Hannie Kartapradja

2015-01-01

Full Text Available We report an exceptional complex chromosomal rearrangement (CCR found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband’s mother, which was confirmed using the whole chromosome painting (WCP FISH. High resolution whole genome microarray analysis of DNA from the proband’s mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother’s and grandmother’s CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations.

NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

Science.gov (United States)

Sugita, Shintaro; Arai, Yasuhito; Aoyama, Tomoyuki; Asanuma, Hiroko; Mukai, Wakako; Hama, Natsuko; Emori, Makoto; Shibata, Tatsuhiro; Hasegawa, Tadashi

2017-07-01

CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion. Copyright © 2017. Published by Elsevier Inc.

Free energy landscape and cooperatively rearranging region in a hard sphere glass

Science.gov (United States)

Yoshidome, Takashi; Yoshimori, Akira; Odagaki, Takashi

2007-08-01

Exploiting the density functional theory, we calculate the free energy landscape (FEL) of the hard sphere glass in three dimensions. From the FEL, we estimate the number of the particles in the cooperatively rearranging region (CRR). We find that the density dependence of the number of the particles in the CRR is expressed as a power law function of the density. Analyzing the relaxation process in the CRR, we also find that the string motion is the elementary process for the structural relaxation, which leads to the natural definition of the simultaneously rearranging region as the particles displaced in the string motion.

Conversion and non-conversion approach to preimplantation diagnosis for chromosomal rearrangements in 475 cycles.

Science.gov (United States)

Kuliev, Anver; Janzen, Jeanine Cieslak; Zlatopolsky, Zev; Kirillova, Irina; Ilkevitch, Yury; Verlinsky, Yury

2010-07-01

Due to the limitations of preimplantation genetic diagnosis (PGD) for chromosomal rearrangements by interphase fluorescent in-situ hybridization (FISH) analysis, a method for obtaining chromosomes from single blastomeres was introduced by their fusion with enucleated or intact mouse zygotes, followed by FISH analysis of the resulting heterokaryons. Although this allowed a significant improvement in the accuracy of testing of both maternally and paternally derived translocations, it is still labour intensive and requires the availability of fertilized mouse oocytes, also creating ethical issues related to the formation of interspecies heterokaryons. This method was modified with a chemical conversion procedure that has now been clinically applied for the first time on 877 embryos from PGD cycles for chromosomal rearrangements and has become the method of choice for performing PGD for structural rearrangements. This is presented within the context of overall experience of 475 PGD cycles for translocations with pre-selection and transfer of balanced or normal embryos in 342 (72%) of these cycles, which resulted in 131 clinical pregnancies (38%), with healthy deliveries of 113 unaffected children. The spontaneous abortion rate in these cycles was as low as 17%, which confirms an almost five-fold reduction of spontaneous abortion rate following PGD for chromosomal rearrangements. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Imaging Molecular Motion: Femtosecond X-Ray Scattering of an Electrocyclic Chemical Reaction

Science.gov (United States)

Minitti, M. P.; Budarz, J. M.; Kirrander, A.; Robinson, J. S.; Ratner, D.; Lane, T. J.; Zhu, D.; Glownia, J. M.; Kozina, M.; Lemke, H. T.; Sikorski, M.; Feng, Y.; Nelson, S.; Saita, K.; Stankus, B.; Northey, T.; Hastings, J. B.; Weber, P. M.

2015-06-01

Structural rearrangements within single molecules occur on ultrafast time scales. Many aspects of molecular dynamics, such as the energy flow through excited states, have been studied using spectroscopic techniques, yet the goal to watch molecules evolve their geometrical structure in real time remains challenging. By mapping nuclear motions using femtosecond x-ray pulses, we have created real-space representations of the evolving dynamics during a well-known chemical reaction and show a series of time-sorted structural snapshots produced by ultrafast time-resolved hard x-ray scattering. A computational analysis optimally matches the series of scattering patterns produced by the x rays to a multitude of potential reaction paths. In so doing, we have made a critical step toward the goal of viewing chemical reactions on femtosecond time scales, opening a new direction in studies of ultrafast chemical reactions in the gas phase.

Structural evolution and reaction mechanism of lithium nickelate (LiNiO2 during the carbonation reaction

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Daniela González-Varela

2018-03-01

Full Text Available Lithium nickelate (LiNiO2 was synthesized using the lithium excess method, and then characterized by X-ray diffraction, scanning electron microscopy and N2 adsorption-desorption. Finally, differential thermal and thermogravimetric analyses were performed in CO2 presence, at high temperatures. Results show that LiNiO2 is able to react with CO2 through a complex structural evolution process, where lithium atoms are released to produce Li2CO3, while some nickel atoms are rearranged on different Li1-xNi1+xO2 crystalline phases. LiNiO2-CO2 reaction kinetic parameters were determined assuming a first-order reaction, where kinetic constants tended to increase as a function of temperature. However, kinetic constant values did not follow a linear trend. This atypical behavior was attributed to LiNiO2 sintering and crystalline evolution performed as a function of temperature.

Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

DEFF Research Database (Denmark)

Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders

2009-01-01

BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovaria...

Preimplantation genetic diagnosis for chromosomal rearrangements with the use of array comparative genomic hybridization at the blastocyst stage.

Science.gov (United States)

Christodoulou, Christodoulos; Dheedene, Annelies; Heindryckx, Björn; van Nieuwerburgh, Filip; Deforce, Dieter; De Sutter, Petra; Menten, Björn; Van den Abbeel, Etienne

2017-01-01

To establish the value of array comparative genomic hybridization (CGH) for preimplantation genetic diagnosis (PGD) in embryos of translocation carriers in combination with vitrification and frozen embryo transfer in nonstimulated cycles. Retrospective data analysis study. Academic centers for reproductive medicine and genetics. Thirty-four couples undergoing PGD for chromosomal rearrangements from October 2013 to December 2015. Trophectoderm biopsy at day 5 or day 6 of embryo development and subsequently whole genome amplification and array CGH were performed. This approach revealed a high occurrence of aneuploidies and structural rearrangements unrelated to the parental rearrangement. Nevertheless, we observed a benefit in pregnancy rates of these couples. We detected chromosomal abnormalities in 133/207 embryos (64.2% of successfully amplified), and 74 showed a normal microarray profile (35.7%). In 48 of the 133 abnormal embryos (36.1%), an unbalanced rearrangement originating from the parental translocation was identified. Interestingly, 34.6% of the abnormal embryos (46/133) harbored chromosome rearrangements that were not directly linked to the parental translocation in question. We also detected a combination of unbalanced parental-derived rearrangements and aneuploidies in 27 of the 133 abnormal embryos (20.3%). The use of trophectoderm biopsy at the blastocyst stage is less detrimental to the survival of the embryo and leads to a more reliable estimate of the genomic content of the embryo than cleavage-stage biopsy. In this small cohort PGD study, we describe the successful implementation of array CGH analysis of blastocysts in patients with a chromosomal rearrangement to identify euploid embryos for transfer. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Aberrant immunoglobulin and c-myc gene rearrangements in patients with nonmalignant monoclonal cryoglobulinemia

International Nuclear Information System (INIS)

Perl, A.; Wang, N.; Williams, J.M.; Hunt, M.J.; Rosenfeld, S.I.; Condemi, J.J.; Packman, C.H.; Abraham, G.N.

1987-01-01

The status of the immunoglobulin (Ig) genes was investigated in patients with idiopathic nonmalignant monoclonal IgG cryoglobulinemia (NCG). In NCG, monoclonal antibodies are synthesized at an accelerated rate by nonmalignant B lymphocytes. In order to determine whether this high production rate is related to a clonal B cell expansion, the rearrangement of the Ig genes was investigated by Southern blot analysis of genomic, 32 P-labelled, DNA extracted from the peripheral blood lymphocytes of four NCG patients. In three of four (VI, BR, and CH) clonal expansion of B cells was detected using probes specific for the genes. BamHI digestion of DNA from VI and BR produced three rearranged fragments which cohybridized with two of the probes. This finding suggested the presence of additional nonsecretory B cell clones and/or disruption of the gene segments spanned by and detected with the probes. In addition, the possibility of aberrant gene rearrangements was supported by noting the alteration of the c-myc gene locus in genomic DNA from peripheral blood leukocytes of VI and CH. Northern blot analysis of RNA isolated from peripheral blood B cells of VI and CH demonstrated aberrant transcripts of the c-myc gene, showing an active role of the altered c-myc locus. Detection of c-myc rearrangement in NCG patients clearly shows that this event may not be a final step in malignant B cell transformation

Simple and Rapid In Vivo Generation of Chromosomal Rearrangements using CRISPR/Cas9 Technology

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Rafael B. Blasco

2014-11-01

Full Text Available Generation of genetically engineered mouse models (GEMMs for chromosomal translocations in the endogenous loci by a knockin strategy is lengthy and costly. The CRISPR/Cas9 system provides an innovative and flexible approach for genome engineering of genomic loci in vitro and in vivo. Here, we report the use of the CRISPR/Cas9 system for engineering a specific chromosomal translocation in adult mice in vivo. We designed CRISPR/Cas9 lentiviral vectors to induce cleavage of the murine endogenous Eml4 and Alk loci in order to generate the Eml4-Alk gene rearrangement recurrently found in non-small-cell lung cancers (NSCLCs. Intratracheal or intrapulmonary inoculation of lentiviruses induced Eml4-Alk gene rearrangement in lung cells in vivo. Genomic and mRNA sequencing confirmed the genome editing and the production of the Eml4-Alk fusion transcript. All mice developed Eml4-Alk-rearranged lung tumors 2 months after the inoculation, demonstrating that the CRISPR/Cas9 system is a feasible and simple method for the generation of chromosomal rearrangements in vivo.

Micellar dipolar rearrangement is sensitive to hydrophobic chain length: Implication for structural switchover of piroxicam.

Science.gov (United States)

Sethy, Dasaratha; Chakraborty, Hirak

2016-10-01

The interfacial properties of the membrane are exceptionally vital in drug-membrane interaction. They not only select out a particular prototropic form of the drug molecule for incorporation, but are also potent enough to induce structural switchover of these drugs in several cases. In this work, we quantitatively monitored the change in dipolar rearrangement of the micellar interface (as a simplified membrane mimic) by measuring the dielectric constant and dipole potential with the micellization of SDS at pH 3.6. The dielectric constant and dipole potential were measured utilizing the fluorescence of polarity sensitive probe, pyrene and potential-sensitive probe, di-8-ANEPPS, respectively. Our study demonstrates that the change in dipolar rearrangement directly influences the switchover equilibrium between the anionic and neutral from of piroxicam. We have further extended our work to evaluate the effect of hydrophobic chain length of the surfactants on the dipolar rearrangement and its effect on the structural switchover of piroxicam. It is interesting that the extent of switchover of piroxicam is directly correlated with the dipolar rearrangement induced bythe varying hydrophobic chain length of the surfactants. To the best of our knowledge, our results constitute the first report to show the dependence of dipole potential on the hydrophobic chain length of the surfactant and demonstrate that the dipolar rearrangement directly tunes the extent of structural switchover of piroxicam, which was so far only intuitive. We consider that this new finding would have promising implication in drug distribution and drug efficacy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Extensive gene rearrangements in the mitochondrial genomes of two egg parasitoids, Trichogramma japonicum and Trichogramma ostriniae (Hymenoptera: Chalcidoidea: Trichogrammatidae).

Science.gov (United States)

Chen, Long; Chen, Peng-Yan; Xue, Xiao-Feng; Hua, Hai-Qing; Li, Yuan-Xi; Zhang, Fan; Wei, Shu-Jun

2018-05-04

Animal mitochondrial genomes usually exhibit conserved gene arrangement across major lineages, while those in the Hymenoptera are known to possess frequent rearrangements, as are those of several other orders of insects. Here, we sequenced two complete mitochondrial genomes of Trichogramma japonicum and Trichogramma ostriniae (Hymenoptera: Chalcidoidea: Trichogrammatidae). In total, 37 mitochondrial genes were identified in both species. The same gene arrangement pattern was found in the two species, with extensive gene rearrangement compared with the ancestral insect mitochondrial genome. Most tRNA genes and all protein-coding genes were encoded on the minority strand. In total, 15 tRNA genes and seven protein-coding genes were rearranged. The rearrangements of cox1 and nad2 as well as most tRNA genes were novel. Phylogenetic analysis based on nucleotide sequences of protein-coding genes and on gene arrangement patterns produced identical topologies that support the relationship of (Agaonidae + Pteromalidae) + Trichogrammatidae in Chalcidoidea. CREx analysis revealed eight rearrangement operations occurred from presumed ancestral gene order of Chalcidoidea to form the derived gene order of Trichogramma. Our study shows that gene rearrangement information in Chalcidoidea can potentially contribute to the phylogeny of Chalcidoidea when more mitochondrial genome sequences are available.

Conjugated polyaniline as a result of the benzidine rearrangement

Czech Academy of Sciences Publication Activity Database

Sapurina, Irina; Tenkovtsev, A. V.; Stejskal, Jaroslav

2015-01-01

Roč. 64, č. 4 (2015), s. 453-465 ISSN 0959-8103 R&D Projects: GA MŠk(CZ) LH14199; GA ČR(CZ) GA13-00270S Institutional support: RVO:61389013 Keywords : aniline * aniline oligomers * benzidine rearrangement Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.414, year: 2015

T-cell receptor gene rearrangement in Epstein-Barr virus infectious mononucleosis.

Science.gov (United States)

Marbello, L; Riva, M; Veronese, S; Nosari, A M; Ravano, E; Colosimo, A; Paris, L; Morra, E

2012-09-01

This report describes the case of a previously healthy young man who presented with fever, pharyngitis, cervical lymphadenopathy, lymphocytosis, and severe thrombocytopenia. Serological tests for Epstein-Barr virus were diagnostic of a primary Epstein-Barr virus infectious mononucleosis but severe thrombocytopenia aroused the suspicion of a lymphoproliferative disease. T-cell receptor gene analysis performed on peripheral and bone marrow blood revealed a T-cell receptor γ-chain rearrangement without the evidence of malignancy using standard histologic and immunophenotype studies. Signs and symptoms of the infectious disease, blood count, and T-cell receptor gene rearrangement resolved with observation without the evidence of emergence of a lymphoproliferative disease. In the contest of a suspected lymphoproliferative disease, molecular results should be integrated with all available data for an appropriate diagnosis.

Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

International Nuclear Information System (INIS)

Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf; Hayward, Simon W.; Weier, Jingly F.; Zitzelsberger, Horst F.

2009-01-01

Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

Energy Technology Data Exchange (ETDEWEB)

Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf; Hayward, Simon W.; Weier, Jingly F.; Zitzelsberger, Horst F.

2009-07-07

Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

Clinical significance of productive immunoglobulin heavy chain gene rearrangements in childhood acute lymphoblastic leukemia.

Science.gov (United States)

Katsibardi, Katerina; Braoudaki, Maria; Papathanasiou, Chrissa; Karamolegou, Kalliopi; Tzortzatou-Stathopoulou, Fotini

2011-09-01

We analyzed the CDR3 region of 80 children with B-cell acute lymphoblastic leukemia (B-ALL) using the ImMunoGeneTics Information System and JOINSOLVER. In total, 108 IGH@ rearrangements were analyzed. Most of them (75.3%) were non-productive. IGHV@ segments proximal to IGHD-IGHJ@ were preferentially rearranged (45.3%). Increased utilization of IGHV3 segments IGHV3-13 (11.3%) and IGHV3-15 (9.3%), IGHD3 (30.5%), and IGHJ4 (34%) was noted. In pro-B ALL more frequent were IGHV3-11 (33.3%) and IGHV6-1 (33.3%), IGHD2-21 (50%), IGHJ4 (50%), and IGHJ6 (50%) segments. Shorter CDR3 length was observed in IGHV@6, IGHD7, and IGHJ1 segments, whereas increased CDR3 length was related to IGHV3, IGHD2, and IGHJ4 segments. Increased risk of relapse was found in patients with productive sequences. Specifically, the relapse-free survival rate at 5 years in patients with productive sequences at diagnosis was 75% (standard error [SE] ±9%), whereas in patients with non-productive sequences it was 97% (SE ±1.92%) (p-value =0.0264). Monoclonality and oligoclonality were identified in 81.2% and 18.75% cases at diagnosis, respectively. Sequence analysis revealed IGHV@ to IGHDJ joining only in 6.6% cases with oligoclonality. The majority (75%) of relapsed patients had monoclonal IGH@ rearrangements. The preferential utilization of IGHV@ segments proximal to IGHDJ depended on their location on the IGHV@ locus. Molecular mechanisms occurring during IGH@ rearrangement might play an essential role in childhood ALL prognosis. In our study, the productivity of the rearranged sequences at diagnosis proved to be a significant prognostic factor.

Chromosomal instability can be induced by the formation of breakage-prone chromosome rearrangement junctions

International Nuclear Information System (INIS)

Allen, R.N.; Ritter, L.; Moore, S.R.; Grosovsky, A.J.

2003-01-01

Full text: Studies in our lab have led to the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in chromosomal instability acting predominantly in cis. For example, specific breakage of large blocks of centromeric region heterochromatin on chromosome 16q by treatment with 2,6-diaminopurine (DAP) is associated with repeated rearrangement of chromosome 16q during outgrowth of DAP-treated clones, thereby establishing a link between the initial site of damage and the occurrence of persistent chromosomal instability. Similarly, karyotypic analysis of gamma ray induced instability demonstrated that chromosomal rearrangements in sub-clones were significantly clustered near the site of previously identified chromosomal rearrangement junctions in unstable parental clones. This study investigates the hypothesis that integration of transfected sequences into host chromosomes could create breakage-prone junction regions and persistent genomic instability without exposure to DNA-damage agents. These junctions may mimic the unstable chromosomal rearrangements induced by DAP or radiation, and thus provide a test of the broader hypothesis that instability can to some extent be attributed to the formation of novel chromosomal breakage hot spots. These experiments were performed using human-hamster hybrid AL cells containing a single human chromosome 11, which was used to monitor instability in a chromosomal painting assay. AL cells were transfected with a 2.5 Kb fragment containing multiple copies of the 180 bp human alpha heterochromatic repeat, which resulted in chromosomal instability in 41% of the transfected clones. Parallel exposure to gamma-radiation resulted in a similar level of chromosomal instability, although control transfections with plasmid alone did not lead to karyotypic instability. Chromosomal instability induced by integration of alpha heterochromatic repeats was also frequently associated with delayed reproductive

Triazole–Au(I complex as chemoselective catalyst in promoting propargyl ester rearrangements

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Dawei Wang

2011-07-01

Full Text Available Triazole–Au (TA–Au catalysts were employed in several transformations involving propargyl ester rearrangement. Good chemoselectivity was observed, which allowed the effective activation of the alkyne without affecting the reactivity of the allene ester intermediates. These results led to the investigation of the preparation of allene ester intermediates with TA–Au catalysts under anhydrous conditions. As expected, the desired 3,3-rearrangement products were obtained in excellent yields (generally >90% yields with 1% loading. Besides the typical ester migrating groups, carbonates and carbamates were also found to be suitable for this transformation, which provided a highly efficient, practical method for the preparation of substituted allenes.

On the role of string-junction in hadron reactions

International Nuclear Information System (INIS)

Imachi, Masahiro; Otsuki, Shoichiro; Toyoda, Fumihiko.

1977-01-01

By taking a model that hadrons are confined composite systems of the urbaryon q linked by the string, possible roles of a three-string junction J in hadron reactions are examined. The junction brings about new patterns to the conventional urbaryon rearrangement diagram. The leading behaviour of anti BB annihilation cross section is naturally explained by the exchange of one junction pair (J anti J). The Regge intercept is related to the number of the exchanged q and J, satisfying the sum rule α sub(P) (0) + α sub(B) (0) = 2α sub(M) (0). The rearrangement diagram of q and J divides exotic exchange amplitude into two classes, one with rather slow s dependence and the other with rapid one, in agreement with experiment. In addition to the pole-pole type duality, a new type of duality (pole-cut) is expected for some components of anti BB amplitude. Both of q and J carrying four momentum lead to a successful counting rule at large momentum transfers. (auth.)

The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR.

Science.gov (United States)

Yang, Hua; Cao, Tingting; Gao, Li; Wang, Lili; Zhu, Chengying; Xu, Yuanyuan; Jing, Yu; Zhu, Haiyan; Lv, Na; Yu, Li

2017-07-20

Occurrence of MLL (Mixed Lineage Leukemia) gene rearrangements indicates poor prognosis in acute myeloid leukemia (AML) patients. This is the first study to report the positive rate and distribution characteristics of MLL rearrangements in AML patients in north China. We used multiplex nested real time PCR (RT-PCR) to screen for incidence of 11 MLL rearrangements in 433 AML patients. Eleven MLL rearrangements included (MLL-PTD, MLL-AF9, MLL-ELL, MLL-AF10, MLL-AF17, MLL-AF6, MLL-ENL, MLL-AF1Q, MLL-CBP, MLL-AF1P, MLL-AFX1). There were 68 AML patients with MLL rearrangements, and the positive rate was 15.7%. MLL-PTD (4.84%) was detected in 21 patients, MLL-AF9 in 15, (3.46%), MLL-ELL in 10 (2.31%), MLL-AF10 in 8 (1.85%), MLL-AF1Q in 2 (0.46%), 3 cases each of MLL-AF17, MLL-AF6, MLL-ENL (0.69% each), a and single case each of MLL-CBP, MLL-AF1P, and MLL-AFX1 (0.23% each). The highest rate of MLL rearrangements was found in 24 patients with M5 subtype AML, occurring in 24 cases (35.3%). MLL rearrangements occurred in 21 patients with M2 subtype AML (30.9%), and in 10 patients with M4 subtype AML (14.7%). Screening fusion genes by multiplex nested RT-PCR is a convenient, fast, economical, and accurate method for diagnosis and predicting prognosis of AML.

Anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related human papillary thyroid carcinoma after the Chernobyl accident.

Science.gov (United States)

Arndt, Annette; Steinestel, Konrad; Rump, Alexis; Sroya, Manveer; Bogdanova, Tetiana; Kovgan, Leonila; Port, Matthias; Abend, Michael; Eder, Stefan

2018-04-06

Childhood radiation exposure has been associated with increased papillary thyroid carcinoma (PTC) risk. The role of anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related PTC remains unclear, but STRN-ALK fusions have recently been detected in PTCs from radiation exposed persons after Chernobyl using targeted next-generation sequencing and RNA-seq. We investigated ALK and RET gene rearrangements as well as known driver point mutations in PTC tumours from 77 radiation-exposed patients (mean age at surgery 22.4 years) and PTC tumours from 19 non-exposed individuals after the Chernobyl accident. ALK rearrangements were detected by fluorescence in situ hybridisation (FISH) and confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS genes were detected by DNA pyrosequencing. Among the 77 tumours from exposed persons, we identified 7 ALK rearrangements and none in the unexposed group. When combining ALK and RET rearrangements, we found 24 in the exposed (31.2%) compared to two (10.5%) in the unexposed group. Odds ratios increased significantly in a dose-dependent manner up to 6.2 (95%CI: 1.1, 34.7; p = 0.039) at Iodine-131 thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS genes, yet logistic regression analysis failed to identify significant dose association. To our knowledge we are the first to describe ALK rearrangements in post-Chernobyl PTC samples using routine methods such as FISH and IHC. Our findings further support the hypothesis that gene rearrangements, but not oncogenic driver mutations, are associated with ionizing radiation-related tumour risk. IHC may represent an effective method for ALK-screening in PTCs with known radiation aetiology, which is of clinical value since oncogenic ALK activation might represent a valuable target for small molecule inhibitors. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and

Rationalization of the selectivity between 1,3- and 1,2-migration: a DFT study on gold(i)-catalyzed propargylic ester rearrangement.

Science.gov (United States)

Jiang, Jingxing; Liu, Yan; Hou, Cheng; Li, Yinwu; Luan, Zihong; Zhao, Cunyuan; Ke, Zhuofeng

2016-04-14

Gold catalyzed rearrangement of propargylic esters can undergo 1,3-acyloxy migration to form allenes, or undergo 1,2-acyloxy migration to access gold-carbenoids. The variation in migration leads to different reactivities and diverse cascade transformations. The effect of terminal substituents is very important for the rearrangement. However, it remains ambiguous how terminal substituents govern the selectivity of the rearrangement. This study presents a theoretical model based on the resonance structure of gold activated propargylic ester complexes to rationalize the rearrangement selectivity. Substrates with a major resonance contributor A prefer 5-exo-dig cyclization (1,2-migration), while those with a major resonance contributor B prefer 6-endo-dig cyclization (1,3-migration). This concise model would be helpful in understanding and tuning the selectivity of the metal catalyzed rearrangement of propargylic esters.

Cytological evidence of chromosomal rearrangement in the second meiotic division after exposure to X-rays

Energy Technology Data Exchange (ETDEWEB)

Szemere, G. (Orvostudomanyi Egyetem, Szeged (Hungary). Orvosbiologiai Intezet)

1982-01-01

Metaphase II cells with unequal dyad-arms and obvious X/autosomal rearrangements were found after an exposure to X-rays (2 Gy) of male mice at different stages of meiosis (pachytene, diplotene and diakinesis) with a frequency of 0.2, 1.26 and 0.6%, respectively, giving a direct cytological evidence of structural chromosomal rearrangements in metaphase II cells, partly with autosomal and partly with X/autosomal partners.

Cytological evidence of chromosomal rearrangement in the second meiotic division after exposure to X-rays

International Nuclear Information System (INIS)

Szemere, G.

1982-01-01

Metaphase II cells with unequal dyad-arms and obvious X/autosomal rearrangements were found after an exposure to X-rays (2 Gy) of male mice at different stages of meiosis (pachytene, diplotene and diakinesis) with a frequency of 0.2, 1.26 and 0.6%, respectively, giving a direct cytological evidence of structural chromosomal rearrangements in metaphase II cells, partly with autosomal and partly with X/autosomal partners. (author)

Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement mechanisms and biomarker development.

Science.gov (United States)

Koga, Tomoyuki; Li, Bin; Figueroa, Javier M; Ren, Bing; Chen, Clark C; Carter, Bob S; Furnari, Frank B

2018-04-12

Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM) generated by deletion of exons two to seven of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron one, presenting significant challenges in terms of PCR-based mapping. Molecular mechanisms underlying these deletions remain unclear. We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative polymerase chain reaction (qPCR), arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific breakpoint PCR was performed on tumors, plasma and cerebrospinal fluid (CSF) samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were analyzed to elucidate the underlying biogenic mechanism. PCR mapping and WGS independently unveiled eight EGFRvIII breakpoints in six tumors. Patient-specific primers yielded EGFRvIII PCR amplicons in matched tumors, and in cell-free DNA (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from plasma. The breakpoint analysis revealed nucleotide insertions in four, an insertion of a region outside of EGFR locus in one, microhomologies in three, as well as a duplication or an inversion accompanied by microhomologies in two, suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII EGFR were identical, suggesting that these rearrangements arose from amplified non-vIII EGFR. Our approach efficiently "fingerprints" each sample's EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent breakpoints arose from precursor amplified non-vIII EGFR through different DNA repair mechanisms.

Nitrene-carbene-carbene rearrangement. Photolysis and thermolysis of tetrazolo[5,1- a ]phthalazine with formation of 1-phthalazinylnitrene, o-cyanophenylcarbene, and phenylcyanocarbene

DEFF Research Database (Denmark)

Høj, Martin; Kvaskoff, David; Wentrup, Curt

2014-01-01

). The rearrangement of 12 â., 13 â., 14 constitutes a carbene-carbene rearrangement. 1-Phthalazinylnitrene 310 is observed by means of its UV-vis spectrum in Ar matrix following FVT of 9 above 550 C. Rearrangement to cyanophenylcarbenes also takes place on FVT of 9 as evidenced by observation of the products of ring...... contraction, viz., fulvenallenes and ethynylcyclopentadienes 16-18. Thus the overall rearrangement 10 → 11 → 12 â., 13 â., 14 can be formulated. © 2013 American Chemical Society....

Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

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Colovati Mileny ES

2012-01-01

Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

Meiotic Recombination Analyses in Pigs Carrying Different Balanced Structural Chromosomal Rearrangements.

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Nicolas Mary

Full Text Available Correct pairing, synapsis and recombination between homologous chromosomes are essential for normal meiosis. All these events are strongly regulated, and our knowledge of the mechanisms involved in this regulation is increasing rapidly. Chromosomal rearrangements are known to disturb these processes. In the present paper, synapsis and recombination (number and distribution of MLH1 foci were studied in three boars (Sus scrofa domestica carrying different chromosomal rearrangements. One (T34he was heterozygote for the t(3;4(p1.3;q1.5 reciprocal translocation, one (T34ho was homozygote for that translocation, while the third (T34Inv was heterozygote for both the translocation and a pericentric inversion inv(4(p1.4;q2.3. All three boars were normal for synapsis and sperm production. This particular situation allowed us to rigorously study the impact of rearrangements on recombination. Overall, the rearrangements induced only minor modifications of the number of MLH1 foci (per spermatocyte or per chromosome and of the length of synaptonemal complexes for chromosomes 3 and 4. The distribution of MLH1 foci in T34he was comparable to that of the controls. Conversely, the distributions of MLH1 foci on chromosome 4 were strongly modified in boar T34Inv (lack of crossover in the heterosynaptic region of the quadrivalent, and crossover displaced to the chromosome extremities, and also in boar T34ho (two recombination peaks on the q-arms compared with one of higher magnitude in the controls. Analyses of boars T34he and T34Inv showed that the interference was propagated through the breakpoints. A different result was obtained for boar T34ho, in which the breakpoints (transition between SSC3 and SSC4 chromatin on the bivalents seemed to alter the transmission of the interference signal. Our results suggest that the number of crossovers and crossover interference could be regulated by partially different mechanisms.

Frequent Chromatin Rearrangements in Myelodysplastic Syndromes - What Stands Behind?

Czech Academy of Sciences Publication Activity Database

Pagáčová, Eva; Falk, Martin; Falková, Iva; Lukášová, Emilie; Michalová, K.; Oltová, A.; Raška, I.; Kozubek, Stanislav

2014-01-01

Roč. 60, č. 2014 (2014), s. 1-7 ISSN 0015-5500 R&D Projects: GA ČR(CZ) GBP302/12/G157; GA MŠk(CZ) EE2.3.30.0030 Institutional support: RVO:68081707 Keywords : myelodysplastic syndromes * chromosomal rearrangements * chromosome 5 deletions Subject RIV: BO - Biophysics Impact factor: 1.000, year: 2014

Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome

DEFF Research Database (Denmark)

Ohm-Laursen, Line; Nielsen, Christian; Fisker, Niels

2008-01-01

rearrangements to those of age-matched controls, cord blood, and adults revealed an almost total lack of nonproductive rearrangements (2.7% versus 14.7%, 27.6%, and 19.8% in the controls, respectively) indicating failure to correct out-of-frame rearrangements by a second rearrangement on the homologous...

Identification of a structural chromosomal rearrangement in the karyotype of a root vole from Chernobyl

International Nuclear Information System (INIS)

Nadzhafova, R.S.; Bulatova, N.Sh.; Kozlovskii, A.I.; Ryabov, I.N.

1994-01-01

Karyological studies of rodents within a 30-km radius of the Chernobyl nuclear power plant revealed one female root vole (Microtus oeconomus) with an abnormal karyotype. The use of C, G, and AgNOR banding methods allowed determination that morphological changes in two nonhomologous autosomes, which were accompanied by rearrangements in distribution of G bands, heterochromatin, and NOR, are the result of a reciprocal translocation. Chromosomal aberrations were probably inherited or appeared in embryogenesis, since none of the analyzed cells of the studied vole had a normal karyotype. It is important to note that this rearrangement was detected five years after the meltdown. Both breaks and reunions of the chromosomes that participate in this rearrangement are probably located in regions that are not important for functioning of these chromosomes. Thus, it can be supposed that the detected rearrangement did not influence the viability of the vole. This karyotype was compared to a standard karyotype of a root vole from another area of the species range. The heteromorphism of the first pair of chromosomes in both voles, which was detected for the first time, is probably normal for the karyotype of M. oeconomus and is not linked with any radiation-induced intrachromosomal aberrations

The Role of SPINK1 in ETS Rearrangement Negative Prostate Cancers

Science.gov (United States)

Tomlins, Scott A.; Rhodes, Daniel R.; Yu, Jianjun; Varambally, Sooryanarayana; Mehra, Rohit; Perner, Sven; Demichelis, Francesca; Helgeson, Beth E.; Laxman, Bharathi; Morris, David S.; Cao, Qi; Cao, Xuhong; Andrén, Ove; Fall, Katja; Johnson, Laura; Wei, John T.; Shah, Rajal B.; Al-Ahmadie, Hikmat; Eastham, James A.; Eggener, Scott E.; Fine, Samson W.; Hotakainen, Kristina; Stenman, Ulf-Håkan; Tsodikov, Alex; Gerald, William L.; Lilja, Hans; Reuter, Victor E.; Kantoff, Phillip W.; Scardino, Peter T.; Rubin, Mark A.; Bjartell, Anders S.; Chinnaiyan, Arul M.

2009-01-01

Summary ETS gene fusions have been characterized in a majority of prostate cancers, however the key molecular alterations in ETS negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier-expression exclusively in a subset of ETS rearrangement negative cancers (~10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier-expression can be detected non-invasively in urine and observed that SPINK1 outlier-expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier-expression model, and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement negative prostate cancers. PMID:18538735

Structural Characterization of Amadori Rearrangement Product of Glucosylated Nα-Acetyl-Lysine by Nuclear Magnetic Resonance Spectroscopy

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Chuanjiang Li

2014-01-01

Full Text Available Maillard reaction is a nonenzymatic reaction between reducing sugars and free amino acid moieties, which is known as one of the most important modifications in food science. It is essential to characterize the structure of Amadori rearrangement products (ARPs formed in the early stage of Maillard reaction. In the present study, the Nα-acetyl-lysine-glucose model had been successfully set up to produce ARP, Nα-acetyl-lysine-glucose. After HPLC purification, ARP had been identified by ESI-MS with intense [M+H]+ ion at 351 m/z and the purity of ARP was confirmed to be over 90% by the relative intensity of [M+H]+ ion. Further structural characterization of the ARP was accomplished by using nuclear magnetic resonance (NMR spectroscopy, including 1D 1H NMR and 13C NMR, the distortionless enhancement by polarization transfer (DEPT-135 and 2D 1H-1H and 13C-1H correlation spectroscopy (COSY and 2D nuclear overhauser enhancement spectroscopy (NOESY. The complexity of 1D 1H NMR and 13C NMR was observed due to the presence of isomers in glucose moiety of ARP. However, DEPT-135 and 2D NMR techniques provided more structural information to assign the 1H and 13C resonances of ARP. 2D NOESY had successfully confirmed the glycosylated site between 10-N in Nα-acetyl-lysine and 7′-C in glucose.

A New Pathway to 3-Hetaryl-2-oxo-2H-chromenes: On the Proposed Mechanisms for the Reaction of 3-Carbamoyl-2-iminochromenes with Dinucleophiles

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Yaroslav V. Bilokin

2000-10-01

Full Text Available The present account summarizes the author's studies to elucidate the mechanisms of the recently reported rearrangements resulting from inter- and/or intramolecular reactions of 2-imino-2H-chromene-3-carboxamides with different dinucleophiles.

Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

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Francesca Duraturo

2013-01-01

Full Text Available Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency. This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

Theoretical Studies of [2,3]-Sigmatropic Rearrangements of Allylic Selenoxides and Selenimides

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Sonia Antony

2009-08-01

Full Text Available Density-functional theory is used to model the endo and exo transition states for [2,3]-sigmatropic rearrangement of allylic aryl-selenoxides and -selenimides. The endo transition state is generally preferred for selenoxides if there is no substitution at the 2 position of the allyl group. Based upon the relative energies of the endo and exo transition states, enantioselectivity of rearrangements is expected to be greatest for molecules with substitutions at the 1- or (E-3- position of the allyl group. Ortho substitution of a nitro group on the ancillary selenoxide phenyl ring reduces the activation barriers, increases the difference between the endo and exo activation barriers and shifts the equilibrium toward products.

The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster

International Nuclear Information System (INIS)

Wakimoto, B.T.; Hearn, M.G.

1990-01-01

The light (lt) gene of Drosophila melanogaster is located at the base of the left arm of chromosome 2, within or very near centromeric heterochromatin (2Lh). Chromosome rearrangements that move the lt + gene from its normal proximal position and place the gene in distal euchromatin result in mosaic or variegated expression of the gene. The cytogenetic and genetic properties of 17 lt-variegated rearrangements induced by X radiation are described in this report. The authors show that five of the heterochromatic genes adjacent to lt are subject to inactivation by these rearrangements and that the euchromatic loci in proximal 2L are not detectably affected. The properties of the rearrangements suggest that proximity to heterochromatin is an important regulatory requirement for at least six 2Lh genes. They discuss how the properties of the position effects on heterochromatic genes relate to other proximity-dependent phenomena such as transvection

"Toward High School Biology": Helping Middle School Students Understand Chemical Reactions and Conservation of Mass in Nonliving and Living Systems

Science.gov (United States)

Herrmann-Abell, Cari F.; Koppal, Mary; Roseman, Jo Ellen

2016-01-01

Modern biology has become increasingly molecular in nature, requiring students to understand basic chemical concepts. Studies show, however, that many students fail to grasp ideas about atom rearrangement and conservation during chemical reactions or the application of these ideas to biological systems. To help provide students with a better…

Bond rearrangement caused by sudden single and multiple ionization of water molecules

International Nuclear Information System (INIS)

Ben-Itzhak, I.; Sayler, A. Max; Leonard, M.; Maseberg, J.W.; Hathiramani, D.; Wells, E.; Smith, M.A.; Xia, Jiangfan; Wang, Pengqian; Carnes, K.D.; Esry, B.D.

2005-01-01

Bond rearrangement, namely the dissociation of water into H 2 + +O q+ following ionization by fast proton and highly charged ion impact, was investigated. Single ionization by fast proton impact exhibits a strong isotopic effect, the dissociation of H 2 O + ->H 2 + +O being about twice as likely as D 2 O + ->D 2 + +O, with HDO + ->HD + +O in between. This suggests that the bond rearrangement does not happen during the slow dissociation, but rather during the very fast ionization, and thus H 2 + should also be produced when the water molecule is multiply ionized. We observed that the H 2 + +O + and H 2 + +O 2+ production in 1MeV/amu F 7+ +H 2 O collisions are 0.209+/-0.006% and 0.0665+/-0.003%, respectively, of the main double-ionization dissociation product, H 2 O 2+ ->H + +OH + . This ratio is similar to the triple to double ionization ratio in similar collisions with atomic targets thus suggesting that the bond-rearrangement fraction out of each ionization level is approximately constant. Similar dissociation channels in the heavier water isotopes, which are expected to be smaller, are under study. Finally, the fragmentation of HDO exhibits very strong isotopic preference for breaking the OH bond over the OD bond

Comparative analysis of clinicoradiologic characteristics of lung adenocarcinomas with ALK rearrangements or EGFR mutations

Energy Technology Data Exchange (ETDEWEB)

Zhou, J.Y.; Zheng, J.; Chen, X.; Zhou, J.Y. [Zhejiang University, Department of Respiratory Disease, Thoracic Disease Center, First Affiliated Hospital, College of Medicine, Hangzhou (China); Yu, Z.F.; Xiao, W.B.; Jiang, L.N. [Zhejiang University, Department of Radiology, First Affiliated Hospital, College of Medicine, Hangzhou (China); Zhao, J.; Sun, K.; Wang, B.; Ding, W. [Zhejiang University, Department of Pathology, First Affiliated Hospital, College of Medicine, Hangzhou (China)

2015-05-01

To compare the clinicoradiologic features of tumours with echinoderm anaplastic lymphoma kinase (ALK) rearrangements, epidermal growth factor receptor (EGFR) mutations, or wild type (WT) for both genes in a cohort of patients with lung adenocarcinoma to identify useful characteristics of different gene statuses. In 346 lung adenocarcinoma patients, ALK rearrangements were confirmed with fluorescence in situ hybridisation, and EGFR mutations were determined by pyrosequencing assay. Patients were divided into three groups: ALK rearrangement (ALK+ group, n = 48), EGFR mutation (EGFR+ group, n = 166), and WT for both genes (WT group, n = 132). Chest computed tomography (CT) examinations were performed in all patients. The percentages of ground-glass opacity volume (pGGO) and tumour shadow disappearance rate (TDR) were measured using semi-automated nodule assessment software. The pGGO was significantly lower in the ALK+ group (25.1 % ± 24.3) than in the EGFR+ group (37.2 % ± 25.7, p < 0.001) and the WT group (36.1 % ± 24.6, p = 0.001). The TDR in the ALK+ group (17.3 % ± 25.1) was significantly lower than in the EGFR+ group (26.8 % ± 24.9, p = 0.002) and the WT group (25.7 % ± 24.6, p = 0.003). Solid pattern with lower incidence of lobulated border, finely spiculated margins, pleural retraction, and bubble-like lucency on CT imaging are the main characteristics of ALK rearrangement tumours. (orig.)

Screening for genomic rearrangements at BRCA1 locus in Iranian ...

Indian Academy of Sciences (India)

2016-08-26

Aug 26, 2016 ... Home; Journals; Journal of Genetics; Volume 92; Issue 1. Screening for genomic rearrangements at BRCA1 locus in Iranian women with breast cancer using multiplex ligation-dependent probe amplification. Vahid R. Yassaee Babak Emamalizadeh Mir Davood Omrani. Research Note Volume 92 Issue 1 ...

Carbamoyl anion-initiated cascade reaction for stereoselective synthesis of substituted α-hydroxy-β-amino amides.

Science.gov (United States)

Lin, Chao-Yang; Ma, Peng-Ju; Sun, Zhao; Lu, Chong-Dao; Xu, Yan-Jun

2016-01-18

A carbamoyl anion-initiated cascade reaction with acylsilanes and imines has been used to rapidly construct substituted α-hydroxy-β-amino amides. The Brook rearrangement-mediated cascade allows the formation of two C-C bonds and one O-Si bond in a single pot. Using this approach, a range of α-aryl α-hydroxy-β-amino amides has been synthesized in high yields with excellent diastereoselectivities.

Synthesis of Biologically Active Natural Component 4-Hydroxyderricin Through Water-Accelerated [3,3]-Sigmatropic Rearrangement

Energy Technology Data Exchange (ETDEWEB)

Kim, Sijun; Lee, Jaejun; Yoon, Hyunho; Jun, Jonggab [Hallym Univ., Chuncheon (Korea, Republic of)

2013-09-15

We report herein the practical and effective total synthesis of biologically active 4-hydroxyderricin, a poly-phenolic chalcone compound containing m-prenyl group at ring A. The key steps of the synthesis are Claisen-Schmidt condensation of the the two phenolic units 17 and 18 to chalcone 19 and the water-accelerated [3,3]-sigma-tropic rearrangement of 1,1-dimethyl-2-propenyl aryl ether 20 to introduce the m-prenyl unit in 4-hydroxyderricin. Two types of polyphenolic chalcones, 4-hydroxyderricin (1) and xanthoangelol (2), are especially rich in the plant, and the 4-hydroxyderricin exhibited the major responsibility for the various biological activities. Sugamoto reported the synthesis of 4-hydroxy-derricin via [1,3]-sigmatropic rearrangement of chalcone ether using montmorillonite K10 which showed relatively low rearrangement yield (Scheme 1), and this is the only reported total synthesis of 1 as far as we know.

Immobilization of styrene-substituted 1,3,4-oxadiazoles into thermoreversible luminescent organogels and their unexpected photocatalyzed rearrangement.

Science.gov (United States)

Dumur, Frédéric; Contal, Emmanuel; Wantz, Guillaume; Phan, Trang N T; Bertin, Denis; Gigmes, Didier

2013-01-21

A series of styrene-substituted 1,3,4-oxadiazoles has been designed and investigated as new low-molecular-weight organogelators. The photophysical properties of the resulting thermoreversible organogels have been characterized by UV/Vis absorption and luminescence spectroscopies. Surprisingly, the gelation ability of the oxadiazoles depended on the presence of the styrene moiety as gelation of the investigated oxadiazoles did not take place in its absence. Gel formation was accompanied by a modification of the fluorescence of the organogelators in the supramolecular state. UV irradiation of the gels caused a rearrangement of the immobilized 1,3,4-oxadiazoles bearing a styrene moiety by a tandem [4+2] and [3+2] cascade reaction. Structure modification and color change of the gels were also evident upon irradiation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ultrafast infrared studies of chemical reaction dynamics in room-temperature liquids

Energy Technology Data Exchange (ETDEWEB)

Yang, Haw [Univ. of California, Berkeley, CA (United States)

1999-11-01

Femtosecond infrared spectroscopy provides sufficient spectral and temporal resolution to support a detailed investigation of the early events of a photochemical reaction. Previously unreported transient species that arise as intermediates during the course of a reaction may have lifetimes that are too short for conventional characterization. For these species, quantum-mechanical (density functional theoretical and ab initio) electronic structure calculations provide invaluable insight into chemical properties including molecular structure and energetic. With the combination of experimental and theoretical results, it is possible to assemble a comprehensive picture of the reaction dynamics of a system that is intricately influenced by the surrounding solvent molecules. The mechanisms of several important organometallic reactions, such as alkane C– H bond activation by η³-Tp*Rh(CO), silane Si–H bond activation by η⁵-CpMn(CO)₂ and η⁵-CpRe(CO)₂, as well as chlorinated methane C–Cl bond cleavage by the Re(CO)₅ radical are elucidated. The results demonstrate the importance of molecular morphology change (C–H and Si–H act ivat ion), solvent rearrangement (Si–H activation), intersystem crossing (Si–H activation), and solvent caging (C–Cl cleavage) in understanding the reactivity of the organometallic species, The nature of the apparent free-energy barrier for C–H, Si–H, and C–Cl bond activation reaction is found to be- cleavage of an alkane C–H bond, rearrangement of a silane molecule HSiR₃ (R = alkyl group) from a nonreactive alkyl site to the reactive Si–H bond, and Cl atom transfer from a chlorinated methane molecule to Re(CO)₅, respectively. These results support previous d initio calculations for C–H and Si–H bond activation reaction profiles which suggest that cleavage of an alkane C–H bond by a transition metal center, unlike that of a silane

Magnetic field re-arrangement after prominence eruption

International Nuclear Information System (INIS)

Kopp, R.A.; Poletto, G.

1986-01-01

It has long been known that magnetic reconnection plays a fundamental role in a variety of solar events. Although mainly invoked in flare problems, large-scale loops interconnecting active regions, evolving coronal hole boundaries, the solar magnetic cycle itself, provide different evidence of phenomena which involve magnetic reconnection. A further example might be given by the magnetic field rearrangement which occurs after the eruption of a prominence. Since most often a prominence reforms after its disappearance and may be observed at about the same position it occupied before erupting, the magnetic field has to undergo a temporary disruption to relax back, via reconnection, to a configuration similar to the previous one. The above sequence of events is best observable in the case of two-ribbon (2-R) flares but most probably is associated with all filament eruptions. Even if the explanation of the magnetic field rearrangement after 2-R flares in terms of reconnection is generally accepted, the lack of a three-dimensional model capable of describing the field reconfiguration, has prevented, up to now, a thorough analysis of its topology as traced by Hα/x-ray loops. The purpose of the present work is to present a numerical technique which enables one to predict and visualize the reconnected configuration, at any time t, and therefore allows one to make a significant comparison of observations and model predictions throughout the whole process. 5 refs., 3 figs

Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells

International Nuclear Information System (INIS)

Kodama, S.; Okumura, Y.; Komatsu, K.; Sasaki, M.S.

1991-01-01

Chromosomal alterations were studied during the acquisition of malignant phenotypes in two karyotypically distinct cells isolated from transformed foci induced by x-irradiation in mouse m5S cells. Because the transformants, despite foci origin, showed low ability to grow in agar, they were cultured in vitro with serial transfer schedules to allow further cell generations and assayed for anchorage independence (AI) at each passage level. The AI frequency increased with the cell doubling numbers. Chromosome analysis showed that a focus was one cell origin, but the transformants showed karyotypic instability during cell proliferation, giving rise to the rearrangements clustered in the distal region of the specific chromosomes. These rearrangements appeared to be directed toward the acquisition of malignant phenotypes. Analysis of the types and sites of rearrangements indicated that a mechanism exists that induces frequent rearrangements of the specific region of a chromosome during the process of transformation into the malignant state

Low rate of interchromosomal rearrangements during old radiation of gekkotan lizards (Squamata: Gekkota).

Science.gov (United States)

Johnson Pokorná, Martina; Trifonov, Vladimir A; Rens, Willem; Ferguson-Smith, Malcolm A; Kratochvíl, Lukáš

2015-06-01

Gekkotan lizards are a highly specious (∼1600 described species) clade of squamate lizards with nearly cosmopolitan distribution in warmer areas. The clade is primarily nocturnal and forms an ecologically dominant part of the world nocturnal herpetofauna. However, molecular cytogenetic methods to study the evolution of karyotypes have not been widely applied in geckos. Our aim here was to uncover the extent of chromosomal rearrangements across the whole group Gekkota and to search for putative synapomorphies supporting the newly proposed phylogenetic relationships within this clade. We applied cross-species chromosome painting with the recently derived whole-chromosomal probes from the gekkonid species Gekko japonicus to members of the major gekkotan lineages. We included members of the families Diplodactylidae, Carphodactylidae, Pygopodidae, Eublepharidae, Phyllodactylidae and Gekkonidae. Our study demonstrates relatively high chromosome conservatism across the ancient group of gekkotan lizards. We documented that many changes in chromosomal shape across geckos can be attributed to intrachromosomal rearrangements. The documented rearrangements are not totally in agreement with the recently newly erected family Phyllodactylidae. The results also pointed to homoplasy, particularly in the reuse of chromosome breakpoints, in the evolution of gecko karyotypes.

ETV6-RUNX1 Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic Leukemia

Directory of Open Access Journals (Sweden)

Abir Gmidène

2009-01-01

Full Text Available In this study, Forty-one out of fifty-seven Tunisian children with B-lineage acute lymphoblastic leukemia (B-ALL, and without cytogenetically detectable recurrent abnormalities at the time of the diagnosis, were evaluated by fluorescence in situ hybridization (FISH for the t(12;21. This translocation leads ETV6-RUNX1 (previously TEL-AML1 fusion gene. 16 patients (28% had ETV6-RUNX1 rearrangement. In addition to this rearrangement, two cases showed a loss of the normal ETV6 allele, and three others showed an extra signal of the RUNX1 gene. Seven patients without ETV6-RUNX1 rearrangement showed extra signals of the RUNX1 gene. One out of the 7 patients was also associated with a t(3;12 identified by FISH. This is the first Tunisian study in which we report the incidence of t(12;21 among childhood B-lineage ALL and in which we have found multiple copies of RUNX1. Finally, our findings confirm that additional or secondary genetic changes are commonly encountered in pediatric B-lineage ALL with ETV6-RUNX1 gene fusion which is envisaged to play a pivotal role in disease progression.

Level rearrangement in exotic atoms and quantum dots

International Nuclear Information System (INIS)

Combescure, Monique; Khare, Avinash; Raina, Ashok; Richard Jean-Marc; Weydert, Carole

2007-01-01

A presentation and a generalisation are given of the phenomenon of level rearrangement, which occurs when an attractive long-range potential is supplemented by a short-range attractive potential of increasing strength. This problem has been discovered in condensate-matter physics and has also been studied in the physics of exotic atoms. A similar phenomenon occurs in a situation inspired by quantum dots, where a short-range interaction is added to an harmonic confinement. (authors)

Reaction of Pentanol isomers with OH radical – A theoretical perspective

Science.gov (United States)

Aazaad, Basheer; Lakshmipathi, Senthilkumar

2018-05-01

The stability of all the three isomeric forms of Pentanol has been examined with relative energy analysis. Even though 2-Pentanol is predicted to be most stable isomeric form, all the three isomeric forms undergo hydrogen atom abstraction reaction with OH radical. Among the proposed 18 different hydrogen atom abstraction reaction, the abstraction from CH2 and CH functional group is found to be a favourable reactive site with low energy barrier in M06-2X/6-311+G(d,p) level of theory. Wiberg bond order analysis shows all the abstraction reactions are concreted but not synchronic in nature. Using force analysis, the calculated work done of individual reaction regions illustrates that structural rearrangements drive the reaction with higher contribution to the energy barrier. The rate constant calculated at M06-2X method for the most favourable reaction is well matched with available experimental data. Using the reported atmospheric OH concentration (1 × 106 molecules/cm3), the life time of 1-Pentanol, 2-Pentanol and 3-Pentanol has calculated to be 18.66, 0.36 and 2.86 days, respectively.

Conjugation-promoted reaction of open-cage fullerene: a density functional theory study.

Science.gov (United States)

Guo, Yong; Yan, Jingjing; Khashab, Niveen M

2012-02-01

Density functional theory calculations are performed to study the addition mechanism of e-rich moieties such as triethyl phosphite to a carbonyl group on the rim of a fullerene orifice. Three possible reaction channels have been investigated. The obtained results show that the reaction of a carbonyl group on a fullerene orifice with triethyl phosphite most likely proceeds along the classical Abramov reaction; however, the classical product is not stable and is converted into the experimental product. An attack on a fullerene carbonyl carbon will trigger a rearrangement of the phosphate group to the carbonyl oxygen as the conversion transition state is stabilized by fullerene conjugation. This work provides a new insight on the reactivity of open-cage fullerenes, which may prove helpful in designing new switchable fullerene systems. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Unexpected catalytic reactions of silyl-protected enol diazoacetates with nitrile oxides that form 5-arylaminofuran-2(3H)-one-4-carboxylates.

Science.gov (United States)

Xu, Xinfang; Shabashov, Dmitry; Zavalij, Peter Y; Doyle, Michael P

2012-02-03

Silyl-protected enol diazoacetates undergo dirhodium(II)-catalyzed reactions with nitrile oxides to form acid-labile ketenimines via dipolar cycloaddition of nitrile oxides to a donor/acceptor cyclopropene and Lossen rearrangement of the dipolar adduct; acid catalysis converts the ketenimine to the furan product. © 2012 American Chemical Society

TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia

DEFF Research Database (Denmark)

Willer, Anton; Jakobsen, Janus Schou; Ohlsson, E

2015-01-01

orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). TGIF1/TGIF2 are relatively uncharacterized TALE transcription factors, which, in contrast to the remaining family, have been shown to act as transcriptional repressors. Given the general......Members of the TALE (three-amino-acid loop extension) family of atypical homeodomain-containing transcription factors are important downstream effectors of oncogenic fusion proteins involving the mixed lineage leukemia (MLL) gene. A well-characterized member of this protein family is MEIS1, which...... influence the clinical outcome. Collectively, these findings demonstrate that TALE family members can act both positively and negatively on transcriptional programs responsible for leukemic maintenance and provide novel insights into the regulatory gene expression circuitries in MLL-rearranged AML.Leukemia...

Ontology aided modeling of organic reaction mechanisms with flexible and fragment based XML markup procedures.

Science.gov (United States)

Sankar, Punnaivanam; Aghila, Gnanasekaran

2007-01-01

The mechanism models for primary organic reactions encoding the structural fragments undergoing substitution, addition, elimination, and rearrangements are developed. In the proposed models, each and every structural component of mechanistic pathways is represented with flexible and fragment based markup technique in XML syntax. A significant feature of the system is the encoding of the electron movements along with the other components like charges, partial charges, half bonded species, lone pair electrons, free radicals, reaction arrows, etc. needed for a complete representation of reaction mechanism. The rendering of reaction schemes described with the proposed methodology is achieved with a concise XML extension language interoperating with the structure markup. The reaction scheme is visualized as 2D graphics in a browser by converting them into SVG documents enabling the desired layouts normally perceived by the chemists conventionally. An automatic representation of the complex patterns of the reaction mechanism is achieved by reusing the knowledge in chemical ontologies and developing artificial intelligence components in terms of axioms.

Conditional genomic rearrangement by designed meiotic recombination using VDE (PI-SceI) in yeast.

Science.gov (United States)

Fukuda, Tomoyuki; Ohya, Yoshikazu; Ohta, Kunihiro

2007-10-01

Meiotic recombination plays critical roles in the acquisition of genetic diversity and has been utilized for conventional breeding of livestock and crops. The frequency of meiotic recombination is normally low, and is extremely low in regions called "recombination cold domains". Here, we describe a new and highly efficient method to modulate yeast meiotic gene rearrangements using VDE (PI-SceI), an intein-encoded endonuclease that causes an efficient unidirectional meiotic gene conversion at its recognition sequence (VRS). We designed universal targeting vectors, by use of which the strain that inserts the VRS at a desired site is acquired. Meiotic induction of the strains provided unidirectional gene conversions and frequent genetic rearrangements of flanking genes with little impact on cell viability. This system thus opens the way for the designed modulation of meiotic gene rearrangements, regardless of recombinational activity of chromosomal domains. Finally, the VDE-VRS system enabled us to conduct meiosis-specific conditional knockout of genes where VDE-initiated gene conversion disrupts the target gene during meiosis, serving as a novel approach to examine the functions of genes during germination of resultant spores.

Early dengue virus protein synthesis induces extensive rearrangement of the endoplasmic reticulum independent of the UPR and SREBP-2 pathway.

Directory of Open Access Journals (Sweden)

José Peña

Full Text Available The rearrangement of intracellular membranes has been long reported to be a common feature in diseased cells. In this study, we used dengue virus (DENV to study the role of the unfolded protein response (UPR and sterol-regulatory-element-binding-protein-2 (SREBP-2 pathway in the rearrangement and expansion of the endoplasmic reticulum (ER early after infection. Using laser scanning confocal and differential interference contrast microscopy, we demonstrate that rearrangement and expansion of the ER occurs early after DENV-2 infection. Through the use of mouse embryonic fibroblast cells deficient in XBP1 and ATF6, we show that ER rearrangement early after DENV infection is independent of the UPR. We then demonstrate that enlargement of the ER is independent of the SREBP-2 activation and upregulation of 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway. We further show that this ER rearrangement is not inhibited by the treatment of DENV-infected cells with the cholesterol-inhibiting drug lovastatin. Using the transcription inhibitor actinomycin D and the translation elongation inhibitor cycloheximide, we show that de novo viral protein synthesis but not host transcription is necessary for expansion and rearrangement of the ER. Lastly, we demonstrate that viral infection induces the reabsorption of lipid droplets into the ER. Together, these results demonstrate that modulation of intracellular membrane architecture of the cell early after DENV-2 infection is driven by viral protein expression and does not require the induction of the UPR and SREBP-2 pathways. This work paves the way for further study of virally-induced membrane rearrangements and formation of cubic membranes.

Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

International Nuclear Information System (INIS)

Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C.; Grzeschik, K.H.

1988-01-01

Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

Directory of Open Access Journals (Sweden)

Grzegorz Mlostoń

2015-04-01

Full Text Available Selected hetaryl and aryl thioketones react with acetylenecarboxylates under thermal conditions in the presence of LiClO4 or, alternatively, under high-pressure conditions (5 kbar at room temperature yielding thiopyran derivatives. The hetero-Diels–Alder reaction occurs in a chemo- and regioselective manner. The initially formed [4 + 2] cycloadducts rearrange via a 1,3-hydrogen shift sequence to give the final products. The latter were smoothly oxidized by treatment with mCPBA to the corresponding sulfones.

Multi-step rearrangement mechanism for acetyl cedrene to the hydrocarbon follower

DEFF Research Database (Denmark)

Paknikar, Shashikumar Keshav; Kamounah, Fadhil S.; Hansen, Poul Erik

2017-01-01

Conversion of acetyl cedrene (2) to its follower (3) using acetic anhydride and polyphosphoric acid involves a multi-step cationic molecular rearrangement, which is consistent with deuteriation and 1-13C labeling studies of acetyl cedrene. The key step involves cyclopropylcarbinyl cation-cyclopro...

Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies Report of the BIOMED-2 Concerted Action BHM4 CT98-3936

NARCIS (Netherlands)

Brüggemann, M.; White, H.; Gaulard, P.; Garcia-Sanz, R.; Gameiro, P.; Oeschger, S.; Jasani, B.; Ott, M.; Delsol, G.; Orfao, A.; Tiemann, M.; Herbst, H.; Langerak, A. W.; Spaargaren, M.; Moreau, E.; Groenen, P. J. T. A.; Sambade, C.; Foroni, L.; Carter, G. I.; Hummel, M.; Bastard, C.; Davi, F.; Delfau-Larue, M.-H.; Kneba, M.; van Dongen, J. J. M.; Beldjord, K.; Molina, T. J.

2007-01-01

Polymerase chain reaction (PCR) assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms. However, lack of standardized primers and PCR protocols has hampered comparability of data in previous clonality studies.

Aluminum triiodide induced complexation and structural rearrangement of the hexaphospha-pentaprismane cage, P6C4tBu4

International Nuclear Information System (INIS)

Al-Ktaifani, M. M.

2009-01-01

Treatment of P 6 C 4 t Bu 4 with the Lewis acid AlI 3 in toluene at room temperature unexpectedly results in a structural rearrangement affording the ionic complex [P 6 C 4 t Bu 4 H][AlI 4 ] which was fully characterized by multinuclear NMR spectroscopy and a single crystal X-ray diffraction study. Supportive evidence that the reaction might involve a simple intermediate Lewis acid-base adduct [AlI 3 (η 1 -P 6 C 4 t Bu 4 )] came from the isolation on one occasion of small number of crystals of the bis-Al adduct [(AlI)μ-(P 6 C 4 t Bu 4 )(AlI 3 )], whose molecular structure was also confirmed by a single crystal X-ray diffraction study. (author)

TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements.

Directory of Open Access Journals (Sweden)

Kamila Maliszewska-Olejniczak

2015-07-01

Full Text Available Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs. Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium

Chromogenic in situ hybridization is a reliable assay for detection of ALK rearrangements in adenocarcinomas of the lung.

Science.gov (United States)

Schildhaus, Hans-Ulrich; Deml, Karl-Friedrich; Schmitz, Katja; Meiboom, Maren; Binot, Elke; Hauke, Sven; Merkelbach-Bruse, Sabine; Büttner, Reinhard

2013-11-01

Reliable detection of anaplastic lymphoma kinase (ALK) rearrangements is a prerequisite for personalized treatment of lung cancer patients, as ALK rearrangements represent a predictive biomarker for the therapy with specific tyrosine kinase inhibitors. Currently, fluorescent in situ hybridization (FISH) is considered to be the standard method for assessing formalin-fixed and paraffin-embedded tissue for ALK inversions and translocations. However, FISH requires a specialized equipment, the signals fade rapidly and it is difficult to detect overall morphology and tumor heterogeneity. Chromogenic in situ hybridization (CISH) has been successfully introduced as an alternative test for the detection of several genetic aberrations. This study validates a newly developed ALK CISH assay by comparing FISH and CISH signal patterns in lung cancer samples with and without ALK rearrangements. One hundred adenocarcinomas of the lung were included in this study, among them 17 with known ALK rearrangement. FISH and CISH were carried out and evaluated according to the manufacturers' recommendations. For both assays, tumors were considered positive if ≥15% of tumor cells showed either isolated 3' signals or break-apart patterns or a combination of both. A subset of tumors was exemplarily examined by using a novel EML4 (echinoderm microtubule-associated protein-like 4) CISH probe. Red, green and fusion CISH signals were clearcut and different signal patterns were easily recognized. The percentage of aberrant tumor cells was statistically highly correlated (PCISH. On the basis of 86 samples that were evaluable by ALK CISH, we found a 100% sensitivity and 100% specificity of this assay. Furthermore, EML4 rearrangements could be recognized by CISH. CISH is a highly reliable, sensitive and specific method for the detection of ALK gene rearrangements in pulmonary adenocarcinomas. Our results suggest that CISH might serve as a suitable alternative to FISH, which is the current gold

Deletional rearrangement in the human T-cell receptor α-chain locus

International Nuclear Information System (INIS)

de Villartay, J.P.; Lewis, D.; Hockett, R.; Waldmann, T.A.; Korsmeyer, S.J.; Cohen, D.I.

1987-01-01

The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed α and β. In the course of characterizing human T-cell tumors with an immature (CD4 - , CD8 - ) surface phenotype, the authors detected a 2-kilobase α-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early α) located between the α-chain variable- and joining-region genes had been spliced to the α constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the α gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature α gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the γδ heterodimeric receptor and is deleted from mature (αβ-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (γδ-expressing) T cells and mature (αβ-expressing) T cells

Interleukin-1 beta gene deregulation associated with chromosomal rearrangement: A candidate initiating event for murine radiation-myeloid leukemogenesis

International Nuclear Information System (INIS)

Silver, A.; Boultwood, J.; Breckon, G.; Masson, W.; Adam, J.; Shaw, A.R.; Cox, R.

1989-01-01

The incidence of acute myeloid leukemia (AML) in CBA/H mice following exposure to single acute doses of ionizing radiation has previously been determined. A high proportion of these AMLs are characterized by rearrangement of murine chromosome 2 in the C2 and/or E5-F regions, and there is evidence that these events are a direct consequence of radiation damage to multipotential hemopoietic cells. Using a combination of in situ chromosome hybridization and mRNA analyses, we show that the cytokine gene interleukin-1 beta (IL-1 beta) is encoded in the chromosome 2 F region and is translocated in a chromosome 2---2 rearrangement in an x-ray-induced AML (N36). Also, IL-1 beta is specifically deregulated in N36 and in two other chromosome 2-rearranged AMLs but not in a fourth, which has two cytogenetically normal chromosome 2 copies. We suggest that radiation-induced specific chromosome 2 rearrangement associated with IL-1 beta deregulation may initiate murine leukemogenesis through the uncoupling of normal proliferative control mechanisms in multipotential hemopoietic cells

Reproductive Incompatibility Involving Senegalese Aedes aegypti (L Is Associated with Chromosome Rearrangements.

Directory of Open Access Journals (Sweden)

Laura B Dickson

2016-04-01

staining was used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3.

Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements

Science.gov (United States)

Dickson, Laura B.; Sharakhova, Maria V.; Timoshevskiy, Vladimir A.; Fleming, Karen L.; Caspary, Alex; Sylla, Massamba; Black, William C.

2016-01-01

was used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere) inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3. PMID:27105225

Phylogenetic signal from rearrangements in 18 Anopheles species by joint scaffolding extant and ancestral genomes.

Science.gov (United States)

Anselmetti, Yoann; Duchemin, Wandrille; Tannier, Eric; Chauve, Cedric; Bérard, Sèverine

2018-05-09

Genomes rearrangements carry valuable information for phylogenetic inference or the elucidation of molecular mechanisms of adaptation. However, the detection of genome rearrangements is often hampered by current deficiencies in data and methods: Genomes obtained from short sequence reads have generally very fragmented assemblies, and comparing multiple gene orders generally leads to computationally intractable algorithmic questions. We present a computational method, ADSEQ, which, by combining ancestral gene order reconstruction, comparative scaffolding and de novo scaffolding methods, overcomes these two caveats. ADSEQ provides simultaneously improved assemblies and ancestral genomes, with statistical supports on all local features. Compared to previous comparative methods, it runs in polynomial time, it samples solutions in a probabilistic space, and it can handle a significantly larger gene complement from the considered extant genomes, with complex histories including gene duplications and losses. We use ADSEQ to provide improved assemblies and a genome history made of duplications, losses, gene translocations, rearrangements, of 18 complete Anopheles genomes, including several important malaria vectors. We also provide additional support for a differentiated mode of evolution of the sex chromosome and of the autosomes in these mosquito genomes. We demonstrate the method's ability to improve extant assemblies accurately through a procedure simulating realistic assembly fragmentation. We study a debated issue regarding the phylogeny of the Gambiae complex group of Anopheles genomes in the light of the evolution of chromosomal rearrangements, suggesting that the phylogenetic signal they carry can differ from the phylogenetic signal carried by gene sequences, more prone to introgression.

Density, viscosity and surface tension of liquid phase Beckmann rearrangement mixtures

NARCIS (Netherlands)

Zuidhof, K.T.; Croon, de M.H.J.M.; Schouten, J.C.; Tinge, J.T.

2015-01-01

We have determined the density, dynamic viscosity, and surface tension of liquid phase Beckmann rearrangement mixtures, consisting of e-caprolactam and fuming oleum. These important properties have been measured in wide ranges of both temperature and molar ratios of acid and e-caprolactam, covering

Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer

Science.gov (United States)

Nilsson, R. Jonas A.; Karachaliou, Niki; Berenguer, Jordi; Gimenez-Capitan, Ana; Schellen, Pepijn; Teixido, Cristina; Tannous, Jihane; Kuiper, Justine L.; Drees, Esther; Grabowska, Magda; van Keulen, Marte; Heideman, Danielle A.M.; Thunnissen, Erik; Dingemans, Anne-Marie C.; Viteri, Santiago; Tannous, Bakhos A.; Drozdowskyj, Ana; Rosell, Rafael; Smit, Egbert F.; Wurdinger, Thomas

2016-01-01

Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK− platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone. PMID:26544515

Detection of genomic rearrangements in cucumber using genomecmp software

Science.gov (United States)

Kulawik, Maciej; Pawełkowicz, Magdalena Ewa; Wojcieszek, Michał; PlÄ der, Wojciech; Nowak, Robert M.

2017-08-01

Comparative genomic by increasing information about the genomes sequences available in the databases is a rapidly evolving science. A simple comparison of the general features of genomes such as genome size, number of genes, and chromosome number presents an entry point into comparative genomic analysis. Here we present the utility of the new tool genomecmp for finding rearrangements across the compared sequences and applications in plant comparative genomics.

Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci

NARCIS (Netherlands)

M.B. Rother (Magdalena); R.-J.T.S. Palstra (Robert-Jan); S. Jhunjhunwala (Suchit); K.A.M. Van Kester (Kevin A. M.); W.F.J. van IJcken (Wilfred); R.W. Hendriks (Rudi); J.J.M. van Dongen (Jacques); C. Murre (Cornelis); M.C. van Zelm (Menno)

2016-01-01

textabstractProgenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag-/- progenitor-B cells to determine whether Ig

Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

Science.gov (United States)

Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

2015-10-01

The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.

Science.gov (United States)

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

2014-06-05

The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Three-dimensional rearrangement of single atoms using actively controlled optical microtraps.

Science.gov (United States)

Lee, Woojun; Kim, Hyosub; Ahn, Jaewook

2016-05-02

We propose and demonstrate three-dimensional rearrangements of single atoms. In experiments performed with single 87Rb atoms in optical microtraps actively controlled by a spatial light modulator, we demonstrate various dynamic rearrangements of up to N = 9 atoms including rotation, 2D vacancy filling, guiding, compactification, and 3D shuffling. With the capability of a phase-only Fourier mask to generate arbitrary shapes of the holographic microtraps, it was possible to place single atoms at arbitrary geometries of a few μm size and even continuously reconfigure them by conveying each atom. For this purpose, we loaded a series of computer-generated phase masks in the full frame rate of 60 Hz of the spatial light modulator, so the animation of phase mask transformed the holographic microtraps in real time, driving each atom along the assigned trajectory. Possible applications of this method of transformation of single atoms include preparation of scalable quantum platforms for quantum computation, quantum simulation, and quantum many-body physics.

Insights into the formation of carlactone from in-depth analysis of the CCD8-catalyzed reactions

KAUST Repository

Bruno, Mark; Vermathen, Martina; Alder, Adrian; Wü st, Florian; Schaub, Patrick; van der Steen, Rob; Beyer, Peter; Ghisla, Sandro; Al-Babili, Salim

2017-01-01

Strigolactones (SLs) are a new class of phytohormones synthesized from carotenoids via carlactone. The complex structure of carlactone is not easily deducible from its precursor, a cis-configured β-carotene cleavage product, and is thus formed via a poorly understood series of reactions and molecular rearrangements, all catalyzed by only one enzyme, the carotenoid cleavage dioxygenase 8 (CCD8). Moreover, the reactions leading to carlactone are expected to form a second, yet unidentified product. In this study, we used (13) C and (18) O-labelling to shed light on the reactions catalyzed by CCD8. The characterization of the resulting carlactone by LC-MS and NMR, and the identification of the assumed, less accessible second product allowed us to formulate a minimal reaction mechanism for carlactone generation. This article is protected by copyright. All rights reserved.

Insights into the formation of carlactone from in-depth analysis of the CCD8-catalyzed reactions

KAUST Repository

Bruno, Mark

2017-02-10

Strigolactones (SLs) are a new class of phytohormones synthesized from carotenoids via carlactone. The complex structure of carlactone is not easily deducible from its precursor, a cis-configured β-carotene cleavage product, and is thus formed via a poorly understood series of reactions and molecular rearrangements, all catalyzed by only one enzyme, the carotenoid cleavage dioxygenase 8 (CCD8). Moreover, the reactions leading to carlactone are expected to form a second, yet unidentified product. In this study, we used (13) C and (18) O-labelling to shed light on the reactions catalyzed by CCD8. The characterization of the resulting carlactone by LC-MS and NMR, and the identification of the assumed, less accessible second product allowed us to formulate a minimal reaction mechanism for carlactone generation. This article is protected by copyright. All rights reserved.

Rh-Catalyzed rearrangement of vinylcyclopropane to 1,3-diene units attached to N-heterocycles

Directory of Open Access Journals (Sweden)

Alberto Brandi

2011-03-01

Full Text Available Dienes embedded in quinolizidine and indolizidine structures can be prepared in four steps from cyclic nitrones and bicyclopropylidene. The key intermediates α-spirocyclopropanated N-heterocyclic ketones, generated via a domino 1,3-dipolar cycloaddition/thermal rearrangement sequence, were converted by Wittig methylenation to the corresponding vinylcyclopropanes (VCPs, which underwent rearrangement to 1,3-dienes in the presence of the Wilkinson Rh(I complex under microwave heating. The previously unexplored Rh(I-catalyzed opening of the VCP moiety embedded in an azapolycyclic system occurs at high temperature (110–130 °C to afford the corresponding 1,3-dienes in moderate yield (34–53%.

HOXA9 is required for survival in human MLL-rearranged acute leukemias

NARCIS (Netherlands)

J. Faber (Joerg); A.V. Krivtsov (Andrei); M.C. Stubbs (Matthew); R. Wright (Renee); T.N. Davis (Tina); M.M. van den Heuvel-Eibrink (Marry); C.M. Zwaan (Christian Michel); A.L. Kung (Andrew); S.A. Armstrong (Scott)

2009-01-01

textabstractLeukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biologic characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression

Molecular Mechanisms and Diagnosis of Chromosome 22q11.2 Rearrangements

Science.gov (United States)

Emanuel, Beverly S.

2008-01-01

Several recurrent, constitutional genomic disorders are present on chromosome 22q. These include the translocations and deletions associated with DiGeorge and velocardiofacial syndrome and the translocations that give rise to the recurrent t(11;22) supernumerary der(22) syndrome (Emanuel syndrome). The rearrangement breakpoints on 22q cluster…

FASEB Summer Research Conference. Genetic Recombination and Chromosome Rearrangements

Energy Technology Data Exchange (ETDEWEB)

Jinks-Robertson, Sue

2002-02-01

The 2001 meeting entitled ''Genetic Recombination and Genome Rearrangements'' was held July 21-26 in Snowmass, Colorado. The goal of the meeting was to bring together scientists using diverse approaches to study all aspects of genetic recombination. This goal was achieved by integrating talks covering the genetics, biochemistry and structural biology of homologous recombination, site-specific recombination, and nonhomologous recombination. The format of the meeting consisted of a keynote address on the opening evening, two formal plenary sessions on each of the four full meeting days, a single afternoon workshop consisting of short talks chosen from among submitted abstracts, and afternoon poster sessions on each of the four full meeting days. The eight plenary session were entitled: (1) Recombination Mechanisms, (2) Prokaryotic Recombination, (3) Repair and Recombination, (4) Site-specific Recombination and Transposition, (5) Eukaryotic Recombination I, (6) Genome Rearrangements, (7) Meiosis, and (8) Eukaryotic Recombination II. Each session included a mix of genetic, biochemical and structural talks; talks were limited to 20 minutes, followed by 10 minutes of very lively, general discussion. Much of the data presented in the plenary sessions was unpublished, thus providing attendees with the most up-to-date knowledge of this rapidly-moving field.

Total synthesis of broussonetine F: the orthoamide Overman rearrangement of an allylic diol.

Science.gov (United States)

Hama, Naoto; Aoki, Toshihiro; Miwa, Shohei; Yamazaki, Miki; Sato, Takaaki; Chida, Noritaka

2011-02-18

A first total synthesis of broussonetine F from diethyl L-tartrate was achieved. The cornerstone of our synthesis was an orthoamide Overman rearrangement, which provided an allylic amino alcohol with complete diastereoselectivity.

Production of isomers in compound and transfer reactions with 4He ions

International Nuclear Information System (INIS)

Karamyan, S.A.; Aksenov, N.V.; Albin, Yu.A.; Bozhikov, G.A.; Dmitriev, S.N.; Starodub, G.Ya.; Vostokin, G.K.; Carroll, J.J.

2011-01-01

A well-known island of nuclear isomerism appears near A = 175-180 due to the deformation alignment of single-particle orbits at high angular momentum. This sometimes results in the formation of multi-quasiparticle states with record spin that are long-lived because of 'K-hindrance', i.e., symmetry rearrangement. Production methods and spectroscopic studies of these isomers remain a challenge for modern nuclear reaction and nuclear structure physics. Activities were produced by irradiation of 176 Yb(97.6%) enriched and nat Lu targets with 35-MeV 4 He ions from the internal beam of the U200 cyclotron. Induced activities were analyzed applying methods of radiochemistry and gamma spectroscopy. Yields of compound and nucleon-transfer reactions were measured and the isomer-to-ground state ratios were deduced. Calculated results were obtained using standard procedures to reproduce the (α, xn) cross sections, and the systematic behavior of the nucleon-transfer yields was established. The isomer-to-ground state ratios for direct reactions with 4 He ions were examined, resulting in a new characterization of the reaction mechanism

Insights into reaction mechanisms in heterogeneous catalysis revealed by in situ NMR spectroscopy.

Science.gov (United States)

Blasco, Teresa

2010-12-01

This tutorial review intends to show the possibilities of in situ solid state NMR spectroscopy in the elucidation of reaction mechanisms and the nature of the active sites in heterogeneous catalysis. After a brief overview of the more usual experimental devices used for in situ solid state NMR spectroscopy measurements, some examples of applications taken from the recent literature will be presented. It will be shown that in situ NMR spectroscopy allows: (i) the identification of stable intermediates and transient species using indirect methods, (ii) to prove shape selectivity in zeolites, (iii) the study of reaction kinetics, and (iv) the determination of the nature and the role played by the active sites in a catalytic reaction. The approaches and methodology used to get this information will be illustrated here summarizing the most relevant contributions on the investigation of the mechanisms of a series of reactions of industrial interest: aromatization of alkanes on bifunctional catalysts, carbonylation reaction of methanol with carbon monoxide, ethylbenzene disproportionation, and the Beckmann rearrangement reaction. Special attention is paid to the research carried out on the role played by carbenium ions and alkoxy as intermediate species in the transformation of hydrocarbon molecules on solid acid catalysts.

Unique mosaicism of structural chromosomal rearrangement: is chromosome 18 preferentially involved?

NARCIS (Netherlands)

Pater, J.M. de; Smeets, D.F.C.M.; Scheres, J.M.J.C.

2003-01-01

The mentally normal mother of a 4-year-old boy with del(18)(q21.3) syndrome was tested cytogenetically to study the possibility of an inherited structural rearrangement of chromosome 18. She was found to carry an unusual mosaicism involving chromosomes 18 and 21. Two unbalanced cell lines were seen

Aryl nitrene rearrangements: spectroscopic observation of a benzazirine and its ring expansion to a ketenimine by heavy-atom tunneling.

Science.gov (United States)

Inui, Hiroshi; Sawada, Kazuhiro; Oishi, Shigero; Ushida, Kiminori; McMahon, Robert J

2013-07-17

In the photodecompositions of 4-methoxyphenyl azide (1) and 4-methylthiophenyl azide (5) in argon matrixes at cryogenic temperatures, benzazirine intermediates were identified on the basis of IR spectra. As expected, the benzazirines photochemically rearranged to the corresponding ketenimines and triplet nitrenes. Interestingly, with the methylthio substituent, the rearrangement of benzazirine 8 to ketenimine 7 occurred at 1.49 × 10(-5) s(-1) even in the dark at 10 K, despite a computed activation barrier of 3.4 kcal mol(-1). Because this rate is 10(57) times higher than that calculated for passing over the barrier and because it shows no temperature dependence, the rearrangement mechanism is interpreted in terms of heavy-atom tunneling.

Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

International Nuclear Information System (INIS)

Huang, Xionggao; Wei, Yantao; Ma, Haizhi; Zhang, Shaochong

2012-01-01

Highlights: ► Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. ► Rac1 is activated in vitreous-transformed RPE cells. ► Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. ► Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. ► The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous-transformed human RPE cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and

Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Huang, Xionggao [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Department of Ophthalmology, Hainan Medical College, Haikou (China); Wei, Yantao; Ma, Haizhi [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Zhang, Shaochong, E-mail: zhshaochong@163.com [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. Black-Right-Pointing-Pointer Rac1 is activated in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous

Transesterification of Jatropha curcas oil glycerides: Theoretical and experimental studies of biodiesel reaction

Energy Technology Data Exchange (ETDEWEB)

Neyda C. Om Tapanes; Donato A. Gomes Aranda; Jose W. de Mesquita Carneiro; Octavio A. Ceva Antunes [Universidade Federal do Rio de Janeiro, Rio de Janeiro (Brazil). Laboratorio GREENTEC

2008-08-15

Vegetal oil, also known as triglycerides, is a mixture of fatty acid triesters of glycerol. In the triglycerides alkyl chains of Jatropha curcas oil, predominate the palmitic, oleic and linoleic fatty acids. The process usually used to convert these triglycerides to biodiesel is called transesterification. The overall process is a sequence of three equivalent, consecutive and reversible reactions, in which di- and monoglycerides are formed as intermediates. Semi-empirical AM1 molecular orbital calculations were used to investigate the reaction pathways of base-catalyzed transesterification of glycerides of palmitic, oleic and linoleic acid. The most probable pathway and the rate determining-step of the reactions were estimated from the molecular orbital calculations. Our results suggest the formation of only one tetrahedral intermediate, which in a subsequent step rearranges to form the products. The rate determining-step is the break of this tetrahedral intermediate. 27 refs., 6 figs., 4 tabs.

Actin cytoskeleton rearrangements in Arabidopsis roots under stress and during gravitropic response

Science.gov (United States)

Pozhvanov, Gregory; Medvedev, Sergei; Suslov, Dmitry; Demidchik, Vadim

Among environmental factors, gravity vector is the only one which is constant in direction and accompanies the whole plant ontogenesis. That said, gravity vector can be considered as an essential factor for correct development of plants. Gravitropism is a plant growth response against changing its position relative to the gravity vector. It is well estableshed that gravitropism is directed by auxin redistribution across the gravistimulated organ. In addition to auxin, actin cytoskeleton was shown to be involved in gravitropism at different stages: gravity perception, signal transduction and gravitropic bending formation. However, the relationship between IAA and actin is still under discussion. In this work we studied rearrangements of actin cytoskeleton during root gravitropic response. Actin microfilaments were visualized in vivo in GFP-fABD2 transgenic Arabidopsis plants, and their angle distribution was acquired from MicroFilament Analyzer software. The curvature of actin microfilaments in root elongation zone was shown to be increased within 30-60 min of gravistimulation, the fraction of axially oriented microfilaments decreased with a concomitant increase in the fraction of oblique and transversally oriented microfilaments. In particular, the fraction of transversally oriented microfilaments (i.e. parallel to the gravity vector) increased 3-5 times. Under 10 min of sub-lethal salt stress impact, actin microfilament orientations widened from an initial axial orientation to a set of peaks at 15(°) , 45(°) and 90(°) . We conclude that the actin cytoskeleton rearrangements observed are associated with the regulation of basic mechanisms of cell extension growth by which the gravitropic bending is formed. Having common stress-related features, gravity-induced actin cytoskeleton rearrangement is slower but results in higher number of g-vector-parallel microfilaments when compared to salt stress-induced rearrangement. Also, differences in gravistimulated root

Screening for ROS1 gene rearrangements in non-small cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target

Science.gov (United States)

Selinger, Christina I; Li, Bob T; Pavlakis, Nick; Links, Matthew; Gill, Anthony J; Lee, Adrian; Clarke, Stephen; Tran, Thang N; Lum, Trina; Yip, Po Yee; Horvath, Lisa; Yu, Bing; Kohonen-Corish, Maija RJ; O’Toole, Sandra A; Cooper, Wendy A

2016-01-01

Aims To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. Methods A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective NSCLC cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in situ hybridisation (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with ≥15% of cells with split signals considered positive for rearrangement. Results Eighty eight cases (32%) from the retrospective cohort showed staining by ROS1 IHC, and one case (0.4%) showed ROS1 rearrangement by FISH. Nineteen of the prospective diagnostic cases showed ROS1 IHC staining of which 12 (12%) cases were confirmed as ROS1 rearranged by FISH. There were no ROS1 rearranged cases that showed no expression of ROS1 with IHC. The ROS1 rearranged cases in the prospective cohort were all EGFR wildtype and ALK rearrangement negative. The sensitivity of ROS1 IHC in the retrospective cohort was 100% and specificity was 76%. Conclusions ROS1 rearrangements are rare events in lung adenocarcinomas. Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK positive cases and use of IHC to screen for potentially positive cases can be used to enrich for the likelihood of a identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time consuming FISH testing in all cases. PMID:27599111

[Synthetic biology and rearrangements of microbial genetic material].

Science.gov (United States)

Liang, Quan-Feng; Wang, Qian; Qi, Qing-Sheng

2011-10-01

As an emerging discipline, synthetic biology has shown great scientific values and application prospects. Although there have been many reviews of various aspects on synthetic biology over the last years, this article, for the first time, attempted to discuss the relationship and difference between microbial genetics and synthetic biology. We summarized the recent development of synthetic biology in rearranging microbial genetic materials, including synthesis, design and reduction of genetic materials, standardization of genetic parts and modularization of genetic circuits. The relationship between synthetic biology and microbial genetic engineering was also discussed in the paper.

Conjugation-promoted reaction of open-cage fullerene: A density functional theory study

KAUST Repository

Guo, Yong

2012-01-20

Density functional theory calculations are performed to study the addition mechanism of e-rich moieties such as triethyl phosphite to a carbonyl group on the rim of a fullerene orifice. Three possible reaction channels have been investigated. The obtained results show that the reaction of a carbonyl group on a fullerene orifice with triethyl phosphite most likely proceeds along the classical Abramov reaction; however, the classical product is not stable and is converted into the experimental product. An attack on a fullerene carbonyl carbon will trigger a rearrangement of the phosphate group to the carbonyl oxygen as the conversion transition state is stabilized by fullerene conjugation. This work provides a new insight on the reactivity of open-cage fullerenes, which may prove helpful in designing new switchable fullerene systems. Not that classical: The reaction of a carbonyl group on the fullerene orifice with triethyl phosphite most likely proceeds following the Abramov reaction to firstly form a classical product. However, this product is not stable and turns into an experimental product as the conversion transition state is stabilized by fullerene conjugation (see picture). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms

Directory of Open Access Journals (Sweden)

Meller Jaroslaw

2007-03-01

Full Text Available Abstract Background Identifying syntenic regions, i.e., blocks of genes or other markers with evolutionary conserved order, and quantifying evolutionary relatedness between genomes in terms of chromosomal rearrangements is one of the central goals in comparative genomics. However, the analysis of synteny and the resulting assessment of genome rearrangements are sensitive to the choice of a number of arbitrary parameters that affect the detection of synteny blocks. In particular, the choice of a set of markers and the effect of different aggregation strategies, which enable coarse graining of synteny blocks and exclusion of micro-rearrangements, need to be assessed. Therefore, existing tools and resources that facilitate identification, visualization and analysis of synteny need to be further improved to provide a flexible platform for such analysis, especially in the context of multiple genomes. Results We present a new tool, Cinteny, for fast identification and analysis of synteny with different sets of markers and various levels of coarse graining of syntenic blocks. Using Hannenhalli-Pevzner approach and its extensions, Cinteny also enables interactive determination of evolutionary relationships between genomes in terms of the number of rearrangements (the reversal distance. In particular, Cinteny provides: i integration of synteny browsing with assessment of evolutionary distances for multiple genomes; ii flexibility to adjust the parameters and re-compute the results on-the-fly; iii ability to work with user provided data, such as orthologous genes, sequence tags or other conserved markers. In addition, Cinteny provides many annotated mammalian, invertebrate and fungal genomes that are pre-loaded and available for analysis at http://cinteny.cchmc.org. Conclusion Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances

Reactions of carbon radicals generated by 1,5-transposition of reactive centers

Directory of Open Access Journals (Sweden)

ZIVORAD CEKOVIC

2005-03-01

Full Text Available Radical intermediates can undergo specific reactions, such as intramolecular rearrangements, i.e., the transpositions of radical centers, which are not known in classical ionic organic reactions. 1,5-Transposition of a radical center to a non-activated carbon atom are of great synthetic importance. It can be successfully applied for the introduction of different functional groups (oxygen, nitrogen, sulfur, halogens onto a carbon atom remote from the present functional group. In addition to functionalization of a remote non-activated carbon atom, the formation of new C-C bonds on the d-carbon atom have also been achieved. 1,5-Transposition of the radical centers takes place from alkoxyl, aminyl and carbon radicals to a remote carbon atom. Relocation of the radical centers preferentially involves 1,5-transfer of a hydrogen atom, although migrations of some other groups are known. The reactions of the carbon radical generated by 1,5-relocation of the radical center are presented and their synthetic applications are reviewed.

Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder

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Hooper Sean D

2012-12-01

Full Text Available Abstract Background Tourette Syndrome (TS is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood. Methods Using cytogenetics and FISH analysis, we identified an apparently balanced t(6,22(q16.2;p13 in a male patient with TS and obsessive-compulsive disorder (OCD. In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband. Results Sequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32 and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband’s mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome. Conclusions We conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.

Aminocyclopentanols as sugar mimics. Synthesis from unsaturated bicyclic lactones by Overman rearrangement

DEFF Research Database (Denmark)

Bøjstrup, Marie; Fanefjord, Mette; Lundt, Inge

2007-01-01

Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta-D-N-acetylglucosaminid...

The diverse effects of complex chromosome rearrangements and chromothripsis in cancer development

NARCIS (Netherlands)

De Pagter, Mirjam S.; Kloosterman, Wigard P.

2015-01-01

In recent years, enormous progress has been made with respect to the identification of somatic mutations that contribute to cancer development. Mutation types range from small substitutions to large structural genomic rearrangements, including complex reshuffling of the genome. Sets of mutations in

Prenylcoumarins in One or Two Steps by a Microwave-Promoted Tandem Claisen Rearrangement/Wittig Olefination/Cyclization Sequence.

Science.gov (United States)

Schultze, Christiane; Schmidt, Bernd

2018-05-04

The one-pot synthesis of 8-prenylcoumarins from 1,1-dimethylallylated salicylaldehydes and the stabilized ylide [(ethoxycarbonyl)methylene]triphenylphosphorane under microwave conditions was found to have a limited scope. The sequence suffers from a difficult and sometimes low-yielding synthesis of the precursors and from a competing deprenylation upon microwave irradiation. This side reaction occurs in particular with electron rich arenes with two or more alkoxy groups at adjacent positions, a prominent substitution pattern in naturally occurring 8-prenylcoumarins. Both limitations of this one-step sequence were overcome by a two-step synthesis consisting of a microwave-promoted tandem allyl ether Claisen rearrangement/Wittig olefination and a subsequent olefin cross metathesis with 2-methyl-2-butene. The cross metathesis step proceeds with a high selectivity and yields exclusively the desired prenyl, rather than the alternative crotyl substituent. Several naturally occurring 8-prenylcoumarins that were previously inaccessible have been synthesized in good overall yields along this route.

Insights into structural variations and genome rearrangements in prokaryotic genomes.

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Periwal, Vinita; Scaria, Vinod

2015-01-01

Structural variations (SVs) are genomic rearrangements that affect fairly large fragments of DNA. Most of the SVs such as inversions, deletions and translocations have been largely studied in context of genetic diseases in eukaryotes. However, recent studies demonstrate that genome rearrangements can also have profound impact on prokaryotic genomes, leading to altered cell phenotype. In contrast to single-nucleotide variations, SVs provide a much deeper insight into organization of bacterial genomes at a much better resolution. SVs can confer change in gene copy number, creation of new genes, altered gene expression and many other functional consequences. High-throughput technologies have now made it possible to explore SVs at a much refined resolution in bacterial genomes. Through this review, we aim to highlight the importance of the less explored field of SVs in prokaryotic genomes and their impact. We also discuss its potential applicability in the emerging fields of synthetic biology and genome engineering where targeted SVs could serve to create sophisticated and accurate genome editing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Gas phase reactions of protonated 1,3-diphenylpropyne and some isomeric [C15H13]+ ions

OpenAIRE

Bäther, Wolfgang; Kuck, Dietmar; Grützmacher, Hans-Friedrich

1985-01-01

Metastable (3-phenyl-2-propynyl)benzenium ions, generated by electron impact induced fragmentation from the appropriately substituted 1,4-dihydrobenzoic acid, react by loss of ·CH3 and C6H6. The study of deuterated derivatives reveals that hydrogen/deuterium exchanges involving all hydrogen and deuterium atoms precede the fragmentations. The results suggest a skeletal rearrangement by electrophilic ring-closure reactions giving rise to protonated phenylindene and protonated 9,10-methano-9,10-...

Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.

Science.gov (United States)

Akyurek, Nalan; Uner, Aysegul; Benekli, Mustafa; Barista, Ibrahim

2012-09-01

Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases. Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients. MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non-GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors. Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis. Copyright © 2011 American Cancer Society.

Recent applications of ring-rearrangement metathesis in organic synthesis

Directory of Open Access Journals (Sweden)

Sambasivarao Kotha

2015-10-01

Full Text Available Ring-rearrangement metathesis (RRM involves multiple metathesis processes such as ring-opening metathesis (ROM/ring-closing metathesis (RCM in a one-pot operation to generate complex targets. RRM delivers complex frameworks that are difficult to assemble by conventional methods. The noteworthy point about this type of protocol is multi-bond formation and it is an atom economic process. In this review, we have covered literature that appeared during the last seven years (2008–2014.

Clonality assessment of lymphoproliferative lesions using the polymerase chain reaction: An analysis of two methods

Directory of Open Access Journals (Sweden)

Nikhil Moorchung

2011-01-01

Full Text Available Background: Lymphoid malignancies are a heterogeneous group of disorders which may be difficult to differentiate from reactive proliferations even after immunohistochemistry. Polymerase chain reaction (PCR is believed to be a good adjunct tool for diagnosis. Materials and Methods: We examined 24 cases of neoplastic and non-neoplastic lymphoproliferative lesions in this study and evaluated the PCR as an additional tool in the confirmation of the diagnosis. Two different PCR methodologies were evaluated. Results: In the evaluation of the T-cell PCR, it was seen that the correlation using both the commercial kits and the custom-synthesized primers was highly significant at a P value of 0.05. Conclusions: Both the methods showed an excellent concordance for T-cell γ gene rearrangements, However, the same was not seen in the B-cell receptor rearrangements. This may be because of the small sample size or the inability of consensus V primers to recognize complementary DNA sequences in all of the V segments.

A DFT exploration of the enantioselective rearrangement of cyclohexene oxide to cyclohexenol

DEFF Research Database (Denmark)

Brandt, Peter; Norrby, Per-Ola; Andersson, Pher G.

2003-01-01

In this paper, we present computational results for the (1S,3R,4R)-3-(pyrrolidinyl)-methyl-2-azabicyclo[2.2.1]heptane mediated rearrangement of cyclohexene oxide. The results nicely explain the differences in enantioselectivities between catalytic and stoichiometric mode between different ligands...

Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus

NARCIS (Netherlands)

Ulasli, M.; Verheije, M.H.; de Haan, C.A.M.; Reggiori, F.M.

2011-01-01

Coronaviruses (CoV) are enveloped positive-strand RNA viruses that induce different membrane rearrangements in infected cells in order to efficiently replicate and assemble. The origin, the protein composition and the function of these structures are not well established. To shed further light on

The formation and recovery of two-break chromosome rearrangements from irradiated spermatozoa of Drosophila melanogaster

International Nuclear Information System (INIS)

Leigh, B.

1978-01-01

Chromosome and chromatid-type rearrangements can be induced by exposure of spermatozoa of Drosophila to ionising radiation. A model, proposed to explain the formation and recovery of compound autosomes, has been extended to account for the induction of centric fragments capped by a duplication of paternal chromosome material. Three basic assumptions have been used; (1) that the sperm nucleus contains a haploid set of unreplicated chromosomes, (2) that the broken chromosome ends can be joined together before or after replication, and (3) that one of the first two cleavage nuclei may be lost and an adult organism derived from the other. The present paper reports a theoretical application of this combination of aasumptions to the general case of the formation and recovery of two-break rearrangements. This has led to an elucidation of the relation between repeats, compounds, fragments, and deficiencies on the one hand and inversions and translocations on the other hand. Dicentric chromosomes and segmental aneuploidy can be simply explained. A selective screen is formed by the segregation of chromatid rearrangements and the aneuploidy tolerance levels of the early cleavage nuclei. Thus there is an alternative way of explaining observations which might indicate preferential breakage or joining

Rearrangement and convergence improvement of the Born series in scattering theory on the basis of orthogonal projections

International Nuclear Information System (INIS)

Kukulin, V.I.; Pomerantsev, V.N.

1976-01-01

Method of rearrangement of the Born series in scattering theory is proposed which uses the corthogonal projecting pseudopotentials (OPP) proposed recently. It is proved vigorously that the rearranged Born series will converge for all negative and small positive energy value seven in the presence of bound states. Method of correct introduction of scattering operators in orthogonal subspaces is displayed. Comparison of the OPP method with the projection technique developed by Feschbach is given. Physical applications of the method formulated are discussed

Design of collimating and rearrangement systems of laser diode array beam

Science.gov (United States)

Gao, Runmei; Fang, Tao; Fu, Rulian; Yao, Jianquan

2015-10-01

To improve the laser diode output beam quality, micro-cylindrical lens and the step-type lens combination are designed. The former is used to collimate beam in fast-axis direction, while the latter plays a role in the slow-axis of splitting and the rearrangement. The micro-column semi-elliptical lens is made with the drops of spherical zoom lensin electric field and with the help of the material properties of light-cured production, which can reduce the reflection of the front surface and total reflection loss of the after. The divergence angle in the fast axis is compressed to roughly the same as that in the slow-axis direction; Stepped lens splits compressed long strip beam in the slow axis, with parallelogram style of level equidistant and rearrange in the fast axis direction. The spot in the slow axis gets smaller and the spot becomes larger in the fast axis. At last divergence angle and the beam spot achieve balanced in the fast axis and slow axis, optical parameters BPP integrates approximate the same, and beam quality can be improved.

Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci.

Science.gov (United States)

Rother, Magdalena B; Palstra, Robert-Jan; Jhunjhunwala, Suchit; van Kester, Kevin A M; van IJcken, Wilfred F J; Hendriks, Rudi W; van Dongen, Jacques J M; Murre, Cornelis; van Zelm, Menno C

2016-01-08

Progenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag(-/-) progenitor-B cells to determine whether Ig locus contraction or nuclear positioning is decisive for stepwise rearrangements. We found that both Ig loci were contracted in pro-B and pre-B cells. Igh relocated from the nuclear lamina to central domains only at the pro-B cell stage, whereas, Igκ remained sequestered at the lamina, and only at the pre-B cell stage located to central nuclear domains. Finally, in vitro induced re-positioning of Ig alleles away from the nuclear periphery increased germline transcription of Ig loci in pre-pro-B cells. Thus, Ig locus contraction juxtaposes genomically distant elements to mediate efficient recombination, however, sequential positioning of Ig loci away from the nuclear periphery determines stage-specific accessibility of Ig loci. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chromosomal rearrangements and gene flow over time in an inter-specific hybrid zone of the Sorex araneus group.

Science.gov (United States)

Yannic, G; Basset, P; Hausser, J

2009-06-01

Most hybrid zones have existed for hundreds or thousands of years but have generally been observed for only a short time period. Studies extending over periods long enough to track evolutionary changes in the zones or assess the ultimate outcome of hybridization are scarce. Here, we describe the evolution over time of the level of genetic isolation between two karyotypically different species of shrews (Sorex araneus and Sorex antinorii) at a hybrid zone located in the Swiss Alps. We first evaluated hybrid zone movement by contrasting patterns of gene flow and changes in cline parameters (centre and width) using 24 microsatellite loci, between two periods separated by 10 years apart. Additionally, we tested the role of chromosomal rearrangements on gene flow by analysing microsatellite loci located on both rearranged and common chromosomes to both species. We did not detect any movement of the hybrid zone during the period analysed, suggesting that the zone is a typical tension zone. However, the gene flow was significantly lower among the rearranged than the common chromosomes for the second period, whereas the difference was only marginally significant for the first period. This further supports the role of chromosomal rearrangements on gene flow between these taxa.

Myeloid neoplasm with prominent eosinophilia and PDGFRA rearrangement treated with imatinib mesylate

DEFF Research Database (Denmark)

Rathe, Mathias; Kielsgaard Kristensen, Thomas; Møller, Michael Boe

2010-01-01

of FIP1L1-PDGFRA positive disease has been reported. We report a 2-year-old female with a myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRA. Treatment with imatinib resulted in complete and durable clinical, hematological, and molecular remission within 3 months after starting...

Transient spontaneous remission in congenital MLL-AF10 rearranged acute myeloid leukemia presenting with cardiorespiratory failure and meconium ileus.

Science.gov (United States)

Gyárfás, Tobias; Wintgens, Juergen; Biskup, Wolfgang; Oschlies, Ilske; Klapper, Wolfram; Siebert, Reiner; Bens, Susanne; Haferlach, Claudia; Meisel, Roland; Kuhlen, Michaela; Borkhardt, Arndt

2016-12-01

Neonatal leukemia is a rare disease with an estimated prevalence of about one to five in a million neonates. The majority being acute myeloid leukemia (AML), neonatal leukemia can present with a variety of symptoms including hyperleucocytosis, cytopenia, hepatosplenomegaly, and skin infiltrates. Chromosomal rearrangements including mixed lineage leukemia (MLL) translocations are common in neonatal AML. A female neonate born at 34 weeks gestation presented with cardiorespiratory failure, hepatosplenomegaly, pancytopenia, and coagulopathy. She required intensive care treatment including mechanical ventilation, high-dose catecholamine therapy, and multiple transfusions. Small intestinal biopsy obtained during laparotomy for meconium ileus revealed an infiltrate by an undifferentiated monoblastic, MLL-rearranged leukemia. No other manifestations of leukemia could be detected. After spontaneous clinical remission, lasting 5 months without any specific treatment, the patient presented with leukemia cutis and full-blown monoblastic leukemia. MLL-AF10-rearranged AML could be re-diagnosed and successfully treated with chemotherapy and hematopoietic stem cell transplantation. Our patient exhibited a unique manifestation of neonatal MLL-AF10 rearranged AML with cardiorespiratory failure and intestinal infiltration. It highlights the importance of leukemia in the differential diagnosis of neonatal distress, congenital hematological abnormalities, and skin lesions.

Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle-Kirmse Reaction of α-Diazo Pyrazoleamides.

Science.gov (United States)

Lin, Xiaobin; Tang, Yu; Yang, Wei; Tan, Fei; Lin, Lili; Liu, Xiaohua; Feng, Xiaoming

2018-03-07

Although high enantioselectivity of [2,3]-sigmatropic rearrangement of sulfonium ylides (Doyle-Kirmse reaction) has proven surprisingly elusive using classic chiral Rh(II) and Cu(I) catalysts, in principle it is due to the difficulty in fine discrimination of the heterotopic lone pairs of sulfur and chirality inversion at sulfur of sulfonium ylides. Here, we show that the synergistic merger of new α-diazo pyrazoleamides and a chiral N, N'-dioxide-nickel(II) complex catalyst enables a highly enantioselective Doyle-Kirmse reaction. The pyrazoleamide substituent serves as both an activating and a directing group for the ready formation of a metal-carbene- and Lewis-acid-bonded ylide intermediate in the assistance of a dual-tasking nickel(II) complex. An alternative chiral Lewis-acid-bonded ylide pathway greatly improves the product enantiopurity even for the reaction of a symmetric diallylsulfane. The majority of transformations over a series of aryl- or vinyl-substituted α-diazo pyrazoleamindes and sulfides proceed rapidly (within 5-20 min in most cases) with excellent results (up to 99% yield and 96% ee), providing a breakthrough in enantioselective Doyle-Kirmse reaction.

Analysis of TCRAD gene recombination: radio-induct rearrangement and signal joint structure

International Nuclear Information System (INIS)

Touvrey, C.

2005-09-01

We have shown that irradiation of pre-TCR-deficient CD3ε -/- mice restores thymocyte differentiation, by a p53-dependent and by a p53-independent pathway. Events normally associated during normal thymocyte development are dissociated in response to radiation exposure. Both of these pathways require LAT expression. Therefore, radiation exposure activates pre-TCR-like signals. TCRA gene rearrangement is induced following radiation exposure. The signal joints resulting from TCRA gene rearrangement have the same structure than those found in wild type mice. All signal joint analyzed in un-manipulated wild type mice do exhibit junctional diversity. This diversity results mainly from TdT activity. We present evidences that proteins involved in DNA repair and genomic stability participated in SJ formation. We propose that signal joint diversity is not an aberrant process but is a key feature of V(D)J recombination. All our work increases our understanding of molecular events associated with V(D)J recombination. (author)

Reactivity of N-heterocyclic carbene-pyridine palladacyclopentadiene complexes toward halogen addition. The unpredictable course of the reaction.

Science.gov (United States)

Visentin, Fabiano; Santo, Claudio; Scattolin, Thomas; Demitri, Nicola; Canovese, Luciano

2017-08-08

As an extension of a previously published work we have reacted some palladacyclopentadiene complexes stabilized by bidentate N-heterocyclic carbene-pyridine or monodentate N-heterocyclic carbene-pyridine and isocyanide ligands with the halogens I 2 and Br 2 . All the bidentate and monodentate complexes react with halogens to give at first the expected σ-coordinated butadienyl fragment. However, two of the less hindered NHC carbene-pyridine bidentate butadienyl iodo derivatives undergo a further rearrangement and novel Pd(ii) complexes characterized by a ten term coordinative ring were isolated and characterized. In the most favorable case we were able to carry out the kinetics of rearrangement and measure its reaction rate. Moreover, we have surmised a plausible mechanism on the basis of a dedicated computational approach and in one case the surprising structure characterized by the ten term coordinative ring was resolved by X-ray diffraction.

Rearrangement of Upstream Sequences of the hTERT Gene During Cellular Immortalization

Science.gov (United States)

Zhao, Yuanjun; Wang, Shuwen; Popova, Evgenya Y.; Grigoryev, Sergei A.; Zhu, Jiyue

2010-01-01

Telomerase expression, resulting from transcriptional activation of the hTERT gene, allows cells to acquire indefinite proliferative potential during cellular immortalization and tumorigenesis. However, mechanisms of hTERT gene activation in many immortal cell lines and cancer cells are poorly understood. Here, we report our studies on hTERT activation using genetically related pairs of telomerase-negative (Tel−) and -positive (Tel+) fibroblast lines. First, whereas transiently transfected plasmid reporters did not recapitulate the endogenous hTERT promoter, the promoter in chromosomally integrated bacterial artificial chromosome (BAC) reporters was activated in a subset of Tel+ cells, indicating that activation of the hTERT promoter required native chromatin context and/or distal regulatory elements. Second, the hTERT gene, located near the telomere of chromosome 5p, was translocated in all three Tel+ cell lines but not in their parental pre-crisis cells and Tel− immortal siblings. The breakage points were mapped to regions upstream of the hTERT promoter, indicating that the hTERT gene was the target of these chromosomal rearrangements. In two Tel+ cell lines, translocation of the endogenous hTERT gene appeared to be the major mechanism of its activation as the activity of hTERT promoter in many chromosomally integrated BAC reporters, with intact upstream and downstream neighboring loci, remained relatively low. Therefore, our results suggest that rearrangement of upstream sequences is an important new mechanism of hTERT promoter activation during cellular immortalization. The chromosomal rearrangements likely occurred during cellular crisis and facilitated by telomere dysfunction. Such translocations allowed the hTERT promoter to escape from the native condensed chromatin environment. PMID:19672873

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

Directory of Open Access Journals (Sweden)

José Enrique Barquera-Lozada

2017-09-01

Full Text Available It has been proposed that elemanes are biogenetically formed from germacranes by Cope sigmatropic rearrangements. Normally, this reaction proceeds through a transition state with a chair conformation. However, the transformation of schkuhriolide (germacrane into elemanschkuhriolide (elemane may occur through a boat transition state due to the final configuration of the elemanschkuhriolide, but this transition state is questionable due to its high energy. The possible mechanisms of this transformation were studied in the density functional theory frame. The mechanistic differences between the transformation of (Z,E-germacranes and (E,E-germacranes were also studied. We found that (Z,E-germacranolides are significantly more stable than (E,E-germacranolides and elemanolides. In the specific case of schkuhriolide, even when the boat transition state is not energetically favored, a previous hemiacetalization lowers enough the energetic barrier to allow the formation of a very stable elemanolide that is even more stable than its (Z,E-germacrane.

The TEL-AML1 real-time quantitative polymerase chain reaction (PCR) might replace the antigen receptor-based genomic PCR in clinical minimal residual disease studies in children with acute lymphoblastic leukaemia

NARCIS (Netherlands)

de Haas, V.; Breunis, W. B.; dee, R.; Verhagen, O. J. H. M.; Kroes, W.; van Wering, E. R.; van Dongen, J. J. M.; van den Berg, H.; van der Schoot, C. E.

2002-01-01

Prospective studies in children with B-precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T-cell receptor (TCR) gene rearrangements as targets can be used to identify patients

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

Science.gov (United States)

Aoki, Yuki; Watanabe, Takashi; Saito, Yoriko; Kuroki, Yoko; Hijikata, Atsushi; Takagi, Masatoshi; Tomizawa, Daisuke; Eguchi, Mariko; Eguchi-Ishimae, Minenori; Kaneko, Akiko; Ono, Rintaro; Sato, Kaori; Suzuki, Nahoko; Fujiki, Saera; Koh, Katsuyoshi; Ishii, Eiichi; Shultz, Leonard D.; Ohara, Osamu; Mizutani, Shuki

2015-01-01

Translocation of the mixed-lineage leukemia (MLL) gene with AF4, AF9, or ENL results in acute leukemia with both lymphoid and myeloid involvement. We characterized leukemia-initiating cells (LICs) in primary infant MLL-rearranged leukemia using a xenotransplantation model. In MLL-AF4 patients, CD34+CD38+CD19+ and CD34−CD19+ cells initiated leukemia, and in MLL-AF9 patients, CD34−CD19+ cells were LICs. In MLL-ENL patients, either CD34+ or CD34− cells were LICs, depending on the pattern of CD34 expression. In contrast, in patients with these MLL translocations, CD34+CD38−CD19−CD33− cells were enriched for normal hematopoietic stem cells (HSCs) with in vivo long-term multilineage hematopoietic repopulation capacity. Although LICs developed leukemic cells with clonal immunoglobulin heavy-chain (IGH) rearrangement in vivo, CD34+CD38−CD19−CD33− cells repopulated recipient bone marrow and spleen with B cells, showing broad polyclonal IGH rearrangement and recipient thymus with CD4+ single positive (SP), CD8+ SP, and CD4+CD8+ double-positive (DP) T cells. Global gene expression profiling revealed that CD9, CD32, and CD24 were over-represented in MLL-AF4, MLL-AF9, and MLL-ENL LICs compared with normal HSCs. In patient samples, these molecules were expressed in CD34+CD38+ and CD34− LICs but not in CD34+CD38−CD19−CD33− HSCs. Identification of LICs and LIC-specific molecules in primary human MLL-rearranged acute lymphoblastic leukemia may lead to improved therapeutic strategies for MLL-rearranged leukemia. PMID:25538041

PMS2 inactivation by a complex rearrangement involving an HERV retroelement and the inverted 100-kb duplicon on 7p22.1.

Science.gov (United States)

Vogt, Julia; Wernstedt, Annekatrin; Ripperger, Tim; Pabst, Brigitte; Zschocke, Johannes; Kratz, Christian; Wimmer, Katharina

2016-11-01

Biallelic PMS2 mutations are responsible for more than half of all cases of constitutional mismatch repair deficiency (CMMRD), a recessively inherited childhood cancer predisposition syndrome. The mismatch repair gene PMS2 is partly embedded within one copy of an inverted 100-kb low-copy repeat (LCR) on 7p22.1. In an individual with CMMRD syndrome, PMS2 was found to be homozygously inactivated by a complex chromosomal rearrangement, which separates the 5'-part from the 3'-part of the gene. The rearrangement involves sequences of the inverted 100-kb LCR and a human endogenous retrovirus element and may be associated with an inversion that is indistinguishable from the known inversion polymorphism affecting the ~0.7-Mb sequence intervening the LCR. Its formation is best explained by a replication-based mechanism (RBM) such as fork stalling and template switching/microhomology-mediated break-induced replication (FoSTeS/MMBIR). This finding supports the hypothesis that the inverted LCR can not only facilitate the formation of the non-allelic homologous recombination-mediated inversion polymorphism but it also promotes the occurrence of more complex rearrangements that can be associated with a large inversion, as well, but are mediated by a RBM. This further suggests that among the inversion polymorphism on 7p22.1, more complex rearrangements might be hidden. Furthermore, as the locus is embedded in a common fragile site (CFS) region, this rearrangement also supports the recently raised hypothesis that CFS sequence motifs may facilitate replication-based rearrangement mechanisms.

Reactions of oxygen containing structures in coal pyrolysis

Energy Technology Data Exchange (ETDEWEB)

Hodek, W.; Kirschstein, J.; Van Heek, K.-H. (DMT-Gesellschaft fuer Forschung und Pruefung mbH, Essen (Germany, F.R.))

1991-03-01

In coal pyrolysis O-containing structures such as ether bridges and phenolic groups play an important role. Their reactions were studied by non-isothermal pyrolysis of a high volatile bituminous coal and some model polymers with gas chromatographic detection of the gaseous pyrolysis products. The coal was separated into the maceral groups vitrinite, exinite and inertinite, which showed markedly different pyrolysis behaviour. The formation of CO, methane and benzene was measured versus temperature. By comparison with polyphenyleneoxide and phenol-formaldehyde resins, it was found that the main volatilization, during which most of the tar is evolved, is initiated by cleavage of alkyl-aryl-ethers. Rearrangements of the primarily formed radicals lead to the formation of CO and methane at higher temperatures. 5 refs., 8 figs., 1 tab.

Acid Rearrangement of Secoiridoids Related to Oleuropein and Secologanin

DEFF Research Database (Denmark)

Bianco, Armandodoriano; Jensen, Søren Rosendal; Olesen, Jens

2003-01-01

Acid treatment of an iridoid glycoside results in the cleavage of the acetal bond between the sugar unit and the monoterpenoid aglycon. Iridoids possessing non-conjugated enol ether systems, however, undergo the hydration of the iridoid enol ether functionality in acid medium, as well as the hydr...... as the hydrolysis of the bond. We examined the acid rearrangement of secoiridoids such as oleuropein (1) and secologanin (2) and their reduction products oleuropeinol (3) and secologaninol (4), to examine whether similar behaviour also occurs in this case....

Thermally rearranged (TR) bismaleimide-based network polymers for gas separation membranes.

Science.gov (United States)

Do, Yu Seong; Lee, Won Hee; Seong, Jong Geun; Kim, Ju Sung; Wang, Ho Hyun; Doherty, Cara M; Hill, Anita J; Lee, Young Moo

2016-11-15

Highly permeable, thermally rearranged polymer membranes based on bismaleimide derivatives that exhibit excellent CO 2 permeability up to 5440 Barrer with a high BET surface area (1130 m 2 g -1 ) are reported for the first time. In addition, the membranes can be easily used to form semi-interpenetrating networks with other polymers endowing them with superior gas transport properties.

Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

International Nuclear Information System (INIS)

Mattsson, Johanna S. M.; Brunnström, Hans; Jabs, Verena; Edlund, Karolina; Jirström, Karin; Mindus, Stephanie; Fleur, Linnéa la; Pontén, Fredrik; Karlsson, Mats G.; Karlsson, Christina; Koyi, Hirsh; Brandén, Eva; Botling, Johan; Helenius, Gisela; Micke, Patrick; Svensson, Maria A.

2016-01-01

Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data. ALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients. ALK rearrangements were detected in 1.7 % in the complete cohort and 2.0 % in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.8 and 1.4 % when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (> 98 %), while the sensitivity was between 69 % (Ventana) and 62 % (in house Dako protocol). Furthermore, only 67 % of the ALK IHC positive cases were positive with both IHC assays. Gene expression analysis revealed that 6/194 (3 %) tumors showed high ALK gene expression (≥ 6 AU) and of them only three were positive by either FISH or IHC. The overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC. The online version of this article (doi:10.1186/s12885-016-2646-x) contains

Gold-Catalyzed Formal C-C Bond Insertion Reaction of 2-Aryl-2-diazoesters with 1,3-Diketones.

Science.gov (United States)

Ren, Yuan-Yuan; Chen, Mo; Li, Ke; Zhu, Shou-Fei

2018-06-29

The transition-metal-catalyzed formal C-C bond insertion reaction of diazo compounds with monocarbonyl compounds is well established, but the related reaction of 1,3-diketones instead gives C-H bond insertion products. Herein, we report a protocol for a gold-catalyzed formal C-C bond insertion reaction of 2-aryl-2-diazoesters with 1,3-diketones, which provides efficient access to polycarbonyl compounds with an all-carbon quaternary center. The aryl ester moiety plays a crucial role in the unusual chemoselectivity, and the addition of a Brønsted acid to the reaction mixture improves the yield of the C-C bond insertion product. A reaction mechanism involving cyclopropanation of a gold carbenoid with an enolate and ring-opening of the resulting donor-acceptor-type cyclopropane intermediate is proposed. This mechanism differs from that of the traditional Lewis-acid-catalyzed C-C bond insertion reaction of diazo compounds with monocarbonyl compounds, which involves a rearrangement of a zwitterion intermediate as a key step. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

NARCIS (Netherlands)

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it

Recent Syntheses of 1,2,3,4-Tetrahydroquinolines, 2,3-Dihydro-4(1H-quinolinones and 4(1H-Quinolinones using Domino Reactions

Directory of Open Access Journals (Sweden)

Baskar Nammalwar

2013-12-01

Full Text Available A review of the recent literature is given focusing on synthetic approaches to 1,2,3,4-tetrahydroquinolines, 2,3-dihydro-4(1H-quinolinones and 4(1H-quinolinones using domino reactions. These syntheses involve: (1 reduction or oxidation followed by cyclization; (2 SNAr-terminated sequences; (3 acid-catalyzed ring closures or rearrangements; (4 high temperature cyclizations and (5 metal-promoted processes as well as several less thoroughly studied reactions. Each domino method is presented with a brief discussion of mechanism, scope, yields, simplicity and potential utility.

Reaction studies of hot silicon, germanium and carbon atoms

International Nuclear Information System (INIS)

Gaspar, P.P.

1990-01-01

The goal of this project was to increase the authors understanding of the interplay between the kinetic and electronic energy of free atoms and their chemical reactivity by answering the following questions: (1) what is the chemistry of high-energy carbon silicon and germanium atoms recoiling from nuclear transformations; (2) how do the reactions of recoiling carbon, silicon and germanium atoms take place - what are the operative reaction mechanisms; (3) how does the reactivity of free carbon, silicon and germanium atoms vary with energy and electronic state, and what are the differences in the chemistry of these three isoelectronic atoms? This research program consisted of a coordinated set of experiments capable of achieving these goals by defining the structures, the kinetic and internal energy, and the charge states of the intermediates formed in the gas-phase reactions of recoiling silicon and germanium atoms with silane, germane, and unsaturated organic molecules, and of recoiling carbon atoms with aromatic molecules. The reactions of high energy silicon, germanium, and carbon atoms created by nuclear recoil were studied with substrates chosen so that their products illuminated the mechanism of the recoil reactions. Information about the energy and electronic state of the recoiling atoms at reaction was obtained from the variation in end product yields and the extent of decomposition and rearrangement of primary products (usually reactive intermediates) as a function of total pressure and the concentration of inert moderator molecules that remove kinetic energy from the recoiling atoms and can induce transitions between electronic spin states. 29 refs

Automation of ALK gene rearrangement testing with fluorescence in situ hybridization (FISH): a feasibility study.

Science.gov (United States)

Zwaenepoel, Karen; Merkle, Dennis; Cabillic, Florian; Berg, Erica; Belaud-Rotureau, Marc-Antoine; Grazioli, Vittorio; Herelle, Olga; Hummel, Michael; Le Calve, Michele; Lenze, Dido; Mende, Stefanie; Pauwels, Patrick; Quilichini, Benoit; Repetti, Elena

2015-02-01

In the past several years we have observed a significant increase in our understanding of molecular mechanisms that drive lung cancer. Specifically in the non-small cell lung cancer sub-types, ALK gene rearrangements represent a sub-group of tumors that are targetable by the tyrosine kinase inhibitor Crizotinib, resulting in significant reductions in tumor burden. Phase II and III clinical trials were performed using an ALK break-apart FISH probe kit, making FISH the gold standard for identifying ALK rearrangements in patients. FISH is often considered a labor and cost intensive molecular technique, and in this study we aimed to demonstrate feasibility for automation of ALK FISH testing, to improve laboratory workflow and ease of testing. This involved automation of the pre-treatment steps of the ALK assay using various protocols on the VP 2000 instrument, and facilitating automated scanning of the fluorescent FISH specimens for simplified enumeration on various backend scanning and analysis systems. The results indicated that ALK FISH can be automated. Significantly, both the Ikoniscope and BioView system of automated FISH scanning and analysis systems provided a robust analysis algorithm to define ALK rearrangements. In addition, the BioView system facilitated consultation of difficult cases via the internet. Copyright © 2015 Elsevier Inc. All rights reserved.

Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments

NARCIS (Netherlands)

Baer, R.; Boehm, T.; Yssel, H.; Spits, H.; Rabbitts, T. H.

1988-01-01

We have examined DNA rearrangements within a 120 kb cloned region of the human T cell receptor J delta-C delta/J alpha-C alpha locus. Three types of pattern emerge from an analysis of T cell lines and clones. Firstly, cells with two rearrangements within J delta-C delta; secondly, cells with one

PKCζ and PKMζ are overexpressed in TCF3-rearranged paediatric acute lymphoblastic leukaemia and are associated with increased thiopurine sensitivity

Science.gov (United States)

Hartsink-Segers, S A; Beaudoin, J J; Luijendijk, M W J; Exalto, C; Pieters, R; Den Boer, M L

2015-01-01

Both tumour suppressor and oncogenic functions have been ascribed to the atypical zeta isoform of protein kinase C (PKCζ), whereas its constitutively active form PKMζ is almost exclusively expressed in the brain where it has a role in long-term memory. Using primers unique for either isoform, we found that both PKCζ and PKMζ were expressed in a subset of paediatric acute lymphoblastic leukaemia (ALL) cases carrying a TCF3 (E2A) chromosomal rearrangement. Combined PKCζ and PKMζ (PKC/Mζ) protein as well as phosphorylation levels were elevated in ALL cases, especially TCF3-rearranged precursor B-ALL cases, compared with normal bone marrow (Pmercaptopurine (Pstabilize mismatch-repair protein MSH2, facilitating thiopurine responsiveness in T-ALL. However, PKC/Mζ knockdown in a TCF3-rearranged cell line model decreased MSH2 expression but did not induce thiopurine resistance, indicative that the link between high PKC/Mζ levels and thiopurine sensitivity in paediatric precursor B-ALL is not directly causal. Collectively, our data indicate that thiopurine treatment may be effective, especially in paediatric TCF3-rearranged ALL and other patients with a high expression of PKC/Mζ. PMID:24990612

Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

International Nuclear Information System (INIS)

Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y.; Hayashi, Y.

2012-01-01

Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

New progress in snake mitochondrial gene rearrangement.

Science.gov (United States)

Chen, Nian; Zhao, Shujin

2009-08-01

To further understand the evolution of snake mitochondrial genomes, the complete mitochondrial DNA (mtDNA) sequences were determined for representative species from two snake families: the Many-banded krait, the Banded krait, the Chinese cobra, the King cobra, the Hundred-pace viper, the Short-tailed mamushi, and the Chain viper. Thirteen protein-coding genes, 22-23 tRNA genes, 2 rRNA genes, and 2 control regions were identified in these mtDNAs. Duplication of the control region and translocation of the tRNAPro gene were two notable features of the snake mtDNAs. These results from the gene rearrangement comparisons confirm the correctness of traditional classification schemes and validate the utility of comparing complete mtDNA sequences for snake phylogeny reconstruction.

Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

DEFF Research Database (Denmark)

Staaf, Johan; Törngren, Therese; Rambech, Eva

2008-01-01

Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic hybridizat......Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic...... deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...... from several 100 kb, including large flanking regions, to rearrangements, allowing convenient design...

Negative ion electrospray ionization mass spectrometry of nucleoside phosphoramidate monoesters: elucidation of novel rearrangement mechanisms by multistage mass spectrometry incorporating in-source deuterium labelling.

Science.gov (United States)

Xu, Peng-Xiang; Hu, An-Fu; Hu, Dan; Gao, Xiang; Zhao, Yu-Fen

2008-10-01

Several O-2',3'-isopropylideneuridine-O-5'-phosphoramidate monoesters were synthesized and analyzed by negative ion electrospray ionization tandem mass spectrometry (ESI-MS(n)). Two kinds of novel rearrangement reactions were observed due to the difference in the amino acid in the nucleoside phosphoramidate monoesters, and possible mechanisms were proposed. One involves a five-membered cyclic transition state. The other is formation of a stable five-membered ring intermediate by Michael addition. Results were confirmed by tandem mass spectrometry and isotopically labeled hydrogen atoms. Furthermore, the internal hydrogen exchange between active hydrogen and methyl acrylate in the heated capillary of the mass spectrometer was found. The characteristic fragmentation behavior in ESI-MS may be used to monitor this kind of compounds in the biological metabolism.

Quantum and Statistical Mechanics Applied to Singlet Carbenes, Pericyclic Reactions, and Condensed Phase Phenomena

Science.gov (United States)

Evanseck, Jeffrey Donald

The completed research covers a broad range of theoretical applications in organic chemistry. It is divided into three chapters which covers the chemistry of singlet carbenes (Chapter 1), substituent effects in pericyclic rearrangements (Chapter 2), and the effects of solvent on the reactivity of organic reactions (Chapter 3). The selectivity between 1,2- and 1,4-intramolecular additions to restricted diene systems has been investigated. A decrease in activation energy for the intramolecular cycloaddition is noted for systems which approach the idealized geometry found with intermolecular addition of carbenes to olefins. Direct substitution at the carbene site dramatically effects the predicted activation barriers for 1,2-hydrogen shifts. An excellent correlation between the activation energy and a substituents sigma_sp {rm R}{rm o} parameters has been demonstrated. The long standing problem of orbital alignment influences on the selectivity of 1,2-hydrogen arrangements shows significant geometric distortions, yet has little influence on the rates of singlet alkylcarbene rearrangements. The exo-selectivities observed for 1,2-shifts in rigid systems are explained by torsional and steric interactions which develop in the transition structures. Substituent effects on pericyclic reactions have been computed for several conrotatory and disrotatory electrocyclizations. The six-electron disrotatory electrocyclization of 1-substituted hexatrienes displays a strong electronic component in determining stereoselectivity, despite incredible steric interference. The eight-electron conrotatory electrocyclization transition structure of 1-substituted octatetraene has an unusual helical transition structure which does not differentiate between substituent position. The effects of solvents on the acidity differences between E and Z esters has supplemented earlier ab initio quantum mechanical results on the enhanced acidity of Meldrum's acid. Monte Carlo simulations predict a

Detection of ALK gene rearrangement in non-small cell lung cancer: a comparison of fluorescence in situ hybridization and chromogenic in situ hybridization with correlation of ALK protein expression.

Science.gov (United States)

Kim, Hyojin; Yoo, Seol-Bong; Choe, Ji-Young; Paik, Jin Ho; Xu, Xianhua; Nitta, Hiroaki; Zhang, Wenjun; Grogan, Thomas M; Lee, Choon-Taek; Jheon, Sanghoon; Chung, Jin-Haeng

2011-08-01

Accurate determination of ALK rearrangement is important in lung cancer patients, especially in determining their eligibility for crizotinib therapy. Fluorescence in situ hybridization (FISH) has been regarded as the gold standard method for detecting ALK rearrangement. However, FISH requires a fluorescence microscope, and the signals are labile and rapidly fade over time. This study evaluates the concordance between ALK gene rearrangement in non-small cell lung cancer assessed by ALK FISH and a newly developed ALK chromogenic in situ hybridization (CISH) and correlates the results with ALK protein expression assessed by immunohistochemistry. A total of 465 formalin-fixed, paraffin-embedded non-small cell lung cancer samples were analyzed by ALK FISH (PathVysion, Vysis, Abbott) and ALK CISH. For comparison, all specimens were stained by immunohistochemistry (clone 5A4, Novocastra) and interobserver reproducibility was assessed. We found that agreement between the pathologists on the CISH-determined ALK status was achieved in 449 patients (96.6%), and ALK rearrangement was identified in 18 patients (4.0%) in CISH method. Among these cases, 443 cases (95.3%) had results matching the corresponding FISH results: 17 rearranged, 425 wild types, and 1 discordant case. There was high concordance in the assessment of ALK gene rearrangement between FISH and CISH techniques (κ = 0.92) and between observers (κ = 0.97). In addition, there was high concordance in the ALK gene status and ALK protein expression between CISH and IHC tests (κ = 0.82). CISH is a highly reproducible and practical method to detect ALK gene rearrangement and correlated well with ALK protein expression. Here, we present a diagnostic algorithm (Chung's SNUBH ALK protocol) to detect lung cancer with ALK rearrangements using IHC, FISH and CISH. Because CISH allows a concurrent analysis of histological features of the tumors and gene rearrangement, it appears to be a useful method in determining ALK gene

Mechanism of the Ru–Allenylidene to Ru–Indenylidene Rearrangement in Ruthenium Precatalysts for Olefin Metathesis

KAUST Repository

Pump, Eva

2015-06-30

The intramolecular allenylidene RuCl2(PR3)2(C═C═CPh2) to indenylidene RuCl2(PR3)2(Ind) rearrangement that occurs during the synthesis of Ru-based precatalysts for olefin metathesis is presented. In the absence of acid, the ring closure via C–H activation was shown to be unfavored for energy barriers up to 70 kcal/mol. Thus, it turned out to be HCl (or other acid) that plays a crucial role during formation of the indenylidene, as the upper energy barrier decreases to a reasonable 35 kcal/mol. Moreover, we proved computationally that depending on the nature of the phosphine the intramolecular rearrangement is either facilitated (PPh3) or slightly hampered (PCy3), which is in line with experimental results.

Mechanism of the Ru–Allenylidene to Ru–Indenylidene Rearrangement in Ruthenium Precatalysts for Olefin Metathesis

KAUST Repository

Pump, Eva; Slugovc, Christian; Cavallo, Luigi; Poater, Albert

2015-01-01

The intramolecular allenylidene RuCl2(PR3)2(C═C═CPh2) to indenylidene RuCl2(PR3)2(Ind) rearrangement that occurs during the synthesis of Ru-based precatalysts for olefin metathesis is presented. In the absence of acid, the ring closure via C–H activation was shown to be unfavored for energy barriers up to 70 kcal/mol. Thus, it turned out to be HCl (or other acid) that plays a crucial role during formation of the indenylidene, as the upper energy barrier decreases to a reasonable 35 kcal/mol. Moreover, we proved computationally that depending on the nature of the phosphine the intramolecular rearrangement is either facilitated (PPh3) or slightly hampered (PCy3), which is in line with experimental results.

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

Directory of Open Access Journals (Sweden)

Sosale Chandrasekhar

2012-08-01

Full Text Available The titled approaches were effected with various 2-substituted benzoylacetic acid oximes 3 (Beckmann and 2-substituted malonamic acids 9 (Hofmann, their carboxyl groups being masked as a 2,4,10-trioxaadamantane unit (an orthoacetate. The oxime mesylates have been rearranged with basic Al2O3 in refluxing CHCl3, and the malonamic acids with phenyliodoso acetate and KOH/MeOH. Both routes are characterized by excellent overall yields. Structure confirmation of final products was conducted with X-ray diffraction in selected cases. The final N-benzoyl and N-(methoxycarbonyl products are α-amino acids with both carboxyl and amino protection; hence, they are of great interest in peptide synthesis.

Analysis of perturbation methods for rearrangement collisions: Comparison of distorted-wave and coupled-channel-wave transition amplitudes

International Nuclear Information System (INIS)

Suck Salk, S.H.

1985-01-01

With the use of projection operators, the formal expressions of distorted-wave and coupled-channel-wave transition amplitudes for rearrangement collisions are derived. Use of projection operators (for the transition amplitudes) sharpens our understanding of the structural differences between the two transition amplitudes. The merit of each representation of the transition amplitudes is discussed. Derived perturbation potentials are found to have different structures. The rigorously derived distorted-wave Born-approximation (DWBA) transition amplitude is shown to be a generalization of the earlier DWBA expression obtained from the assumption of the dominance of elastic scattering in rearrangement collisions

Ph1 chromosomes and bcr gene rearrangements in chronic myelocytic leukemia patients developed from atomic bomb survivors

International Nuclear Information System (INIS)

Tanaka, Kimio; Takechi, Miho; Shigeta, Chiharu; Sakatani, Keiko; Oguma, Nobuo; Kamada, Nanao; Takimoto, Yasuo; Kuramoto, Atsushi

1989-01-01

This study compared findings of chronic myelocytic leukemia (CML) in A-bomb survivors (n=8) developing CML within 10 years after the bombing and in non-exposed CML patients (n=14). Both Ph 1 chromosomes and bcr rearrangement were observed in all patients in both exposed and non-exposed groups. There was no significant difference in distribution sites of bcr rearrangement between the groups. These results suggest that bcr-abl chimera mRNA and chimera protein associated with Ph 1 chromosomes have an important role in the development of CML among A-bomb survivors, as well as among non-exposed patients. (N.K.)

TQ-bifurcations in discrete dynamical systems: Analysis of qualitative rearrangements of the oscillation mode

Energy Technology Data Exchange (ETDEWEB)

Makarenko, A. V., E-mail: avm.science@mail.ru [Constructive Cybernetics Research Group (Russian Federation)

2016-10-15

A new class of bifurcations is defined in discrete dynamical systems, and methods for their diagnostics and the analysis of their properties are presented. The TQ-bifurcations considered are implemented in discrete mappings and are related to the qualitative rearrangement of the shape of trajectories in an extended space of states. Within the demonstration of the main capabilities of the toolkit, an analysis is carried out of a logistic mapping in a domain to the right of the period-doubling limit point. Five critical values of the parameter are found for which the geometric structure of the trajectories of the mapping experiences a qualitative rearrangement. In addition, an analysis is carried out of the so-called “trace map,” which arises in the problems of quantum-mechanical description of various properties of discrete crystalline and quasicrystalline lattices.

Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.

Science.gov (United States)

Pailler, Emma; Oulhen, Marianne; Borget, Isabelle; Remon, Jordi; Ross, Kirsty; Auger, Nathalie; Billiot, Fanny; Ngo Camus, Maud; Commo, Frédéric; Lindsay, Colin R; Planchard, David; Soria, Jean-Charles; Besse, Benjamin; Farace, Françoise

2017-05-01

The duration and magnitude of clinical response are unpredictable in ALK -rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK -FISH patterns [ ALK -rearrangement, ALK -copy number gain ( ALK -CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK -rearranged patients. Thirty-nine ALK -rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively. Blood samples were collected at baseline and at an early time-point (2 months) on crizotinib. Aberrant ALK -FISH patterns were examined in CTCs using immunofluorescence staining combined with filter-adapted FISH after filtration enrichment. CTCs were classified into distinct subsets according to the presence of ALK -rearrangement and/or ALK -CNG signals. No significant association between baseline numbers of ALK -rearranged or ALK -CNG CTCs and PFS was observed. However, we observed a significant association between the decrease in CTC number with ALK -CNG on crizotinib and a longer PFS (likelihood ratio test, P = 0.025). In multivariate analysis, the dynamic change of CTC with ALK -CNG was the strongest factor associated with PFS (HR, 4.485; 95% confidence interval, 1.543-13.030, P = 0.006). Although not dominant, ALK -CNG has been reported to be one of the mechanisms of acquired resistance to crizotinib in tumor biopsies. Our results suggest that the dynamic change in the numbers of CTCs with ALK -CNG may be a predictive biomarker for crizotinib efficacy in ALK -rearranged NSCLC patients. Serial molecular analysis of CTC shows promise for real-time patient monitoring and clinical outcome prediction in this population. Cancer Res; 77(9); 2222-30. ©2017 AACR . ©2017 American Association for Cancer Research.

The effect of substrate size in the Beckmann rearrangement: MOFs vs. zeolites

Czech Academy of Sciences Publication Activity Database

Opanasenko, Maksym; Shamzhy, Mariya; Lamač, Martin; Čejka, Jiří

2013-01-01

Roč. 204, APR 2013 (2013), s. 94-100 ISSN 0920-5861 R&D Projects: GA ČR GBP106/12/G015 Grant - others:European Commission(XE) FP7/2007-2013, contract 228862 Institutional support: RVO:61388955 Keywords : Beckmann rearrangement * oximes * CuBTC Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.309, year: 2013

Need for reaction coordinates to ensure a complete basis set in an adiabatic representation of ion-atom collisions

Science.gov (United States)

Rabli, Djamal; McCarroll, Ronald

2018-02-01

This review surveys the different theoretical approaches, used to describe inelastic and rearrangement processes in collisions involving atoms and ions. For a range of energies from a few meV up to about 1 keV, the adiabatic representation is expected to be valid and under these conditions, inelastic and rearrangement processes take place via a network of avoided crossings of the potential energy curves of the collision system. In general, such avoided crossings are finite in number. The non-adiabatic coupling, due to the breakdown of the Born-Oppenheimer separation of the electronic and nuclear variables, depends on the ratio of the electron mass to the nuclear mass terms in the total Hamiltonian. By limiting terms in the total Hamiltonian correct to first order in the electron to nuclear mass ratio, a system of reaction coordinates is found which allows for a correct description of both inelastic channels. The connection between the use of reaction coordinates in the quantum description and the electron translation factors of the impact parameter approach is established. A major result is that only when reaction coordinates are used, is it possible to introduce the notion of a minimal basis set. Such a set must include all avoided crossings including both radial coupling and long range Coriolis coupling. But, only when reactive coordinates are used, can such a basis set be considered as complete. In particular when the centre of nuclear mass is used as centre of coordinates, rather than the correct reaction coordinates, it is shown that erroneous results are obtained. A few results to illustrate this important point are presented: one concerning a simple two-state Landau-Zener type avoided crossing, the other concerning a network of multiple crossings in a typical electron capture process involving a highly charged ion with a neutral atom.

Evaluation of NGS and RT-PCR methods for ALK rearrangement in European NSCLC patients

DEFF Research Database (Denmark)

Letovanec, Igor; Finn, Stephen; Zygoura, Panagiota

2018-01-01

INTRODUCTION: The reported prevalence of ALK rearrangement in NSCLC ranges from 2%-7%. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proven to be a reproducible and sensitive technique. Reverse transcriptase...

Stereoselective synthesis of functionalized cyclic amino acid derivatives via a [2,3]-Stevens rearrangement and ring-closing metathesis.

Science.gov (United States)

Nash, Aaron; Soheili, Arash; Tambar, Uttam K

2013-09-20

Unnatural cyclic amino acids are valuable tools in biomedical research and drug discovery. A two-step stereoselective strategy for converting simple glycine-derived aminoesters into unnatural cyclic amino acid derivatives has been developed. The process includes a palladium-catalyzed tandem allylic amination/[2,3]-Stevens rearrangement followed by a ruthenium-catalyzed ring-closing metathesis. The [2,3]-rearrangement proceeds with high diastereoselectivity through an exo transition state. Oppolzer's chiral auxiliary was utilized to access an enantiopure cyclic amino acid by this approach, which will enable future biological applications.

Replication stalling by catalytically impaired Twinkle induces mitochondrial DNA rearrangements in cultured cells

NARCIS (Netherlands)

Pohjoismaki, J.L.; Goffart, S.; Spelbrink, J.N.

2011-01-01

Pathological mitochondrial DNA (mtDNA) rearrangements have been proposed to result from repair of double-strand breaks caused by blockage of mitochondrial DNA (mtDNA) replication. As mtDNA deletions are seen only in post-mitotic tissues, it has been suggested that they are selected out in actively

Effects of structural rearrangements on the rheology of rennet-induced casein particle gels

NARCIS (Netherlands)

Mellema, M.; Walstra, P.; Opheusden, van J.H.J.; Vliet, van T.

2002-01-01

During ageing of casein or skim milk gels, structural changes take place that affect gel parameters, such as pore size and storage modulus. These changes can be explained in terms of rearrangements of the gel network at various length scales. In this paper, rheological experiments on rennet-induced

Configurational rearrangements of bistable centers in covalent semiconductors - phase transitions of the second type

International Nuclear Information System (INIS)

Ivanyukovich, V.A.; Karas', V.I.; Lomako, V.M.

1989-01-01

A new radiation configurational-bistable defect diffring from the known similar defects by the fact that it possessestemperature inversion of states is detected in gallium arsenide. Configurational-bistable rearrangements are shown to be considered as phase transitions of the second type

Oxygen vacancy defects in Ta{sub 2}O{sub 5} showing long-range atomic re-arrangements

Energy Technology Data Exchange (ETDEWEB)

Guo, Yuzheng; Robertson, John [Engineering Department, Cambridge University, Cambridge CB2 1PZ (United Kingdom)

2014-03-17

The structure, formation energy, and energy levels of the various oxygen vacancies in Ta{sub 2}O{sub 5} have been calculated using the λ phase model. The intra-layer vacancies give rise to unusual, long-range bonding rearrangements, which are different for each defect charge state. The 2-fold coordinated intra-layer vacancy is the lowest cost vacancy and forms a deep level 1.5 eV below the conduction band edge. The 3-fold intra-layer vacancy and the 2-fold inter-layer vacancy are higher cost defects, and form shallower levels. The unusual bonding rearrangements lead to low oxygen migration barriers, which are useful for resistive random access memory applications.

Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication.

Science.gov (United States)

Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E; Ventura, Mario

2008-01-01

Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Human bacterial artificial chromosome/p1 artificial chromosome probes spanning the length of chromosome 17 were used in FISH experiments on great apes, Old World monkeys and New World monkeys to study the evolutionary history of this chromosome. We observed that the macaque marker order represents the ancestral organization. Human, chimpanzee and gorilla homologous chromosomes differ by a paracentric inversion that occurred specifically in the Homo sapiens/Pan troglodytes/Gorilla gorilla ancestor. Detailed analyses of the paracentric inversion revealed that the breakpoints mapped to two regions syntenic to human 17q12/21 and 17q23, both rich in segmental duplications. Sequence analyses of the human and macaque organization suggest that the duplication events occurred in the catarrhine ancestor with the duplication blocks continuing to duplicate or undergo gene conversion during evolution of the hominoid lineage. We propose that the presence of these duplicons has mediated the inversion in the H. sapiens/P. troglodytes/G. gorilla ancestor. Recently, the same duplication blocks have been shown to be polymorphic in the human population and to be involved in triggering microdeletion and duplication in human. These results further support a model where genomic architecture has a direct role in both rearrangement involved in karyotype evolution and genomic instability in human.

Rearrangement and energy transfer collisions of few-body molecular systems

International Nuclear Information System (INIS)

Gentry, W.R.

1981-01-01

A great variety of experimental techniques now makes it possible to obtain dynamical information on single bimolecular collisions in a very direct way. These methods are too numerous to permit a comprehensive review in this article, but a few examples have been chosen to illustrate briefly the types of results being obtained in several areas. These include measurements of state-to-state differential cross sections for rotationally and vibrationally inelastic collisions, and rearrangement collisions studies by crossed-beam and merged-beam methods. (orig.)

Gestalt Theory Rearranged: Back to Wertheimer

Directory of Open Access Journals (Sweden)

Shelia Guberman

2017-10-01

Full Text Available Wertheimer's seminal paper of 1923 was of gerat influence in psychology and other sciences. Wertheimer also emphasized the weaknesses of the newborn Gestalt theory: too many basic laws, and the ambiguity of definitions. At the same time, the paper contained potential solutions to these problems, in the form of a number of very important ideas, some of which were presented implicitly: perception through imitation, communicative nature of linear drawings and writings, transfer from the visual domain to motor domain, linguistic interpretation of the Gestalt. In this paper it will be shown that based on these ideas the Gestalt theory can be rearranged so that the main notions can be well defined, and the general principle of Gestalt perception, which overarches all known laws and unifies different Gestalt phenomena (the imitation principle can be introduced. The presented model of Gestalt perception is supported by fundamental neurophysiological data—the mirror neurons phenomenon and simulation theory.

Gestalt Theory Rearranged: Back to Wertheimer.

Science.gov (United States)

Guberman, Shelia

2017-01-01

Wertheimer's seminal paper of 1923 was of gerat influence in psychology and other sciences. Wertheimer also emphasized the weaknesses of the newborn Gestalt theory: too many basic laws, and the ambiguity of definitions. At the same time, the paper contained potential solutions to these problems, in the form of a number of very important ideas, some of which were presented implicitly: perception through imitation, communicative nature of linear drawings and writings, transfer from the visual domain to motor domain, linguistic interpretation of the Gestalt. In this paper it will be shown that based on these ideas the Gestalt theory can be rearranged so that the main notions can be well defined, and the general principle of Gestalt perception, which overarches all known laws and unifies different Gestalt phenomena (the imitation principle) can be introduced. The presented model of Gestalt perception is supported by fundamental neurophysiological data-the mirror neurons phenomenon and simulation theory.

Secondary deuterium isotope effects and transition state structure in the aromatic claisen rearrangement

International Nuclear Information System (INIS)

McMichael, K.D.; Korver, G.L.

1979-01-01

Kinetic experiments were carried out simultaneously on separate methyl salicylate solutions of allyl phenyl ether and its deuterated phenyl analogues at 170 to 195 0 C. Gas chromatographic analysis for allyl phenyl ether using an internal standard (anisole) and mechanical integration produced concentration/time data which were fitted to the exponential form of the first-order rate equation by a standard and nonlinear least-square program. At least 15 points were obtained for each run, covering 10 to 85% reaction. The derived isotope effects show no temperature dependence. Averages for 6 runs with each compound are k/sub H//k/sub α-D 2 / = 1.18 and K/sub H//k/sub γ-D 2 / = 0.95. An equilibrium α effect of 1.30 and a γ effect of 0.87 may be calculated for both deuterium atoms at 185 0 C. These results show that the C--H vibration frequencies are approximately (1.18 - 1)/(1.27 - 1) or 57 to 77% of the way from those of allyl phenyl ether to those of the cyclohexadiene intermediate. The C--H frequencies of the γ carbon in the transition state are about (0.95 - 1)/(0.88 - 1) or 22 to 62% of the way to those of the intermediate. The structure of the transition state, as far as these bonding frequencies are concerned, is consistent with the Claisen rearrangement

Single Particle Potential of a Σ Hyperon in Nuclear Matter. II Rearrangement Effects

International Nuclear Information System (INIS)

Dabrowski, J.

2000-01-01

The rearrangement contribution to the real part of the single particle potential of a Σ hyperon in nuclear matter, U Σ , is investigated. The isospin and spin dependent parts of U Σ are considered. Results obtained for four models of the Nijmegen baryon-baryon interaction are presented and discussed. (author)

Correlating Structural Order with Structural Rearrangement in Dusty Plasma Liquids: Can Structural Rearrangement be Predicted by Static Structural Information?

Science.gov (United States)

Su, Yen-Shuo; Liu, Yu-Hsuan; I, Lin

2012-11-01

Whether the static microstructural order information is strongly correlated with the subsequent structural rearrangement (SR) and their predicting power for SR are investigated experimentally in the quenched dusty plasma liquid with microheterogeneities. The poor local structural order is found to be a good alarm to identify the soft spot and predict the short term SR. For the site with good structural order, the persistent time for sustaining the structural memory until SR has a large mean value but a broad distribution. The deviation of the local structural order from that averaged over nearest neighbors serves as a good second alarm to further sort out the short time SR sites. It has the similar sorting power to that using the temporal fluctuation of the local structural order over a small time interval.

Synthesis of N-protected Galactosamine Building Blocks from D-Tagatose via the Heyns Rearrangement

DEFF Research Database (Denmark)

Wrodnigg, Tanja M.; Lundt, Inge; Stütz, Arnold E.

2006-01-01

N-Acetyl-D-galactosamine (11), a very important naturally occurring building block of oligosaccharides, is easily accessible via the Heyns rearrangement of D-tagatose (3) with benzylamine. The short and efficient synthesis of various differently N-protected D-galactosamine derivatives is reported....

New type of cells with multiple chromosome rearrangements

Energy Technology Data Exchange (ETDEWEB)

Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail: dom@blood.ru

2010-04-15

A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

Management as a Symbolizing Construction? Re-Arranging the Understanding of Management

Directory of Open Access Journals (Sweden)

Katharina Mayr

2010-09-01

Full Text Available In this article, we outline the concept of management as a symbolizing construction. According to Niklas LUHMANN, organizations process by referring to decisions. But decisions are not simply "given" and in principle invisible. This is the reason why organizations institute formalities like protocols, signatures or other insignia of the official that symbolize the decision—without actually being a decision. These symbols allow for making decisions "process-able." And just like a protocol or a signature, management symbolizes decisions as well. Management provides an organizational practice with symbols of decision making without being the "unity" of the decisions, as decisions perpetually have to be reconstructed, redefined and rearranged in the communication of all organizational units. Therefore management symbolizes on the one hand more than it can achieve. On the other hand the importance of management as a symbolizing construction lies in allowing the reconstruction, redefining and rearrangement of decisions by making them visible and recognizable. Heroic managers, meetings, management tools and procedures are solutions to the paradox of decision making. By symbolizing decidedness they create credibilities that conceal the self-referential construction of organizational communication and the paradox of its decision praxis. URN: urn:nbn:de:0114-fqs1003218

M to T Rearrangement: An Approach to Correct Webbed Neck Deformity

Directory of Open Access Journals (Sweden)

Ananth S. Murthy

2014-01-01

Full Text Available For the Noonan syndrome patient, the most concerning physical defect is often congenital webbing of the neck or pterygium colli. We present a patient with pterygium colli and a low and laterally displaced nuchal hairline. Since its description, various surgical approaches have been implemented to correct the deformity. Previously reported posterior and lateral approaches have notable disadvantages with regard to hairline displacement and recurrence. In order to address these disadvantages, a new surgical technique was used on this patient. We have termed this technique an M to T rearrangement. Using a lateral approach, the M and T incisions are made and the trapezial fascial web is directly visualized and able to be completely excised. This prevents the recurrence seen with the use of posterior techniques. Inferolateral displacement of hair-bearing skin can be removed with resection of the superior intervening triangle and improves the appearance of the low nuchal hairline. The excision of excess skin along with the zig-zag closure also prevents postoperative scar contraction and recurrence. An important effect of this technique is the prevention of anterior displacement of hair bearing skin. M to T rearrangement is an effective technique for the correction of webbed neck deformities seen in Noonan and Turner syndromes.

Synthesis and Rearrangement of Dewar Benzenes Into Biaryls: Experimental Evidence for Conrotatory Ring Opening

Czech Academy of Sciences Publication Activity Database

Janková, Š.; Dračínský, Martin; Císařová, I.; Kotora, Martin

-, č. 1 (2008), s. 47-51 ISSN 1434-193X R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : Dewar benzene * biaryls * alkynes * Hammett * rearrangement Subject RIV: CC - Organic Chemistry Impact factor: 3.016, year: 2008

Immunoglobulin kappa deleting element rearrangements in precursor-B acute lymphoblastic leukemia are stable targets for detection of minimal residual disease by real-time quantitative PCR

NARCIS (Netherlands)

van der Velden, V. H. J.; Willemse, M. J.; van der Schoot, C. E.; Hählen, K.; van Wering, E. R.; van Dongen, J. J. M.

2002-01-01

Immunoglobulin gene rearrangements are used as PCR targets for detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We Investigated the occurrence of monoclonal immunoglobulin kappa-deleting element (IGK-Kde) rearrangements by Southern blotting and PCR/heteroduplex

Recurrent rearrangements of the PLAG1 and HMGA2 genes in lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma

DEFF Research Database (Denmark)

Andreasen, Simon; von Holstein, Sarah L; Homøe, Preben

2018-01-01

PURPOSE: Lacrimal gland tumours constitute a wide spectrum of neoplastic lesions that are histologically similar to tumours of the salivary gland. In the salivary gland, pleomorphic adenoma (PA) is frequently characterized by recurrent chromosomal rearrangements of the PLAG1 and HMGA2 genes......, a genetic feature retained in carcinoma ex pleomorphic adenoma (ca-ex-PA) that makes it possible to distinguish ca-ex-PA from de novo carcinomas. However, whether PLAG1 and HMGA2 gene rearrangements are found in lacrimal gland PA and ca-ex-PA is not known. METHODS: Twenty-one lacrimal gland PAs and four ca......-ex-PAs were retrospectively reviewed and subjected to break-apart fluorescence in situ hybridization (FISH) for rearrangements of the PLAG1 gene. Cases without PLAG1 abnormalities were subjected to HMGA2 break-apart FISH. Immunohistochemical staining for PLAG1 and HMGA2 protein was performed and correlated...

Real-time 3D visualization of cellular rearrangements during cardiac valve formation.

Science.gov (United States)

Pestel, Jenny; Ramadass, Radhan; Gauvrit, Sebastien; Helker, Christian; Herzog, Wiebke; Stainier, Didier Y R

2016-06-15

During cardiac valve development, the single-layered endocardial sheet at the atrioventricular canal (AVC) is remodeled into multilayered immature valve leaflets. Most of our knowledge about this process comes from examining fixed samples that do not allow a real-time appreciation of the intricacies of valve formation. Here, we exploit non-invasive in vivo imaging techniques to identify the dynamic cell behaviors that lead to the formation of the immature valve leaflets. We find that in zebrafish, the valve leaflets consist of two sets of endocardial cells at the luminal and abluminal side, which we refer to as luminal cells (LCs) and abluminal cells (ALCs), respectively. By analyzing cellular rearrangements during valve formation, we observed that the LCs and ALCs originate from the atrium and ventricle, respectively. Furthermore, we utilized Wnt/β-catenin and Notch signaling reporter lines to distinguish between the LCs and ALCs, and also found that cardiac contractility and/or blood flow is necessary for the endocardial expression of these signaling reporters. Thus, our 3D analyses of cardiac valve formation in zebrafish provide fundamental insights into the cellular rearrangements underlying this process. © 2016. Published by The Company of Biologists Ltd.

Non-random distribution of instability-associated chromosomal rearrangement breakpoints in human lymphoblastoid cells

International Nuclear Information System (INIS)

Moore, Stephen R.; Papworth, David; Grosovsky, Andrew J.

2006-01-01

Genomic instability is observed in tumors and in a large fraction of the progeny surviving irradiation. One of the best-characterized phenotypic manifestations of genomic instability is delayed chromosome aberrations. Our working hypothesis for the current study was that if genomic instability is in part attributable to cis mechanisms, we should observe a non-random distribution of chromosomes or sites involved in instability-associated rearrangements, regardless of radiation quality, dose, or trans factor expression. We report here the karyotypic examination of 296 instability-associated chromosomal rearrangement breaksites (IACRB) from 118 unstable TK6 human B lymphoblast, and isogenic derivative, clones. When we tested whether IACRB were distributed across the chromosomes based on target size, a significant non-random distribution was evident (p < 0.00001), and three IACRB hotspots (chromosomes 11, 12, and 22) and one IACRB coldspot (chromosome 2) were identified. Statistical analysis at the chromosomal band-level identified four IACRB hotspots accounting for 20% of all instability-associated breaks, two of which account for over 14% of all IACRB. Further, analysis of independent clones provided evidence within 14 individual clones of IACRB clustering at the chromosomal band level, suggesting a predisposition for further breaks after an initial break at some chromosomal bands. All of these events, independently, or when taken together, were highly unlikely to have occurred by chance (p < 0.000001). These IACRB band-level cluster hotspots were observed independent of radiation quality, dose, or cellular p53 status. The non-random distribution of instability-associated chromosomal rearrangements described here significantly differs from the distribution that was observed in a first-division post-irradiation metaphase analysis (p = 0.0004). Taken together, these results suggest that genomic instability may be in part driven by chromosomal cis mechanisms

Alignment-free microbial phylogenomics under scenarios of sequence divergence, genome rearrangement and lateral genetic transfer.

Science.gov (United States)

Bernard, Guillaume; Chan, Cheong Xin; Ragan, Mark A

2016-07-01

Alignment-free (AF) approaches have recently been highlighted as alternatives to methods based on multiple sequence alignment in phylogenetic inference. However, the sensitivity of AF methods to genome-scale evolutionary scenarios is little known. Here, using simulated microbial genome data we systematically assess the sensitivity of nine AF methods to three important evolutionary scenarios: sequence divergence, lateral genetic transfer (LGT) and genome rearrangement. Among these, AF methods are most sensitive to the extent of sequence divergence, less sensitive to low and moderate frequencies of LGT, and most robust against genome rearrangement. We describe the application of AF methods to three well-studied empirical genome datasets, and introduce a new application of the jackknife to assess node support. Our results demonstrate that AF phylogenomics is computationally scalable to multi-genome data and can generate biologically meaningful phylogenies and insights into microbial evolution.

Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: case report

Directory of Open Access Journals (Sweden)

Rongen Michel A

2009-07-01

Full Text Available Abstract Background Complex chromosomal rearrangements (CCR are rare cytogenetic findings that are difficult to karyotype by conventional cytogenetic analysis partially because of the relative low resolution of this technique. High resolution genotyping is necessary in order to identify cryptic imbalances, for instance near the multiple breakpoints, to explain the abnormal phenotype in these patients. We applied several molecular techniques to elucidate the complexity of the CCRs of two adult patients with abnormal phenotypes. Results Multicolour fluorescence in situ hybridization (M-FISH showed that in patient 1 the chromosomes 1, 10, 15 and 18 were involved in the rearrangement whereas for patient 2 the chromosomes 5, 9, 11 and 13 were involved. A 250 k Nsp1 SNP-array analysis uncovered a deletion in chromosome region 10p13 for patient 1, harbouring 17 genes, while patient 2 showed no pathogenic gains or losses. Additional FISH analysis with locus specific BAC-probes was performed, leading to the identification of cryptic interstitial structural rearrangements in both patients. Conclusion Application of M-FISH and SNP-array analysis to apparently balanced CCRs is useful to delineate the complex chromosomal rearrangement in detail. However, it does not always identify cryptic imbalances as an explanation for the abnormal phenotype in patients with a CCR.

SYNTHESIS OF ALLYL PHENYL ETHER AND CLAISEN REARRANGEMENT

Directory of Open Access Journals (Sweden)

Gagik Torosyan

2011-12-01

Full Text Available It has been established the possibility for phenol allylation on natural zeolites and them analogs. Here is demonstrated the synthesis of allyl phenol, which has wide industrial applications. The offered method in comparison with the traditional methods has more advantages – higher selectivity, smaller material and power resources consumption. It has been obtained the mixture of allylating phenols (30% in general with allyl phenyl ether (1 with 80% yields. At 600 K is obtained allylphenyl ether, at 700 K beginning the formation of allyl phenols, which is the result of direct C-allylation of the aromatic ring. It has been investigated the possibility of Claisen rearrangement in the same conditions. All of that are established by gas-liquid chromatography and liquid chromatography data.

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

Directory of Open Access Journals (Sweden)

Marc Enßle

2012-03-01

Full Text Available Methionine, S-benzylcysteine and S-allylcysteine were converted into 2-diazo-3-oxo-4-phthalimidocarboxylic esters 8a–c in three steps. Upon rhodium-catalysed dediazoniation, two intramolecular carbenoid reactions competed, namely the formation of a cyclic sulfonium ylide and that of a six-ring carbonyl ylide. The S-methyl and S-benzyl ylides 12a and b could be isolated, while S-allyl ylide 12c underwent a [2,3]-sigmatropic rearrangement. The short-lived carbonyl ylides derived from methionine and S-benzylcysteine formed head-to-tail dimers by a [3 + 3]-cycloaddition and could be trapped with external dipolarophiles, while the S-allyl derivative 14c yielded the pentacyclic compound 17 by an intramolecular [3 + 2]-cycloaddition reaction.

Precision medicine approaches may be the future for CRLF2 rearranged Down Syndrome Acute Lymphoblastic Leukaemia patients.

Science.gov (United States)

Page, Elyse C; Heatley, Susan L; Yeung, David T; Thomas, Paul Q; White, Deborah L

2018-06-04

Breakthrough studies over the past decade have uncovered unique gene fusions implicated in acute lymphoblastic leukaemia (ALL). The critical gene, cytokine receptor-like factor 2 (CRLF2), is rearranged in 5-16% of B-ALL, comprising 50% of Philadelphia-like ALL and cooperates with genomic lesions in the Jak, Mapk and Ras signalling pathways. Children with Down Syndrome (DS) have a predisposition to developing CRLF2 rearranged-ALL which is observed in 60% of DS-ALL patients. These patients experience a poor survival outcome. Mutations of genes involved in epigenetic regulation are more prevalent in DS-ALL patients than non-DS ALL patients, highlighting the potential for alternative treatment strategies. DS-ALL patients also suffer greater treatment-related toxicity from current ALL treatment regimens compared to non-DS-ALL patients. An increased gene dosage of critical genes on chromosome 21 which have roles in purine synthesis and folate transport may contribute. As the genomic landscape of DS-ALL patients is different to non-DS-ALL patients, targeted therapies for individual lesions may improve outcomes. Therapeutically targeting each rearrangement with targeted or combination therapy that will perturb the transforming signalling pathways will likely improve the poor survival rates of this subset of patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Diagnosis of Familial Wolf-Hirschhorn Syndrome due to a Paternal Cryptic Chromosomal Rearrangement by Conventional and Molecular Cytogenetic Techniques

Science.gov (United States)

Venegas-Vega, Carlos A.; Zepeda, Luis M.; Garduño-Zarazúa, Luz M.; Berumen, Jaime; Kofman, Susana; Cervantes, Alicia

2013-01-01

The use of conventional cytogenetic techniques in combination with fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarrays is necessary for the identification of cryptic rearrangements in the diagnosis of chromosomal syndromes. We report two siblings, a boy of 9 years and 9 months of age and his 7-years- and 5-month-old sister, with the classic Wolf-Hirschhorn syndrome (WHS) phenotype. Using high-resolution GTG- and NOR-banding karyotypes, as well as FISH analysis, we characterized a pure 4p deletion in both sibs and a balanced rearrangement in their father, consisting in an insertion of 4p material within a nucleolar organizing region of chromosome 15. Copy number variant (CNV) analysis using SNP arrays showed that both siblings have a similar size of 4p deletion (~6.5 Mb). Our results strongly support the need for conventional cytogenetic and FISH analysis, as well as high-density microarray mapping for the optimal characterization of the genetic imbalance in patients with WHS; parents must always be studied for recognizing cryptic balanced chromosomal rearrangements for an adequate genetic counseling. PMID:23484094

Selective molecular recognition, C-H bond activation, and catalysis in nanoscale reaction vessels

Energy Technology Data Exchange (ETDEWEB)

Fiedler, Dorothea; Leung, Dennis H.; Raymond, Kenneth N.; Bergman, Robert G.

2004-11-27

Supramolecular chemistry represents a way to mimic enzyme reactivity by using specially designed container molecules. We have shown that a chiral self-assembled M{sub 4}L{sub 6} supramolecular tetrahedron can encapsulate a variety of cationic guests, with varying degrees of stereoselectivity. Reactive iridium guests can be encapsulated and the C-H bond activation of aldehydes occurs, with the host cavity controlling the ability of substrates to interact with the metal center based upon size and shape. In addition, the host container can act as a catalyst by itself. By restricting reaction space and preorganizing the substrates into reactive conformations, it accelerates the sigmatropic rearrangement of enammonium cations.

scid Thymocytes with TCRbeta gene rearrangements are targets for the oncogenic effect of SCL and LMO1 transgenes.

Science.gov (United States)

Chervinsky, D S; Lam, D H; Melman, M P; Gross, K W; Aplan, P D

2001-09-01

SCL and LMO1 were both discovered by virtue of their activation by chromosomaltranslocation in patients with T-cell acute lymphoblastic leukemia (T-ALL). Overexpression of SCL and LMO1 in the thymus of transgenic mice leads to T-ALL at a young age. scid (severe combined immunodeficient) mice are unable to efficiently recombine antigen receptor genes and consequently display a developmental block at the CD4-CD8- to CD4+CD8+ transition. To test the hypothesis that this developmental block would protect SCL/LMO1 transgenic mice from developing T-ALL, we crossed the SCL and LMO1 transgenes onto a scid background. The age of onset for T-ALL in the SCL/LMO1/scid mice was significantly delayed (P < 0.001) compared with SCL/LMO1/wild-type mice. Intriguingly, all of the SCL/LMO1/scid malignancies displayed clonal, in-frame TCRbeta gene rearrangements. Taken together, these findings suggest that the "leaky" scid thymocyte that undergoes a productive TCRbeta gene rearrangement is susceptible to the oncogenic action of SCL and LMO1 and additionally suggests that TCRbeta gene rearrangements may be required for the oncogenic action of SCL and LMO1.

Recurrent Rearrangements of Human Amylase Genes Create Multiple Independent CNV Series.

Science.gov (United States)

Shwan, Nzar A A; Louzada, Sandra; Yang, Fengtang; Armour, John A L

2017-05-01

The human amylase gene cluster includes the human salivary (AMY1) and pancreatic amylase genes (AMY2A and AMY2B), and is a highly variable and dynamic region of the genome. Copy number variation (CNV) of AMY1 has been implicated in human dietary adaptation, and in population association with obesity, but neither of these findings has been independently replicated. Despite these functional implications, the structural genomic basis of CNV has only been defined in detail very recently. In this work, we use high-resolution analysis of copy number, and analysis of segregation in trios, to define new, independent allelic series of amylase CNVs in sub-Saharan Africans, including a series of higher-order expansions of a unit consisting of one copy each of AMY1, AMY2A, and AMY2B. We use fiber-FISH (fluorescence in situ hybridization) to define unexpected complexity in the accompanying rearrangements. These findings demonstrate recurrent involvement of the amylase gene region in genomic instability, involving at least five independent rearrangements of the pancreatic amylase genes (AMY2A and AMY2B). Structural features shared by fundamentally distinct lineages strongly suggest that the common ancestral state for the human amylase cluster contained more than one, and probably three, copies of AMY1. © 2017 WILEY PERIODICALS, INC.

Reaction mechanisms of ruthenium tetroxide mediated oxidations of organic compounds

Energy Technology Data Exchange (ETDEWEB)

Froehaug, Astrid Elisabeth

1995-12-31

This thesis reports a study of the mechanism of ruthenium tetroxide mediated oxidations of saturated hydrocarbons, ethers, alkenes and alcohols. Several methods were used. The RuO{sub 4}-mediated oxidations of adamantane and cis-decalin were studied in CCl{sub 4}-CH{sub 3}CN-H{sub 2}O and in acetone-water. The rate of reaction was found to be moderately influenced by the polarity of the solvent. Solvent properties other than the polarity were also found to influence the reaction rates. From the oxidations of adamantane and adamantane-1,3,5,7-d{sub 4} two primary kinetic deuterium isotope effects were found. These were comparable with the deuterium isotope effects found for the analogous oxidations of cis-decalin and cis-decalin-d{sub 18}. The results seem to exclude both a one step hydride abstraction reaction mechanism and a one step concerted mechanism, as well as a scheme where two such mechanisms compete. The observations may be explained by a two step reaction mechanism consisting of a pre-equilibrium with formation of a substrate-RuO{sub 4} complex followed by a concerted rate determining reaction. The RuO{sub 4}-mediated oxidation of ethers was of kinetic second order with a small enthalpy of activation and a large negative entropy of activation. Oxidation of cyclopropylmethyl methyl ether gave methyl cyclopropanecarboxylate, no rearranged products were observed. On RuO{sub 4} oxidations in CCl{sub 4} with NaIO{sub 4} as stoichiometric oxidant, no chlorinated products were observed. Several observations not in agreement with a hydride or a hydrogen abstraction mechanism may be explained by assuming that the reaction proceeds by either a concerted reaction or by a reversible oxidative addition of the ether to RuO{sub 4} followed by a slow concerted step. 228 refs., 9 figs., 27 tabs.

Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes

NARCIS (Netherlands)

Vaandrager, J W; Schuuring, E; Raap, T; Philippo, K; Kleiverda, K; Kluin, P

Rearrangement of the BCL2 gene is an important parameter for the differential diagnosis of non-Hodgkin lymphomas. Although a relatively large proportion of breakpoints is clustered, many are missed by standard PCR. A FISH assay is therefore desired. Up to now, a lack of probes flanking the BCL2 gene

The role of hydrogen bonding on kinetics of rearrangement of heterocyclic aldoximes in perchloric acide

International Nuclear Information System (INIS)

Azzouz, A.S.; Abdullah, K.A.; Al-Niemi, I.

1995-01-01

Four paris of syn and anti aromatic heterocyclic aldoximes as 2-thiophenealdoxime, 2- furfuraladoxime, 2-pyridinealdoxime and 2-pyrrolealdoxime are prepared. The strcutures of these geometrical isomers are confirmed by the meaasurements of their U.V. I, R and melting points. Experiments show the existence of these aldoximers in an intramolecular hy-drogen bonding with variable strength depending on the hetero ztoms in the aldoximes. The first order rate constants of the rearrangement of syn aldoximes follow the order of hetero S>O>N, while the anti aldoximes show irregular order, Factors governing the aniti constants of the rearrangement of syn and anti aldoximes are analysed. Activation parameters are estimated and discussed on the basis of isokinetic relation-ship. The differences in physical and spectroscpic behavior of aldoximes lead to an important suggestion regarding the configuration of oxime. (author). 27 refs., 2 figs., 2 tabs

Mitochondrial genome of the Komodo dragon: efficient sequencing method with reptile-oriented primers and novel gene rearrangements.

Science.gov (United States)

Kumazawa, Yoshinori; Endo, Hideki

2004-04-30

The mitochondrial genome of the Komodo dragon (Varanus komodoensis) was nearly completely sequenced, except for two highly repetitive noncoding regions. An efficient sequencing method for squamate mitochondrial genomes was established by combining the long polymerase chain reaction (PCR) technology and a set of reptile-oriented primers designed for nested PCR amplifications. It was found that the mitochondrial genome had novel gene arrangements in which genes from NADH dehydrogenase subunit 6 to proline tRNA were extensively shuffled with duplicate control regions. These control regions had 99% sequence similarity over 700 bp. Although snake mitochondrial genomes are also known to possess duplicate control regions with nearly identical sequences, the location of the second control region suggested independent occurrence of the duplication on lineages leading to snakes and the Komodo dragon. Another feature of the mitochondrial genome of the Komodo dragon was the considerable number of tandem repeats, including sequences with a strong secondary structure, as a possible site for the slipped-strand mispairing in replication. These observations are consistent with hypotheses that tandem duplications via the slipped-strand mispairing may induce mitochondrial gene rearrangements and may serve to maintain similar copies of the control region.

Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Ye, Qing; Xu-Monette, Zijun Y; Tzankov, Alexandar

2016-01-01

Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2...... frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma...

Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

DEFF Research Database (Denmark)

Xu-Monette, Zijun Y; Dabaja, Bouthaina S; Wang, Xiaoxiao

2015-01-01

MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about...

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with I-131 radiation dose and other characteristics

Science.gov (United States)

Leeman-Neill, Rebecca J.; Brenner, Alina V.; Little, Mark P.; Bogdanova, Tetiana I.; Hatch, Maureen; Zurnadzy, Liudmyla Y.; Mabuchi, Kiyohiko; Tronko, Mykola D.; Nikiforov, Yuri E.

2012-01-01

Background Childhood exposure to I-131 from the 1986 Chernobyl accident led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. Methods We performed mutational analysis of 62 PTCs diagnosed in a Ukrainian cohort of patients who were Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with I-131 dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and I-131 exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. PMID:23436219

A Consensus Map in Cultivated Hexaploid Oat Reveals Conserved Grass Synteny with Substantial Subgenome Rearrangement

Directory of Open Access Journals (Sweden)

Ashley S. Chaffin

2016-07-01

Full Text Available Hexaploid oat ( L., 2 = 6 = 42 is a member of the Poaceae family and has a large genome (∼12.5 Gb containing 21 chromosome pairs from three ancestral genomes. Physical rearrangements among parental genomes have hindered the development of linkage maps in this species. The objective of this work was to develop a single high-density consensus linkage map that is representative of the majority of commonly grown oat varieties. Data from a cDNA-derived single-nucleotide polymorphism (SNP array and genotyping-by-sequencing (GBS were collected from the progeny of 12 biparental recombinant inbred line populations derived from 19 parents representing oat germplasm cultivated primarily in North America. Linkage groups from all mapping populations were compared to identify 21 clusters of conserved collinearity. Linkage groups within each cluster were then merged into 21 consensus chromosomes, generating a framework consensus map of 7202 markers spanning 2843 cM. An additional 9678 markers were placed on this map with a lower degree of certainty. Assignment to physical chromosomes with high confidence was made for nine chromosomes. Comparison of homeologous regions among oat chromosomes and matches to orthologous regions of rice ( L. reveal that the hexaploid oat genome has been highly rearranged relative to its ancestral diploid genomes as a result of frequent translocations among chromosomes. Heterogeneous chromosome rearrangements among populations were also evident, probably accounting for the failure of some linkage groups to match the consensus. This work contributes to a further understanding of the organization and evolution of hexaploid grass genomes.

Clinical outcomes of myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement.

Science.gov (United States)

Umino, Kento; Fujiwara, Shin-Ichiro; Ikeda, Takashi; Toda, Yumiko; Ito, Shoko; Mashima, Kiyomi; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Ashizawa, Masahiro; Hatano, Kaoru; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Muroi, Kazuo; Kanda, Yoshinobu

2018-02-28

Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient. The primary diagnoses were myeloproliferative neoplasm (MPN) or myelodysplastic syndromes (MDS) in 14 and acute leukemia or LBL in 31. In MPN and MDS patients, the cumulative incidence of transformation to blast phase (BP) at 12 months was 46.2%. The 1-year overall survival (OS) from diagnosis in all cases was 43.1%. With regard to the impact of treatment response on survival, the achievement of complete response with a landmark at 2 months after diagnosis of BP was associated with a superior OS (40.0% vs. 26.0% P = 0.011 for 1-year OS from BP). Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 13 patients, and the 1-year OS from allogeneic HSCT was 61.5%. The hazard ratio for mortality was 0.34 (95% CI, 0.08-1.51, P = 0.15) for allogeneic HSCT treated as a time-dependent covariate, which suggests that allogeneic HSCT may confer a clinical benefit. The further accumulation of clinical data is needed to determine the optimal therapeutic approach for these neoplasms.

Iridium-Catalyzed Dynamic Kinetic Isomerization: Expedient Synthesis of Carbohydrates from Achmatowicz Rearrangement Products.

Science.gov (United States)

Wang, Hao-Yuan; Yang, Ka; Bennett, Scott R; Guo, Sheng-rong; Tang, Weiping

2015-07-20

A highly stereoselective dynamic kinetic isomerization of Achmatowicz rearrangement products was discovered. This new internal redox isomerization provided ready access to key intermediates for the enantio- and diastereoselective synthesis of a series of naturally occurring sugars. The nature of the de novo synthesis also enables the preparation of both enantiomers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of chromosomal rearrangements in the evolution of Silene latifolia sex chromosomes

Czech Academy of Sciences Publication Activity Database

Hobza, Roman; Kejnovský, Eduard; Vyskot, Boris; Widmer, A.

2007-01-01

Roč. 278, č. 6 (2007), s. 633-638 ISSN 1617-4615 R&D Projects: GA ČR(CZ) GA204/05/2097; GA ČR(CZ) GA521/06/0056 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : chromosomal rearrangements * sex chromosomes * FISH Subject RIV: BO - Biophysics Impact factor: 2.978, year: 2007

Two girls with a de novo Xq rearrangement of paternal origin: t(X;9(q24;q12 or rea(Xdup q

Directory of Open Access Journals (Sweden)

Ana I. Vásquez-Velásquez

2016-04-01

Full Text Available Objective: We report on two rare Xq rearrangements, namely a t(X;9(q24;q12 found in a mildly-affected girl (Patient 1 and a rea(Xdup q concomitant with a rob(14;21mat in a Down syndrome girl (Patient 2. Case report: Both rearrangements were characterized by banding techniques [Giemsa (G, constitutive heterochromatin (C, and bromodeoxyuridine (BrdU pulse], fluorescence in situ hybridization (FISH assays, human androgen receptor (HUMAR assays, and microarray analyses. Patient 1 had a t(X;9(q24;q12dn. Patient 2 had a de novo rea(X(qter→q23 or q24::p11.2→qter concomitant with an unbalanced rob(14;21mat. X-Inactivation studies in metaphases and DNA revealed a fully skewed inactivation: the normal homolog was silenced in Patient 1 and the rea(X in Patient 2. Both rearranged X chromosomes were of paternal descent. Microarray analyses revealed no imbalances in Patient 1 whereas loss of Xp (∼52 Mb and duplication of Xq (∼44 Mb and 21q were confirmed in Patient 2. Conclusion: Our observations further document the cytogenetic heterogeneity and predominant paternal origin of certain de novo X-chromosome rearrangements.

A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia

NARCIS (Netherlands)

Gröschel, Stefan; Sanders, Mathijs A; Hoogenboezem, Remco; de Wit, Elzo; Bouwman, Britta A M; Erpelinck, Claudia; van der Velden, Vincent H J; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J; van Duin, Mark; Döhner, Konstanze; Beverloo, H Berna; Bradner, James E; Döhner, Hartmut; Löwenberg, Bob; Valk, Peter J M; Bindels, Eric M J; de Laat, Wouter; Delwel, Ruud

2014-01-01

Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional

Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype

NARCIS (Netherlands)

Fantes, J.; Redeker, B.; Breen, M.; Boyle, S.; Brown, J.; Fletcher, J.; Jones, S.; Bickmore, W.; Fukushima, Y.; Mannens, M.

1995-01-01

Current evidence suggests that aniridia (absence of iris) is caused by loss of function of one copy of the PAX6 gene, which maps to 11p13. We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not

Curtius rearrangement reactions of 3-(4-azidocarbonyl ...

Indian Academy of Sciences (India)

Unknown

Aedes aegypti mosquito is the vector responsible for dangerous diseases like dengue hemorrhagic fever and yellow fever. An attempt has been made to study the newly synthesized carbamate compounds with respect to their insecticidal properties against fourth instar larvae of Aedes aegypti under labora- tory conditions.

New type of cells with multiple chromosome rearrangements

International Nuclear Information System (INIS)

Aseeva, E.A.; Domracheva, E.V.; Neverova, A.L; Bogomazova, A.N.; Snigiryova, G.P.; Novitskaya, N.N.; Khazins, E.D.

2008-01-01

Full text: A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. MAC were found in most of the examined groups and they were absent in the control population. A highest MAC frequency was observed in people exposed to alpha radiation (Pu, Ra). This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the FISH method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods is discussed

Evidence for compact cooperatively rearranging regions in a supercooled liquid

International Nuclear Information System (INIS)

Elenius, M; Dzugutov, M

2009-01-01

We examine structural relaxation in a supercooled glass-forming liquid simulated by constant-energy constant-volume (NVE) molecular dynamics. Time correlations of the total kinetic energy fluctuations are used as a comprehensive measure of the system's approach to the ergodic equilibrium. We find that, under cooling, the total structural relaxation becomes delayed as compared with the decay of the component of the intermediate scattering function corresponding to the main peak of the structure factor. This observation can be explained by collective movements of particles preserving many-body structural correlations within compact three-dimensional (3D) cooperatively rearranging regions.

Hadronic J/psi and charmed particle production and correlating quark rearrangement model

International Nuclear Information System (INIS)

Nishitani, Tadashi

1979-01-01

On the basis of the correlating quark rearrangement model, the exclusive and inclusive production cross sections of J/psi and charmed particles in hadron collisions are calculated. It is shown that the inclusive production cross section of charmed particles is several tens of μb at p sub( l) -- 100 GeV/c in hadron collisions. The OZI rule is discussed in connection with the production mechanism of J/psi particles. (author)

Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy

DEFF Research Database (Denmark)

Mefford, Heather C; Clauin, Severine; Sharp, Andrew J

2007-01-01

predisposed to recurrent rearrangement, by array-based comparative genomic hybridization. We found that 6% of fetal material showed evidence of microdeletion or microduplication, including three independent events that likely resulted from unequal crossing-over between segmental duplications. One...

Data re-arranging techniques leading to proper variable selections in high energy physics

Science.gov (United States)

Kůs, Václav; Bouř, Petr

2017-12-01

We introduce a new data based approach to homogeneity testing and variable selection carried out in high energy physics experiments, where one of the basic tasks is to test the homogeneity of weighted samples, mainly the Monte Carlo simulations (weighted) and real data measurements (unweighted). This technique is called ’data re-arranging’ and it enables variable selection performed by means of the classical statistical homogeneity tests such as Kolmogorov-Smirnov, Anderson-Darling, or Pearson’s chi-square divergence test. P-values of our variants of homogeneity tests are investigated and the empirical verification through 46 dimensional high energy particle physics data sets is accomplished under newly proposed (equiprobable) quantile binning. Particularly, the procedure of homogeneity testing is applied to re-arranged Monte Carlo samples and real DATA sets measured at the particle accelerator Tevatron in Fermilab at DØ experiment originating from top-antitop quark pair production in two decay channels (electron, muon) with 2, 3, or 4+ jets detected. Finally, the variable selections in the electron and muon channels induced by the re-arranging procedure for homogeneity testing are provided for Tevatron top-antitop quark data sets.

Comparison between the Oxygen Reduction Reaction Activity of Pd₅Ce and Pt₅Ce

DEFF Research Database (Denmark)

Tripkovic, Vladimir; Zheng, Jian; Rizzi, Gian Andrea

2015-01-01

A set of electrochemical and X-ray spectroscopy measurements have been used conjointly with density functional theory (DFT) simulations to study the activity and stability of Pd5Ce for the oxygen reduction reaction. A polycrystalline Pd5Ce rod has been selected as a model catalyst to test if resu......-Pd5Ce is more facile, requires less atom rearrangement, than transformation from Pt5Ce to Pt3Ce, which might explain the kinetic stability of Pt5Ce at low temperatures....

Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas.

Science.gov (United States)

Kokovic, Ira; Jezersek Novakovic, Barbara; Novakovic, Srdjan

2015-03-01

Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.

Degradation of Perfluorooctanoic Acid and Perfluoroctane Sulfonate by Enzyme Catalyzed Oxidative Humification Reactions

Science.gov (United States)

Huang, Q.

2016-12-01

Poly- and perfluoroalkyl substances (PFASs) are alkyl based chemicals having multiple or all hydrogens replaced by fluorine atoms, and thus exhibit high thermal and chemical stability and other unusual characteristics. PFASs have been widely used in a wide variety of industrial and consumer products, and tend to be environmentally persistent. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are two representative PFASs that have drawn particular attention because of their ubiquitous presence in the environment, resistance to degradation and toxicity to animals. This study examined the decomposition of PFOA and PFOS in enzyme catalyzed oxidative humification reactions (ECOHR), a class of reactions that are ubiquitous in the environment involved in natural organic humification. Reaction rates and influential factors were examined, and high-resolution mass spectrometry was used to identify possible products. Fluorides and partially fluorinated compounds were identified as likely products from PFOA and PFOS degradation, which were possibly formed via a combination of free radical decomposition, rearrangements and coupling processes. The findings suggest that PFOA and PFOS may be transformed during humification, and ECOHR can potentially be used for the remediation of these chemicals.

Effects of cooling rate on particle rearrangement statistics: Rapidly cooled glasses are more ductile and less reversible.

Science.gov (United States)

Fan, Meng; Wang, Minglei; Zhang, Kai; Liu, Yanhui; Schroers, Jan; Shattuck, Mark D; O'Hern, Corey S

2017-02-01

Amorphous solids, such as metallic, polymeric, and colloidal glasses, display complex spatiotemporal response to applied deformations. In contrast to crystalline solids, during loading, amorphous solids exhibit a smooth crossover from elastic response to plastic flow. In this study, we investigate the mechanical response of binary Lennard-Jones glasses to athermal, quasistatic pure shear as a function of the cooling rate used to prepare them. We find several key results concerning the connection between strain-induced particle rearrangements and mechanical response. We show that the energy loss per strain dU_{loss}/dγ caused by particle rearrangements for more rapidly cooled glasses is larger than that for slowly cooled glasses. We also find that the cumulative energy loss U_{loss} can be used to predict the ductility of glasses even in the putative linear regime of stress versus strain. U_{loss} increases (and the ratio of shear to bulk moduli decreases) with increasing cooling rate, indicating enhanced ductility. In addition, we characterized the degree of reversibility of particle motion during a single shear cycle. We find that irreversible particle motion occurs even in the linear regime of stress versus strain. However, slowly cooled glasses, which undergo smaller rearrangements, are more reversible during a single shear cycle than rapidly cooled glasses. Thus, we show that more ductile glasses are also less reversible.

Using positive-ion electrospray ionization mass spectrometry and H/D exchange study phosphoryl group transfer reactions involved in amino acid ester isopropyl phosphoramidates of Brefeldin A

International Nuclear Information System (INIS)

Fang, Mei-Juan; Zhang, He; Liao, Chao; Qiu, Ying-Kun; Fang, Hua; Zheng, Zhen-Yu; Gao, Xiang; Zhao, Yu-Fen; Wu, Zhen

2015-01-01

Highlights: • ESI-MS n , HRMS and H/D exchange were used. • The fragmentation pathways of NPAAE-BFA in ESI-MS n were described. • Fragment ions involved in phosphorus group’s rearrangement reactions were observed. • Two rearrangement mechanisms about phosphorylation–dephosphorylation were proposed. - Abstract: As mini-chemical models, amino acid ester isopropyl phosphoramidates of Brefeldin A (compounds 2a–2d) were synthesized and investigated by electrospray ionization tandem mass spectrometry in combination with H/D exchange. To further confirm the fragments’s structures, off-line Fourier transform resonance tandem mass spectrometry (FT-ICR-MS/MS) was also performed. The fragmentation rules of compounds 2a–2d have been summarized and the plausible schemes for the fragmentation pathways were proposed. In this study, one dephosphorylated ion and two phosphorylated ions were observed in ESI-MS 2 spectra of [M + Na] + ions for compounds 2a–2d. The possible mechanisms about phosphorylation and dephosphorylation were proposed and confirmed by H/D exchange. For the “dephosphorylation” rearrangement, a nitrogen atom was migrated from the phosphoryl group to the carbon atom of Brefeldin A’s backbone with losing a molecule of C 3 H 7 PO 3 (122 Da). For the “phosphorylation” rearrangement, an oxygen atom of one phosphoryl group attacked the sideward phosphorus atom to form a nine-member ring intermediate, then two steps of C-H covalent bond cleavage with consecutive migration of hydrogen atom to lose a molecule of C 16 H 20 O 2 (244 Da). The two proposed rearrangement mechanisms about phosphoryl group transfer might be valuable for the structure analysis of other analogs and provide insights into elucidating the dynamic process of the phosphorylation–dephosphorylation of proteins

Using positive-ion electrospray ionization mass spectrometry and H/D exchange study phosphoryl group transfer reactions involved in amino acid ester isopropyl phosphoramidates of Brefeldin A

Energy Technology Data Exchange (ETDEWEB)

Fang, Mei-Juan; Zhang, He; Liao, Chao; Qiu, Ying-Kun [School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102 (China); Fang, Hua [The Third Institute of Oceanography of the State Oceanic Administration, Xiamen 361005 (China); Zheng, Zhen-Yu [College of Chemistry and Chemical Engineering, Department of Chemistry, Xiamen University, Xiamen 361005 (China); Gao, Xiang [School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102 (China); Zhao, Yu-Fen [School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102 (China); College of Chemistry and Chemical Engineering, Department of Chemistry, Xiamen University, Xiamen 361005 (China); Wu, Zhen, E-mail: wuzhen@xmu.edu.cn [School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102 (China)

2015-01-01

Highlights: • ESI-MS{sup n}, HRMS and H/D exchange were used. • The fragmentation pathways of NPAAE-BFA in ESI-MS{sup n} were described. • Fragment ions involved in phosphorus group’s rearrangement reactions were observed. • Two rearrangement mechanisms about phosphorylation–dephosphorylation were proposed. - Abstract: As mini-chemical models, amino acid ester isopropyl phosphoramidates of Brefeldin A (compounds 2a–2d) were synthesized and investigated by electrospray ionization tandem mass spectrometry in combination with H/D exchange. To further confirm the fragments’s structures, off-line Fourier transform resonance tandem mass spectrometry (FT-ICR-MS/MS) was also performed. The fragmentation rules of compounds 2a–2d have been summarized and the plausible schemes for the fragmentation pathways were proposed. In this study, one dephosphorylated ion and two phosphorylated ions were observed in ESI-MS{sup 2} spectra of [M + Na]{sup +} ions for compounds 2a–2d. The possible mechanisms about phosphorylation and dephosphorylation were proposed and confirmed by H/D exchange. For the “dephosphorylation” rearrangement, a nitrogen atom was migrated from the phosphoryl group to the carbon atom of Brefeldin A’s backbone with losing a molecule of C{sub 3}H{sub 7}PO{sub 3} (122 Da). For the “phosphorylation” rearrangement, an oxygen atom of one phosphoryl group attacked the sideward phosphorus atom to form a nine-member ring intermediate, then two steps of C-H covalent bond cleavage with consecutive migration of hydrogen atom to lose a molecule of C{sub 16}H{sub 20}O{sub 2} (244 Da). The two proposed rearrangement mechanisms about phosphoryl group transfer might be valuable for the structure analysis of other analogs and provide insights into elucidating the dynamic process of the phosphorylation–dephosphorylation of proteins.