Interaction of quinones with three pyrimidine bases: A laser flash photolysis study

International Nuclear Information System (INIS)

Bose, Adity; Basu, Samita

2009-01-01

The interaction between three different pyrimidine bases, uracil (U), cytosine (C) and thymine (T) and two quinones, 2-methyl-1,4-naphthoquinone or menadione (MQ) and 9,10-anthraquinone (AQ) have been studied using laser flash photolysis technique in organic homogeneous medium. The three pyrimidines have revealed a difference in their extent of reactivity towards the quinones, which has been attributed to their structural difference. Our works have revealed that the difference in structural dimension of the quinones is also responsible for affecting the reactivity of these pyrimidines in homogeneous medium.

Rapid method for detecting base damage in DNA of mammalian cells: assay of U. V. -induced pyrimidine dimers in human cells

Energy Technology Data Exchange (ETDEWEB)

Bryant, P E [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit; Jansson, G; Ahnstroem, G

1978-11-01

Simple and rapid techniques are described for the detection of pyrimidine dimers in DNA. Human cells derived from embryonic lung tissue were UV-irradiated and subjected to either an osmotic shock procedure or detergent lysis, then treated with UV-endonuclease from Micrococcus luteus and the DNA partially denatured by treatment with weak alkali. Brief sonication reduced the molecular weight of the DNA, and the single- and double-stranded DNA could then be separated by hydroxylapatite chromatography. Approximately 40% of the expected number of pyrimidine dimers were detected by the enzyme treatment technique. The mean value of numbers of strand breaks per 10/sup 9/ dalton per J/m/sup 2/ was approximately 50% of the expected value. The method has advantages of speed and reproducibility and a large reduction in the quantities of materials used, particularly at the scintillation-counting stage.

Studies on Synthesis of Pyrimidine Derivatives and their Pharmacological Evaluation

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T. A. Naik

2007-01-01

Full Text Available 1,3,4-Oxadiazoles were associated with broad spectrum of biological activities including antituberculosis, anticonvulsant, anti-inflammatory, insecticidal, antifungal, analgesic and antitumor properties. Morpholine derivatives find their wide spectrum of antimicrobial activity and exhibit anthelmintic, bactericidal and insecticidal activity. Pyrimidine derivatives are also reported to possess antibacterial, antimicrobial, antifungal, anticancer and anticonvulsant activities. Encouraged by this observations we decided to synthesised novel pyrimidine derivatives.

Pyrimidines in antimalarial drug design

CSIR Research Space (South Africa)

Moleele, SS

2008-09-01

Full Text Available of the routes attempted are shown in Scheme 1. Pyrimidines In Antimalarial Drug Design S S Moleele1, D Gravestock1, A L Rousseau1, R L Van Zyl2 1Discovery Chemistry, CSIR, Biosciences, Private Bag X2, Modderfontein, 1645, South Africa; SMoleele@csir.co.za 2...

Chemical evolution. XXIX - Pyrimidines from hydrogen cyanide

Science.gov (United States)

Ferris, J. P.; Joshi, P. C.; Lawless, J. G.

1978-01-01

Compounds obtained by hydrolysis of HCN oligomers formed by allowing pH 9.2, 0.1 M cyanide to stand at room temperature for 4 to 12 months were analyzed. Hydrolysis of HCN oligomers yielded 4,5-dihydroxypyrimidine and 5-hydroxyuracil; orotic acid was detected after hydrolysis at pH 8.5. A unified pathway from diaminofumaronitrile to the pyrimidines observed is suggested. As purines, pyrimidines and amino acids are released by hydrolysis of HCN oligomers in either acidic or mildly basic aqueous solutions, they could have been formed on the primitive earth in spite of fluctuations in pH. 4,5-dihydroxypyrimidines appear to be likely candidates for incorporation into primitive nucleic acids, as they should undergo Watson-Crick hydrogen bonding with adenine.

Rhodium(III)-Catalyzed ortho-Alkylation of Phenoxy Substrates with Diazo Compounds via C-H Activation: A Case of Decarboxylative Pyrimidine/Pyridine Migratory Cyclization Rather than Removal of Pyrimidine/Pyridine Directing Group.

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Ravi, Manjula; Allu, Srinivasarao; Swamy, K C Kumara

2017-03-03

An efficient Rh(III)-catalyzed ortho-alkylation of phenoxy substrates with diazo compounds has been achieved for the first time using pyrimidine or pyridine as the directing group. Furthermore, bis-alkylation has also been achieved using para-substituted phenoxypyrimidine and 3 mol equiv of the diazo ester. The ortho-alkylated derivatives of phenoxy products possessing the ester functionality undergo decarboxylative pyrimidine/pyridine migratory cyclization (rather than deprotection of pyrimidine/pyridine group) using 20% NaOEt in EtOH affording a novel class of 3-(pyrimidin-2(1H)-ylidene)benzofuran-2(3H)-ones and 6-methyl-3-(pyridin-2(1H)-ylidene)benzofuran-2(3H)-one. The ortho-alkylated phenoxypyridine possessing ester functionality also undergoes decarboxylative pyridine migratory cyclization using MeOTf/NaOMe in toluene providing 6-methyl-3-(1-methylpyridin-2(1H)-ylidene)benzofuran-2(3H)-one.

Gene set analysis of purine and pyrimidine antimetabolites cancer therapies.

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Fridley, Brooke L; Batzler, Anthony; Li, Liang; Li, Fang; Matimba, Alice; Jenkins, Gregory D; Ji, Yuan; Wang, Liewei; Weinshilboum, Richard M

2011-11-01

Responses to therapies, either with regard to toxicities or efficacy, are expected to involve complex relationships of gene products within the same molecular pathway or functional gene set. Therefore, pathways or gene sets, as opposed to single genes, may better reflect the true underlying biology and may be more appropriate units for analysis of pharmacogenomic studies. Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually. A gene set analysis of 3821 gene sets is presented assessing the association between basal messenger RNA expression and drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for two classes of drugs: pyrimidines [gemcitabine (dFdC) and arabinoside] and purines [6-thioguanine and 6-mercaptopurine]. The gene set nucleoside-diphosphatase activity was found to be significantly associated with both dFdC and arabinoside, whereas gene set γ-aminobutyric acid catabolic process was associated with dFdC and 6-thioguanine. These gene sets were significantly associated with the phenotype even after adjusting for multiple testing. In addition, five associated gene sets were found in common between the pyrimidines and two gene sets for the purines (3',5'-cyclic-AMP phosphodiesterase activity and γ-aminobutyric acid catabolic process) with a P value of less than 0.0001. Functional validation was attempted with four genes each in gene sets for thiopurine and pyrimidine antimetabolites. All four genes selected from the pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one (PDE4D) was validated for the thiopurine gene sets. In summary, results from the gene set analysis of pyrimidine and purine therapies, used often in the treatment of various cancers, provide novel insight into the relationship between genomic variation and drug response.

Catabolism of pyrimidines in yeast: A tool to understand degradation of anticancer drugs

DEFF Research Database (Denmark)

Andersen, Gorm; Merico, A.; Bjornberg, O.

2006-01-01

The pyrimidine catabolic pathway is of crucial importance in cancer patients because it is involved in degradation of several chemotherapeutic drugs, such as 5-fluorouracil; it also is important in plants, unicellular eukaryotes, and bacteria for the degradation of pyrimidine-based biocides/antib...

Blockage of the pyrimidine biosynthetic pathway affects riboflavin production in Ashbya gossypii.

Science.gov (United States)

Silva, Rui; Aguiar, Tatiana Q; Domingues, Lucília

2015-01-10

The Ashbya gossypii riboflavin biosynthetic pathway and its connection with the purine pathway have been well studied. However, the outcome of genetic alterations in the pyrimidine pathway on riboflavin production by A. gossypii had not yet been assessed. Here, we report that the blockage of the de novo pyrimidine biosynthetic pathway in the recently generated A. gossypii Agura3 uridine/uracil auxotrophic strain led to improved riboflavin production on standard agar-solidified complex medium. When extra uridine/uracil was supplied, the production of riboflavin by this auxotroph was repressed. High concentrations of uracil hampered this (and the parent) strain growth, whereas excess uridine favored the A. gossypii Agura3 growth. Considering that the riboflavin and the pyrimidine pathways share the same precursors and that riboflavin overproduction may be triggered by nutritional stress, we suggest that overproduction of riboflavin by the A. gossypii Agura3 may occur as an outcome of a nutritional stress response and/or of an increased availability in precursors for riboflavin biosynthesis, due to their reduced consumption by the pyrimidine pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

A study of anti-inflammatory and analgesic activity of new 2,4,6-trisubstituted pyrimidines.

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Yejella, Rajendra Prasad; Atla, Srinivasa Rao

2011-01-01

Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with various substituted aromatic and hetero aromatic aldehydes according to Claisen-Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in quantitative yields. All the newly synthesized pyrimidines were characterized by means of IR, ¹H- and ¹³C-NMR, Electron Ionization (EI)-mass and elemental analyses and screened for anti-inflammatory and analgesic activities by in vivo. 2-amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4-aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent anti-inflammatory and analgesic activity compared with ibuprofen, reference standard. And also it was found that compound 5b identified as lead structure among all in both the activities. Pyrimidines which showed good anti-inflammatory activity also displayed better analgesic activity.

Increase in urinary purines and pyrimidines in patients with methylmalonic aciduria combined with homocystinuria.

Science.gov (United States)

Porcu, Simona; Corda, Marcella; Lilliu, Franco; Contini, Liliana; Era, Benedetta; Traldi, Pietro; Fais, Antonella

2010-06-03

Methylmalonic aciduria combined with homocystinuria (MMA-HC) is the biochemical trait of a metabolic disorder resulting from impaired conversion of dietary cobalamin (cbl, or vitamin B12) to its two metabolically active forms. Effects on urinary purine and pyrimidine levels have not been described for this condition. Urine samples were collected from three patients with methylmalonic aciduria combined with homocystinuria and from 70 healthy subjects. Urinary purine and pyrimidine levels were quantitated by the use of LC/UV-Vis and LC/ESI/MS. Higher urine levels of pyrimidines were detected with both methods in patients compared to controls. Methylmalonic aciduria with homocystinuria is due to deficiency of the enzyme, cobalamin reductase. The enzyme defect leads to altered hepatic metabolism, which appears to modify circulating pyrimidine levels. Copyright 2010 Elsevier B.V. All rights reserved.

Electrochemical behavior of some new pyrimidine derivatives

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MUSTAFA LUTFU BERKEM

2004-09-01

Full Text Available Electrochemical reduction of two recently synthesized pyrimidine compounds, 1-amino-5-benzoyil-4-phenyl-1H-pyrimidine-2-one (I, and 1-amino-5-benzoil-4-phenyl-1H-pyrimidine-2-thione (II were investigated by cyclic volatmmetry at a hanging mercury drop electrode in aqueous methanol (36 % v/v and in non-aqueous methanol. A series of cathodic peaks without the corresponding anodic peaks were observed for I. As the pH of the solution was increased, some of the cathodic peaks overlapped resulting in the loss of the previously observed peaks. For II, three cathodic peaks and one anodic peak were observed in addition to those observed for I. The peak potentials shifted in the negative direction with increasing pH. This shift was measured over a large pH range (1.80 – 12.30 to determine the pKa values of the compounds. The acidity constants related to the amino groups were 4.80 and 9.80 for I and 5.50 and 9.80 for II. A thiol-thione tautomerization was observed for II, which was more pronounced in the non-aqueous methanol medium. The pK values for both protonation and deprotonation of the thiocarbonyl group were also determined. The pK values were 5.80 and 9.80 for protonation and deprotonation in aqueous methanol and 6.80 and 10.80 in non-aqueous methanol.

Privileged substructure-based diversity-oriented synthesis pathway for diverse pyrimidine-embedded polyheterocycles

DEFF Research Database (Denmark)

Kim, Heejun; Thanh Tung, Truong; Park, Seung Bum

2013-01-01

A new diversity-oriented synthesis pathway for the fabrication of a pyrimidine-embedded polyheterocycles library was developed for potential interactions with diverse biopolymers. Five different pyrimidine-embedded core skeletons were synthesized from ortho-alkynylpyrimidine carbaldehydes by a si...... by a silver- or iodine-mediated tandem cyclization strategy. The resulting polyheterocycles possess diverse fused ring sizes and positions with potential functionalities for further modification....

Of the Nine Cytidine Deaminase-Like Genes in Arabidopsis, Eight Are Pseudogenes and Only One Is Required to Maintain Pyrimidine Homeostasis in Vivo.

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Chen, Mingjia; Herde, Marco; Witte, Claus-Peter

2016-06-01

CYTIDINE DEAMINASE (CDA) catalyzes the deamination of cytidine to uridine and ammonia in the catabolic route of C nucleotides. The Arabidopsis (Arabidopsis thaliana) CDA gene family comprises nine members, one of which (AtCDA) was shown previously in vitro to encode an active CDA. A possible role in C-to-U RNA editing or in antiviral defense has been discussed for other members. A comprehensive bioinformatic analysis of plant CDA sequences, combined with biochemical functionality tests, strongly suggests that all Arabidopsis CDA family members except AtCDA are pseudogenes and that most plants only require a single CDA gene. Soybean (Glycine max) possesses three CDA genes, but only two encode functional enzymes and just one has very high catalytic efficiency. AtCDA and soybean CDAs are located in the cytosol. The functionality of AtCDA in vivo was demonstrated with loss-of-function mutants accumulating high amounts of cytidine but also CMP, cytosine, and some uridine in seeds. Cytidine hydrolysis in cda mutants is likely caused by NUCLEOSIDE HYDROLASE1 (NSH1) because cytosine accumulation is strongly reduced in a cda nsh1 double mutant. Altered responses of the cda mutants to fluorocytidine and fluorouridine indicate that a dual specific nucleoside kinase is involved in cytidine as well as uridine salvage. CDA mutants display a reduction in rosette size and have fewer leaves compared with the wild type, which is probably not caused by defective pyrimidine catabolism but by the accumulation of pyrimidine catabolism intermediates reaching toxic concentrations. © 2016 American Society of Plant Biologists. All Rights Reserved.

Pyrimidine nucleobase radical reactivity in DNA and RNA

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Greenberg, Marc M.

2016-11-01

Nucleobase radicals are major products of the reactions between nucleic acids and hydroxyl radical, which is produced via the indirect effect of ionizing radiation. The nucleobase radicals also result from hydration of cation radicals that are produced via the direct effect of ionizing radiation. The role that nucleobase radicals play in strand scission has been investigated indirectly using ionizing radiation to generate them. More recently, the reactivity of nucleobase radicals resulting from formal hydrogen atom or hydroxyl radical addition to pyrimidines has been studied by independently generating the reactive intermediates via UV-photolysis of synthetic precursors. This approach has provided control over where the reactive intermediates are produced within biopolymers and facilitated studying their reactivity. The contributions to our understanding of pyrimidine nucleobase radical reactivity by this approach are summarized.

A spectroscopic study of the molecular interactions of harmane with pyrimidine and other diazines.

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Muñoz, M A; Guardado, P; Galán, M; Carmona, C; Balón, M

2000-01-17

FTIR, UV-vis, steady state and time-resolved fluorescence measurements show that harmane (1-methyl-9H-pyrido/3,4-b/indole) interacts with pyrimidine and its isomers pyrazine and pyridazine in its ground and lowest singlet states. The mechanisms of interaction are dependent on both the structure of the diazine and the nature of the solvent. Thus, in a low polar solvent such as toluene, harmane forms ground state 1:1 hydrogen-bonded complexes with all the diazines. These complexes quench the fluorescence of harmane and diminish its fluorescence lifetime. Conversely, in buffered (pH 8.7) aqueous solutions, pyrimidine behaves differently from the other diazines. Thus, whereas pyrimidine only interacts with harmane in its ground state, pyrazine and pyridazine also interact in the excited state. The harmane-pyrimidine ground state interaction is an entropic controlled process. Therefore, we propose the formation of pi-pi stacked 1:1 complexes between these substrates. Association constants for the different types of complexes and quenching parameters are reported.

Photoreactivation of ultraviolet radiation-induced pyrimidine dimers in neonatal BALB/c mouse skin

International Nuclear Information System (INIS)

Ananthaswamy, H.N.; Fisher, M.S.

1981-01-01

The numbers of ultraviolet light (uv)-induced pyrimidine dimers in the DNA of neonatal BALB/c mouse skin were measured by assessing the sensitivity of the DNA to Micrococcus luteus uv endonuclease. Irradiation of neonatal BALB/c mice with FS40 sunlamps caused a dose-dependent induction of endonuclease-sensitive sites (pyrimidine dimers) in DNA extracted from back skin. Exposure of these uv-irradiated neonatal mice to photoreactivating (PR) light (cool white fluorescent lamp and incandescent lamp) caused a reduction in the number of pyrimidine dimers in the DNA, as revealed by a shift in low-molecular-weight DNA to high-molecular-weight DNA. In contrast, DNA profiles of the skin of either uv-irradiated mice or uv-irradiated mice kept in the dark for the same duration as those exposed to PR light did not show a loss of uv-induced endonuclease-sensitive sites. Furthermore, reversing the order of treatment, i.e., administering PR light first and then uv, did not produce a reduction in pyrimidine dimers. These results demonstrate that PR or uv-induced pyrimidine dimers occurs in neonatal BALB/c mouse skin. The optimal wavelength range for in vivo PR appears to be in the visible region of the spectrum (greater than 400 nm). Although dimer formation could be detected in both dermis and epidermis, PR occurred only in the dermis. Furthermore, the PR phenomenon could not be detected in the skin of adult mice from the same inbred strain

A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes

DEFF Research Database (Denmark)

Andersen, Gorm; Bjornberg, Olof; Polakova, Silvia

2008-01-01

Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyv...... of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date.......Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces......, respectively. The gene products of URC1 and URC4 are highly conserved proteins with so far unknown functions and they are present in a variety of prokaryotes and fungi. In bacteria and in some fungi, URC1 and URC4 are linked on the genome together with the gene for uracil phosphoribosyltransferase (URC6). Urc1...

Interaction of benzoate pyrimidine analogues with class 1A dihydroorotate dehydrogenase from Lactococcus lactis

DEFF Research Database (Denmark)

Wolfe, Abigail E; Thymark, Majbritt; Gattis, Samuel G

2007-01-01

Dihydroorotate dehydrogenases (DHODs) catalyze the oxidation of dihydroorotate to orotate in the only redox reaction in pyrimidine biosynthesis. The pyrimidine binding sites are very similar in all structurally characterized DHODs, suggesting that the prospects for identifying a class-specific in......-system of the flavin, resulting in a green color....

Heteroaromatization with 4-Hydroxycoumarin Part II: Synthesis of Some New Pyrano[2,3-d]pyrimidines, [1,2,4]triazolo[1,5-c]pyrimidines and Pyrimido[1,6-b]-[1,2,4]triazine Derivatives

Directory of Open Access Journals (Sweden)

A. H. Bedair

2001-05-01

Full Text Available A variety of novel [1,2,4]triazolo[1,5-c]pyrimidine-13-ones (4a-f and (5b-d could be obtained via reaction of 9-amino-7-(4’-chlorophenyl-8,9-dihydro-8-imino-6H,7H-[1]benzopyrano[3`,4`:5,6]pyrano[2,3-d]pyrimidine-6-one (3 with a variety of reagents. Pyrano[2,3-d]pyrimidine-6-ones 5a, 8a-c and pyrimido[1,6-b][1,2,4]-triazine-3,14-dione (6 were also prepared. The antimicrobial activity of some of the synthesized compounds was tested.

Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific neurological symptoms using high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry.

Science.gov (United States)

Schmidt, C; Hofmann, U; Kohlmüller, D; Mürdter, T; Zanger, U M; Schwab, M; Hoffmann, G F

2005-01-01

To evaluate the significance of inborn metabolic disorders of the pyrimidine degradation pathway, 450 children with unspecific neurological symptoms were comprehensively studied; 200 healthy children were recruited as controls. Uracil and thymine as well as their degradation products in urine were determined with an improved method based on reversed-phase HPLC coupled with electrospray ionization tandem mass spectrometry and detection by multiple-reaction monitoring using stable-isotope-labelled reference compounds as internal standards. From the results of the control group we established age-related reference ranges of all pyrimidine degradation products. In the patient group, two children with dihydropyrimidine dehydrogenase (DPYD) deficiency were identified; one of these was homozygous for the exon 14-skipping mutation of the DPYD gene. In addition, two patients with high uracil, dihydrouracil and beta-ureidopropionate were found to have ornithine transcarbamylase deficiency. In the urine of 9 patients, beta-alanine was markedly elevated owing to treatment with vigabatrin, an irreversible inhibitor of GABA transaminase, which interferes with beta-alanine breakdown. Four patients had exclusively high levels of beta-aminoisobutyrate (beta-AIB) due to a low activity of the D-beta-AIB-pyruvate aminotransferase, probably without clinical significance. In conclusion, quantitative investigation of pyrimidine metabolites in children with unexplained neurological symptoms, particularly epileptic seizures with or without psychomotor retardation, can be recommended as a helpful tool for diagnosis in clinical practice. Sensitive methods and age-related reference ranges enable the detection of partial enzyme deficiencies.

Effect of substituent structure on pyrimidine electrophilic substitution

CSIR Research Space (South Africa)

Van der Westhuyzen, CW

2007-01-01

Full Text Available In an investigation into the electrophilic nitrosation reactions of a series of 4,6-disubstituted pyrimidine derivatives, a subtle interplay between the electronic nature of the C-4 and C-6 substituents and reactivity was found where these were...

Tetraoxane-pyrimidine nitrile hybrids as dual stage antimalarials.

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Oliveira, Rudi; Guedes, Rita C; Meireles, Patrícia; Albuquerque, Inês S; Gonçalves, Lídia M; Pires, Elisabete; Bronze, Maria Rosário; Gut, Jiri; Rosenthal, Philip J; Prudêncio, Miguel; Moreira, Rui; O'Neill, Paul M; Lopes, Francisca

2014-06-12

The use of artemisinin or other endoperoxides in combination with other drugs is a strategy to prevent development of resistant strains of Plasmodium parasites. Our previous work demonstrated that hybrid compounds, comprising endoperoxides and vinyl sulfones, were capable of high activity profiles comparable to artemisinin and chloroquine while acting through two distinct mechanisms of action: oxidative stress and falcipain inhibition. In this study, we adapted this approach to a novel class of falcipain inhibitors: peptidomimetic pyrimidine nitriles. Pyrimidine tetraoxane hybrids displayed potent nanomolar activity against three strains of Plasmodium falciparum and falcipain-2, combined with low cytotoxicity. In vivo, a decrease in parasitemia and an increase in survival of mice infected with Plasmodium berghei was observed when compared to control. All tested compounds combined good blood stage activity with significant effects on liver stage parasitemia, a most welcome feature for any new class of antimalarial drug.

Isotope exchange reactions of the hydrogen H-5 of selected pyrimidine derivatives and the preparation of tritium-labeled pyrimidines

Czech Academy of Sciences Publication Activity Database

Dračínský, Martin; Jansa, Petr; Elbert, Tomáš

2011-01-01

Roč. 76, č. 12 (2011), s. 1567-1577 ISSN 0010-0765 R&D Projects: GA AV ČR KJB400550903; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : isotopic labeling * NMR spectroscopy * nucleobases * pyrimidines Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

UV light-induced cyclobutane pyrimidine dimers are mutagenic in mammalian cells

International Nuclear Information System (INIS)

Protic-Sabljic, M.; Tuteja, N.; Munson, P.J.; Hauser, J.; Kraemer, K.H.; Dixon, K.

1986-01-01

We used a simian virus 40-based shuttle vector plasmid, pZ189, to determine the role of pyrimidine cyclobutane dimers in UV light-induced mutagenesis in monkey cells. The vector DNA was UV irradiated and then introduced into monkey cells by transfection. After replication, vector DNA was recovered from the cells and tested for mutations in its supF suppressor tRNA marker gene by transformation of Escherichia coli carrying a nonsense mutation in the beta-galactosidase gene. When the irradiated vector was treated with E. coli photolyase prior to transfection, pyrimidine cyclobutane dimers were removed selectively. Removal of approximately 90% of the pyrimidine cyclobutane dimers increased the biological activity of the vector by 75% and reduced its mutation frequency by 80%. Sequence analysis of 72 mutants recovered indicated that there were significantly fewer tandem double-base changes and G X C----A X T transitions (particularly at CC sites) after photoreactivation of the DNA. UV-induced photoproducts remained (although at greatly reduced levels) at all pyr-pyr sites after photoreactivation, but there was a relative increase in photoproducts at CC and TC sites and a relative decrease at TT and CT sites, presumably due to a persistence of (6-4) photoproducts at some CC and TC sites. These observations are consistent with the fact that mutations were found after photoreactivation at many sites at which only cyclobutane dimers would be expected to occur. From these results we conclude that UV-induced pyrimidine cyclobutane dimers are mutagenic in DNA replicated in monkey cells

Synthesis and biological evaluation of some novel pyrido[1,2-a]pyrimidin-4-ones as antimalarial agents.

Science.gov (United States)

Mane, Uttam R; Mohanakrishnan, D; Sahal, Dinkar; Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2014-05-22

Novel pyrido[1,2-a]pyrimidin-4-ones have been synthesized and evaluated for their antimalarial activity by SYBR Green I assay against erythrocytic stages of chloroquine (CQ) sensitive Pf 3D7 strain. The antimalarial screening of 42 different compounds revealed that 3-Fluorobenzyl(4-oxo-4H-pyrido [1,2-a]pyrimidin-3-yl)carbamate (21, IC50 value 33 μM) and 4-Oxo-N-[4-(trifluoromethyl)benzyl]-4H-pyrido[1,2-a]pyrimidine-3-carboxamide (37, IC50 value 37 μM) showed moderate antimalarial activity. Cytotoxicity study was performed against mammalian cell line (Huh-7) by using the MTT assay for the moderately active compounds. Structural activity relationship (SAR) studies displayed that B-ring unsubstituted pyrido[1,2-a]pyrimidine scaffold is responsible for the antimalarial activities of the evaluated derivatives. This SAR based antimalarial screening supported that pyrido[1,2-a]pyrimidin-4-one can be considered as a lead heterocyclic structure for further development of more potent derivatives for antimalarial activity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Synthesis of some pyridine and pyrimidine derivatives via Michael-Addition

International Nuclear Information System (INIS)

El-Baih, Fatma E.M.; Al-Rasheed, Hessa H.; Al-Hazimi, Hassan M.

2006-01-01

Synthesis of pyridine and pyrimidine analogues 4 and 6-9 were achieved by Michael-addition of compounds containing either active methylene groups like, malononitrile , ethyl cyanoacetate and 1-tetralone or compounds containing active hydrogen atoms like, guanidine in the presence of an oxidizing agent and thiourea to 2-arylmethylidine-1-tetralone and 2-arylmethylidine-6-methoxy-1-tetralone (2) (enones). Addition of malononitrile in piperidine at room temperature to 2-amino-3-cyno-naphtho [1, 2-malonoitrile in sodium alkoxide or sodium hydroxide to 2 gave 4. Cyclization of 3a with acetic anhydride in the presence of conc. H2sO4 gave the naphtha-pyrano[2, 3-d]pyrimidin-8-one (5). Condensation of the pyrimidine thione derivatives 9 with chloroacetic acid gave the 3-oxobenzo[h]thiazoladino[2, 3-b]quinazoline derivatives (10), which were reacted through their active methylene groups with aromatic aldehydes to give the arylidine derivatives 11. These compounds were also prepared in one step by reacting 9 with chloroacetic acid and aromatic aldehydes. Condensation of 9 with 3-bromopropanoic acid gave 4-oxo-benzo[h]1, 3-thiazino[2, 3-b]quinazoline derivatives (12). The structures of the prepared compounds were mainly confirmed on the basis of spectroscopic methods. (author)

Ultraviolet Irradiation of Pyrimidine in Interstellar Ice Analogs: Formation and Photo-Stability of Nucleobases

Science.gov (United States)

Nuevo, Michel; Milam, Stefanie N.; Sandford, Scott A.; Elsila, Jamie E.; Dworkin, Jason P.

2010-01-01

Astrochemistry laboratory experiments recently showed that molecules of prebiotic interest can potentially form in space, as supported by the detection of amino acids in organic residues formed by the UV photolysis of ices simulating interstellar and cometary environments (H2O, CO, CO2, CH3OH, NH3, etc.). Although the presence of amino acids in the interstellar medium (ISM) is still under debate, experiments and the detection of amino acids in meteorites both support a scenario in which prebiotic molecules could be of extraterrestrial origin, before they are delivered to planets by comets, asteroids, and interplanetary dust particles. Nucleobases, the informational subunits of DNA and RNA, have also been detected in meteorites, although they have not yet been observed in the ISM. Thus, these molecules constitute another family of prebiotic compounds that can possibly form via abiotical processes in astrophysical environments. Nucleobases are nitrogen-bearing cyclic aromatic species with various functional groups attached, which are divided into two classes: pyrimidines (uracil, cytosine, and thymine) and purines (adenine and guanine). In this work, we study how UV irradiation affects pyrimidine mixed in interstellar ice analogs (H2O, NH3, CH3OH). In particular, we show that the UV irradiation of H2O:pyrimidine mixtures leads to the production of oxidized compounds including uracil, and show that both uracil and cytosine are formed upon irradiation of H2O:NH3:pyrimidine mixtures. We also study the photostability of pyrimidine and its photoproducts formed during these experiments.

How study patients who receive fluo pyrimidines to prevent ischemic events

International Nuclear Information System (INIS)

Saldombide, L.

2010-01-01

Introduction: Ischemic heart disease is the main cause of death in Uruguay and cancer is the second. The pillar of the systemic treatment of colorectal cancer are fluo pyrimidines and cause acute ischemic events in 3-8% of t rated patients. The 5 fluorouracil is the third anticancer drug most used Objective: Due to the high incidence of the two diseases and the risk of death caused by the ischemic treatment complications, the literature is analyzed to define how to study patients who receive fluo pyrimidines as a medium of preventing the same. Development: fluo pyrimidines cardio-toxicity can occur by myocardial toxicity, vasospasm, dihydropyrimidine dehydrogenase deficiency, autoimmune phenomena, platelet hyper aggregability, etc. The clinic is varied and underestimated: angina, abnormal ST silent and reversible, arrhythmias, heart failure, hypertension and heart failure. It is the most common complication with continuous infusion of 5 Fu and its equivalent capecitabine with bolus f lou pyrimidines. It is common that ischemic heart disease prioritises the risk increase of complications, but their absence does not exist. Without ischemic heart disease it is difficult to prevent ischemic events, however proposes that the older higher risk. Results: No uniform guidelines is advised: detailed history, determine if risk factors such as smoking, hypertension, diabetes and dyslipidemia and They are present electrocardiogram and cardiac evaluation. Warn the patient about angina l pain as early symptom and monitor symptoms during chemotherapy including cardio-vascular hypotension. Discontinue the medication and perform classic anti-angina l symptoms and / or signs of ischemia. Not reintroduce unless it is the only therapeutic option, since mortality may exceed

Synthesis of pyrimidine carboxamide derivatives catalyzed by uranyl

African Journals Online (AJOL)

2014-09-02

(Received September 2, 2014; revised January 1, 2016). ABSTRACT. An efficient and simple method was developed for the synthesis pyrimidine-5-carboxamides using. UO2(NO3)2.6H2O catalyst under conventional and microwave irradiation. The synthesis of dihydropyrimidine using uranyl nitrate had shown many ...

Spin crossover and high spin filtering behavior in Co-Pyridine and Co-Pyrimidine molecules

Science.gov (United States)

Wen, Zhongqian; Zhou, Liping; Cheng, Jue-Fei; Li, Shu-Jin; You, Wen-Long; Wang, Xuefeng

2018-03-01

We present a theoretical study on a series of cobalt complexes, which are constructed with cobalt atoms and pyridine/pyrimidine rings, using density functional theory. We investigate the structural and electric transport properties of spin crossover (SCO) Co complex with two spin states, namely low-spin configuration [LS] and high-spin configuration [HS]. Energy analyses of the two spin states imply that the SCO Co-Pyridine2 and Co-Pyrimidine2 complexes may display a spin transition process accompanied by a geometric modification driven by external stimuli. A nearly perfect spin filtering effect is observed in the Co-Pyrimidine2 complex with [HS] state. In addition, we also discover the contact-dependent transmission properties of Co-Pyridine2. These findings indicate that SCO Co complexes are promising materials for molecular spintronic devices.

Synthesis and fluorescence of new 3-biphenylpyrrolo[1,2-c]pyrimidines

Directory of Open Access Journals (Sweden)

Marian-Laurentiu Tatu

2017-07-01

Full Text Available New pyrrolo[1,2-c]pyrimidines derivates having a biphenyl moiety at position 3 have been synthesized by 1,3-dipolar cycloaddition of their corresponding N-ylides with activated alkynes. FTIR, 1H and 13C NMR spectroscopy and elemental analysis have been used to characterize the structures of the new nine pyrrolo[1,2-c]pyrimidine derivates. Absorption and fluorescence spectra have been recorded. The appropriate solvent for the photoluminescence properties of the studied compounds has been found to be chloroform:acetonitrile mixture (1:1. The main spectral features such as molar extinction coefficients (ε, Stokes shifts, quantum yields using quinine sulphate as standard, fluorescence quenching in the presence of benzoquinone and Stern-Volmer constants have been calculated. The substituent effects on intensity of absorption, maximum absorbance wavelengths and fluorescence parameters have been discussed. The highest quantum yield value was found for ethyl 3-(4-biphenylyl-7-(3,4-dimethoxybenzoylpyrrolo[1,2-c]pyrimidine-5-carboxylate (0.55. The obtained results suggest that the studied compounds are promising candidates for future study in order to evaluate their use in practical applications in fluorescent chemical sensors.

Intermediate energy cross sections for electron-impact vibrational-excitation of pyrimidine

Energy Technology Data Exchange (ETDEWEB)

Jones, D. B. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, SA 5001 (Australia); Ellis-Gibbings, L.; García, G. [Instituto de Física Fundamental, CSIC, Serrano 113-bis, 28006 Madrid (Spain); Nixon, K. L. [Departamento de Física, Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora, Minas Gerais (Brazil); School of Biology, Chemistry and Forensic Science, University of Wolverhampton, Wolverhampton WV1 1LY (United Kingdom); Lopes, M. C. A. [Departamento de Física, Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora, Minas Gerais (Brazil); Brunger, M. J., E-mail: Michael.Brunger@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, SA 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)

2015-09-07

We report differential cross sections (DCSs) and integral cross sections (ICSs) for electron-impact vibrational-excitation of pyrimidine, at incident electron energies in the range 15–50 eV. The scattered electron angular range for the DCS measurements was 15°–90°. The measurements at the DCS-level are the first to be reported for vibrational-excitation in pyrimidine via electron impact, while for the ICS we extend the results from the only previous condensed-phase study [P. L. Levesque, M. Michaud, and L. Sanche, J. Chem. Phys. 122, 094701 (2005)], for electron energies ⩽12 eV, to higher energies. Interestingly, the trend in the magnitude of the lower energy condensed-phase ICSs is much smaller when compared to the corresponding gas phase results. As there is no evidence for the existence of any shape-resonances, in the available pyrimidine total cross sections [Baek et al., Phys. Rev. A 88, 032702 (2013); Fuss et al., ibid. 88, 042702 (2013)], between 10 and 20 eV, this mismatch in absolute magnitude between the condensed-phase and gas-phase ICSs might be indicative for collective-behaviour effects in the condensed-phase results.

Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy

Directory of Open Access Journals (Sweden)

Khalid J.H. Alzahrani

2017-08-01

Full Text Available Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU and 5F,2′deoxyuridine (5F,2′dUrd, and was designated uridine-uracil transporter 1 (UUT1; the other transporter mediated uptake of adenosine, uridine, 5F,2′dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1. To verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the corresponding L. major and L. mexicana genes, expressing each in T. brucei. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [3H]-uridine but not of [3H]-inosine. Conversely, the NT2-like genes mediated uptake of [3H]-inosine but not [3H]-uridine. Among pyrimidine antimetabolites tested, 5-FU and 5F,2′dUrd were the most effective antileishmanials; resistance to both analogs was induced in L. major and L. mexicana. In each case it was found that the resistant cells had lost the transport capacity for the inducing drug. Metabolomics analysis found that the mechanism of action of 5-FU and 5F-2′dUrd was similar in both Leishmania species, with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine salvage system is highly conserved in Leishmania species - essential information for the development of pyrimidine-based chemotherapy. Keywords: Leishmania, Pyrimidine metabolism, Uracil

Synthesis and comparing the antibacterial activities of pyrimidine ...

Indian Academy of Sciences (India)

heterocyclic ring substituted in pyrimidine derivatives have moderate inhibition against ... moved by boiling in presence of catalyst and hydrazine .... by Biginelli reaction. The structures of the synthesized compounds were confirmed by IR, 1H and 13C NMR,. GC-MS and CHN analysis. Formation of 2a was con- firmed by the ...

Intramolecular inverse electron demand Diels-Alder reactions of pyrimidines

NARCIS (Netherlands)

Frissen, A.E.

1990-01-01

This thesis deals with the intramolecular inverse electron demand Diels-Alder reaction of pyrimidines. The main objective of the study was to investigate the synthetic applicability of this reaction and to get more insight in the electronic and steric effects which determine the reactivity

The photochemistry of pyrimidine in realistic astrophysical ices and the production of nucleobases

International Nuclear Information System (INIS)

Nuevo, Michel; Materese, Christopher K.; Sandford, Scott A.

2014-01-01

Nucleobases, together with deoxyribose/ribose and phosphoric acid, are the building blocks of DNA and RNA for all known life. The presence of nucleobase-like compounds in carbonaceous chondrites delivered to the Earth raises the question of an extraterrestrial origin for the molecules that triggered life on our planet. Whether these molecules are formed in interstellar/protostellar environments, in small parent bodies in the solar system, or both, is currently unclear. Recent experiments show that the UV irradiation of pyrimidine (C 4 H 4 N 2 ) in H 2 O-rich ice mixtures that contain NH 3 , CH 3 OH, or CH 4 leads to the formation of the pyrimidine-based nucleobases uracil, cytosine, and thymine. In this work, we discuss the low-temperature UV irradiation of pyrimidine in realistic astrophysical ice mixtures containing H 2 O, CH 3 OH, and NH 3 , with or without CH 4 , to search for the production of nucleobases and other prebiotic compounds. These experiments show the presence of uracil, urea, glycerol, hexamethylenetetramine, small amino acids, and small carboxylic acids in all samples. Cytosine was only found in one sample produced from ices irradiated with a higher UV dose, while thymine was not found in any sample, even after irradiation with a higher UV dose. Results are discussed to evaluate the role of the photochemistry of pyrimidine in the inventory of organic molecules detected in meteorites and their astrophysical/astrobiological implications.

Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities

Directory of Open Access Journals (Sweden)

Hafez Hend N.

2016-09-01

Full Text Available 6ʹ-(4-Chlorophenyl-spiro[cyclohexane-1,2ʹ-thieno[3,2-d][1,3] oxazin]-4ʹ(1ʹH-one (1 was synthesized and used as a starting material for the synthesis of a novel series of spiro compounds having biologically active sulfonamide 2a-e and 3ʹ-(4-acetylphenyl-6ʹ- (4-chlorophenyl-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d] pyrimidine-4ʹ(3ʹH-one (3. Compound 2a was used as a key intermediate for the synthesis of sulfonyl carbothioamide derivatives 4a-c. Also, compound 3 was used as an intermediate for the synthesis of 3ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidin]-3ʹ-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl-1,2-dihydropyridine- 3-carbonitrile derivatives 5a-e, 3ʹH-spiro[cyclohexane- 1,2ʹ- thieno[3,2-d]pyrimidin]-3ʹ-yl]phenyl}-2-oxo-4-(substituted phenyl and/or thienyl-1,2-dihydropyridine-3-carbonitrile derivatives 6a-e, and 4-[(2Z-3-substituted-arylprop-2-enoyl] phenyl-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6ʹ-(4-chlorophenyl-3ʹ-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-ylphenyl]-1ʹH-spiro[cyclohexane-1,2ʹ-thieno- [3,2-d]pyrimidin]-4ʹ(3ʹH-ones 8a-e but with hydroxylamine hydrochloride afforded the corresponding isoxazoline derivatives 9a-e. Also, cyclocondensation by thiourea afforded 2-thioxo-1,2- dihydropyrimidin-4-yl-phenyl-spiro-{cyclohexanethieno[3,2-d] pyrimidin}-4-one derivatives 10a-e. The new compounds were investigated for antimicrobial activity. Compounds 2c, 8b,c, 9b and 10b were the most potent ones against both Gram-negative and Gram-positive bacteria. Compound 8c exhibited higher antifungal activity towards the examined fungi with MIC of 1-2 μmol mL-1 compared to ketoconazole (MIC 2-3 μmol mL-1 .

Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach-Part 2

Energy Technology Data Exchange (ETDEWEB)

Labroli, Marc; Paruch, Kamil; Dwyer, Michael P.; Alvarez, Carmen; Keertikar, Kartik; Poker, Cory; Rossman, Randall; Duca, Jose S.; Fischmann, Thierry O.; Madison, Vincent; Parry, David; Davis, Nicole; Seghezzi, Wolfgang; Wiswell, Derek; Guzi, Timothy J. [Merck

2013-11-20

Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors.

Photoreactivation and excision repair of UV induced pyrimidine dimers in the unicellular cyanobacterium Gloeocapsa alpicola (Synechocystis PCC 6308)

International Nuclear Information System (INIS)

O'Brien, P.A.; Houghton, J.A.

1982-01-01

The survival curve obtained after UV irradiation of the unicellular cyanobacterium Synechocystis is typical of a DNA repair competent organism. Inhibition of DNA replication, by incubating cells in the dark, increased resistance to the lethal effects of UV at higher fluences. Exposure of irradiated cells to near ultraviolet light (350-500 nm) restored viability to pre-irradiation levels. In order to measure DNA repair activity, techniques have been developed for the chromatographic analysis of pyrimidine dimers in synechocystis. The specificity of this method was established using a haploid strain of Saccharomyces cerevisiae. In accordance with the physiological responses of irradiated cells to photoreactivating light, pyrimidine dimers were not detected after photoreactivation treatment. Incubation of irradiated cells under non-photoreactivating growth conditions for 15h resulted in complete removal of pyrimidine dimers. It is concluded that Synechocystis contains photoreactivation and excision repair systems for the removal of pyrimidine dimers. (author)

Synthesis and Anticancer Activity of Some New Pyrazolo[3,4-d]pyrimidin-4-one Derivatives

Directory of Open Access Journals (Sweden)

Khaled R. A. Abdellatif

2014-03-01

Full Text Available 3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d][1,3]oxazin-4-one (3 was prepared by hydrolysis of ethyl 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate (1 to afford the corresponding carboxylic acid 2, which was reacted with acetic anhydride to give 3. The pyrazolo[3,4-d][1,3]oxazin-4-one 3 was reacted with hydroxylamine hydrochloride, urea, thiourea, thiosemicarbazide, phenylhydrazine and aromatic amines to afford the corresponding pyrazolo[3,4-d]pyrimidin-4-ones 4, 5a,b, 6, 7, 8a–e, respectively. Condensation of pyrazoloxazine derivative 3 with 99% hydrazine hydrate afforded the 5-aminopyrazolo[3,4-d] pyrimidine derivative 9. Coupling of 9 with aromatic aldehydes yielded a series of 3,6-dimethyl-5-(4-substitutedbenzylideneamino-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin- 4-ones 10a–e. The new compounds were tested for their antitumor activity on the MCF-7 human breast adenocarcinoma cell line. Almost all the tested compounds revealed antitumor activity, especially 3,6-dimethyl-5-(4-nitrobenzylideneamino-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one (10e which displayed the most potent inhibitory activity with a half maximal inhibitory concentration (IC50 of 11 µM.

Polyurethane Foams with Pyrimidine Rings

Directory of Open Access Journals (Sweden)

Kania Ewelina

2014-09-01

Full Text Available Oligoetherols based on pyrimidine ring were obtained upon reaction of barbituric acid with glycidol and alkylene carbonates. These oligoetherols were then used to obtain polyurethane foams in the reaction of oligoetherols with isocyanates and water. The protocol of foam synthesis was optimized by the choice of proper kind of oligoetherol and synthetic composition. The thermal resistance was studied by dynamic and static methods with concomitant monitoring of compressive strength. The polyurethane foams have similar physical properties as the classic ones except their enhanced thermal resistance. They stand long-time heating even at 200°C. Moreover thermal exposition of foams results generally in increase of their compressive strength.

New insights on pyrimidine signalling within the arterial vasculature

DEFF Research Database (Denmark)

Haanes, Kristian Agmund; Spray, Stine; Syberg, Susanne

2016-01-01

Extracellular pyrimidines activate P2Y receptors on both smooth muscle cells and endothelial cells, leading to vasoconstriction and relaxation respectively. The aim of this study was to utilize P2Y knock-out (KO) mice to determine which P2Y receptor subtype are responsible for the contraction and...

Analysis of pyrimidine dimer content of isolated DNA by nuclease digestion

International Nuclear Information System (INIS)

Farland, W.H.; Sutherland, B.M.

1980-01-01

Isolated DNA is highly susceptible to degradation by exogenous nucleases. Complete digestion is possible with a number of well-characterized enzymes from a variety of sources. Treatment of DNA with a battery of enzymes including both phosphodiesterase and phosphatase activities yields a mixture of nucleosides and inorganic phosphate (P/sub i/) as a final product. Unlike native DNA, ultraviolet-irradiated DNA is resistant to complete digestion. Setlow et al. demonstrated that the structural changes in the DNA responsible for the nuclease resistance were the formation of cyclobutyl pyrimidine dimers, the major photoproduct in UV-irradiated DNA. Using venom phosphodiesterase, they demonstrated that UV irradiation of DNA affected both the rate and extent of enzymatic hydrolysis. In addition, it was demonstrated that the major nuclease-resistant product of this hydrolysis was an oligonucleotide containing dimerized pyrimidines. Treatment of the DNA to split the dimers, either photochemically or photoenzymatically, rendered the polymer more susceptible to hydrolysis by the phosphodiesterase. The specificity of photoreactivating enzyme for pyrimidine dimers lends support to the role of these structures in conferring nuclease resistance to UV-irradiated DNA. The nuclease resistance of DNA containing dimers has been the basis of several assays for the measurement of these photoproducts. Sutherland and Chamberlin reported the development of a rapid and sensitive assay for dimers in 32 P-labeled DNA

PET imaging of HSV1-tk mutants with acquired specificity toward pyrimidine- and acycloguanosine-based radiotracers

Energy Technology Data Exchange (ETDEWEB)

Likar, Yury; Dobrenkov, Konstantin; Olszewska, Malgorzata; Shenker, Larissa; Hricak, Hedvig; Ponomarev, Vladimir [Memorial Sloan-Kettering Cancer Center, Molecular Imaging Laboratory, Department of Radiology, New York, NY (United States); Cai, Shangde [Memorial Sloan-Kettering Cancer Center, Radiochemistry/Cyclotron Core Facility, New York, NY (United States)

2009-08-15

The aim of this study was to create an alternative mutant of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene with reduced phosphorylation capacity for acycloguanosine derivatives, but not pyrimidine-based compounds that will allow for successful PET imaging. A new mutant of HSV1-tk reporter gene, suitable for PET imaging using pyrimidine-based radiotracers, was developed. The HSV1-tk mutant contains an arginine-to-glutamine substitution at position 176 (HSV1-R176Qtk) of the nucleoside binding region of the enzyme. The mutant-gene product showed favorable enzymatic characteristics toward pyrimidine-based nucleosides, while exhibiting reduced activity with acycloguanosine derivatives. In order to enhance HSV1-R176Qtk reporter activity with pyrimidine-based radiotracers, we introduced the R176Q substitution into the more active HSV1-sr39tk mutant. U87 human glioma cells transduced with the HSV1-R176Qsr39tk double mutant reporter gene showed high {sup 3}H-FEAU pyrimidine nucleoside and low {sup 3}H-penciclovir acycloguanosine analog uptake in vitro. PET imaging also demonstrated high {sup 18}F-FEAU and low {sup 18}F-FHBG accumulation in HSV1-R176Qsr39tk+ xenografts. The feasibility of imaging two independent nucleoside-specific HSV1-tk mutants in the same animal with PET was demonstrated. Two opposite xenografts expressing the HSV1-R176Qsr39tk reporter gene and the previously described acycloguanosine-specific mutant of HSV1-tk, HSV1-A167Ysr39tk reporter gene, were imaged using a short-lived pyrimidine-based {sup 18}F-FEAU and an acycloguanosine-based {sup 18}F-FHBG radiotracer, respectively, administered on 2 consecutive days. We conclude that in combination with acycloguanosine-specific HSV1-A167Ysr39tk reporter gene, a HSV1-tk mutant containing the R176Q substitution could be used for PET imaging of two different cell populations or concurrent molecular biological processes in the same living subject. (orig.)

Nucleotide metabolism in Lactococcus lactis: Salvage pathways of exogenous pyrimidines

DEFF Research Database (Denmark)

Martinussen, Jan; Andersen, Paal Skytt; Hammer, Karin

1994-01-01

By measuring enzyme activities in crude extracts and studying the effect of toxic analogs (5-fluoropyrimidines) on cell growth, the metabolism of pyrimidines in Lactococcus lactis was analyzed. Pathways by which uracil, uridine, deoxyuridine, cytidine, and deoxycytidine are metabolized in L. lact...

Synthesis of 7-arylethyl-5-arylpyrazolo pyrimidines through an aza ...

Indian Academy of Sciences (India)

ZHENG LI

2017-10-09

Oct 9, 2017 ... During the past decade, the synthesis of pyrazolo[1,5-a] pyrimidine derivatives ... importance due to pharmaceutical reasons.1,2 For exam- ple, the hypnotic ... In this paper, we report an efficient method for the syn- thesis of ...

Pyrimidine dimers block simian virus 40 replication forks

International Nuclear Information System (INIS)

Berger, C.A.; Edenberg, H.J.

1986-01-01

UV light produces lesions, predominantly pyrimidine dimers, which inhibit DNA replication in mammalian cells. The mechanism of inhibition is controversial: is synthesis of a daughter strand halted at a lesion while the replication fork moves on and reinitiates downstream, or is fork progression itself blocked for some time at the site of a lesion? We directly addressed this question by using electron microscopy to examine the distances of replication forks from the origin in unirradiated and UV-irradiated simian virus 40 chromosomes. If UV lesions block replication fork progression, the forks should be asymmetrically located in a large fraction of the irradiated molecules; if replication forks move rapidly past lesions, the forks should be symmetrically located. A large fraction of the simian virus 40 replication forks in irradiated molecules were asymmetrically located, demonstrating that UV lesions present at the frequency of pyrimidine dimers block replication forks. As a mechanism for this fork blockage, we propose that polymerization of the leading strand makes a significant contribution to the energetics of fork movement, so any lesion in the template for the leading strand which blocks polymerization should also block fork movement

Total cross sections for positron and electron scattering from pyrimidine

International Nuclear Information System (INIS)

Zecca, A; Chiari, L; Trainotti, E; GarcIa, G; Blanco, F; Brunger, M J

2010-01-01

In this paper we report original measurements of total cross sections for positron scattering from the important biomolecule pyrimidine. The energy range of these measurements was 0.3-45 eV, while the energy resolution was ∼260 meV. In addition, we report theoretical results, calculated within the independent atom-screened additivity rule (IAM-SCAR) formalism, for the corresponding electron impact total cross sections. In that case the energy range is 1-10 000 eV. Total cross sections are very important input data for codes that seek to simulate charged-particle tracks in matter, as they define the mean-free path between collisions. As the present data and computations are to the best of our knowledge the first total cross sections to be reported for either positron or electron scattering from pyrimidine, they fill an important void in our available knowledge in the literature.

DENV gene of bacteriophage T4 codes for both pyrimidine dimer-DNA glycosylase and apyrimidinic endonuclease activities

International Nuclear Information System (INIS)

McMillan, S.; Edenberg, H.J.; Radany, E.H.; Friedberg, R.C.; Friedberg, E.C.

1981-01-01

Recent studies have shown that purified preparations of phage T4 UV DNA-incising activity (T4 UV endonuclease or endonuclease V of phase T4) contain a pyrimidine dimer-DNA glycosylase activity that catalyzes hydrolysis of the 5' glycosyl bond of dimerized pyrimidines in UV-irradiated DNA. Such enzyme preparations have also been shown to catalyze the hydrolysis of phosphodiester bonds in UV-irradiated DNA at a neutral pH, presumably reflecting the action of an apurinic/apyrimidinic endonuclease at the apyrimidinic sites created by the pyrimidine dimer-DNA glycosylase. In this study we found that preparations of T4 UV DNA-incising activity contained apurinic/apyrimidinic endonuclease activity that nicked depurinated form I simian virus 40 DNA. Apurinic/apyrimidinic endonuclease activity was also found in extracts of Escherichia coli infected with T4 denV + phage. Extracts of cells infected with T4 denV mutants contained significantly lower levels of apurinic/apyrimidinic endonuclease activity; these levels were no greater than the levels present in extracts of uninfected cells. Furthermore, the addition of DNA containing UV-irradiated DNA and T4 enzyme resulted in competition for pyrimidine dimer-DNA glycosylase activity against the UV-irradiated DNA. On the basis of these results, we concluded that apurinic/apyrimidinic endonuclease activity is encoded by the denV gene of phage T4, the same gene that codes for pyrimidine dimer-DNA glycosylase activity

Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy

DEFF Research Database (Denmark)

Patti, M E; McMahon, G; Mun, E C

2005-01-01

AIMS/HYPOTHESIS: Postprandial hypoglycaemia following gastric bypass for obesity is considered a late manifestation of the dumping syndrome and can usually be managed with dietary modification. We investigated three patients with severe postprandial hypoglycaemia and hyperinsulinaemia unresponsive...... was assessed in all three patients. RESULTS: All three patients had evidence of severe postprandial hyperinsulinaemia and hypoglycaemia. In one patient, reversal of gastric bypass was ineffective in reversing hypoglycaemia. All three patients ultimately required partial pancreatectomy for control...

Heteroaryl ethers by oxidative palladium catalysis of pyridotriazol-1-yloxy pyrimidines with arylboronic acids.

Science.gov (United States)

Bardhan, Sujata; Wacharasindhu, Sumrit; Wan, Zhao-Kui; Mansour, Tarek S

2009-06-18

The oxidative palladium-catalyzed cross-coupling of pyrimidines containing pyridotriazol-1-yloxy (OPt) as either a urea or an amide functional group with arylboronic acids in the presence of Cs(2)CO(3) in DME containing 0.6-1.0% H(2)O is described for the preparation of heteroaryl ethers. The bromo substitution in the case of 3-(5-bromo-pyrimidin-2-yloxy)-3H-[1,2,3]triazolo[4,5-b]pyridine 1 could serve as a handle for further elaborations such as Suzuki coupling for attaching varied aryl groups.

Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

OpenAIRE

Gajanan Khanage, Shantaram; Raju, Appala; Baban Mohite, Popat; Bhanudas Pandhare, Ramdas

2013-01-01

Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives con...

Intramolecular Diels-Alder reactions of pyrimidines, a synthetic and computational study

NARCIS (Netherlands)

Stolle, W.A.W.

1992-01-01

This thesis deals with an investigation on the ringtransformation reactions of 2and 5-(ω-alkynyl)pyrimidine derivatives, which undergo upon heating an intramolecular Diels-Alder reaction and subsequently a spontaneous retro Diels- Alder reaction. To get a better insight into the

Tumour radiosensitization with the halogenated pyrimidines 5'-bromo-and 5'-iododeoxyuridine

International Nuclear Information System (INIS)

Epstein, A.H.; Cook, J.A.; Goffman, T.; Glatstein, E.

1993-01-01

The authors review studies of the use of iododeoxyuridine (IdUrd) and bromodeoxyuridine as radiosensitizers and attempt to correlate the clinical outcome for patients treated with radiation and IdUrd with the extent of halogenated pyrimidine cellular uptake and incorporation. (U.K.)

Fluorescent property of 3-hydroxymethyl imidazo[1,2-a]pyridine and pyrimidine derivatives

Directory of Open Access Journals (Sweden)

Velázquez-Olvera Stephania

2012-08-01

Full Text Available Abstract Background Imidazo[1,2-a]pyridines and pyrimidines are important organic fluorophores which have been investigated as biomarkers and photochemical sensors. The effect on the luminescent property by substituents in the heterocycle and phenyl rings, have been studied as well. In this investigation, series of 3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines were synthesized and evaluated in relation to fluorescence emission, based upon the hypothesis that the hydroxymethyl group may act as an enhancer of fluorescence intensity. Results Compounds of both series emitted light in organic solvents dilutions as well as in acidic and alkaline media. Quantitative fluorescence spectroscopy determined that both fused heterocycles fluoresced more intensely than the parent unsubstituted imidazo[1,2-a]azine fluorophore. In particular, 3-hydroxymethyl imidazo[1,2-a]pyridines fluoresced more intensely than 3-hydroxymethyl imidazo[1,2-a]pyrimidines, the latter emitting blue light at longer wavelengths, whereas the former emitted purple light. Conclusion It was concluded that in most cases the hydroxymethyl moiety did act as an enhancer of the fluorescence intensity, however, a comparison made with the fluorescence emitted by 2-aryl imidazo[1,2-a]azines revealed that in some cases the hydroxymethyl substituent decreased the fluorescence intensity.

Radiation-induced DNA damage in halogenated pyrimidine incorporated cells and its correlation with radiosensitivity

International Nuclear Information System (INIS)

Watanabe, R.; Nikjoo, H.

2003-01-01

Cells with DNA containing 5-halogenated pyrimidines in place of thymidine show significant reductions of slope (Do) and shoulder (Dq) of their radiation survival curves. Similar radiosensitization has also been observed in the yield of DNA strand breaks. The purpose of this study is to obtain an insight into the mechanism of cell lethality by examining the relationship between the spectrum of DNA damage and the cell survival. In this study we estimated the enhancement of strand breaks due to incorporation of halogenated pyrimidine, the complexity of DNA damage and the probability of the initial DNA damage leading to cell inactivation. Monte Carlo track structure methods were used to model and simulate the induction of strand breakage by X-rays. The increase of DNA strand break was estimated by assuming the excess strand break was caused by the highly reactive uracil radicals at the halouracil substituted sites. The assumption of the enhancement mechanism of strand breaks was examined and verified by comparison with experimental data for induction of SSB and DSB. The calculated DNA damage spectrum shows the increase in complexity of strand breaks is due to incorporation of halogenated pyrimidines. The increase in the yield of DSB and cell lethality show similar trend at various degrees of halogenated pyrimidine substitution. We asked the question whether this agreement supports the hypothesis that DSB is responsible for cell lethality? The estimated number of lethal damage from the cell survival using a linear-quadratic model is much less than the initial yield of DSB. This work examines the correlation of cell lethality as a function of frequencies of complex form of double strand breaks

Pyrimidine dimer sites associated with the daughter DNA strands in uv-irradiated human fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Lehmann, A R; Kirk-Bell, S [Sussex Univ., Brighton (UK)

1978-03-01

Pyrimidine dimer sites associated with the newly-synthesized DNA were detected during post-replication repair of DNA in uv-irradiated human fibroblasts. These pyrimidine dimer sites were inferred from a decrease in the molecular weight of pulse-labelled DNA after treatment with an extract of Micrococcus luteus containing uv-specific endonuclease activity. In DNA synthesized immediately after irradiation, the frequency of these daughter strand dimer sites was 7 to 20% of that in the parental DNA. Such sites were found in fibroblasts from normal donors and from xeroderma pigmentosum patients (with defects in excision-repair or post-replication repair). They were excised from the DNA of normal cells. As the time between uv irradiation and pulse-labelling was increased, the frequency of dimer sites associated with the labelled DNA decreased. If the pulse-label was delivered 6 h after irradiation of normal cells or excision-defective xeroderma pigmentosum cells, no dimer sites were detected in the labelled DNA. It has usually been assumed that daughter-strand dimer sites were the result of recombinational exchanges. The assay procedure used in these experiments and in similar experiments of others did not distinguish between labelled DNA containing pyrimidine dimers within the labelled section, and labelled DNA which did not contain pyrimidine dimers but was attached to unlabelled DNA which did contain dimers. The latter structures would arise during normal replication immediately following uv irradiation of mammalian cells. Calculations are presented which suggest that a significant proportion and conceivably all of the dimer sites associated with the daughter strands may have arisen in this way, rather than from recombinational exchanges as has been generally assumed.

Pyrimidine dimer sites associated with the daughter DNA strands in UV-irradiated human fibroblasts

International Nuclear Information System (INIS)

Lehmann, A.R.; Kirk-Bell, S.

1978-01-01

Pyrimidine dimer sites associated with the newly-synthesized DNA were detected during post-replication repair of DNA in UV-irradiated human fibroblasts. These pyrimidine dimer sites were inferred from a decrease in the molecular weight of pulse-labelled DNA after treatment with an extract of Micrococcus luteus containing UV-specific endonuclease activity. In DNA synthesized immediately after irradiation the frequency of these daughter strand dimer sites was 7-20% of that in the parental DNA. Such sites were found in fibroblasts from normal donors and from xeroderma pigmentosum patients (with defects in excision-repair or post-replication repair). They were excised from the DNA of normal cells. As the time between UV-irradiation and pulse-labelling was increased, the frequency of dimer sites associated with the labelled DNA decreased. If the pulse-label was delivered 6 h after irradiation of normal cells or excision-defective xeroderma pigmentosum cells, no dimer sites were detected in the labelled DNA. It has usually been assumed that daughter-strand dimer sites were the result of recombinational exchanges. The assay procedure used in these experiments and in similar experiments of others did not distinguish between labelled DNA containing pyrimidine dimers within the labelled section, and labelled DNA which did not contain pyrimidine dimers but was attached to unlabelled DNA which did contain dimers. The latter structures would arise during normal replication immediately following UV-irradiation of mammalian cells. Calculations are presented which suggest that a significant proportion and conceivably all of the dimer sites associated with the daughter strands may have arisen in this way, rather than from recombinational exchanges as has been generally assumed. (author)

The pyrimidine operon pyrRPB-carA from Lactococcus lactis

DEFF Research Database (Denmark)

Martinussen, Jan; Schallert, J.; Andersen, Birgit

2001-01-01

The four genes pyrR, pyrP, pyrB, and carA were found to constitute an operon in Lactococcus lactis subsp, lactis MG1363. The functions of the different genes were established by mutational analysis. The first gene in the operon is the pyrimidine regulatory gene, pyrR, which is responsible...

Oxidation of pyrimidine nucleosides and nucleotides by osmium tetroxide.

Science.gov (United States)

Burton, K

1967-08-01

1. Pyrimidine nucleosides such as thymidine, uridine or cytidine are oxidized readily at 0 degrees by osmium tetroxide in ammonium chloride buffer. There is virtually no oxidation in bicarbonate buffer of similar pH. Oxidation of 1-methyluracil yields 5,6-dihydro-4,5,6-trihydroxy-1-methyl-2-pyrimidone. 2. Osmium tetroxide and ammonia react reversibly in aqueous solution to form a yellow 1:1 complex, probably OsO(3)NH. A second molecule of ammonia must be involved in the oxidation of UMP since the rate of this reaction is approximately proportional to the square of the concentration of unprotonated ammonia. 3. 4-Thiouridine reacts with osmium tetroxide much more rapidly than does uridine. The changes of absorption spectra are different in sodium bicarbonate buffer and in ammonium chloride buffer. They occur faster in the latter buffer and, under suitable conditions, cytidine is a major product. 4. Polyuridylic acid is oxidized readily by ammoniacal osmium tetroxide, but its oxidation is inhibited by polyadenylic acid. Pyrimidines of yeast amino acid-transfer RNA are oxidized more slowly than the corresponding mononucleosides, especially the thymine residues. Appreciable oxidation can occur without change of sedimentation coefficient.

Effect of some pyrimidinic Schiff bases on the corrosion of mild steel in hydrochloric acid solution

International Nuclear Information System (INIS)

Ashassi-Sorkhabi, H.; Shaabani, B.; Seifzadeh, D.

2005-01-01

The efficiency of benzylidene-pyrimidin-2-yl-amine (A) (4-methyl-benzylidene)-pyrimidine-2-yl-amine (B) and (4-chloro-benzylidene)-pyrimidine-2-yl-amine, as corrosion inhibitors for mild steel in 1 M HCl have been determined by weight loss measurements and electrochemical polarization method. The results showed that these inhibitors revealed a good corrosion inhibition even at very low concentrations. Polarization curves indicate that all compounds are mixed type inhibitors. The effect of various parameters such as temperature and inhibitor concentration on the efficiency of the inhibitors has been studied. Activation energies of corrosion reaction in the presence and absence of inhibitors have been calculated. The adsorption of used compounds on the steel surface obeys Langmuir's isotherm. It appears that an efficient inhibition is characterized by a relatively greater decrease in free energy of adsorption. Significant correlations are obtained between inhibition efficiency and quantum chemical parameters using quantitative structure-activity relationship (QSAR) method

Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy.

Science.gov (United States)

Alzahrani, Khalid J H; Ali, Juma A M; Eze, Anthonius A; Looi, Wan Limm; Tagoe, Daniel N A; Creek, Darren J; Barrett, Michael P; de Koning, Harry P

2017-08-01

Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2'deoxyuridine (5F,2'dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other transporter mediated uptake of adenosine, uridine, 5F,2'dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1). To verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the corresponding L. major and L. mexicana genes, expressing each in T. brucei. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [ 3 H]-uridine but not of [ 3 H]-inosine. Conversely, the NT2-like genes mediated uptake of [ 3 H]-inosine but not [ 3 H]-uridine. Among pyrimidine antimetabolites tested, 5-FU and 5F,2'dUrd were the most effective antileishmanials; resistance to both analogs was induced in L. major and L. mexicana. In each case it was found that the resistant cells had lost the transport capacity for the inducing drug. Metabolomics analysis found that the mechanism of action of 5-FU and 5F-2'dUrd was similar in both Leishmania species, with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine salvage system is highly conserved in Leishmania species - essential information for the development of pyrimidine-based chemotherapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights

Crystal structures of 2-[(4,6-di-amino-pyrimidin-2-yl)sulfan-yl]-N-(naphthalen-1-yl)acetamide and 2-[(4,6-di-amino-pyrimidin-2-yl)sulfan-yl]-N-(4-fluoro-phen-yl)acetamide.

Science.gov (United States)

Subasri, S; Kumar, Timiri Ajay; Sinha, Barij Nayan; Jayaprakash, Venkatesan; Viswanathan, Vijayan; Velmurugan, Devadasan

2017-02-01

The title compounds, C 16 H 15 N 5 OS, (I), and C 12 H 12 FN 5 OS, (II), are [(di-amino-pyrimidine)-sulfan-yl]acetamide derivatives. In (I), the pyrimidine ring is inclined to the naphthalene ring system by 55.5 (1)°, while in (II), the pyrimidine ring is inclined to the benzene ring by 58.93 (8)°. In (II), there is an intra-molecular N-H⋯N hydrogen bond and a short C-H⋯O contact. In the crystals of (I) and (II), mol-ecules are linked by pairs of N-H⋯N hydrogen bonds, forming inversion dimers with R 2 2 (8) ring motifs. In the crystal of (I), the dimers are linked by bifurcated N-H⋯(O,O) and C-H⋯O hydrogen bonds, forming layers parallel to (100). In the crystal of (II), the dimers are linked by N-H⋯O hydrogen bonds, also forming layers parallel to (100). The layers are linked by C-H⋯F hydrogen bonds, forming a three-dimensional architecture.

Tandem Aldol-Michael Reactions in Aqueous Diethylamine Medium: A Greener and Efficient Approach to Bis-Pyrimidine Derivatives

Directory of Open Access Journals (Sweden)

Abdullah M. Al-Majid

2013-12-01

Full Text Available A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a–i and 4a–e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%–99%.

cis-Aquadichlorido[pyrimidin-2(1H-one-κN3]copper(II

Directory of Open Access Journals (Sweden)

A. Guy Orpen

2008-07-01

Full Text Available In the title compound, [CuCl2(C4H4N2O(H2O], the CuII cation is coordinated by two chloride anions, one pyrimidin-2-one N atom and one water molecule, giving a slightly distorted square-planar geometry. In the crystal structure, the pyrimidin-2-one rings stack along the b axis, with an interplanar distance of 3.306 Å, as do the copper coordination planes (interplanar spacing = 2.998 Å. The coordination around the Jahn–Teller-distorted CuII ion is completed by long Cu...O [3.014 (5 Å] and Cu...Cl [3.0194 (15 Å] interactions with adjacent molecules involved in this stacking. Several N—H...Cl, O—H...Cl and O—H...O intermolecular hydrogen bonds form a polar three-dimensional network.

Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops.

Science.gov (United States)

Phan, Andy; Mailey, Katherine; Saeki, Jessica; Gu, Xiaobo; Schroeder, Susan J

2017-05-01

Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased toward small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with >6 nucleotides (nt) that occur frequently in viral RNA. This article presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Uracil and protonated cytosine base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with >6 nt are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2 × 2 have been measured. These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites. © 2017 Phan et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by alpha-tocopherol

International Nuclear Information System (INIS)

Chen, W.; Barthelman, M.; Martinez, J.; Alberts, D.; Gensler, H.L.

1997-01-01

Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis

The role of pyrimidine and water as underlying molecular constituents for describing radiation damage in living tissue: A comparative study

Energy Technology Data Exchange (ETDEWEB)

Fuss, M. C.; Ellis-Gibbings, L. [Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas (CSIC), Serrano 113-bis, 28006 Madrid (Spain); Jones, D. B. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Brunger, M. J. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia); Blanco, F. [Departamento de Física Atómica, Molecular y Nuclear, Universidad Complutense de Madrid, Avenida Complutense, 28040 Madrid (Spain); Muñoz, A. [Centro de Investigaciones Energéticas Medioambientales y Tecnológicas, Avenida Complutense 22, 28040 Madrid (Spain); Limão-Vieira, P. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Laboratório de Colisões Atómicas e Moleculares, CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); García, G., E-mail: g.garcia@csic.es [Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas (CSIC), Serrano 113-bis, 28006 Madrid (Spain); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

2015-06-07

Water is often used as the medium for characterizing the effects of radiation on living tissue. However, in this study, charged-particle track simulations are employed to quantify the induced physicochemical and potential biological implications when a primary ionising particle with energy 10 keV strikes a medium made up entirely of water or pyrimidine. Note that pyrimidine was chosen as the DNA/RNA bases cytosine, thymine, and uracil can be considered pyrimidine derivatives. This study aims to assess the influence of the choice of medium on the charged-particle transport, and identify how appropriate it is to use water as the default medium to describe the effects of ionising radiation on living tissue. Based on the respective electron interaction cross sections, we provide a model, which allows the study of radiation effects not only in terms of energy deposition (absorbed dose and stopping power) but also in terms of the number of induced molecular processes. Results of these parameters for water and pyrimidine are presented and compared.

(3,5-Dimethylpyrazol-1-yl-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminophenyl]methanone

Directory of Open Access Journals (Sweden)

Rania B. Bakr

2016-11-01

Full Text Available In an attempt to enhance cytotoxic activity of pyrazolo[3,4-d]pyrimidine core, we synthesized (3,5-dimethylpyrazol-1-yl-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminophenyl]methanone (4 by reacting 4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminobenzohydrazide (3 with acetylacetone. Antiproliferative activity of this compound was screened against breast (MCF-7, colon (HCT-116, and liver (HEPG-2 cancer cell lines. The tested compound exhibited cytotoxic activity with IC50 = 5.00–32.52 μM. Moreover, inhibitory activity of this compound was evaluated against the epidermal growth factor receptor (EGFR, the fibroblast growth factor receptor (FGFR, the insulin receptor (IR, and the vascular endothelial growth factor receptor (VEGFR. This target compound showed potent inhibitory activity, especially against FGFR with IC50 = 5.18 μM.

Analysis of pyrimidine synthesis "de novo" intermediates in urine and dried urine filter- paper strips with HPLC-electrospray tandem mass spectrometry

NARCIS (Netherlands)

van Kuilenburg, André B. P.; van Lenthe, Henk; Löffler, Monika; van Gennip, Albert H.

2004-01-01

BACKGROUND: The concentrations of the pyrimidine "de novo" metabolites and their degradation products in urine are useful indicators for the diagnosis of an inborn error of the pyrimidine de novo pathway or a urea-cycle defect. Until now, no procedure was available that allowed the analysis of all

Pyrimidine dimers in Drosophila chromatin become increasingly accessible after irradiation

International Nuclear Information System (INIS)

Harris, P.V.; Boyd, J.B.

1987-01-01

A prokaryotic DNA-repair enzyme has been utilized as a probe for changes in the accessibility of pyrimidine dimers in Drosophila chromatin following UV irradiation. The results demonstrate a rapid cellular response to physiologically relevant doses of radiation which results in at least a 40% increase in accessible dimers. This increase occurs in two incision-deficient mutants which indicates that the excision-repair process, at or beyond the incision step, is not required or responsible for the increase. In the absence of excision the increase in accessibility persists for a least 2 days following irradiation. The observed increase in accessibility is inhibited by both novobiocin and coumermycin. These inhibitors do not inhibit the initial rate of incision, but do reduce dimer excision measured over more extended periods. A pre-incision process is proposed which actively exposes DNA lesions to excision repair. A fraction of the genome is postulated to be accessible without the intervention of that process. (Auth.)

Differences in pyrimidine dimer removal between rat skin cells in vitro and in vivo

International Nuclear Information System (INIS)

Mullaart, E.; Lohman, P.H.; Vijg, J.

1988-01-01

Pyrimidine dimers, the most abundant type of DNA lesions induced by ultraviolet light (UV), are rapidly repaired in human skin fibroblasts in vitro. In the same cell type from rats, however, there is hardly any removal of such dimers. To investigate whether this low capacity of rat skin cells to repair lesions in their DNA is an inherent characteristic of this species or an artifact due to cell culturing, we measured the removal of UV-induced pyrimidine dimers from rat epidermal keratinocytes both in vitro and in vivo. Epidermal keratinocytes in vitro were unable to remove any dimers over the first 3 h after UV-irradiation, while only about 20% was removed during a repair period of 24 h. In this respect, these cells were not different from cultured rat fibroblasts. In contrast to the results obtained with keratinocytes in vitro, we observed a rapid repair of pyrimidine dimers in UV-irradiated keratinocytes in vivo over the first 3 h; this rapid repair phase was followed by a much slower repair phase between 3 and 24 h. These results are discussed in terms of the possibility that mammalian cells are able to switch from one DNA repair pathway to another

Inwerking van stikstofhoudende nucleofielen op enige 15N-gemerkte pyrimidine- en chinazolinederivaten

NARCIS (Netherlands)

Kroon, A.P.

1974-01-01

In this thesis an investigation is described on the mechanism of aminations of pyrimidine- and quinazoline derivatives with nitrogen containing bases.

In the introduction a survey is given of investigations, reported in the literature, concerning σ-complex formation on azahetarenes and their

77 FR 5454 - Modifications to Minimum Present Value Requirements for Partial Annuity Distribution Options...

Science.gov (United States)

2012-02-03

... Modifications to Minimum Present Value Requirements for Partial Annuity Distribution Options Under Defined... guidance relating to the minimum present value requirements applicable to certain defined benefit pension plans. These proposed regulations would change the regulations regarding the minimum present value...

Absorption and Intermediary Metabolism of Purines and Pyrimidines in Lactating Dairy Cows

DEFF Research Database (Denmark)

Nielsen, Charlotte Stentoft; Røjen, Betina Amdisen; Jensen, Søren Krogh

2015-01-01

About 20 % of ruminal microbial N in dairy cows derives from purines and pyrimidines; however, their intermediary metabolism and contribution to the overall N metabolism has sparsely been described. In the present study, the postprandial patterns of net portal-drained viscera (PDV) and hepatic...

In vivo excision of pyrimidine dimers is mediated by a DNA N-glycosylase in Micrococcus luteus but not in human fibroblasts

International Nuclear Information System (INIS)

La Belle, M.; Linn, S.

1982-01-01

It has been previously shown that Micrococcus luteus possesses a pyrimidine dimer-specific endonuclease which in vitro, functions as both an endonuclease and DNA-glycosylase. To determine if these combined activities function in vivo, the excision products of UV-irradiated M. luteus were isolated and examined. In addition, a procedure was devised to isolate and examine the excision products from UV-irradiated human fibroblasts to determine if an endonuclease/glycosylase activity functions in the excision of UV-induced pyrimidine dimers in human fibroblasts. It was shown that, in vivo, an endonuclease/glycosylase mechanism is utilized extensively in the repair of pyrimidine dimers by M. luteus, but that human fibroblasts do not appear to use this mechanism. (author)

In vivo excision of pyrimidine dimers is mediated by a DNA N-glycosylase in Micrococcus luteus but not in human fibroblasts

Energy Technology Data Exchange (ETDEWEB)

La Belle, M; Linn, S [California Univ., Berkeley (USA). Dept. of Biochemistry

1982-09-01

It has been previously shown that Micrococcus luteus possesses a pyrimidine dimer-specific endonuclease which in vitro, functions as both an endonuclease and DNA-glycosylase. To determine if these combined activities function in vivo, the excision products of UV-irradiated M. luteus were isolated and examined. In addition, a procedure was devised to isolate and examine the excision products from UV-irradiated human fibroblasts to determine if an endonuclease/glycosylase activity functions in the excision of UV-induced pyrimidine dimers in human fibroblasts. It was shown that, in vivo, an endonuclease/glycosylase mechanism is utilized extensively in the repair of pyrimidine dimers by M. luteus, but that human fibroblasts do not appear to use this mechanism.

Purification, crystallization and preliminary X-ray diffraction study on pyrimidine nucleoside phosphorylase TTHA1771 from Thermus thermophilus HB8

International Nuclear Information System (INIS)

Shimizu, Katsumi; Kunishima, Naoki

2007-01-01

The pyrimidine nucleoside phosphorylase TTHA1771 from T. thermophilus HB8 has been overexpressed, purified and crystallized. The crystals diffract X-rays to 1.8 Å resolution using synchrotron radiation. Pyrimidine nucleoside phosphorylase (PYNP) catalyzes the reversible phosphorolysis of pyrimidines in the nucleotide-synthesis salvage pathway. In order to study the structure–thermostability relationship of this enzyme, PYNP from the extreme thermophile Thermus thermophilus HB8 (TTHA1771) has been cloned, overexpressed and purified. The TTHA1771 protein was crystallized at 291 K using the oil-microbatch method with PEG 4000 as a precipitant. A native data set was collected to 1.8 Å resolution using synchrotron radiation. The crystal belongs to the monoclinic space group P2 1 , with unit-cell parameters a = 58.83, b = 76.23, c = 103.86 Å, β = 91.3°

Removal of pyrimidine dimers from Saccharomyces cerevisiae nuclear DNA under nongrowth conditions as detected by a sensitive, enzymatic assay

Energy Technology Data Exchange (ETDEWEB)

Reynolds, R J [Tennessee Univ., Oak Ridge (USA). Graduate School of Biomedical Sciences

1978-04-01

A sensitive and quantitative procedure for the detection of pyrimidine dimers in yeast nuclear DNA is described. The assay employs dimer-specific, endonuclease activities from Micrococcus luteus together with DNA sedimentation through calibrated, alkaline sucrose gradients to detect endonuclease-induced, single-strand breaks. Breaks were induced in a dose-dependent manner from 0 to 80 J m/sup -2/ at 254 nm and in numbers equivalent to the numbers of dimers induced by similar doses. Endonuclease-sensitive sites in the wild-type, haploid strain S288C, after irradiation with 5 J m/sup -2/ (254 nm), were removed in less than 5 min when cells were incuba ted in buffer (pH 7.0) at 28/sup 0/C. After irra diation with dos es from 30 to 100 J m/sup -2/ site removal in S288C required longer postirradiation incubations and was about 90% complete. In a radiation-sensitive strain carrying the mutant allele rad 4-3 the number of endonuclease-sensitive sites remained constant for 6 h after irradiation with 5 J m/sup -2/. The retention of sites in this strain indicates that it is defective in the excision of pyrimidine dimers. (Auth.

Comparison of the cleavage of pyrimidine dimers by the bacteriophage T4 and Micrococcus luteus uv-specific endonucleases

International Nuclear Information System (INIS)

Gordon, L.K.; Haseltine, W.A.

1980-01-01

A comparison was made of the activity of the uv-specific endonucleases of bacteriophage T4 (T4 endonuclease V) and of Micrococcus luteus on ultraviolet light-irradiated DNA substrates of defined sequence. The two enzyms cleave DNA at the site of pyrimidine dimers with the same frequency. The products of the cleavage reaction are the same. The pyrimidine dimer DNA-glycosylase activity of both enzymes is more active on double-stranded DNA than it is on single-stranded DNA

77 FR 14321 - Modifications to Minimum Present Value Requirements for Partial Annuity Distribution Options...

Science.gov (United States)

2012-03-09

... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 [REG-110980-10] RIN 1545-BJ55 Modifications to Minimum Present Value Requirements for Partial Annuity Distribution Options Under Defined... FR 5454), providing guidance relating to the minimum present value requirements applicable to certain...

Preconcentration and Extraction of Copper ion on Activated Carbon using α-Benzoinoxime and Pyrimidin 2-Thiole

International Nuclear Information System (INIS)

Ghaedi, M.; Mortazavi, K.; Janbezar, M.; Parham, H.

2006-01-01

Activated carbon modified methods were used for preconcentration and determination of copper in some real sample by flame atomic absorption spectrometry. The copper was adsorbed quantitatively on activated carbon due to their complexation with α-benzoinoxime and pyrimidin 2-thiole. The adsorbed copper on solid phase was eluted quantitatively using nitric acid. The important parameters such as pH, amount of carrier, flow rate, amount of activated carbon and type and concentration of eluting agent for obtaining maximum recovery was optimized. The methods based on α- benzoinoxime and pyrimidin 2-thiole at optimum conditions is linear over concentration range of 0.05-1.3 ug mL and 0.06-1.2 ug mL of copper with correlation coefficient of 0.9997 and 0.9994 and both detection limit of 1.2 ngmL, respectively. The preconcentration leads to enrichment factor of 200 and 240 and break through volume of 1200 mL for methods based on α- benzoinoxime and pyrimidin 2-thiole, respectively. The methods have good tolerance limit of interfering ion and selectivity that has been successfully applied for determination of copper content in real sample such as blood, wastewater and river sample. (author)

Microwave-Assisted Synthesis and Antimicrobial Evaluation of Novel Spiroisoquinoline and Spiropyrido[4,3-d]pyrimidine Derivatives

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Rasha M. Faty

2015-01-01

Full Text Available Bromination of N-substituted homophthalimides and tetrahydropyrido[4,3-d]- pyrimidine-5,7-diones produces 4,4-dibromohomophthalimide and 8,8-dibromo-tetrahydropyrido[4,3-d]pyrimidine-5,7-dione derivatives, respectively, that can be used as precursors for spiro derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiroisoquinoline and spirotetrahydropyrido[4,3-d]- pyrimidine-5,7-dione derivatives, respectively. Reaction of the dibromo derivatives with malononitrile produces dicyanomethylene derivatives which react with different binucleophiles to produce new spiro derivatives. All new compounds are prepared by using the usual chemical conditions and microwave assisted conditions. The latter conditions improved the reaction yields, reduced reaction times and ameliorated the effects on the surrounding environment as the reactions are carried out in closed systems. Structures of the newly synthesized compounds are proved using spectroscopic methods such as IR, MS, 1H-NMR and 13C-NMR and elemental analyses. Some of the newly synthesized compounds were tested for their antimicrobial activities, whereby four of them showed moderate activities and the rest showed low or no activities towards the investigated species.

Photorepair and excision repair removal of UV-induced pyrimidine dimers and (6-4) photoproducts in the tail fin of the Medaka, Oryzias latipes

International Nuclear Information System (INIS)

Funayama, Tomoo; Mitani, Hiroshi; Shima, Akihiro; Ishigaki, Yasuhito; Matsunaga, Tsukasa; Nikaido, Osamu.

1994-01-01

Induction and repair of UV-B induced DNA damage in the tail fin of the Medaka, were examined immunohistochemically and by the enzyme-linked immunosorbent assay (ELISA). UV-induced DNA damage was detected only in the outermost layer of epithelial cells and did not differ in fishes having different degree of melanization. Both pyrimidine dimers and (6-4) photoproducts in the fin cells were removed by excision repair in the dark, the excision of (6-4) photoproducts being about twice as efficient as that of pyrimidine dimers. The rate of excision repair of UV-induced lesions in fin tissue was three to four times that in cultured Medaka cells, OL32.. In the fin cells, reductions in the numbers of pyrimidine dimers and (6-4) photoproducts were seen after treatment with fluorescent light, whereas less reductions of pyrimidine dimers and no reductions of (6-4) photoproducts were observed in OL32 cells. (author)

Comparative studies on the correlation between pyrimidine dimer formation and tyrosinase activity in Cloudman S91 melanoma cells after ultraviolet-irradiation

International Nuclear Information System (INIS)

Niggli, H.J.

1990-01-01

The authors compared the induction of pyrimidine dimer densities after UV-irradiation in mouse melanoma cells before and after treatment with cholera toxin. Treatment with cholera toxin stimulated tyrosinase activity up to 50-fold, leading to a marked, visually apparent increase in cellular melanin concentrations. Results indicate that de novo melanin pigmentation induced via the c-AMP pathway is not involved in protection against UV-induced thymine-containing pyrimidine dimers. In separate experiments, irradiation of toxin-treated and untreated mouse melanoma cells with UVC or UVB light produced a 20-30% lower dimer density compared to irradiated human skin fibroblasts. This finding suggests that melanin has some protection properties against UV-induced pyrimidine dimers, although the exact defense mechanism seems highly complex. (author)

Tumour radiosensitization with the halogenated pyrimidines 5'-bromo-and 5'-iododeoxyuridine

Energy Technology Data Exchange (ETDEWEB)

Epstein, A.H.; Cook, J.A.; Goffman, T. (National Cancer Inst., Bethesda, MD (United States)); Glatstein, E. (Texas Univ., Dallas, TX (United States). Southwestern Medical Center)

1993-02-01

The authors review studies of the use of iododeoxyuridine (IdUrd) and bromodeoxyuridine as radiosensitizers and attempt to correlate the clinical outcome for patients treated with radiation and IdUrd with the extent of halogenated pyrimidine cellular uptake and incorporation. (U.K.).

Exploring pyrazolo[3,4-d]pyrimidine phosphodiesterase 1 (PDE1) inhibitors: a predictive approach combining comparative validated multiple molecular modelling techniques.

Science.gov (United States)

Amin, Sk Abdul; Bhargava, Sonam; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

2018-02-01

Phosphodiesterase 1 (PDE1) is a potential target for a number of neurodegenerative disorders such as Schizophrenia, Parkinson's and Alzheimer's diseases. A number of pyrazolo[3,4-d]pyrimidine PDE1 inhibitors were subjected to different molecular modelling techniques [such as regression-based quantitative structure-activity relationship (QSAR): multiple linear regression, support vector machine and artificial neural network; classification-based QSAR: Bayesian modelling and Recursive partitioning; Monte Carlo based QSAR; Open3DQSAR; pharmacophore mapping and molecular docking analyses] to get a detailed knowledge about the physicochemical and structural requirements for higher inhibitory activity. The planarity of the pyrimidinone ring plays an important role for PDE1 inhibition. The N-methylated function at the 5th position of the pyrazolo[3,4-d]pyrimidine core is required for interacting with the PDE1 enzyme. The cyclopentyl ring fused with the parent scaffold is necessary for PDE1 binding potency. The phenylamino substitution at 3rd position is crucial for PDE1 inhibition. The N2-substitution at the pyrazole moiety is important for PDE1 inhibition compared to the N1-substituted analogues. Moreover, the p-substituted benzyl side chain at N2-position helps to enhance the PDE1 inhibitory profile. Depending on these observations, some new molecules are predicted that may possess better PDE1 inhibition.

29 CFR 516.21 - Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b)(3) of the Act. 516.21 Section 516.21 Labor Regulations Relating to Labor....21 Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

Pyrimidine dimer excision in human cells and skin cancer

International Nuclear Information System (INIS)

Regan, J.D.; Carrier, W.L.; Smith, D.P.; Waters, R.

1977-01-01

We have compared three different methods for estimating the induction and removal of uv induced pyrimidine dimers from the DNA of human fibroblasts. Results indicate that after uv doses of 5-20 J/m 2 50% of the dimers are removed by 24 hours after irradiation. Almost complete excision can be observed if the cells are incubated for periods not less than 72 hours after 5 J/m 2 . After higher doses it probably takes even longer fr such complete removal to be seen

Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

Directory of Open Access Journals (Sweden)

Ramdas Bhanudas Pandhare

2013-02-01

Full Text Available Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives containing 1,2,4-triazole ring were subjected to study their in vivo analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted derivatives showed excellent analgesic activity and dimethylamino, furan and phenyl substituted derivatives showed moderate analgesic activity in both of the methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj IV3a and IIj were found to be superior analgesic agents after screening by Acetic acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb, IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after screening of Hot plate method. Conclusion: All tested compounds containing 1,2,4-triazole were found to be promising analgesic agents, for this activity pyrazole, tetrazole, isoxazole and pyrimidine leads might be supported.

Mechanism for the abiotic synthesis of uracil via UV-induced oxidation of pyrimidine in pure H2O ices under astrophysical conditions

International Nuclear Information System (INIS)

Bera, Partha P.; Nuevo, Michel; Sandford, Scott A.; Lee, Timothy J.; Milam, Stefanie N.

2010-01-01

The UV photoirradiation of pyrimidine in pure H 2 O ices has been explored using second-order Moeller-Plesset perturbation theory and density functional theory methods, and compared with experimental results. Mechanisms studied include those starting with neutral pyrimidine or cationic pyrimidine radicals, and reacting with OH radical. The ab initio calculations reveal that the formation of some key species, including the nucleobase uracil, is energetically favored over others. The presence of one or several water molecules is necessary in order to abstract a proton which leads to the final products. Formation of many of the photoproducts in UV-irradiated H 2 O:pyrimidine=20:1 ice mixtures was established in a previous experimental study. Among all the products, uracil is predicted by quantum chemical calculations to be the most favored, and has been identified in experimental samples by two independent chromatography techniques. The results of the present study strongly support the scenario in which prebiotic molecules, such as the nucleobase uracil, can be formed under abiotic processes in astrophysically relevant environments, namely in condensed phase on the surface of icy, cold grains before being delivered to the telluric planets, like Earth.

Synthesis and antitumor activity of some novel thiophene, pyrimidine, coumarin, pyrazole and pyridine derivatives

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Albratty Mohammed

2017-03-01

Full Text Available 2-Cyano-N-(thiazol-2-yl acetamide (2a and 2-cyano-N-(oxazol- 2-yl acetamide (2b were obtained via the reaction of ethyl cyanoacetate with either 2-aminothiazole (1a or 2-aminooxazole (1b. The formed products were directed toward the reaction with cyclopentanone and elemental sulfur in the presence of triethylamine to give cyclopenta[b]thiophene derivatives (3a,b. The latter products were reacted with either ethyl cyanoacetate or malononitrile to form compounds 4a,b and 5a,b, respectively. Compounds 4a,b were aimed at synthesizing some heterocyclic compounds; thus internal cyclization reactions were introduced to form compounds 6a,b. Also, compounds 4a,b reacted with salicylaldehyde, hydrazine derivatives and either urea or thiourea to produce coumarin derivatives (7a,b, pyrazole derivatives (8a-d and pyrimidine derivatives (9a-d, respectively. Reaction of either benzaldehyde or benzene diazonium chloride (11 with compounds 4a,b afforded compounds 10a,b and 12a,b, respectively. On the other hand, compounds 5a,b underwent internal cyclization to form pyrimidine derivatives 13a,b. Also, when compounds 5a,b reacted with either ethyl cyanoacetate or malononitrile, they gave pyridine derivatives (15a-d through the formation of intermediates (14a-d. Finally, formation of fused pyrimidine derivatives (17a,b was achieved through the reaction of compounds 5a,b and salicylaldehyde applying two different pathways. The first pathway used a catalytic amount of piperidine to form compounds 16a,b; the latter products underwent cyclization to give compounds 17a,b. The second pathway, using a catalytic amount of sodium ethoxide solution directly in one step, afforded compounds 17a,b. Structures of the newly synthesized compounds were established using IR, 1H NMR, 13C NMR and mass spectrometry and their antitumor activity was investigated. Some of these compounds showed promising inhibitory effects on three different cell lines. However, fused pyrimidine

Pyrimidine dimer formation and repair in human skin

International Nuclear Information System (INIS)

Sutherland, B.M.; Harber, L.C.; Kochevar, I.E.

1980-01-01

Cyclobutyl pyrimidine dimers have been detected in the DNA of human skin following in vivo irradiation with suberythermal doses of ultraviolet (UV) radiation from FS-20 sun lamp fluorescent tubes. Dimers were assayed by treatment of extracted DNA with Micrococus luteus UV-specific endonuclease, alkaline agarose electrophoresis, and ethidum bromide staining. This technique, in contrast to conventional dimer assays, can be used with nonradioactive DNA and is optimal at low UV light doses. These data suggest that some dimer disappearance by excision repair occurs within 20 min of UV irradiation and that photoreactivation of dimers can make a contribution to the total repair process

Electron gain and electron loss radicals stabilized on the purine and pyrimidine of a cocrystal exhibiting base-base interstacking: ESR-ENDOR of X-irradiated adenosine:5-bromouracil

International Nuclear Information System (INIS)

Kar, L.; Bernhard, W.A.

1983-01-01

The predominant free radicals trapped in cocrystals of adenosine:5-bromouracil X-irradiated at 12 0 K were identified by ESR-ENDOR spectroscopy and the radical reactions were followed upon annealing to 480 0 K. The dominant electron abstraction and electron addition products stabilized on the bases at 12 0 K are observed to be the bromouracil π-cation and the adenine π-cation and π-anion. The formation of an anion on bromouracil is inferred from the presence of a radical formed by deuterium addition to C 6 of bromouracil at higher temperatures. Above 40 0 K the bromouracil π-cation appears to decay by recombination and is reduced to undetectable levels at approx.170 0 K. Both adenine π-ions are also observed to decay within the same temperature range. Above 200 0 K hydrogen adducts are stabilized on the bases. Experiments using partially deuterated cocrystals indicate that the H-adducts are formed via both hydrogen addition and protonation of the respective anions. Two hydrogen abstraction radicals stabilized on the sugar residue are detectable at temperatures above 200 0 K, but these may be present at much lower temperatures. The results presented here question the generally accepted hypothesis that, in the presence of purine:pyrimidine stacking interactions, holes are predominantly transferred to the purines while electrns are predominantly transferred to the pyrimidines

Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1-phenylpyrazolo[3,4-d]pyrimidine derivatives.

Science.gov (United States)

Bakr, Rania B; Azouz, Amany A; Abdellatif, Khaled R A

2016-01-01

A new group of 1-phenylpyrazolo[3,4-d]pyrimidine derivatives 14a-d-21 were synthesized from 2-(6-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)acetohydrazide (12). All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All the target compounds were more potential in inhibiting COX-2 than COX-1. Compounds having pyrazolyl moiety in a hybrid structure with pyrazolo[3,4-d]pyrimidine scaffold (14a-d, 16 and 17) showed higher edema inhibition percentage activities (34-68%) and the 5-aminopyrazole derivative (14c, ED 50  =   87.9 μmol/kg) was the most potent one > celecoxib (ED 50  =   91.9 μmol/kg). While, the in vivo potent compounds (14a-d, 16, 17 and 21) caused variable ulceration effect (ulcer index   = 0.33-4.0) comparable to that of celecoxib (ulcer index   = 0.33), the pyrazol-3-one derivative (16) and the acetohydrazide (21) were the least ulcerogenic derivatives showing the same ulcerogenic potential of celecoxib.

In vitro anti-Giardia lamblia activity of 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines, individually and in combination with albendazole.

Science.gov (United States)

Velázquez-Olvera, Stephanía; Salgado-Zamora, Héctor; Jiménez-Cardoso, Enedina; Campos-Aldrete, Maria-Elena; Pérez-González, Cuauhtémoc; Ben Hadda, Taibi

2016-03-01

Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced repair of cyclobutane pyrimidine dimers and improved UV resistance in photolyase transgenic mice

NARCIS (Netherlands)

W. Schul; J. Jans (Judith); Y.M. Rijksen (Yvonne); K.H. Klemann; J. de Wit (Jan); O. Nikaido; S. Nakajima; A. Yasui (Akira); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); A.P.M. Eker (André)

2002-01-01

textabstractDuring evolution, placental mammals appear to have lost cyclobutane pyrimidine dimer (CPD) photolyase, an enzyme that efficiently removes UV-induced CPDs from DNA in a light-dependent manner. As a consequence, they have to rely solely on the more complex, and for this lesion less

Facile synthesis of indole-pyrimidine hybrids and evaluation of their anticancer and antimicrobial activity

Directory of Open Access Journals (Sweden)

Nikhila Gokhale

2017-11-01

Full Text Available The paper describes the facile synthesis of new N-cyclopropyl-1-methyl-1H-indole-2-carboxamide derivatives bearing substituted 2-amino pyrimidine moiety at position-3 of the indole ring. All the intermediate and title compounds were characterized adeptly by 1H NMR, 13C NMR, ESI–MS and elemental analyses. These compounds were evaluated for their in vitro anticancer activity against HeLa, HepG2 and MCF-7 cells. Three among 22 molecules, showed more than 70% growth inhibition against all three tested cancer cells. The nature of the substituent group on the pyrimidine ring (R2 affected significantly the anti-proliferative activity of the molecules. The anti-microbial evaluation of the title molecules revealed the significance of fluoro/chloro groups (R2 in enhancing their inhibition activity. Eight molecules which contain fluoro/chloro groups showed potent anti-microbial activity. In addition, the active molecules displayed negligible toxicity to benign Vero cells.

Uridine 5'-Monophosphate Synthase Is Transcriptionally Regulated by Pyrimidine Levels in Nicotiana plumbaginifolia

Science.gov (United States)

Santoso; Thornburg

1998-02-01

To understand the regulation and expression of pyrimidine biosynthesis in plants, we have examined the effect of the metabolic inhibitor 5-fluoroorotic acid (FOA) on uridine-5'-monophosphate synthase (UMPSase) expression in cell cultures of Nicotiana plumbaginifolia. UMPSase is the rate-limiting step of pyrimidine biosynthesis in plants. Addition of FOA causes an up-regulation of UMPSase enzyme activity in cell cultures after a lag phase of several days. Western-blot analysis demonstrated that the up-regulation in enzyme activity was caused by increased expression of the UMPSase protein. Northern-blot analysis demonstrated a higher level of UMPSase mRNA in the FOA-induced tissues than in control tissues. Run-on transcriptional assays showed that the UMPSase gene was transcriptionally activated after FOA treatment. The mechanism of toxicity of FOA is through thymine starvation. We found that addition of thymine abrogated the FOA-mediated up-regulation of UMPSase. In addition, methotrexate and aminopterin, which affect thymine levels by inhibiting dihydrofolate reductase, also up-regulate UMPSase in N. plumbaginifolia cells.

Pyrimidine and nucleoside gamma-esters of L-Glu-Sar

DEFF Research Database (Denmark)

Eriksson, André H; Elm, Peter L; Begtrup, Mikael

2005-01-01

-tetrahydrofuran-3-yl ester)-Sar (I), l-Glu(thymine-1-yl-methyl ester)-Sar (II) and l-Glu(acyclothymidine)-Sar (III) were synthesised and in vitro stability was studied in various aqueous and biological media. Affinity to and translocation via hPEPT1 was investigated in mature Caco-2 cell monolayers, grown......The aim of the present study was to improve the synthetic pathway of bioreversible dipeptide derivatives as well as evaluate the potential of using l-Glu-Sar as a pro-moiety for delivering three newly synthesised nucleoside and pyrimidine l-Glu-Sar derivatives. l-Glu(trans-2-thymine-1-yl...

Formation of pyrimidine dimers in Simian virus 40 chromosomes and DNA in vitro: effects of salt

International Nuclear Information System (INIS)

Edenberg, H.J.

1984-01-01

Simian virus 40 chromosomes were used to determine whether packaging of DNA into chromatin affected the yield of cylcobutane pyrimidine dimers introduced by ultraviolet light (254 nm). SV40 chromatin and purified SV40 DNA (radioactively labeled with different isotopes) were mixed and irradiated in vitro. The proteins were extracted and pyrimidine dimers detected as sites sensitive to the UV-endonuclease encoded by bacteriophage T4. When irradiation was carried out in the presence of at least 0.05 M NaCl the same number of dimers were formed in chromatin as in free DNA. Irradiation in the absence of NaCl, however, reduced the relative yield of dimers in chromatin to 89% of that in free DNA. Different methods of chromatin preparation did not influence these results. (author)

VUV Study of Electron-Pyrimidine Dissociative Excitation

Science.gov (United States)

Hein, Jeff; Al-Khazraji, Hajar; Tiessen, Collin; Lukic, Dragan; Trocchi, Joshuah; McConkey, William

2013-05-01

A crossed electron-gas beam system coupled to a VUV spectrometer has been used to investigate the dissociation of pyrimidine (C4H4N2) into excited atomic fragments in the electron-impact energy range from threshold to 375 eV. Data have been made absolute using Lyman- α from H2 as a secondary standard. The main features in the spectrum are the H Lyman series lines. The emission cross section of Lyman- α is measured to be (2.44 +/- 0.25) 10-18 cm2 at 100 eV impact energy. The probability of extracting C or N atoms from the ring is shown to be very small. Possible dissociation channels and excitation mechanisms in the parent molecule will be discussed. The authors thank NSERC (Canada) for financial support.

Harman inhibits the removal of pyrimidine dimers from the DNA of human cells

International Nuclear Information System (INIS)

Castellani, A.; Setlow, R.B.

1981-01-01

Normal human fibroblasts were UV-irradiated and incubated for 6 hr with harman. The losses of sites, in the extracted DNA, sensitive to a UV specific endonuclease were determined as precision measures of the excision of UV-induced pyrimidine dimers. Harman inhibited excision, rising from approx. 30% inhibition at 200 μM to 75% inhibition at 500 μM

Cellular distribution, purification and electrophoretic properties of malate dehydrogenase in Trichuris ovis and inhibition by benzimidazoles and pyrimidine derivatives.

Science.gov (United States)

Sanchez-Moreno, M; Ortega, J E; Valero, A

1989-12-01

High levels of malate dehydrogenase were found in Trichuris ovis. Two molecular forms of the enzyme, of different cellular location and electrophoretic pattern, were isolated and purified. The activity of soluble malate dehydrogenase was greater than that of mitochondrial malate dehydrogenase. Both forms also displayed different electrophoretic profiles in comparison with purified extracts from goat (Capra hircus) liver. Substrate concentration directly affected enzyme activity. Host and parasite malate dehydrogenase activity were both inhibited by a series of benzimidazoles and pyrimidine-derived compounds, some of which markedly reduced parasite enzyme activity, but not host enzyme activity. Percentage inhibition by some pyrimidine derivatives was greater than that produced by benzimidazoles.

A General Regioselective Approach to 2,4-Disubstituted Pyrimidin-5-yl C-2-Deoxyribonucleosides

Czech Academy of Sciences Publication Activity Database

Kubelka, Tomáš; Slavětínská, Lenka; Hocek, Michal

2012-01-01

Roč. 44, č. 6 (2012), s. 953-965 ISSN 0039-7881 R&D Projects: GA MŠk LC512; GA AV ČR IAA400550902 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleosides * pyrimidines * cross - coupling * Heck reaction Subject RIV: CC - Organic Chemistry Impact factor: 2.500, year: 2012

An efficient synthesis of novel pyrano[2,3-d]- and furopyrano[2,3-d]pyrimidines via indium-catalyzed multi-component domino reaction

Directory of Open Access Journals (Sweden)

Gohain Mukut

2006-06-01

Full Text Available Abstract Various novel pyrano [2,3-d]pyrimidines 5 and furopyrano [2,3-d]pyrimidines 7 were synthesized in 80–99% yields via a multicomponent domino Knoevenagel/hetero-Diels-Alder reaction of 1,3-dimethyl barbituric acid with an aromatic aldehyde and ethyl vinyl ether/2,3-dihydrofuran in presence of 1 mol% of indium(III chloride. The reaction also proceeds in aqueous media without using any catalyst, but the yield is comparatively less (65–70%.

Quantitation of pyrimidine dimers in DNA from UVB-irradiated alfalfa (Medicago sativa L.) seedlings

International Nuclear Information System (INIS)

Quaite, F.E.; Sutherland, B.M.; Sutherland, J.C.

1991-01-01

Depletion of stratospheric ozone will increase the solar ultraviolet radiation in the range from 290-320 nm (UVB) that reaches the surface of the earth, placing an increased UV burden on exposed organisms. One consequence of increased UVB may be decreased productivity of crop plants. A principal lesion caused by UV in DNA is the cyclobutyl pyrimidine dimer. We have adapted a method for measuring these dimers in nanogram quantities of non-radioactive DNA for use in UV-irradiated plants. We find that biologically relevant doses of broad band UVB radiation induce easily detectable frequencies of pyrimidine dimers in the DNA of irradiated alfalfa sprout leaves and that the dose response for dimer formation is linear up to doses of at least 690 J/m 2 . We also find easily measurable frequencies of dimers in the leaves of seedlings grown in glass filtered sunlight but not exposed to additional UVB, suggesting that significant number of dimers are formed in plants exposed to normal sunlight. 27 refs., 3 figs., 1 tab

Scaffold hopping from (5-hydroxymethyl) isophthalates to multisubstituted pyrimidines diminishes binding affinity to the C1 domain of protein kinase C.

Science.gov (United States)

Provenzani, Riccardo; Tarvainen, Ilari; Brandoli, Giulia; Lempinen, Antti; Artes, Sanna; Turku, Ainoleena; Jäntti, Maria Helena; Talman, Virpi; Yli-Kauhaluoma, Jari; Tuominen, Raimo K; Boije Af Gennäs, Gustav

2018-01-01

Protein kinase C (PKC) isoforms play a pivotal role in the regulation of numerous cellular functions, making them extensively studied and highly attractive drug targets. Utilizing the crystal structure of the PKCδ C1B domain, we have developed hydrophobic isophthalic acid derivatives that modify PKC functions by binding to the C1 domain of the enzyme. In the present study, we aimed to improve the drug-like properties of the isophthalic acid derivatives by increasing their solubility and enhancing the binding affinity. Here we describe the design and synthesis of a series of multisubstituted pyrimidines as analogs of C1 domain-targeted isophthalates and characterize their binding affinities to the PKCα isoform. In contrast to our computational predictions, the scaffold hopping from phenyl to pyrimidine core diminished the binding affinity. Although the novel pyrimidines did not establish improved binding affinity for PKCα compared to our previous isophthalic acid derivatives, the present results provide useful structure-activity relationship data for further development of ligands targeted to the C1 domain of PKC.

Unconventional hydrogen bonding to organic ions in the gas phase: Stepwise association of hydrogen cyanide with the pyridine and pyrimidine radical cations and protonated pyridine

Energy Technology Data Exchange (ETDEWEB)

Hamid, Ahmed M.; El-Shall, M. Samy, E-mail: mselshal@vcu.edu [Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284 (United States); Hilal, Rifaat; Elroby, Shaaban; Aziz, Saadullah G. [Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589 (Saudi Arabia)

2014-08-07

Equilibrium thermochemical measurements using the ion mobility drift cell technique have been utilized to investigate the binding energies and entropy changes for the stepwise association of HCN molecules with the pyridine and pyrimidine radical cations forming the C{sub 5}H{sub 5}N{sup +·}(HCN){sub n} and C{sub 4}H{sub 4}N{sub 2}{sup +·}(HCN){sub n} clusters, respectively, with n = 1–4. For comparison, the binding of 1–4 HCN molecules to the protonated pyridine C{sub 5}H{sub 5}NH{sup +}(HCN){sub n} has also been investigated. The binding energies of HCN to the pyridine and pyrimidine radical cations are nearly equal (11.4 and 12.0 kcal/mol, respectively) but weaker than the HCN binding to the protonated pyridine (14.0 kcal/mol). The pyridine and pyrimidine radical cations form unconventional carbon-based ionic hydrogen bonds with HCN (CH{sup δ+}⋯NCH). Protonated pyridine forms a stronger ionic hydrogen bond with HCN (NH{sup +}⋯NCH) which can be extended to a linear chain with the clustering of additional HCN molecules (NH{sup +}⋯NCH··NCH⋯NCH) leading to a rapid decrease in the bond strength as the length of the chain increases. The lowest energy structures of the pyridine and pyrimidine radical cation clusters containing 3-4 HCN molecules show a strong tendency for the internal solvation of the radical cation by the HCN molecules where bifurcated structures involving multiple hydrogen bonding sites with the ring hydrogen atoms are formed. The unconventional H-bonds (CH{sup δ+}⋯NCH) formed between the pyridine or the pyrimidine radical cations and HCN molecules (11–12 kcal/mol) are stronger than the similar (CH{sup δ+}⋯NCH) bonds formed between the benzene radical cation and HCN molecules (9 kcal/mol) indicating that the CH{sup δ+} centers in the pyridine and pyrimidine radical cations have more effective charges than in the benzene radical cation.

Poly(alizarin red)/Graphene modified glassy carbon electrode for simultaneous determination of purine and pyrimidine

International Nuclear Information System (INIS)

Ba Xi; Luo Liqiang; Ding Yaping; Zhang Zhen; Chu Yuliang; Wang Bijun; Ouyang Xiaoqian

2012-01-01

Graphical abstract: DPVs of PAR/Graphene/GCE (a) and the bare GCE (c) in 0.1 M PBS containing 50.0 μM G, 50.0 μM A, 100.0 μM T and 100.0 μM C, (b) PAR/Graphene/GCE in 0.1 M PBS. Highlights: ► The sensor exhibited well-separated peaks and low detection limit. ► The sensor possesses high sensitivity and wide linear range. ► The sensor was used for simultaneous detection of G, A, T and C successfully. ► The sensor was applied in a fish sperm DNA sample with satisfactory results. ► The proposed sensor has good stability and reproducibility. - Abstract: In this work, a poly(alizarin red)/Graphene composite film modified glassy carbon electrode (PAR/Graphene/GCE) was prepared for simultaneous determination of four DNA bases (guanine, adenine, thymine and cytosine) without any pretreatment. The morphology and interface property of PAR/Graphene films were examined by scanning electron microscopy and electrochemical impedance spectroscopy. The PAR/Graphene/GCE exhibited excellent electrocatalytic activity toward purine (guanine and adenine) and pyrimidine (thymine and cytosine) in 0.1 M phosphate buffer solution (pH 7.4). Under optimum conditions, differential pulse voltammetry was used to detect the oxidation of purine and pyrimidine. The results showed that PAR/Graphene/GCE exhibited well-separated peaks, low detection limit, high sensitivity and wide linear range for simultaneous detection of purine and pyrimidine. The proposed sensor also has good stability and reproducibility. Furthermore, the modified electrode was applied for the detection of DNA bases in a fish sperm DNA sample with satisfactory results.

The orotate transporter oroP from Lactococcus lactis is required for orotate uptake and can be used both as a food-grade selection and counter-selection marker

DEFF Research Database (Denmark)

Defoor, Els Marie Celine; Martinussen, Jan

The plasmid pDBORO conferred sensitivity of Lactococcus lactis towards 5´-Fluoroorotate. Moreover, by transformation, this plasmid was found to be essential for orotate dependent growth in a pyrimidine requiring strain. A single gene on pDBORO was required for growth on orotate, and was termed oro......P. Since the corresponding open reading frame, OroP showed the features of a membrane protein, OroP most likely is an orotate transporter. A number of strains like L. lactis and Bacillus subtilus have been shown to be unable to metabolize orotate. If the oroP gene was introduced into these strains......, they acquired the ability to utilize orotate. If the strains had a pyrimidine requirement, the oroP gene could function as a selectable marker when growing in the presence of orotate as sole pyrimidine source. In an otherwise resistant strain, oroP was shown to sensitize the strain towards the analog 5...

The EGF repeat-specific O-GlcNAc-transferase Eogt interacts with notch signaling and pyrimidine metabolism pathways in Drosophila.

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Reto Müller

Full Text Available The O-GlcNAc transferase Eogt modifies EGF repeats in proteins that transit the secretory pathway, including Dumpy and Notch. In this paper, we show that the Notch ligands Delta and Serrate are also substrates of Eogt, that mutation of a putative UDP-GlcNAc binding DXD motif greatly reduces enzyme activity, and that Eogt and the cytoplasmic O-GlcNAc transferase Ogt have distinct substrates in Drosophila larvae. Loss of Eogt is larval lethal and disrupts Dumpy functions, but does not obviously perturb Notch signaling. To identify novel genetic interactions with eogt, we investigated dominant modification of wing blister formation caused by knock-down of eogt. Unexpectedly, heterozygosity for several members of the canonical Notch signaling pathway suppressed wing blister formation. And importantly, extensive genetic interactions with mutants in pyrimidine metabolism were identified. Removal of pyrimidine synthesis alleles suppressed wing blister formation, while removal of uracil catabolism alleles was synthetic lethal with eogt knock-down. Therefore, Eogt may regulate protein functions by O-GlcNAc modification of their EGF repeats, and cellular metabolism by affecting pyrimidine synthesis and catabolism. We propose that eogt knock-down in the wing leads to metabolic and signaling perturbations that increase cytosolic uracil levels, thereby causing wing blister formation.

Glutamine domain of the chimeric protein, CAD, that initiates pyrimidine biosynthesis in mammalian cells

International Nuclear Information System (INIS)

Kelly, R.E.; Kim, H.; Evans, D.R.

1986-01-01

Glutamine dependent carbamyl phosphate synthesis, the first step in mammalian de novo pyrimidine biosynthesis, is catalyzed by a 240 kDa chimeric protein, CAD, that also has the aspartate transcarbamylase and dihydroorotase activities. The complex was found to have a separate glutaminase activity of 0.04 μmol/min/mg, that increased five fold in the presence of bicarbonate and ATP. To determine whether the glutaminase activity, which provides ammonia for carbamyl phosphate synthesis, is associated with a separate structural domain (GLN), CAD was subjected to controlled proteolysis with elastase. The glutaminase, glutamine and ammonia dependent carbamyl phosphate synthetase activities, as well as the partial reactions; carbamyl phosphate dependent ATP synthesis and bicarbonate dependent ATPase, were correlated with the concentration of the various proteolytic fragments that accumulated in the digest. While the glutamine dependent carbamyl phosphate synthetase was rapidly inactivated, the glutaminase activity was found to be very resistant to proteolysis. The glutamine binding site of CAD was also specifically modified with 6-diazo-5-oxo-L-norleucine (DON). The modification was accompanied by a loss of both glutaminase and glutamine dependent carbamyl phosphate synthetase activities. Bicarbonate and ATP increased the rate of reaction of CAD with DON, while glutamine protected against inactivation. The stoichiometry of the reaction and the identity of the modified proteolytic fragments was determined using 14 C labelled DON

Ultraviolet-endonuclease activity in cell extracts of Saccharomyces cerevisiae mutants defective in excision of pyrimidine dimers

International Nuclear Information System (INIS)

Bekker, M.L.; Kaboev, O.K.; Akhmedov, A.T.; Luchkina, L.A.

1980-01-01

Cell-free extracts of ultraviolet-sensitive mutants of Saccharomyces cerevisiae defective in excision of pyrimidine dimers, rad1, rad2, rad3, rad4, rad10, and rad16, as well as the extracts of the wild-type strain RAD+, display ultraviolet-endonuclease activity

Synthesis and biological evaluation of new pyrazolo[3,4-d]pyrimidine derivatives

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Asma Agrebi

2014-05-01

Full Text Available Several new pyrazolopyrimidine compounds were achieved from aminocyanopyarazole 1. The starting material 1 was initially coupled with orthoester at refluxed with various primary amines, ammonia, hydrazines and hydroxylamine to furnish a series of pyrazolo[3,4-d]pyrimidines. The reaction of imidate 2a-b with hydrazide derivatives led to the formation of pyrazolo[3,4-d][1,2,4]triazolo[4,3-c]pyrimidines. Some of the synthesized compounds 3a and 4c were evaluated for their anti-inflammatory, antipyretic and nociceptive activities. We start by studing the toxicity of these two molecules by measuring the corresponding DL50. The DL50 of 3a and 4c are estimated to 1333.2mg / kg and 1593.5mg / kg respectively. Pharmacological evaluation showed that compounds 3a and 4c at doses (5.5-22.2 mg / Kg, i.p exhibited anti-inflammatory activities compared to Ibuprofen (150 mg / Kg, i.p, used as a refer ence drug. Further, our study showed that the injection of derived pyrazolopyrimidines on hyperthermic animal leads to a decrease in temperature after 1 hours of treatment compared to paracetamol used as reference. In addition, the injection of derived pyrazolopyrimidines at different doses contains a potent nociceptive activity. This effect is dose-dependent compared to aspirin.

Simultaneous establishment of monoclonal antibodies specific for either cyclobutane pyrimidine dimer or (6-4)photoproduct from the same mouse immunized with ultraviolet irradiated DNA

International Nuclear Information System (INIS)

Mori, Toshio; Nakane, Misa; Hattori, Tsuyoshi; Matsunaga, Tsukasa; Nikaido, Osamu; Ihara, Makoto

1991-01-01

Six new monoclonal antibodies (TDM-2, TDM-3, 64M-2, 64M-3 64M-4 and 64M-5) specific for ultraviolet (UV) induced DNA damage have been established. In the antibody characterization experiments, two TDM antibodies were found to show a dose-dependent binding to UV-irradiated DNA (UV-DNA), decrease of binding to UV-DNA after cyclobutane pyrimidine dimer photoreactivation, binding to DNA containing cyclobutane thymine dimers, and unchanged binding to UV-DNA after photoisomerization of (6-4)photoproducts to Dewar photoproducts. These results indicated that the epitope of TDM monoclonal antibodies was the cyclobutane pyrimidine dimer in DNA. On the other hand, four 64M antibodies were found to show a dose-dependent binding to UV-DNA, unchanged binding to UV-DNA after cyclobutane pyrimidine dimer photoreactivation, undetectable binding to DNA containing thymine dimers, and decrease of binding to UV-DNA after photoisomerization of (6-4)photoproducts. These results indicated that the epitope of 64M antibodies was the (6-4)photoproduct in DNA. This is the first report of the simultaneous establishment of monoclonal antibodies against the two different types of photolesions from the same mouse. By using these monoclonal antibodies, we have succeeded in measuring both cyclobutane pyrimidine dimers and (6-4)photoproducts in the DNA from human primary cells irradiated with physiological UV doses. (author)

Cyclobutane pyrimidine dimers are photosensitised by carprofen plus UVA in human HaCaT cells.

Science.gov (United States)

Robinson, K S; Traynor, N J; Moseley, H; Ferguson, J; Woods, J A

2010-06-01

Every year in the UK about 75,000 cases of non-melanoma skin cancer (NMSC) are registered, and about 9500 people are diagnosed with cutaneous melanoma (CM). The main risk factor for these cancers is exposure to sunlight. The effects of light on skin are wavelength dependent, with wavelengths in the UVB waveband (280-315 nm) being the most carcinogenic. UVB is directly absorbed by DNA, producing dimeric pyrimidine photoproducts including cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimodone photoproducts (6-4PP). However UVA (315-400 nm) can also produce CPD, induce skin tumours in mice, and has been shown to be mutagenic in cell culture. Although the precise role of UVA in human skin cancer remains to be elucidated, it comprises the major portion of solar UV radiation, transmits through window glass and can be delivered in high doses from tanning lamps. Non-steroidal anti-inflammatory drugs (NSAIDs), in particular the 2-aryl propionic acid derivatives, are a well-documented group of photosensitising chemicals producing clinical phototoxic and photoallergic reactions. We have used carprofen, a model compound from this group to see if it could amplify the effects of UVA and contribute to the formation of CPD by UVA. Preliminary work has shown that carprofen combined with low doses of UVA (lambda(max): 365 nm; 5 J/cm(2)) can produce both strand breaks (SB) and CPD in human skin or blood cells. CPD were detected indirectly by both an immunofluorescence method and as T4 endonuclease V sensitive sites in the comet assay. These findings show that compounds other than fluoroquinolones and psoralen derivatives may contribute to CPD formation in skin cells in combination with UVA. Copyright 2010 Elsevier Ltd. All rights reserved.

Poly(alizarin red)/Graphene modified glassy carbon electrode for simultaneous determination of purine and pyrimidine

Energy Technology Data Exchange (ETDEWEB)

Ba Xi; Luo Liqiang [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Ding Yaping, E-mail: wdingyp@sina.com [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Zhang Zhen [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Chu Yuliang [Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444 (China); Wang Bijun; Ouyang Xiaoqian [Department of Chemistry, Shanghai University, Shanghai 200444 (China)

2012-11-08

Graphical abstract: DPVs of PAR/Graphene/GCE (a) and the bare GCE (c) in 0.1 M PBS containing 50.0 {mu}M G, 50.0 {mu}M A, 100.0 {mu}M T and 100.0 {mu}M C, (b) PAR/Graphene/GCE in 0.1 M PBS. Highlights: Black-Right-Pointing-Pointer The sensor exhibited well-separated peaks and low detection limit. Black-Right-Pointing-Pointer The sensor possesses high sensitivity and wide linear range. Black-Right-Pointing-Pointer The sensor was used for simultaneous detection of G, A, T and C successfully. Black-Right-Pointing-Pointer The sensor was applied in a fish sperm DNA sample with satisfactory results. Black-Right-Pointing-Pointer The proposed sensor has good stability and reproducibility. - Abstract: In this work, a poly(alizarin red)/Graphene composite film modified glassy carbon electrode (PAR/Graphene/GCE) was prepared for simultaneous determination of four DNA bases (guanine, adenine, thymine and cytosine) without any pretreatment. The morphology and interface property of PAR/Graphene films were examined by scanning electron microscopy and electrochemical impedance spectroscopy. The PAR/Graphene/GCE exhibited excellent electrocatalytic activity toward purine (guanine and adenine) and pyrimidine (thymine and cytosine) in 0.1 M phosphate buffer solution (pH 7.4). Under optimum conditions, differential pulse voltammetry was used to detect the oxidation of purine and pyrimidine. The results showed that PAR/Graphene/GCE exhibited well-separated peaks, low detection limit, high sensitivity and wide linear range for simultaneous detection of purine and pyrimidine. The proposed sensor also has good stability and reproducibility. Furthermore, the modified electrode was applied for the detection of DNA bases in a fish sperm DNA sample with satisfactory results.

A QSAR study of integrase strand transfer inhibitors based on a large set of pyrimidine, pyrimidone, and pyridopyrazine carboxamide derivatives

Science.gov (United States)

de Campos, Luana Janaína; de Melo, Eduardo Borges

2017-08-01

In the present study, 199 compounds derived from pyrimidine, pyrimidone and pyridopyrazine carboxamides with inhibitory activity against HIV-1 integrase were modeled. Subsequently, a multivariate QSAR study was conducted with 54 molecules employed by Ordered Predictors Selection (OPS) and Partial Least Squares (PLS) for the selection of variables and model construction, respectively. Topological, electrotopological, geometric, and molecular descriptors were used. The selected real model was robust and free from chance correlation; in addition, it demonstrated favorable internal and external statistical quality. Once statistically validated, the training model was used to predict the activity of a second data set (n = 145). The root mean square deviation (RMSD) between observed and predicted values was 0.698. Although it is a value outside of the standards, only 15 (10.34%) of the samples exhibited higher residual values than 1 log unit, a result considered acceptable. Results of Williams and Euclidean applicability domains relative to the prediction showed that the predictions did not occur by extrapolation and that the model is representative of the chemical space of test compounds.

Uridine 5′-Monophosphate Synthase Is Transcriptionally Regulated by Pyrimidine Levels in Nicotiana plumbaginifolia1

Science.gov (United States)

Santoso, Djoko; Thornburg, Robert

1998-01-01

To understand the regulation and expression of pyrimidine biosynthesis in plants, we have examined the effect of the metabolic inhibitor 5-fluoroorotic acid (FOA) on uridine-5′-monophosphate synthase (UMPSase) expression in cell cultures of Nicotiana plumbaginifolia. UMPSase is the rate-limiting step of pyrimidine biosynthesis in plants. Addition of FOA causes an up-regulation of UMPSase enzyme activity in cell cultures after a lag phase of several days. Western-blot analysis demonstrated that the up-regulation in enzyme activity was caused by increased expression of the UMPSase protein. Northern-blot analysis demonstrated a higher level of UMPSase mRNA in the FOA-induced tissues than in control tissues. Run-on transcriptional assays showed that the UMPSase gene was transcriptionally activated after FOA treatment. The mechanism of toxicity of FOA is through thymine starvation. We found that addition of thymine abrogated the FOA-mediated up-regulation of UMPSase. In addition, methotrexate and aminopterin, which affect thymine levels by inhibiting dihydrofolate reductase, also up-regulate UMPSase in N. plumbaginifolia cells. PMID:9490773

T.C.G triplet in an antiparallel purine.purine.pyrimidine DNA triplex. Conformational studies by NMR.

Science.gov (United States)

Dittrich, K; Gu, J; Tinder, R; Hogan, M; Gao, X

1994-04-12

The antiparallel purine.purine.pyrimidine DNA triplex, RRY6, which contains a T.C.G inverted triplet in the center of the sequence, was examined by proton and phosphorous two-dimensional NMR spectroscopy. The local conformation of the T.C.G triplet (T4.C11.G18) and the effect of this triplet on the global helical structure were analyzed in detail. The formation of the T.C.G triplet is confirmed by a set of cross-strand NOEs, including unusual cross-strand NOEs between the third strand and the pyrimidine strand as opposed to the purine strand of the duplex. NMR data suggest that the T.C.G triplet may be present in an equilibrium between a non-hydrogen-bonded form and a T(O4)-C(NH2) hydrogen-bonded form and that there is a distortion of the in-plane alignment of the three bases. The flanking G.G.C base triplets are well-defined on the 5'-side of T4, but somewhat interrupted on the 3'-side of T4. The effect of the third strand binding on the Watson-Crick duplex was probed by an NMR study of the free duplex RY6. NMR parameters are affected mostly around the T.C.G inversion site. The perturbations extend to at least two adjacent base triplets on either side. The binding of the third purine strand and the accommodation of a central T.C.G inversion in RRY6 does not require a readjustment in sugar pucker, which remains in the range of C2'-endo. 31P resonances of RRY6 distribute over a range of 2.2 ppm. The H-P coupling patterns of the third strand differ from those of the duplex. General spectral patterns defined by the marker protons of the RRY and YRY triplexes are compared.

Photoreactivation of ultraviolet light-induced damage in cultured fish cells as revealed by increased colony forming ability and decreased content of pyrimidine dimers

International Nuclear Information System (INIS)

Shima, A.; Ikenaga, M.; Egami, N.

1981-01-01

Cultured cells derived from a goldfish were irradiated with 254 nm ultraviolet light. Cell survival and splitting of pyrimidine dimers after photoreactivation treatment with white fluorescent lamps were examined by colony forming ability and by a direct dimer assay, respectively. When UV-irradiated (5 J/m 2 ) cells were illuminated by photoreactivating light, cell survival was enhanced up to a factor of 9(40 min) followed by a decline after prolonged exposures. Exposure of UV-irradiated (15 J/m 2 ) cells to radiation from white fluorescent lamps reduced the amounts of thymine-containing dimers in a photoreactivating fluence dependent manner, up to about 60% reduction at 120 min exposure. Keeping UV-irradiated cells in the dark for up to 120 min did not affect either cell survival or the amount of pyrimidine dimers in DNA, indicating that there were not detectable levels of a dark-repair system in the cells under our conditions. Correlation between photoreactivation of colony forming ability and photoreactivation of the pyrimidine dimers was demonstrated, at least at relatively low fluences of photoreactivating light. (author)

Photoreactivation of ultraviolet light-induced damage in cultured fish cells as revealed by increased colony forming ability and decreased content of pyrimidine dimers

Energy Technology Data Exchange (ETDEWEB)

Shima, A. (Shiga University of Medical Science, Otsu (Japan)); Ikenaga, M. (Osaka Univ. (Japan). Faculty of Medicine); Nikaido, O.; Takebe, H. (Kyoto Univ. (Japan)); Egami, N. (Tokyo Univ. (Japan). Faculty of Science)

1981-03-01

Cultured cells derived from a goldfish were irradiated with 254 nm ultraviolet light. Cell survival and splitting of pyrimidine dimers after photoreactivation treatment with white fluorescent lamps were examined by colony forming ability and by a direct dimer assay, respectively. When UV-irradiated (5 J/m/sup 2/) cells were illuminated by photoreactivating light, cell survival was enhanced up to a factor of 9(40 min) followed by a decline after prolonged exposures. Exposure of UV-irradiated (15 J/m/sup 2/) cells to radiation from white fluorescent lamps reduced the amounts of thymine-containing dimers in a photoreactivating fluence dependent manner, up to about 60% reduction at 120 min exposure. Keeping UV-irradiated cells in the dark for up to 120 min did not affect either cell survival or the amount of pyrimidine dimers in DNA, indicating that there were not detectable levels of a dark-repair system in the cells under our conditions. Correlation between photoreactivation of colony forming ability and photoreactivation of the pyrimidine dimers was demonstrated, at least at relatively low fluences of photoreactivating light.

Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

International Nuclear Information System (INIS)

Masek, F.; Sedliakova, M.

1978-01-01

The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm 2 and at different time intervals with a second fluence of 500 ergs/mm 2 . After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr + and E.coli 15 555-7, but not in E.coli K12 SR20. (author)

Crystal structure of 4-allylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine

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Mohammed El Fal

2014-09-01

Full Text Available In the title compound, C8H8N4S, the pyrazolo[3,4-d]pyrimidine ring system is essentially planar, with a maximum deviation from the mean plane of 0.025 (3 Å. The allyl group is disordered over two sites in a 0.512 (6:0.488 (6 ratio. In the crystal, molecules are linked by pairs of N—H...N hydrogen bonds, forming inversion dimers with an R22(8 graph-set motif.

Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Masek, F; Sedliakova, M [Slovenska Akademia Vied, Bratislava (Czechoslovakia)

1978-11-15

The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm/sup 2/ and at different time intervals with a second fluence of 500 ergs/mm/sup 2/. After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr/sup +/ and E.coli 15 555-7, but not in E.coli K12 SR20.

How study patients who receive fluo pyrimidines to prevent ischemic events; Como estudiar los pacientes que recibiran fluopirimidinas para prevenir eventos isquemicos

Energy Technology Data Exchange (ETDEWEB)

Saldombide, L. [Hospital de Clinicas. Montevideo (Uruguay)

2010-11-15

Introduction: Ischemic heart disease is the main cause of death in Uruguay and cancer is the second. The pillar of the systemic treatment of colorectal cancer are fluo pyrimidines and cause acute ischemic events in 3-8% of t rated patients. The 5 fluorouracil is the third anticancer drug most used Objective: Due to the high incidence of the two diseases and the risk of death caused by the ischemic treatment complications, the literature is analyzed to define how to study patients who receive fluo pyrimidines as a medium of preventing the same. Development: fluo pyrimidines cardio-toxicity can occur by myocardial toxicity, vasospasm, dihydropyrimidine dehydrogenase deficiency, autoimmune phenomena, platelet hyper aggregability, etc. The clinic is varied and underestimated: angina, abnormal ST silent and reversible, arrhythmias, heart failure, hypertension and heart failure. It is the most common complication with continuous infusion of 5 Fu and its equivalent capecitabine with bolus f lou pyrimidines. It is common that ischemic heart disease prioritises the risk increase of complications, but their absence does not exist. Without ischemic heart disease it is difficult to prevent ischemic events, however proposes that the older higher risk. Results: No uniform guidelines is advised: detailed history, determine if risk factors such as smoking, hypertension, diabetes and dyslipidemia and They are present electrocardiogram and cardiac evaluation. Warn the patient about angina l pain as early symptom and monitor symptoms during chemotherapy including cardio-vascular hypotension. Discontinue the medication and perform classic anti-angina l symptoms and / or signs of ischemia. Not reintroduce unless it is the only therapeutic option, since mortality may exceed.

Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives

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Dong Cai

2015-09-01

Full Text Available A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H2SO4. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities.

Solid supported microwave induced synthesis of imidazole–pyrimidine hybrids: Antimicrobial evaluation and docking study as 14DM-CPY51 inhibitors

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Naziyanaz B. Pathan

2016-09-01

Full Text Available As part of our exploration for new antifungal agents, substituted 4,5-diphenyl imidazolyl pyrimidine hybrids were synthesized. A series of substituted ethyl 1,2,3,6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenyl-1-(4,5-diphenyl-1-H-imidazol-2-yl pyrimidine-5-carboxylates have been studied for their binding active sites of cytochrome P450 14α-sterol demethylase CPY51 enzyme. For comparison, the binding behavior of known 14DM selective (Fluconazole and non-selective (Clotrimazole, Miconazole, Griesofulvin drugs has also been studied. Synthesized compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus, Salmonella typhi, Pseudomonas aurogenosa and Klebsiella pneumonae and also antifungal activity against the opportunistic pathogens Candida albicans.

ESR study of radiation damage in pyrimidines. Progress report, August 1, 1975--April 1, 1976

International Nuclear Information System (INIS)

Benson, B.W.

1976-04-01

The primary objective of this project is to develop general mechanisms for radiation damage to biomolecules using substituted pyrimidines as a model system. Results this year include a single crystal ESR study of 5-ethyl-5-isopropylbarbituric acid, development of the k-band microwave bridge, dose response measurements on methylated barbituric acid derivatives, and synthesis of several specifically deuterated uracil derivatives

Resonance effects in elastic cross sections for electron scattering on pyrimidine: Experiment and theory.

Science.gov (United States)

Regeta, Khrystyna; Allan, Michael; Winstead, Carl; McKoy, Vincent; Mašín, Zdeněk; Gorfinkiel, Jimena D

2016-01-14

We measured differential cross sections for elastic (rotationally integrated) electron scattering on pyrimidine, both as a function of angle up to 180(∘) at electron energies of 1, 5, 10, and 20 eV and as a function of electron energy in the range 0.1-14 eV. The experimental results are compared to the results of the fixed-nuclei Schwinger variational and R-matrix theoretical methods, which reproduce satisfactorily the magnitudes and shapes of the experimental cross sections. The emphasis of the present work is on recording detailed excitation functions revealing resonances in the excitation process. Resonant structures are observed at 0.2, 0.7, and 4.35 eV and calculations for different symmetries confirm their assignment as the X̃(2)A2, Ã(2)B1, and B̃(2)B1 shape resonances. As a consequence of superposition of coherent resonant amplitudes with background scattering the B̃(2)B1 shape resonance appears as a peak, a dip, or a step function in the cross sections recorded as a function of energy at different scattering angles and this effect is satisfactorily reproduced by theory. The dip and peak contributions at different scattering angles partially compensate, making the resonance nearly invisible in the integral cross section. Vibrationally integrated cross sections were also measured at 1, 5, 10 and 20 eV and the question of whether the fixed-nuclei cross sections should be compared to vibrationally elastic or vibrationally integrated cross section is discussed.

An Efficient and Facile Methodology for Bromination of Pyrimidine and Purine Nucleosides with Sodium Monobromoisocyanurate (SMBI

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Roger Stromberg

2013-10-01

Full Text Available An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI. Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in moderate to high yields following this procedure.

Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

DEFF Research Database (Denmark)

Kelemen, Linda E; Terry, Kathryn L; Goodman, Marc T

2014-01-01

SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds rat...

Modification of potentially lethal damage in irradiated Chinese hamster V79 cells after incorporation of halogenated pyrimidines

NARCIS (Netherlands)

Franken, N. A.; van Bree, C. V.; Kipp, J. B.; Barendsen, G. W.

1997-01-01

Radiosensitization of exponentially growing and plateau phase Chinese hamster V79 cells by incorporation of halogenated pyrimidines (HP) was investigated for different culture conditions that influenced repair. For this purpose cells were grown for 72 h with 0, 1, 2 and 4 microM of chloro-(CldUrd),

Studies on Synthesis of Some Novel Heterocyclic Chalcone, Pyrazoline, Pyrimidine - 2 - One, Pyrimidine - 2 - Thione, para-Acetanilide Sulphonyl and Benzoyl Derivatives and their Antimicrobial Activity

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Rakesh N. Mistry

2005-01-01

Full Text Available 1, 2 - Dichloro benzene on chlorosulphonation by chlorosulphonic acid gives 1, 2 - [dichloro] - benzene sulphonyl chloride which on condensation with p –amino acetophenone gives 1-[acetyl] - 1’ , 2’ - [dichloro] - dibenz sulphonamide derivative. This derivative undergo condensation with 2,4- dichloro benzaldehyde gives 1- [3” - (sub. phenyl - 2” - propene - 1” - one] - 1’ , 2’ - [dichloro] - dibenz sulphonamide derivative which on reaction with 99% hydrazine hydrate and glacial acetic acid gives 1-[acetyl]-3- [1’ , 2’ - (dichloro - dibenz sulphonamide] -5 - [2” , 4” - dichloro phenyl] - 2 - pyrazoline derivative. This derivative reacts with various substituted aldehydes to give corresponding substituted chalcone derivatives [1(a-j]. Now, these chalcone derivatives [1(a-j] on condensation with urea gives corresponding substituted pyrimidine - 2 - one derivatives [2(a-j] and on condensation with thio-urea gives corresponding substituted pyrimidine- 2 -thione derivatives [3(a-j]. Further, these chalcone derivatives [1(a-j] on reaction with 99% hydrazine hydrate gives 1 - [1’ - (H - 5’ - (sub. phenyl - 2’ - pyrazoline]- 3 - [1” , 2” - (dichloro - dibenz sulphonamide] - 5 - [2’’’ , 4’’’ - dichloro phenyl]-2- pyrazoline derivatives [4(a-j] as an intermediate compounds, which on condensation with p-acetanilide sulphonyl chloride gives corresponding substituted p - acetanilide sulphonyl derivatives [5(a-j] and on condensation with benzoyl chloride gives corresponding substituted benzoyl derivatives [6(a-j]. Structure elucidation of synthesised compounds has been made on the basis of elemental analysis, I.R. spectral studies and 1H N.M.R. spectral studies. The antimicrobial activity of the synthesised compounds has been studied against the cultures “Staphylococcus aureus”, “Escherichia coli” and “Candela albicans”.

Understanding the requirements of geographical data for blind and partially sighted people to make journeys more independently.

Science.gov (United States)

Chandler, Edward; Worsfold, John

2013-11-01

Previous research has highlighted that blind and partially sighted people find various factors inhibit their abilities to make journeys. This paper proposes that the lack of accurate, appropriate and usable geographical data is one of the reasons for this and these can be tracked back to core human factors issues such as situational awareness, mental workload and environmental ergonomics. Following a review of applicable literature a hierarchical task analysis was performed to better understand the problems in terms of the complexity of various journey types and to identify the geographical data requirements in order to make successful journeys. The task analysis produced a number of results including highlighting four underlying principles which have an impact on the data requirements during any given journey. Finally the need for accessible and accurate geographical data requirements is introduced as a result of the literature review and the task analysis. These highlight the information required in order to facilitate more accessible travel for blind and partially sighted people by providing geographical information about their surroundings in a relevant, meaningful and usable way. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Design, Synthesis, and Herbicidal Activity of Pyrimidine-Biphenyl Hybrids as Novel Acetohydroxyacid Synthase Inhibitors.

Science.gov (United States)

Li, Ke-Jian; Qu, Ren-Yu; Liu, Yu-Chao; Yang, Jing-Fang; Devendar, Ponnam; Chen, Qiong; Niu, Cong-Wei; Xi, Zhen; Yang, Guang-Fu

2018-04-18

The issue of weed resistance to acetohydroxyacid synthase (EC 2.2.1.6, AHAS) inhibitors has become one of the largest obstacles for the application of this class of herbicides. In a continuing effort to discover novel AHAS inhibitors to overcome weed resistance, a series of pyrimidine-biphenyl hybrids (4aa-bb and 5aa-ah) were designed and synthesized via a scaffold hopping strategy. Among these derivatives, compounds 4aa ( K i = 0.09 μM) and 4bb ( K i = 0.02 μM) displayed higher inhibitory activities against Arabidopsis thaliana AHAS than those of the controls bispyribac ( K i = 0.54 μM) and flumetsulam ( K i = 0.38 μM). Remarkably, compounds 4aa, 4bb, 5ah, and 5ag exhibited excellent postemergence herbicidal activity and a broad spectrum of weed control at application rates of 37.5-150 g of active ingredient (ai)/ha. Furthermore, 4aa and 4bb showed higher herbicidal activity against AHAS inhibitor-resistant Descurainia sophia, Ammannia arenaria, and the corresponding sensitive weeds than that of bispyribac at 0.94-0.235 g ai/ha. Therefore, the pyrimidine-biphenyl motif and lead compounds 4aa and 4bb have great potential for the discovery of novel AHAS inhibitors to combat AHAS-inhibiting herbicide-resistant weeds.

Acyclic nucleoside bisphosphonates: Synthesis and properties of chiral 2-amino-4,6-bis[(phosphonomethoxy)alkoxy]pyrimidines

Czech Academy of Sciences Publication Activity Database

Doláková, Petra; Dračínský, Martin; Masojídková, Milena; Šolínová, Veronika; Kašička, Václav; Holý, Antonín

2009-01-01

Roč. 44, č. 6 (2009), s. 2408-2424 ISSN 0223-5234 R&D Projects: GA MŠk 1M0508 Grant - others:NIH(US) 1UC1AIO62540-01 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * pyrimidine * bisphosphonates Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2009

Synthesis and structure-activity relationship studies of polysubstituted pyrimidines as inhibitors of immune-activated nitric oxide production

Czech Academy of Sciences Publication Activity Database

Jansa, Petr; Holý, Antonín; Dračínský, Martin; Kolman, Viktor; Janeba, Zlatko; Kmoníčková, Eva; Zídek, Zdeněk

2015-01-01

Roč. 24, č. 5 (2015), s. 2154-2166 ISSN 1054-2523 R&D Projects: GA ČR(CZ) GAP303/12/0172; GA MV VG20102015046 Institutional support: RVO:61388963 ; RVO:68378041 Keywords : pyrimidine * nitric oxide * NO * anti-inflammatory Subject RIV: CC - Organic Chemistry Impact factor: 1.436, year: 2015

Crystal structure of 1-methyl-4-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine

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Mohammed El Fal

2014-12-01

Full Text Available In the title compound, C7H8N4S, the non-H atoms of the pyrazolo[3,4-d]pyrimidine ring system and the methylsulfanyl group lie on a crystallographic mirror plane. In the crystal, molecules are linked via a number of π–π interactions [centroid–centroid distances vary from 3.452 (7 to 3.6062 (8 Å], forming a three-dimensional structure.

Low-energy electron scattering from pyrimidine: Similarities and differences with benzene

Science.gov (United States)

Jones, D. B.; Bellm, S. M.; Limão-Vieira, P.; Brunger, M. J.

2012-05-01

Differential cross sections for low-energy electron-impact excitation of the unresolved combinations of 23B2 + 21A1 and 31A1 + 21B2 electronic states of pyrimidine are reported. Comparisons are made with recent differential cross section measurements for the electron-impact excitation of the 1E1u and unresolved 1B1u + 3E2g electronic states of benzene [H. Kato, M. Hoshino, H. Tanaka, P. Limão-Vieira, O. Ingolfsson, L. Campbell, M.J. Brunger, J. Chem. Phys. 134 (2011) 134308.], in order to evaluate the nature of electron impact π-π∗ transitions in aromatic species.

Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Compliance to the Dosimetry Requirements of RTOG-0413

Energy Technology Data Exchange (ETDEWEB)

Wen Bixiu [Department of Radiation Oncology, New York University Medical Center, New York, New York (United States); Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Hsu, Howard; Formenti-Ujlaki, George F.; Lymberis, Stella; Magnolfi, Chiara; Zhao Xuan; Chang Jenghwa; DeWyngaert, J. Keith; Jozsef, Gabor [Department of Radiation Oncology, New York University Medical Center, New York, New York (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University Medical Center, New York, New York (United States)

2012-11-15

Purpose: The dosimetric results from our institution's trials of prone accelerated partial breast irradiation are compared with the dosimetric requirements of RTOG-0413. Methods and Materials: Trial 1 and Trial 2 are 2 consecutive trials of prone-accelerated partial breast irradiation. Eligible for both trials were stage I breast cancer patients with negative margins after breast-conserving surgery. The planning target tumor volume (PTV) was created by extending the surgical cavity 2.0 cm for Trial 1 and 1.5 cm for Trial 2, respectively. Contralateral breast, heart, lungs, and thyroid were contoured. Thirty Gray was delivered in five daily fractions of 6 Gy by a three-dimensional conformal radiation therapy technique in Trial 1 and were by image-guided radiation therapy/intensity-modulated radiation therapy in Trial 2. Dosimetric results from the trials are reported and compared with RTOG 0413 requirements. Results: One hundred forty-six consecutive plans were analyzed: 67 left and 79 right breast cancers. The plans from the trials complied with the required >90% of prescribed dose covering 90% of PTV{sub E}VAL (=generated from the PTV by cropping 0.5 cm from the skin edge and excluding the chest wall): V90% was 98.1 {+-} 3.0% (with V100% and V95%, 89.4 {+-} 12.8%, 96.4 {+-} 5.1%, respectively). No significant difference between laterality was found (Student's t test). The dose constraints criteria of the RTOG-0413 protocol for ipsilateral and contralateral lung (V30 <15% and Dmax <3%), heart (V5 <40%), and thyroid (Dmax <3%) were satisfied because the plans showed an average V5% of 0.6% (range, 0-13.4) for heart, an average V30% of 0.6% (range, 0-9.1%) for ipsilateral lung, and <2% maximum dose to the thyroid. However, our partial breast irradiation plans demonstrated a higher dose to contralateral breast than that defined by RTOG constraints, with a median value of maximum doses of 4.1% (1.2 Gy), possibly as a result of contouring differences

Retained sensitivity to cytotoxic pyrimidine nucleoside analogs in thymidine kinase 2 deficient human fibroblasts

OpenAIRE

Bjerke, Mia; Solaroli, Nicola; Lesko, Nicole; Balzarini, Jan; Johansson, Magnus; Karlsson, Anna

2010-01-01

Thymidine kinase 2 (TK2) is a mitochondrial deoxyribonucleoside kinase that phosphorylates several nucleoside analogs used in anti-viral and anti-cancer therapy. A fibroblast cell line with decreased TK2 activity was investigated in order to obtain insights in the effects of TK2 deficiency on nucleotide metabolism. The role of TK2 for the sensitivity against cytotoxic nucleoside analogs was also investigated. The TK2 deficient cells retained their sensitivity against all pyrimidine nucleoside...

Identification of a large genomic region in UV-irradiated human cells which has fewer cyclobutane pyrimidine dimers than most genomic regions

International Nuclear Information System (INIS)

Kantor, G.J.; Deiss-Tolbert, D.M.

1995-01-01

Size separation after UV-endonuclease digestion of DNA from UV-irradiated human cells using denaturing conditions fractionates the genome based on cyclobutane pyrimidine dimer content. We have examined the largest molecules available (50-80 kb; about 5% of the DNA) after fractionation and those of average size (5-15 kb) for content of some specific genes. We find that the largest molecules are not a representative sampling of the genome. Three contiguous genes located in a G+C-rich isochore (tyrosine hydroxylase, insulin, insulin-like growth factor II) have concentrations two to three times greater in the largest molecules. This shows that this genomic region has fewer pyrimidine dimers than most other genomic regions. In contrast, the β-actin genomic region, which has a similar G+C content, has an equal concentration in both fractions as do the p53 and β-globin genomic regions, which are A+T-rich. These data show that DNA damage in the form of cyclobutane pyrimidine dimers occurs with different probabilities in specific isochores. Part of the reason may be the relative G-C content, but other factors must play a significant role. We also report that the transcriptionally inactive insulin region is repaired at the genome-overall rate in normal cells and is not repaired in xeroderma pigmentosum complementation group C cells. (author)

Electro-optical and charge injection investigations of the donor-π-acceptor triphenylamine, oligocene–thiophene–pyrimidine and cyanoacetic acid based multifunctional dyes

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Ahmad Irfan

2015-10-01

Full Text Available The corner stone of present study is to tune the electro-optical and charge transport properties of donor-bridge-acceptor (D-π-A triphenylamine (TPA derivatives. In the present investigation, an electron deficient moiety (pyrimidine, electron-rich moiety (thiophene and oligocene (benzene, naphthalene, anthracene, tetracene and pentacene have been incorporated as π-spacer between the donor TPA unit and cyanoacetic acid acceptor and anchoring group. The elongation of bridge usually affects the energy levels, i.e., higher the highest occupied molecular orbital (HOMO while lower the lowest unoccupied molecular orbital (LUMO thus reduces the HOMO–LUMO energy gap. The lowered LUMO energy levels of cyano-{2-[6-(4-diphenylamino-phenyl-pyrimidin-4-yl]-tetraceno[2,3-b]thiophen-8-yl}-acetic acid (TPA-PTT4 and cyano-{2-[6-(4-diphenylamino-phenyl-pyrimidin-4-yl]-pentaceno[2,3-b]thiophen-9-yl}-acetic acid (TPA-PPT5 dyes revealed that electron injected from dye to semiconductor surface might be auxiliary stable resulting in impediment of quenching. The broken co-planarity between the π-spacer conceiving LUMO and the TPA moiety would help to impede the recombination process. Moreover, it is expected that TPA derivatives with the tetracenothiophene and pentacenothiophene moieties as π-bridge would show better photovoltaic performance due to lowered LUMO energy level, higher electronic coupling constant, light harvesting efficiency and electron injection values.

Pyrimidine nucleoside analogues, potential chemotherapeutic agents, and substrates/inhibitors in various enzyme systems

International Nuclear Information System (INIS)

Kulikowski, T.; Bretner, M.; Felczak, K.; Drabikowska, A.; Shugar, D.

1998-01-01

Full text. Pyrimidine nucleoside analogues are an important class of compounds with antimetabolic (antitumor, antiparasitic and antiviral) properties. The synthesis of thiated nucleoside and nucleotide analogues, determination of structures, conformation and dissociation constans, their potential chemotherapeutic activities, and their substrate/inhibitor properties in various enzyme systems, with emphasis on enzymes related to chemotherapeutic activities, were investigated. In the series of thionated inhibitors of thymidylate synthase (TS), potential antitumor agents, regioselective syntheses were elaborated for 2- and 4-thio, and 2,4-dithio derivatives of 2'-deoxyuridine (dUrd), 5-fluoro-2'-deoxyuridine (FdUrd), and several other 5-fluoro-, 5-bromo- and 5-trifluoromethyl congeners, and the 2-thio derivatives of FdUrd and its α-anomer, which proved to be selective agents with high cytotoxicities correlated with the inhibitory activities vs TS of their corresponding 5'-monophosphates. Regioslective syntheses were also elaborated for 2'-deoxycytidin e and 5-fluoro-2'-deoxycitidine derivatives. Solution conformation of these nucleosides were deduced from high-resolution (500 MHz) 1 H NMR spectra. Substrate/inhibitor properties of 2-thio-2'-deoxycitidine (S 2 dCyd) and 5-fluoro-2-thio-2'-deoxycitidine ( S 2 FdCyd) with respect to human leukemic spleen deoxycytidine kinase have been examined. Both are substrates, and also good inhibitors, of phosphorylation of 2'-deoxycitidine and 2'-deoxyadenosine. Particular attention was directed to the specificity of t he NTP phosphate donor for several nucleoside kinases, and procedures have been developed for distinguishing between ATP and other NTP donors, a problem of importance in chemotherapy with nucleoside analogues. Biological properties of the newly synthetize d thiated pyrimidine 2',3'-dideoxy-3'-fluoronucleosides, S 2 ,3'-FddUrd and S 2 ,3'-FddThd, were also investigated. Thiated 3'-fluoronucleosides were moderate

[Separation of purines, pyrimidines, pterins and flavonoids on magnolol-bonded silica gel stationary phase by high performance liquid chromatography].

Science.gov (United States)

Chen, Hong; Li, Laishen; Zhang, Yang; Zhou, Rendan

2012-10-01

A new magnolol-bonded silica gel stationary phase (MSP) was used to separate the basic drugs including four purines, eight pyrimidines, four pterins and five flavonoids as polar representative samples by high performance liquid chromatography (HPLC). To clarify the separation mechanism, a commercial ODS column was also tested under the same chromatographic conditions. The high selectivities and fast baseline separations of the above drugs were achieved by using simple mobile phases on MSP. Although there is no end-caped treatment, the peak shapes of basic drugs containing nitrogen such as purines, pyrimidines and pterins were rather symmetrical on MSP, which indicated the the magnolol as ligand with multi-sites could shield the side effect of residual silanol groups on the surface of silica gel. Although somewhat different in the separation resolution, it was found that the elution orders of some drugs were generally similar on both MSP and ODS. The hydrophobic interaction should play a significant role in the separations of the above basic drugs, which was attributed to their reversed-phase property in the nature. However, MSP could provide the additional sites for many polar solutes, which was a rational explanation for the high selectivity of MSP. For example, in the separation of purines, pyrimidines and pterins on MSP, hydrogen-bonding and dipole-dipole interactions played leading roles besides hydrophobic interaction. Some solute molecules (such as mercaptopurine, vitexicarpin) and MSP can form the strong pi-pi stacking in the separation process. All enhanced the retention and improved the separation selectivity of MSP, which facilitated the separation of the basic drugs.

Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity

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Ameen Ali Abu-Hashem

2011-02-01

Full Text Available 6-[(4-Methoxy/4,9-dimethoxy-7-methylfurochromen-5-ylideneamino]-2-thioxo-2,3-dihydropyrimidin-4-ones 1a,b were prepared by reaction of 6-amino-2-thiouracil with visnagen or khellin, respectively. Reaction of 1a,b with methyl iodide afforded furochromenylideneaminomethylsulfanylpyrimidin-4-ones 2a,b. Compounds 2a,b were reacted with secondary aliphatic amines to give the corresponding furochromen-ylideneamino-2-substituted pyrimidin-4-ones 3a–d. Reaction of 3a–d with phosphorus oxychloride yielded 6-chlorofurochromenylidenepyrimidinamines 4a–d, which were reacted with secondary amines to afford furochromenylideneamino-2,6-disubstituted pyrimidin-4-ones 5a–d. In addition, reaction of 5a–d with 3-chloropentane-2,4-dione gave 3-chloro-furochromenylpyrimidopyrimidines 6a–d. The latter were reacted with piperazine and morpholine to give 1-(furochromenyl-pyrimidopyrimidine-3,6,8-triylpiperazines or -3,6,8-triylmorpholines 7a–d. The chemical structures of the newly synthesized compound ware characterized by IR, 1H-NMR, 13C-NMR and mass spectral analysis. These compounds were also screened for their analgesic and anti-inflammatory activities. Some of them, particularly 3–7, exhibited promising activities.

Depression of pyrimidine dimer excision from the aspects of uv reversibility of irradiated cells

Energy Technology Data Exchange (ETDEWEB)

Slamenova, D; Slezarikova, V; Masek, F [Slovenska Akademia Vied, Bratislava (Czechoslovakia)

1977-04-01

Depression of pyrimidine dimer excision induced in uv-irradiated E.coli B/r T/sup -/trp/sup -/Hcr/sup +/ cells by preirradiation cultivation in conditions of starving for the essential amino acid and thymine does not increase uv-reversibility of irradiated cells and does not influence the time of expression of trp/sup +/ reversions. The expression of mutations becomes completed in control and prestarved cells prior to restoration of postradiation division. Genetic deficiency leads up to their high sensitivity to the mutagenic activity of uv irradiation. Expression of trp/sup +/ revertants in Hcr/sup -/ type cells does not become completed until after commencement of the postradiation division of irradiated cells. Prestarved E.coli B/r T/sup -/trp/sup -/Hcr/sup +/ cells exhibited depression of excision even with postradiation cultivation in the absence of an essential amino acid, which is associated with greater stability of newly synthesized DNA and overall decrease of the death rate of cells. In postradiation starvation for the essential amino acid E.coli B/r T/sup -/trp/sup -/Hcr/sup -/ cells irradiated with low uv light doses behaved similarly. Control E.coli B/r T/sup -/trp/sup -/Hcr/sup +/ cells, cultivated after irradiation without amino acid, excised pyrimidine dimers; they are characterised by high degradation of newly synthesized DNA and increased death rate of cells.

MULTICOMPONENT AND REGIOSELECTIVE SYNTHESIS OF DIHYDROPYRAZOLO[1,5-a]PYRIMIDINES FROM AROMATIC ALDEHYDES, MELDRUM'S ACID AND AMINOPYRAZOLE CAN508

Czech Academy of Sciences Publication Activity Database

Jedinák, L.; Kryštof, Vladimír; Trávníček, Z.; Cankař, P.

2014-01-01

Roč. 89, č. 8 (2014), s. 1892-1904 ISSN 0385-5414 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Pyrazolo[1,5-a]pyrimidine * Cyclization * Multicomponent Reaction Subject RIV: CC - Organic Chemistry Impact factor: 1.079, year: 2014

Chemical display of pyrimidine bases flipped out by modification-dependent restriction endonucleases of MspJI and PvuRts1I families.

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Evelina Zagorskaitė

Full Text Available The epigenetic DNA modifications 5-methylcytosine (5mC and 5-hydroxymethylcytosine (5hmC in eukaryotes are recognized either in the context of double-stranded DNA (e.g., by the methyl-CpG binding domain of MeCP2, or in the flipped-out state (e.g., by the SRA domain of UHRF1. The SRA-like domains and the base-flipping mechanism for 5(hmC recognition are also shared by the recently discovered prokaryotic modification-dependent endonucleases of the MspJI and PvuRts1I families. Since the mechanism of modified cytosine recognition by many potential eukaryotic and prokaryotic 5(hmC "readers" is still unknown, a fast solution based method for the detection of extrahelical 5(hmC would be very useful. In the present study we tested base-flipping by MspJI- and PvuRts1I-like restriction enzymes using several solution-based methods, including fluorescence measurements of the cytosine analog pyrrolocytosine and chemical modification of extrahelical pyrimidines with chloroacetaldehyde and KMnO4. We find that only KMnO4 proved an efficient probe for the positive display of flipped out pyrimidines, albeit the method required either non-physiological pH (4.3 or a substitution of the target cytosine with thymine. Our results imply that DNA recognition mechanism of 5(hmC binding proteins should be tested using a combination of all available methods, as the lack of a positive signal in some assays does not exclude the base flipping mechanism.

Depression of pyrimidine dimer excision from the aspects of U.V. reversibility of irradiated cells

International Nuclear Information System (INIS)

Slamenova, D.; Slezarikova, V.; Masek, F.

1977-01-01

Depression of pyrimidine dimer excision induced in U.V. irradiated E.coli B/r T - trp - Hcr + cells by preirradiation cultivation in conditions of starving for the essential amino acid and thymine does not increase U.V.-reversibility of irradiated cells and does not influence the time of expression of trp + reversions. The expression of mutations becomes completed in control and prestarved cells prior to restoration of postradiation division. Genetic deficiency leads up to their high sensitivity to the mutagenic activity of U.V. irradiation. Expression of trp + revertants in Hcr - type cells does not become completed until after commencement of the postradiation division of irradiated cells. Prestarved E.coli B/r T - trp - Hcr + cells exhibited depression of excision even with postradiation cultivation in the absence of an essential amino acid, which is associated with greater stability of newly synthesized DNA and overall decrease of the death rate of cells. In postradiation starvation for the essential amino acid E.coli B/r T - trp - Hcr - cells irradiated with low U.V. light doses behaved similarly. Control E.coli B/r T - trp - Hcr + cells, cultivated after irradiation without amino acid, excised pyrimidine dimers; they are characterised by high degradation of newly synthesized DNA and increased death rate of cells. (author)

Steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone: A convenient synthesis, antiproliferation activity, structure-activity relationships, and role of heterocyclic moiety

Science.gov (United States)

Ke, Shaoyong; Shi, Liqiao; Zhang, Zhigang; Yang, Ziwen

2017-01-01

A series of steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone were designed and prepared by a convenient heterocyclization reaction. The in vitro anticancer activities for these obtained compounds were evaluated against human cancer cell lines (HepG2, Huh-7, and SGC-7901), which demonstrated that some of these heterocyclic pyrimidine derivatives exhibited significantly good cytotoxic activities against all tested cell lines compared with 5-fluorouracil (5-FU), especially, compound 3b exhibited high potential growth inhibitory activities against all tested cell lines with the IC50 values of 5.41 ± 1.34, 5.65 ± 1.02 and 10.64 ± 1.49 μM, respectively, which might be used as promising lead scaffold for discovery of novel anticancer agents. PMID:28290501

31P-NMR study of human pyrimidine 5'-nucleotidase deficient erythrocytes

International Nuclear Information System (INIS)

Higaki, Tsuyoshi; Kagimoto, Tadashi; Nagata, Koichi; Tanase, Sumio; Morino, Yoshimasa; Takatsuki, Kiyoshi

1982-01-01

Metabolic disorder of nucleotides in human pyrimidine 5'-nucleotidase (P5N) deficient erythrocytes was studied by 31 P-NMR with high resolution. Identification by combination of high-speed liquid chromatography revealed two-fold increases from the normal in the spectra in the α-, β- and γ-zones of nucleoside triphosphates of P5N deficient erythrocytes, 2,3-diphosphoglycerate shifted to the 0.3 ppm low magnetic field and signals of NAD and UDP-sugars(s) in the diphosphodiester zone. These results were obtained from the 31 P-NMR spectrum about one hour after blood sampling, indicating the high utility of this NMR for the diagnosis of P5N deficiency. (Chiba, N.)

Synthesis, reactions, and antiarrhythmic activities of some novel pyrimidines and pyridines fused with thiophene moiety

OpenAIRE

AMR, Abdel-Galil El-Sayed; ABDEL-HAFEZ, Naglaa Abdel-Samei

2009-01-01

We report herein the synthesis and antiarrhythmic activities of some newly synthesized heterocyclic theino[2,3-c]pyrimidine and theino[2,3-c]pyridine derivatives fused with thiophene moiety. Initially the acute toxicity of the compounds was assayed via the determination of their LD50. The antiarrhythmic activities for the compounds were determined and all the tested compounds were found more potent than Procaine amide\\textregistered and Lidocaine\\textregistered as positive antiarrhyth...

Synthesis, reactions, and antiarrhythmic activities of some novel pyrimidines and pyridines fused with thiophene moiety

OpenAIRE

AMR, Abdel-Galil El-Sayed; ABDEL-HAFEZ, Naglaa Abdel-Samei; MOHAMED, Salwa Fahem; ABDALLA, Mohamed Mostafa

2014-01-01

We report herein the synthesis and antiarrhythmic activities of some newly synthesized heterocyclic theino[2,3-c]pyrimidine and theino[2,3-c]pyridine derivatives fused with thiophene moiety. Initially the acute toxicity of the compounds was assayed via the determination of their LD50. The antiarrhythmic activities for the compounds were determined and all the tested compounds were found more potent than Procaine amide\\textregistered and Lidocaine\\textregistered as positive antiarrhyth...

Design, Synthesis, and X-ray Crystal Structures of 2,4-Diaminofuro[2,3-d]pyrimidines as Multireceptor Tyrosine Kinase and Dihydrofolate Reductase Inhibitors

Science.gov (United States)

Gangjee, Aleem; Li, Wei; Lin, Lu; Zeng, Yibin; Ihnat, Michael; Warnke, Linda A.; Green, Dixy W.; Cody, Vivian; Pace, Jim; Queener, Sherry F.

2009-01-01

To optimize dual receptor tyrosine kinase (RTK) and dihydrofolate reductase (DHFR) inhibition, the E- and Z-isomers of 5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines (1a and 1b) were separated by HPLC and the X-ray crystal structures (2.0 Å and 1.4 Å respectively) with mouse DHFR and NADPH as well as 1b with human DHFR (1.5 Å) were determined. The E- and Z-isomers adopt different binding modes when bound to mouse DHFR. A series of 2,4-diaminofuro[2,3-d]pyrimidines 2–13 were designed and synthesized using the X-ray crystal structures of 1a and 1b with DHFR to increase their DHFR inhibitory activity. Wittig reactions of appropriate 2-methoxyphenyl ketones with 2,4-diamino-6-chloromethyl furo[2,3-d]pyrimidine afforded the C8–C9 unsaturated compounds 2–7 and catalytic reduction gave the saturated 8–13. Homologation of the C9-methyl analog maintains DHFR inhibitory activity. In addition, inhibition of EGFR and PDGFR-β were discovered for saturated C9-homologated analogs 9 and 10 that were absent in the saturated C9-methyl analogs. PMID:19748785

TD-DFT Investigation of the Magnetic Circular Dichroism Spectra of Some Purine and Pyrimidine Bases of Nucleic Acids

DEFF Research Database (Denmark)

Fahleson, Tobias; Kauczor, Joanna; Norman, Patrick

2015-01-01

We present a computational study of the magnetic circular dichroism (MCD) spectra in the 200–300 nm wavelength region of purine and its derivative hypoxanthine, as well as of the pyrimidine bases of nucleic acids uracil, thymine, and cytosine, using the B3LYP and CAM–B3LYP functionals. Solvent...

Physical association of pyrimidine dimer DNA glycosylase and apurinic/apyrimidinic DNA endonuclease essential for repair of ultraviolet-damaged DNA

International Nuclear Information System (INIS)

Nakabeppu, Y.; Sekiguchi, M.

1981-01-01

T4 endonuclease, which is involved in repair of uv-damaged DNA, has been purified to apparent physical homogeneity. Incubation of uv-irradiated poly(dA).poly(dT) with the purified enzyme preparations resulted in production of alkali-labile apyrimidinic sites, followed by formation of nicks in the polymer. By performing a limited reaction with T4 endonuclease V at pH 8.5, irradiated polymer was converted to an intermediate form that carried a large number of alkali-labile sites but only a few nicks. The intermediate was used as substrate for the assay of apurinic/apyrimidinic DNA endonuclease activity. The two activities, a pyrimidine dimer DNA glycosylase and an apurinic/apyrimidinic DNA endonuclease, were copurified and found in enzyme preparations that contained only a 16,000-dalton polypeptide. These results strongly suggested that a DNA glycosylase specific for pyrimidine dimers and an apurinic/apyrimidinic DNA endonuclease reside in a single polypeptide chain coded by the denV gene of bacteriophage T4

One-electron oxidation reactions of purine and pyrimidine bases in cellular DNA.

Science.gov (United States)

Cadet, Jean; Wagner, J Richard; Shafirovich, Vladimir; Geacintov, Nicholas E

2014-06-01

The aim of this survey is to critically review the available information on one-electron oxidation reactions of nucleobases in cellular DNA with emphasis on damage induced through the transient generation of purine and pyrimidine radical cations. Since the indirect effect of ionizing radiation mediated by hydroxyl radical is predominant in cells, efforts have been made to selectively ionize bases using suitable one-electron oxidants that consist among others of high intensity UVC laser pulses. Thus, the main oxidation product in cellular DNA was found to be 8-oxo-7,8-dihydroguanine as a result of direct bi-photonic ionization of guanine bases and indirect formation of guanine radical cations through hole transfer reactions from other base radical cations. The formation of 8-oxo-7,8-dihydroguanine and other purine and pyrimidine degradation products was rationalized in terms of the initial generation of related radical cations followed by either hydration or deprotonation reactions in agreement with mechanistic pathways inferred from detailed mechanistic studies. The guanine radical cation has been shown to be implicated in three other nucleophilic additions that give rise to DNA-protein and DNA-DNA cross-links in model systems. Evidence was recently provided for the occurrence of these three reactions in cellular DNA. There is growing evidence that one-electron oxidation reactions of nucleobases whose mechanisms have been characterized in model studies involving aqueous solutions take place in a similar way in cells. It may also be pointed out that the above cross-linked lesions are only produced from the guanine radical cation and may be considered as diagnostic products of the direct effect of ionizing radiation.

Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

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Hua Bai

Full Text Available Mutations of the insulin/IGF signaling (IIS pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging. One candidate is target of rapamycin complex 1 (TORC1. Reduced TORC1 activity is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The eukaryotic translation initiation factor 4E binding protein (4E-BP is repressed by TORC1, and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis analyses to test whether longevity assurance mutants of chico, the Drosophila insulin receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes, which are robustly long-lived, d4eBP is required but not sufficient to slow aging. Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity. Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction and most measures of growth affected by either chico genotype are always independent of d4eBP. In females, chico heterozygotes paradoxically produce more rather than less phosphorylated 4E-BP (p4E-BP. Altered IRS function within the IIS pathway of Drosophila appears to have partial, conditional capacity to regulate aging through an unconventional interaction with 4E-BP.

Bis-guanylhydrazone diimidazo[1,2-a:1,2-c]pyrimidine as a novel and specific G-quadruplex binding motif.

Science.gov (United States)

Sparapani, Silvia; Bellini, Stefania; Gunaratnam, Mekala; Haider, Shozeb M; Andreani, Aldo; Rambaldi, Mirella; Locatelli, Alessandra; Morigi, Rita; Granaiola, Massimiliano; Varoli, Lucilla; Burnelli, Silvia; Leoni, Alberto; Neidle, Stephen

2010-08-21

A bis-guanylhydrazone derivative of diimidazo[1,2-a:1,2-c]pyrimidine has unexpectedly been found to be a potent stabiliser of several quadruplex DNAs, whereas there is no significant interaction with duplex DNA. Molecular modeling suggests that the guanylhydrazone groups play an active role in quadruplex binding.

Syntheses and anti-microbial evaluation of new quinoline scaffold derived pyrimidine derivatives

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Shikha S. Dave

2016-09-01

Full Text Available A series of diversely substituted chalcones derived from a quinoline scaffold, e.g. (E-3-(2-chloroquinolin-3-yl-1-(2-hydroxyphenyl prop-2-en-1-one and its pyrimidine analogues e.g. 2-[2-amino-6-(2-chloroquinolin-3-yl-5,6-dihydropyrimidin-4-yl]phenols have been prepared by condensation of 2-chloro-3-formyl quinoline with differently substituted 2-hydroxy acetophenones and further treatment with guanidine carbonate. All the newly synthesized compounds have been evaluated for their in vitro growth inhibitory activity against Escherichia coli, Pseudomonas vulgaris, Bacillus subtilis, Staphylococcus aureus, Staphylococcus typhi, Candida albicans, Aspergillus niger and Pseudomonas chrysogenum.

Excision of pyrimidine dimers from epidermal DNA and nonsemiconservative epidermal DNA synthesis following ultraviolet irradiation of mouse skin

International Nuclear Information System (INIS)

Bowden, G.T.; Trosko, J.E.; Shapas, B.G.; Boutwell, R.K.

1975-01-01

Pyrimidine dimer production and excision in epidermal DNA were studied at five different dose levels of ultraviolet light in the skin of intact mice. Dimer production increased with dose up to 50,400 ergs/sq mm. Approximately 30 percent of the thymine-containing dimers were excised by 24 hr after irradiation at three lower dose levels of ultraviolet light. Nonsemiconservative DNA replication in ultraviolet-irradiated mouse skin was shown to continue for at least 18 hr. The rate of nonsemiconservative replication decreased with time, but did so slowly. The initial rates of nonsemiconservative replication increased with ultraviolet light dose levels up to about 4200 ergs/sq mm, after which the initial rates were decreased. Semiconservative epidermal DNA synthesis was shown to be inhibited by hydroxyurea, but hydroxyurea had no effect on ultraviolet light-induced nonsemiconservative DNA replication. The observed pyrimidine dimer excision and nonsemiconservative DNA replication suggest that in the intact mouse the cells of the epidermis are capable of DNA excision repair after ultraviolet irradiation of mouse skin

Ultrasound assisted one pot expeditious synthesis of new pyrido[2,3-d]pyrimidine analogues using mild and inexpensive 4-dimethylaminopyridine (DMAP catalyst

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Ajmal R. Bhat

2017-09-01

Full Text Available The one-pot three-component reaction for the synthesis of pyrido[2,3-d]pyrimidine derivatives has been reported via initial Knoevenagel, subsequent addition and final heterocyclization of substituted aromatic aldehydes, cyanoacetamide and 6-aminouracil in N,N-dimethylformamide (DMF solvent using 4-dimethylaminopyridine (DMAP as new organocatalyst under ultrasound irradiation. The results showed that a series of aromatic aldehydes were successfully used to prepare the targeted pyrido[2,3-d]pyrimidine derivatives with good to excellent yields (81–93% and there is no major effect on the yield of product by electron donating/withdrawing substituents. Short reaction time, environment friendly procedure, excellent yields, inexpensive and readily available catalyst are the advantages of this procedure. All synthesized compounds were characterized by IR, 1HNMR, 13CNMR and mass spectral data.

Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2-(phosphonomethoxy)ethoxy]pyrimidine and related compounds

Czech Academy of Sciences Publication Activity Database

Hocková, Dana; Holý, Antonín; Masojídková, Milena; Andrei, G.; Snoeck, R.; De Clercq, E.; Balzarini, J.

2004-01-01

Roč. 12, č. 12 (2004), s. 3197-3202 ISSN 0968-0896 R&D Projects: GA AV ČR IBS4055109 Grant - others:ISEP/FORTIS(US) GOA-00/12; European Commission(XE) HPAW-2002-90001 Institutional research plan: CEZ:AV0Z4055905 Keywords : nucleotide analogues * antiviral * pyrimidines Subject RIV: CC - Organic Chemistry Impact factor: 2.018, year: 2004

Crystal structure of 1-ethylpyrazolo[3,4-d]pyrimidine-4(5H-thione

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Mohammed El Fal

2014-09-01

Full Text Available In the title compound, C7H8N4S, the methyl C atom is displaced by 1.232 (7 Å from the mean plane of the pyrazolo[3,4-d]pyrimidine ring system (r.m.s. deviation = 0.007 Å. The N—N—C—Cm (m = methyl torsion angle is −60.3 (6°. In the crystal, molecules are linked by N—H...S hydrogen bonds, generating [010] chains, which are reinforced by C—H...N interactions. The chains are cross-linked by weak C—H...S hydrogen bonds, generating (001 sheets.

Temperature dependence of desoxyribosylation of pyrimidine derivatives labelled with carbon-14 and tritium

International Nuclear Information System (INIS)

Pritasil, L.; Filip, J.

1977-01-01

The effect of the temperature and concentration of the enzyme preparation from Escherichia coli B on the reaction of pyrimidine bases with 2-desoxy-α-D-riboso-l-phosphate or α-D-riboso-l-phosphate was studied. It was found that at +2 deg C and low enzyme concentration higher yields of nucleosides are obtained than at the commonly used temperature of 37 deg C. The reaction time, however, must be protracted. The prepared [2- 14 C] uridine, 2'-deoxy[2- 14 C] uridine and [2- 14 C] thymidine had a high specific activity and radiochemical purity

Synthesis, Molecular Docking, and Antimycotic Evaluation of Some 3-Acyl Imidazo[1,2-a]pyrimidines

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Omar Gómez-García

2018-03-01

Full Text Available A series of 3-benzoyl imidazo[1,2-a]pyrimidines, obtained from N-heteroarylformamidines in good yields, was tested in silico and in vitro for binding and inhibition of seven Candida species (Candida albicans (ATCC 10231, Candida dubliniensis (CD36, Candida glabrata (CBS138, Candida guilliermondii (ATCC 6260, Candida kefyr, Candida krusei (ATCC 6358 and Candida tropicalis (MYA-3404. To predict binding mode and energy, each compound was docked in the active site of the lanosterol 14α-demethylase enzyme (CYP51, essential for fungal growth of Candida species. Antimycotic activity was evaluated as the 50% minimum inhibitory concentration (MIC50 for the test compounds and two reference drugs, ketoconazole and fluconazole. All test compounds had a better binding energy (range: −6.11 to −9.43 kcal/mol than that found for the reference drugs (range: 48.93 to −6.16 kcal/mol. In general, the test compounds showed greater inhibitory activity of yeast growth than the reference drugs. Compounds 4j and 4f were the most active, indicating an important role in biological activity for the benzene ring with electron-withdrawing substituents. These compounds show the best MIC50 against C. guilliermondii and C. glabrata, respectively. The current findings suggest that the 3-benzoyl imidazo[1,2-a]pyrimidine derivatives, herein synthesized by an accessible methodology, are potential antifungal drugs.

Synthesis and In Vitro Inhibition Effect of New Pyrido[2,3-d]pyrimidine Derivatives on Erythrocyte Carbonic Anhydrase I and II

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Hilal Kuday

2014-01-01

Full Text Available In vitro inhibition effects of indolylchalcones and new pyrido[2,3-d]pyrimidine derivatives on purified human carbonic anhydrase I and II (hCA I and II were investigated by using CO2 as a substrate. The results showed that all compounds inhibited the hCA I and hCA II enzyme activities. Among all the synthesized compounds, 7e (IC50=6.79 µM was found to be the most active compound for hCA I inhibitory activity and 5g (IC50=7.22 µM showed the highest hCA II inhibitory activity. Structure-activity relationships study showed that indolylchalcone derivatives have higher inhibitory activities than pyrido[2,3-d]pyrimidine derivatives on hCA I and hCA II. Additionally, methyl group bonded to uracil ring increases inhibitory activities on both hCA I and hCA II.

Study of hydrogen mobility by hydrogen-deuterium exchange. II. Theoretical kinetic study in alkyl and amino-alkyl pyrimidines

International Nuclear Information System (INIS)

Pompon, Alain

1975-01-01

Alkyl groups bound to the pyrimidine ring can be deuterium substituted on the carbon adjacent to the ring, in acidic D 2 O; kinetic equations corresponding to various exchange mechanism hypothesis are established. It is shown that theoretical and experimental results can be compared in order to precise the mechanism and to measure the characteristic parameters of the exchange reaction [fr

Synthesis and antibacterial activity of some derivatives of 1,3,4-thia-dia-zol[3,2-a]pyrimidine

International Nuclear Information System (INIS)

Sangov, Z.G.

2004-01-01

The purpose of this work is direct synthesis of derivatives of 1,3,4-thia-dia-zol[3,2-a]pyrimidine containing functional groups in second and sixth position of cycle, studying antibacterial activity obtained compounds on culture fungus, typical for this region and searching for new high-effective biologically active matters with low toxicity which let wide assortment of medicinal preparations

Pyrimidine-5'-nucleotidase Campinas, a new mutation (p.R56G) in the NT5C3 gene associated with pyrimidine-5'-nucleotidase type I deficiency and influence of Gilbert's Syndrome on clinical expression.

Science.gov (United States)

Santos, Andrey dos; Dantas, Larissa Elizabeth Cordeiro; Traina, Fabiola; Albuquerque, Dulcineia Martins de; Chaim, Elinton Adami; Saad, Sara T Olalla

2014-12-01

Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans. Copyright © 2014 Elsevier Inc. All rights reserved.

One pyrimidine dimer inactivates expression of a transfected gene in xeroderma pigmentosum cells

International Nuclear Information System (INIS)

Protic-Sabljic, M.; Kraemer, K.H.

1985-01-01

The authors have developed a host cell reactivation assay of DNA repair utilizing UV-treated plasmid vectors. The assay primarily reflects cellular repair of transcriptional activity of damaged DNA measured indirectly as enzyme activity of the transfected genes. They studied three plasmids (pSV2cat, 5020 base pairs; pSV2catSVgpt, 7268 base pairs; and pRSVcat, 5027 base pairs) with different sizes and promoters carrying the bacterial cat gene (CAT, chloramphenicol acetyltransferase) in a construction that permits cat expression in human cells. All human simian virus 40-transformed cells studied expressed high levels of the transfected cat gene. UV treatment of the plasmids prior to transfection resulted in differential decrease in CAT activity in different cell lines. With pSV2catSVgpt, UV inactivation of CAT expression was greater in the xeroderma pigmentosum group A and D lines than in the other human cell lines tested. The D 0 of the CAT inactivation curve was 50 J X m-2 for pSV2cat and for pRSVcat in the xeroderma pigmentosum group A cells. The similarity of the D0 data in the xeroderma pigmentosum group A cells for three plasmids of different size and promoters implies they all have similar UV-inactivation target size. UV-induced pyrimidine dimer formation in the plasmids was quantified by assay of the number of UV-induced T4 endonuclease V-sensitive sites. In the most sensitive xeroderma pigmentosum cells, with all three plasmids, one UV-induced pyrimidine dimer inactivates a target of about 2 kilobases, close to the size of the putative CAT mRNA

Repair of pyrimidine dimers in nuclear and mitochondrial DNA of yeast irradiated with low doses of ultraviolet light

Energy Technology Data Exchange (ETDEWEB)

Prakash, L [Rochester Univ., N.Y. (USA). Dept. of Radiation Biology and Biophysics

1975-01-01

The repair of damage induced by ultraviolet light has been examined in both the nuclear and mitochondrial DNA of the yeast Saccharomyces cerevisiae. The sensitive assay used in this study is based on the capacity of the bacteriophage T4 u.v. endonuclease to produce single-strand breaks in DNA that contains pyrimidine dimers, thus permitting the use of low fluences (doses) of u.v. The results demonstrate that virtually all of the dimers induced in the nuclear DNA of a repair-proficient strain (RAD+) are removed following dark incubation for four hours in growth medium. In contrast, the dimers induced in mitochondrial DNA by the same u.v. fluence are retained under the same conditions. In the excision-deficient mutant, rad1-2, no evidence was obtained for removal of pyrimidine dimers from nuclear DNA. Photoreactivation of both RAD + and rad1-2 cultures resulted in decreases of dimers from both nuclear and mitochondrial DNA. It is concluded that an excision-repair mechanism operates on nuclear but not mitochondrial DNA in repair-proficient yeast, and that the rad1-2 mutant is defective in this process.

Exploiting the pyrazolo[3,4-d]pyrimidin-4-one ring system as a useful template to obtain potent adenosine deaminase inhibitors.

Science.gov (United States)

La Motta, Concettina; Sartini, Stefania; Mugnaini, Laura; Salerno, Silvia; Simorini, Francesca; Taliani, Sabrina; Marini, Anna Maria; Da Settimo, Federico; Lavecchia, Antonio; Novellino, Ettore; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado; Del Tacca, Mario

2009-03-26

A number of pyrazolo[3,4-d]pyrimidin-4-ones bearing either alkyl or arylalkyl substituents in position 2 of the nucleus were synthesized and tested for their ability to inhibit adenosine deaminase (ADA) from bovine spleen. The 2-arylalkyl derivatives exhibited excellent inhibitory activity, showing Ki values in the nanomolar/subnanomolar range. The most active compound, 1-(4-((4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidin-2-yl)methyl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea, 14d, was tested in rats with colitis induced by 2,4-dinitrobenzenesulfonic acid to assess its efficacy to attenuate bowel inflammation. The treatment with 14d induced a significant amelioration of both systemic and intestinal inflammatory alterations in animals with experimental colitis. Docking simulations of the synthesized compounds into the ADA catalytic site were also performed to rationalize the structure-activity relationships observed and to highlight the key pharmacophoric elements of these products, thus prospectively guiding the design of novel ADA inhibitors.

Pyrazolo[3,4-d]pyrimidines as novel inhibitors of O-acetyl-L-serine sulfhydrylase of Entamoeba histolytica: an in silico study.

Science.gov (United States)

Yadava, Umesh; Shukla, Bindesh Kumar; Roychoudhury, Mihir; Kumar, Devesh

2015-04-01

Amoebiasis, a worldwide explosive epidemic, caused by the gastrointestinal anaerobic protozoan parasite Entamoeba histolytica, infects the large intestine and, in advance stages, liver, kidney, brain and lung. Metronidazole (MNZ)-the first line medicament against amoebiasis-is potentially carcinogenic to humans and shows significant side-effects. Pyrazolo[3,4-d]pyrimidine compounds have been reported to demonstrate antiamoebic activity. In silico molecular docking simulations on nine pyrazolo[3,4-d]pyrimidine molecules without linkers (molecules 1-9) and nine pyrazolo[3,4-d]pyrimidine molecules with a trimethylene linker (molecules 10-18) along with the reference drug metronidazole (MNZ) were conducted using the modules of the programs Glide-SP, Glide-XP and Autodock with O-acetyl-L-serine sulfhydrylase (OASS) enzyme-a promising target for inhibiting the growth of Entamoeba histolytica. Docking simulations using Glide-SP demonstrate good agreement with reported biological activities of molecules 1-9 and indicate that molecules 2 and 4 may act as potential high affinity inhibitors. Trimethylene linker molecules show improved binding affinities among which molecules 15 and 16 supersede. MD simulations on the best docked poses of molecules 2, 4, 15, 16 and MNZ were carried out for 20 ns using DESMOND. It was observed that the docking complexes of molecules 4, 15 and MNZ remain stable in aqueous conditions and do not undergo noticeable fluctuations during the course of the dynamics. Relative binding free energy calculations of the ligands with the enzyme were executed on the best docked poses using the molecular mechanics generalized Born surface area (MM-GBSA) approach, which show good agreement with the reported biological activities.

Design, synthesis and antifungal activities of novel strobilurin derivatives containing pyrimidine moieties

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xiang; Geo, Yongxin; Liu, Huijun; Guo, Baoyuan; Wang, Huili [Research Center for Eco-Environmental Sciences/Chinese Academy of Sciences, Beijing (China)

2012-04-15

Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel β-methoxy acrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, {sup 1}H nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbicular, Botrytis cinerea Pers and Protoporphyria caps ici Leon ian at the concentration of 50 μg/mL. Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial stilbenetriol fungicide azoxystrobin.

Development of novel (1-H benzimidazole bearing pyrimidine-trione based MAO-A inhibitors: Synthesis, docking studies and antidepressant activity

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Bijo Mathew

2016-09-01

Full Text Available The synthesis of some novel (1-H benzimidazole bearing pyrimidine-trione based MAO-A inhibitors were achieved by the reaction between 2E-1-(1H-benzimidazol-2-yl-3-phenylprop-2-en-1-ones(4a–f and barbituric acid in the presence of a catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, 1HNMR and mass spectra analyses. All the synthesized derivatives showed good antidepressant activity when compared to the standard clomipiramine at a dose level of 20 mg/kg. The compound (5d 5-{(2E-1-(1H-benzimidazol-2-yl-3-[4-(dimethylaminophenyl] prop-2-en-1-ylidene} pyrimidine-2, 4, 6(1H,3H,5H-trione significantly reduced the duration of immobility times at 50 mg/kg−1 dose level when compared to the standard drug. Molecular docking studies revealed the need for an extra hydrophobic interaction in the titled scaffold for acquiring the promising experimental values. It has been concluded that the computational values obtained after the docking calculation are in good agreement with the experimental values.

Spectroscopic and theoretical investigation of conformational changes of proteins by synthesized pyrimidine derivative and its sensitivity towards FRET application

Science.gov (United States)

Ghosh, Swadesh; Singharoy, Dipti; Bhattacharya, Subhash Chandra

2018-04-01

Interest in synthesizing and characterizing (IR, NMR and HRMS spectroscopic methods) a pyrimidine based Schiff-base ligand, 2-(2-(Anthracen-9-ylmethylene) hydrazinyl)-4,6-dimethyl pyrimidine (ANHP) has been developed for its application to ascertain the conformational change of protein and sensitivity towards fluorescence resonance energy transfer (FRET) process. Location of ANHP in bovine serum albumin (BSA) and human serum albumin (HSA) proteins environment has been determined using different spectroscopic techniques. Weakly fluorescent ANHP have shown greater protein induced fluorescence enhancement (PIFE) in case of HSA than BSA, though in both cases energy transfer efficiency are almost same but difference in binding constant values encourages us to find the location of ANHP within the complex protein environment. From the FRET parameter and α-helicity change, it has been found that ANHP bound with Trp-214 of HSA and surface Trp-134 of BSA. Conformational changes of proteins have been observed more for HSA than BSA in presence of ANHP, which has confirmed the location of ANHP in both the protein environments. Coupled with experimental studies, molecular docking analysis has also been done to explain the locations and distance dependent FRET process of ANHP in both proteins.

Review of the first partial licence for the Muelheim-Kaerlich reactor on the basis of the licensing requirements under nuclear law

International Nuclear Information System (INIS)

Hahn, L.; Wimmer, J.

1990-11-01

The expert opinion is restricted in the main to the licensing requirements in connection with the latest state-of-the-art precautionary measures against damage, i.e. subsection 3 of paragraph 7 section 2 Atomic Energy Act. Subject of the evaluations regarding the required new scope of licensing were the cancelled first partial licence, subsequent partial licences, the TUEV (Technical Control Board) expert opinion, the safety report with its continuations as well as the judgments of the Higher Administrative Court in Koblenz and the Federal Administrative Court. For determining the state-of-the-art, the expert opinion refers to the valid body of regulations, the latest concepts for PWRs in particular in the Federal Republic of Germany, and more recent results in reactor safety research. (orig./DG) [de

MD study of pyrimidine base damage on DNA and its recognition by repair enzyme

International Nuclear Information System (INIS)

Pinak, M.

2000-01-01

The molecular dynamics (MD) simulation was used on the study of two specific damages of pyrimidine bases of DNA. Pyrimidine bases are major targets either of free radicals induced by ionizing radiation in DNA surrounding environment or UV radiation. Thymine dimer (TD) is UV induced damage, in which two neighboring thymines in one strand are joined by covalent bonds of C(5)-C(5) and C(6)-C(6) atoms of thymines. Thymine glycol (TG) is ionizing radiation induced damage in which the free water radical adds to unsaturated bond C(5)-C(6) of thymine. Both damages are experimentally suggested to be mutagenetic and carcinogenic unless properly repaired by repair enzymes. In the case of MD of TD, there is detected strong kink around the TD site that is not observed in native DNA. In addition there is observed the different value of electrostatic energy at the TD site - negative '-10 kcal/mol', in contrary to nearly neutral value of native thymine site. Structural changes and specific electrostatic energy - seems to be important for proper recognition of TD damaged site, formation of DNA-enzyme complex and thus for subsequent repair of DNA. In the case of TG damaged DNA there is major structural distortion at the TG site, mainly the increased distance between TG and the C5' of adjacent nucleotide. This enlarged gap between the neighboring nucleotides may prevent the insertion of complementary base during replication causing the replication process to stop. In which extend this structural feature together with energy properties of TG contributes to the proper recognition of TG by repair enzyme Endonuclease III is subject of further computational MD study. (author)

TD-DFT investigation of the magnetic circular dichroism spectra of some purine and pyrimidine bases of nucleic acids.

Science.gov (United States)

Fahleson, Tobias; Kauczor, Joanna; Norman, Patrick; Santoro, Fabrizio; Improta, Roberto; Coriani, Sonia

2015-05-28

We present a computational study of the magnetic circular dichroism (MCD) spectra in the 200-300 nm wavelength region of purine and its derivative hypoxanthine, as well as of the pyrimidine bases of nucleic acids uracil, thymine, and cytosine, using the B3LYP and CAM-B3LYP functionals. Solvent effects are investigated within the polarizable continuum model and by inclusion of explicit water molecules. In general, the computed spectra are found to be in good agreement with the experimental ones, apart from some overall blue shifts. Both the pseudo-A term shape of the MCD spectra of the purines and the B term shape of the spectra of pyrimidine bases are reproduced. Our calculations also correctly reproduce the reversed phase of the MCD bands in purine compared to that of its derivatives present in nucleic acids. Solvent effects are sizable and system specific, but they do not in general alter the qualitative shape of the spectra. The bands are dominated by the bright π → π* transitions, and our calculations in solution nicely reproduce their energy differences, improving the estimates obtained in the gas phase. Shoulders are predicted for purine and uracil due to n → π* excitations, but they are too weak to be observed in the experiment.

MULTICOMPONENT AND REGIOSELECTIVE SYNTHESIS OF DIHYDROPYRAZOLO[1,5-a]PYRIMIDINES FROM AROMATIC ALDEHYDES, MELDRUM'S ACID AND AMINOPYRAZOLE CAN508

OpenAIRE

Jedinák, L.; Kryštof, V. (Vladimír); Trávníček, Z.; Cankař, P.

2014-01-01

A regioselective synthesis of dihydropyrazolo[1,5-a]pyrimidines is reported. The multicomponent reaction of readily available arylaldehydes, Meldrum's acid, and aminopyrazole CAN508 afforded fused pyrazolopyrimidines in high yields. The reaction proceeded regioselectively via initial Michael addition of the exocyclic amino group to arylidene Meldrum's acid intermediate followed by a ring closure at the endocyclic nitrogen of aminopyrazole. The regioselectivity of the reaction was determined b...

Retained sensitivity to cytotoxic pyrimidine nucleoside analogs in thymidine kinase 2 deficient human fibroblasts.

Science.gov (United States)

Bjerke, Mia; Solaroli, Nicola; Lesko, Nicole; Balzarini, Jan; Johansson, Magnus; Karlsson, Anna

2010-01-01

Thymidine kinase 2 (TK2) is a mitochondrial deoxyribonucleoside kinase that phosphorylates several nucleoside analogs used in anti-viral and anti-cancer therapy. A fibroblast cell line with decreased TK2 activity was investigated in order to obtain insights in the effects of TK2 deficiency on nucleotide metabolism. The role of TK2 for the sensitivity against cytotoxic nucleoside analogs was also investigated. The TK2 deficient cells retained their sensitivity against all pyrimidine nucleoside analogs tested. This study suggests that nucleoside analog phosphorylation mediated by TK2 may be less important, compared to other deoxyribonucleoside kinases, for the cytotoxic effects of these compounds.

Cloning and characterization of a gene (UVR3) required for photorepair of 6-4 photoproducts in Arabidopsis thaliana

International Nuclear Information System (INIS)

Nakajima, S.; Sugiyama, M.; Iwai, S.; Hitomi, K.; Otoshi, E.; Kim SangTae; Jiang CaiZhong; Todo, T.; Britt, A.B.; Yamamoto, K.

1998-01-01

UV radiation induces two major classes of pyrimidine dimers: the pyrimidine [6-4] pyrimidone photoproduct (6-4 product) and the cyclobutane pyrimidine dimer (CPD). Many organisms produce enzymes, termed photolyases, that specifically bind to these damage products and split them via a UV-A/blue light-dependent mechanism, thereby reversing the damage. These photolyases are specific for either CPDs or 6-4 products. A gene that expresses a protein with 6-4 photolyase activity in vitro was recently cloned from Drosophila melanogaster and Xenopus laevis. We report here the isolation of a homolog of this gene, cloned on the basis of sequence similarity, from the higher plant Arabidopsis thaliana. This cloned gene produces a protein with 6-4 photolyase activity when expressed in Escherichia coli. We also find that a previously described mutant of Arabidopsis (uvr3) that is defective in photoreactivation of 6-4 products carries a nonsense mutation in this 6-4 photolyase homolog. We have therefore termed this gene UVR3. Although homologs of this gene have previously been shown to produce a functional 6-4 photolyase when expressed in heterologous systems, this is the first demonstration of a requirement for this gene for photoreactivation of 6-4 products in vivo

Cyclobutane-type pyrimidine photodimer formation and induction of ornithine decarboxylase in human skin fibroblasts after UV irradiation

International Nuclear Information System (INIS)

Niggli, H.J.; Roethlisberger, R.

1988-01-01

Cyclobutane-type pyrimidine photodimers as well as the induction of ornithine decarboxylase (ODC) may serve as biochemical markers of the mutagenic and carcinogenic effects of ultraviolet light (UV). For this reason, it is important to compare the formation of pyrimidine dimers with the induction of ODC in human skin fibroblasts after irradiation with UVC (200-290 nm) and UVB (290-320 nm). In our studies we determined cytosine-thymine (C-T) as well as thymine-thymine dimer yields (T-T) by high-pressure liquid chromatography in cultures of neonatal normal human foreskin-derived fibroblasts after irradiation with UVC and UVB light. It was found that the yield of dimerization and the ratio of T-T/C-T decreased from the UVC to the UVB region. Time-course studies of ODC-induction in the same cells indicated that the maximal activity after UVB irradiation was retarded compared to UVC exposure. For the UV-induced ODC-levels, however, no significant difference in maximal induction could be measured after UVC and UVB irradiation at fluences where comparable yields of thymine dimerization are produced. Similar ODC-maxima were obtained with strains from children, while cells from adults showed significantly less pronounced ODC induction, indicating that ODC-response decreases with age and may therefore be used as a marker of aging

Glutamine-dependent carbamoyl-phosphate synthetase and other enzyme activities related to the pyrimidine pathway in spleen of Squalus acanthias (spiny dogfish).

Science.gov (United States)

Anderson, P M

1989-01-01

The first two steps of urea synthesis in liver of marine elasmobranchs involve formation of glutamine from ammonia and of carbamoyl phosphate from glutamine, catalysed by glutamine synthetase and carbamoyl-phosphate synthetase, respectively [Anderson & Casey (1984) J. Biol. Chem. 259, 456-462]; both of these enzymes are localized exclusively in the mitochondrial matrix. The objective of this study was to establish the enzymology of carbamoyl phosphate formation and utilization for pyrimidine nucleotide biosynthesis in Squalus acanthias (spiny dogfish), a representative elasmobranch. Aspartate carbamoyltransferase could not be detected in liver of dogfish. Spleen extracts, however, had glutamine-dependent carbamoyl-phosphate synthetase, aspartate carbamoyltransferase, dihydro-orotase, and glutamine synthetase activities, all localized in the cytosol; dihydro-orotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine-5'-decarboxylase activities were also present. Except for glutamine synthetase, the levels of all activities were very low. The carbamoyl-phosphate synthetase activity is inhibited by UTP and is activated by 5-phosphoribosyl 1-pyrophosphate. The first three enzyme activities of the pyrimidine pathway were eluted in distinctly different positions during gel filtration chromatography under a number of different conditions; although complete proteolysis of inter-domain regions of a multifunctional complex during extraction cannot be excluded, the evidence suggests that in dogfish, in contrast to mammalian species, these three enzymes of the pyrimidine pathway exist as individual polypeptide chains. These results: (1) establish that dogfish express two different glutamine-dependent carbamoyl-phosphate synthetase activities, (2) confirm the report [Smith, Ritter & Campbell (1987) J. Biol. Chem. 262, 198-202] that dogfish express two different glutamine synthetases, and (3) provide indirect evidence that glutamine may not be available in liver for

Novel N-(pyrimidin-4-ylthiazol-2-amine derivatives as dual-action hypoglycemic agents that activate GK and PPARγ

Directory of Open Access Journals (Sweden)

Hui-peng Song

2011-10-01

Full Text Available A series of novel N-(pyrimidin-4-ylthiazol-2-amine derivatives have been synthesized and evaluated as glucokinase (GK activators. Ethyl 2-(6-(4-(2-hydroxyethylpiperazin-1-yl-2-methylpyrimidin-4-yl-aminothiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating both GK and PPARγ. When given orally to normal mice, the compound demonstrated significant efficacy in decreasing the glucose level after oral glucose loading.

Evaluation and structure-activity relationship analysis of a new series of 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines as potential antibacterial agents

Science.gov (United States)

Beyzaei, Hamid; Aryan, Reza; Moghaddam-Manesh, Mohammadreza; Ghasemi, Behzad; Karimi, Pouya; Samareh Delarami, Hojat; Sanchooli, Mahmood

2017-09-01

The synthesis of pyrazolo[3,4-d]pyrimidine derivatives is important due to their presence in various biologically active compounds such as anticancer, antimicrobial, antiparasitic, anti-inflammatory and antidiabetic agents. In this project, a new and efficient approach for the synthesis of some novel 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines from reaction of 5-amino-pyrazole-4-carbonitrile with various hydrazides in ethanolic sodium ethoxide medium was reported. Antimicrobial activities of all synthesized derivatives were evaluated against eight Gram-positive and five Gram-negative pathogenic bacteria. The moderate to good inhibitory effects were observed based on inhibition zone diameter (IZD), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. In order to determine the reasonable relationship between antibacterial activities and physiochemical properties of the derivatives, computational studies were carried out in terms of geometry optimization, short-range van der Waals forces, dipole moments, atomic charges and frontier orbital energies. It was found that both short-range forces and covalent bonds are important in the observed inhibitory effects of the molecules. The results suggested that pyrazolo[3,4-d]pyrimidine derivatives prefer a soft nucleophilic attack on bio-macromolecular targets. Furthermore, our models proposed that the antibacterial activities of these derivatives can be improved by substituting large electron donating groups on the 6-phenyl rings.

Prodrugs of Pyrazolo[3,4-d]pyrimidines: From Library Synthesis to Evaluation as Potential Anticancer Agents in an Orthotopic Glioblastoma Model.

Science.gov (United States)

Vignaroli, Giulia; Iovenitti, Giulia; Zamperini, Claudio; Coniglio, Federica; Calandro, Pierpaolo; Molinari, Alessio; Fallacara, Anna Lucia; Sartucci, Andrea; Calgani, Alessia; Colecchia, David; Mancini, Andrea; Festuccia, Claudio; Dreassi, Elena; Valoti, Massimo; Musumeci, Francesca; Chiariello, Mario; Angelucci, Adriano; Botta, Maurizio; Schenone, Silvia

2017-07-27

Pyrazolo[3,4-d]pyrimidines are potent protein kinase inhibitors with promising antitumor activity but suboptimal aqueous solubility, consequently worth being further optimized. Herein, we present the one-pot two-step procedure for the synthesis of a set of pyrazolo[3,4-d]pyrimidine prodrugs (1a-8a and 9a-e) with higher aqueous solubility and enhanced pharmacokinetic and therapeutic properties. ADME studies demonstrated for the most promising prodrugs a better aqueous solubility, a favorable hydrolysis in human and murine serum, and an increased ability to cross cell membranes with respect to the parental drugs, explaining their better 24 h in vitro cytotoxicity against human glioblastoma U87 cell line. Finally, the 4-4a couple of drug/prodrug was also evaluated in vivo, revealing a profitable pharmacokinetic profile of the prodrug associated with a good efficacy. The application of the prodrug approach demonstrated to be a successful strategy for improving aqueous solubility of the parental drugs, determining a positive impact also in their biological efficacy.

Fenarimol, a Pyrimidine-Type Fungicide, Inhibits Brassinosteroid Biosynthesis

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Keimei Oh

2015-07-01

Full Text Available The plant steroid hormone brassinosteroids (BRs are important signal mediators that regulate broad aspects of plant growth and development. With the discovery of brassinoazole (Brz, the first specific inhibitor of BR biosynthesis, several triazole-type BR biosynthesis inhibitors have been developed. In this article, we report that fenarimol (FM, a pyrimidine-type fungicide, exhibits potent inhibitory activity against BR biosynthesis. FM induces dwarfism and the open cotyledon phenotype of Arabidopsis seedlings in the dark. The IC50 value for FM to inhibit stem elongation of Arabidopsis seedlings grown in the dark was approximately 1.8 ± 0.2 μM. FM-induced dwarfism of Arabidopsis seedlings could be restored by brassinolide (BL but not by gibberellin (GA. Assessment of the target site of FM in BR biosynthesis by feeding BR biosynthesis intermediates indicated that FM interferes with the side chain hydroxylation of BR biosynthesis from campestanol to teasterone. Determination of the binding affinity of FM to purified recombinant CYP90D1 indicated that FM induced a typical type II binding spectrum with a Kd value of approximately 0.79 μM. Quantitative real-time PCR analysis of the expression level of the BR responsive gene in Arabidopsis seedlings indicated that FM induces the BR deficiency in Arabidopsis.

Partial Cancellation

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. Partial Cancellation. Full Cancellation is desirable. But complexity requirements are enormous. 4000 tones, 100 Users billions of flops !!! Main Idea: Challenge: To determine which cross-talker to cancel on what “tone” for a given victim. Constraint: Total complexity is ...

Decreased UV light resistance of spores of Bacillus subtilis strains deficient in pyrimidine dimer repair and small, acid-soluble spore proteins

International Nuclear Information System (INIS)

Setlow, B.; Setlow, P.

1988-01-01

Loss of small, acid-soluble spore protein alpha reduced spore UV resistance 30- to 50-fold in Bacillus subtilis strains deficient in pyrimidine dimer repair, but gave only a 5- to 8-fold reduction in UV resistance in repair-proficient strains. However, both repair-proficient and -deficient spores lacking this protein had identical heat and gamma-radiation resistance

Sequence analysis and identification of the pyrKDbF operon from Lactococcus lactis including a novel gene, pyrK, involved in pyrimidine biosynthesis

DEFF Research Database (Denmark)

Andersen, Paal Skytt; Martinussen, Jan; Hammer, Karin

1996-01-01

Three genes encoding enzymes involved in the biosynthesis of pyrimidines have been found to constitute an operon in Lactococcus lactis. Two of the genes are the well-known pyr genes pyrDb and pyrF, encoding dihydroorotate dehydrogenase and orotidine monophosphate decarboxylase, respectively....... The third gene encodes a protein which was shown to be necessary for the activity of the pyrDb-encoded dihydroorotate dehydrogenase; we propose to name the gene pyrK. The pyrK-encoded protein is homologous to a number of proteins which are involved in electron transfer. The lactococcal pyrKDbF operon...... is highly homologous to the corresponding part of the much-larger pyr operon of Bacillus subtilis. orf2, the pyrK homolog in B. subtilis, has also been shown to be necessary for pyrimidine biosynthesis (A.E. Kahler and R.L. Switzer, J. Bacteriol. 178:5013-5016, 1996). Four genes adjacent to the operon, i...

Repair of closely opposed cyclobutyl pyrimidine dimers in UV-sensitive human diploid fibroblasts

International Nuclear Information System (INIS)

Lam, L.H.; Reynolds, R.J.

1986-01-01

An enzyme-sensitive site assay has been used to examine the fate of closely opposed pyrimidine dimers in fibroblasts from individuals afflicted with various genetic disorders that confer increased cellular sensitivity to UV radiation. The disappearance of bifilar enzyme-sensitive sites was found to be normal in cells from individuals with Fanconi's anemia, Cockayne's syndrome, dyskeratosis congenita and the variant form of xeroderma pigmentosum. The rate of bifilar enzyme-sensitive site removal in XP cells assigned to complementation group C was reduced by an amount similar to that observed for the repair of isolated dimers. Our results indicate that the initiation of repair at closely opposed dimers is slow in XP-C cells but normal in all other cells examined. (Auth.)

Structure, stability, and thermodynamics of a short intermolecular purine-purine-pyrimidine triple helix

International Nuclear Information System (INIS)

Pilch, D.S.; Shafer, R.H.; Levenson, C.

1991-01-01

The authors have investigated the structure and physical chemistry of the d(C 3 T 4 C 3 )·2[d(G 3 A 4 G 3 )] triple helix by polyacrylamide gel electrophoresis (PAGE), 1 H NMR, and ultraviolet (UV) absorption spectroscopy. The triplex was stabilized with MgCl 2 at neutral pH. PAGE studies verify the stoichiometry of the strands comprising the triplex and indicate that the orientation of the third strand in purine-purine-pyrimidine (pur-pur-pyr) triplexes is antiparallel with respect to the purine strand of the underlying duplex. Imino proton NMR spectra provide evidence for the existence of new purine-purine (pur·pur) hydrogen bonds, in addition to those of the Watson-Crick (W-C) base pairs, in the triplex structure. These new hydrogen bonds are likely to correspond to the interaction between third-strand guanine NH1 imino protons and the N7 atoms of guanine residues on the puring strand of the underlying duplex. Thermal denaturation of the triplex proceeds to single strands in one step, under the conditions used in this study. Binding of the third strand appears to enhance the thermal stability of the duplex by 1-3 C, depending on the DNA concentration. This marked enhancement in stability, coupled with the lack of an acidic pH requirement, suggests that pur-pur-pyr triplexes are appealing choices for use in applications involving oligonucleotide targeting of duplex DNA in vitro and in vivo

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 301 (FGE.301): A sulphur substituted pyrimidin-derivative and its hydrochloride salt

DEFF Research Database (Denmark)

Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate two flavouring substances, 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one [FL-no: 16.116] and 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H...... on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that the two substances [FL-no: 16.116 and 16.120] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis...

Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes

DEFF Research Database (Denmark)

Ussery, David; Bohlin, J; Hardy, SP

2009-01-01

BACKGROUND: The genomic fractions of purine (RR) and alternating pyrimidine/purine (YR) stretches of 10 base pairs or more, have been linked to genomic AT content, the formation of different DNA helices, strand-biased gene distribution, DNA structure, and more. Although some of these factors are ...... phyla. RR stretches are overrepresented in all phyla except for the Actinobacteria and beta-Proteobacteria. In contrast, YR tracts are underrepresented in all phyla except for the beta-Proteobacterial group. YR-stretches are associated with phylum, pathogenicity and habitat, whilst RR...

One-Pot Synthesis of Some New Pyrido[2,3-d]pyrimidine Derivatives Catalyzed by Sodium Lauryl Sulfate in Aqueous Media

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Sheng-Hui Li

2010-01-01

Full Text Available A series of pyrido[2,3-d]pyrimidine derivatives were synthesized by the three-component reaction of aromatic aldehyde, malononitrile and 6-amino-4-hydroxy-2-mercaptopyrimidine catalyzed by sodium lauryl sulfate (SDS in aqueous media. It was interesting that further aromatization took place automatically. This method provides several advantages such as easier work-up, milder reaction conditions and environmental friendly.

Partial differential equations

CERN Document Server

Evans, Lawrence C

2010-01-01

This text gives a comprehensive survey of modern techniques in the theoretical study of partial differential equations (PDEs) with particular emphasis on nonlinear equations. The exposition is divided into three parts: representation formulas for solutions; theory for linear partial differential equations; and theory for nonlinear partial differential equations. Included are complete treatments of the method of characteristics; energy methods within Sobolev spaces; regularity for second-order elliptic, parabolic, and hyperbolic equations; maximum principles; the multidimensional calculus of variations; viscosity solutions of Hamilton-Jacobi equations; shock waves and entropy criteria for conservation laws; and, much more.The author summarizes the relevant mathematics required to understand current research in PDEs, especially nonlinear PDEs. While he has reworked and simplified much of the classical theory (particularly the method of characteristics), he primarily emphasizes the modern interplay between funct...

Selective inhibition by methoxyamine of the apurinic/apyrimidinic endonuclease activity associated with pyrimidine dimer-DNA glycosylases from Micrococcus luteus and bacteriophage T4

International Nuclear Information System (INIS)

Liuzzi, M.; Weinfeld, M.; Paterson, M.C.

1987-01-01

The UV endonucleases from Micrococcus luteus and bacteriophage T4 possess two catalytic activities specific for the site of cyclobutane pyrimidine dimers in UV-irradiated DNA: a DNA glycosylase that cleaves the 5'-glycosyl bond of the dimerized pyrimidines and an apurinic/apyrimidinic (AP) endonuclease that thereupon incises the phosphodiester bond 3' to the resulting apyrimidinic site. The authors have explored the potential use of methoxyamine, a chemical that reacts at neutral pH with AP sites in DNA, as a selective inhibitor of the AP endonuclease activities residing in the M. luteus and T4 enzymes. The presence of 50 mM methoxyamine during incubation of UV-treated, [ 3 H]thymine-labeled poly(dA) x poly(dT) with either enzyme preparation was found to protect completely the irradiated copolymer from endonucleolytic attack at dimer sites, as assayed by yield of acid-soluble radioactivity. In contrast, the dimer-DNA glycosylase activity of each enzyme remained fully functional, as monitored retrospectively by release of free thymine after either photochemical-(5 kJ/m 2 , 254 nm) or photoenzymic- (Escherichia coli photolyase plus visible light) induced reversal of pyrimidine dimers in the UV-damaged substrate. The data demonstrate that the inhibition of the strand-incision reaction arises because of chemical modification of the AP sites and is not due to inactivation of the enzyme by methoxyamine. The results, combined with earlier findings for 5'-acting AP endonucleases, strongly suggest that methoxyamine is a highly specific inhibitor of virtually all AP endonucleases, irrespective of their modes of action, and may therefore prove useful in a wide variety of DNA repair studies

Heterocycles X V- one pot synthesis of indenyl pyrimidine- 2 - ones

International Nuclear Information System (INIS)

EL-Rayyes, R. N.

1997-01-01

Condensation of 1- indanone, aryl aldehydes (Ia-k) and urea revealed the formation of the corresponding dihydropyrimidinones (I Ia - k). these were acetaldeyde and brominated to give compounds (III) and (IV) respective l. Dehydrogenation of (II) gave the corresponding pyrimuidunones (V). The structures of the products (II - V) were substantiated by chemical and spectral methods. In a previous work, 1- indanone was reacted with guanidine to produce 2- amino - isopropylenediamine (1) . On the other hand, indenyl pyrimidine - 2- ones were previously prepared through a multi - step synthesis (2,3). The present investigation describes a one - pot synthesis of some new dihydropyrimidinones (I Ia - K). Thus 1- indanone and urea were condensed with aryl aldehydes (Ia - K) to produce the corresponding 4- aryl - 3,4- dihydro - 5 [H] - indenyl (1,2 -e) py rimidin - 2 (I H) ones (I Ia - K) (2,3). The structure of these products was substantiated by chemical and spectral methods as well as elemental analysis.(author). 11 refs., 3 table

Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives.

Science.gov (United States)

Sahin, Zafer; Ertas, Merve; Berk, Barkın; Biltekin, Sevde Nur; Yurttas, Leyla; Demirayak, Seref

2018-05-01

Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC 50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC 50 :0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site. Copyright © 2018 Elsevier Ltd. All rights reserved.

Xeroderma pigmentosum complementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes

International Nuclear Information System (INIS)

Venema, J.; van Hoffen, A.; Karcagi, V.; Natarajan, A.T.; van Zeeland, A.A.; Mullenders, L.H.

1991-01-01

The authors have measured the removal of UV-induced pyrimidine dimers from DNA fragments of the adenosine deaminase (ADA) and dihydrofolate reductase (DHFR) genes in primary normal human and xeroderma pigmentosum complementation group C (XP-C) cells. Using strand-specific probes, we show that in normal cells, preferential repair of the 5' part of the ADA gene is due to the rapid and efficient repair of the transcribed strand. Within 8 h after irradiation with UV at 10 J m-2, 70% of the pyrimidine dimers in this strand are removed. The nontranscribed strand is repaired at a much slower rate, with 30% dimers removed after 8 h. Repair of the transcribed strand in XP-C cells occurs at a rate indistinguishable from that in normal cells, but the nontranscribed strand is not repaired significantly in these cells. Similar results were obtained for the DHFR gene. In the 3' part of the ADA gene, however, both normal and XP-C cells perform fast and efficient repair of either strand, which is likely to be caused by the presence of transcription units on both strands. The factor defective in XP-C cells is apparently involved in the processing of DNA damage in inactive parts of the genome, including nontranscribed strands of active genes. These findings have important implications for the understanding of the mechanism of UV-induced excision repair and mutagenesis in mammalian cells

A Novel and Efficient Five-Component Synthesis of Pyrazole Based Pyrido[2,3-d]pyrimidine-diones in Water: A Triply Green Synthesis

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Majid M. Heravi

2016-04-01

Full Text Available A novel one pot synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine-diones, via a five-component reaction, involving, hydrazine hydrate, ethyl acetoacetate, and 1,3-dimethyl barbituric acid, an appropriate aryl aldehydes and ammonium acetate catalyzed via both of heterogeneous and homogeneous catalysis in water, is reported.

Synthesis of Pyrrolo[1,2-a]pyrimidine Enantiomers via Domino Ring-Closure followed by Retro Diels-Alder Protocol

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Beáta Fekete

2017-04-01

Full Text Available From 2-aminonorbornene hydroxamic acids, a simple and efficient method for the preparation of pyrrolo[1,2-a]pyrimidine enantiomers is reported. The synthesis is based on domino ring-closure followed by microwave-induced retro Diels-Alder (RDA protocols, where the chirality of the desired products is transferred from norbornene derivatives. The stereochemistry of the synthesized compounds was proven by X-ray crystallography. The absolute configuration of the product is determined by the configuration of the starting amino hydroxamic acid.

Synthesis of Pyrrolo[1,2-a]pyrimidine Enantiomers via Domino Ring-Closure followed by Retro Diels-Alder Protocol.

Science.gov (United States)

Fekete, Beáta; Palkó, Márta; Haukka, Matti; Fülöp, Ferenc

2017-04-13

From 2-aminonorbornene hydroxamic acids, a simple and efficient method for the preparation of pyrrolo[1,2- a ]pyrimidine enantiomers is reported. The synthesis is based on domino ring-closure followed by microwave-induced retro Diels-Alder (RDA) protocols, where the chirality of the desired products is transferred from norbornene derivatives. The stereochemistry of the synthesized compounds was proven by X-ray crystallography. The absolute configuration of the product is determined by the configuration of the starting amino hydroxamic acid.

NSAI activity study of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

Science.gov (United States)

Darias, V; Abdallah, S S; Tello, M L; Delgado, L D; Vega, S

1994-12-01

A series of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives endowed with anti-inflammatory and related pharmacological properties were submitted to a more extensive study to know their exact pharmacological profile and their possible side effects. The studied compounds possess a remarkable analgesic activity, devoid of central effects. They also show an interesting anti-inflammatory profile evidenced by their effectiveness in different experimental models of inflammation. In addition, these compounds exhibit none or very little activity on CNS, scarce toxicity and low gastrointestinal aggressivity.

Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

DEFF Research Database (Denmark)

Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo

2007-01-01

The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate...

On Degenerate Partial Differential Equations

OpenAIRE

Chen, Gui-Qiang G.

2010-01-01

Some of recent developments, including recent results, ideas, techniques, and approaches, in the study of degenerate partial differential equations are surveyed and analyzed. Several examples of nonlinear degenerate, even mixed, partial differential equations, are presented, which arise naturally in some longstanding, fundamental problems in fluid mechanics and differential geometry. The solution to these fundamental problems greatly requires a deep understanding of nonlinear degenerate parti...

Quantum Mechanical Scoring: Structural and Energetic Insights into Cyclin-Dependent Kinase 2 Inhibition by Pyrazolo[1,5-a]pyrimidines

Czech Academy of Sciences Publication Activity Database

Brahmkshatriya, Pathik; Dobeš, P.; Fanfrlík, Jindřich; Řezáč, Jan; Paruch, K.; Bronowska, A.; Lepšík, Martin; Hobza, Pavel

2013-01-01

Roč. 9, č. 1 (2013), s. 118-129 ISSN 1573-4099 R&D Projects: GA ČR GBP208/12/G016 Grant - others:Operational Program Research and Development for Innovations(XE) CZ.1.05/2.1.00/03.0058 Institutional support: RVO:61388963 Keywords : binding affinity * cyclin-dependent kinase 2 * QM/SQM/MM * PM6 * pyrazolo[1,5-a]pyrimidine * semiempirical quantum mechanics * scoring function Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.942, year: 2013

4-Aminoquinoline-pyrimidine hybrids: synthesis, antimalarial activity, heme binding and docking studies.

Science.gov (United States)

Kumar, Deepak; Khan, Shabana I; Tekwani, Babu L; Ponnan, Prija; Rawat, Diwan S

2015-01-07

A series of novel 4-aminoquinoline-pyrimidine hybrids has been synthesized and evaluated for their antimalarial activity. Several compounds showed promising in vitro antimalarial activity against both CQ-sensitive and CQ-resistant strains with high selectivity index. All the compounds were found to be non-toxic to the mammalian cell lines. Selected compound 7g exhibited significant suppression of parasitemia in the in vivo assay. The heme binding studies were conducted to determine the mode of action of these hybrid molecules. These compounds form a stable 1:1 complex with hematin suggesting that heme may be one of the possible targets of these hybrids. The interaction of these conjugate hybrids was also investigated by the molecular docking studies in the binding site of PfDHFR. The pharmacokinetic property analysis of best active compounds was also studied using ADMET prediction. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

(15)N NMR spectroscopy unambiguously establishes the coordination mode of the diimine linker 2-(2'-pyridyl)pyrimidine-4-carboxylic acid (cppH) in Ru(ii) complexes.

Science.gov (United States)

Battistin, Federica; Balducci, Gabriele; Demitri, Nicola; Iengo, Elisabetta; Milani, Barbara; Alessio, Enzo

2015-09-21

We investigated the reactivity of three Ru(ii) precursors -trans,cis,cis-[RuCl2(CO)2(dmso-O)2], cis,fac-[RuCl2(dmso-O)(dmso-S)3], and trans-[RuCl2(dmso-S)4] - towards the diimine linker 2-(2'-pyridyl)pyrimidine-4-carboxylic acid (cppH) or its parent compound 4-methyl-2-(2'-pyridyl)pyrimidine ligand (mpp), in which a methyl group replaces the carboxylic group on the pyrimidine ring. In principle, both cppH and mpp can originate linkage isomers, depending on how the pyrimidine ring binds to ruthenium through the nitrogen atom ortho (N(o)) or para (N(p)) to the group in position 4. The principal aim of this work was to establish a spectroscopic fingerprint for distinguishing the coordination mode of cppH/mpp also in the absence of an X-ray structural characterization. By virtue of the new complexes described here, together with the others previously reported by us, we successfully recorded {(1)H,(15)N}-HMBC NMR spectra at natural abundance of the (15)N isotope on a consistent number of fully characterized Ru(ii)-cppH/mpp compounds, most of them being stereoisomers and/or linkage isomers. Thus, we found that (15)N NMR chemical shifts unambiguously establish the binding mode of cppH and mpp - either through N(o) or N(p)- and can be conveniently applied also in the absence of the X-ray structure. In fact, coordination of cppH to Ru(ii) induces a marked upfield shift for the resonance of the N atoms directly bound to the metal, with coordination induced shifts (CIS) ranging from ca.-45 to -75 ppm, depending on the complex, whereas the unbound N atom resonates at a frequency similar to that of the free ligand. Similar results were found for the complexes of mpp. This work confirmed our previous finding that cppH has no binding preference, whereas mpp binds exclusively through N(p). Interestingly, the two cppH linkage isomers trans,cis-[RuCl2(CO)2(cppH-κN(p))] (5) and trans,cis-[RuCl2(CO)2(cppH-κN(o))] (6) were easily obtained in pure form by exploiting their different

Mechanochemical Solvent-Free and Catalyst-Free One-Pot Synthesis of Pyrano[2,3-d]Pyrimidine-2,4(1H,3H-Diones with Quantitative Yields

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M. Reza Naimi-Jamal

2009-01-01

Full Text Available Solvent-free synthesis of pyrano[2,3-d]pyrimidine-2,4(1H,3H-diones by ball-milling and without any catalyst is described. This method provides several advantages such as being environmentally friendly, using a simple workup procedure, and affording high yields.

Hardware requirements: A new generation partial reflection radar for studies of the equatorial mesosphere

Science.gov (United States)

Vincent, R. A.

1986-01-01

A new partial reflection (PR) radar is being developed for operation at the proposed Equatorial Observatory. The system is being designed to make maximum use of recent advances in solid-state technology in order to minimize the power requirements. In particular, it is planned to use a solid-state transmitter in place of the tube transmitters previously used in PR systems. Solid-state transmitters have the advantages that they do not need high voltage supplies, they do not require cathode heaters with a corresponding saving in power consumption and parts are readily available and inexpensive. It should be possible to achieve 15 kW peak powers with recently announced fast switching transistors. Since high mean powers are desirable for obtaining good signal-to-noise ratios, it is also planned to phase code the transmitted pulses and decode after coherent integration. All decoding and signal processing will be carried out in dedicated microprocessors before the signals are passed to a microcomputer for on-line analysis. Recent tests have shown that an Olivetti M24 micro (an IBM compatible) running an 8-MHz clock with a 8087 coprocessor can analyze data at least as fast as the minicomputers presently being used with the Adelaide PR rad ar and at a significantly lower cost. The processed winds data will be stored in nonvolatile CMOS RAM modules; about 0.5 to 1 Mbyte is required to store one week's information.

An irresolute linker: separation, and structural and spectroscopic characterization of the two linkage isomers of a Ru(ii)-(2-(2'-pyridyl)pyrimidine-4-carboxylic acid) complex.

Science.gov (United States)

Iengo, E; Demitri, N; Balducci, G; Alessio, E

2014-08-28

For the first time the two linkage isomers of a Ru(ii) complex with 2-(2'-pyridyl)pyrimidine-4-carboxylic acid (cppH) - that form in comparable amounts - have been fully characterized individually. The X-ray structure of each isomer is related to its NMR spectrum in solution.

Synthesis of Fluorescent 2-Substituted 6-(Het)aryl-7-deazapurine Bases {4-(Het)aryl-pyrrolo[2,3-d]pyrimidines} by Aqueous Suzuki-Miyaura Cross-Coupling Reactions

Czech Academy of Sciences Publication Activity Database

Sabat, Nazarii; Nauš, Petr; Matyašovský, Ján; Dziuba, Dmytro; Poštová Slavětínská, Lenka; Hocek, Michal

2016-01-01

Roč. 48, č. 7 (2016), s. 1029-1045 ISSN 0039-7881 R&D Projects: GA ČR GAP207/11/0344 Institutional support: RVO:61388963 Keywords : nucleobases * deazapurines * pyrrolo[2,3-d]pyrimidines * Suzuki cross - coupling * arylation Subject RIV: CC - Organic Chemistry Impact factor: 2.650, year: 2016

The relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and photoproducts in Escherichia coli cells

International Nuclear Information System (INIS)

Tang, Moon-shong; Hrncir, J.; Mitchell, D.; Ross, J.; Clarkson, J.

1986-01-01

In order to calculate the relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and photoproducts, the authors have measured survival and mutation induction in UV-irradiated excision-deficient E. coli uvrA cells, with or without complete photoreactivation of the dimers. Radioimmunoassays with specificity for dimers or photoproducts have shown that maximum photoreactivation eliminates all of the dimers produce up to 10 Jm -2 254-nm light, while it has no effect on photoproducts. These results were confirmed by measuring the frequency of T4 endonuclease V-sensitive sites. Based on the best fit equations for survival and mutation induction, the authors have found that the calculated cytotoxicity of photoproducts is similar to that of dimers; however, the former is much more mutagenic than the latter. (Auth.)

Replication of UV-irradiated DNA in human cell extracts: Evidence for mutagenic bypass of pyrimidine dimers

International Nuclear Information System (INIS)

Thomas, D.C.; Kunkel, T.A.

1993-01-01

The authors have examined the efficiency and fidelity of simian virus 40-origin-dependent replication of UV-irradiated double-stranded DNA in extracts of human cells. Using as a mutational target the α-complementation domain of the Escherichia coli lacZ gene in bacteriophage M13mp2DNA, replication of undamaged DNA in HeLa cell extracts was highly accurate, whereas replication of DNA irradiated with UV light (280-320 nm) was both less efficient and less accurate. Replication was inhibited by irradiation in a dose-dependent manner. Nonetheless, covalently closed, monomer-length circular products were generated that were resistant to digestion by Dpn I, showing that they resulted from semiconservative replication. These products were incised by T4 endonuclease V, whereas the undamaged replication products were not, suggesting that pyrimidine dimers were bypassed during replication. When replicated, UV-irradiated DNA was used to transfect an E. coli α-complementation host strain to score mutant M13mp2 plaques, the mutant plaque frequency was substantially higher than that obtained with either unirradiated, replicated DNA, or unreplicated, UV-irradiated DNA. Both the increased mutagenicity and the inhibition of replication associated with UV irradiation were reversed by treatment of the irradiated DNA with photolyase before replication. Sequence analysis of mutants resulting from replication of UV-irradiated DNA demonstrated that most mutants contained C → T transition errors at dipyrimidine sites. A few mutants contained 1-nt frameshift errors or tandem double CC → TT substitutions. The data are consistent with the interpretation that pyrimidine dimers are bypassed during replication by the multiprotein replication apparatus in human cell extracts and that this bypass is mutagenic primarily via misincorporation of dAMP opposite a cytosine (or uracil) in the dimer. 56 refs., 2 figs., 3 tabs

Photoreactivation of pyrimidine dimers in the DNA of normal and xeroderma pigmentosum cells

International Nuclear Information System (INIS)

Sutherland, B.M.; Oliver, R.; Fuselier, C.O.; Sutherland, J.C.

1976-01-01

Photoproducts formed in the DNA of human cells irradiated with ultraviolet light (uv) were identified as cyclobutyl pyrimidine dimers by their chromatographic mobility, reversibility to monomers upon short wavelength uv irradiation, and comparison of the kinetics of this monomerization with that of authentic cis--syn thymine--thymine dimers prepared by irradiation of thymine in ice. The level of cellular photoreactivation of these dimers reflects the level of photoreactivating enzyme measured in cell extracts. Action spectra for cellular dimer photoreactivation in the xeroderma pigmentosum line XP12BE agree in range (300 nm to at least 577 nm) and maximum (near 400 nm) with that for photoreactivation by purified human photoreactivating enzyme. Normal human cells can also photoreactivate dimers in their DNA. The action spectrum for the cellular monomerization of dimers is similar to that for photoreactivation by the photoreactivating enzyme in extracts of normal human fibroblasts

Differences in substrate specificity of C(5)-substituted or C(5)-unsubstituted pyrimidine nucleotides by DNA polymerases from thermophilic bacteria, archaea, and phages.

Science.gov (United States)

Sawai, Hiroaki; Nagashima, Junichi; Kuwahara, Msayasu; Kitagata, Rina; Tamura, Takehiro; Matsui, Ikuo

2007-09-01

The pyrimidine bases of RNA are uracil (U) and cytosine (C), while thymine (T) and C are used for DNA. The C(5) position of C and U is unsubstituted, whereas the C(5) of T is substituted with a Me group. Miller et al. hypothesized that various C(5)-substituted uracil derivatives were formed during chemical evolution, and that C(5)-substituted U derivatives may have played important roles in the transition from an 'RNA world' to a 'DNA-RNA-protein world'. Hyperthermophilic bacteria and archaea are considered to be primitive organisms that are evolutionarily close to the universal ancestor of all life on earth. Thus, we examined the substrate specificity of several C(5)-substituted or C(5)-unsubstituted dUTP and dCTP analogs for several DNA polymerases from hyperthermophilic bacteria, hyperthermophilic archaea, and viruses during PCR or primer extension reaction. The substrate specificity of the C(5)-substituted or C(5)-unsubstituted pyrimidine nucleotides varied greatly depending on the type of DNA polymerase. The significance of this difference in substrate specificity in terms of the origin and evolution of the DNA replication system is discussed briefly.

Crystal structure of a mixed-ligand silver(I complex of the non-steroidal anti-inflammatory drug diclofenac and pyrimidine

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Sevim Hamamci Alisir

2016-10-01

Full Text Available In the title mixed-ligand silver(I coordination polymeric complex with the non-steroidal anti-inflammatory drug diclofenac (C14H11Cl2NO2 (diclH and pyrimidine (pym, namely poly[{μ2-2-[2-(2,6-dichloroanilinophenyl]acetato-κ2O:O′}(μ2-pyrimidine-κ2N1:N3silver(I], [Ag(C14H10Cl2NO2(C4H4N2]n or [Ag(μ-dicl(μ-pym]n, the very distorted tetrahedral AgN2O2 coordination centres comprise two N-atom donors from bridging pym ligands [Ag—N = 2.381 (3 and 2.412 (3 Å] and two carboxylate O-atom donors from dicl ligands [Ag—O = 2.279 (2 and 2.280 (2 Å], which bridge Ag atoms, giving a centrosymmetric dinuclear units with a short Ag...Ag separation [2.8931 (5 Å]. Within the units are short intraligand C—Cl...π(pym interactions [3.6409 (15 Å]. The units are linked through the bridging N atoms of the pym ligand into a two-dimensional sheet–polymer structure lying parallel to (100 and stabilized by inter-ring π–π interactions between the pym ligands [Cg...Cg = 3.4199 (17 Å]. Additional inter-unit C—H...O and C—H...Cg hydrogen-bonding interactions between the sheets give an overall three-dimensional structure.

Antioxidant, DNA interaction, VEGFR2 kinase, topoisomerase I and in vitro cytotoxic activities of heteroleptic copper(II) complexes of tetrazolo[1,5-a]pyrimidines and diimines

Energy Technology Data Exchange (ETDEWEB)

Haleel, A.; Mahendiran, D. [Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai 600 014 (India); Veena, V.; Sakthivel, N. [Department of Biotechnology, Pondicherry University, Pondicherry 605 014 (India); Rahiman, A. Kalilur, E-mail: akrahmanjkr@gmail.com [Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai 600 014 (India)

2016-11-01

A series of heteroleptic mononuclear copper(II) complexes of the type [Cu(L{sup 1–3})(diimine)]ClO{sub 4} (1–6) containing three tetrazolo[1,5-a]pyrimidine core ligands, ethyl 5-methyl-7-(2-hydroxyphenyl)-4,7-dihydrotetrazolo[1,5-a] pyrimidine-6-carboxylate (HL{sup 1}), ethyl 5-methyl-7-(4-diethylamino-2-hydroxyphenyl)-4,7-dihydrotetrazolo[1,5-a] pyrimidine-6-carboxylate (HL{sup 2}) or ethyl 5-methyl-7-(2-hydroxy-4-nitrophenyl)-4,7-dihydrotetrazolo[1,5-a] pyrimidine-6-carboxylate (HL{sup 3}), and two diimine coligands, 2,2′-bipyridyl (bpy) or 1,10-phenanthroline (phen) have been synthesized and characterized by spectral methods. The geometry of complexes have been determined with the help of electronic absorption and EPR splitting patterns, which suggest four coordinated square planar geometry around copper(II) ion. The lowering of HOMO–LUMO band gap value of complex 4 implies its higher biological activity compared to other complexes. Antioxidant studies revealed that the complexes possess considerable radical scavenging potency against DPPH. The binding studies of the complexes with calf thymus DNA (CT–DNA) revealed groove mode of binding, which was further supported by docking simulation. The complexes 3 and 4 strongly inhibit the topoisomerase I, and also strongly interact with VEGFR2 kinase receptor via π–π, σ–π and hydrogen bonding interaction. Gel electrophoresis experiments demonstrated the ability of the complexes to cleave plasmid DNA in the absence of activators. In vitro cytotoxic activities of the complexes were examined on three cancerous cell lines such as human lung (A549), cervical (HeLa) and colon (HCT-15), and two normal cells such as human embryonic kidney (HEK) and peripheral blood mononuclear cells (PBMCs). The live cell and fluorescent imaging of cancer cells were observed with acridine orange/ethidium bromide staining assay. All encouraging chemical and biological findings indicate that the complex 4 is a suitable candidate

Micrococcus luteus correndonucleases. II. Mechanism of action of two endonucleases specific for DNA containing pyrimidine dimers

International Nuclear Information System (INIS)

Riazuddin, S.; Grossman, L.

1977-01-01

Py--Py correndonucleases I and II from Micrococcus luteus act exclusively on thymine-thymine, cytosine-cytosine, and thymine-cytosine cyclobutyl dimers in DNA, catalyzing incision 5' to the damage and generating 3'-hydroxyl and 5'-phosphoryl termini. Both enzymes initiate excision of pyrimidine dimers in vitro by correxonucleases and DNA polymerase I. The respective incised DNAs, however, differ in their ability to act as substrate for phage T4 polynucleotide ligase or bacterial alkaline phosphatase, suggesting that each endonuclease is specific for a conformationally unique site. The possibility that their respective action generates termini which represent different degrees of single strandedness is suggested by the unequal protection by Escherichia coli binding protein from the hydrolytic action of exonuclease VII

40 CFR Table 7 to Subpart Vvvvvv... - Partially Soluble HAP

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 14 2010-07-01 2010-07-01 false Partially Soluble HAP 7 Table 7 to... Pt. 63, Subpt. VVVVVV, Table 7 Table 7 to Subpart VVVVVV of Part 63—Partially Soluble HAP As required... partially soluble HAP listed in the following table. Partially soluble HAP name CAS No. 1. 1,1,1...

High-resolution pyrimidine- and ribose-specific 4D HCCH-COSY spectra of RNA using the filter diagonalization method

International Nuclear Information System (INIS)

Douglas, Justin T.; Latham, Michael P.; Armstrong, Geoffrey S.; Bendiak, Brad; Pardi, Arthur

2008-01-01

The NMR spectra of nucleic acids suffer from severe peak overlap, which complicates resonance assignments. 4D NMR experiments can overcome much of the degeneracy in 2D and 3D spectra; however, the linear increase in acquisition time with each new dimension makes it impractical to acquire high-resolution 4D spectra using standard Fourier transform (FT) techniques. The filter diagonalization method (FDM) is a numerically efficient algorithm that fits the entire multi-dimensional time-domain data to a set of multi-dimensional oscillators. Selective 4D constant-time HCCH-COSY experiments that correlate the H5-C5-C6-H6 base spin systems of pyrimidines or the H1'-C1'-C2'-H2' spin systems of ribose sugars were acquired on the 13 C-labeled iron responsive element (IRE) RNA. FDM-processing of these 4D experiments recorded with only 8 complex points in the indirect dimensions showed superior spectral resolution than FT-processed spectra. Practical aspects of obtaining optimal FDM-processed spectra are discussed. The results here demonstrate that FDM-processing can be used to obtain high-resolution 4D spectra on a medium sized RNA in a fraction of the acquisition time normally required for high-resolution, high-dimensional spectra

Absence of photoreactivation of pyrimidine dimers in the epidermis of hairless mice following exposures to ultraviolet light

Energy Technology Data Exchange (ETDEWEB)

Ley, R D; Sedita, B A; Grube, D D

1978-01-01

The influence of photoreactivating light on the fate of uv-induced DNA damage has been measured in the epidermis of hairless mice using damage-specific endonuclease from Micrococcus luteus. Groups of mice were exposed to varying fluences of uv at 297 nm or from an FS40 fluorescent sun lamp to induce uv photoproducts. The same fluence-dependent DNA damage was observed in high molecular weight epidermal DNA regardless of whether the mice were killed immediately, or maintained in the dark or under photorectivating light for 20 h after uv. Thus, no detectable photoreactivation of uv-induced pyrimidine dimers could be demonstrated in mouse epithelial cells in vivo.

Semantics and correctness proofs for programs with partial functions

International Nuclear Information System (INIS)

Yakhnis, A.; Yakhnis, V.

1996-01-01

This paper presents a portion of the work on specification, design, and implementation of safety-critical systems such as reactor control systems. A natural approach to this problem, once all the requirements are captured, would be to state the requirements formally and then either to prove (preferably via automated tools) that the system conforms to spec (program verification), or to try to simultaneously generate the system and a mathematical proof that the requirements are being met (program derivation). An obstacle to this is frequent presence of partially defined operations within the software and its specifications. Indeed, the usual proofs via first order logic presuppose everywhere defined operations. Recognizing this problem, David Gries, in ''The Science of Programming,'' 1981, introduced the concept of partial functions into the mainstream of program correctness and gave hints how his treatment of partial functions could be formalized. Still, however, existing theorem provers and software verifiers have difficulties in checking software with partial functions, because of absence of uniform first order treatment of partial functions within classical 2-valued logic. Several rigorous mechanisms that took partiality into account were introduced [Wirsing 1990, Breu 1991, VDM 1986, 1990, etc.]. However, they either did not discuss correctness proofs or departed from first order logic. To fill this gap, the authors provide a semantics for software correctness proofs with partial functions within classical 2-valued 1st order logic. They formalize the Gries treatment of partial functions and also cover computations of functions whose argument lists may be only partially available. An example is nuclear reactor control relying on sensors which may fail to deliver sense data. This approach is sufficiently general to cover correctness proofs in various implementation languages

Synthesis of 2-[4-(10H-Substituted Phenothiazine-3-yl-6-Pyrimidin-2-Phenylthiol/ol/amine/thiol] Pyrroles

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Meghasham Narule

2007-01-01

Full Text Available 2-[4-Hydroxy benz-1(propene-1-one]Pyrrole II on treatment with phenyl thiourea, guanidine carbonate, urea and thiourea in alcoholic KOH yielded compounds III, IV, V, VI which on treatment with different aryl anilines gave compounds VII, VIII, IX, X which under goes cyclisation with sulphur and iodine to give 2-[4-(10H-substituted phenothiazine-3-yl-6-pyrimidin-2-phenylthiol/-ol/-amine/-thiol] pyrrole XI(a-j, XII(a-j, XIII(a-j and XIV(a-j respectively. The structural products were characterized by elemental analysis and spectral data.

Design and synthesis of potent, orally-active DGAT-1 inhibitors containing a dioxino[2,3-d]pyrimidine core.

Science.gov (United States)

Dow, Robert L; Andrews, Melissa; Aspnes, Gary E; Balan, Gayatri; Michael Gibbs, E; Guzman-Perez, Angel; Karki, Kapil; Laperle, Jennifer L; Li, Jian-Cheng; Litchfield, John; Munchhof, Michael J; Perreault, Christian; Patel, Leena

2011-10-15

A novel series of potent DGAT-1 inhibitors was developed originating from the lactam-based clinical candidate PF-04620110. Incorporation of a dioxino[2,3-d]pyrimidine-based core afforded good alignment of pharmacophore features and resulted in improved passive permeability. Development of an efficient, homochiral synthesis of these targets facilitated confirmation of predictions regarding the stereochemical-dependence of DGAT-1 inhibition for this series. Compound 10 was shown to be a potent inhibitor of human DGAT-1 (10 nM) and to suppress triglyceride synthesis at oral doses of <3mg/kg. Copyright © 2011 Elsevier Ltd. All rights reserved.

Partial dynamical systems, fell bundles and applications

CERN Document Server

Exel, Ruy

2017-01-01

Partial dynamical systems, originally developed as a tool to study algebras of operators in Hilbert spaces, has recently become an important branch of algebra. Its most powerful results allow for understanding structural properties of algebras, both in the purely algebraic and in the C*-contexts, in terms of the dynamical properties of certain systems which are often hiding behind algebraic structures. The first indication that the study of an algebra using partial dynamical systems may be helpful is the presence of a grading. While the usual theory of graded algebras often requires gradings to be saturated, the theory of partial dynamical systems is especially well suited to treat nonsaturated graded algebras which are in fact the source of the notion of "partiality". One of the main results of the book states that every graded algebra satisfying suitable conditions may be reconstructed from a partial dynamical system via a process called the partial crossed product. Running in parallel with partial dynamica...

A new Ni(II complex as a novel and efficient recyclable catalyst for the synthesis of pyrano[2,3-d]pyrimidines

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M. Habibi Kheirabadi

2016-12-01

Full Text Available A simple and highly efficient one-pot three-component synthesis of a series of pyrido[2,3-d]pyrimidines from the condensation of barbituric acid, malononitrile and aromatic aldehydes using catalytic amount of a new Ni(II complex based on 5-nitro-N1-((pyridin-2-ylmethylene benzene-1,2-diamine (NiL is reported. This new heterogeneous catalyst has the advantages of being environmentally friendly, simple work-up and high yields character.

Memory retrieval in response to partial cues requires NMDA receptor-dependent neurotransmission in the medial prefrontal cortex.

Science.gov (United States)

Jo, Yong Sang; Choi, June-Seek

2014-03-01

The medial prefrontal cortex (mPFC) has been suggested to play a crucial role in retrieving detailed contextual information about a previous learning episode in response to a single retrieval cue. However, few studies investigated the neurochemical mechanisms that mediate the prefrontal retrieval process. In the current study, we examined whether N-methyl-D-aspartate receptors (NMDARs) in the mPFC were necessary for retrieval of a well-learned spatial location on the basis of partial or degraded spatial cues. Rats were initially trained to find a hidden platform in the Morris water maze using four extramaze cues in the surrounding environment. Their retrieval performance was subsequently tested under different cue conditions. Infusions of DL-2-amino-5-phosphonovaleric acid (APV), a NMDAR antagonist, significantly disrupted memory retrieval when three of the original cues were removed. By contrast, APV injections into the mPFC did not affect animals' retrieval performance when the original cues were presented or when three novels landmarks were added alongside the original cues. These results indicate that prefrontal NMDARs are required for memory retrieval when allocentric spatial information is degraded. NMDAR-dependent neurotransmission in the mPFC may facilitate an active retrieval process to reactivate complete contextual representations associated with partial retrieval cues. Copyright © 2013 Elsevier Inc. All rights reserved.

Repair of pyrimidine dimers in radiation-sensitive mutants rad3, rad4, rad6, and rad9 of Saccharomyces cerevisiae. [nicking

Energy Technology Data Exchange (ETDEWEB)

Prakash, L [Rochester Univ., N.Y. (USA). Dept. of Radiation Biology and Biophysics; Rochester Univ., N.Y. (USA). School of Medicine and Dentistry)

1977-10-01

The ability to remove ultraviolet-induced pyrimidine dimers was examined in four radiation-sensitive mutants of Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by either the T4 uv-endonuclease or an endonuclease activity found in crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad3 and rad4 mutants are shown to be defective in dimer excision whereas the rad6 and rad9 mutants are proficient in dimer excision.

Molecular interaction of the first 3 enzymes of the de novo pyrimidine biosynthetic pathway of Trypanosoma cruzi

International Nuclear Information System (INIS)

Nara, Takeshi; Hashimoto, Muneaki; Hirawake, Hiroko; Liao, Chien-Wei; Fukai, Yoshihisa; Suzuki, Shigeo; Tsubouchi, Akiko; Morales, Jorge; Takamiya, Shinzaburo; Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko; Fan, Chia-Kwung; Inaoka, Daniel Ken; Inoue, Masayuki; Tanaka, Akiko; Harada, Shigeharu; Kita, Kiyoshi

2012-01-01

Highlights: ► An Escherichia coli strain co-expressing CPSII, ATC, and DHO of Trypanosoma cruzi was constructed. ► Molecular interactions between CPSII, ATC, and DHO of T. cruzi were demonstrated. ► CPSII bound with both ATC and DHO. ► ATC bound with both CPSII and DHO. ► A functional tri-enzyme complex might precede the establishment of the fused enzyme. -- Abstract: The first 3 reaction steps of the de novo pyrimidine biosynthetic pathway are catalyzed by carbamoyl-phosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), respectively. In eukaryotes, these enzymes are structurally classified into 2 types: (1) a CPSII-DHO-ATC fusion enzyme (CAD) found in animals, fungi, and amoebozoa, and (2) stand-alone enzymes found in plants and the protist groups. In the present study, we demonstrate direct intermolecular interactions between CPSII, ATC, and DHO of the parasitic protist Trypanosoma cruzi, which is the causative agent of Chagas disease. The 3 enzymes were expressed in a bacterial expression system and their interactions were examined. Immunoprecipitation using an antibody specific for each enzyme coupled with Western blotting-based detection using antibodies for the counterpart enzymes showed co-precipitation of all 3 enzymes. From an evolutionary viewpoint, the formation of a functional tri-enzyme complex may have preceded—and led to—gene fusion to produce the CAD protein. This is the first report to demonstrate the structural basis of these 3 enzymes as a model of CAD. Moreover, in conjunction with the essentiality of de novo pyrimidine biosynthesis in the parasite, our findings provide a rationale for new strategies for developing drugs for Chagas disease, which target the intermolecular interactions of these 3 enzymes.

Synthesis of silylated pyrimidines nucleosides. Catalytic condensations with organo-zinc, organo-zirconium, and organo-borane compounds

International Nuclear Information System (INIS)

Vincent, Patrice

1982-01-01

This research thesis addressed the synthesis of new desoxy-2' uridines substituted in C-5. The starting compound was the iodo-5 0-3',5' bis(trimethylsilyl) dUrd. It has been coupled with acetylenic organo-zinc in presence of organo-palladium and nickel compounds to obtain alkynyl-5 dUrd, with ethylenic organo-zirconium compounds in presence of organo-palladium complexes to obtain (E)-alkenyl-5 dUrd, with ethylenic organo-boranes in presence of organo-palladium complexes to obtain (E) and (Z) alkenyl-5 uRd, and with cyclic or heterocyclic organo-zinc compounds in presence of organo-palladium complexes. Thirty new pyrimidine nucleosides have thus been obtained, and some of them have been used for biological tests [fr

Influence exerted by new pyrimidine derivatives on cerebral circulation auto-regulation and vasodilatating function of vessels endothelium in rats' brains under chronic hemic hypoxia

Directory of Open Access Journals (Sweden)

A.V. Voronkov

2018-03-01

Full Text Available Our research goal was to examine influences exerted by new pyrimidine derivatives coded as BL0 and BL2 on cerebral hemodynamics auto-regulation parameters and vasodilatating function of vessels endothelium as risk factors causing ischemic and hemorrhagic strokes under chronic hemic hypoxia. We performed an experiment on white Wistar rats to prove that endothelial dysfunction which evolves under chronic hemic hypoxia leads to disorders in endothelium-mediated mechanisms for cerebral circulation auto-regulation in rats. We modeled hypoxia in animals via granting them free access to 0.2 % sodium nitrite solution instead of ordinary drinking water. Endothelial dysfunction was confirmed as per disorders in vasodilatation and vasoconstriction reactions at intravenous introduction of acetyl choline (0.1 mg/kg and methyl ether hydrochloride nitro-L-arginine (10 mg/kg. Cerebral blood flow speed was measured with MM-D-K-Minimax v.2.1. ultrasound Doppler. We assessed cerebral circulation auto-regulation as per compression test results which allowed us to calculate overshoot coefficient and auto-regulation power. Examined pyrimidine derivatives and comparison preparations were introduced orally 60 minutes prior to taking readings. Mexidol doses were calculated on the basis of interspecific recalculation of a maximum daily dose for a man. Nicergoline dose was taken as a most effective one as per literature data. When new pyrimidine derivatives BL0 and BL2 are applied under chronic hemic hypoxia, it causes overshoot coefficient to grow authentically higher than in a negative control group but it doesn't exert any positive influence on collateral reserve parameter, namely auto-regulation power. BL0 and BL2 improve endothelium vasodilatating function at intravenous acetylcholine introduction (0.1 mg/kg and don't exert any influence on vasoconstricting function at L-NAME intravenous introduction (10 mg/kg. The examined substance BL0 has more apparent

A novel pyrimidine derivative as a fluorescent chemosensor for highly selective detection of aluminum (III) in aqueous media.

Science.gov (United States)

Suryawanshi, Vishwas D; Gore, Anil H; Dongare, Pravin R; Anbhule, Prashant V; Patil, Shivajirao R; Kolekar, Govind B

2013-10-01

An efficient fluorescent chemosensor Al(3+) receptor based on pyrimidine derivative,2-amino-6-hydroxy-4-(4-N,N-dimethylaminophenyl)-pyrimidine-5-carbonitrile (DMAB), has been synthesized by three-component condensation of aromatic aldehyde, ethyl cyanoacetate and guanidine hydrochloride in ethanol under alkaline medium. High selectivity and sensitivity of DMAB towards Aluminum ion (Al(3+)) in water: ethanol and acetate buffer at pH 4.0 makes it suitable to detect Al(3+) with steady-state UV-vis and fluorescence spectroscopy. Method shows good selectivity towards Al(3+) over other coexisting metal ions tested, viz. Fe(2+), Ni(2+), Cu(2+), Co(2+), Pb(2+), Sb(3+), Na(+), Ca(2+), Mg(2+), Zn(2+), Hg(2+), Ba(2+), Cd(2+) and K(+). A good linearity between the Stern-Volmer plots of F0/F versus concentration of Al(3+) was observed over the range from 10 to 60 μg mL(-1) with correlation coefficient of 0.991. The accuracy and reliability of the method were further confirmed by recovery studies via standard addition method with percent recoveries in the range of 101.03-103.44% and lowest detection limit (LOD=7.35 μg mL(-1)) for Al(3+) was established. This method may offer a new cost-effective, rapid, and simple key to the inspection of Al(3+) ions in water samples in the presence of a complex matrix and can be capable of evaluating the exceeding standard of Al(3+) in environmental water samples. The probable mechanism for fluorescence quenching was also discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Image Reconstruction For Bioluminescence Tomography From Partial Measurement

OpenAIRE

Jiang, M.; Zhou, T.; Cheng, J. T.; Cong, W. X.; Wang, Ge

2007-01-01

The bioluminescence tomography is a novel molecular imaging technology for small animal studies. Known reconstruction methods require the completely measured data on the external surface, although only partially measured data is available in practice. In this work, we formulate a mathematical model for BLT from partial data and generalize our previous results on the solution uniqueness to the partial data case. Then we extend two of our reconstruction methods for BLT to this case. The first m...

Asymmetric Synthesis of Potential Precursors of the HIV Drug MC1220 and Its Analogues by Hydrogenation of (1-Arylvinyl)pyrimidines

DEFF Research Database (Denmark)

Loksha, Yasser M.; Pedersen, Erik B.

2018-01-01

Because MC1220 is a promising microbicide with anti-HIV-1 activity, the possibility for asymmetric synthesis of its potential precursors is explored. Here, we investigate asymmetric reduction of the vinyl double bond of 6-(1-arylvinyl)pyrimidine derivatives to their corresponding ethylidene analo...... analogues. Catalysts with ligands bearing trivalent phosphorus ligating the soft metals rhodium(I), ruthenium(II), or iridium(I) are used for asymmetric reduction of the vinyl derivatives 5a-e. The enantioselective reduction reaches 92% ee and about 71% conversion for reduction of the 6...

Synthesis of 2,6-Substituted 7-(Het)aryl-7-deazapurine Nucleobases (2,4-Disubstituted 5-(Het)aryl-pyrrolo[2,3-d]pyrimidines)

Czech Academy of Sciences Publication Activity Database

Sabat, Nazarii; Smolen, Sabina; Nauš, Petr; Perlíková, Pavla; Cebová, M.; Poštová Slavětínská, Lenka; Hocek, Michal

2017-01-01

Roč. 49, č. 20 (2017), s. 4623-4650 ISSN 0039-7881 R&D Projects: GA ČR(CZ) GA16-00178S; GA MZd(CZ) NV15-31984A Grant - others:AV ČR(CZ) AP1501 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:61388963 Keywords : deazapurines * pyrrolo[2,3-d]pyrimidines * nucleobases * Suzuki-Miyaura cross-coupling * deprotection * demethylation Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.650, year: 2016

[4,6-Dimethyl­pyrimidine-2(1H)-thione-κS]iodidobis(triphenyl­phosphane-κP)copper(I)

Science.gov (United States)

Pakawatchai, Chaveng; Wattanakanjana, Yupa; Choto, Patcharanan; Nimthong, Ruthairat

2012-01-01

In the mononuclear title complex, [CuI(C6H8N2S)(C18H15P)2], the CuI ion is in a slightly distorted tetra­hedral coordination geometry formed by two P atoms from two triphenyl­phosphane ligands, one S atom from a 4,6-dimethyl­pyrimidine-2(1H)-thione ligand and one iodide ion. There is an intra­molecular N—H⋯I hydrogen bond. In the crystal, π–π stacking inter­actions [centroid–centroid distance = 3.594 (1) Å] are observed. PMID:22719327

Photomonomerization of pyrimidine dimers by indoles and proteins

Energy Technology Data Exchange (ETDEWEB)

Chen, J.; Huang, C.W.; Hinman, L.; Gordon, M.P.; Deranleau, D.A.

1976-01-01

Model systems for the study of photoreactivation have been developed that utilize a variety of indole derivatives. These systems can split uracil cis-syn cyclobutadipyrimidine, either free or in RNA, when irradiated at wavelengths absorbed only by the indole moiety. The ability of indole compounds to split dimers is closely related to their electronic properties. Those of high electron-donor capacity such as indole, 3-methylindole, indole-3-acetic acid, 5-hydroxytryptophan and tryptophan are good photosensitizers, with efficacy in that order. Indoles with electron-withdrawing substituents such as indole-3-carboxylic acid, indole-3-aldehyde and oxindole are inactive in the monomerization reaction. These findings support the proposed mechanism that the photosensitized monomerization occurs as a result of electron transfer from the excited indole molecules to the pyrimidine bases. Proteins containing fully exposed tryptophan residues (chicken egg white lysozyme and bovine diisopropylphosphoryltrypsin) also cause the splitting of the /sup 14/C-labeled dimers under the same conditions. In the case of lysozyme the quantum yield of monomerization is similar to that of free tryptophan. Much of the monomerization ability of lysozyme was lost after the solvent-available tryptophan had been oxidized by treatment with N-bromosuccinimide. Bovine pancreatic ribonuclease A, a protein devoid of tryptophan, failed to exhibit photosensitized monomerization of uracil dimers. The biological implication of these reactions involving a protein with an exposed tryptophan residue is discussed. Although indoles are able to split the dimers in RNA, they fail to photoreactivate uv-damaged TMV-RNA. Indole-3-acetic acid, 3-methylindole and 5-hydroxytryptophan rapidly inactive viral RNA when irradiated at 313 nm, possibly because of side reactions.

Enhanced DNA repair of cyclobutane pyrimidine dimers changes the biological response to UV-B radiation

Energy Technology Data Exchange (ETDEWEB)

Yarosh, Daniel B

2002-11-30

The goal of DNA repair enzyme therapy is the same as that for gene therapy: to rescue a defective proteome/genome by introducing a substitute protein/DNA. The danger of inadequate DNA repair is highlighted in the genetic disease xeroderma pigmentosum. These patients are hypersensitive to sunlight and develop multiple cutaneous neoplasms very early in life. The bacterial DNA repair enzyme T4 endonuclease V was shown over 25 years ago to be capable of reversing the defective repair in xeroderma pigmentosum cells. This enzyme, packaged in an engineered delivery vehicle, has been shown to traverse the stratum corneum, reach the nuclei of living cells of the skin, and enhance the repair of UV-induced cyclobutane pyrimidine dimers (CPD). In such a system, changes in DNA repair, mutagenesis, and cell signaling can be studied without manipulation of the genome.

Expression of the pyr operon of Lactobacillus plantarum is regulated by inorganic carbon availability through a second regulator, PyrR2, homologous to the pyrimidine-dependent regulator PyrR1

DEFF Research Database (Denmark)

Arsène-Ploetze, Florence; Valérie Kugler, Valérie; Martinussen, Jan

2006-01-01

Inorganic carbon (IC), such as bicarbonate or carbon dioxide, stimulates the growth of Lactobacillus plantarum. At low IC levels, one-third of natural isolated L. plantarum strains are nutritionally dependent on exogenous arginine and pyrimidine, a phenotype previously defined as high-CO2-requiri...

Preparation of Benzo[c]carbazol-6-amines via Manganese-Catalyzed Enaminylation of 1-(Pyrimidin-2-yl)-1H-indoles with Ketenimines and Subsequent Oxidative Cyclization.

Science.gov (United States)

Zhou, Xiaorong; Li, Zhenmin; Zhang, Zhiyin; Lu, Ping; Wang, Yanguang

2018-03-02

Manganese-catalyzed C 2 -H enaminylation of 1-(pyrimidin-2-yl)-1H-indoles with ketenimines is reported. The reaction provided 2-enaminylated indole derivatives in moderate to excellent yields with a broad substrate scope. A migration of the directing group pyrimidinyl occurred during this process. The synthesized 2-enaminyl indoles could be conveniently converted into 5-aryl-7H-benzo[c]carbazol-6-amines.

Reaction of Aldehydes/Ketones with Electron-Deficient 1,3,5-Triazines Leading to Functionalized Pyrimidines as Diels-Alder/Retro-Diels-Alder Reaction Products: Reaction Development and Mechanistic Studies.

Science.gov (United States)

Yang, Kai; Dang, Qun; Cai, Pei-Jun; Gao, Yang; Yu, Zhi-Xiang; Bai, Xu

2017-03-03

Catalytic inverse electron demand Diels-Alder (IEDDA) reactions of heterocyclic aza-dienes are rarely reported since highly reactive and electron-rich dienophiles are often found not compatible with strong acids such as Lewis acids. Herein, we disclose that TFA-catalyzed reactions of electron-deficient 1,3,5-triazines and electron-deficient aldehydes/ketones can take place. These reactions led to highly functionalized pyrimidines as products in fair to good yields. The reaction mechanism was carefully studied by the combination of experimental and computational studies. The reactions involve a cascade of stepwise inverse electron demand hetero-Diels-Alder (ihDA) reactions, followed by retro-Diels-Alder (rDA) reactions and elimination of water. An acid was required for both ihDA and rDA reactions. This mechanism was further verified by comparing the relative reactivity of aldehydes/ketones and their corresponding vinyl ethers in the current reaction system.

Aqua[bis(pyrimidin-2-yl-kappa N)amine](carbonato-kappa 2O,O')copper(II) dihydrate.

Science.gov (United States)

van Albada, Gerard A; Mutikainen, Ilpo; Turpeinen, Urho; Reedijk, Jan

2002-03-01

The title mononuclear complex, [Cu(CO(3))(C(8)H(7)N(5))(H(2)O)] x 2H(2)O, was obtained by fixation of CO(2) by a mixture of copper(II) tetrafluoroborate and the ligand bis(pyrimidin-2-yl)amine in ethanol/water. The Cu(II) ion of the complex has a distorted square-pyramidal environment, with a basal plane formed by two N atoms of the ligand and two chelating O atoms of the carbonate group, while the apical position is occupied by the O atom of the coordinating water molecule. In the solid state, hydrogen-bonding interactions are dominant, the most unusual being the Watson-Crick-type coplanar ligand pairing through two N--H...N bonds. Lattice water molecules also participate in hydrogen bonding.

Manipulating the Electronic Excited State Energies of Pyrimidine-Based Thermally Activated Delayed Fluorescence Emitters To Realize Efficient Deep-Blue Emission.

Science.gov (United States)

Komatsu, Ryutaro; Ohsawa, Tatsuya; Sasabe, Hisahiro; Nakao, Kohei; Hayasaka, Yuya; Kido, Junji

2017-02-08

The development of efficient and robust deep-blue emitters is one of the key issues in organic light-emitting devices (OLEDs) for environmentally friendly, large-area displays or general lighting. As a promising technology that realizes 100% conversion from electrons to photons, thermally activated delayed fluorescence (TADF) emitters have attracted considerable attention. However, only a handful of examples of deep-blue TADF emitters have been reported to date, and the emitters generally show large efficiency roll-off at practical luminance over several hundreds to thousands of cd m -2 , most likely because of the long delayed fluorescent lifetime (τ d ). To overcome this problem, we molecularly manipulated the electronic excited state energies of pyrimidine-based TADF emitters to realize deep-blue emission and reduced τ d . We then systematically investigated the relationships among the chemical structure, properties, and device performances. The resultant novel pyrimidine emitters, called Ac-XMHPMs (X = 1, 2, and 3), contain different numbers of bulky methyl substituents at acceptor moieties, increasing the excited singlet (E S ) and triplet state (E T ) energies. Among them, Ac-3MHPM, with a high E T of 2.95 eV, exhibited a high external quantum efficiency (η ext,max ) of 18% and an η ext of 10% at 100 cd m -2 with Commission Internationale de l'Eclairage chromaticity coordinates of (0.16, 0.15). These efficiencies are among the highest values to date for deep-blue TADF OLEDs. Our molecular design strategy provides fundamental guidance to design novel deep-blue TADF emitters.

Explicit treatment of active-site waters enhances quantum mechanical/implicit solvent scoring: Inhibition of CDK2 by new pyrazolo[1,5-a]pyrimidines

Czech Academy of Sciences Publication Activity Database

Hylsová, M.; Carbain, B.; Fanfrlík, Jindřich; Musilová, L.; Haldar, Susanta; Köprülüoglu, Cemal; Ajani, Haresh; Brahmkshatriya, Pathik; Jorda, Radek; Kryštof, Vladimír; Hobza, Pavel; Echalier, A.; Paruch, K.; Lepšík, Martin

2017-01-01

Roč. 126, Jan 27 (2017), s. 1118-1128 ISSN 0223-5234 R&D Projects: GA ČR(CZ) GA15-15264S; GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388963 ; RVO:61389030 Keywords : cyclin-dependent kinase 2 * ATP-competitive type I inhibitors * pyrazolo[1,5-a]pyrimidine * quantum mechanical scoring * protein-ligand binding * molecular dynamics Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 4.519, year: 2016

UV-B-inducible and temperature-sensitive photoreactivation of cyclobutane pyrimidine dimers in Arabidopsis thaliana

International Nuclear Information System (INIS)

Pang, Qishen; Hays, J.B.

1991-01-01

Removal of cyclobutane pyrimidine dimers (CBPDs) in vivo from the DNA of UV-irradiated eight-leaf seedlings of Arabidopsis thaliana was rapid in the presence of visible light (half-life about 1 hour); removal of CBPDs in the dark, presumably via excision repair, was an order of magnitude slower. Extracts of plants contained significant photolyase in vitro, as assayed by restoration of transforming activity to UV-irradiated Escherichia coli plasmids; activity was maximal from four-leaf to 12-leaf stages. UV-B treatment of seedlings for 6 hours increased photolyase specific activity in extracts twofold. Arabidopsis photolyase was markedly temperature-sensitive, both in vitro (half-life at 30C about 12 minutes) and in vivo (half-life at 30C, 30 to 45 minutes). The wavelength dependency of the photoreactivation cross-section showed a broad peak at 375 to 400 nm, and is thus similar to that for maize pollen; it overlaps bacterial and yeast photolyase action spectra

Triple resonance experiments for the simultaneous correlation of H6/H5 and exchangeable protons of pyrimidine nucleotides in 13C,15N-labeled RNA applicable to larger RNA molecules

International Nuclear Information System (INIS)

Woehnert, Jens; Goerlach, Matthias; Schwalbe, Harald

2003-01-01

Triple-resonance two-dimensional H6/H5(C4N)H and C6/C5(C4N)H experiments are described that provide through-bond H6/H5 or C6/C5 to imino/amino correlations in pyrimidine bases in 13 C, 15 N-labeled RNA. The experiments simultaneously transfer H6/H5 magnetization by an INEPT step to the C6/C5 nuclei and by homonuclear CC- and heteronuclear CN-TOCSY steps via the intervening C4 nucleus to the N3/N4 nuclei and then by a reverse INEPT step to the imino/amino hydrogens. The sensitivity of these experiments is high as demonstrated using a 30-nucleotide pyrimidine rich RNA at a concentration of 0.9 mM at temperatures of 10 deg. C and 25 deg. C. This indicates the general applicability of the experiments and the possibility to obtain correlations for imino resonances in non-canonical regions of the target RNA

Synthesis of new annulated pyrano[2,3-d]pyrimidine derivatives using organo catalyst (DABCO in aqueous media

Directory of Open Access Journals (Sweden)

Ajmal R. Bhat

2017-01-01

Full Text Available A selective method for the synthesis of annulated pyrano[2,3-d]pyrimidines has been developed. It was shown that base catalysis is more efficient in this reaction, rather than acid catalysis as it is believed that 1,4-diazabicyclo[2.2.2]octane (DABCO is N-type base catalyst used for the synthesis of pyrano[2,3-d]pyramidine derivatives via one-pot three component condensation reactions of various aromatic aldehydes, active methylene compounds and barbituric acid in aqueous ethanol carried at normal temperature. The potential application of DABCO in organic synthesis increasing rapidly because of its reaction simplicity, less pollution, and minimum reaction time, high yields of the biological active products, uses less toxic solvents and low cost chemicals.

The growth rate of pyrimidine auxotrophic mutants of Lactococcus lactis MG1363 is reduced in the presence of exogenous aspartate

DEFF Research Database (Denmark)

Hansen, Steen Lyders Lerche; Martinussen, Jan

1998-01-01

Nucleotide metabolism is important for all cells as supplier of building blocks for the synthesis of nucleic acids and coenzymes. Furthermore, they act as intracellular energy carriers and allosteric effectors in a large number of enzymatic reactions. Nucleotides can either be made de novo or from...... encoding enzymes in the distal part of the pyrimidine biosynthetic pathway of L. lactis MG1363, results in reduction of the growth rate if exogenous aspartate is supplied to the growth medium. This observation can be explained by an increased accumulation of a toxic intermediate, most likely carbamoyl...... aspartate, provoked by high concentrations of aspartate....

The Roles of Several Residues of Escherichia coli DNA Photolyase in the Highly Efficient Photo-Repair of Cyclobutane Pyrimidine Dimers

Directory of Open Access Journals (Sweden)

Lei Xu

2010-01-01

Full Text Available Escherichia coli DNA photolyase is an enzyme that repairs the major kind of UV-induced lesions, cyclobutane pyrimidine dimer (CPD in DNA utilizing 350–450 nm light as energy source. The enzyme has very high photo-repair efficiency (the quantum yield of the reaction is ~0.85, which is significantly greater than many model compounds that mimic photolyase. This suggests that some residues of the protein play important roles in the photo-repair of CPD. In this paper, we have focused on several residues discussed their roles in catalysis by reviewing the existing literature and some hypotheses.

The partial-birth stratagem.

Science.gov (United States)

1998-06-01

In Wisconsin, physicians stopped performing abortions when a Federal District Court Judge refused to issue a temporary restraining order against the state's newly enacted "partial birth" abortion ban that was couched in such vague language it actually covered all abortions. While ostensibly attempting to ban late-term "intact dilation and extraction," the language of the law did not refer to that procedure or to late terms. Instead, it prohibited all abortions in which a physician "partially vaginally delivers a living child, causes the death of the partially delivered child with the intent to kill the child and then completes the delivery of the child." The law also defined "child" as "a human being from the time of fertilization" until birth. It is clear that this abortion ban is unconstitutional under Row v. Wade, and this unconstitutionality is compounded by the fact that the law allowed no exception to protect a woman's health, which is required by Roe for abortion bans after fetal viability. Wisconsin is only one of about 28 states that have enacted similar laws, and only two have restricted the ban to postviability abortions. Many of these laws have been struck down in court, and President Clinton has continued to veto the Federal partial-birth bill. The Wisconsin Judge acknowledged that opponents of the ban will likely prevail when the case is heard, but his action in denying the temporary injunction means that many women in Wisconsin will not receive timely medical care. The partial birth strategy is really only another anti-abortion strategy.

Partial QoS-Aware Opportunistic Relay Selection Over Two-Hop Channels: End-to-End Performance Under Spectrum-Sharing Requirements

KAUST Repository

Yuli Yang,

2014-10-01

In this paper, we propose a partial quality-of-service (QoS)-oriented relay selection scheme with a decode-and-forward (DF) relaying protocol, to reduce the feedback amount required for relay selection. In the proposed scheme, the activated relay is the one with the maximum signal-to-noise power ratio (SNR) in the second hop among those whose packet loss rates (PLRs) in the first hop achieve a predetermined QoS level. For the purpose of evaluating the performance of the proposed scheme, we exploit it with transmission constraints imposed on the transmit power budget and interference to other users. By analyzing the statistics of received SNRs in the first and second hops, we obtain the end-to-end PLR of this scheme in closed form under the considered scenario. Moreover, to compare the proposed scheme with popular relay selection schemes, we also derive the closed-form PLR expressions for partial relay selection (PRS) and opportunistic relay selection (ORS) criteria in the same scenario under study. Illustrative numerical results demonstrate the accuracy of our derivations and substantiate that the proposed relay selection scheme is a promising alternative with respect to the tradeoff between performance and complexity.

Construction of Pyrrolo[1,2-a]indoles via Cobalt(III)-Catalyzed Enaminylation of 1-(Pyrimidin-2-yl)-1H-indoles with Ketenimines and Subsequent Base-Promoted Cyclization.

Science.gov (United States)

Zhou, Xiaorong; Fan, Zili; Zhang, Zhiyin; Lu, Ping; Wang, Yanguang

2016-09-16

A cobalt(III)-catalyzed cross-coupling reaction of 1-(pyrimidin-2-yl)-1H-indoles with ketenimines is reported. The reaction provided 2-enaminylated indole derivatives in moderate to excellent yields with a broad substrate scope. The prepared 2-enaminylated indoles could be conveniently converted into pyrrolo[1,2-a]indoles, which are an important class of compounds in medicinal chemistry.

Computing the partial volume of pressure vessels

Energy Technology Data Exchange (ETDEWEB)

Wiencke, Bent [Nestle USA, Corporate Engineering, 800 N. Brand Blvd, Glendale, CA 91203 (United States)

2010-06-15

The computation of the partial and total volume of pressure vessels with various type of head profiles requires detailed knowledge of the head profile geometry. Depending on the type of head profile the derivation of the equations can become very complex and the calculation process cumbersome. Certain head profiles require numerical methods to obtain the partial volume, which for most application is beyond the scope of practicability. This paper suggests a unique method that simplifies the calculation procedure for the various types of head profiles by using one common set of equations without the need for numerical or complex computation methods. For ease of use, all equations presented in this paper are summarized in a single table format for horizontal and vertical vessels. (author)

Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

Directory of Open Access Journals (Sweden)

Simon Gemble

2015-07-01

Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H and their docking and urease inhibitory activity

Directory of Open Access Journals (Sweden)

Ghodsi Mohammadi Ziarani

2013-01-01

Full Text Available A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported.ResultsReactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 muM.DiscussionThe compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H and their docking and urease inhibitory activity

Directory of Open Access Journals (Sweden)

Ziarani Ghodsi Mohammadi

2013-01-01

Full Text Available Abstract Background A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported. Results Reactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 μM. Discussion The compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

Approximate thermodynamic state relations in partially ionized gas mixtures

International Nuclear Information System (INIS)

Ramshaw, John D.

2004-01-01

Thermodynamic state relations for mixtures of partially ionized nonideal gases are often approximated by artificially partitioning the mixture into compartments or subvolumes occupied by the pure partially ionized constituent gases, and requiring these subvolumes to be in temperature and pressure equilibrium. This intuitively reasonable procedure is easily shown to reproduce the correct thermal and caloric state equations for a mixture of neutral (nonionized) ideal gases. The purpose of this paper is to point out that (a) this procedure leads to incorrect state equations for a mixture of partially ionized ideal gases, whereas (b) the alternative procedure of requiring that the subvolumes all have the same temperature and free electron density reproduces the correct thermal and caloric state equations for such a mixture. These results readily generalize to the case of partially degenerate and/or relativistic electrons, to a common approximation used to represent pressure ionization effects, and to two-temperature plasmas. This suggests that equating the subvolume electron number densities or chemical potentials instead of pressures is likely to provide a more accurate approximation in nonideal plasma mixtures

Supramolecular Isomers of Metal-Organic Frameworks Derived from a Partially Flexible Ligand with Distinct Binding Motifs

KAUST Repository

Abdul Halim, Racha Ghassan

2016-01-04

Three novel metal-organic frameworks (MOFs) were isolated upon reacting a heterofunctional ligand 4 (pyrimidin-5 yl)benzoic acid (4,5-pmbc) with mixed valence Cu(I,II) under solvothermal conditions. X-ray crystal structural analysis reveals that the first compound is a layered structure composed of one type of inorganic building block, dinuclear paddlewheel [Cu2(O2C–)4], which are linked through 4,5-pmbc ligands. The two other supramolecular isomers are composed of the same Cu(II) dinuclear paddlewheel and a dinuclear Cu2I2 cluster, which are linked via the 4,5-pmbc linkers to yield two different 3-periodic frameworks with underlying topologies related to lvt and nbo. The observed structural diversity in these structures is due to the distinct coordination modes of the two coordinating moieties (the carboxylate group on the phenyl ring and the N-donor atoms from the pyrimidine moiety).

Supramolecular Isomers of Metal-Organic Frameworks Derived from a Partially Flexible Ligand with Distinct Binding Motifs

KAUST Repository

AbdulHalim, Rasha; Shkurenko, Aleksander; Al Kordi, Mohamed; Eddaoudi, Mohamed

2016-01-01

Three novel metal-organic frameworks (MOFs) were isolated upon reacting a heterofunctional ligand 4 (pyrimidin-5 yl)benzoic acid (4,5-pmbc) with mixed valence Cu(I,II) under solvothermal conditions. X-ray crystal structural analysis reveals that the first compound is a layered structure composed of one type of inorganic building block, dinuclear paddlewheel [Cu2(O2C–)4], which are linked through 4,5-pmbc ligands. The two other supramolecular isomers are composed of the same Cu(II) dinuclear paddlewheel and a dinuclear Cu2I2 cluster, which are linked via the 4,5-pmbc linkers to yield two different 3-periodic frameworks with underlying topologies related to lvt and nbo. The observed structural diversity in these structures is due to the distinct coordination modes of the two coordinating moieties (the carboxylate group on the phenyl ring and the N-donor atoms from the pyrimidine moiety).

Quantitative characterization of pyrimidine dimer excision from UV-irradiated DNA (excision capacity) by cell-free extracts of the yeast Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Bekker, M.L.; Kaboev, O.K.; Akhmedov, A.T.; Luchkina, L.A.

1984-01-01

Cell-free extracts from wild-type yeast (RAD + ) and from rad mutants belonging to the RAD3 epistatic group (rad1-1, rad2-1, rad3-1, rad4-1) contain activities catalyzing the excision of pyrimidine dimers (PD) from purified ultraviolet-irradiated DNA which was not pre-treated with exogenous UV-endonuclease. The level of these activities in cell-free extracts from rad mutants did not differ from that in wild-type extract and was close to the in vivo excision capacity of the latter calculated from the LD 37 (about 10 4 PD per haploid genome). (Auth.)

Isolation and properties of strains of Micrococcus (Deinococcus) radiodurans unable to excise ultraviolet light-induced pyrimidine dimers from DNA: evidence for two excision pathways

International Nuclear Information System (INIS)

Moseley, B.E.B.; Evans, D.M.

1983-01-01

A mutant of Deinococcus (formerly Micrococcus) radiodurans sensitive to both the lethal effect of mitomycin C and the mutagenic effect of simple alkylating agents, but having wild-type resistance to UV light, was treated with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine. Three strains were isolated that were UV-sensitive, but had wild-type resistance to the lethal effect of methyl methanesulphonate and all were shown to be unable to excise pyrimidine dimers. The three strains UVS9, UVS25 and UVS78 had, in addition to the mutation in mtcA, mutations in loci designated uvsC, uvsD and uvsE, respectively. When the mutant mtcA gene was replaced by its wild-type allele in all three strains they became UV- and mitomycin C-resistant. On incubating the double mutants UVS9, UVS25 and UVS78 with wild-type DNA about 50% of the transformants selected for UV resistance were mitomycin C-sensitive and about 50% resistant depending on whether the mutant mtcA or the uvsC, D or E genes had been replaced by their wild-type alleles. Although strains mutant singly in uvsC, D or E were UV-resistant the rates of excision of pyrimidine dimers differed between them and was slower in all of them than in the wild-type and strain 302. (author)

Parachute technique for partial penectomy

Directory of Open Access Journals (Sweden)

Fernando Korkes

2010-04-01

Full Text Available PURPOSE: Penile carcinoma is a rare but mutilating malignancy. In this context, partial penectomy is the most commonly applied approach for best oncological results. We herein propose a simple modification of the classic technique of partial penectomy, for better cosmetic and functional results. TECHNIQUE: If partial penectomy is indicated, the present technique can bring additional benefits. Different from classical technique, the urethra is spatulated only ventrally. An inverted "V" skin flap with 0.5 cm of extension is sectioned ventrally. The suture is performed with vicryl 4-0 in a "parachute" fashion, beginning from the ventral portion of the urethra and the "V" flap, followed by the "V" flap angles and than by the dorsal portion of the penis. After completion of the suture, a Foley catheter and light dressing are placed for 24 hours. CONCLUSIONS: Several complex reconstructive techniques have been previously proposed, but normally require specific surgical abilities, adequate patient selection and staged procedures. We believe that these reconstructive techniques are very useful in some specific subsets of patients. However, the technique herein proposed is a simple alternative that can be applied to all men after a partial penectomy, and takes the same amount of time as that in the classic technique. In conclusion, the "parachute" technique for penile reconstruction after partial amputation not only improves the appearance of the penis, but also maintains an adequate function.

Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

Science.gov (United States)

Toledo-Sherman, Leticia M; Prime, Michael E; Mrzljak, Ladislav; Beconi, Maria G; Beresford, Alan; Brookfield, Frederick A; Brown, Christopher J; Cardaun, Isabell; Courtney, Stephen M; Dijkman, Ulrike; Hamelin-Flegg, Estelle; Johnson, Peter D; Kempf, Valerie; Lyons, Kathy; Matthews, Kimberly; Mitchell, William L; O'Connell, Catherine; Pena, Paula; Powell, Kendall; Rassoulpour, Arash; Reed, Laura; Reindl, Wolfgang; Selvaratnam, Suganathan; Friley, Weslyn Ward; Weddell, Derek A; Went, Naomi E; Wheelan, Patricia; Winkler, Christin; Winkler, Dirk; Wityak, John; Yarnold, Christopher J; Yates, Dawn; Munoz-Sanjuan, Ignacio; Dominguez, Celia

2015-02-12

We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis.

Science.gov (United States)

Moreno-Morcillo, María; Grande-García, Araceli; Ruiz-Ramos, Alba; Del Caño-Ochoa, Francisco; Boskovic, Jasminka; Ramón-Maiques, Santiago

2017-06-06

CAD, the multifunctional protein initiating and controlling de novo biosynthesis of pyrimidines in animals, self-assembles into ∼1.5 MDa hexamers. The structures of the dihydroorotase (DHO) and aspartate transcarbamoylase (ATC) domains of human CAD have been previously determined, but we lack information on how these domains associate and interact with the rest of CAD forming a multienzymatic unit. Here, we prove that a construct covering human DHO and ATC oligomerizes as a dimer of trimers and that this arrangement is conserved in CAD-like from fungi, which holds an inactive DHO-like domain. The crystal structures of the ATC trimer and DHO-like dimer from the fungus Chaetomium thermophilum confirm the similarity with the human CAD homologs. These results demonstrate that, despite being inactive, the fungal DHO-like domain has a conserved structural function. We propose a model that sets the DHO and ATC complex as the central element in the architecture of CAD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mathematical Modelling of Intraretinal Oxygen Partial Pressure

African Journals Online (AJOL)

Erah

oxygen availability) is required for retinal oxidative metabolism. .... retina was described using Hill's equation and Fick's law. ... ganglion cell / nerve fiber layer and the superficial ..... parameter values producing the best. Figure 2: Partial ...

Design improvement for partial penetration welds of Pressurizer heater sleeves to head junctures

International Nuclear Information System (INIS)

Kim, Jin-Seon; Lee, Kyoung-Jin; Park, Tae-Jung; Kim, Moo-Yong

2007-01-01

ASME Code, Section III allows partial penetration welds for openings for instrumentation on which there are substantially no piping reactions and requires to have interference fit or limited diametral clearance between nozzles and vessel penetrations for the partial penetration welds. Pressurizer heater sleeves are nonaxisymmetrically attached on the hill-side of bottom head by partial penetration welds. The excessive stresses in the partial penetration weld regions of the heater sleeves are induced by pressure and thermal transient loads and also by the deformation due to manual welding process. The purpose of this study is 1) to improve design for the partial penetration welds between heater sleeves to head junctures, 2) to demonstrate the structural integrity according to the requirements of ASME Code, Section III and 3) to improve welding procedure considering the proposed design

Removable partial dentures: The clinical need for innovation.

Science.gov (United States)

Campbell, Stephen D; Cooper, Lyndon; Craddock, Helen; Hyde, T Paul; Nattress, Brian; Pavitt, Sue H; Seymour, David W

2017-09-01

The number of partially dentate adults is increasing, and many patients will require replacement of missing teeth. Although current treatment options also include fixed partial dentures and implants, removable partial dentures (RPDs) can have advantages and are widely used in clinical practice. However, a significant need exists to advance materials and fabrication technologies because of the unwanted health consequences associated with current RPDs. The purpose of this review was to assess the current state of and future need for prosthetics such as RPDs for patients with partial edentulism, highlight areas of weakness, and outline possible solutions to issues that affect patient satisfaction and the use of RPDs. The data on treatment for partial edentulism were reviewed and summarized with a focus on currently available and future RPD designs, materials, means of production, and impact on oral health. Data on patient satisfaction and compliance with RPD treatment were also reviewed to assess patient-centered care. Design, materials, ease of repair, patient education, and follow-up for RPD treatment all had a significant impact on treatment success. Almost 40% of patients no longer use their RPD within 5 years because of factors such as sociodemographics, pain, and esthetics. Research on RPD-based treatment for partial edentulism for both disease-oriented and patient-centered outcomes is lacking. Future trials should evaluate new RPD materials and design technologies and include both long-term follow-up and health-related and patient-reported outcomes. Advances in materials and digital design/production along with patient education promise to further the application of RPDs and improve the quality of life for patients requiring RPDs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Partially composite Higgs models

DEFF Research Database (Denmark)

Alanne, Tommi; Buarque Franzosi, Diogo; Frandsen, Mads T.

2018-01-01

We study the phenomenology of partially composite-Higgs models where electroweak symmetry breaking is dynamically induced, and the Higgs is a mixture of a composite and an elementary state. The models considered have explicit realizations in terms of gauge-Yukawa theories with new strongly...... interacting fermions coupled to elementary scalars and allow for a very SM-like Higgs state. We study constraints on their parameter spaces from vacuum stability and perturbativity as well as from LHC results and find that requiring vacuum stability up to the compositeness scale already imposes relevant...... constraints. A small part of parameter space around the classically conformal limit is stable up to the Planck scale. This is however already strongly disfavored by LHC results. in different limits, the models realize both (partially) composite-Higgs and (bosonic) technicolor models and a dynamical extension...

Calibration Of Partial-Pressure-Of-Oxygen Sensors

Science.gov (United States)

Yount, David W.; Heronimus, Kevin

1995-01-01

Report and analysis of, and discussion of improvements in, procedure for calibrating partial-pressure-of-oxygen sensors to satisfy Spacelab calibration requirements released. Sensors exhibit fast drift, which results in short calibration period not suitable for Spacelab. By assessing complete process of determining total drift range available, calibration procedure modified to eliminate errors and still satisfy requirements without compromising integrity of system.

Wavelength-dependent ultraviolet induction of cyclobutane pyrimidine dimers in the human cornea.

Science.gov (United States)

Mallet, Justin D; Rochette, Patrick J

2013-08-01

Exposition to ultraviolet (UV) light is involved in the initiation and the progression of skin cancer. The genotoxicity of UV light is mainly attributed to the induction of cyclobutane pyrimidine dimers (CPDs), the most abundant DNA damage generated by all UV types (UVA, B and C). The human cornea is also exposed to the harmful UV radiations, but no UV-related neoplasm has been reported in this ocular structure. The probability that a specific DNA damage leads to a mutation and eventually to cellular transformation is influenced by its formation frequency. To shed light on the genotoxic effect of sunlight in the human eye, we have analyzed CPD induction in the cornea and the iris following irradiation of ex vivo human eyes with UVA, B or C. The extent of CPD induction was used to establish the penetrance of the different UV types in the human cornea. We show that UVB- and UVC-induced CPDs are concentrated in the corneal epithelium and do not penetrate deeply beyond this corneal layer. On the other hand, UVA wavelengths penetrate deeper and induce CPDs in the entire cornea and in the first layers of the iris. Taken together, our results are undoubtedly an important step towards better understanding the consequences of UV exposure to the human eye.

Energy considerations in the partial space elevator

Science.gov (United States)

Woo, Pamela; Misra, Arun K.

2014-06-01

The space elevator has been proposed as an alternate method for space transportation. A partial elevator is composed of a tether of several hundreds of kilometres, held vertically in tension between two end masses, with its centre of orbit placed at the geosynchronous orbit. A spacecraft can dock at the lower end, and then use the climber on the elevator to ascend to higher altitudes. In this paper, energy calculations are performed, to determine whether a partial elevator can provide sufficient savings in operational costs, compared to the traditional rocket-powered launch. The energy required to launch a spacecraft from a Low Earth Orbit (LEO) to the geostationary orbit (GEO) is calculated for two trajectories. In the first trajectory, the spacecraft travels from LEO to GEO via a Hohmann transfer. In the second trajectory, the spacecraft travels from LEO to the lower end of the partial space elevator with a Hohmann transfer, and then uses the elevator to climb to GEO. The total energy required is compared between the two trajectories. The effects of tether length, spacecraft-to-climber mass ratio, altitude of LEO, and tether material are investigated.

Synthesis, antimalarial activity, heme binding and docking studies of N-substituted 4-aminoquinoline-pyrimidine molecular hybrids.

Science.gov (United States)

Maurya, Shiv Shyam; Khan, Shabana I; Bahuguna, Aparna; Kumar, Deepak; Rawat, Diwan S

2017-03-31

A series of novel N-substituted 4-aminoquinoline-pyrimidine hybrids have been synthesized via simple and economic route and evaluated for their antimalarial activity. Most compounds showed potent antimalarial activity against both CQ-sensitive and CQ-resistant strains with high selectivity index. All the compounds were found to be non-toxic to the mammalian cell lines. The most active compound 7b was analysed for heme binding activity using UV-spectrophotometer. Compound was found to interact with heme and a complex formation between compound and heme in a 1:1 stoichiometry ratio was determined using job plots. The interaction of these hybrids was also investigated by the molecular docking studies in the binding site of wild type Pf-DHFR-TS and quadruple mutant Pf-DHFR-TS. The pharmacokinetic property analysis of best active compounds was also studied by ADMET prediction. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines.

Science.gov (United States)

Abe, Masahito; Seto, Mabel; Gogliotti, Rocco G; Loch, Matthew T; Bollinger, Katrina A; Chang, Sichen; Engelberg, Eileen M; Luscombe, Vincent B; Harp, Joel M; Bubser, Michael; Engers, Darren W; Jones, Carrie K; Rodriguez, Alice L; Blobaum, Anna L; Conn, P Jeffrey; Niswender, Colleen M; Lindsley, Craig W

2017-10-12

Herein, we report the structure-activity relationships within a series of mGlu 7 PAMs based on a pyrazolo[1,5- a ]pyrimidine core with excellent CNS penetration ( K p s > 1 and K p,uu s > 1). Analogues in this series proved to display a range of Group III mGlu receptor selectivity, but VU6005649 emerged as the first dual mGlu 7/8 PAM, filling a void in the Group III mGlu receptor PAM toolbox and demonstrating in vivo efficacy in a mouse contextual fear conditioning model.

Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin

Energy Technology Data Exchange (ETDEWEB)

Komura, Jun-ichiro, E-mail: junkom@med.tohoku.ac.jp [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Ikehata, Hironobu [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Mori, Toshio [Radioisotope Research Center, Nara Medical University, Kashihara, Nara 634-8521 (Japan); Ono, Tetsuya [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)

2012-03-10

During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. -- Highlights: Black-Right-Pointing-Pointer Global genome repair of (6-4) photoproducts is fully active in mitotic cells. Black-Right-Pointing-Pointer DNA in condensed mitotic chromatin does not seem inaccessible or inert. Black-Right-Pointing-Pointer Mitotic transcriptional repression may impair transcription-coupled repair.

Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin

International Nuclear Information System (INIS)

Komura, Jun-ichiro; Ikehata, Hironobu; Mori, Toshio; Ono, Tetsuya

2012-01-01

During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. -- Highlights: ► Global genome repair of (6-4) photoproducts is fully active in mitotic cells. ► DNA in condensed mitotic chromatin does not seem inaccessible or inert. ► Mitotic transcriptional repression may impair transcription-coupled repair.

Partial gravity - Human impacts on facility design

Science.gov (United States)

Capps, Stephen; Moore, Nathan

1990-01-01

Partial gravity affects the body differently than earth gravity and microgravity environments. The main difference from earth gravity is human locomotion; while the main dfference from microgravity is the specific updown orientation and reach envelopes which increase volume requirements. Much data are available on earth gravity and microgravity design; however, very little information is available on human reactions to reduced gravity levels in IVA situations (without pressure suits). Therefore, if humans commit to permanent lunar habitation, much research should be conducted in the area of partial gravity effects on habitat design.

REE and Isotopic Compositions of Lunar Basalts Demonstrate Partial Melting of Hybridized Mantle Sources after Cumulate Overturn is Required

Science.gov (United States)

Dygert, N. J.; Liang, Y.

2017-12-01

Lunar basalts maintain an important record of the composition of the lunar interior. Much of our understanding of the Moon's early evolution comes from studying their petrogenesis. Recent experimental work has advanced our knowledge of major and trace element fractionation during lunar magma ocean (LMO) crystallization [e.g., 1-3], which produced heterogeneous basalt sources in the Moon's mantle. With the new experimental constraints, we can evaluate isotopic and trace element signatures in lunar basalts in unprecedented detail, refining inferences about the Moon's dynamic history. Two petrogenetic models are invoked to explain the compositions of the basalts. The assimilation model argues they formed as primitive melts of early LMO cumulates that assimilated late LMO cumulates as they migrated upward. The cumulate overturn model argues that dense LMO cumulates sank into the lunar interior, producing hybridized sources that melted to form the basalts. Here we compare predicted Ce/Yb and Hf and Nd isotopes of partial melts of LMO cumulates with measured compositions of lunar basalts to evaluate whether they could have formed by end-member petrogenetic models. LMO crystallization models suggest all LMO cumulates have chondrite normalized Ce/Yb 1.5; these could not have formed by assimilation of any LMO cumulate or residual liquid (or KREEP basalt, which has isotopically negative ɛNd and ɛHf). In contrast, basalt REE patterns and isotopes can easily be modeled assuming partial melting of hybridized mantle sources, indicating overturn may be required. A chemical requirement for overturn independently confirms that late LMO cumulates are sufficiently low in viscosity to sink into the lunar interior, as suggested by recent rock deformation experiments [4]. Overturned, low viscosity late LMO cumulates would be relatively stable around the core [5]. High Ce/Yb basalts require that overturned cumulates were mixed back into the overlying mantle by convection within a few

5-Bromo-2-[5-(4-nitrophenyl-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]pyrimidine

Directory of Open Access Journals (Sweden)

B. Kalluraya

2009-12-01

Full Text Available In the title pyrazoline compound, C19H14BrN5O2, the essentially planar pyrazoline and pyrimidine rings [maximum deviations = 0.013 (1 and 0.009 (1 Å, respectively] are inclined slightly to one another, making a dihedral angle of 10.81 (10°. The nitrobenzene unit is almost perpendicular to the attached pyrazoline ring, as indicated by the dihedral angle of 84.61 (8°. In the crystal structure, intermolecular C—H...N contacts link the molecules into dimers in an antiparallel manner. These dimers are further linked into one-dimensional chains along the b axis via C—H...O contacts. The crystal structure is consolidated by three different intermolecular π–π interactions [range of centroid–centroid distances = 3.5160 (11–3.6912 (11 Å].

The regulation of aortic endothelial cells by purines and pyrimidines involves co-existing P2y-purinoceptors and nucleotide receptors linked to phospholipase C.

OpenAIRE

Wilkinson, G. F.; Purkiss, J. R.; Boarder, M. R.

1993-01-01

1. We have examined the phospholipase C responses in bovine aortic endothelial cells to purines (ATP, ADP and analogues) and the pyrimidine, uridine triphosphate (UTP). 2. The cells responded to purines in a manner consistent with the presence of P2y purinoceptors; both 2-methylthioadenosine 5'-triphosphate (2MeSATP) and adenosine 5'-0-(2-thiodiphosphate) (ADP beta S) were potent agonists (EC50 0.41 microM and 0.85 microM respectively) while beta, gamma-methylene ATP at 300 microM was not. 3....

Post-operative complications and owner satisfaction following partial caudectomies: 22 cases (2008 to 2013).

Science.gov (United States)

Simons, M C; Ben-Amotz, R; Popovitch, C

2014-10-01

To report complications and owner satisfaction for dogs and cats following partial caudectomy. Medical records of dogs and cats (n = 22) that underwent partial caudectomy between 2008 and 2013 were retrospectively reviewed. Signalment, reason for amputation, level of amputation, and complications were recorded. Owners were contacted via telephone to obtain follow-up data. The most common reason for partial caudectomy was tail wounds (16 of 22; 72 · 7%). Complications were typically minor incisional crusting (4 of 20; 20%). Major complications (3 of 20; 15%) included prolonged healing after partial incisional dehiscence, continued self-trauma requiring revision surgery, and severe inflammation with ulceration requiring revision surgery. The majority of owners surveyed (10 of 12; 83 · 3%) were satisfied with the post-operative outcome and would recommend this procedure if warranted. Partial caudectomy is well tolerated in both dogs and cats with no loss of function. Pet owners did not perceive any behavioural changes following partial caudectomy. However, in cases of continued self-mutilation and/or incisional dehiscence, revision procedures may be required. © 2014 British Small Animal Veterinary Association.

Synthesis of Substituted Thieno[2,3-d]pyrimidin-4-ones and Their Testing for Evaluation of Cytotoxic Activity on Mammalian Cell Models

Directory of Open Access Journals (Sweden)

Kh. A. Bozorov

2013-01-01

Full Text Available From 2-amino-3-ethoxycarbonyl-4,5-dimethyl-, -polymethylenethiophenes (1-4 were synthesized 2,3-disubstituted thieno[2,3-d]dihydropyrrolo-, tetrahydropyrido-, and tetrahydroazepino[1,2-a]pyrimidin-4-ones (5-16 for pharmacological investigations. The 12 compounds (5-16 were individually evaluated for their antiproliferative activities on mammalian cancer cell models. All tested compounds showed weak affection on human cervix adenocarcinoma cells (HeLa whereas some of the tested compounds exhibited more consistent inhibition of cell growth on murine myeloma cells (P3X. In both cases some compounds enhanced cell proliferation.

3D-QSAR (CoMFA, CoMSIA), molecular docking and molecular dynamics simulations study of 6-aryl-5-cyano-pyrimidine derivatives to explore the structure requirements of LSD1 inhibitors.

Science.gov (United States)

Ding, Lina; Wang, Zhi-Zheng; Sun, Xu-Dong; Yang, Jing; Ma, Chao-Ya; Li, Wen; Liu, Hong-Min

2017-08-01

Recently, Histone Lysine Specific Demethylase 1 (LSD1) was regarded as a promising anticancer target for the novel drug discovery. And several small molecules as LSD1 inhibitors in different structures have been reported. In this work, we carried out a molecular modeling study on the 6-aryl-5-cyano-pyrimidine fragment LSD1 inhibitors using three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to generate 3D-QSAR models. The results show that the best CoMFA model has q 2 =0.802, r 2 ncv =0.979, and the best CoMSIA model has q 2 =0.799, r 2 ncv =0.982. The electrostatic, hydrophobic and H-bond donor fields play important roles in the models. Molecular docking studies predict the binding mode and the interactions between the ligand and the receptor protein. Molecular dynamics simulations results reveal that the complex of the ligand and the receptor protein are stable at 300K. All the results can provide us more useful information for our further drug design. Copyright © 2017. Published by Elsevier Ltd.

Arthroscopic partial medial meniscectomy

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Dašić Žarko

2011-01-01

Full Text Available Background/Aim. Meniscal injuries are common in professional or recreational sports as well as in daily activities. If meniscal lesions lead to physical impairment they usually require surgical treatment. Arthroscopic treatment of meniscal injuries is one of the most often performed orthopedic operative procedures. Methods. The study analyzed the results of arthroscopic partial medial meniscectomy in 213 patients in a 24-month period, from 2006, to 2008. Results. In our series of arthroscopically treated medial meniscus tears we noted 78 (36.62% vertical complete bucket handle lesions, 19 (8.92% vertical incomplete lesions, 18 (8.45% longitudinal tears, 35 (16.43% oblique tears, 18 (8.45% complex degenerative lesions, 17 (7.98% radial lesions and 28 (13.14% horisontal lesions. Mean preoperative International Knee Documentation Committee (IKDC score was 49.81%, 1 month after the arthroscopic partial medial meniscectomy the mean IKDC score was 84.08%, and 6 months after mean IKDC score was 90.36%. Six months after the procedure 197 (92.49% of patients had good or excellent subjective postoperative clinical outcomes, while 14 (6.57% patients subjectively did not notice a significant improvement after the intervention, and 2 (0.93% patients had no subjective improvement after the partial medial meniscectomy at all. Conclusion. Arthroscopic partial medial meniscetomy is minimally invasive diagnostic and therapeutic procedure and in well selected cases is a method of choice for treatment of medial meniscus injuries when repair techniques are not a viable option. It has small rate of complications, low morbidity and fast rehabilitation.

Three additional genes involved in pyrimidine dimer removal in Saccharomyces cerevisiae: RAD7, RAD14, and MMS19

Energy Technology Data Exchange (ETDEWEB)

Prakash, L; Prakash, S

1979-01-01

The ability to remove ultraviolet (uv)-induced pyrimidine dimers from the nuclear DNA of yeast was examined in two radiation-sensitive (rad) mutants and one methyl methanesulfonate-sensitive (mms) mutant of the yeast Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by an endonuclease activity prepared from crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad7, rad14, and mms19 mutants were found to be defective in their ability to remove uv-induced dimers from nuclear DNA. All three mutants belong to the same episatic group as the other mutants involved in excision-repair. All three mutants show enhanced uv-induced mutations. The rad 14 mutant also shows epistatic interactions with genes in the other two uv repair pathways.

6-Butyl-5-(4-methoxyphenoxy-3-phenyl-3H-1,2,3-triazolo[4,5-d]pyrimidin-7(6H-one

Directory of Open Access Journals (Sweden)

Hong-Mei Wang

2009-12-01

Full Text Available The asymmetric unit of the title compound, C21H21N5O3, consists of two geometrically similar molecules. The fused rings of the triazolo[4,5-d]pyrimidine system are nearly coplanar, making dihedral angels of 1.48 (18 and 1.34 (16°, and the phenyl rings are twisted by 12.3 (1 and 8.7 (1° with respect to the triazolopyrimidine plane. The ethyl groups of the n-butyl side chains are disordered over two sites in each of the independent molecules, the ratios of occupancies being 0.60:0.40 and 0.61:0.39.

Cast Partial Denture versus Acrylic Partial Denture for Replacement of Missing Teeth in Partially Edentulous Patients

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Pramita Suwal

2017-03-01

Full Text Available Aim: To compare the effects of cast partial denture with conventional all acrylic denture in respect to retention, stability, masticatory efficiency, comfort and periodontal health of abutments. Methods: 50 adult partially edentulous patient seeking for replacement of missing teeth having Kennedy class I and II arches with or without modification areas were selected for the study. Group-A was treated with cast partial denture and Group-B with acrylic partial denture. Data collected during follow-up visit of 3 months, 6 months, and 1 year by evaluating retention, stability, masticatory efficiency, comfort, periodontal health of abutment. Results: Chi-square test was applied to find out differences between the groups at 95% confidence interval where p = 0.05. One year comparison shows that cast partial denture maintained retention and stability better than acrylic partial denture (p< 0.05. The masticatory efficiency was significantly compromising from 3rd month to 1 year in all acrylic partial denture groups (p< 0.05. The comfort of patient with cast partial denture was maintained better during the observation period (p< 0.05. Periodontal health of abutment was gradually deteriorated in all acrylic denture group (p

7 CFR 765.101 - Borrower graduation requirements.

Science.gov (United States)

2010-01-01

... reasonable rates and terms. (b) The Agency may require partial or full graduation. (1) In a partial... 7 Agriculture 7 2010-01-01 2010-01-01 false Borrower graduation requirements. 765.101 Section 765..., DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS DIRECT LOAN SERVICING-REGULAR Borrower Graduation § 765.101...

Partial dynamical symmetries in quantal many-body systems

International Nuclear Information System (INIS)

Van Isacker, P.

2001-01-01

Partial dynamical symmetries are associated with Hamiltonians that are partially solvable. The determination of the properties of a quantal system of N interacting particles moving in an external potential requires the solution of the eigenvalue equation associated with a second-quantised Hamiltonian. In many situations of interest the Hamiltonian commutes with transformations that constitute a symmetry algebra G sym . This characteristic opens a way to find all analytically solvable Hamiltonians. The author gives a brief review of some recent developments

The Fanconi anemia associated protein FAAP24 uses two substrate specific binding surfaces for DNA recognition

NARCIS (Netherlands)

Wienk, H.L.J.; Slootweg, J.C.; Speerstra, S.; Kaptein, R.; Boelens, R.; Folkers, G.E.

2013-01-01

To maintain the integrity of the genome, multiple DNA repair systems exist to repair damaged DNA. Recognition of altered DNA, including bulky adducts, pyrimidine dimers and interstrand crosslinks (ICL), partially depends on proteins containing helix-hairpin-helix (HhH) domains. To understand how ICL

[Routine oral examinations and specific after-care for removable partial dentures].

Science.gov (United States)

de Baat, C; Witter, D J; Keltjens, H M A M; Creugers, N H J

2011-01-01

Following treatment with a removable partial denture, routine oral examinations are required to stabilize the existing condition in a sustainable way and to make possible the timely treatment of anomalies which have appeared. In cases of problems assessed during a routine oral examination in relation to the removable partial dentures, maintenance, restorative and prosthetic treatment may be indicated. Maintenance treatments are indicated for small and easily retrievable alterations. In removable partial denture treatment, adequate space between prepared tooth and denture is essential. Possible prosthetic treatments of a removable partial denture are relining, rebasing, improving or renewing the maxillomandibular relation, repairment, and extension.

Does friendship give us non-derivative partial reasons ?

Directory of Open Access Journals (Sweden)

Andrew Reisner

2008-02-01

Full Text Available One way to approach the question of whether there are non-derivative partial reasons of any kind is to give an account of what partial reasons are, and then to consider whether there are such reasons. If there are, then it is at least possible that there are partial reasons of friendship. It is this approach that will be taken here, and it produces several interesting results. The first is a point about the structure of partial reasons. It is at least a necessary condition of a reason’s being partial that it has an explicit relational component. This component, technically, is a relatum in the reason relation that itself is a relation between the person to whom the reason applies and the person whom the action for which there is a reason concerns. The second conclusion of the paper is that this relational component is also required for a number of types of putatively impartial reasons. In order to avoid trivialising the distinction between partial and impartial reasons, some further sufficient condition must be applied. Finally, there is some prospect for a way of distinguishing between impartial reasons that contain a relational component and partial reasons, but that this approach suggests that the question of whether ethics is partial or impartial will be settled at the level of normative ethical discourse, or at least not at the level of discourse about the nature of reasons for action.

Explicit treatment of active-site waters enhances quantum mechanical/implicit solvent scoring: Inhibition of CDK2 by new pyrazolo[1,5-a]pyrimidines.

Science.gov (United States)

Hylsová, Michaela; Carbain, Benoit; Fanfrlík, Jindřich; Musilová, Lenka; Haldar, Susanta; Köprülüoğlu, Cemal; Ajani, Haresh; Brahmkshatriya, Pathik S; Jorda, Radek; Kryštof, Vladimír; Hobza, Pavel; Echalier, Aude; Paruch, Kamil; Lepšík, Martin

2017-01-27

We present comprehensive testing of solvent representation in quantum mechanics (QM)-based scoring of protein-ligand affinities. To this aim, we prepared 21 new inhibitors of cyclin-dependent kinase 2 (CDK2) with the pyrazolo[1,5-a]pyrimidine core, whose activities spanned three orders of magnitude. The crystal structure of a potent inhibitor bound to the active CDK2/cyclin A complex revealed that the biphenyl substituent at position 5 of the pyrazolo[1,5-a]pyrimidine scaffold was located in a previously unexplored pocket and that six water molecules resided in the active site. Using molecular dynamics, protein-ligand interactions and active-site water H-bond networks as well as thermodynamics were probed. Thereafter, all the inhibitors were scored by the QM approach utilizing the COSMO implicit solvent model. Such a standard treatment failed to produce a correlation with the experiment (R 2  = 0.49). However, the addition of the active-site waters resulted in significant improvement (R 2  = 0.68). The activities of the compounds could thus be interpreted by taking into account their specific noncovalent interactions with CDK2 and the active-site waters. In summary, using a combination of several experimental and theoretical approaches we demonstrate that the inclusion of explicit solvent effects enhance QM/COSMO scoring to produce a reliable structure-activity relationship with physical insights. More generally, this approach is envisioned to contribute to increased accuracy of the computational design of novel inhibitors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The Human SLC25A33 and SLC25A36 Genes of Solute Carrier Family 25 Encode Two Mitochondrial Pyrimidine Nucleotide Transporters*

Science.gov (United States)

Di Noia, Maria Antonietta; Todisco, Simona; Cirigliano, Angela; Rinaldi, Teresa; Agrimi, Gennaro; Iacobazzi, Vito; Palmieri, Ferdinando

2014-01-01

The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family, many of which have been shown to transport inorganic anions, amino acids, carboxylates, nucleotides, and coenzymes across the inner mitochondrial membrane, thereby connecting cytosolic and matrix functions. Here two members of this family, SLC25A33 and SLC25A36, have been thoroughly characterized biochemically. These proteins were overexpressed in bacteria and reconstituted in phospholipid vesicles. Their transport properties and kinetic parameters demonstrate that SLC25A33 transports uracil, thymine, and cytosine (deoxy)nucleoside di- and triphosphates by an antiport mechanism and SLC25A36 cytosine and uracil (deoxy)nucleoside mono-, di-, and triphosphates by uniport and antiport. Both carriers also transported guanine but not adenine (deoxy)nucleotides. Transport catalyzed by both carriers was saturable and inhibited by mercurial compounds and other inhibitors of mitochondrial carriers to various degrees. In confirmation of their identity (i) SLC25A33 and SLC25A36 were found to be targeted to mitochondria and (ii) the phenotypes of Saccharomyces cerevisiae cells lacking RIM2, the gene encoding the well characterized yeast mitochondrial pyrimidine nucleotide carrier, were overcome by expressing SLC25A33 or SLC25A36 in these cells. The main physiological role of SLC25A33 and SLC25A36 is to import/export pyrimidine nucleotides into and from mitochondria, i.e. to accomplish transport steps essential for mitochondrial DNA and RNA synthesis and breakdown. PMID:25320081

Partial Thickness Rotator Cuff Tears: Current Concepts

Science.gov (United States)

Matthewson, Graeme; Beach, Cara J.; Nelson, Atiba A.; Woodmass, Jarret M.; Ono, Yohei; Boorman, Richard S.; Lo, Ian K. Y.; Thornton, Gail M.

2015-01-01

Partial thickness rotator cuff tears are a common cause of pain in the adult shoulder. Despite their high prevalence, the diagnosis and treatment of partial thickness rotator cuff tears remains controversial. While recent studies have helped to elucidate the anatomy and natural history of disease progression, the optimal treatment, both nonoperative and operative, is unclear. Although the advent of arthroscopy has improved the accuracy of the diagnosis of partial thickness rotator cuff tears, the number of surgical techniques used to repair these tears has also increased. While multiple repair techniques have been described, there is currently no significant clinical evidence supporting more complex surgical techniques over standard rotator cuff repair. Further research is required to determine the clinical indications for surgical and nonsurgical management, when formal rotator cuff repair is specifically indicated and when biologic adjunctive therapy may be utilized. PMID:26171251

Partial Thickness Rotator Cuff Tears: Current Concepts

Directory of Open Access Journals (Sweden)

Graeme Matthewson

2015-01-01

Full Text Available Partial thickness rotator cuff tears are a common cause of pain in the adult shoulder. Despite their high prevalence, the diagnosis and treatment of partial thickness rotator cuff tears remains controversial. While recent studies have helped to elucidate the anatomy and natural history of disease progression, the optimal treatment, both nonoperative and operative, is unclear. Although the advent of arthroscopy has improved the accuracy of the diagnosis of partial thickness rotator cuff tears, the number of surgical techniques used to repair these tears has also increased. While multiple repair techniques have been described, there is currently no significant clinical evidence supporting more complex surgical techniques over standard rotator cuff repair. Further research is required to determine the clinical indications for surgical and nonsurgical management, when formal rotator cuff repair is specifically indicated and when biologic adjunctive therapy may be utilized.

Derivation of a macroscale formulation for a class of nonlinear partial differential equations

International Nuclear Information System (INIS)

Pantelis, G.

1995-05-01

A macroscale formulation is constructed from a system of partial differential equations which govern the microscale dependent variables. The construction is based upon the requirement that the solutions of the macroscale partial differential equations satisfy, in some approximate sense, the system of partial differential equations associated with the microscale. These results are restricted to the class of nonlinear partial differential equations which can be expressed as polynomials of the dependent variables and their partial derivatives up to second order. A linear approximation of transformations of second order contact manifolds is employed. 6 refs

5-(2-amimo-4-styryl pyrimidine-4-yl-4-methoxybenzofuran-6-ol

Directory of Open Access Journals (Sweden)

Atteyat A Labib

2013-05-01

Full Text Available This study describes the organic synthesis of 5-(2-amimo-4-styryl pyrimidine-4-yl-4-methoxy benzofuran-6-ol (SPBF as an example of a benzofuran derivative used as a new series of amyloid imaging agents. These benzofuran derivatives may be useful amyloid imaging agents for detecting B-amyloid plagues in the brain of Alzheimer’s disease. The precursor is 1-[6-hydroxy-4-methoxybenzofuran-5-yl]-phenyl butadiene ketone, which react with guanidine hydrochloride. The purification process was done via crystallization using solvent ethanol. The overall yield was 75% and the structure of the synthesized compound was confirmed by correct analytical and spectral data. Also, The synthesized compound was labeled with radioactive iodine -125 via electrophilic substitution reaction, in the presence of iodogen as an oxidizing agent, the labeling process was carried out at 95oC for 20min. The radiochemical yield was determined by using a thin layer chromatography and the yield was equal to 80%. Preliminary an in-vivo study examined normal mice after intravenous injection through the tail vein and the data showed the labeling compound was quickly cleared from most body organs. The radioiodinated compound showed high brain uptake.The results of this study suggest that radioiodinated (SPBF may be useful as a brain imaging agents.

Partial discharges in spheroidal voids: Void orientation

DEFF Research Database (Denmark)

McAllister, Iain Wilson

1997-01-01

Partial discharge transients can be described in terms of the charge induced on the detecting electrode. The influence of the void parameters upon the induced charge is examined and discussed for spheroidal voids. It is shown that a quantitative interpretation of the induced charge requires...

Partially Adaptive STAP Algorithm Approaches to functional MRI

Science.gov (United States)

Huang, Lejian; Thompson, Elizabeth A.; Schmithorst, Vincent; Holland, Scott K.; Talavage, Thomas M.

2010-01-01

In this work, the architectures of three partially adaptive STAP algorithms are introduced, one of which is explored in detail, that reduce dimensionality and improve tractability over fully adaptive STAP when used in construction of brain activation maps in fMRI. Computer simulations incorporating actual MRI noise and human data analysis indicate that element space partially adaptive STAP can attain close to the performance of fully adaptive STAP while significantly decreasing processing time and maximum memory requirements, and thus demonstrates potential in fMRI analysis. PMID:19272913

Vibrational spectroscopic analysis of 2-chloro-5-(2,5-dimethoxy-benzylidene)-1,3-diethyl-dihydro-pyrimidine-4,6(1H,5H)-dione

Science.gov (United States)

Soliman, H. S.; Eid, Kh. M.; Ali, H. A. M.; Atef, S. M.; El-Mansy, M. A. M.

2012-11-01

In the present work, a combined experimental and computational study for the optimized molecular structural parameters, FT-IR spectra, thermo-chemical parameters, total dipole moment and HOMO-LUMO energy gap for 2-chloro-5-(2,5-dimethoxy-benzylidene)-1,3-diethyl-dihydro-pyrimidine-4,6(1H,5H)-dione have been investigated using B3LYP/6-311G basis set. Our calculated results have showed that the investigated compound possesses a dipole moment of 4.9 Debye and HOMO-LUMO energy gap of 3 eV which indicate high recommendations for photovoltaic devices fabrication.

Possible Effect of 5, 6- Dimethyl -4 Isothiocyanate Thieno [2, 3-d] Pyrimidine and I or Irradiation on Ehrlich Carcinoma in Mice

International Nuclear Information System (INIS)

Mansour, S.Z.; Anis, L.M.

2010-01-01

Considerable attention has been devoted to the construction of new derivatives of [2,3-d] pyrimidines on the account of their reported biological activities. The aim of the present work is to evaluate the antitumour activity of 5, 6- dimethyl -4- isothiocyanate- thieno [2,3-d] pyrimidine (DMITCTP) in solid Ehrlich carcinoma (SEC) bearing mice. DMITCTP was administered on the 10th day after tumor inoculation at a dose of 150 mg/kg BW, day after day, during a period of 3 weeks. Whole body exposure to one dose of 2Gy gamma irradiation was carried out two weeks after DMITCTP administration. Biochemical analysis in the blood of solid Ehrlich carcinoma (SEC) bearing mice showed significant increase in MDA content and GSH-Px activity level a significant decrease in GSH content and SOD activity level, IL 10 concentration and TNF- α concentration was detected associated with significant alteration in kidney and liver functions, as compared to control. Administration of DMITCTP alone or in combination with gamma-irradiation has significantly decrease MDA content and GSH-Px activity level associated with significant increase in GSH content, SOD activity level, IL-10 concentration and TNF-a concentration, compared to SEC bearing mice. These results supported by significant improvement in liver and kidney functions. Treatment solid Ehrlich carcinoma (SEC) bearing mice with gamma-irradiation or DMITCTP combined with y-irradiation showed significant increase in MDA content, GSH-Px and GST activities levels and in amount of metabolites of CYP450 and significant decrease in GSH content, and SOD activity level, as compared to SEC bearing mice. Administration of DMITCTP alone or combined with gamma- irradiation has significantly decreased tumor volume

Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light

International Nuclear Information System (INIS)

Freeman, S.E.; Hacham, H.; Gange, R.W.; Maytum, D.J.; Sutherland, J.C.; Sutherland, B.M.

1989-01-01

The UV components of sunlight are believed to be a major cause of human skin caner, and DNA is though to be the principal molecular target. Alterations of the intensity and wavelength distribution of solar UV radiation reaching the surface of the earth, for example by depletion of stratospheric ozone, will change the effectiveness of solar radiation in damaging DNA in human skin. Evaluation of the magnitude of such effects requires knowledge of the altered sunlight spectrum and of the action spectrum for damaging DNA in human skin. The authors have determined an action spectrum for the frequency of pyrimidine dimer formation induced in the DNA of human skin per unit dose of UV incident on the skin surface. The peak of this action spectrum is near 300 nm and decreases rapidly at both longer and shorter wavelengths. The decrease in the action spectrum for wavelengths <300 nm is attributed to the absorption of the upper layers of the skin. Convolution of the dimer action spectrum with the solar spectra corresponding to a solar angle of 40 degree under current levels of stratospheric ozone and those for 50% ozone depletion, indicate about a 2.5-fold increase in dimer formation. If the action spectrum for DNA damage that results in skin cancer resembles that for dimer induction in skin, these results suggest that a 50% decrease in stratospheric ozone would increase the incidence of nonmelanoma skin cancers among white males in Seattle, Washington, by 7.5- to 8-fold, to a higher incidence than is presently seen in the corresponding population of Albuquerque, New Mexico

Isomeric signatures in the fragmentation of pyridazine and pyrimidine induced by fast ion impact

Energy Technology Data Exchange (ETDEWEB)

Wolff, Wania, E-mail: wania@if.ufrj.br; Luna, Hugo; Montenegro, Eduardo C. [Instituto de Física, Universidade Federal do Rio de Janeiro, 21941-972 Rio de Janeiro, RJ (Brazil)

2015-07-28

We present fast proton impact induced fragmentations of pyrimidine and pyridazine as an experimental resource to investigate isomeric signatures. Major isomeric imprints are identified for few fragment ions and differences of more than an order of magnitude for the cross sections of fragments of the same mass were measured. The observation of the molecular structure of these isomers gives no apparent indication for the reasons for such substantial differences. It is verified that the simple displacement of the position of one nitrogen atom strongly inhibits or favors the production of some ionic fragment species. The dependency of the fragmentation cross sections on the proton impact energy, investigated by means of time of flight mass spectroscopy and of a model calculation based in first order perturbation theory, allows us to disentangle the complex collision dynamics of the ionic fragments. The proton-induced fragmentation discriminates rather directly the association between a molecular orbital ionization and the fragment-ions creation and abundance, as well as how the redistribution of the energy imparted to the molecules takes place, triggering not only single but also double vacancy and leads to specific fragmentation pathways.

The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells

Energy Technology Data Exchange (ETDEWEB)

Franzolin, Elisa; Miazzi, Cristina; Frangini, Miriam; Palumbo, Elisa; Rampazzo, Chiara [Department of Biology, University of Padova, Via Ugo Bassi 58B, I-35131 Padova (Italy); Bianchi, Vera, E-mail: vbianchi@bio.unipd.it [Department of Biology, University of Padova, Via Ugo Bassi 58B, I-35131 Padova (Italy)

2012-10-15

In cycling cells cytosolic de novo synthesis of deoxynucleotides is the main source of precursors for mitochondrial (mt) DNA synthesis. The transfer of deoxynucleotides across the inner mt membrane requires protein carriers. PNC1, a SLC25 family member, exchanges pyrimidine nucleoside triphosphates in liposomes and its downregulation decreases mtUTP concentration in cultured cells. By an isotope-flow protocol we confirmed transport of uridine nucleotides by PNC1 in intact cultured cells and investigated PNC1 involvement in the mt trafficking of thymidine phosphates. Key features of our approach were the manipulation of PNC1 expression by RNA interference or inducible overexpression, the employment of cells proficient or deficient for cytosolic thymidine kinase (TK1) to distinguish the direction of flow of thymidine nucleotides across the mt membrane during short pulses with [{sup 3}H]-thymidine, the determination of mtdTTP specific radioactivity to quantitate the rate of mtdTTP export to the cytoplasm. Downregulation of PNC1 in TK1{sup -} cells increased labeled dTTP in mitochondria due to a reduced rate of export. Overexpression of PNC1 in TK1{sup +} cells increased mtdTTP pool size and radioactivity, suggesting an involvement in the import of thymidine phosphates. Thus PNC1 is a component of the network regulating the mtdTTP pool in human cells. -- Highlights: Black-Right-Pointing-Pointer Thymidine phosphates exchange between mitochondria and cytosol in mammalian cells. Black-Right-Pointing-Pointer siRNA-downregulation of PNC1 delays mitochondrial dTTP export in TK1{sup -} cells. Black-Right-Pointing-Pointer PNC1 overexpression accumulates dTTP in mitochondria of TK1{sup +} cells. Black-Right-Pointing-Pointer PNC1 exchanges thymidine nucleotides across the mitochondrial inner membrane. Black-Right-Pointing-Pointer PNC1 participates in the regulation of the mtdTTP pool supporting mtDNA synthesis.

The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells

International Nuclear Information System (INIS)

Franzolin, Elisa; Miazzi, Cristina; Frangini, Miriam; Palumbo, Elisa; Rampazzo, Chiara; Bianchi, Vera

2012-01-01

In cycling cells cytosolic de novo synthesis of deoxynucleotides is the main source of precursors for mitochondrial (mt) DNA synthesis. The transfer of deoxynucleotides across the inner mt membrane requires protein carriers. PNC1, a SLC25 family member, exchanges pyrimidine nucleoside triphosphates in liposomes and its downregulation decreases mtUTP concentration in cultured cells. By an isotope-flow protocol we confirmed transport of uridine nucleotides by PNC1 in intact cultured cells and investigated PNC1 involvement in the mt trafficking of thymidine phosphates. Key features of our approach were the manipulation of PNC1 expression by RNA interference or inducible overexpression, the employment of cells proficient or deficient for cytosolic thymidine kinase (TK1) to distinguish the direction of flow of thymidine nucleotides across the mt membrane during short pulses with [ 3 H]-thymidine, the determination of mtdTTP specific radioactivity to quantitate the rate of mtdTTP export to the cytoplasm. Downregulation of PNC1 in TK1 − cells increased labeled dTTP in mitochondria due to a reduced rate of export. Overexpression of PNC1 in TK1 + cells increased mtdTTP pool size and radioactivity, suggesting an involvement in the import of thymidine phosphates. Thus PNC1 is a component of the network regulating the mtdTTP pool in human cells. -- Highlights: ► Thymidine phosphates exchange between mitochondria and cytosol in mammalian cells. ► siRNA-downregulation of PNC1 delays mitochondrial dTTP export in TK1 − cells. ► PNC1 overexpression accumulates dTTP in mitochondria of TK1 + cells. ► PNC1 exchanges thymidine nucleotides across the mitochondrial inner membrane. ► PNC1 participates in the regulation of the mtdTTP pool supporting mtDNA synthesis.

Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study

Directory of Open Access Journals (Sweden)

Shailee V. Tiwari

2018-02-01

Full Text Available Herein, we report an environmentally friendly, rapid, and convenient ionic liquid ([Et3NH][HSO4]-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H-chromen-3-yl-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 4(a–f and 4-(6-substituted-4-oxo-4H-chromen-3-yl-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives 6(a–f. All the synthesized derivatives 4(a–f and 6(a–f were evaluated for their in vitro antifungal and antibacterial activity, by method recommended by National Committee for Clinical Laboratory Standards (NCCLS. The compound 6c bearing a fluoro group on the chromone ring and oxygen and a hydrazino group (–NHNH2 on the pyrimidine ring, was found to be the most potent antibacterial compound amongst the synthesized derivatives. The compound 6f bearing a methoxy group (–OCH3 on the chromone ring and sulphur group on the pyrimidine ring, was found to exhibit equipotent antifungal activity when compared with the standard drug miconazole. A d-alanine-d-alanine ligase (DdlB enzyme assay study and an ergosterol extraction and quantitation assay study were performed to predict the mode of action of the synthesized compounds. A molecular docking study was performed to predict the binding interactions with receptors and mode of action of the synthesized derivatives. Further, analysis of the ADMET parameters for the synthesized compounds has shown that these compounds have good oral drug-like properties and can be developed as oral drug candidates. To establish the antimicrobial selectivity and safety, the most active compounds 6c and 6f were further tested for cytotoxicity against the human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 6c and 6f and the results indicated that the compounds are non-toxic in nature.

Fitting partially upgraded oils into pipelines and refinery markets

International Nuclear Information System (INIS)

Flaherty, G.

2000-01-01

The logistics of transporting partially upgraded crudes in feeder and trunk pipeline systems is discussed. Logistic alternatives are evaluated against economic drivers for partial upgrading, and the impact of crude transportation logistics on the quality of crude that reaches refinery gates is assessed. The potential advantages of partial upgrading in the field are reviewed (including reduction of diluent required to meet pipeline density and viscosity specifications, cost and availability of diluent, limitations in diluent transportation infrastructure, increased chemical stability, increased attractiveness to refineries, shortage of refinery coking capacity, higher market value). The pros and cons of various upgrading processes, and the implications of each for producers and refiners are explained. The advantages of moving to large common streams, as opposed to the concept of 'boutique' crudes, are stressed as the surest way for producers to realize the maximum value of partially upgraded crudes

Introduction to partial differential equations

CERN Document Server

Borthwick, David

2016-01-01

This modern take on partial differential equations does not require knowledge beyond vector calculus and linear algebra. The author focuses on the most important classical partial differential equations, including conservation equations and their characteristics, the wave equation, the heat equation, function spaces, and Fourier series, drawing on tools from analysis only as they arise.Within each section the author creates a narrative that answers the five questions: (1) What is the scientific problem we are trying to understand? (2) How do we model that with PDE? (3) What techniques can we use to analyze the PDE? (4) How do those techniques apply to this equation? (5) What information or insight did we obtain by developing and analyzing the PDE? The text stresses the interplay between modeling and mathematical analysis, providing a thorough source of problems and an inspiration for the development of methods.

Comparative action spectra for pyrimidine dimer formation in Cloudman S91 mouse melanoma and EMT6 mouse mammary carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Hill, H Z [New Jersey, Medical School, Newark (USA); Setlow, R B [Brookhaven National Lab., Upton, NY (USA)

1982-05-01

Pyrimidine dimer formation in melanotic mouse melanoma cells, Cloudman S91H-, and in mouse mammary carcinoma cells, EMT6, was compared as a function of wavelength by irradiating equal numbers of cells from the two cell lines simultaneously. More dimers were formed in EMT6 than in S91H- by light of wavelengths less than 289nm, while light of higher wavelengths caused equivalent dimer formation, as measured by the Micrococcus luteus UV-endonuclease assay. The cells of S91H- are lightly melanotic, yet shielding at lower wavelengths is considerable. It is speculated that melanin pigmentation arose by selection during an evolutionary period when UV-C light reaching the earth's surface was significantly greater than it is today.

Splenectomy for Children With Thalassemia: Total or Partial Splenectomy, Open or Laparoscopic Splenectomy.

Science.gov (United States)

Al-Salem, Ahmed H

2016-01-01

Splenomegaly and hypersplenism are common complications among children with thalassemia necessitating splenectomy. Thirty-six children (27 β-thalassemia major, 3 Hb H disease, and 6 thalassemia intermediate) had total splenectomy (11 laparoscopic and 13 open splenectomy) or partial splenectomy (12 patients). In the partial splenectomy group, 2 with Hb H required no transfusions. For those with β-thalassemia major who had partial splenectomy (9 patients), there was a reduction in the number of transfusions from a preoperative mean of 15.2 transfusions per year to a postoperative mean of 8.2 transfusions per year. Subsequently and as a result of increase in the size of splenic remnant, their transfusions increased, but none required total splenectomy. Twenty-four patients had total splenectomy (13 open and 11 laparoscopic splenectomy). Their postsplenectomy transfusions decreased from a preoperative mean of 17.8 transfusions per year to a postoperative mean of 10 transfusions per year. There was no mortality, and none developed postoperative sepsis or thrombotic complications. Total splenectomy is beneficial for children with β-thalassemia major and hypersplenism by reducing their transfusion requirements. Laparoscopic splenectomy is however more beneficial. Partial splenectomy reduces their transfusion requirements, but only as a temporary measure, and so it is recommended for children younger than 5 years of age.

ppcor: An R Package for a Fast Calculation to Semi-partial Correlation Coefficients.

Science.gov (United States)

Kim, Seongho

2015-11-01

Lack of a general matrix formula hampers implementation of the semi-partial correlation, also known as part correlation, to the higher-order coefficient. This is because the higher-order semi-partial correlation calculation using a recursive formula requires an enormous number of recursive calculations to obtain the correlation coefficients. To resolve this difficulty, we derive a general matrix formula of the semi-partial correlation for fast computation. The semi-partial correlations are then implemented on an R package ppcor along with the partial correlation. Owing to the general matrix formulas, users can readily calculate the coefficients of both partial and semi-partial correlations without computational burden. The package ppcor further provides users with the level of the statistical significance with its test statistic.

The regulation of aortic endothelial cells by purines and pyrimidines involves co-existing P2y-purinoceptors and nucleotide receptors linked to phospholipase C.

Science.gov (United States)

Wilkinson, G F; Purkiss, J R; Boarder, M R

1993-03-01

1. We have examined the phospholipase C responses in bovine aortic endothelial cells to purines (ATP, ADP and analogues) and the pyrimidine, uridine triphosphate (UTP). 2. The cells responded to purines in a manner consistent with the presence of P2y purinoceptors; both 2-methylthioadenosine 5'-triphosphate (2MeSATP) and adenosine 5'-0-(2-thiodiphosphate) (ADP beta S) were potent agonists (EC50 0.41 microM and 0.85 microM respectively) while beta, gamma-methylene ATP at 300 microM was not. 3. The cells also responded to UTP. The maximal response to UTP was less than that for either 2MeSATP and ADP beta S while adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S) gave the largest maximal response. 4. The concentration-effect curve to UTP was additive in the presence of either 2MeSATP or ADP beta S. However, the concentration-effect curves to ATP gamma S reached the same maximum in the presence or absence of UTP. 5. Suramin, at concentrations between 10 microM and 100 microM was a competitive antagonist for the response to ADP beta S and 2MeSATP but not the response to UTP. 6. The results show that there are two separate, co-existing, receptor populations: P2y-purinoceptors (responding to purines) and nucleotide receptors (responding to both purines and pyrimidines). We conclude that purines such as ATP/ADP may regulate aortic endothelial cells by interacting with two phospholipase C-linked receptors.

Recurrent Partial Words

Directory of Open Access Journals (Sweden)

Francine Blanchet-Sadri

2011-08-01

Full Text Available Partial words are sequences over a finite alphabet that may contain wildcard symbols, called holes, which match or are compatible with all letters; partial words without holes are said to be full words (or simply words. Given an infinite partial word w, the number of distinct full words over the alphabet that are compatible with factors of w of length n, called subwords of w, refers to a measure of complexity of infinite partial words so-called subword complexity. This measure is of particular interest because we can construct partial words with subword complexities not achievable by full words. In this paper, we consider the notion of recurrence over infinite partial words, that is, we study whether all of the finite subwords of a given infinite partial word appear infinitely often, and we establish connections between subword complexity and recurrence in this more general framework.

The human SLC25A33 and SLC25A36 genes of solute carrier family 25 encode two mitochondrial pyrimidine nucleotide transporters.

Science.gov (United States)

Di Noia, Maria Antonietta; Todisco, Simona; Cirigliano, Angela; Rinaldi, Teresa; Agrimi, Gennaro; Iacobazzi, Vito; Palmieri, Ferdinando

2014-11-28

The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family, many of which have been shown to transport inorganic anions, amino acids, carboxylates, nucleotides, and coenzymes across the inner mitochondrial membrane, thereby connecting cytosolic and matrix functions. Here two members of this family, SLC25A33 and SLC25A36, have been thoroughly characterized biochemically. These proteins were overexpressed in bacteria and reconstituted in phospholipid vesicles. Their transport properties and kinetic parameters demonstrate that SLC25A33 transports uracil, thymine, and cytosine (deoxy)nucleoside di- and triphosphates by an antiport mechanism and SLC25A36 cytosine and uracil (deoxy)nucleoside mono-, di-, and triphosphates by uniport and antiport. Both carriers also transported guanine but not adenine (deoxy)nucleotides. Transport catalyzed by both carriers was saturable and inhibited by mercurial compounds and other inhibitors of mitochondrial carriers to various degrees. In confirmation of their identity (i) SLC25A33 and SLC25A36 were found to be targeted to mitochondria and (ii) the phenotypes of Saccharomyces cerevisiae cells lacking RIM2, the gene encoding the well characterized yeast mitochondrial pyrimidine nucleotide carrier, were overcome by expressing SLC25A33 or SLC25A36 in these cells. The main physiological role of SLC25A33 and SLC25A36 is to import/export pyrimidine nucleotides into and from mitochondria, i.e. to accomplish transport steps essential for mitochondrial DNA and RNA synthesis and breakdown. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Unilateral removable partial dentures.

Science.gov (United States)

Goodall, W A; Greer, A C; Martin, N

2017-01-27

Removable partial dentures (RPDs) are widely used to replace missing teeth in order to restore both function and aesthetics for the partially dentate patient. Conventional RPD design is frequently bilateral and consists of a major connector that bridges both sides of the arch. Some patients cannot and will not tolerate such an extensive appliance. For these patients, bridgework may not be a predictable option and it is not always possible to provide implant-retained restorations. This article presents unilateral RPDs as a potential treatment modality for such patients and explores indications and contraindications for their use, including factors relating to patient history, clinical presentation and patient wishes. Through case examples, design, material and fabrication considerations will be discussed. While their use is not widespread, there are a number of patients who benefit from the provision of unilateral RPDs. They are a useful treatment to have in the clinician's armamentarium, but a highly-skilled dental team and a specific patient presentation is required in order for them to be a reasonable and predictable prosthetic option.

Delayed Partial Nephrectomy for Hydronephrosis After Renal Trauma.

Science.gov (United States)

Setia, Shaan; Jackson, Jessica Nicole; Herndon, C D Anthony; Corbett, Sean T

2017-03-01

Delayed sequelae following conservative management of renal trauma in the pediatric population are uncommon. Reports of delayed operations to manage these sequelae are even less common. Here we present the case of a 16-year-old male patient who had delayed development of upper urinary tract obstruction with recurrent infections following high-grade renal trauma managed conservatively. Ultimately, he required a robotic-assisted partial nephrectomy 2 years after initial nonoperative management. This is unique as no prior studies to our knowledge have described delayed hydronephrosis and delayed partial nephrectomy over a year following renal trauma. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of partial beta-adrenoceptor agonist activity.

Science.gov (United States)

Lipworth, B J; Grove, A

1997-01-01

A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether

The Stone–Čech compactification of a partial frame via ideals and ...

African Journals Online (AJOL)

A partial frame is a meet-semilattice in which certain designated subsets are required to have joins, and finite meets distribute over these. The designated subsets are specified by means of a so-called selection function, denoted by S; these partial frames are called S-frames. We construct free frames over S-frames using ...

Selective metal binding to Cys-78 within endonuclease V causes an inhibition of catalytic activities without altering nontarget and target DNA binding

International Nuclear Information System (INIS)

Prince, M.A.; Friedman, B.; Gruskin, E.A.; Schrock, R.D. III; Lloyd, R.S.

1991-01-01

T4 endonuclease V is a pyrimidine dimer-specific DNA repair enzyme which has been previously shown not to require metal ions for either of its two catalytic activities or its DNA binding function. However, we have investigated whether the single cysteine within the enzyme was able to bind metal salts and influence the various activities of this repair enzyme. A series of metals (Hg2+, Ag+, Cu+) were shown to inactivate both endonuclease Vs pyrimidine dimer-specific DNA glycosylase activity and the subsequent apurinic nicking activity. The binding of metal to endonuclease V did not interfere with nontarget DNA scanning or pyrimidine dimer-specific binding. The Cys-78 codon within the endonuclease V gene was changed by oligonucleotide site-directed mutagenesis to Thr-78 and Ser-78 in order to determine whether the native cysteine was directly involved in the enzyme's DNA catalytic activities and whether the cysteine was primarily responsible for the metal binding. The mutant enzymes were able to confer enhanced ultraviolet light (UV) resistance to DNA repair-deficient Escherichia coli at levels equal to that conferred by the wild type enzyme. The C78T mutant enzyme was purified to homogeneity and shown to be catalytically active on pyrimidine dimer-containing DNA. The catalytic activities of the C78T mutant enzyme were demonstrated to be unaffected by the addition of Hg2+ or Ag+ at concentrations 1000-fold greater than that required to inhibit the wild type enzyme. These data suggest that the cysteine is not required for enzyme activity but that the binding of certain metals to that amino acid block DNA incision by either preventing a conformational change in the enzyme after it has bound to a pyrimidine dimer or sterically interfering with the active site residue's accessibility to the pyrimidine dimer

Expedient Protocols for the Installation of Pyrimidine Based Privileged Templates on 2-Position of Pyrrolo[2,1-c][1,4]-benzodiazepine Nucleus Linked Through a p-phenoxyl Spacer

Directory of Open Access Journals (Sweden)

Anshu Agarwal

2012-01-01

Full Text Available Exceedingly facile single step expedient protocols based on the versatility and reactivity of corresponding intermediates : [2-(dimethylaminomethylene ketone] (5 and chalcone (6, derived from 2-(p-acetyl phenoxyl substituted analogue of pyrrolo[2,1-c][1,4]-benzodiazepine (4, have been developed to provide an easy installation of the pyrimidine based privileged templates at 2-position of pyrrolo[2,1-c][1,4]-benzodiazepine through a p-phenoxyl spacer, by utilizing the synthetic strategy depicted in schemes-1 and 2.

Site-specific analysis of UV-induced cyclobutane pyrimidine dimers in nucleotide excision repair-proficient and -deficient hamster cells: Lack of correlation with mutational spectra

International Nuclear Information System (INIS)

Vreeswijk, Maaike P.G.; Meijers, Caro M.; Giphart-Gassler, Micheline; Vrieling, Harry; Zeeland, Albert A. van; Mullenders, Leon H.F.; Loenen, Wil A.M.

2009-01-01

Irradiation of cells with UVC light induces two types of mutagenic DNA photoproducts, i.e. cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). To investigate the relationship between the frequency of UV-induced photolesions at specific sites and their ability to induce mutations, we quantified CPD formation at the nucleotide level along exons 3 and 8 of the hprt gene using ligation-mediated PCR, and determined the mutational spectrum of 132 UV-induced hprt mutants in the AA8 hamster cell line and of 165 mutants in its nucleotide excision repair-defective derivative UV5. In AA8 cells, transversions predominated with a strong strand bias towards thymine-containing photolesions in the non-transcribed strand. As hamster AA8 cells are proficient in global genome repair of 6-4PP but selectively repair CPD from the transcribed strand of active genes, most mutations probably resulted from erroneous bypass of CPD in the non-transcribed strand. However, the relative incidence of CPD and the positions where mutations most frequently arose do not correlate. In fact some major damage sites hardly gave rise to the formation of mutations. In the repair-defective UV5 cells, mutations were almost exclusively C > T transitions caused by photoproducts at PyC sites in the transcribed strand. Even though CPD were formed at high frequencies at some TT sites in UV5, these photoproducts did not contribute to mutation induction at all. We conclude that, even in the absence of repair, large variations in the level of induction of CPD at different sites throughout the two exons do not correspond to frequencies of mutation induction.

Implant support for removable partial overdentures: a case report.

Science.gov (United States)

Halterman, S M; Rivers, J A; Keith, J D; Nelson, D R

1999-01-01

Functional stability and the preservation of remaining alveolar bone are primary, and often elusive, goals when restoring the partially edentulous arch. The incorporation of dental implants for the partial support of removable prostheses offers a practical adjunct in the fulfillment of these objectives. Planning for complex courses of treatment that include dental implants requires close coordination between the surgeon and the restorative dentist. Decisions that deal with type, location, size, number of implant fixtures, and design of the prosthesis are critical. All of these areas must be discussed and established as acceptable to the patient and each clinician before the initiation of treatment. In this report, we present a course of patient treatment in which a removable partial denture is supported by natural remaining teeth in conjunction with osseointegrated implants.

Partial tooth gear bearings

Science.gov (United States)

Vranish, John M. (Inventor)

2010-01-01

A partial gear bearing including an upper half, comprising peak partial teeth, and a lower, or bottom, half, comprising valley partial teeth. The upper half also has an integrated roller section between each of the peak partial teeth with a radius equal to the gear pitch radius of the radially outwardly extending peak partial teeth. Conversely, the lower half has an integrated roller section between each of the valley half teeth with a radius also equal to the gear pitch radius of the peak partial teeth. The valley partial teeth extend radially inwardly from its roller section. The peak and valley partial teeth are exactly out of phase with each other, as are the roller sections of the upper and lower halves. Essentially, the end roller bearing of the typical gear bearing has been integrated into the normal gear tooth pattern.

Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation

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Manuel J. Muñoz

2017-03-01

Full Text Available We have previously found that UV irradiation promotes RNA polymerase II (RNAPII hyperphosphorylation and subsequent changes in alternative splicing (AS. We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER, and reduced by the absence of XPE, the main NER sensor of PDs. The mechanism involves activation of the protein kinase ATR that mediates the UV-induced RNAPII hyperphosphorylation. Our results define the sequence UV-PDs-NER-ATR-RNAPII-AS as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation.

Simultaneous quantification of purine and pyrimidine bases, nucleosides and their degradation products in bovine blood plasma by high performance liquid chromatography tandem mass spectrometry

DEFF Research Database (Denmark)

Nielsen, Charlotte Stentoft; Vestergaard, Mogens; Løvendahl, Peter

2014-01-01

describes the development and validation of a sensitive and specific method for simultaneous determination of 20 purines (adenine, guanine, guanosine, inosine, 2′-deoxyguanosine, 2′-deoxyinosine, xanthine, hypoxanthine), pyrimidines (cytosine, thymine, uracil, cytidine, uridine, thymidine, 2′-deoxyuridine...... investigated. It was confirmed that using a log-calibration model rather than a linear calibration model resulted in lower CV% and a lack of fit test demonstrated a satisfying linear regression. The method covers concentration ranges for each metabolite according to that in actual samples, e.g. guanine: 0...... veins and, with a few exceptions, also for other species such as chicken, pig, mink, human and rat....

Defining the minimal structural requirements for partial agonism at the type I myo-inositol 1,4,5-trisphosphate receptor.

Science.gov (United States)

Wilcox, R A; Fauq, A; Kozikowski, A P; Nahorski, S R

1997-02-03

The novel synthetic analogues D-3-fluoro-myo-inositol 1,5-bisphosphate-4-phosphorothioate, [3F-Ins(1,5)P2-4PS], D-3-fluoro-myo-inositol 1,4-bisphosphate-5-phosphorothioate [3F-Ins(1,4)P2-5PS], and D-3-fluoro-myo-inositol 1-phosphate-4,5-bisphosphorothioate [3F-Ins(1)P-(4,5)PS2] were utilised to define the structure-activity relationships which could produce partial agonism at the Ca2+ mobilising myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor. Based on prior structure-activity data we hypothesised that the minimal structural requirements for lns(1,4,5)P3 receptor partial agonism, were phosphorothioate substitution of the crucial vicinal 4,5-bisphosphate pair accompanied by another structural perturbation, such fluorination of 3-position of the myo-inositol ring. All the analogues fully displaced [3H]Ins(1,4,5)P3 from a single Ins(1,4,5)P3 binding site in pig cerebellar membranes [3F-Ins(1,5)P2-4PS (1C50 = 26 nM), 3F-Ins(1,4)P2-5PS (IC50 = 80 nM) and 3F-Ins(1)P-(4,5)PS2 (IC50 = 109 nM) cf. Ins(1,4,5)P3 (IC50 = 11 nM)]. In contrast, 3F-Ins(1,5)P2-4PS (IC50 = 424 nM) and 3F-Ins(1,4)P2-5PS (IC50 = 3579 nM) were weak full agonists at the Ca2+ mobilising Ins(1,4,5)P3 receptor of permeabilised SH-SY5Y neuroblastoma cells, being respectively 4- and 36-fold less potent than Ins(1,4,5)P3 (EC50 = 99 nM). While 3F-Ins(1)P-(4,5)PS2 (EC50 = 11345 nM) was a partial agonist releasing only 64.3 +/- 1.9% of the Ins(1,4,5)P3-sensitive intracellular Ca2+ pools. 3F-Ins(1)P-(4,5)PS2 was unique among the Ins(1,4,5)P3 receptor partial agonists so far identified in having a relatively high affinity for the Ins(1,4,5)P3 binding site, accompanied by a significant loss of intrinsic activity for Ca2+ mobilisation. This improved affinity was probably due to the retention of the 1-position phosphate, which enhances interaction with the Ins-(1,4,5)P3 receptor. 3F-Ins(1)P-(4,5)PS2 may be an important lead compound for the development of efficient Ins(1,4,5)P3 receptor antagonists.

Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes.

Directory of Open Access Journals (Sweden)

Justin D Mallet

Full Text Available Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD and pyrimidine (6-4 pyrimidone photoproducts (6-4PP. These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced.

'Stent in a stent'--an alternative technique for removing partially covered stents following sleeve gastrectomy complications.

Science.gov (United States)

Vasilikostas, Georgios; Sanmugalingam, Nimalan; Khan, Omar; Reddy, Marcus; Groves, Chris; Wan, Andrew

2014-03-01

Endoscopic stenting is a relatively new technique for the treatment of post sleeve gastrectomy complications. Partially covered stents are used in this method to minimise the risk of migration but they are associated with difficulties with removal. Patients requiring emergency stenting following sleeve gastrectomy underwent insertion of a partially covered metallic stent. One month later, if the stent was not easily removable, a fully covered overlapping stent was inserted and the patient was readmitted 2 weeks later for removal of both stents. Four patients required stenting following sleeve gastrectomy leaks, and one patient required stenting for a stricture. In these cases, a 'stent in a stent' technique was used for removal. This technique allows the safe removal of partially covered stents inserted following sleeve gastrectomy complications.

On the hierarchy of partially invariant submodels of differential equations

OpenAIRE

Golovin, Sergey V.

2007-01-01

It is noticed, that partially invariant solution (PIS) of differential equations in many cases can be represented as an invariant reduction of some PIS of the higher rank. This introduce a hierarchic structure in the set of all PISs of a given system of differential equations. By using this structure one can significantly decrease an amount of calculations required in enumeration of all PISs for a given system of partially differential equations. An equivalence of the two-step and the direct ...

Apoptosis induced by pyrimidine dimer produced by ultraviolet irradiation in cultured cyprinodont cells. Analysis utilizing the evasion from photolysis

International Nuclear Information System (INIS)

Nishigaki, Reiko

2000-01-01

This is the review of author's investigations on the mechanism of apoptosis induced by UV irradiation in cultured cyprinodont cells highly expressing photolyases of cyclobutane pyrimidine dimer (CPD). Authors found out the evasion from photolysis by UV-induced apoptosis of which cascade had been thought irreversible: the cascade was reversible until the process of DNA fragmentation. In controlling the process, a mechanism to recognize CPD was found concerned. In those cells, morphological changes by UVC were reversible ones in apoptosis from which they evaded if CPD was repaired. Investigations on caspase, which playing important roles in apoptosis, revealed that the DEVD-cleaving enzyme activities were regulated by CPD quantity. However, differing from mammalian cells, elevation of caspase (-7, -3A and -3B) activities did not always induce the morphologic changes and DNA fragmentation. Further studies were thought necessary to elucidate the mechanism of apoptosis in those fish cells. (K.H.)

A 5-4 pyrimidine-pyrimidone photoproduct produced from mixtures of thymine and 4-thiouridine irradiated with 334 nm light

International Nuclear Information System (INIS)

Blazek, E.R.; Alderfer, J.L.; Tabaczynski, W.A.; Stamoudis, V.C.; Churchill, M.E.; Peak, J.G.; Peak, M.J.

1993-01-01

To investigate the photoreaction of 4-thiouridine with DNA or its precursors, the authors irradiated aqueous mixtures of thymine and 4-thiouridine with 334 nm light and separated photoproducts using two or more stages of reversed-phase high performance liquid chromatography. The two equally abundant major photo-products were analyzed by UV absorbance spectrophotometry, fast-atom bombardment and electron-impact mass spectrometry, and 1 H- and 13 C-NMR spectroscopy, and were identified as two diastereomers of 6-hydroxy-5-[1-(β-D-erythro-pentofuranosyl)-4'-pyrimidin-2'-one]dihydrothymine (0 6 hThy[5-4]Pdo), of molecular weight 370.32. These diastereomers, although stable at room temperature or below, are interconvertible by heating (90 o C for 5 min) in aqueous solution. The possible biological significance of this photoproduct is discussed, and an application as a crosslinker for oligonucleotides to selectively block replication suggested. (Author)

Influence of partial replacement of soya bean meal by faba beans or peas in heavy pigs diet on meat quality, residual anti-nutritional factors and phytoestrogen content.

Science.gov (United States)

Gatta, Domenico; Russo, Claudia; Giuliotti, Lorella; Mannari, Claudio; Picciarelli, Piero; Lombardi, Lara; Giovannini, Luca; Ceccarelli, Nello; Mariotti, Lorenzo

2013-06-01

The study evaluated the partial substitution of soybean meal by faba beans (18%) or peas (20%) as additional protein sources in diets destined for typical Italian heavy pig production. It compared animal performances, meat quality, the presence of residual anti-nutritional factors (ANF) and phytoestrogens in plasma and meat and the possible effects on pig health, by evaluating oxidative, inflammatory and pro-atherogenic markers. The results showed that the productive performances, expressed as body weight and feed conversion ratio, of pigs fed with faba bean and pea diets were similar to those of pigs fed only the soybean meal. Meat quality of pigs fed with the three diets was similar in colour, water-holding capacity, tenderness and chemical composition. Despite the higher levels of phytoestrogen in the plasma of pigs fed only the soybean meal, phytoestrogen concentration in the muscle was equivalent to that of animals fed diets with faba beans, whereas pigs fed a diet with peas showed a lower concentration. Inflammation and pro-atherogenic parameters did not show significant differences among the three diets. Overall, the partial substitution of soybean meal by faba beans appears more interesting than with peas, particularly in relation to the higher amount of polyphenols in the diet and the highest concentration of phytoestrogens found in the plasma and muscle of animals, while the pyrimidine anti-nutritional compounds present in the diet did not appear to accumulate and had no effect on the growth performance of animals.

Partial Facetectomy for Lumbar Foraminal Stenosis

Directory of Open Access Journals (Sweden)

Kevin Kang

2014-01-01

Full Text Available Background. Several different techniques exist to address the pain and disability caused by isolated nerve root impingement. Failure to adequately decompress the lumbar foramen may lead to failed back surgery syndrome. However, aggressive treatment often causes spinal instability or may require fusion for satisfactory results. We describe a novel technique for decompression of the lumbar nerve root and demonstrate its effectiveness in relief of radicular symptoms. Methods. Partial facetectomy was performed by removal of the medial portion of the superior facet in patients with lumbar foraminal stenosis. 47 patients underwent the procedure from 2001 to 2010. Those who demonstrated neurogenic claudication without spinal instability or central canal stenosis and failed conservative management were eligible for the procedure. Functional level was recorded for each patient. These patients were followed for an average of 3.9 years to evaluate outcomes. Results. 27 of 47 patients (57% reported no back pain and no functional limitations. Eight of 47 patients (17% reported moderate pain, but had no limitations. Six of 47 patients (13% continued to experience degenerative symptoms. Five of 47 patients (11% required additional surgery. Conclusions. Partial facetectomy is an effective means to decompress the lumbar nerve root foramen without causing spinal instability.

Perturbed Partial Cavity Drag Reduction at High Reynolds Numbers

Science.gov (United States)

Makiharju, Simo; Elbing, Brian; Wiggins, Andrew; Dowling, David; Perlin, Marc; Ceccio, Steven

2010-11-01

Ventilated partial cavities were investigated at Reynolds numbers to 80 million. These cavities could be suitable for friction drag reduction on ocean going vessels and thereby lead to environmental and economical benefits. The test model was a 3.05 m wide by 12.9 m long flat plate, with a 0.18 m backward-facing step and a cavity-terminating beach, which had an adjustable slope, tilt and height. The step and beach trapped a ventilated partial cavity over the longitudinal mid-section of the model. Large-scale flow perturbations, mimicking the effect of ambient ocean waves were investigated. For the conditions tested a cavity could be maintained under perturbed flow conditions when the gas flux supplied was greater than the minimum required to maintain a cavity under steady conditions, with larger perturbations requiring more excess gas flux to maintain the cavity. High-speed video was used to observe the unsteady three dimensional cavity closure, the overall cavity shape, and the cavity oscillations. Cavities with friction drag reduction exceeding 95% were attained at optimal conditions. A simplified energy cost-benefit analysis of partial cavity drag reduction was also performed. The results suggest that PCDR could potentially lead to energy savings.

Robotic partial nephrectomy for complex renal tumors: surgical technique.

Science.gov (United States)

Rogers, Craig G; Singh, Amar; Blatt, Adam M; Linehan, W Marston; Pinto, Peter A

2008-03-01

Laparoscopic partial nephrectomy requires advanced training to accomplish tumor resection and renal reconstruction while minimizing warm ischemia times. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery. We describe our technique, illustrated with video, of robotic partial nephrectomy for complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance was used to resect 14 tumors in eight patients (mean age: 50.3 yr; range: 30-68 yr). Three patients had hereditary kidney cancer. All patients had complex tumor features, including hilar tumors (n=5), endophytic tumors (n=4), and/or multiple tumors (n=3). Robotic partial nephrectomy procedures were performed successfully without complications. Hilar clamping was used with a mean warm ischemia time of 31 min (range: 24-45 min). Mean blood loss was 230 ml (range: 100-450 ml). Histopathology confirmed clear-cell renal cell carcinoma (n=3), hybrid oncocytic tumor (n=2), chromophobe renal cell carcinoma (n=2), and oncocytoma (n=1). All patients had negative surgical margins. Mean index tumor size was 3.6 cm (range: 2.6-6.4 cm). Mean hospital stay was 2.6 d. At 3-mo follow-up, no patients experienced a statistically significant change in serum creatinine or estimated glomerular filtration rate and there was no evidence of tumor recurrence. Robotic partial nephrectomy is safe and feasible for select patients with complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance may facilitate a minimally invasive, nephron-sparing approach for select patients with complex renal tumors who might otherwise require open surgery or total nephrectomy.

Treatment of Ion-Atom Collisions Using a Partial-Wave Expansion of the Projectile Wavefunction

Science.gov (United States)

Wong, T. G.; Foster, M.; Colgan, J.; Madison, D. H.

2009-01-01

We present calculations of ion-atom collisions using a partial-wave expansion of the projectile wavefunction. Most calculations of ion-atom collisions have typically used classical or plane-wave approximations for the projectile wavefunction, since partial-wave expansions are expected to require prohibitively large numbers of terms to converge…

Two-fold sustainability – Adobe with sawdust as partial sand replacement

Science.gov (United States)

Jokhio, Gul A.; Syed Mohsin, Sharifah M.; Gul, Yasmeen

2018-04-01

Adobe is a material that is economic, environment friendly, and provides better indoor air quality. The material required for the preparation of adobe include clay, sand, and sometimes straw or other organic materials. These materials do not require industrial processing or transportation, however, sand mining has been recently posing a threat to the environment. Therefore, to enhance the existing sustainability of adobe, sand can be partially or fully replaced by other waste materials. This approach will not only solve the problem of excessive sand mining, it will also address the issue of waste management. Sawdust is one such waste material that can be used to partially replace sand in Adobe. This paper presents the results of compressive and flexural test carried out on Adobe samples with partial sand replacement by sawdust. The results show that about 4% sand replacement by volume produces higher compressive strength, whereas the flexural strength reduces with the use of sawdust. However, since flexural strength is not a critical property for adobe, it is concluded that replacing sand with sawdust by about 4% of volume will be beneficial.

Elliptic partial differential equations

CERN Document Server

Han, Qing

2011-01-01

Elliptic Partial Differential Equations by Qing Han and FangHua Lin is one of the best textbooks I know. It is the perfect introduction to PDE. In 150 pages or so it covers an amazing amount of wonderful and extraordinary useful material. I have used it as a textbook at both graduate and undergraduate levels which is possible since it only requires very little background material yet it covers an enormous amount of material. In my opinion it is a must read for all interested in analysis and geometry, and for all of my own PhD students it is indeed just that. I cannot say enough good things abo

Experts' understanding of partial derivatives using the Partial Derivative Machine

OpenAIRE

Roundy, David; Dorko, Allison; Dray, Tevian; Manogue, Corinne A.; Weber, Eric

2014-01-01

Partial derivatives are used in a variety of different ways within physics. Most notably, thermodynamics uses partial derivatives in ways that students often find confusing. As part of a collaboration with mathematics faculty, we are at the beginning of a study of the teaching of partial derivatives, a goal of better aligning the teaching of multivariable calculus with the needs of students in STEM disciplines. As a part of this project, we have performed a pilot study of expert understanding...

Characterization of Dengue Virus Resistance to Brequinar in Cell Culture▿

Science.gov (United States)

Qing, Min; Zou, Gang; Wang, Qing-Yin; Xu, Hao Ying; Dong, Hongping; Yuan, Zhiming; Shi, Pei-Yong

2010-01-01

Brequinar is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. Here we report that brequinar has activity against a broad spectrum of viruses. The compound not only inhibits flaviviruses (dengue virus, West Nile virus, yellow fever virus, and Powassan virus) but also suppresses a plus-strand RNA alphavirus (Western equine encephalitis virus) and a negative-strand RNA rhabdovirus (vesicular stomatitis virus). Using dengue virus serotype 2 (DENV-2) as a model, we found that brequinar suppressed the viral infection cycle mainly at the step of RNA synthesis. Supplementing the culture medium with pyrimidines (cytidine or uridine) but not purines (adenine or guanine) could be used to reverse the inhibitory effect of the compound. Continuous culturing of DENV-2 in the presence of brequinar generated viruses that were partially resistant to the inhibitor. Sequencing of the resistant viruses revealed two amino acid mutations: one mutation (M260V) located at a helix in the domain II of the viral envelope protein and another mutation (E802Q) located at the priming loop of the nonstructural protein 5 (NS5) polymerase domain. Functional analysis of the mutations suggests that the NS5 mutation exerts resistance through enhancement of polymerase activity. The envelope protein mutation reduced the efficiency of virion assembly/release; however, the mutant virus became less sensitive to brequinar inhibition at the step of virion assembly/release. Taken together, the results indicate that (i) brequinar blocks DENV RNA synthesis through depletion of intracellular pyrimidine pools and (ii) the compound may also exert its antiviral activity through inhibition of virion assembly/release. PMID:20606073

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

Directory of Open Access Journals (Sweden)

Viktor A. Zapol’skii

2012-04-01

Full Text Available The nitropolychlorobutadienes 3, 4 are valuable building blocks for various amination and successive heterocyclization products. Nucleophilic substitution reactions of the partially protected, bioactive amines 1, 2 with either vinyl, imidoyl or carbonyl chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succeeded. Deprotection of 21, 12 and 28 proved to be only partially feasible.

Substituted 7-amino-5-thio-thiazolo[4,5-d]pyrimidines as potent and selective antagonists of the fractalkine receptor (CX3CR1).

Science.gov (United States)

Karlström, Sofia; Nordvall, Gunnar; Sohn, Daniel; Hettman, Andreas; Turek, Dominika; Åhlin, Kristofer; Kers, Annika; Claesson, Martina; Slivo, Can; Lo-Alfredsson, Yvonne; Petersson, Carl; Bessidskaia, Galina; Svensson, Per H; Rein, Tobias; Jerning, Eva; Malmberg, Åsa; Ahlgen, Charlotte; Ray, Colin; Vares, Lauri; Ivanov, Vladimir; Johansson, Rolf

2013-04-25

We have developed two parallel series, A and B, of CX3CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]pyrimidine core structure, we were able to achieve compounds with high selectivity for CX3CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with α-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX3CR1 antagonists.

When Partial Nephrectomy is Unsuccessful: Understanding the Reasons for Conversion from Robotic Partial to Radical Nephrectomy at a Tertiary Referral Center.

Science.gov (United States)

Kara, Önder; Maurice, Matthew J; Mouracade, Pascal; Malkoç, Ercan; Dagenais, Julien; Nelson, Ryan J; Chavali, Jaya Sai S; Stein, Robert J; Fergany, Amr; Kaouk, Jihad H

2017-07-01

We sought to identify the preoperative factors associated with conversion from robotic partial nephrectomy to radical nephrectomy. We report the incidence of this event. Using our institutional review board approved database, we abstracted data on 1,023 robotic partial nephrectomies performed at our center between 2010 and 2015. Standard and converted cases were compared in terms of patients and tumor characteristics, and perioperative, functional and oncologic outcomes. Logistic regression analysis was done to identify predictors of radical conversion. The overall conversion rate was 3.1% (32 of 1,023 cases). The most common reasons for conversion were tumor involvement of hilar structures (8 cases or 25%), failure to achieve negative margins on frozen section (7 or 21.8%), suspicion of advanced disease (5 or 15.6%) and failure to progress (5 or 15.6%). Patients requiring conversion were older and had a higher Charlson score (both p partial nephrectomy cases had similar short-term oncologic outcomes but better renal functional preservation (p partial nephrectomy conversion to radical nephrectomy was 3.1%, including 2.2% of preoperatively anticipated nephrectomy cases. Increasing tumor size and complexity, and poor preoperative renal function are the main predictors of conversion. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Public-Interest Benefit Evaluation of Partial- Upgrading Technology

Directory of Open Access Journals (Sweden)

G. Kent Fellows

2017-01-01

Full Text Available Approximately 60 per cent of Alberta’s oil sands production is non-upgraded bitumen which, after being mixed with a diluting agent (diluent to allow transport, is exported. A popular view within Alberta — and particularly among Albertan politicians — is that a much larger share of oil sands bitumen should be upgraded in the province. However, without public subsidies or government underwriting, it is uneconomic to build and operate new facilities in Alberta to fully upgrade the bitumen into synthetic crude oil. But there are new partial upgrading technologies being developed that, subject to successful testing at a larger (commercial pilot scale, can prove to be not only economic in Alberta, but also generate large social and economic benefits for the province. The advantages include a much smaller capital investment, a significant increase in the value of the product and market for the product and, even more importantly, a dramatic reduction in the need for large amounts of expensive diluent to transport the product to market. Indeed, the only diluent required will be that to move the bitumen from the production site to the partial upgrader and this can be continually recycled. The market for the synthetic crude oil produced by full upgrading is only getting tougher. Any Alberta bitumen fully upgraded here would compete closely with the rapidly expanding supply of light U.S. unconventional oil. Partial upgrading does not upgrade bitumen to a light crude, but to something resembling more of a medium or heavy crude, and at a lower cost per barrel than full upgrading. Unlike in the increasingly crowded light-crude market, the Alberta Royalty Review Advisory Panel recognized that currently there are gaps in several North American refineries that could be filled by this partially upgraded Alberta oil. A partial upgrader serving that less-competitive market not only appears to hold the potential for investors to make attractive returns in the

Partial report and other sampling procedures overestimate the duration of iconic memory.

Science.gov (United States)

Appelman, I B

1980-03-01

In three experiments, subjects estimated the duration of a brief visual image (iconic memory) either directly by adjusting onset of a click to offset of the visual image, or indirectly with a Sperling partial report (sampling) procedure. The results indicated that partial report and other sampling procedures may reflect other brief phenomena along with iconic memory. First, the partial report procedure yields a greater estimate of the duration of iconic memory than the more direct click method. Second, the partial report estimate of the duration of iconic memory is affected if the subject is required to simultaneously retain a list of distractor items (memory load), while the click method estimate of the duration of iconic memory is not affected by a memory load. Finally, another sampling procedure based on visual cuing yields different estimates of the duration of iconic memory depending on how many items are cued. It was concluded that partial report and other sampling procedures overestimate the duration of iconic memory.

Partial Molar Volumes of Aqua Ions from First Principles.

Science.gov (United States)

Wiktor, Julia; Bruneval, Fabien; Pasquarello, Alfredo

2017-08-08

Partial molar volumes of ions in water solution are calculated through pressures obtained from ab initio molecular dynamics simulations. The correct definition of pressure in charged systems subject to periodic boundary conditions requires access to the variation of the electrostatic potential upon a change of volume. We develop a scheme for calculating such a variation in liquid systems by setting up an interface between regions of different density. This also allows us to determine the absolute deformation potentials for the band edges of liquid water. With the properly defined pressures, we obtain partial molar volumes of a series of aqua ions in very good agreement with experimental values.

Engineering Solution for the Uniform Strength of Partially Cracked Concrete

DEFF Research Database (Denmark)

Hansen, Elin A.; Hansen, Will; Brincker, Rune

2005-01-01

Significant computational resources are required to predict the remaining strength from numerical fracture analysis of a jointed plain concrete pavement that contains a partial depth crack. It is, therefore, advantageous when the failure strength can be adequately predicted with an engineering...

Type-Directed Partial Evaluation

DEFF Research Database (Denmark)

Danvy, Olivier

1998-01-01

Type-directed partial evaluation uses a normalization function to achieve partial evaluation. These lecture notes review its background, foundations, practice, and applications. Of specific interest is the modular technique of offline and online type-directed partial evaluation in Standard ML...

Type-Directed Partial Evaluation

DEFF Research Database (Denmark)

Danvy, Olivier

1998-01-01

Type-directed partial evaluation uses a normalization function to achieve partial evaluation. These lecture notes review its background, foundations, practice, and applications. Of specific interest is the modular technique of offline and online type-directed partial evaluation in Standard ML of ...

DMH1 (4-[6-(4-isopropoxyphenylpyrazolo[1,5-a]pyrimidin-3-yl]quinoline inhibits chemotherapeutic drug-induced autophagy

Directory of Open Access Journals (Sweden)

Yue Sheng

2015-07-01

Full Text Available Our previous work found that DMH1 (4-[6-(4-isopropoxyphenylpyrazolo [1,5-a]pyrimidin-3-yl]quinoline was a novel autophagy inhibitor. Here, we aimed to investigate the effects of DMH1 on chemotherapeutic drug-induced autophagy as well as the efficacy of chemotherapeutic drugs in different cancer cells. We found that DMH1 inhibited tamoxifen- and cispcis-diaminedichloroplatinum (II (CDDP-induced autophagy responses in MCF-7 and HeLa cells, and potentiated the anti-tumor activity of tamoxifen and CDDP for both cells. DMH1 inhibited 5-fluorouracil (5-FU-induced autophagy responses in MCF-7 and HeLa cells, but did not affect the anti-tumor activity of 5-FU for these two cell lines. DMH1 itself did not induce cell death in MCF-7 and HeLa cells, but inhibited the proliferation of these cells. In conclusion, DMH1 inhibits chemotherapeutic drug-induced autophagy response and the enhancement of efficacy of chemotherapeutic drugs by DMH1 is dependent on the cell sensitivity to drugs.

Survey the Effects of Partial Root Zone Deficit Irrigation and Deficit Irrigation on Quantitative, Qualitative and Water Use Efficiency of Pomegranate

Directory of Open Access Journals (Sweden)

mohammad saeed tadaion

2017-12-01

Full Text Available Introduction: One of the latest efficient methods on increment of water use efficiency that confirmed by many scientists all over the world is deficit and alternative partial root zone deficit irrigation. In this experiment the effect of deficit and alternative partial root zone deficit irrigation on fruit yield, quality and water use efficiency of pomegranate (Punicagranatum (L. cv. Zarde-anar were investigatedin Arsenjan semi-arid region. Materials and Methods: The experiment was carried out in a constant plots and randomized complete block design (RCBD with four replicationsin five years.Treatmentswere 1- full flood irrigation (100 percent crop water requirement (T1 2- flood irrigation with 100 percent crop water requirement as alternate partial root-zone irrigation(every irrigation conducted on one side of tree (T2 3- flood irrigation with 50 percent crop water requirement as regular deficit irrigation (T3 4- full two-side drip irrigation(with regard to crop water requirement (eight drippers with twolit/hour flow by two different individual networks (T4 5- alternate partial root-zone drip irrigation with 100 percent crop water requirement (T5 6- regular deficit drip irrigation with 50 percent crop water requirement (T6 in every irrigation period. Each experimental treatment includes four trees and 96 similar twelve years old trees overall. Cultivation practice was conducted similarly on all of the trees. Results and Discussion: Results showed that the highest yield and water use efficiency based on statistical analysis belong to both PRD treatments i.e. alternate partial root-zone drip irrigation with 100 percent crop water requirement and alternate partial root-zone flood irrigation with 100 percent crop water requirement, respectively, that both of them decreased water requirement for irrigation up to 35 and 50 percent in comparison tocontrol. Application of partial root drying irrigation on both traditional flood irrigation and drip

Partially ordered sets in complex networks

International Nuclear Information System (INIS)

Xuan Qi; Du Fang; Wu Tiejun

2010-01-01

In this paper, a partial-order relation is defined among vertices of a network to describe which vertex is more important than another on its contribution to the connectivity of the network. A maximum linearly ordered subset of vertices is defined as a chain and the chains sharing the same end-vertex are grouped as a family. Through combining the same vertices appearing in different chains, a directed chain graph is obtained. Based on these definitions, a series of new network measurements, such as chain length distribution, family diversity distribution, as well as the centrality of families, are proposed. By studying the partially ordered sets in three kinds of real-world networks, many interesting results are revealed. For instance, the similar approximately power-law chain length distribution may be attributed to a chain-based positive feedback mechanism, i.e. new vertices prefer to participate in longer chains, which can be inferred by combining the notable preferential attachment rule with a well-ordered recommendation manner. Moreover, the relatively large average incoming degree of the chain graphs may indicate an efficient substitution mechanism in these networks. Most of the partially ordered set-based properties cannot be explained by the current well-known scale-free network models; therefore, we are required to propose more appropriate network models in the future.

Partial Discharge Monitoring in Power Transformers Using Low-Cost Piezoelectric Sensors.

Science.gov (United States)

Castro, Bruno; Clerice, Guilherme; Ramos, Caio; Andreoli, André; Baptista, Fabricio; Campos, Fernando; Ulson, José

2016-08-10

Power transformers are crucial in an electric power system. Failures in transformers can affect the quality and cause interruptions in the power supply. Partial discharges are a phenomenon that can cause failures in the transformers if not properly monitored. Typically, the monitoring requires high-cost corrective maintenance or even interruptions of the power system. Therefore, the development of online non-invasive monitoring systems to detect partial discharges in power transformers has great relevance since it can reduce significant maintenance costs. Although commercial acoustic emission sensors have been used to monitor partial discharges in power transformers, they still represent a significant cost. In order to overcome this drawback, this paper presents a study of the feasibility of low-cost piezoelectric sensors to identify partial discharges in mineral insulating oil of power transformers. The analysis of the feasibility of the proposed low-cost sensor is performed by its comparison with a commercial acoustic emission sensor commonly used to detect partial discharges. The comparison between the responses in the time and frequency domain of both sensors was carried out and the experimental results indicate that the proposed piezoelectric sensors have great potential in the detection of acoustic waves generated by partial discharges in insulation oil, contributing for the popularization of this noninvasive technique.

Partial Discharge Monitoring in Power Transformers Using Low-Cost Piezoelectric Sensors

Directory of Open Access Journals (Sweden)

Bruno Castro

2016-08-01

Full Text Available Power transformers are crucial in an electric power system. Failures in transformers can affect the quality and cause interruptions in the power supply. Partial discharges are a phenomenon that can cause failures in the transformers if not properly monitored. Typically, the monitoring requires high-cost corrective maintenance or even interruptions of the power system. Therefore, the development of online non-invasive monitoring systems to detect partial discharges in power transformers has great relevance since it can reduce significant maintenance costs. Although commercial acoustic emission sensors have been used to monitor partial discharges in power transformers, they still represent a significant cost. In order to overcome this drawback, this paper presents a study of the feasibility of low-cost piezoelectric sensors to identify partial discharges in mineral insulating oil of power transformers. The analysis of the feasibility of the proposed low-cost sensor is performed by its comparison with a commercial acoustic emission sensor commonly used to detect partial discharges. The comparison between the responses in the time and frequency domain of both sensors was carried out and the experimental results indicate that the proposed piezoelectric sensors have great potential in the detection of acoustic waves generated by partial discharges in insulation oil, contributing for the popularization of this noninvasive technique.

Compatriot partiality and cosmopolitan justice: Can we justify compatriot partiality within the cosmopolitan framework?

Directory of Open Access Journals (Sweden)

Rachelle Bascara

2016-10-01

Full Text Available This paper shows an alternative way in which compatriot partiality could be justified within the framework of global distributive justice. Philosophers who argue that compatriot partiality is similar to racial partiality capture something correct about compatriot partiality. However, the analogy should not lead us to comprehensively reject compatriot partiality. We can justify compatriot partiality on the same grounds that liberation movements and affirmative action have been justified. Hence, given cosmopolitan demands of justice, special consideration for the economic well-being of your nation as a whole is justified if and only if the country it identifies is an oppressed developing nation in an unjust global order.This justification is incomplete. We also need to say why Person A, qua national of Country A, is justified in helping her compatriots in Country A over similarly or slightly more oppressed non-compatriots in Country B. I argue that Person A’s partiality towards her compatriots admits further vindication because it is part of an oppressed group’s project of self-emancipation, which is preferable to paternalistic emancipation.Finally, I identify three benefits in my justification for compatriot partiality. First, I do not offer a blanket justification for all forms of compatriot partiality. Partiality between members of oppressed groups is only a temporary effective measure designed to level an unlevel playing field. Second, because history attests that sovereign republics could arise as a collective response to colonial oppression, justifying compatriot partiality on the grounds that I have identified is conducive to the development of sovereignty and even democracy in poor countries, thereby avoiding problems of infringement that many humanitarian poverty alleviation efforts encounter. Finally, my justification for compatriot partiality complies with the implicit cosmopolitan commitment to the realizability of global justice

The orotate transporter oroP from Lactococcus lactis can be used both as a very efficient, food-grade selection and counter-selection marker for strain construction in many different organisms

DEFF Research Database (Denmark)

Defoor, Els Marie Celine; Martinussen, Jan

frame oroP on pDBORO necessary for the uptake of orotate was identified. A number of industrial important strains like Lactococcus lactis, Bacillus subtilus, and Bacillus licheniformis have been shown to be unable to metabolize orotate. If the oroP gene was introduced into these strains they acquired...... the ability to utilize orotate. If the strains had a pyrimidine requirement, the oroP gene could function as a selectable marker when growing in the presence of orotate as sole pyrimidine source. In an otherwise resistant strain, oroP was shown to sensitize the strain towards the analog 5-Fluoroorotate....... It was shown that strains who have lost the oroP gene could easily be selected in the presence of 5-Fluoroorotate, thus being an efficient counter-selection marker. pyrimidine-requiring strain (pyr B, C or D) orotate negative Counter-selection marker: wild-type strain! Fluoro-orotate resistant Functional...

Chemical polishing of partially oxidized T-111 alloy

International Nuclear Information System (INIS)

Teaney, P.E.

1974-01-01

The specimens were pressure-mounted in Bakelite and ground through 600 grit on silicon carbide papers. The specimens were rough-polished on a vibratory polisher for 4 to 6 h, using a water slurry of one micron alumina on Texmet, followed by 0.3-μ alumina on Texmet overnight. Final polishing was accomplished by continuous swabbing with a chemical polish. A chemical polish consisting of ten parts lactic acid, four parts nitric acid, and four parts hydrofluoric acid worked well for the T-111 parent material specimens; however, in the partially oxidized specimens, considerable pitting and staining occurred in the oxygen-affected zone and in the transition zone between the oxygen-affected zone and the parent material. A chemical polish was developed for the partially oxidized specimens by adjusting the ratio of the acids to ten parts lactic acid, two parts nitric acid, and two parts hydrofluoric acid. This slowed the chemical attack on the oxygen-affected zone considerably and, with continuous swabbing, the pitting and stain could be avoided. The specimens were rinsed and checked occasionally on the metallograph to determine when the proper polish had been obtained. Some specimens required intermittent polishing times up to 1 / 2 hour. No relationship could be established between the oxygen content of the specimen and the time required for chemical polishing in the partially oxidized specimens. However, the microstructure of the transition zone was the most difficult to obtain, and specimens with uniform reaction zones across the width of the specimen polished quicker than those with the transition zone

Essays on partial retirement

NARCIS (Netherlands)

Kantarci, T.

2012-01-01

The five essays in this dissertation address a range of topics in the micro-economic literature on partial retirement. The focus is on the labor market behavior of older age groups. The essays examine the economic and non-economic determinants of partial retirement behavior, the effect of partial

Cell division requirement for activation of murine leukemia virus in cell culture by irradiation

International Nuclear Information System (INIS)

Otten, J.A.; Quarles, J.M.; Tennant, R.W.

1976-01-01

Actively dividing cultures of AKR mouse cells were exposed to relatively low dose-rates of γ radiation and tested for activation of endogenous leukemia viruses. Efficient and reproducible induction of virus was obtained with actively dividing cells, but cultures deprived of serum to inhibit cell division before and during γ irradiation were not activated, even when medium with serum was added immediately after irradiation. These results show that cell division was required for virus induction but that a stable intermediate similar to the state induced by halogenated pyrimidines was not formed. In actively dividing AKR cell cultures, virus activation appeared to be proportional to the dose of γ radiation; the estimated frequency of activation was 1-8 x 10 - 5 per exposed cell and the efficiency of activation was approximately 0.012 inductions per cell per rad. Other normal primary and established mouse cell cultures tested were not activated by γ radiation. The requirement of cell division for radiation and chemical activation may reflect some common mechanism for initiation of virus expression

[{sup 18}F]D.P.A.-714: a novel fluorine-18-labelled pyrazolo[1,5-a]pyrimidine acetamide for imaging the peripheral benzodiazepine receptors with PET - radiosynthesis on a zymate-xp robotic system

Energy Technology Data Exchange (ETDEWEB)

Dolle, F.; Damont, A.; Hinnen, F.; Kuhnast, B.; Chauveau, F.; Van camp, N.; Hantraye, P.; Tavitian, B. [Servvice Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); James, M.; Creelman, A.; Fulton, R.; Kassiou, M. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Vercouillie, J.; Guilloteau, D. [Universite Francois Rabelais de Tours, 37 (France); Vercouillie, J.; Guilloteau, D. [Centre Hospitalier Regional Universitaire, 37 - Tours (France); Selleri, S.; Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia)

2008-02-15

{sup 11}C D.P.A.-713 (N,N-diethyl-2-[2-(4-[{sup 11}C]methoxy-phenyl)-5,7-dimethyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) is a recently developed carbon-11-labelled (half life: 20.4 min)pyrazolo[1,5-a]pyrimidine acetamide for the in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.)). Preliminary results obtained in a rodent-model demonstrates that {sup 11}C D.P.A.-713 showed a high potential to in vivo image neuro-inflammation and additionally, this radioligand allowed a higher contrast between the lesioned area and the corresponding area in the intact contralateral hemisphere when compared to the radioligand of reference. D.P.A-714 (N,N-diethyl-2-[2-[4-(2-fluoro-ethoxy)phenyl] -5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]acetamide), a chemically closely related derivative of D.P.A.-713, had been designed with a fluorine atom in its structure, allowing ultimate labelling with fluorine-18, a longer-lived positron-emitter (half life:109.8 min) and today one of the most attractive PET isotopes for radiopharmaceutical chemistry. D.P.A.-714 as well as its corresponding tosylated derivative have been re-synthesized in 2 chemicals steps from D.P.A.-713. D.P.A.-714 has then been labelled at its aromatic fluoro-ethoxy group from the corresponding tosyl-derivative using the K{sup 18}FF-kryptofix{sub 222} (in CH{sub 3}CN (3 mL) at 85 degrees C for 5 min or D.M.S.O. (600 {mu}L) at 130 degrees C for 5 min). {sup 18}FD.P.A.-714 was then purified using semi preparative X terra reverse phase H.P.L.C., adequately formulated for i.v. injection and was found to be > 95% chemically and radiochemically pure. The total synthesis time was less than 90 min and the specific radioactivities at the end of the radiosynthesis ranged from 1 to 3 Ci/micro-mole. (N.C.)

Cyclobutyl pyrimidine dimer accumulation in relation to UV-B sensitivity in mung bean cultivars

International Nuclear Information System (INIS)

He Junmin; Wang Ruibin; Meng Zhaoni

2006-01-01

The purpose of the experiment is to reveal the relationship between cyclobutyl pyrimidine dimers (CPDs) accumulation and UV-B sensitivity in mung bean cultivars. Two mung bean cultivars (Phaseolus raditus L. cv. Qindou -2 0 and Zhonglü -1 ) were grown in greenhouse with treatment or without treatment of UV-B radiation (0.4 W * m -2 ) for four days. The UV-B-induced CPDs in mung bean DNA were quantified by enzyme-linked immunosorbent assay (ELISA) with specific monoclonal antibody and the relationship between CPDs accumulation and the UV-B sensitivity of mung bean seedlings were discussed. The UV-B-induced inhibition of the biomass and net photosynthetic rate of the primary leaves of cultivar Zhonglü -1 were respectively lower than that of cultivar Qindou -2 0, so that the cultivar Zhonglü -1 was more tolerant to UV-B than the cultivar Qindou -2 0. Meanwhile, the cultivar Zhonglü -1 had lower CPD accumulation and susceptibility to CPD induction, higher photorepair capacity and same dark repair capacity as compared with the cultivar Qindou -2 0. Different UV-B sensitivities between two mung bean cultivars may be mainly caused by the differences in CPD accumulation, which are caused by the different susceptibility to CPD induction and the different photorepair capacities. In addition, the different susceptibility to CPD induction between two mung bean cultivars is related to the different levels of UV-absorbing compounds

Lactobacilli evolve by cumulative DNA degeneration

OpenAIRE

Bringel , Françoise; Hubert , Jean-Claude

2004-01-01

International audience; Lactic acid bacteria require rich media since, due to mutations in their biosynthetic genes, they are unable to synthesise numerous amino acids and nucleobases. The extent of genetic lesions was investigated in two biosynthetic pathways for 150 Lactobacillus plantarum isolates from various origins. Arginine biosynthesis and pyrimidine biosynthesis share a common intermediate, carbamoyl phosphate (CP). No pyrimidine auxotrophs were detected and only 7 L. plantarum strai...

Probabilistic Characterization of Partial Volume Effects in Imaging of Rectangular Objects

Energy Technology Data Exchange (ETDEWEB)

Bulaevskaya, V. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2015-05-06

In imaging, a partial volume effect refers to the problem that arises when the system resolution is low relative to the size of the object being imaged [1, 2]. In this setting, it is likely that most voxels occupied by the object are only partially covered, and that the fraction covered in each voxel is low. This makes the problem of object detection and image segmentation very difficult because the algorithms designed for these purposes rely on pixel summary statistics. If the area covered by the object is very low in relatively many of the total number of the voxels the object occupies, these summary statistics may not reach the thresholds required to detect this object. It is thus important to understand the extent of partial volume effect for a given object size and resolution. This technical report focuses on rectangular objects and derives the probability distributions for three quantities for such objects: 1) the number of fully covered voxels, 2) the number of partially covered voxels, and 3) the fractions of the total volume covered in the partially covered voxels. The derivations are first shown for 2-D settings and are then extended to 3-D settings.

13 CFR 121.412 - What are the size procedures for partial small business set-asides?

Science.gov (United States)

2010-01-01

... Requirements for Government Procurement § 121.412 What are the size procedures for partial small business set... portion of a procurement, and is not required to qualify as a small business for the unrestricted portion. ...

Synthesis of modified oligonucleotides that contain purine and pyrimidine radio-induced base lesions

International Nuclear Information System (INIS)

Romieu, Anthony

1999-01-01

Different factors as oxidizing or carcinogenesis agents, UV and ionizing radiations,.... can generate a wide, spectrum of DNA base damages. In order to study the biochemical and structural features of these DNA damages, it is important to prepare short DNA fragments (20 to 50 bases long) bearing a single or several modifications at specific sites in their sequences. The chemical synthesis is a powerful tool to prepare such modified DNA fragments. This work focusses on the chemical incorporation of several modified nucleosides formed in DNA by ionizing radiations or by photo-sensitization. The first part of this study describes the preparation of a phosphoramidite synthon of 5-hydroxy-2'-deoxyuridine and its subsequent incorporation into synthetic oligonucleotides ranging from 14 to 33 bases long. In a second part (chapters Ill and IV), the synthesis and incorporation of original radiation-induced tandem lesions: the carbon-bridged cyclo-nucleosides are presented. Both (5'R)- and (5'S) diastereomers of 5',8-cyclo-2'-deoxyadenosine and 5',8-cyclo-2'-deoxyguanosine have been individually inserted into various different oligonucleotides (3 to 22 bases long) by using the standard phosphoramidite chemistry. The chemical incorporation of a pyrimidine analogue: (5'S, 6S)-5',6-cyclo-5,6-dihydro-thymidine has been also achieved. The loss of aromaticity of this modified nucleoside and its poor reactivity required the development of a synthetic strategy entirely different from that used for the preparation and subsequent incorporation of the phosphoramidite synthons of 5',8-cyclo-purine-2'-deoxyribo-nucleosides. The third part of this study deals with the synthesis of a phosphoramidite synthon of 4-hydroxy-8-oxo-4,8-dihydro-2'-deoxyguanosine. The two (4R)- and (4S)- diastereomers of this oxidized purine have been separated and individually inserted in several synthetic DNA fragments. No epimerization of C-4 position was observed during the solid-phase synthesis and during the

Optimal transformation for correcting partial volume averaging effects in magnetic resonance imaging

International Nuclear Information System (INIS)

Soltanian-Zadeh, H.; Windham, J.P.; Yagle, A.E.

1993-01-01

Segmentation of a feature of interest while correcting for partial volume averaging effects is a major tool for identification of hidden abnormalities, fast and accurate volume calculation, and three-dimensional visualization in the field of magnetic resonance imaging (MRI). The authors present the optimal transformation for simultaneous segmentation of a desired feature and correction of partial volume averaging effects, while maximizing the signal-to-noise ratio (SNR) of the desired feature. It is proved that correction of partial volume averaging effects requires the removal of the interfering features from the scene. It is also proved that correction of partial volume averaging effects can be achieved merely by a linear transformation. It is finally shown that the optimal transformation matrix is easily obtained using the Gram-Schmidt orthogonalization procedure, which is numerically stable. Applications of the technique to MRI simulation, phantom, and brain images are shown. They show that in all cases the desired feature is segmented from the interfering features and partial volume information is visualized in the resulting transformed images

9 CFR 381.150 - Requirements for the production of fully cooked poultry products and partially cooked poultry...

Science.gov (United States)

2010-01-01

... fully cooked poultry products and partially cooked poultry breakfast strips. 381.150 Section 381.150... ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Entry of Articles Into Official Establishments; Processing...

Pipeline transportation of emerging partially upgraded bitumen

International Nuclear Information System (INIS)

Luhning, R.W.; Anand, A.; Blackmore, T.; Lawson, D.S.

2002-01-01

The recoverable reserves of Canada's vast oil deposits is estimated to be 335 billion barrels (bbl), most of which are in the Alberta oil sands. Canada was the largest import supplier of crude oil to the United States in 2001, followed by Saudi Arabia. By 2011, the production of oil sands is expected to increase to 50 per cent of Canada's oil, and conventional oil production will decline as more production will be provided by synthetic light oil and bitumen. This paper lists the announced oil sands projects. If all are to proceed, production would reach 3,445,000 bbl per day by 2011. The three main challenges regarding the transportation and marketing of this new production were described. The first is to expand the physical capacity of existing pipelines. The second is the supply of low viscosity diluent (such as natural gas condensate or synthetic diluent) to reduce the viscosity and density of the bitumen as it passes through the pipelines. The current pipeline specifications and procedures to transport partially upgraded products are presented. The final challenge is the projected refinery market constraint to process the bitumen and synthetic light oil into consumer fuel products. These challenges can be addressed by modifying refineries and increasing Canadian access in Petroleum Administration Defense District (PADD) II and IV. The technology for partial upgrading of bitumen to produce pipeline specification oil, reduce diluent requirements and add sales value, is currently under development. The number of existing refineries to potentially accept partially upgraded product is listed. The partially upgraded bitumen will be in demand for additional upgrading to end user products, and new opportunities will be presented as additional pipeline capacity is made available to transport crude to U.S. markets and overseas. The paper describes the following emerging partial upgrading methods: the OrCrude upgrading process, rapid thermal processing, CPJ process for

Succinct partial sums and fenwick trees

DEFF Research Database (Denmark)

Bille, Philip; Christiansen, Anders Roy; Prezza, Nicola

2017-01-01

We consider the well-studied partial sums problem in succint space where one is to maintain an array of n k-bit integers subject to updates such that partial sums queries can be efficiently answered. We present two succint versions of the Fenwick Tree – which is known for its simplicity...... and practicality. Our results hold in the encoding model where one is allowed to reuse the space from the input data. Our main result is the first that only requires nk + o(n) bits of space while still supporting sum/update in O(logbn)/O(blogbn) time where 2 ≤ b ≤ log O(1)n. The second result shows how optimal...... time for sum/update can be achieved while only slightly increasing the space usage to nk + o(nk) bits. Beyond Fenwick Trees, the results are primarily based on bit-packing and sampling – making them very practical – and they also allow for simple optimal parallelization....

Computational acceleration for MR image reconstruction in partially parallel imaging.

Science.gov (United States)

Ye, Xiaojing; Chen, Yunmei; Huang, Feng

2011-05-01

In this paper, we present a fast numerical algorithm for solving total variation and l(1) (TVL1) based image reconstruction with application in partially parallel magnetic resonance imaging. Our algorithm uses variable splitting method to reduce computational cost. Moreover, the Barzilai-Borwein step size selection method is adopted in our algorithm for much faster convergence. Experimental results on clinical partially parallel imaging data demonstrate that the proposed algorithm requires much fewer iterations and/or less computational cost than recently developed operator splitting and Bregman operator splitting methods, which can deal with a general sensing matrix in reconstruction framework, to get similar or even better quality of reconstructed images.

Anatomic partial nephrectomy: technique evolution.

Science.gov (United States)

Azhar, Raed A; Metcalfe, Charles; Gill, Inderbir S

2015-03-01

Partial nephrectomy provides equivalent long-term oncologic and superior functional outcomes as radical nephrectomy for T1a renal masses. Herein, we review the various vascular clamping techniques employed during minimally invasive partial nephrectomy, describe the evolution of our partial nephrectomy technique and provide an update on contemporary thinking about the impact of ischemia on renal function. Recently, partial nephrectomy surgical technique has shifted away from main artery clamping and towards minimizing/eliminating global renal ischemia during partial nephrectomy. Supported by high-fidelity three-dimensional imaging, novel anatomic-based partial nephrectomy techniques have recently been developed, wherein partial nephrectomy can now be performed with segmental, minimal or zero global ischemia to the renal remnant. Sequential innovations have included early unclamping, segmental clamping, super-selective clamping and now culminating in anatomic zero-ischemia surgery. By eliminating 'under-the-gun' time pressure of ischemia for the surgeon, these techniques allow an unhurried, tightly contoured tumour excision with point-specific sutured haemostasis. Recent data indicate that zero-ischemia partial nephrectomy may provide better functional outcomes by minimizing/eliminating global ischemia and preserving greater vascularized kidney volume. Contemporary partial nephrectomy includes a spectrum of surgical techniques ranging from conventional-clamped to novel zero-ischemia approaches. Technique selection should be tailored to each individual case on the basis of tumour characteristics, surgical feasibility, surgeon experience, patient demographics and baseline renal function.

Metabolome Profiling of Partial and Fully Reprogrammed Induced Pluripotent Stem Cells.

Science.gov (United States)

Park, Soon-Jung; Lee, Sang A; Prasain, Nutan; Bae, Daekyeong; Kang, Hyunsu; Ha, Taewon; Kim, Jong Soo; Hong, Ki-Sung; Mantel, Charlie; Moon, Sung-Hwan; Broxmeyer, Hal E; Lee, Man Ryul

2017-05-15

Acquisition of proper metabolomic fate is required to convert somatic cells toward fully reprogrammed pluripotent stem cells. The majority of induced pluripotent stem cells (iPSCs) are partially reprogrammed and have a transcriptome different from that of the pluripotent stem cells. The metabolomic profile and mitochondrial metabolic functions required to achieve full reprogramming of somatic cells to iPSC status have not yet been elucidated. Clarification of the metabolites underlying reprogramming mechanisms should enable further optimization to enhance the efficiency of obtaining fully reprogrammed iPSCs. In this study, we characterized the metabolites of human fully reprogrammed iPSCs, partially reprogrammed iPSCs, and embryonic stem cells (ESCs). Using capillary electrophoresis time-of-flight mass spectrometry-based metabolomics, we found that 89% of analyzed metabolites were similarly expressed in fully reprogrammed iPSCs and human ESCs (hESCs), whereas partially reprogrammed iPSCs shared only 74% similarly expressed metabolites with hESCs. Metabolomic profiling analysis suggested that converting mitochondrial respiration to glycolytic flux is critical for reprogramming of somatic cells into fully reprogrammed iPSCs. This characterization of metabolic reprogramming in iPSCs may enable the development of new reprogramming parameters for enhancing the generation of fully reprogrammed human iPSCs.

29 CFR 1904.2 - Partial exemption for establishments in certain industries.

Science.gov (United States)

2010-07-01

... Partial exemption for establishments in certain industries. (a) Basic requirement. (1) If your business establishment is classified in a specific low hazard retail, service, finance, insurance or real estate industry... industry classification exemption apply only to business establishments in the retail, services, finance...

Inhibition of antigen-presenting activity of dendritic cells resulting from UV irradiation of murine skin is restored by in vitro photorepair of cyclobutane pyrimidine dimers

International Nuclear Information System (INIS)

Vink, A.A.; Roza, L.; Moodycliffe, A.M.; Shreedhar, V.

1997-01-01

Exposing skin to UVB (280-320 nm) radiation suppresses contact hypersensitivity by a mechanism that involves an alteration in the activity of cutaneous antigen-presenting cells (APC). UV-induced DNA damage appears to be an important molecular trigger for this effect. The specific target cells in the skin that sustain DNA damage relevant to the immunosuppressive effect have yet to be identified. We tested the hypothesis that UV-induced DNA damage in the cutaneous APC was responsible for their impaired ability to present antigen after in vivo UV irradiation. Cutaneous APC were collected from the draining lymph nodes of UVB-irradiated, hapten-sensitized mice and incubated in vitro with liposomes containing a photolyase, which, upon absorption of photoreactivating light, splits UV-induced cyclobutane pyrimidine dimers. Photosome treatment followed by photoreactivating light reduced the number of dimer-containing APC, restored the in vivo antigen-presenting activity of the draining lymph node cells, and blocked the induction of suppressor T cells. Neither Photosomes nor photoreactivating light alone, nor photoreactivating light given before Photosomes, restored APC activity, and Photosomes treatment did not reverse the impairment of APC function when isopsoralen plus UVA (320-400 nm) radiation was used instead of UVB. These controls indicate that the restoration of APC function matched the requirements of Photosome-mediated DNA repair for dimers and post-treatment photoreactivating light. These results provide compelling evidence that it is UV-induced DNA damage in cutaneous APC that leads to reduced immune function

Partial electron beam hardening of cast iron camshafts

Energy Technology Data Exchange (ETDEWEB)

Csizmazia, A.; Reti, T. [Szechenyi Istvan Univ., Gyoer (Hungary); Horvath, M.; Olah, I. [Audi Hungaria Motor Kft., Gyoer (Hungary)

2005-07-01

In order to improve the local surface properties (hardness, wear and contact fatigue resistance) of cast iron camshafts, detailed experiments with partial electron beam hardening have been performed. It was found that the required case depth of 0.3-0.5 mm and surface hardness of 600-700 HV can be achieved by using appropriately selected, computer-controlled processing parameters (angular speed, specific energy input, beam deflection). (orig.)

Tutorial on Online Partial Evaluation

Directory of Open Access Journals (Sweden)

William R. Cook

2011-09-01

Full Text Available This paper is a short tutorial introduction to online partial evaluation. We show how to write a simple online partial evaluator for a simple, pure, first-order, functional programming language. In particular, we show that the partial evaluator can be derived as a variation on a compositionally defined interpreter. We demonstrate the use of the resulting partial evaluator for program optimization in the context of model-driven development.

A QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP AND MOLECULAR DOCKING STUDY ON A SERIES OF PYRIMIDINES ACTING AS ANTI-HEPATITIS C VIRUS AGENTS

Directory of Open Access Journals (Sweden)

Sakshi Gupta

2013-12-01

Full Text Available A QSAR and molecular modeling study was performed on a series of pyrimidines acting as hepatitis C virus inhibitors. In this case, anti-HCV potency of the compounds was found to be significantly correlated with the hydrophobic property of the molecule, Kier’s first-order valence molecular connectivity index for a particular substituent, total structure connectivity index of the molecule, and an indicator parameter used for the presence of benzothiazole ring. The validity of the correlation was judged by leave-one-out jackknife procedure and predicting the activity of some test compounds. Using the correlation obtained, some new compounds of high potency have been predicted in the series. A docking study using Molegro Virtual Docker was performed on these predicted compounds to decipher their interactions with the receptor. It was observed that all the predicted compounds had better interaction energy and docking score than the ligand complexed with the protein.

[Routine oral examinations and specific after-care for removable partial dentures

NARCIS (Netherlands)

Baat, C. de; Witter, D.J.; Keltjens, H.M.A.M.; Creugers, N.H.J.

2011-01-01

Following treatment with a removable partial denture, routine oral examinations are required to stabilize the existing condition in a sustainable way and to make possible the timely treatment of anomalies which have appeared. In cases of problems assessed during a routine oral examination in

Standing intraoral extractions of cheek teeth aided by partial crown removal in 165 horses (2010-2016).

Science.gov (United States)

Rice, M K; Henry, T J

2018-01-01

Diseased cheek teeth in horses often require invasive extraction techniques that carry a high rate of complications. Techniques and instrumentation were developed to perform partial crown removal to aid standing intraoral extraction of diseased cheek teeth in horses. To analyse success rates and post-surgical complications in horses undergoing cheek teeth extraction assisted by partial crown removal. Retrospective cohort study. This study included 165 horses with 194 diseased cheek teeth that were extracted orally assisted by partial crown removal between 2010 and 2016. Medical records were analysed, including case details, obtained radiographs, surgical reports and follow-up information. Follow-up information (≥2 months) was obtained for 151 horses (91.5%). There were 95 horses examined post-operatively by the authors and, 16 horses by the referring veterinarian; in 40 horses, post-operative follow up was obtained by informal telephone interviews with the owner. Successful standing intraoral extraction of cheek teeth was obtained in 164/165 horses (99.4%). Twenty-five of these horses (15.2%) required additional intraoral extraction methods to complete the extraction, including minimally invasive transbuccal approach (n = 21) and tooth sectioning (n = 4). There was one (0.6%) horse with intraoral extraction failure that required standing repulsion to complete the extraction. The intraoperative complication of fractured root tips occurred in 11/165 horses (6.7%). Post-operative complications occurred in 6/165 horses (3.6%), including alveolar sequestra (n = 4), mild delay of alveolar healing at 2 months (n = 1), and development of a persistent draining tract secondary to a retained root tip (n = 1). Specialised instrumentation and additional training in the technique are recommended to perform partial crown removal in horses. Horses with cheek teeth extraction by partial crown removal have an excellent prognosis for a positive outcome. The term partial coronectomy

Extended abstract: Partial row projection methods

Energy Technology Data Exchange (ETDEWEB)

Bramley, R.; Lee, Y. [Indiana Univ., Bloomington, IN (United States)

1996-12-31

Accelerated row projection (RP) algorithms for solving linear systems Ax = b are a class of iterative methods which in theory converge for any nonsingular matrix. RP methods are by definition ones that require finding the orthogonal projection of vectors onto the null space of block rows of the matrix. The Kaczmarz form, considered here because it has a better spectrum for iterative methods, has an iteration matrix that is the product of such projectors. Because straightforward Kaczmarz method converges slowly for practical problems, typically an outer CG acceleration is applied. Definiteness, symmetry, or localization of the eigenvalues, of the coefficient matrix is not required. In spite of this robustness, work has generally been limited to structured systems such as block tridiagonal matrices because unlike many iterative solvers, RP methods cannot be implemented by simply supplying a matrix-vector multiplication routine. Finding the orthogonal projection of vectors onto the null space of block rows of the matrix in practice requires accessing the actual entries in the matrix. This report introduces a new partial RP algorithm which retains advantages of the RP methods.

Partially Observed Mixtures of IRT Models: An Extension of the Generalized Partial-Credit Model

Science.gov (United States)

Von Davier, Matthias; Yamamoto, Kentaro

2004-01-01

The generalized partial-credit model (GPCM) is used frequently in educational testing and in large-scale assessments for analyzing polytomous data. Special cases of the generalized partial-credit model are the partial-credit model--or Rasch model for ordinal data--and the two parameter logistic (2PL) model. This article extends the GPCM to the…

Partial lesions of the intratemporal segment of the facial nerve: graft versus partial reconstruction.

Science.gov (United States)

Bento, Ricardo F; Salomone, Raquel; Brito, Rubens; Tsuji, Robinson K; Hausen, Mariana

2008-09-01

In cases of partial lesions of the intratemporal segment of the facial nerve, should the surgeon perform an intraoperative partial reconstruction, or partially remove the injured segment and place a graft? We present results from partial lesion reconstruction on the intratemporal segment of the facial nerve. A retrospective study on 42 patients who presented partial lesions on the intratemporal segment of the facial nerve was performed between 1988 and 2005. The patients were divided into 3 groups based on the procedure used: interposition of the partial graft on the injured area of the nerve (group 1; 12 patients); keeping the preserved part and performing tubulization (group 2; 8 patients); and dividing the parts of the injured nerve (proximal and distal) and placing a total graft of the sural nerve (group 3; 22 patients). Fracture of the temporal bone was the most frequent cause of the lesion in all groups, followed by iatrogenic causes (p lesion of the facial nerve is still questionable. Among these 42 patients, the best results were those from the total graft of the facial nerve.

Partial twisting for scalar mesons

International Nuclear Information System (INIS)

Agadjanov, Dimitri; Meißner, Ulf-G.; Rusetsky, Akaki

2014-01-01

The possibility of imposing partially twisted boundary conditions is investigated for the scalar sector of lattice QCD. According to the commonly shared belief, the presence of quark-antiquark annihilation diagrams in the intermediate state generally hinders the use of the partial twisting. Using effective field theory techniques in a finite volume, and studying the scalar sector of QCD with total isospin I=1, we however demonstrate that partial twisting can still be performed, despite the fact that annihilation diagrams are present. The reason for this are delicate cancellations, which emerge due to the graded symmetry in partially quenched QCD with valence, sea and ghost quarks. The modified Lüscher equation in case of partial twisting is given

Gastric volvulus with partial and complete gastric necrosis

Science.gov (United States)

Shukla, Ram Mohan; Mandal, Kartik Chandra; Maitra, Sujay; Ray, Amit; Sarkar, Ruchirendu; Mukhopadhyay, Biswanath; Bhattacharya, Malay

2014-01-01

Here, we report two interesting cases of gastric necrosis in acute gastric volvulus due to eventration of the diaphragm. Both the cases presented with a significant challenge and were managed successfully. The management of the cases is presented and relevant literature is discussed. To the best of our knowledge, this is the first case report of gastric volvulus with gastric necrosis requiring complete and partial gastrectomy in the available English literature. PMID:24604987

Gastric volvulus with partial and complete gastric necrosis

Directory of Open Access Journals (Sweden)

Ram Mohan Shukla

2014-01-01

Full Text Available Here, we report two interesting cases of gastric necrosis in acute gastric volvulus due to eventration of the diaphragm. Both the cases presented with a significant challenge and were managed successfully. The management of the cases is presented and relevant literature is discussed. To the best of our knowledge, this is the first case report of gastric volvulus with gastric necrosis requiring complete and partial gastrectomy in the available English literature.

The Spectral/hp-Finite Element Method for Partial Differential Equations

DEFF Research Database (Denmark)

Engsig-Karup, Allan Peter

2009-01-01

dimensions. In the course the chosen programming environment is Matlab, however, this is by no means a necessary requirement. The mathematical level needed to grasp the details of this set of notes requires an elementary background in mathematical analysis and linear algebra. Each chapter is supplemented......This set of lecture notes provides an elementary introduction to both the classical Finite Element Method (FEM) and the extended Spectral/$hp$-Finite Element Method for solving Partial Differential Equations (PDEs). Many problems in science and engineering can be formulated mathematically...

Partial order infinitary term rewriting

DEFF Research Database (Denmark)

Bahr, Patrick

2014-01-01

We study an alternative model of infinitary term rewriting. Instead of a metric on terms, a partial order on partial terms is employed to formalise convergence of reductions. We consider both a weak and a strong notion of convergence and show that the metric model of convergence coincides with th...... to the metric setting -- orthogonal systems are both infinitarily confluent and infinitarily normalising in the partial order setting. The unique infinitary normal forms that the partial order model admits are Böhm trees....

Beginning partial differential equations

CERN Document Server

O'Neil, Peter V

2011-01-01

A rigorous, yet accessible, introduction to partial differential equations-updated in a valuable new edition Beginning Partial Differential Equations, Second Edition provides a comprehensive introduction to partial differential equations (PDEs) with a special focus on the significance of characteristics, solutions by Fourier series, integrals and transforms, properties and physical interpretations of solutions, and a transition to the modern function space approach to PDEs. With its breadth of coverage, this new edition continues to present a broad introduction to the field, while also addres

Photochemical and electrochemical studies on lanthanide complexes of 6-(hydroxymethylpyridine- 2-carboxaldehyde[2- methyl-pyrimidine-4,6-diyl] bis-hydrazone

Directory of Open Access Journals (Sweden)

María Alejandra Fernandez

2014-01-01

Full Text Available Herein we report the synthesis of the 6-(hydroxymethylpyridine-2- carboxaldehyde[2-methyl-pyrimidine- 4,6-diyl]bis-hydrazone by a condensation reaction between 6-(hydroxymethyl picolinaldehyde with 4,6-(bis-hydrazino-2- methylpyrimidine. This bis-hydrazone can be visualized as a two-arm system which exhibits photochemical induced [E,E]/[E,Z]/[Z,Z’] isomerizations and double coordination to metal centers. Configurational changes, upon UV light irradiation, were followed over time by 1 H NMR, establishing that isomerization, in both arms, is a consecutive reaction that follows first-order kinetics (k1 = 4.06 x 10-4 s-1 and k2 = 2.80 x 10-4 s-1. Furthermore, the synthesis of bis-hydrazone metal complexes with La (III and Sm (III ions was achieved; subsequently, the absorption and emission properties of these complexes were studied, determining the fluorescence quantum yields, La= 0.2024 and Sm= 0.1413. Electrochemical studies of the complexes were conducted by square wave voltammetry, demonstrating that the bis-hydrazone and its complexes are electroactive species between +1.5 and -2.5 V.

Hyperbolic partial differential equations

CERN Document Server

Witten, Matthew

1986-01-01

Hyperbolic Partial Differential Equations III is a refereed journal issue that explores the applications, theory, and/or applied methods related to hyperbolic partial differential equations, or problems arising out of hyperbolic partial differential equations, in any area of research. This journal issue is interested in all types of articles in terms of review, mini-monograph, standard study, or short communication. Some studies presented in this journal include discretization of ideal fluid dynamics in the Eulerian representation; a Riemann problem in gas dynamics with bifurcation; periodic M

Partial Cooperative Equilibria: Existence and Characterization

Directory of Open Access Journals (Sweden)

Amandine Ghintran

2010-09-01

Full Text Available We study the solution concepts of partial cooperative Cournot-Nash equilibria and partial cooperative Stackelberg equilibria. The partial cooperative Cournot-Nash equilibrium is axiomatically characterized by using notions of rationality, consistency and converse consistency with regard to reduced games. We also establish sufficient conditions for which partial cooperative Cournot-Nash equilibria and partial cooperative Stackelberg equilibria exist in supermodular games. Finally, we provide an application to strategic network formation where such solution concepts may be useful.

Partial covariance based functional connectivity computation using Ledoit-Wolf covariance regularization.

Science.gov (United States)

Brier, Matthew R; Mitra, Anish; McCarthy, John E; Ances, Beau M; Snyder, Abraham Z

2015-11-01

Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a complicated covariance structure. Partial covariance assesses the unique variance shared between two brain regions excluding any widely shared variance, hence is appropriate for the analysis of multivariate fMRI datasets. However, calculation of partial covariance requires inversion of the covariance matrix, which, in most functional connectivity studies, is not invertible owing to rank deficiency. Here we apply Ledoit-Wolf shrinkage (L2 regularization) to invert the high dimensional BOLD covariance matrix. We investigate the network organization and brain-state dependence of partial covariance-based functional connectivity. Although RSNs are conventionally defined in terms of shared variance, removal of widely shared variance, surprisingly, improved the separation of RSNs in a spring embedded graphical model. This result suggests that pair-wise unique shared variance plays a heretofore unrecognized role in RSN covariance organization. In addition, application of partial correlation to fMRI data acquired in the eyes open vs. eyes closed states revealed focal changes in uniquely shared variance between the thalamus and visual cortices. This result suggests that partial correlation of resting state BOLD time series reflect functional processes in addition to structural connectivity. Copyright © 2015 Elsevier Inc. All rights reserved.

Successful removable partial dentures.

Science.gov (United States)

Lynch, Christopher D

2012-03-01

Removable partial dentures (RPDs) remain a mainstay of prosthodontic care for partially dentate patients. Appropriately designed, they can restore masticatory efficiency, improve aesthetics and speech, and help secure overall oral health. However, challenges remain in providing such treatments, including maintaining adequate plaque control, achieving adequate retention, and facilitating patient tolerance. The aim of this paper is to review the successful provision of RPDs. Removable partial dentures are a successful form of treatment for replacing missing teeth, and can be successfully provided with appropriate design and fabrication concepts in mind.

Synthesis, spectroscopic and structural characterization of 5-benzoyl-4-phenyl-2-methylthio-1H-pyrimidine with theoretical calculations using density functional theory

Science.gov (United States)

İnkaya, Ersin; Dinçer, Muharrem; Şahan, Emine; Yıldırım, İsmail

2013-10-01

In this paper, we will report a combined experimental and theoretical investigation of the molecular structure and spectroscopic parameters (FT-IR, 1H NMR, 13C NMR) of 5-benzoyl-4-phenyl-2-methylthio-1H-pyrimidine. The compound crystallizes in the triclinic space group P-1 with Z = 2. The molecular geometry was also optimized using density functional theory (DFT/B3LYP) method with the 6-311G(d,p) and 6-311++G(d,p) basis sets in ground state and compared with the experimental data. All the assignments of the theoretical frequencies were performed by potential energy distributions using VEDA 4 program. Information about the size, shape, charge density distribution and site of chemical reactivity of the molecules has been obtained by mapping electron density isosurface with electrostatic potential (ESP). Also, non-linear optical properties of the title compound were performed at B3LYP/6-311++G(d,p) level. The theoretical results showed an excellent agreement with the experimental values.

32 CFR 751.13 - Partial payments.

Science.gov (United States)

2010-07-01

... voucher and all other information related to the partial payment shall be placed in the claim file. Action... 32 National Defense 5 2010-07-01 2010-07-01 false Partial payments. 751.13 Section 751.13 National... Claims Against the United States § 751.13 Partial payments. (a) Partial payments when hardship exists...

[Acrylic resin removable partial dentures].

Science.gov (United States)

de Baat, C; Witter, D J; Creugers, N H J

2011-01-01

An acrylic resin removable partial denture is distinguished from other types of removable partial dentures by an all-acrylic resin base which is, in principle, solely supported by the edentulous regions of the tooth arch and in the maxilla also by the hard palate. When compared to the other types of removable partial dentures, the acrylic resin removable partial denture has 3 favourable aspects: the economic aspect, its aesthetic quality and the ease with which it can be extended and adjusted. Disadvantages are an increased risk of caries developing, gingivitis, periodontal disease, denture stomatitis, alveolar bone reduction, tooth migration, triggering of the gag reflex and damage to the acrylic resin base. Present-day indications are ofa temporary or palliative nature or are motivated by economic factors. Special varieties of the acrylic resin removable partial denture are the spoon denture, the flexible denture fabricated of non-rigid acrylic resin, and the two-piece sectional denture. Furthermore, acrylic resin removable partial dentures can be supplied with clasps or reinforced by fibers or metal wires.

Study on the reactivity behavior partially loaded reactor cores using SIMULATE-3

International Nuclear Information System (INIS)

Holzer, Robert; Zeitz, Andreas; Grimminger, Werner; Lubczyk, Tobias

2009-01-01

The reactor core design for the NPP Gundremmingen unit B and C is performed since several years using the validated 3D reactor core calculation program SIMULATE-3. The authors describe a special application of the program to study the reactivity for different partial core loadings. Based on the comparison with results of the program CASMO-4 the program SIMULATE-3 was validated for the calculation of partially loaded reactor cores. For the planned reactor operation in NPP Gundremmingen using new MOX fuel elements the reactivity behavior was studied with respect to the KTA-Code requirements.

Management of long span partially edentulous maxilla with fixed removable denture prosthesis.

Science.gov (United States)

Jeyavalan, Mahilan I; Narasimman, M; Venkatakrishnan, C J; Philip, Jacob M

2012-07-01

Restoration of a long span partially edentulous maxilla with tooth supported prosthesis is challenging because of inherent anatomic limitations and unfavourable biomechanics present after the loss of teeth. A tooth supported fixed-removable prosthesis is a treatment option for restoration of such long span partially edentulous maxillary arches. This prosthesis meets the requirements for esthetics, phonetics, comfort, and hygiene, as well as favourable biomechanical stress distribution to the remaining natural tooth abutments. This article presents a procedure for fabrication of a fixed-removable prosthesis that has cement-retained custom cast bar metal substructure and a ball attachment retained removable superstructure prosthesis.

Association of poly-purine/poly-pyrimidine sequences with meiotic recombination hot spots

Directory of Open Access Journals (Sweden)

Pitt Joel PW

2006-07-01

Full Text Available Abstract Background Meiotic recombination events have been found to concentrate in 1–2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood. Some previous evidence suggests that poly-purine/poly-pyrimidine (poly-pu/py tracts (PPTs, a class of sequence with distinctive biochemical properties, could be involved in recombination, but no general association of PPTs with meiotic recombination hot spots has previously been reported. Results We used computational methods to investigate in detail the relationship between PPTs and hot spots. We show statistical associations of PPT frequency with hot spots of meiotic recombination initiating lesions, double-strand breaks, in the genome of the yeast S. cerevisiae and with experimentally well characterized human meiotic recombination hot spots. Supporting a possible role of poly-pu/py-rich sequences in hot spot recombination, we also found that all three single nucleotide polymorphisms previously shown to be associated with human hot spot activity changes occur within sequence contexts of 14 bp or longer that are 85% or more poly-pu/py and at least 70% G/C. These polymorphisms are all close to the hot spot mid points. Comparing the sequences of experimentally characterized human hot spots with the orthologous regions of the chimpanzee genome previously shown not to contain hot spots, we found that in all five cases in which comparisons for the hot spot central regions are possible with publicly available sequence data, there are differences near the human hot spot mid points within sequences 14 bp or longer consisting of more than 80% poly-pu/py and at least 50% G/C. Conclusion Our results, along with previous evidence for the unique biochemical properties and recombination-stimulating potential of poly-pu/py-rich sequences, suggest that the possible functional involvement of this type of sequence in meiotic

Nonclassical Symmetries for Nonlinear Partial Differential Equations via Compatibility

International Nuclear Information System (INIS)

El-Sabbagh, Mostafa F.; Ahmad, Ali T.

2011-01-01

The determining equations for the nonclassical symmetry reductions of nonlinear partial differential equations with arbitrary order can be obtained by requiring the compatibility between the original equations and the invariant surface conditions. The (2+1)-dimensional shallow water wave equation, Boussinesq equation, and the dispersive wave equations in shallow water serve as examples illustrating how compatibility leads quickly and easily to the determining equations for their nonclassical symmetries. (general)

Microwave measurements of water vapor partial pressure at high temperatures

International Nuclear Information System (INIS)

Latorre, V.R.

1991-01-01

One of the desired parameters in the Yucca Mountain Project is the capillary pressure of the rock comprising the repository. This parameter is related to the partial pressure of water vapor in the air when in equilibrium with the rock mass. Although there are a number of devices that will measure the relative humidity (directly related to the water vapor partial pressure), they generally will fail at temperatures on the order of 150C. Since thee author has observed borehole temperatures considerably in excess of this value in G-Tunnel at the Nevada Test Site (NTS), a different scheme is required to obtain the desired partial pressure data at higher temperatures. This chapter presents a microwave technique that has been developed to measure water vapor partial pressure in boreholes at temperatures up to 250C. The heart of the system is a microwave coaxial resonator whose resonant frequency is inversely proportional to the square root of the real part of the complex dielectric constant of the medium (air) filling the resonator. The real part of the dielectric constant of air is approximately equal to the square of the refractive index which, in turn, is proportional to the partial pressure of the water vapor in the air. Thus, a microwave resonant cavity can be used to measure changes in the relative humidity or partial pressure of water vapor in the air. Since this type of device is constructed of metal, it is able to withstand very high temperatures. The actual limitation is the temperature limit of the dielectric material in the cable connecting the resonator to its driving and monitoring equipment-an automatic network analyzer in our case. In the following sections, the theory of operation, design, construction, calibration and installation of the microwave diagnostics system is presented. The results and conclusions are also presented, along with suggestions for future work

Microlaparoscopic technique for partial salpingectomy using bipolar electrocoagulation.

Science.gov (United States)

Siegle, J C; Cartmell, L W; Rayburn, W F

2001-07-01

To describe a technique of performing a partial salpingectomy using a small-diameter (2-mm) laparoscope and bipolar electrocoagulation. Sixty consecutive women desiring permanent sterilization underwent laparoscopic partial salpingectomy using a 2-mm transumbilical laparoscope and secondary midline sites suprapubically and midway above the pubis. A midportion of the tube was coagulated using Kleppinger forceps, transected with scissors and removed using grasping forceps. Additional time to remove both coagulated tubal segments averaged 4 minutes (range, 3-10). Each segment (mean, 1.5 cm; range, 0.9-2.4 cm) was confirmed in the operating room, then histologically. The transected tubal edges were separated with no thermal injury to nearby structures and with no mesosalpingeal hemorrhage. No cases required conversion from microlaparoscopy to a traditional method, and recovery time was not prolonged. The puncture sites healed well without sutures. Successful removal of electrocoagulated tubal segments with histologic confirmation was undertaken microlaparoscopically, with minimal additional operative time.

Static and Vibrational Analysis of Partially Composite Beams Using the Weak-Form Quadrature Element Method

Directory of Open Access Journals (Sweden)

Zhiqiang Shen

2012-01-01

Full Text Available Deformation of partially composite beams under distributed loading and free vibrations of partially composite beams under various boundary conditions are examined in this paper. The weak-form quadrature element method, which is characterized by direct evaluation of the integrals involved in the variational description of a problem, is used. One quadrature element is normally sufficient for a partially composite beam regardless of the magnitude of the shear connection stiffness. The number of integration points in a quadrature element is adjustable in accordance with convergence requirement. Results are compared with those of various finite element formulations. It is shown that the weak form quadrature element solution for partially composite beams is free of slip locking, and high computational accuracy is achieved with smaller number of degrees of freedom. Besides, it is found that longitudinal inertia of motion cannot be simply neglected in assessment of dynamic behavior of partially composite beams.

A modified occlusal wafer for managing partially dentate orthognathic patients--a case series.

Science.gov (United States)

Soneji, Bhavin Kiritkumar; Esmail, Zaid; Sharma, Pratik

2015-03-01

A multidisciplinary approach is essential in orthognathic surgery to achieve stable and successful outcomes. The model surgery planning is an important aspect in achieving the desired aims. An occlusal wafer used at the time of surgery aids the surgeon during correct placement of the jaws. When dealing with partially dentate patients, the design of the occlusal wafer requires modification to appropriately position the jaw. Two cases with partially dentate jaws are presented in which the occlusal wafer has been modified to provide stability at the time of surgery.

Partial Actions and Power Sets

Directory of Open Access Journals (Sweden)

Jesús Ávila

2013-01-01

Full Text Available We consider a partial action (X,α with enveloping action (T,β. In this work we extend α to a partial action on the ring (P(X,Δ,∩ and find its enveloping action (E,β. Finally, we introduce the concept of partial action of finite type to investigate the relationship between (E,β and (P(T,β.

Contextual Requirements Prioritization and its Application to Smart Homes

NARCIS (Netherlands)

Sernani, Paolo; Dragoni, Aldo Franco; Serral, Estefanía; Dalpiaz, Fabiano

2017-01-01

When many requirements co-exist for a given system, prioritization is essential to determine which ones have higher priority. While the basic prioritization algorithms result in a total or partial order of the requirements, it is often the case that the priority of the requirements depends on the

Partial elastodynamic cloaking by means of fiber-reinforced composites

International Nuclear Information System (INIS)

Olsson, P; Wall, David J N

2011-01-01

In this paper, we show that if inextensible fibers are embedded in an elastic material (or the material is by some other means made considerably stiffer in a particular but possibly variable direction), one may obtain equations of motion which are form invariant under certain diffeomorphism, allowing for partial cloaking (or 'illusion optics') schemes in both 2D and 3D. The schemes are valid at all frequencies without requiring any active material properties, and will thus work in the time domain without requiring active materials. While being mathematically exact at all frequencies, the applicability is of course limited to where the continuum approximation holds. Additional limits, set by idealization in the modeling of fibers and core material, are also present. However, contrary to some other approaches, the solution does not require metamaterials with non-scalar mass densities, nor does it require the breaking of the supersymmetry of the elasticity tensor

Partial elastodynamic cloaking by means of fiber-reinforced composites

Science.gov (United States)

Olsson, P.; Wall, David J. N.

2011-04-01

In this paper, we show that if inextensible fibers are embedded in an elastic material (or the material is by some other means made considerably stiffer in a particular but possibly variable direction), one may obtain equations of motion which are form invariant under certain diffeomorphism, allowing for partial cloaking (or 'illusion optics') schemes in both 2D and 3D. The schemes are valid at all frequencies without requiring any active material properties, and will thus work in the time domain without requiring active materials. While being mathematically exact at all frequencies, the applicability is of course limited to where the continuum approximation holds. Additional limits, set by idealization in the modeling of fibers and core material, are also present. However, contrary to some other approaches, the solution does not require metamaterials with non-scalar mass densities, nor does it require the breaking of the supersymmetry of the elasticity tensor.

Real-time visualization of the vibrational wavepacket dynamics in electronically excited pyrimidine via femtosecond time-resolved photoelectron imaging

Science.gov (United States)

Li, Shuai; Long, Jinyou; Ling, Fengzi; Wang, Yanmei; Song, Xinli; Zhang, Song; Zhang, Bing

2017-07-01

The vibrational wavepacket dynamics at the very early stages of the S1-T1 intersystem crossing in photoexcited pyrimidine is visualized in real time by femtosecond time-resolved photoelectron imaging and time-resolved mass spectroscopy. A coherent superposition of the vibrational states is prepared by the femtosecond pump pulse at 315.3 nm, resulting in a vibrational wavepacket. The composition of the prepared wavepacket is directly identified by a sustained quantum beat superimposed on the parent-ion transient, possessing a frequency in accord with the energy separation between the 6a1 and 6b2 states. The dephasing time of the vibrational wavepacket is determined to be 82 ps. More importantly, the variable Franck-Condon factors between the wavepacket components and the dispersed cation vibrational levels are experimentally illustrated to identify the dark state and follow the energy-flow dynamics on the femtosecond time scale. The time-dependent intensities of the photoelectron peaks originated from the 6a1 vibrational state exhibit a clear quantum beating pattern with similar periodicity but a phase shift of π rad with respect to those from the 6b2 state, offering an unambiguous picture of the restricted intramolecular vibrational energy redistribution dynamics in the 6a1/6b2 Fermi resonance.

[Right beauty holds the mi organism and propofol for elderly patients with hip fracture surgery ICU sedation effect of comparative study].

Science.gov (United States)

Mao, Ye; Zhao, Jing; Gao, Yufeng

2015-05-19

To compare the microphones organism and propofol in elderly patients with hip fracture surgery ICU clinical effect and safety of sedation. To collect 5 hospitals in Harbin in January 2014-August 2014, 72 cases of senile spinal postoperative ICU patients, randomly divided into the propofol group (group A: 36 cases) and right beautiful mi organism group (group B: 36 cases).Group A: first of all, intravenous 1 mg/kg propofol sedation induction, according to different degree of sedation maintain propofol dosage is 0.5 to 0.5 mg · kg(-1) · h(-1). Group B: give the right pyrimidine load 1 mg · kg(-1) · h(-1) via intravenous 20 min, according to different degree of sedation sustained by intravenous pump right beauty holds 0.3 0.7 mu pyrimidine g · kg(-1) · h(-1). Compare two groups of patients sedation depth, ICU stay time, heart rate, blood pressure, breathing rate, increase analgesic drugs. Within the scope of the dose, propofol and the right supporting pyrimidine required calming effect similar to provide treatment (RamSay score > 3); Calm during the treatment, the right beauty pyrimidine group to the number of additional analgesics is less than the propofol group; Compared with propofol group, the right beauty pyrimidine a significant reduction in patients with ICU stay time. The incidence of adverse reactions in patients with similar between the two groups has no statistical significance (P > 0.05). In certain dose range of ICU in elderly hip fracture patients with postoperative propofol and right the pyrimidine sedation is safe and effective.

A fast exact sequential algorithm for the partial digest problem.

Science.gov (United States)

Abbas, Mostafa M; Bahig, Hazem M

2016-12-22

Restriction site analysis involves determining the locations of restriction sites after the process of digestion by reconstructing their positions based on the lengths of the cut DNA. Using different reaction times with a single enzyme to cut DNA is a technique known as a partial digestion. Determining the exact locations of restriction sites following a partial digestion is challenging due to the computational time required even with the best known practical algorithm. In this paper, we introduce an efficient algorithm to find the exact solution for the partial digest problem. The algorithm is able to find all possible solutions for the input and works by traversing the solution tree with a breadth-first search in two stages and deleting all repeated subproblems. Two types of simulated data, random and Zhang, are used to measure the efficiency of the algorithm. We also apply the algorithm to real data for the Luciferase gene and the E. coli K12 genome. Our algorithm is a fast tool to find the exact solution for the partial digest problem. The percentage of improvement is more than 75% over the best known practical algorithm for the worst case. For large numbers of inputs, our algorithm is able to solve the problem in a suitable time, while the best known practical algorithm is unable.

Cyclobutane pyrimidine dimers photolyase from extremophilic microalga: Remarkable UVB resistance and efficient DNA damage repair

Energy Technology Data Exchange (ETDEWEB)

Li, Chongjie [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Ma, Li [Key Laboratory of Biofuels, and Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101 (China); Mou, Shanli [Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao (China); Wang, Yibin, E-mail: wangyibin@fio.org.cn [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Zheng, Zhou; Liu, Fangming; Qi, Xiaoqing; An, Meiling; Chen, Hao [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Miao, Jinlai, E-mail: miaojinlai@163.com [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); State Key Laboratory of Biological Fermentation Engineering of Beer (In Preparation), Qingdao (China)

2015-03-15

Highlights: • Chlamydomonas sp. ICE-L photolyase gene PHR2 is first cloned and expressed in E. coli. • PHR2 complemented E. coli could efficiently survival from UV radiation. • Expressed PHR2 photolyase has distinct photo-reactivation activity in vitro. - Abstract: Bacteria living in the Antarctic region have developed several adaptive features for growth and survival under extreme conditions. Chlamydomonas sp. ICE-Lis well adapted to high levels of solar UV radiation. A putative photolyase was identified in the Chlamydomonas sp. ICE-L transcriptome. The complete cDNA sequence was obtained by RACE-PCR. This PHR encoding includes a polypeptide of 579 amino acids with clear photolyase signatures belonging to class II CPD-photolyases, sharing a high degree of homology with Chlamydomonas reinhardtii (68%). Real-time PCR was performed to investigate the potential DNA damage and responses following UVB exposure. CPD photolyase mRNA expression level increased over 50-fold in response to UVB radiation for 6 h. Using photolyase complementation assay, we demonstrated that DNA photolyase increased photo-repair more than 116-fold in Escherichia coli strain SY2 under 100 μw/cm{sup 2} UVB radiation. To determine whether photolyase is active in vitro, CPD photolyase was over-expressed. It was shown that pyrimidine dimers were split by the action of PHR2. This study reports the unique structure and high activity of the enzyme. These findings are relevant for further understanding of molecular mechanisms of photo-reactivation, and will accelerate the utilization of photolyase in the medical field.

Cyclobutane pyrimidine dimers photolyase from extremophilic microalga: Remarkable UVB resistance and efficient DNA damage repair

International Nuclear Information System (INIS)

Li, Chongjie; Ma, Li; Mou, Shanli; Wang, Yibin; Zheng, Zhou; Liu, Fangming; Qi, Xiaoqing; An, Meiling; Chen, Hao; Miao, Jinlai

2015-01-01

Highlights: • Chlamydomonas sp. ICE-L photolyase gene PHR2 is first cloned and expressed in E. coli. • PHR2 complemented E. coli could efficiently survival from UV radiation. • Expressed PHR2 photolyase has distinct photo-reactivation activity in vitro. - Abstract: Bacteria living in the Antarctic region have developed several adaptive features for growth and survival under extreme conditions. Chlamydomonas sp. ICE-Lis well adapted to high levels of solar UV radiation. A putative photolyase was identified in the Chlamydomonas sp. ICE-L transcriptome. The complete cDNA sequence was obtained by RACE-PCR. This PHR encoding includes a polypeptide of 579 amino acids with clear photolyase signatures belonging to class II CPD-photolyases, sharing a high degree of homology with Chlamydomonas reinhardtii (68%). Real-time PCR was performed to investigate the potential DNA damage and responses following UVB exposure. CPD photolyase mRNA expression level increased over 50-fold in response to UVB radiation for 6 h. Using photolyase complementation assay, we demonstrated that DNA photolyase increased photo-repair more than 116-fold in Escherichia coli strain SY2 under 100 μw/cm 2 UVB radiation. To determine whether photolyase is active in vitro, CPD photolyase was over-expressed. It was shown that pyrimidine dimers were split by the action of PHR2. This study reports the unique structure and high activity of the enzyme. These findings are relevant for further understanding of molecular mechanisms of photo-reactivation, and will accelerate the utilization of photolyase in the medical field

Recent developments regarding the use of thieno[2,3-d]pyrimidin-4-one derivatives in medicinal chemistry, with a focus on their synthesis and anticancer properties.

Science.gov (United States)

Bozorov, Khurshed; Zhao, Jiang-Yu; Elmuradov, Burkhon; Pataer, Apar; Aisa, Haji A

2015-09-18

It is generally understood that the antitumor properties of synthetic heterocyclic compounds are among the most powerful properties that can be made use in medicinal chemistry. More specifically, their substantial cytotoxic effects against different types of human tumor cells, in addition to their roles as enzymes or receptors for various kinase inhibitors, make them critically important. In recent years, thieno[2,3-d]pyrimidin-4-one derivatives (TPs), which are analogs of quinazoline alkaloids, have frequently attracted the interest of medicinal chemistry researchers due to their promising anticancer properties. The present study is a review of the latest advances (i.e., since 2006) in TP derivative-related research, with a focus on how such derivatives are synthesized and on their anticancer activities. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

DNA polymerase zeta cooperates with polymerases kappa and iota in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients.

Science.gov (United States)

Ziv, Omer; Geacintov, Nicholas; Nakajima, Satoshi; Yasui, Akira; Livneh, Zvi

2009-07-14

Human cells tolerate UV-induced cyclobutane pyrimidine dimers (CPD) by translesion DNA synthesis (TLS), carried out by DNA polymerase eta, the POLH gene product. A deficiency in DNA polymerase eta due to germ-line mutations in POLH causes the hereditary disease xeroderma pigmentosum variant (XPV), which is characterized by sunlight sensitivity and extreme predisposition to sunlight-induced skin cancer. XPV cells are UV hypermutable due to the activity of mutagenic TLS across CPD, which explains the cancer predisposition of the patients. However, the identity of the backup polymerase that carries out this mutagenic TLS was unclear. Here, we show that DNA polymerase zeta cooperates with DNA polymerases kappa and iota to carry out error-prone TLS across a TT CPD. Moreover, DNA polymerases zeta and kappa, but not iota, protect XPV cells against UV cytotoxicity, independently of nucleotide excision repair. This presents an extreme example of benefit-risk balance in the activity of TLS polymerases, which provide protection against UV cytotoxicity at the cost of increased mutagenic load.

DNA polymerase ζ cooperates with polymerases κ and ι in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients

Science.gov (United States)

Ziv, Omer; Geacintov, Nicholas; Nakajima, Satoshi; Yasui, Akira; Livneh, Zvi

2009-01-01

Human cells tolerate UV-induced cyclobutane pyrimidine dimers (CPD) by translesion DNA synthesis (TLS), carried out by DNA polymerase η, the POLH gene product. A deficiency in DNA polymerase η due to germ-line mutations in POLH causes the hereditary disease xeroderma pigmentosum variant (XPV), which is characterized by sunlight sensitivity and extreme predisposition to sunlight-induced skin cancer. XPV cells are UV hypermutable due to the activity of mutagenic TLS across CPD, which explains the cancer predisposition of the patients. However, the identity of the backup polymerase that carries out this mutagenic TLS was unclear. Here, we show that DNA polymerase ζ cooperates with DNA polymerases κ and ι to carry out error-prone TLS across a TT CPD. Moreover, DNA polymerases ζ and κ, but not ι, protect XPV cells against UV cytotoxicity, independently of nucleotide excision repair. This presents an extreme example of benefit-risk balance in the activity of TLS polymerases, which provide protection against UV cytotoxicity at the cost of increased mutagenic load. PMID:19564618

Neuronal Activity in the Subthalamic Cerebrovasodilator Area under Partial-Gravity Conditions in Rats

Directory of Open Access Journals (Sweden)

Zeredo L Zeredo

2014-03-01

Full Text Available The reduced-gravity environment in space is known to cause an upward shift in body fluids and thus require cardiovascular adaptations in astronauts. In this study, we recorded in rats the neuronal activity in the subthalamic cerebrovasodilator area (SVA, a key area that controls cerebral blood flow (CBF, in response to partial gravity. “Partial gravity” is the term that defines the reduced-gravity levels between 1 g (the unit gravity acceleration on Earth and 0 g (complete weightlessness in space. Neuronal activity was recorded telemetrically through chronically implanted microelectrodes in freely moving rats. Graded levels of partial gravity from 0.4 g to 0.01 g were generated by customized parabolic-flight maneuvers. Electrophysiological signals in each partial-gravity phase were compared to those of the preceding 1 g level-flight. As a result, SVA neuronal activity was significantly inhibited by the partial-gravity levels of 0.15 g and lower, but not by 0.2 g and higher. Gravity levels between 0.2–0.15 g could represent a critical threshold for the inhibition of neurons in the rat SVA. The lunar gravity (0.16 g might thus trigger neurogenic mechanisms of CBF control. This is the first study to examine brain electrophysiology with partial gravity as an experimental parameter.

Restoration of u.v.-induced excision repair in Xeroderma D cells transfected with the denV gene of bacteriophage T4

International Nuclear Information System (INIS)

Arrand, J.E.; Squires, S.; Bone, N.M.; Johnson, R.T.

1987-01-01

The heritable DNA repair defect in human Xeroderma D cells, resulting in failure to incise at u.v. light-induced pyrimidine dimers, has been partially but stably corrected by transfection of immortalised cells with the denV pyrimidine dimer glycosylase gene of bacteriophage T4. Transfectants selected either for a dominant marker on the mammalian vector carrying the prokaryotic gene or for dominant marker plus resistance to killing by u.v. light, were shown to express the denV gene to varying degrees. denV expression results in significant phenotypic change in the initially repair-deficient, u.v.-hypersensitive cells. Increased resistance to u.v. light and more rapid recovery of replicative DNA synthesis following u.v. irradiation were correlated with improved repair DNA synthesis and with a novel dimer incision capability present in denV transfected Xeroderma cells but not as evident in transfected normal cells. Most transfectants contain a single integrated copy of the denV gene; increase in denV copy number does not result in either increased gene expression or enhanced survival to u.v. light. Results show that expression of a heterologous prokaryotic repair gene can partially compensate for the genetic defect in a human Xeroderma D cell. (author)

Synthetic, XRD, non-covalent interactions and solvent dependent nonlinear optical studies of Sulfadiazine-Ortho-Vanillin Schiff base: (E)-4-((2-hydroxy-3-methoxy- benzylidene) amino)-N-(pyrimidin-2-yl)benzene-sulfonamide

Science.gov (United States)

Shahid, Muhammad; Salim, Muhammad; Khalid, Muhammad; Tahir, Muhammad Nawaz; Khan, Muhammad Usman; Braga, Ataualpa Albert Carmo

2018-06-01

In this study, Sulfadiazine-Ortho-Vanillin Schiff base namely (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS) was synthesized. Chemical characterization and computational studies using different techniques like XRD, FT-IR, UV-Vis, NBO, FMO, and MEP have been employed. Density functional theory (DFT) calculations have been performed at M06-2X/6-311 + G(d,p) level of theory to obtain optimized geometry and vibrational wave numbers for (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS). The DFT optimized geometry supports the experimental XRD parameters. Frontier molecular orbital (FMO) energies and molecular electrostatic potential (MEP) surfaces have been executed at M06-2X/6-311 + G(d,p) level of theory. NBO analysis has been carried out at M06-2X/6-311 + G(d,p) level which not only discovered the hyper conjugative interactions and stability in title molecule but also reconfirmed the existence of Nsbnd H⋯N hydrogen bonds between the dimer. The findings of small EHOMO-ELUMO gap shows less hardness and larger softness values which suggested the bioactiveness of the title molecule. Finally, the effect of solvent on nonlinear optical (NLO) properties has been executed using M06-2X level of theory and 6-311 + G (d,p) basis set. The solvent polarity enhanced the NLO response from 3.62 × 10-30 esu to 4.66 × 10-30 esu indicating the considerable NLO character hence in general may have potential applications in the development of non-linear optical materials.

Synthesis and Biological Evaluation of a New Acyclic Pyrimidine Derivative as a Probe for Imaging Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression

Directory of Open Access Journals (Sweden)

Simon M. Ametamey

2013-07-01

Full Text Available With the idea of finding a more selective radiotracer for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk gene expression by means of positron emission tomography (PET, a novel [18F]fluorine radiolabeled pyrimidine with 4-hydroxy-3-(hydroxymethylbutyl side chain at N-1 (HHB-5-[18F]FEP was prepared and evaluated as a potential PET probe. Unlabeled reference compound, HHB-5-FEP, was synthesized via a five-step reaction sequence starting from 5-(2-acetoxyethyl-4-methoxypyrimidin-2-one. The radiosynthesis of HHB-[18F]-FEP was accomplished by nucleophilic radiofluorination of a tosylate precursor using [18F]fluoride-cryptate complex in 45% ± 4 (n = 4 radiochemical yields and high purity (>99%. The biological evaluation indicated the feasibility of using HHB-5-[18F]FEP as a PET radiotracer for monitoring HSV1-tk expression in vivo.

Management of long span partially edentulous maxilla with fixed removable denture prosthesis

Directory of Open Access Journals (Sweden)

Mahilan I Jeyavalan

2012-01-01

Full Text Available Restoration of a long span partially edentulous maxilla with tooth supported prosthesis is challenging because of inherent anatomic limitations and unfavourable biomechanics present after the loss of teeth. A tooth supported fixed-removable prosthesis is a treatment option for restoration of such long span partially edentulous maxillary arches. This prosthesis meets the requirements for esthetics, phonetics, comfort, and hygiene, as well as favourable biomechanical stress distribution to the remaining natural tooth abutments. This article presents a procedure for fabrication of a fixed-removable prosthesis that has cement-retained custom cast bar metal substructure and a ball attachment retained removable superstructure prosthesis.

Nilpotent chiral superfield in N=2 supergravity and partial rigid supersymmetry breaking

Energy Technology Data Exchange (ETDEWEB)

Kuzenko, Sergei M. [School of Physics M013, The University of Western Australia,35 Stirling Highway, Crawley W.A. 6009 (Australia); Tartaglino-Mazzucchelli, Gabriele [Instituut voor Theoretische Fysica, KU Leuven,Celestijnenlaan 200D, B-3001 Leuven (Belgium)

2016-03-15

In the framework of N=2 conformal supergravity in four dimensions, we introduce a nilpotent chiral superfield suitable for the description of partial supersymmetry breaking in maximally supersymmetric spacetimes. As an application, we construct Maxwell-Goldstone multiplet actions for partial N=2→N=1 supersymmetry breaking on ℝ×S{sup 3}, AdS{sub 3}×S{sup 1} (or its covering AdS{sub 3}×ℝ), and a pp-wave spacetime. In each of these cases, the action coincides with a unique curved-superspace extension of the N=1 supersymmetric Born-Infeld action, which is singled out by the requirement of U(1) duality invariance.

Logical Specification and Analysis of Fault Tolerant Systems through Partial Model Checking

NARCIS (Netherlands)

Gnesi, S.; Etalle, Sandro; Mukhopadhyay, S.; Lenzini, Gabriele; Lenzini, G.; Martinelli, F.; Roychoudhury, A.

2003-01-01

This paper presents a framework for a logical characterisation of fault tolerance and its formal analysis based on partial model checking techniques. The framework requires a fault tolerant system to be modelled using a formal calculus, here the CCS process algebra. To this aim we propose a uniform

Algorithms over partially ordered sets

DEFF Research Database (Denmark)

Baer, Robert M.; Østerby, Ole

1969-01-01

in partially ordered sets, answer the combinatorial question of how many maximal chains might exist in a partially ordered set withn elements, and we give an algorithm for enumerating all maximal chains. We give (in § 3) algorithms which decide whether a partially ordered set is a (lower or upper) semi......-lattice, and whether a lattice has distributive, modular, and Boolean properties. Finally (in § 4) we give Algol realizations of the various algorithms....

A Partial Equilibrium Theory for Drops and Capillary Liquids

International Nuclear Information System (INIS)

Searcy, Alan W.; Beruto, Dario T.; Barberis, Fabrizio

2006-01-01

The two-century old theory of Young and Laplace retains a powerful influence on surface and interface studies because it quantitatively predicts the height of rise of capillary liquids from the contact angles of drops. But the classical theory does not acknowledge that equilibrium requires separate minimization of partial free energies of one-component liquids bonded to immiscible solids. We generalize a theorem of Gibbs and Curie to obtain a partial equilibrium (PE) theory that does so and that also predicts the height of capillary rise from contact angles of drops. Published observations and our own measurements of contact angles of water bonded to glass and Teflon surfaces support the conclusion of PE theory that contact angles of meniscuses and of drops are different dependent variables. PE theory provides thermodynamic and kinetic guidance to nanoscale processes that the classical theory obscures, as illustrated by examples in our concluding section

Robotic-assisted partial Nephrectomy: initial experience in South America

Directory of Open Access Journals (Sweden)

Gustavo C. Lemos

2011-08-01

Full Text Available OBJECTIVE:To report the initial outcomes of robotic-assisted partial nephrectomy in a tertiary center in South America. MATERIAL AND METHODS: From 11/2008 to 12/2009, a total of 16 transperitoneal robotic-assisted partial nephrectomies were performed in 15 patients to treat 18 kidney tumors. One patient with bilateral tumor had two procedures, while two patients with two synchronous unilateral tumors had a single operation to remove them. Eleven (73% patients were male and the right kidney was affected in 7 (46% patients. The median patient age and tumor size were 57 years old and 30 mm, respectively. Five (28% tumors were hilar and/or centrally located. RESULTS: The median operative time, warm ischemia time and estimated blood loss was 140 min, 27 min and 120 mL, respectively. Blood transfusion was required in one patient with bilateral tumor, and one additional pyelolithotomy was performed due to a 15mm stone located in the renal pelvis. The histopathology analysis showed 15 (83% malignant tumors, which 10 (67% were clear cell carcinoma. The median hospital stay was 72 hrs and no major complication was observed. CONCLUSION: Robotic-assisted partial nephrectomy is safe and represents a valuable option to perform minimally invasive nephron-sparing surgery.

The significance of the clause requiring precautionary measures to assure waste disposal in partial licenses granted under the Atomic Energy Law

International Nuclear Information System (INIS)

Breuer, R.

1981-01-01

This development raises the question as to what extent a waste disposal provision clause of the first few partial construction permits has to be adapted to the factual situation that has changed. Thus the clause is factually outdated according to which the granting of an operating licence for a nuclear power station cannot be expected until the first partial construction permit for the German fuel-cycle centre is in hand. It is not only conceivable that a first partial construction permit for the German fuel-cycle centre will not be in hand at the time when the authorities will decide on a (first) operating licence to be granted for a nuclear power station under construction, but add to this the crucial fact that the condition given in the above-mentioned provision clause on waste disposal is no longer in keeping with the factual situation and the thereto adapted provision principles governing waste management. Special attention has to be given to the significance and impact of this waste disposal provision clause since the situation has changed. (orig./HP) [de

Partial Deconvolution with Inaccurate Blur Kernel.

Science.gov (United States)

Ren, Dongwei; Zuo, Wangmeng; Zhang, David; Xu, Jun; Zhang, Lei

2017-10-17

Most non-blind deconvolution methods are developed under the error-free kernel assumption, and are not robust to inaccurate blur kernel. Unfortunately, despite the great progress in blind deconvolution, estimation error remains inevitable during blur kernel estimation. Consequently, severe artifacts such as ringing effects and distortions are likely to be introduced in the non-blind deconvolution stage. In this paper, we tackle this issue by suggesting: (i) a partial map in the Fourier domain for modeling kernel estimation error, and (ii) a partial deconvolution model for robust deblurring with inaccurate blur kernel. The partial map is constructed by detecting the reliable Fourier entries of estimated blur kernel. And partial deconvolution is applied to wavelet-based and learning-based models to suppress the adverse effect of kernel estimation error. Furthermore, an E-M algorithm is developed for estimating the partial map and recovering the latent sharp image alternatively. Experimental results show that our partial deconvolution model is effective in relieving artifacts caused by inaccurate blur kernel, and can achieve favorable deblurring quality on synthetic and real blurry images.Most non-blind deconvolution methods are developed under the error-free kernel assumption, and are not robust to inaccurate blur kernel. Unfortunately, despite the great progress in blind deconvolution, estimation error remains inevitable during blur kernel estimation. Consequently, severe artifacts such as ringing effects and distortions are likely to be introduced in the non-blind deconvolution stage. In this paper, we tackle this issue by suggesting: (i) a partial map in the Fourier domain for modeling kernel estimation error, and (ii) a partial deconvolution model for robust deblurring with inaccurate blur kernel. The partial map is constructed by detecting the reliable Fourier entries of estimated blur kernel. And partial deconvolution is applied to wavelet-based and learning

Pseudocyclops: two cases of ACL graft partial tears mimicking cyclops lesions on MRI

Energy Technology Data Exchange (ETDEWEB)

Simpfendorfer, Claus; Subhas, Naveen; Winalski, Carl S.; Ilaslan, Hakan [Cleveland Clinic, Department of Radiology, Cleveland, OH (United States); Miniaci, Anthony [Cleveland Clinic, Department of Orthopedics, Cleveland, OH (United States)

2015-08-15

Arthroscopic reconstruction of the anterior cruciate ligament (ACL) using autografts or allografts is a common surgical procedure, particularly in young athletes. Although the procedure has excellent success rates, complications such as mechanical impingement, graft rupture, and arthrofibrosis can occur, often necessitating additional surgery. Magnetic resonance (MR) imaging has become a valuable tool in evaluating complications after ACL reconstruction. We report two cases of ACL reconstruction complicated by arthroscopically proven partial graft tears. In both cases the torn anterior graft fibers were flipped into the intercondylar notch, mimicking anterior arthrofibrosis, i.e., a ''cyclops lesion,'' on MR imaging. Careful review of the direction of graft fibers on MR imaging in the ''pseudocyclops'' lesions can help differentiate these partial tears from the fibrosis of a true cyclops. The ''pseudocyclops'' lesion is a previously undescribed MR imaging sign of partial ACL graft tear. Larger studies are required to determine the sensitivity and specificity of the sign, as well as the clinical importance of these partial graft tears. (orig.)

Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study.

Science.gov (United States)

Kasperaviciūte, Dalia; Catarino, Claudia B; Heinzen, Erin L; Depondt, Chantal; Cavalleri, Gianpiero L; Caboclo, Luis O; Tate, Sarah K; Jamnadas-Khoda, Jenny; Chinthapalli, Krishna; Clayton, Lisa M S; Shianna, Kevin V; Radtke, Rodney A; Mikati, Mohamad A; Gallentine, William B; Husain, Aatif M; Alhusaini, Saud; Leppert, David; Middleton, Lefkos T; Gibson, Rachel A; Johnson, Michael R; Matthews, Paul M; Hosford, David; Heuser, Kjell; Amos, Leslie; Ortega, Marcos; Zumsteg, Dominik; Wieser, Heinz-Gregor; Steinhoff, Bernhard J; Krämer, Günter; Hansen, Jörg; Dorn, Thomas; Kantanen, Anne-Mari; Gjerstad, Leif; Peuralinna, Terhi; Hernandez, Dena G; Eriksson, Kai J; Kälviäinen, Reetta K; Doherty, Colin P; Wood, Nicholas W; Pandolfo, Massimo; Duncan, John S; Sander, Josemir W; Delanty, Norman; Goldstein, David B; Sisodiya, Sanjay M

2010-07-01

Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio<1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.

Laparoscopic partial cystectomy for urachal and bladder cancer

Directory of Open Access Journals (Sweden)

Jose R. Colombo Jr.

2008-01-01

Full Text Available PURPOSE: To report our initial experiences with laparoscopic partial cystectomy for urachal and bladder malignancy. MATERIALS AND METHODS: Between March 2002 and October 2004, laparoscopic partial cystectomy was performed in 6 cases at 3 institutions; 3 cases were urachal adenocarcinomas and the remaining 3 cases were bladder transitional cell carcinomas. All patients were male, with a median age of 55 years (45-72 years. Gross hematuria was the presenting symptom in all patients, and diagnosis was established with trans-urethral resection bladder tumor in 2 patients and by means of cystoscopic biopsy in the remaining 4 patients. Laparoscopic partial cystectomy was performed using the transperitoneal approach under cystoscopic guidance. In each case, the surgical specimen was removed intact entrapped in an impermeable bag. One patient with para-ureteral diverticulum transitional cell carcinoma required concomitant ureteral reimplantation. RESULTS: All six procedures were completed laparoscopically without open conversion. The median operating time was 110 minutes (90-220 with a median estimated blood loss of 70 mL (50-100. Frozen section evaluations of bladder margins were routinely obtained and were negative for cancer in all cases. The median hospital stay was 2.5 days (2-4 and the duration of catheterization was 7 days. There were no intraoperative or postoperative complications. Final histopathology confirmed urachal adenocarcinoma in 3 cases and bladder transitional cell carcinoma in 3 cases. At a median follow-up of 28.5 months (range: 26 to 44 months, there was no evidence of recurrent disease as evidenced by radiologic or cystoscopic evaluation. CONCLUSIONS: Laparoscopic partial cystectomy in carefully selected patients with urachal and bladder cancer is feasible and safe, offering a promising and minimally invasive alternative for these patients.

Marked radiosensitization of cells in culture to x ray by 5-chlorodeoxycytidine coadministered with tetrahydrouridine, and inhibitors of pyrimidine biosynthesis

International Nuclear Information System (INIS)

Perez, L.M.; Mekras, J.A.; Briggle, T.V.; Greer, S.

1984-01-01

The authors approach to overcome the problem of rapid catabolism and general toxicity encountered with 5-halogenated analogues of deoxyuridine (5-bromo, chloro or iododeoxyuridine), which has limited their use as tumor radiosensitizers, is to utilize 5-chlorodeoxycytidine (CldC) with tetrahydrouridine (H 4 U). They propose that CldC, coadministered with H 4 U, is metabolized in the following manner: CldC → CldCMP → CldUMP → → CldUTP → DNA. All the enzymes of this pathway are elevated in many human malignant tumors and in HEp-2 cells. In x irradiation studies with HEp-2 cells, limited to 1 or 2 radiation doses. They obtained 3.0 to 3.8 apparent dose enhancement ratios when cells were preincubated with inhibitors of pyrimidine biosynthesis. Enzymatic studies indicate that this toxicity may be tumor selective. Preliminary toxicity studies indicate that mice will tolerate treatment protocols with marginal weight loss (4%). In this approach the authors seek to obtain preferential conversion of CldC to CldUTP at the tumor site by taking advantage of quantitative differences in enzyme levels between tumors and normal tissues

Experimental and theoretical studies on the coordination chemistry of the N1-hexyl substituted pyrimidines (uracil, 5-fluorouracil and cytosine).

Science.gov (United States)

Barceló-Oliver, Miquel; Baquero, Beatriz Adriana; Bauzá, Antonio; García-Raso, Angel; Vich, Roberto; Mata, Ignasi; Molins, Elies; Terrón, Angel; Frontera, Antonio

2013-06-07

N(1)-Hexyl substituted pyrimidines were shown to present solubility properties closer to the real bases than the commonly used methyl and ethyl derivatives, yielding bi-layered structures in the solid state. The study of their coordination capabilities, mainly with Ag(I) and Hg(II), is presented in order to prove their reactivity. A series of coordination complexes, namely, [Hg(N(1)-hexyl-5-fluorouracilate)2]4·6H2O (1), (Ag(+))·[Ag(N(1)-hexyl-5-fluorouracilate)2](-) (2), [Ag(NO3)(N(1)-hexyluracil-κO(4))4] (3), [ZnBr2(N(1)-hexylcytosine)2] (4), [CdBr2(N(1)-hexylcytosine)2] (5), [HgBr2(N(1)-hexylcytosine)2] (6) and [CoBr2(N(1)-hexylcytosine)2] (7), have been synthesized in good yields and X-ray characterized. The presence of the hexyl chains and the fluorine atoms causes the formation of interesting 3D architectures in the solid state. Their structures have been further characterized by infrared spectra (IR) and elemental analyses. In addition, DFT-D3 calculations are used to study interesting noncovalent interactions observed in the solid state, like fluorine-fluorine, fluorine-π and hydrophobic interactions.

Algebraic partial Boolean algebras

International Nuclear Information System (INIS)

Smith, Derek

2003-01-01

Partial Boolean algebras, first studied by Kochen and Specker in the 1960s, provide the structure for Bell-Kochen-Specker theorems which deny the existence of non-contextual hidden variable theories. In this paper, we study partial Boolean algebras which are 'algebraic' in the sense that their elements have coordinates in an algebraic number field. Several of these algebras have been discussed recently in a debate on the validity of Bell-Kochen-Specker theorems in the context of finite precision measurements. The main result of this paper is that every algebraic finitely-generated partial Boolean algebra B(T) is finite when the underlying space H is three-dimensional, answering a question of Kochen and showing that Conway and Kochen's infinite algebraic partial Boolean algebra has minimum dimension. This result contrasts the existence of an infinite (non-algebraic) B(T) generated by eight elements in an abstract orthomodular lattice of height 3. We then initiate a study of higher-dimensional algebraic partial Boolean algebras. First, we describe a restriction on the determinants of the elements of B(T) that are generated by a given set T. We then show that when the generating set T consists of the rays spanning the minimal vectors in a real irreducible root lattice, B(T) is infinite just if that root lattice has an A 5 sublattice. Finally, we characterize the rays of B(T) when T consists of the rays spanning the minimal vectors of the root lattice E 8

Unconditionally stable difference methods for delay partial differential equations

OpenAIRE

Huang, Chengming; Vandewalle, Stefan

2012-01-01

This paper is concerned with the numerical solution of parabolic partial differential equations with time-delay. We focus in particular on the delay dependent stability analysis of difference methods that use a non-constrained mesh, i.e., the time step-size is not required to be a submultiple of the delay. We prove that the fully discrete system unconditionally preserves the delay dependent asymptotic stability of the linear test problem under consideration, when the following discretizati...

[Removable partial dentures. Oral functions and types].

Science.gov (United States)

Creugers, N H J; de Baat, C

2009-11-01

A removable partial denture enables the restoration or improvement of 4 oral functions: aesthetics, mandibular stability, mastication, and speech. However, wearing a removable partial denture should not cause oral comfort to deteriorate. There are 3 types of removable partial dentures: acrylic tissue-supported dentures, dentures with cast metal frameworks en dentures with cast metal frameworks and (semi)precision attachments. Interrupted tooth arches,free-ending tooth arches, and a combination of interrupted as well as free-ending tooth arches can be restored using these dentures. Well-known disadvantages of removable partial dentures are problematic oral hygiene, negative influence on the remaining dentition and limited oral comfort. Due to the advanced possibilities of fixed tooth- or implant-supported partial dentures, whether or not free-ending, or tooth- as well as implant-supported partial dentures, the indication of removable partial dentures is restricted. Nevertheless, for the time being the demand for removable partial dentures is expected to continue.

Repression of the pyr operon in Lactobacillus plantarum prevents its ability to grow at low carbon dioxide levels

DEFF Research Database (Denmark)

Nicoloff, Hervé; Elagöz, Aram; Arsène-Ploetze, Florence

2005-01-01

Carbamoyl phosphate is a precursor for both arginine and pyrimidine biosynthesis. In Lactobacillus plantarum, carbamoyl phosphate is synthesized from glutamine, ATP, and carbon dioxide by two sets of identified genes encoding carbamoyl phosphate synthase (CPS). The expression of the carAB operon...... to the pyr mRNA attenuation site in response to intracellular UMP/phosphoribosyl pyrophosphate pools. Intracellular pyrimidine triphosphate nucleoside pools were lower in mutant FB335 (carAB deletion) harboring only CPS-P than in the wild-type strain harboring both CPS-A and CPS-P. Thus, CPS-P activity...... compared to wild-type levels. Low pyrimidine-independent expression of the pyr operon was obtained by antiterminator site-directed mutagenesis. The resulting AE1023 strain had reduced UTP and CTP pools and had the phenotype of a high-CO2-requiring auxotroph, since it was able to synthesize sufficient...

[Conventional retaining of removable partial dentures

NARCIS (Netherlands)

Keltjens, H.M.A.M.; Witter, D.J.; Creugers, N.H.J.

2009-01-01

Mechanical and biological criteria have to be met in retaining the metal frame of a removable partial denture. Additionally, a removable partial denture is part of the occlusal interface by the clasps and the denture teeth. With respect to mechanical aspects, all rigid parts of the removable partial

Properties of partial-wave amplitudes in conformal invariant field theories

CERN Document Server

Ferrara, Sergio; Grillo, A F

1975-01-01

Analyticity properties of partial-wave amplitudes of the conformal group O/sub D,2/ (D not necessarily integer) in configuration space are investigated. The presence of Euclidean singularities in the Wilson expansion in conformal invariant field theories is discussed, especially in connection with the program of formulating dynamical bootstrap conditions coming from the requirement of causality. The exceptional case of D-2 is discussed in detail. (18 refs).

Partial list of bipartite Bell inequalities with four binary settings

International Nuclear Information System (INIS)

Brunner, Nicolas; Gisin, Nicolas

2008-01-01

We give a partial list of 26 tight Bell inequalities for the case where Alice and Bob choose among four two-outcome measurements. All tight Bell inequalities with less settings are reviewed as well. For each inequality we compute numerically the maximal quantum violation, the resistance to noise and the minimal detection efficiency required for closing the detection loophole. Surprisingly, most of these inequalities are outperformed by the CHSH inequality

Structural and energetic characterization of the emissive RNA alphabet based on the isothiazolo[4,3-d]pyrimidine heterocycle core

KAUST Repository

Chawla, Mohit

2016-06-01

We present theoretical characterization of fluorescent non-natural nucleobases, tzA, tzG, tzC, and tzU, derived from the isothiazolo[4,3-d]pyrimidine heterocycle. Consistent with the experimental evidence, our calculations show that the non-natural bases have minimal impact on the geometry and stability of the classical Watson-Crick base pairs, allowing them to accurately mimic natural bases in a RNA duplex, in terms of H-bonding. In contrast, our calculations indicate that H-bonded base pairs involving the Hoogsteen edge are destabilized relative to their natural counterparts. Analysis of the photophysical properties of the non-natural bases allowed us to correlate their absorption/emission peaks to the strong impact of the modification on the energy of the lowest unoccupied molecular orbital, LUMO, which is stabilized by roughly 1.0-1.2 eV relative to the natural analogues, while the highest occupied molecular orbital, HOMO, is not substantially affected. As a result, the HOMO-LUMO gap is reduced from 5.3-5.5 eV in the natural bases to 4.0-4.4 eV in the modified ones, with a consequent bathochromic shift in the absorption and emission spectra. © 2016 the Owner Societies.

Structural and energetic characterization of the emissive RNA alphabet based on the isothiazolo[4,3-d]pyrimidine heterocycle core

KAUST Repository

Chawla, Mohit; Poater, Albert; Oliva, Romina; Cavallo, Luigi

2016-01-01

We present theoretical characterization of fluorescent non-natural nucleobases, tzA, tzG, tzC, and tzU, derived from the isothiazolo[4,3-d]pyrimidine heterocycle. Consistent with the experimental evidence, our calculations show that the non-natural bases have minimal impact on the geometry and stability of the classical Watson-Crick base pairs, allowing them to accurately mimic natural bases in a RNA duplex, in terms of H-bonding. In contrast, our calculations indicate that H-bonded base pairs involving the Hoogsteen edge are destabilized relative to their natural counterparts. Analysis of the photophysical properties of the non-natural bases allowed us to correlate their absorption/emission peaks to the strong impact of the modification on the energy of the lowest unoccupied molecular orbital, LUMO, which is stabilized by roughly 1.0-1.2 eV relative to the natural analogues, while the highest occupied molecular orbital, HOMO, is not substantially affected. As a result, the HOMO-LUMO gap is reduced from 5.3-5.5 eV in the natural bases to 4.0-4.4 eV in the modified ones, with a consequent bathochromic shift in the absorption and emission spectra. © 2016 the Owner Societies.

High hRFI expression correlates with resistance to Fluoro pyrimidines in human colon cancer cell lines and in xenografts

International Nuclear Information System (INIS)

Sasaki, S.; Tokyo Univ., Tokyo; Watanabe, T.; Konishi, T.; Kitayama, J.; Nagawa, H.; Kobunai, T.

2005-01-01

We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-α induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoro pyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue micro array consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy

Genetic and phylogenetic characterization of the type II cyclobutane pyrimidine dimer photolyases encoded by Leporipoxviruses

International Nuclear Information System (INIS)

Bennett, C. James; Webb, Melissa; Willer, David O.; Evans, David H.

2003-01-01

Shope fibroma virus and myxoma virus encode proteins predicted to be Type II photolyases. These are enzymes that catalyze light-dependent repair of cyclobutane pyrimidine dimers (CPDs). When the Shope fibroma virus S127L gene was expressed in an Escherichia coli strain lacking functional CPD repair pathways, the expressed gene protected the bacteria from 70-75% of the ultraviolet (UV) light-induced cytotoxic DNA damage. This proportion suggests that Leporipoxvirus photolyases can only repair CPDs, which typically comprise ∼70% of the damage caused by short wavelength UV light. To test whether these enzymes can protect virus genomes from UV, we exposed virus suspensions to UV-C light followed by graded exposure to filtered visible light. Viruses encoding a deletion of the putative photolyase gene were unable to photoreactivate UV damage while this treatment again eliminated 70-90% of the lethal photoproducts in wild-type viruses. Western blotting detected photolyase protein in extracts prepared from purified virions and it can be deduced that the poxvirion interior must be fluid enough to permit diffusion of this ∼50-kDa DNA-binding protein to the sites where it catalyzes photoreactivation. Photolyase promoters are difficult to categorize using bioinformatics methods, as they do not obviously resemble any of the known poxvirus promoter motifs. By fusing the SFV promoter to DNA encoding a luciferase open reading frame, the photolyase promoter was found to exhibit very weak late promoter activity. These data show that the genomes of Leporipoxviruses, similar to that of fowlpox virus, encode catalytically active photolyases. Phylogenetic studies also confirmed the monophyletic origin of poxviruses and suggest an ancient origin for these genes and perhaps poxviruses

Photogenic partial seizures.

Science.gov (United States)

Hennessy, M J; Binnie, C D

2000-01-01

To establish the incidence and symptoms of partial seizures in a cohort of patients investigated on account of known sensitivity to intermittent photic stimulation and/or precipitation of seizures by environmental visual stimuli such as television (TV) screens or computer monitors. We report 43 consecutive patients with epilepsy, who had exhibited a significant EEG photoparoxysmal response or who had seizures precipitated by environmental visual stimuli and underwent detailed assessment of their photosensitivity in the EEG laboratory, during which all were questioned concerning their ictal symptoms. All patients were considered on clinical grounds to have an idiopathic epilepsy syndrome. Twenty-eight (65%) patients reported visually precipitated attacks occurring initially with maintained consciousness, in some instances evolving to a period of confusion or to a secondarily generalized seizure. Visual symptoms were most commonly reported and included positive symptoms such as coloured circles or spots, but also blindness and subjective symptoms such as "eyes going funny." Other symptoms described included nonspecific cephalic sensations, deja-vu, auditory hallucinations, nausea, and vomiting. No patient reported any clear spontaneous partial seizures, and there were no grounds for supposing that any had partial epilepsy excepting the ictal phenomenology of some or all of the visually induced attacks. These findings provide clinical support for the physiological studies that indicate that the trigger mechanism for human photosensitivity involves binocularly innervated cells located in the visual cortex. Thus the visual cortex is the seat of the primary epileptogenic process, and the photically triggered discharges and seizures may be regarded as partial with secondary generalization.

Engineering Requirements for crowds

Directory of Open Access Journals (Sweden)

Rogeiro Silva

2015-12-01

Full Text Available In the software project the interested parts are highly distributed and form numerous and heterogeneous groups, online or face, constituting what could be called crowds. The development of social applications and cloud computing and mobile has generated a marked increase in environments based requirements in crowds. Technical Requirements Engineering (RE traditional face these scalability issues, and require the co-presence of interested and engineers in joint meetings that can not be made in common physical environments. While different approaches have been introduced to partially automate RE in these contexts, still is required a multi-method approach to semi-automate all activities related to work with crowds. In this paper is propose an approach that integrates existing elicitation techniques and requirements analysis and is complemented by introducing new concepts. The information is collected through direct interaction and social collaboration, and through data mining techniques.

Partially massless fields during inflation

Science.gov (United States)

Baumann, Daniel; Goon, Garrett; Lee, Hayden; Pimentel, Guilherme L.

2018-04-01

The representation theory of de Sitter space allows for a category of partially massless particles which have no flat space analog, but could have existed during inflation. We study the couplings of these exotic particles to inflationary perturbations and determine the resulting signatures in cosmological correlators. When inflationary perturbations interact through the exchange of these fields, their correlation functions inherit scalings that cannot be mimicked by extra massive fields. We discuss in detail the squeezed limit of the tensor-scalar-scalar bispectrum, and show that certain partially massless fields can violate the tensor consistency relation of single-field inflation. We also consider the collapsed limit of the scalar trispectrum, and find that the exchange of partially massless fields enhances its magnitude, while giving no contribution to the scalar bispectrum. These characteristic signatures provide clean detection channels for partially massless fields during inflation.

Gravity Effects Observed In Partially Premixed Flames

Science.gov (United States)

Puri, Ishwar K.; Aggarwal, Suresh K.; Lock, Andrew J.; Gauguly, Ranjan; Hegde, Uday

2003-01-01

Partially premixed flames (PPFs) contain a rich premixed fuel air mixture in a pocket or stream, and, for complete combustion to occur, they require the transport of oxidizer from an appropriately oxidizer-rich (or fuel-lean) mixture that is present in another pocket or stream. Partial oxidation reactions occur in fuel-rich portions of the mixture and any remaining unburned fuel and/or intermediate species are consumed in the oxidizer-rich portions. Partial premixing, therefore, represents that condition when the equivalence ratio (phi) in one portion of the flowfield is greater than unity, and in another section its value is less than unity. In general, for combustion to occur efficiently, the global equivalence ratio is in the range fuel-lean to stoichiometric. These flames can be established by design by placing a fuel-rich mixture in contact with a fuel-lean mixture, but they also occur otherwise in many practical systems, which include nonpremixed lifted flames, turbulent nonpremixed combustion, spray flames, and unwanted fires. Other practical applications of PPFs are reported elsewhere. Although extensive experimental studies have been conducted on premixed and nonpremixed flames under microgravity, there is a absence of previous experimental work on burner stabilized PPFs in this regard. Previous numerical studies by our group employing a detailed numerical model showed gravity effects to be significant on the PPF structure. We report on the results of microgravity experiments conducted on two-dimensional (established on a Wolfhard-Parker slot burner) and axisymmetric flames (on a coannular burner) that were investigated in a self-contained multipurpose rig. Thermocouple and radiometer data were also used to characterize the thermal transport in the flame.

Anarchic Yukawas and top partial compositeness: the flavour of a successful marriage

Science.gov (United States)

Cacciapaglia, Giacomo; Cai, Haiying; Flacke, Thomas; Lee, Seung J.; Parolini, Alberto; Serôdio, Hugo

2015-06-01

The top quark can be naturally singled out from other fermions in the Standard Model due to its large mass, of the order of the electroweak scale. We follow this reasoning in models of pseudo Nambu Goldstone Boson composite Higgs, which may derive from an underlying confining dynamics. We consider a new class of flavour models, where the top quark obtains its mass via partial compositeness, while the lighter fermions acquire their masses by a deformation of the dynamics generated at a high flavour scale. One interesting feature of such scenario is that it can avoid all the flavour constraints without the need of flavour symmetries, since the flavour scale can be pushed high enough. We show that both flavour conserving and violating constraints can be satisfied with top partial compositeness without invoking any flavour symmetry for the up-type sector, in the case of the minimal SO(5)/SO(4) coset with top partners in the four-plet and singlet of SO(4). In the down-type sector, some degree of alignment is required if all down-type quarks are elementary. We show that taking the bottom quark partially composite provides a dynamical explanation for the hierarchy causing this alignment. We present explicit realisations of this mechanism which do not require to include additional bottom partner fields. Finally, these conclusions are generalised to scenarios with non-minimal cosets and top partners in larger representations.

Anarchic Yukawas and top partial compositeness: the flavour of a successful marriage

Energy Technology Data Exchange (ETDEWEB)

Cacciapaglia, Giacomo; Cai, Haiying [Université de Lyon, F-69622 Lyon (France); Université Lyon 1, Villeurbanne (France); CNRS/IN2P3, UMR5822, Institut de Physique Nucléaire de Lyon,F-69622 Villeurbanne Cedex (France); Flacke, Thomas [Department of Physics, Korea Advanced Institute of Science and Technology,335 Gwahak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Lee, Seung J. [Department of Physics, Korea Advanced Institute of Science and Technology,335 Gwahak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); School of Physics, Korea Institute for Advanced Study, Seoul 130-722 (Korea, Republic of); Parolini, Alberto [Department of Physics, Korea Advanced Institute of Science and Technology,335 Gwahak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Center for Axion and Precision Physics, IBS,291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Serôdio, Hugo [Department of Physics, Korea Advanced Institute of Science and Technology,335 Gwahak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of)

2015-06-15

The top quark can be naturally singled out from other fermions in the Standard Model due to its large mass, of the order of the electroweak scale. We follow this reasoning in models of pseudo Nambu Goldstone Boson composite Higgs, which may derive from an underlying confining dynamics. We consider a new class of flavour models, where the top quark obtains its mass via partial compositeness, while the lighter fermions acquire their masses by a deformation of the dynamics generated at a high flavour scale. One interesting feature of such scenario is that it can avoid all the flavour constraints without the need of flavour symmetries, since the flavour scale can be pushed high enough. We show that both flavour conserving and violating constraints can be satisfied with top partial compositeness without invoking any flavour symmetry for the up-type sector, in the case of the minimal SO(5)/SO(4) coset with top partners in the four-plet and singlet of SO(4). In the down-type sector, some degree of alignment is required if all down-type quarks are elementary. We show that taking the bottom quark partially composite provides a dynamical explanation for the hierarchy causing this alignment. We present explicit realisations of this mechanism which do not require to include additional bottom partner fields. Finally, these conclusions are generalised to scenarios with non-minimal cosets and top partners in larger representations.

Anarchic Yukawas and top partial compositeness: the flavour of a successful marriage

International Nuclear Information System (INIS)

Cacciapaglia, Giacomo; Cai, Haiying; Flacke, Thomas; Lee, Seung J.; Parolini, Alberto; Serôdio, Hugo

2015-01-01

The top quark can be naturally singled out from other fermions in the Standard Model due to its large mass, of the order of the electroweak scale. We follow this reasoning in models of pseudo Nambu Goldstone Boson composite Higgs, which may derive from an underlying confining dynamics. We consider a new class of flavour models, where the top quark obtains its mass via partial compositeness, while the lighter fermions acquire their masses by a deformation of the dynamics generated at a high flavour scale. One interesting feature of such scenario is that it can avoid all the flavour constraints without the need of flavour symmetries, since the flavour scale can be pushed high enough. We show that both flavour conserving and violating constraints can be satisfied with top partial compositeness without invoking any flavour symmetry for the up-type sector, in the case of the minimal SO(5)/SO(4) coset with top partners in the four-plet and singlet of SO(4). In the down-type sector, some degree of alignment is required if all down-type quarks are elementary. We show that taking the bottom quark partially composite provides a dynamical explanation for the hierarchy causing this alignment. We present explicit realisations of this mechanism which do not require to include additional bottom partner fields. Finally, these conclusions are generalised to scenarios with non-minimal cosets and top partners in larger representations.

Azomethines, isoxazole, N-substituted pyrazoles and pyrimidine containing curcumin derivatives: Urease inhibition and molecular modeling studies.

Science.gov (United States)

Ahmed, Mahmood; Qadir, Muhammad Abdul; Hameed, Abdul; Arshad, Muhammad Nadeem; Asiri, Abdullah M; Muddassar, Muhammad

2017-08-19

Curcumin has shown large number of pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its various derivatives for diverse biological functions. In this study, curcumin derived azomethine, isoxazole, pyrimidines and N-substituted pyrazoles were synthesized to investigate their urease enzyme inhibition. The structures of newly synthesized compounds were described by IR, MS, 1 H NMR and 13 C NMR spectral data. Urease enzyme inhibition was evaluated through in vitro assays in which compound 8b was found to be the most potent (IC 50  = 2.44 ± 0.07 μM) among the tested compounds. The compounds with diazine ring system except the 4d showed better urease inhibition (IC 50  = 11.43 ± 0.21-19.63 ± 0.28 μM) than the standard urease inhibitor thiourea (IC 50  = 22.61 ± 0.23 μM). Similarly enzyme kinetics data revealed that compounds 3c-3e and 8b were competitive inhibitors with Ki values of 20.0, 19.87, 20.23 and 19.11 μM respectively while the compounds 4b, 4c and 4e were mixed type of inhibitors with Ki values 6.72, 19.69 and 6.72 μM respectively. Molecular docking studies were also performed to identify the plausible binding modes of the most active compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

The strategic value of partial vertical integration

OpenAIRE

Fiocco, Raffaele

2014-01-01

We investigate the strategic incentives for partial vertical integration, namely, partial ownership agreements between manufacturers and retailers, when retailers privately know their costs and engage in differentiated good price competition. The partial misalignment between the profit objectives within a partially integrated manufacturer-retailer hierarchy entails a higher retail price than under full integration. This `information vertical effect' translates into an opposite ...

The Effect of Influent Characteristics and Operational Conditions over the Performance and Microbial Community Structure of Partial Nitritation Reactors

Directory of Open Access Journals (Sweden)

Alejandro Rodriguez-Sanchez

2014-06-01

Full Text Available Nitrogen is a main contaminant of wastewater worldwide. Novel processes for nitrogen removal have been developed over the last several decades. One of these is the partial nitritation process. This process includes the oxidation of ammonium to nitrite without the generation of nitrate. The partial nitritation process has several advantages over traditional nitrification-denitrification processes for nitrogen removal from wastewaters. In addition, partial nitritation is required for anammox elimination of nitrogen from wastewater. Partial nitritation is affected by operational conditions and substances present in the influent, such as quinolone antibiotics. In this review, the impact that several operational conditions, such as temperature, pH, dissolved oxygen concentration, hydraulic retention time and solids retention time, have over the partial nitritation process is covered. The effect of quinolone antibiotics and other emerging contaminants are discussed. Finally, future perspectives for the partial nitritation process are commented upon.

Glocal assessment of integrated wastewater treatment and recovery concepts using partial nitritation/Anammox and microalgae for environmental impacts.

Science.gov (United States)

Khiewwijit, Rungnapha; Rijnaarts, Huub; Temmink, Hardy; Keesman, Karel J

2018-07-01

This study explored the feasibility and estimated the environmental impacts of two novel wastewater treatment configurations. Both include combined bioflocculation and anaerobic digestion but apply different nutrient removal technologies, i.e. partial nitritation/Anammox or microalgae treatment. The feasibility of such configurations was investigated for 16 locations worldwide with respect to environmental impacts, such as net energy yield, nutrient recovery and effluent quality, CO 2 emission, and area requirements. The results quantitatively support the applicability of partial nitritation/Anammox in tropical regions and some locations in temperate regions, whereas microalgae treatment is only applicable the whole year round in tropical regions that are close to the equator line. Microalgae treatment has an advantage over the configuration with partial nitritation/Anammox with respect to aeration energy and nutrient recovery, but not with area requirements. Differential sensitivity analysis points out the dominant influence of microalgal biomass yield and wastewater nutrient concentrations on area requirements and effluent quality. This study provides initial selection criteria for worldwide feasibility and corresponding environmental impacts of these novel municipal wastewater treatment plant configurations. Copyright © 2018. Published by Elsevier B.V.

Physics of partially ionized plasmas

CERN Document Server

Krishan, Vinod

2016-01-01

Plasma is one of the four fundamental states of matter; the other three being solid, liquid and gas. Several components, such as molecular clouds, diffuse interstellar gas, the solar atmosphere, the Earth's ionosphere and laboratory plasmas, including fusion plasmas, constitute the partially ionized plasmas. This book discusses different aspects of partially ionized plasmas including multi-fluid description, equilibrium and types of waves. The discussion goes on to cover the reionization phase of the universe, along with a brief description of high discharge plasmas, tokomak plasmas and laser plasmas. Various elastic and inelastic collisions amongst the three particle species are also presented. In addition, the author demonstrates the novelty of partially ionized plasmas using many examples; for instance, in partially ionized plasma the magnetic induction is subjected to the ambipolar diffusion and the Hall effect, as well as the usual resistive dissipation. Also included is an observation of kinematic dynam...

Decontamination and partial dismantling of the Eurochemic plant. Part 1

International Nuclear Information System (INIS)

Detilleux, E.; Geens, L.; Hild, W.; Klonk, W.

1980-09-01

A description is given of the partial dismantling of the dissolver used for fuel elements of up to 1.6 wt % 235 U enrichment, and of the total dismantling of the dissolver for highly enriched fuel elements. The corresponding head-end cells have been decontaminated, allowing prolonged interventions, either in view of refurbishing or complete dismantling. An assessment of required manpower, dose commitments, material consumption, and waste production for all operations is given. (author)

Partial coherence and imperfect optics at a synchrotron radiation source modeled by wavefront propagation

Science.gov (United States)

Laundy, David; Alcock, Simon G.; Alianelli, Lucia; Sutter, John P.; Sawhney, Kawal J. S.; Chubar, Oleg

2014-09-01

A full wave propagation of X-rays from source to sample at a storage ring beamline requires simulation of the electron beam source and optical elements in the beamline. The finite emittance source causes the appearance of partial coherence in the wave field. Consequently, the wavefront cannot be treated exactly with fully coherent wave propagation or fully incoherent ray tracing. We have used the wavefront code Synchrotron Radiation Workshop (SRW) to perform partially coherent wavefront propagation using a parallel computing cluster at the Diamond Light Source. Measured mirror profiles have been used to correct the wavefront for surface errors.

Hidden physics models: Machine learning of nonlinear partial differential equations

Science.gov (United States)

Raissi, Maziar; Karniadakis, George Em

2018-03-01

While there is currently a lot of enthusiasm about "big data", useful data is usually "small" and expensive to acquire. In this paper, we present a new paradigm of learning partial differential equations from small data. In particular, we introduce hidden physics models, which are essentially data-efficient learning machines capable of leveraging the underlying laws of physics, expressed by time dependent and nonlinear partial differential equations, to extract patterns from high-dimensional data generated from experiments. The proposed methodology may be applied to the problem of learning, system identification, or data-driven discovery of partial differential equations. Our framework relies on Gaussian processes, a powerful tool for probabilistic inference over functions, that enables us to strike a balance between model complexity and data fitting. The effectiveness of the proposed approach is demonstrated through a variety of canonical problems, spanning a number of scientific domains, including the Navier-Stokes, Schrödinger, Kuramoto-Sivashinsky, and time dependent linear fractional equations. The methodology provides a promising new direction for harnessing the long-standing developments of classical methods in applied mathematics and mathematical physics to design learning machines with the ability to operate in complex domains without requiring large quantities of data.

Partial Epilepsy with Auditory Features

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2004-07-01

Full Text Available The clinical characteristics of 53 sporadic (S cases of idiopathic partial epilepsy with auditory features (IPEAF were analyzed and compared to previously reported familial (F cases of autosomal dominant partial epilepsy with auditory features (ADPEAF in a study at the University of Bologna, Italy.

Thioxopyrimidine in Heterocyclic Synthesis I: Synthesis of Some Novel 6-(Heteroatom-substituted-(thiopyrimidine Derivatives

Directory of Open Access Journals (Sweden)

Yuh-Wen Ho

2013-01-01

Full Text Available A series of novel N-cycloalkanes, morpholine, piperazines, pyrazole, pyrimidine, benzimidazolo[1,2-a]pyrimidine, 1,2,3,4-tetrazolo[1,5-a]pyrimidine, azopyrazolo[1,5- a]pyrimidine, pyrimido[4', 5':3,4]pyrazolo[1,5-a]pyrimidines and pyridine derivatives incorporating a 5-cyano-4-methyl-2-phenyl-(thiopyrimidine moiety were obtained by the intramolecular cyclization of 6-methylthio-pyrimidine, 6-(benzoylmethylthio- pyrimidine and 2-[(5-cyano-4-methyl-2-phenylpyrimidin-6-ylthio]-3-dimethyl- amino-1-phenyl-prop-2-en-1-one with appropriate amines and enaminone compounds, respectively. The structure of all new synthesized compounds was established from their spectral data, elemental analysis and the X-ray crystal analysis.

[Postoperative management of partial or reconstructive pharyngo-laryngectomies].

Science.gov (United States)

Monziols, F; Verhulst, J; Lenoir, J L; Alix, M; Larricque, J; Krispel, N

1995-01-01

The multidisciplinary management of patients following pharyngolaryngeal surgery is an essential condition for its functional and socio-professional success. Early, overall rehabilitation, geared to each type of exeresis and to the personality of each patient, will enable both the voice and swallowing to regain their autonomy. A series of 195 patients after partial or reconstructive laryngectomy or pharyngectomy is analysed. The maintenance of a functional crico-arytenoid unity, the preservation of the mucosal sensitivity, the establishment of a facilitating posture and the dynamisation of the neoglottic sphincter are all equally important elements requiring the mobilisation of the entire health care team.

[Removable partial dentures. Oral functions and types

NARCIS (Netherlands)

Creugers, N.H.J.; Baat, C. de

2009-01-01

A removable partial denture enables the restoration or improvement of 4 oral functions: aesthetics, mandibular stability, mastication, and speech. However, wearing a removable partial denture should not cause oral comfort to deteriorate. There are 3 types of removable partial dentures: acrylic

Zonal differences in the distribution and morphology of lipid droplets using 4-amino-pyrazolo-(3,4 d) pyrimidine to lower cholesterol level in the rat adrenal.

Science.gov (United States)

Szabó, D; Somogyi, J; Acs, Z; Mihály, K

1980-01-01

The effect of reduced blood and adrenal cholesterol levels on adrenocortical lipid droplets have been examined by treating adult rats with 4-amino-pyrazolo-(3,4 d) pyrimidine (4-APP), a drug that inhibits hepatic secretion of lipoproteins. Lowering the blood cholesterol level and the cholesterol content of the adrenals was associated with a marked reduction in the lipid droplets and with a simultaneous increase in their electron density in the inner cortical zones. In the zona glomerulosa cells, no perceptible differences were found in the quantity and morphology of lipid droplets. These data suggest that reduced blood and adrenal cholesterol levels do not affect lipids located in the zona glomerulosa and in the inner cortical zones in the same way, probably due to differences in their intracellular lipid dynamism. Noteworthy, that in spite of the marked lipid depletion, the adrenal glands retained their responsiveness to ACTH stimulation.

Beginning partial differential equations

CERN Document Server

O'Neil, Peter V

2014-01-01

A broad introduction to PDEs with an emphasis on specialized topics and applications occurring in a variety of fields Featuring a thoroughly revised presentation of topics, Beginning Partial Differential Equations, Third Edition provides a challenging, yet accessible,combination of techniques, applications, and introductory theory on the subjectof partial differential equations. The new edition offers nonstandard coverageon material including Burger's equation, the telegraph equation, damped wavemotion, and the use of characteristics to solve nonhomogeneous problems. The Third Edition is or

Recent research directions in Fribourg: nuclear dynamics in resonances revealed by 2-dimensional EEL spectra, electron collisions with ionic liquids and electronic excitation of pyrimidine

International Nuclear Information System (INIS)

Allan, M.; Regeta, K.; Gorfinkiel, J.D.; Masin, Z.; Grimme, S.; Bannwarth, C.

2016-01-01

The article briefly reviews three subjects recently investigated in Fribourg: 1) electron collisions with surfaces of ionic liquids, 2) two-dimensional (2D) electron energy loss spectra and 3) resonances in absolute cross sections for electronic excitation of unsaturated compounds. Electron energy loss spectra of four ionic liquids revealed a number of excited states, including triplet states. A solution of a dye in an ionic liquid showed an energy-loss band of the solute, but not in all ionic liquids. 2D spectra reveal state-to-state information (given resonance to given final state) and are shown to be an interesting means to gain insight into dynamics of nuclear motion in resonances. Absolute cross sections for pyrimidine are reported as a function of scattering angle and as a function of electron energy. They reveal resonant structure which was reproduced very nicely by R-matrix calculations. The calculation provided an assignment of the resonances which reveals common patterns in compounds containing double bonds. (authors)

[Acrylic resin removable partial dentures

NARCIS (Netherlands)

Baat, C. de; Witter, D.J.; Creugers, N.H.J.

2011-01-01

An acrylic resin removable partial denture is distinguished from other types of removable partial dentures by an all-acrylic resin base which is, in principle, solely supported by the edentulous regions of the tooth arch and in the maxilla also by the hard palate. When compared to the other types of

Effects of Impression Material, Impression Tray Type, and Type of Partial Edentulism on the Fit of Cobalt-Chromium Partial Denture Frameworks on Initial Clinical Insertion: A Retrospective Clinical Evaluation.

Science.gov (United States)

Baig, Mirza Rustum; Akbar, Jaber Hussain; Qudeimat, Muawia; Omar, Ridwaan

2018-02-15

To evaluate the effects of impression material, impression tray type, and type of partial edentulism (ie, Kennedy class) on the accuracy of fit of cobalt-chromium (Co-Cr) partial removable dental prostheses (PRDP) in terms of the number of fabricated frameworks required until the attainment of adequate fit. Electronic case documentations of 120 partially edentulous patients provided with Co-Cr PRDP treatment for one or both arches were examined. Statistical analyses of data were performed using analysis of variance and Tukey honest significant difference test to compare the relationships between the different factors and the number of frameworks that needed to be fabricated for each patient (α = .05). Statistical analysis of data derived from 143 records (69 maxillary and 74 mandibular) revealed no significant correlation between impression material, tray type, or Kennedy class and the number of construction attempts for the pooled or individual arch data (P ≥ .05). In PRDP treatment, alginate can be chosen as a first-choice material, and metal stock trays can be a preferred option for making final impressions to fabricate Co-Cr frameworks.

PARALLEL SOLUTION METHODS OF PARTIAL DIFFERENTIAL EQUATIONS

Directory of Open Access Journals (Sweden)

Korhan KARABULUT

1998-03-01

Full Text Available Partial differential equations arise in almost all fields of science and engineering. Computer time spent in solving partial differential equations is much more than that of in any other problem class. For this reason, partial differential equations are suitable to be solved on parallel computers that offer great computation power. In this study, parallel solution to partial differential equations with Jacobi, Gauss-Siedel, SOR (Succesive OverRelaxation and SSOR (Symmetric SOR algorithms is studied.

Partial Fourier techniques in single-shot cross-term spatiotemporal encoded MRI.

Science.gov (United States)

Zhang, Zhiyong; Frydman, Lucio

2018-03-01

Cross-term spatiotemporal encoding (xSPEN) is a single-shot approach with exceptional immunity to field heterogeneities, the images of which faithfully deliver 2D spatial distributions without requiring a priori information or using postacquisition corrections. xSPEN, however, suffers from signal-to-noise ratio penalties due to its non-Fourier nature and due to diffusion losses-especially when seeking high resolution. This study explores partial Fourier transform approaches that, acting along either the readout or the spatiotemporally encoded dimensions, reduce these penalties. xSPEN uses an orthogonal (e.g., z) gradient to read, in direct space, the low-bandwidth (e.g., y) dimension. This substantially changes the nature of partial Fourier acquisitions vis-à-vis conventional imaging counterparts. A suitable theoretical analysis is derived to implement these procedures, along either the spatiotemporally or readout axes. Partial Fourier single-shot xSPEN images were recorded on preclinical and human scanners. Owing to their reduction in the experiments' acquisition times, this approach provided substantial sensitivity gains vis-à-vis previous implementations for a given targeted in-plane resolution. The physical origins of these gains are explained. Partial Fourier approaches, particularly when implemented along the low-bandwidth spatiotemporal dimension, provide several-fold sensitivity advantages at minimal costs to the execution and processing of the single-shot experiments. Magn Reson Med 79:1506-1514, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Partial processing

International Nuclear Information System (INIS)

1978-11-01

This discussion paper considers the possibility of applying to the recycle of plutonium in thermal reactors a particular method of partial processing based on the PUREX process but named CIVEX to emphasise the differences. The CIVEX process is based primarily on the retention of short-lived fission products. The paper suggests: (1) the recycle of fission products with uranium and plutonium in thermal reactor fuel would be technically feasible; (2) it would, however, take ten years or more to develop the CIVEX process to the point where it could be launched on a commercial scale; (3) since the majority of spent fuel to be reprocessed this century will have been in storage for ten years or more, the recycling of short-lived fission products with the U-Pu would not provide an effective means of making refabrication fuel ''inaccessible'' because the radioactivity associated with the fission products would have decayed. There would therefore be no advantage in partial processing

Development of Partial Discharging Simulation Test Equipment

Science.gov (United States)

Kai, Xue; Genghua, Liu; Yan, Jia; Ziqi, Chai; Jian, Lu

2017-12-01

In the case of partial discharge training for recruits who lack of on-site work experience, the risk of physical shock and damage of the test equipment may be due to the limited skill level and improper operation by new recruits. Partial discharge simulation tester is the use of simulation technology to achieve partial discharge test process simulation, relatively true reproduction of the local discharge process and results, so that the operator in the classroom will be able to get familiar with and understand the use of the test process and equipment.The teacher sets up the instrument to display different partial discharge waveforms so that the trainees can analyze the test results of different partial discharge types.