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Sample records for class ib ribonucleotide

Streptococcus sanguinis Class Ib Ribonucleotide Reductase

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Makhlynets, Olga; Boal, Amie K.; Rhodes, DeLacy V.; Kitten, Todd; Rosenzweig, Amy C.; Stubbe, JoAnne

2014-01-01

Streptococcus sanguinis is a causative agent of infective endocarditis. Deletion of SsaB, a manganese transporter, drastically reduces S. sanguinis virulence. Many pathogenic organisms require class Ib ribonucleotide reductase (RNR) to catalyze the conversion of nucleotides to deoxynucleotides under aerobic conditions, and recent studies demonstrate that this enzyme uses a dimanganese-tyrosyl radical (MnIII2-Y•) cofactor in vivo. The proteins required for S. sanguinis ribonucleotide reduction (NrdE and NrdF, α and β subunits of RNR; NrdH and TrxR, a glutaredoxin-like thioredoxin and a thioredoxin reductase; and NrdI, a flavodoxin essential for assembly of the RNR metallo-cofactor) have been identified and characterized. Apo-NrdF with FeII and O2 can self-assemble a diferric-tyrosyl radical (FeIII2-Y•) cofactor (1.2 Y•/β2) and with the help of NrdI can assemble a MnIII2-Y• cofactor (0.9 Y•/β2). The activity of RNR with its endogenous reductants, NrdH and TrxR, is 5,000 and 1,500 units/mg for the Mn- and Fe-NrdFs (Fe-loaded NrdF), respectively. X-ray structures of S. sanguinis NrdIox and MnII2-NrdF are reported and provide a possible rationale for the weak affinity (2.9 μm) between them. These streptococcal proteins form a structurally distinct subclass relative to other Ib proteins with unique features likely important in cluster assembly, including a long and negatively charged loop near the NrdI flavin and a bulky residue (Thr) at a constriction in the oxidant channel to the NrdI interface. These studies set the stage for identifying the active form of S. sanguinis class Ib RNR in an animal model for infective endocarditis and establishing whether the manganese requirement for pathogenesis is associated with RNR. PMID:24381172
The Dimanganese(II) Site of Bacillus subtilis Class Ib Ribonucleotide Reductase

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Boal, Amie K.; Cotruvo, Jr., Joseph A.; Stubbe, JoAnne; Rosenzweig, Amy C. (MIT); (NWU)

2014-10-02

Class Ib ribonucleotide reductases (RNRs) use a dimanganese-tyrosyl radical cofactor, Mn{sub 2}{sup III}-Y{sm_bullet}, in their homodimeric NrdF ({beta}2) subunit to initiate reduction of ribonucleotides to deoxyribonucleotides. The structure of the Mn{sub 2}{sup II} form of NrdF is an important component in understanding O{sub 2}-mediated formation of the active metallocofactor, a subject of much interest because a unique flavodoxin, NrdI, is required for cofactor assembly. Biochemical studies and sequence alignments suggest that NrdF and NrdI proteins diverge into three phylogenetically distinct groups. The only crystal structure to date of a NrdF with a fully ordered and occupied dimanganese site is that of Escherichia coli Mn{sub 2}{sup II}-NrdF, prototypical of the enzymes from actinobacteria and proteobacteria. Here we report the 1.9 {angstrom} resolution crystal structure of Bacillus subtilis Mn{sub 2}{sup II}-NrdF, representative of the enzymes from a second group, from Bacillus and Staphylococcus. The structures of the metal clusters in the {beta}2 dimer are distinct from those observed in E. coli Mn{sub 2}{sup II}-NrdF. These differences illustrate the key role that solvent molecules and protein residues in the second coordination sphere of the Mn{sub 2}{sup II} cluster play in determining conformations of carboxylate residues at the metal sites and demonstrate that diverse coordination geometries are capable of serving as starting points for Mn{sub 2}{sup III}-Y{sm_bullet} cofactor assembly in class Ib RNRs.
Escherichia coli class Ib ribonucleotide reductase contains a dimanganese(III)-tyrosyl radical cofactor in vivo†

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Cotruvo, Joseph A.; Stubbe, JoAnne

2011-01-01

Escherichia coli class Ib ribonucleotide reductase (RNR) converts nucleoside 5′-diphosphates to deoxynucleoside 5′-diphosphates in iron-limited and oxidative stress conditions. We have recently demonstrated in vitro that this RNR is active with both diferric-tyrosyl radical (FeIII2-Y•) and dimanganese(III)-Y• (MnIII2-Y•) cofactors in the β2 subunit, NrdF [Cotruvo J.A., Jr. and Stubbe J., Biochemistry (2010) 49, 1297–1309]. Here we demonstrate, by purification of this protein from its endogenous levels in an E. coli strain deficient in its five known iron uptake pathways and grown under iron-limited conditions, that the MnIII2-Y• cofactor is assembled in vivo. This is the first definitive determination of the active cofactor of a class Ib RNR purified from its native organism without overexpression. From 88 g of cell paste, 150 μg of NrdF was isolated with ~95% purity, with 0.2 Y•/β2, 0.9 Mn/β2, and a specific activity of 720 nmol/min/mg. In these conditions, the class Ib RNR is the primary active RNR in the cell. Our results strongly suggest that E. coli NrdF is an obligate manganese protein in vivo and that the MnIII2-Y• cofactor assembly pathway we have identified in vitro involving the flavodoxin-like protein NrdI, present inside the cell at catalytic levels, is operative in vivo. PMID:21250660
Streptococcus sanguinis class Ib ribonucleotide reductase: high activity with both iron and manganese cofactors and structural insights.

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Makhlynets, Olga; Boal, Amie K; Rhodes, Delacy V; Kitten, Todd; Rosenzweig, Amy C; Stubbe, JoAnne

2014-02-28

Streptococcus sanguinis is a causative agent of infective endocarditis. Deletion of SsaB, a manganese transporter, drastically reduces S. sanguinis virulence. Many pathogenic organisms require class Ib ribonucleotide reductase (RNR) to catalyze the conversion of nucleotides to deoxynucleotides under aerobic conditions, and recent studies demonstrate that this enzyme uses a dimanganese-tyrosyl radical (Mn(III)2-Y(•)) cofactor in vivo. The proteins required for S. sanguinis ribonucleotide reduction (NrdE and NrdF, α and β subunits of RNR; NrdH and TrxR, a glutaredoxin-like thioredoxin and a thioredoxin reductase; and NrdI, a flavodoxin essential for assembly of the RNR metallo-cofactor) have been identified and characterized. Apo-NrdF with Fe(II) and O2 can self-assemble a diferric-tyrosyl radical (Fe(III)2-Y(•)) cofactor (1.2 Y(•)/β2) and with the help of NrdI can assemble a Mn(III)2-Y(•) cofactor (0.9 Y(•)/β2). The activity of RNR with its endogenous reductants, NrdH and TrxR, is 5,000 and 1,500 units/mg for the Mn- and Fe-NrdFs (Fe-loaded NrdF), respectively. X-ray structures of S. sanguinis NrdIox and Mn(II)2-NrdF are reported and provide a possible rationale for the weak affinity (2.9 μM) between them. These streptococcal proteins form a structurally distinct subclass relative to other Ib proteins with unique features likely important in cluster assembly, including a long and negatively charged loop near the NrdI flavin and a bulky residue (Thr) at a constriction in the oxidant channel to the NrdI interface. These studies set the stage for identifying the active form of S. sanguinis class Ib RNR in an animal model for infective endocarditis and establishing whether the manganese requirement for pathogenesis is associated with RNR.
Genetic characterization and role in virulence of the ribonucleotide reductases of Streptococcus sanguinis.

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Rhodes, DeLacy V; Crump, Katie E; Makhlynets, Olga; Snyder, Melanie; Ge, Xiuchun; Xu, Ping; Stubbe, JoAnne; Kitten, Todd

2014-02-28

Streptococcus sanguinis is a cause of infective endocarditis and has been shown to require a manganese transporter called SsaB for virulence and O2 tolerance. Like certain other pathogens, S. sanguinis possesses aerobic class Ib (NrdEF) and anaerobic class III (NrdDG) ribonucleotide reductases (RNRs) that perform the essential function of reducing ribonucleotides to deoxyribonucleotides. The accompanying paper (Makhlynets, O., Boal, A. K., Rhodes, D. V., Kitten, T., Rosenzweig, A. C., and Stubbe, J. (2014) J. Biol. Chem. 289, 6259-6272) indicates that in the presence of O2, the S. sanguinis class Ib RNR self-assembles an essential diferric-tyrosyl radical (Fe(III)2-Y(•)) in vitro, whereas assembly of a dimanganese-tyrosyl radical (Mn(III)2-Y(•)) cofactor requires NrdI, and Mn(III)2-Y(•) is more active than Fe(III)2-Y(•) with the endogenous reducing system of NrdH and thioredoxin reductase (TrxR1). In this study, we have shown that deletion of either nrdHEKF or nrdI completely abolishes virulence in an animal model of endocarditis, whereas nrdD mutation has no effect. The nrdHEKF, nrdI, and trxR1 mutants fail to grow aerobically, whereas anaerobic growth requires nrdD. The nrdJ gene encoding an O2-independent adenosylcobalamin-cofactored RNR was introduced into the nrdHEKF, nrdI, and trxR1 mutants. Growth of the nrdHEKF and nrdI mutants in the presence of O2 was partially restored. The combined results suggest that Mn(III)2-Y(•)-cofactored NrdF is required for growth under aerobic conditions and in animals. This could explain in part why manganese is necessary for virulence and O2 tolerance in many bacterial pathogens possessing a class Ib RNR and suggests NrdF and NrdI may serve as promising new antimicrobial targets.
Genetic Characterization and Role in Virulence of the Ribonucleotide Reductases of Streptococcus sanguinis * ♦

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Rhodes, DeLacy V.; Crump, Katie E.; Makhlynets, Olga; Snyder, Melanie; Ge, Xiuchun; Xu, Ping; Stubbe, JoAnne; Kitten, Todd

2014-01-01

Streptococcus sanguinis is a cause of infective endocarditis and has been shown to require a manganese transporter called SsaB for virulence and O2 tolerance. Like certain other pathogens, S. sanguinis possesses aerobic class Ib (NrdEF) and anaerobic class III (NrdDG) ribonucleotide reductases (RNRs) that perform the essential function of reducing ribonucleotides to deoxyribonucleotides. The accompanying paper (Makhlynets, O., Boal, A. K., Rhodes, D. V., Kitten, T., Rosenzweig, A. C., and Stubbe, J. (2014) J. Biol. Chem. 289, 6259–6272) indicates that in the presence of O2, the S. sanguinis class Ib RNR self-assembles an essential diferric-tyrosyl radical (FeIII2-Y•) in vitro, whereas assembly of a dimanganese-tyrosyl radical (MnIII2-Y•) cofactor requires NrdI, and MnIII2-Y• is more active than FeIII2-Y• with the endogenous reducing system of NrdH and thioredoxin reductase (TrxR1). In this study, we have shown that deletion of either nrdHEKF or nrdI completely abolishes virulence in an animal model of endocarditis, whereas nrdD mutation has no effect. The nrdHEKF, nrdI, and trxR1 mutants fail to grow aerobically, whereas anaerobic growth requires nrdD. The nrdJ gene encoding an O2-independent adenosylcobalamin-cofactored RNR was introduced into the nrdHEKF, nrdI, and trxR1 mutants. Growth of the nrdHEKF and nrdI mutants in the presence of O2 was partially restored. The combined results suggest that MnIII2-Y•-cofactored NrdF is required for growth under aerobic conditions and in animals. This could explain in part why manganese is necessary for virulence and O2 tolerance in many bacterial pathogens possessing a class Ib RNR and suggests NrdF and NrdI may serve as promising new antimicrobial targets. PMID:24381171
HLA class Ib in pregnancy and pregnancy-related disorders.

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Persson, Gry; Melsted, Wenna Nascimento; Nilsson, Line Lynge; Hviid, Thomas Vauvert F

2017-08-01

The HLA class Ib genes, HLA-E, HLA-F, and HLA-G, were discovered long after the classical HLA class Ia genes. The elucidation of their functions had a modest beginning. However, their basic functions and involvement in pathophysiology and a range of diseases are now emerging. Although results from a range of studies support the functional roles for the HLA class Ib molecules in adult life, especially HLA-G and HLA-F have most intensively been, and were also primarily, studied in relation to reproduction and pregnancy. The expression of HLA class Ib proteins at the feto-maternal interface in the placenta seems to be important for the maternal acceptance of the semi-allogenic fetus. In contrast to the functions of HLA class Ia, HLA-G possesses immune-modulatory and tolerogenic functions. Here, we review an accumulating amount of data describing the functions of HLA class Ib molecules in relation to fertility, reproduction, and pregnancy, and a possible role for these molecules in certain pregnancy complications, such as implantation failure, recurrent spontaneous abortions, and pre-eclampsia. The results from different kinds of studies point toward a role for HLA class Ib, especially HLA-G, throughout the reproductive cycle from conception to the birth weight of the child.
A New Type of YumC-Like Ferredoxin (Flavodoxin) Reductase Is Involved in Ribonucleotide Reduction

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Chen, Jun; Shen, Jing; Solem, Christian

2015-01-01

. subtilis but that the addition of deoxynucleosides cannot compensate for the lethal phenotype displayed by the B. subtilis yumC knockout mutant. Ferredoxin (flavodoxin) reductase (FdR) is involved in many important reactions in both eukaryotes and prokaryotes, such as photosynthesis, nitrate reduction, etc. The recently...... ribonucleotide reductase, which represents the workhorse for the bioconversion of nucleotides to deoxynucleotides in many prokaryotes and eukaryotic pathogens under aerobic conditions. As the partner of the flavodoxin (NrdI), the key FdR is missing in the current model describing the class Ib system...
Peroxo-Type Intermediates in Class I Ribonucleotide Reductase and Related Binuclear Non-Heme Iron Enzymes

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Kepp, Kasper Planeta; Bell, Caleb B.; Clay, MIchael D.

2009-01-01

We have performed a systematic study of chemically possible peroxo-type intermediates occurring in the non-heme di-iron enzyme class la ribonucleotide reductase, using spectroscopically calibrated computational chemistry. Density functional computations of equilibrium structures, Fe-O and O-O str...
Spectroscopic studies of the iron and manganese reconstituted tyrosyl radical in Bacillus cereus ribonucleotide reductase R2 protein.

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Ane B Tomter

Full Text Available Ribonucleotide reductase (RNR catalyzes the rate limiting step in DNA synthesis where ribonucleotides are reduced to the corresponding deoxyribonucleotides. Class Ib RNRs consist of two homodimeric subunits: R1E, which houses the active site; and R2F, which contains a metallo cofactor and a tyrosyl radical that initiates the ribonucleotide reduction reaction. We studied the R2F subunit of B. cereus reconstituted with iron or alternatively with manganese ions, then subsequently reacted with molecular oxygen to generate two tyrosyl-radicals. The two similar X-band EPR spectra did not change significantly over 4 to 50 K. From the 285 GHz EPR spectrum of the iron form, a g(1-value of 2.0090 for the tyrosyl radical was extracted. This g(1-value is similar to that observed in class Ia E. coli R2 and class Ib R2Fs with iron-oxygen cluster, suggesting the absence of hydrogen bond to the phenoxyl group. This was confirmed by resonance Raman spectroscopy, where the stretching vibration associated to the radical (C-O, ν(7a = 1500 cm(-1 was found to be insensitive to deuterium-oxide exchange. Additionally, the (18O-sensitive Fe-O-Fe symmetric stretching (483 cm(-1 of the metallo-cofactor was also insensitive to deuterium-oxide exchange indicating no hydrogen bonding to the di-iron-oxygen cluster, and thus, different from mouse R2 with a hydrogen bonded cluster. The HF-EPR spectrum of the manganese reconstituted RNR R2F gave a g(1-value of ∼2.0094. The tyrosyl radical microwave power saturation behavior of the iron-oxygen cluster form was as observed in class Ia R2, with diamagnetic di-ferric cluster ground state, while the properties of the manganese reconstituted form indicated a magnetic ground state of the manganese-cluster. The recent activity measurements (Crona et al., (2011 J Biol Chem 286: 33053-33060 indicates that both the manganese and iron reconstituted RNR R2F could be functional. The manganese form might be very important, as it has 8
Genome instabilities arising from ribonucleotides in DNA.

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Klein, Hannah L

2017-08-01

Genomic DNA is transiently contaminated with ribonucleotide residues during the process of DNA replication through misincorporation by the replicative DNA polymerases α, δ and ε, and by the normal replication process on the lagging strand, which uses RNA primers. These ribonucleotides are efficiently removed during replication by RNase H enzymes and the lagging strand synthesis machinery. However, when ribonucleotides remain in DNA they can distort the DNA helix, affect machineries for DNA replication, transcription and repair, and can stimulate genomic instabilities which are manifest as increased mutation, recombination and chromosome alterations. The genomic instabilities associated with embedded ribonucleotides are considered here, along with a discussion of the origin of the lesions that stimulate particular classes of instabilities. Copyright © 2017 Elsevier B.V. All rights reserved.
Role of Ribonucleotide Reductase in Bacillus subtilis Stress-Associated Mutagenesis.

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Castro-Cerritos, Karla Viridiana; Yasbin, Ronald E; Robleto, Eduardo A; Pedraza-Reyes, Mario

2017-02-15

The Gram-positive microorganism Bacillus subtilis relies on a single class Ib ribonucleotide reductase (RNR) to generate 2'-deoxyribonucleotides (dNDPs) for DNA replication and repair. In this work, we investigated the influence of RNR levels on B. subtilis stationary-phase-associated mutagenesis (SPM). Since RNR is essential in this bacterium, we engineered a conditional mutant of strain B. subtilis YB955 (hisC952 metB5 leu427) in which expression of the nrdEF operon was modulated by isopropyl-β-d-thiogalactopyranoside (IPTG). Moreover, genetic inactivation of ytcG, predicted to encode a repressor (NrdR) of nrdEF in this strain, dramatically increased the expression levels of a transcriptional nrdE-lacZ fusion. The frequencies of mutations conferring amino acid prototrophy in three genes were measured in cultures under conditions that repressed or induced RNR-encoding genes. The results revealed that RNR was necessary for SPM and overexpression of nrdEF promoted growth-dependent mutagenesis and SPM. We also found that nrdEF expression was induced by H 2 O 2 and such induction was dependent on the master regulator PerR. These observations strongly suggest that the metabolic conditions operating in starved B. subtilis cells increase the levels of RNR, which have a direct impact on SPM. Results presented in this study support the concept that the adverse metabolic conditions prevailing in nutritionally stressed bacteria activate an oxidative stress response that disturbs ribonucleotide reductase (RNR) levels. Such an alteration of RNR levels promotes mutagenic events that allow Bacillus subtilis to escape from growth-limited conditions. Copyright © 2017 American Society for Microbiology.
Hydroxyurea-Mediated Cytotoxicity Without Inhibition of Ribonucleotide Reductase.

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Liew, Li Phing; Lim, Zun Yi; Cohen, Matan; Kong, Ziqing; Marjavaara, Lisette; Chabes, Andrei; Bell, Stephen D

2016-11-01

In many organisms, hydroxyurea (HU) inhibits class I ribonucleotide reductase, leading to lowered cellular pools of deoxyribonucleoside triphosphates. The reduced levels for DNA precursors is believed to cause replication fork stalling. Upon treatment of the hyperthermophilic archaeon Sulfolobus solfataricus with HU, we observe dose-dependent cell cycle arrest, accumulation of DNA double-strand breaks, stalled replication forks, and elevated levels of recombination structures. However, Sulfolobus has a HU-insensitive class II ribonucleotide reductase, and we reveal that HU treatment does not significantly impact cellular DNA precursor pools. Profiling of protein and transcript levels reveals modulation of a specific subset of replication initiation and cell division genes. Notably, the selective loss of the regulatory subunit of the primase correlates with cessation of replication initiation and stalling of replication forks. Furthermore, we find evidence for a detoxification response induced by HU treatment. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Ribonucleotide reductase class III, an essential enzyme for the anaerobic growth of Staphylococcus aureus, is a virulence determinant in septic arthritis.

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Kirdis, Ebru; Jonsson, Ing-Marie; Kubica, Malgorzata; Potempa, Jan; Josefsson, Elisabet; Masalha, Mahmud; Foster, Simon J; Tarkowski, Andrzej

2007-01-01

Staphylococcus aureus is the most common cause of joint infections. It also contributes to several other diseases such as pneumonia, osteomyelitis, endocarditis, and sepsis. Bearing in mind that S. aureus becomes rapidly resistant to new antibiotics, many studies survey the virulence factors, with the aim to find alternative prophylaxis/treatment regimens. One potential virulence factor is the bacterial ability to survive at different oxygen tensions. S. aureus expresses ribonucleotide reductases (RNRs), which help it to grow under both aerobic and anaerobic conditions, by reducing ribonucleotides to deoxyribonucleotides. In this study, we investigated the role of RNR class III, which is required for anaerobic growth, as a virulence determinant in the pathogenesis of staphylococcal arthritis. The wild-type S. aureus strain and its isogenic mutant nrdDG mutant were inoculated intravenously into mice. Mice inoculated with the wild-type strain displayed significantly more severe arthritis, with significantly more synovitis and destruction of the bone and cartilage versus mutant strain inoculated mice. Further, the persistence of bacteria in the kidneys was significantly more pronounced in the group inoculated with the wild-type strain. Together these results indicate that RNR class III is an important virulence factor for the establishment of septic arthritis.
Human leucocyte antigen class Ib molecules in pregnancy success and early pregnancy loss

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Dahl, Mette; Hviid, Thomas Vauvert F

2013-01-01

AND CONCLUSIONS The HLA class Ib molecules seem to induce suppression of the maternal immune system, but are not necessarily fundamental factors for pregnancy success. However, evidence points towards low expression of these proteins, especially HLA-G, being associated with reduced fertility. To clarify...
Unusual evolutionary conservation and further species-specific adaptations of a large family of nonclassical MHC class Ib genes across different degrees of genome ploidy in the amphibian subfamily Xenopodinae.

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Edholm, Eva-Stina; Goyos, Ana; Taran, Joseph; De Jesús Andino, Francisco; Ohta, Yuko; Robert, Jacques

2014-06-01

Nonclassical MHC class Ib (class Ib) genes are a family of highly diverse and rapidly evolving genes wherein gene numbers, organization, and expression markedly differ even among closely related species rendering class Ib phylogeny difficult to establish. Whereas among mammals there are few unambiguous class Ib gene orthologs, different amphibian species belonging to the anuran subfamily Xenopodinae exhibit an unusually high degree of conservation among multiple class Ib gene lineages. Comparative genomic analysis of class Ib gene loci of two divergent (~65 million years) Xenopodinae subfamily members Xenopus laevis (allotetraploid) and Xenopus tropicalis (diploid) shows that both species possess a large cluster of class Ib genes denoted as Xenopus/Silurana nonclassical (XNC/SNC). Our study reveals two distinct phylogenetic patterns among these genes: some gene lineages display a high degree of flexibility, as demonstrated by species-specific expansion and contractions, whereas other class Ib gene lineages have been maintained as monogenic subfamilies with very few changes in their nucleotide sequence across divergent species. In this second category, we further investigated the XNC/SNC10 gene lineage that in X. laevis is required for the development of a distinct semi-invariant T cell population. We report compelling evidence of the remarkable high degree of conservation of this gene lineage that is present in all 12 species of the Xenopodinae examined, including species with different degrees of ploidy ranging from 2, 4, 8 to 12 N. This suggests that the critical role of XNC10 during early T cell development is conserved in amphibians.
The Incorporation of Ribonucleotides Induces Structural and Conformational Changes in DNA.

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Meroni, Alice; Mentegari, Elisa; Crespan, Emmanuele; Muzi-Falconi, Marco; Lazzaro, Federico; Podestà, Alessandro

2017-10-03

Ribonucleotide incorporation is the most common error occurring during DNA replication. Cells have hence developed mechanisms to remove ribonucleotides from the genome and restore its integrity. Indeed, the persistence of ribonucleotides into DNA leads to severe consequences, such as genome instability and replication stress. Thus, it becomes important to understand the effects of ribonucleotides incorporation, starting from their impact on DNA structure and conformation. Here we present a systematic study of the effects of ribonucleotide incorporation into DNA molecules. We have developed, to our knowledge, a new method to efficiently synthesize long DNA molecules (hundreds of basepairs) containing ribonucleotides, which is based on a modified protocol for the polymerase chain reaction. By means of atomic force microscopy, we could therefore investigate the changes, upon ribonucleotide incorporation, of the structural and conformational properties of numerous DNA populations at the single-molecule level. Specifically, we characterized the scaling of the contour length with the number of basepairs and the scaling of the end-to-end distance with the curvilinear distance, the bending angle distribution, and the persistence length. Our results revealed that ribonucleotides affect DNA structure and conformation on scales that go well beyond the typical dimension of the single ribonucleotide. In particular, the presence of ribonucleotides induces a systematic shortening of the molecules, together with a decrease of the persistence length. Such structural changes are also likely to occur in vivo, where they could directly affect the downstream DNA transactions, as well as interfere with protein binding and recognition. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Structural basis for decreased induction of class IB PI3-kinases expression by MIF inhibitors

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Singh, Abhay Kumar [Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis MO USA; Pantouris, Georgios [Department of Pharmacology, Yale University School of Medicine, New Haven CT USA; Borosch, Sebastian [Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen Germany; Rojanasthien, Siripong [Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis MO USA; Cho, Thomas Yoonsang [Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis MO USA

2016-09-13

Macrophage migration inhibitory factor (MIF) is a master regulator of proinflammatory cytokines and plays pathological roles when not properly regulated in rheumatoid arthritis, lupus, atherosclerosis, asthma and cancer. Unlike canonical cytokines, MIF has vestigial keto-enol tautomerase activity. Most of the current MIF inhibitors were screened for the inhibition of this enzymatic activity. However, only some of the enzymatic inhibitors inhibit receptor-mediated biological functions of MIF, such as cell recruitment, through an unknown molecular mechanism. The goal of this study was to understand the molecular basis underlying the pharmacological inhibition of biological functions of MIF. Here, we demonstrate how the structural changes caused upon inhibitor binding translate into the alteration of MIF-induced downstream signalling. Macrophage migration inhibitory factor activates phosphoinositide 3-kinases (PI3Ks) that play a pivotal role in immune cell recruitment in health and disease. There are several different PI3K isoforms, but little is known about how they respond to MIF. We demonstrate that MIF up-regulates the expression of Class IB PI3Ks in leucocytes. We also demonstrate that MIF tautomerase active site inhibitors down-regulate the expression of Class IB PI3Ks as well as leucocyte recruitment in vitro and in vivo. Finally, based on our MIF:inhibitor complex crystal structures, we hypothesize that the reduction in Class IB PI3K expression occurs because of the displacement of Pro1 towards the second loop of MIF upon inhibitor binding, which results in increased flexibility of the loop 2 and sub-optimal MIF binding to its receptors. These results will provide molecular insights for fine-tuning the biological functions of MIF.
HLA class Ia and Ib molecules and FOXP3+ TILs in relation to the prognosis of malignant melanoma patients

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Melsted, Wenna Nascimento; Johansen, Lasse Lindholm; Lock-Andersen, Jørgen

2017-01-01

HLA class Ia (HLA-ABC) and HLA class Ib (HLA-E, -F and -G) molecules and FOXP3+ tumor-infiltrating lymphocytes (TILs) are often reported as relevant factors of tumor immune regulation. We investigated their expression as prognostic factors in 200 patients with primary cutaneous melanoma (PCM...
Nucleotide pools dictate the identity and frequency of ribonucleotide incorporation in mitochondrial DNA.

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Anna-Karin Berglund

2017-02-01

Full Text Available Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication.

Nucleotide pools dictate the identity and frequency of ribonucleotide incorporation in mitochondrial DNA.

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Berglund, Anna-Karin; Navarrete, Clara; Engqvist, Martin K M; Hoberg, Emily; Szilagyi, Zsolt; Taylor, Robert W; Gustafsson, Claes M; Falkenberg, Maria; Clausen, Anders R

2017-02-01

Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication.
Post-Infectious IBS (IBS-PI)

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... for IBS Signs and Symptoms Overview Recognizing Symptoms Diagnosis of IBS Pain in IBS IBS with Constipation Constipated Diarrhea IBS ... for IBS Signs and Symptoms Overview Recognizing Symptoms Diagnosis of IBS Pain in IBS IBS with Constipation Constipated Diarrhea IBS ...
Ribonucleotide Reductases from Bifidobacteria Contain Multiple Conserved Indels Distinguishing Them from All Other Organisms: In Silico Analysis of the Possible Role of a 43 aa Bifidobacteria-Specific Insert in the Class III RNR Homolog

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Seema Alnajar

2017-07-01

Full Text Available Bifidobacteria comprises an important group/order of bacteria whose members have widespread usage in the food and health industry due to their health-promoting activity in the human gastrointestinal tract. However, little is known about the underlying molecular properties that are responsible for the probiotic effects of these bacteria. The enzyme ribonucleotide reductase (RNR plays a key role in all organisms by reducing nucleoside di- or tri- phosphates into corresponding deoxyribose derivatives required for DNA synthesis, and RNR homologs belonging to classes I and III are present in either most or all Bifidobacteriales. Comparative analyses of these RNR homologs have identified several novel sequence features in the forms of conserved signature indels (CSIs that are exclusively found in bifidobacterial RNRs. Specifically, in the large subunit of the aerobic class Ib RNR, three CSIs have been identified that are uniquely found in the Bifidobacteriales homologs. Similarly, the large subunit of the anaerobic class III RNR contains five CSIs that are also distinctive characteristics of bifidobacteria. Phylogenetic analyses indicate that these CSIs were introduced in a common ancestor of the Bifidobacteriales and retained by all descendants, likely due to their conferring advantageous functional roles. The identified CSIs in the bifidobacterial RNR homologs provide useful tools for further exploration of the novel functional aspects of these important enzymes that are exclusive to these bacteria. We also report here the results of homology modeling studies, which indicate that most of the bifidobacteria-specific CSIs are located within the surface loops of the RNRs, and of these, a large 43 amino acid insert in the class III RNR homolog forms an extension of the allosteric regulatory site known to be essential for protein function. Preliminary docking studies suggest that this large CSI may be playing a role in enhancing the stability of the RNR
Pseudomonas aeruginosa Exhibits Deficient Biofilm Formation in the Absence of Class II and III Ribonucleotide Reductases Due to Hindered Anaerobic Growth.

Science.gov (United States)

Crespo, Anna; Pedraz, Lucas; Astola, Josep; Torrents, Eduard

2016-01-01

Chronic lung infections by the ubiquitous and extremely adaptable opportunistic pathogen Pseudomonas aeruginosa correlate with the formation of a biofilm, where bacteria grow in association with an extracellular matrix and display a wide range of changes in gene expression and metabolism. This leads to increased resistance to physical stress and antibiotic therapies, while enhancing cell-to-cell communication. Oxygen diffusion through the complex biofilm structure generates an oxygen concentration gradient, leading to the appearance of anaerobic microenvironments. Ribonucleotide reductases (RNRs) are a family of highly sophisticated enzymes responsible for the synthesis of the deoxyribonucleotides, and they constitute the only de novo pathway for the formation of the building blocks needed for DNA synthesis and repair. P. aeruginosa is one of the few bacteria encoding all three known RNR classes (Ia, II, and III). Class Ia RNRs are oxygen dependent, class II are oxygen independent, and class III are oxygen sensitive. A tight control of RNR activity is essential for anaerobic growth and therefore for biofilm development. In this work we explored the role of the different RNR classes in biofilm formation under aerobic and anaerobic initial conditions and using static and continuous-flow biofilm models. We demonstrated the importance of class II and III RNR for proper cell division in biofilm development and maturation. We also determined that these classes are transcriptionally induced during biofilm formation and under anaerobic conditions. The molecular mechanism of their anaerobic regulation was also studied, finding that the Anr/Dnr system is responsible for class II RNR induction. These data can be integrated with previous knowledge about biofilms in a model where these structures are understood as a set of layers determined by oxygen concentration and contain cells with different RNR expression profiles, bringing us a step closer to the understanding of this
Function and Regulation of Yeast Ribonucleotide Reductase: Cell Cycle, Genotoxic Stress, and Iron Bioavailability

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Nerea Sanvisens

2013-04-01

Full Text Available Ribonucleotide reductases (RNRs are essential enzymes that catalyze the reduction of ribonucleotides to desoxyribonucleotides, thereby providing the building blocks required for de novo DNA biosynthesis. The RNR function is tightly regulated because an unbalanced or excessive supply of deoxyribonucleoside triphosphates (dNTPs dramatically increases the mutation rates during DNA replication and repair that can lead to cell death or genetic anomalies. In this review, we focus on Saccharomyces cerevisiae class Ia RNR as a model to understand the different mechanisms controlling RNR function and regulation in eukaryotes. Many studies have contributed to our current understanding of RNR allosteric regulation and, more recently, to its link to RNR oligomerization. Cells have developed additional mechanisms that restrict RNR activity to particular periods when dNTPs are necessary, such as the S phase or upon genotoxic stress. These regulatory strategies include the transcriptional control of the RNR gene expression, inhibition of RNR catalytic activity, and the subcellular redistribution of RNR subunits. Despite class Ia RNRs requiring iron as an essential cofactor for catalysis, little is known about RNR function regulation depending on iron bioavailability. Recent studies into yeast have deciphered novel strategies for the delivery of iron to RNR and for its regulation in response to iron deficiency. Taken together, these studies open up new possibilities to explore in order to limit uncontrolled tumor cell proliferation via RNR.
Measuring the Levels of Ribonucleotides Embedded in Genomic DNA.

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Meroni, Alice; Nava, Giulia M; Sertic, Sarah; Plevani, Paolo; Muzi-Falconi, Marco; Lazzaro, Federico

2018-01-01

Ribonucleotides (rNTPs) are incorporated into genomic DNA at a relatively high frequency during replication. They have beneficial effects but, if not removed from the chromosomes, increase genomic instability. Here, we describe a fast method to easily estimate the amounts of embedded ribonucleotides into the genome. The protocol described is performed in Saccharomyces cerevisiae and allows us to quantify altered levels of rNMPs due to different mutations in the replicative polymerase ε. However, this protocol can be easily applied to cells derived from any organism.
Molecular mechanisms of drug resistance and tumor promotion involving mammalian ribonucleotide reductase

Energy Technology Data Exchange (ETDEWEB)

Choy, B.B.K.

1991-01-01

Mammalian ribonucleotide reductase is a highly regulated, rate-limiting activity responsible for converting ribonucleoside diphosphates to the deoxyribonucleotide precursors of DNA. The enzyme consists of two nonidentical proteins called M1 and M2, both of which are required for activity. Hydroxyurea is an antitumor agent which inhibits ribonucleotide reductase by interacting with the M2 component specifically at a unique tyrosyl free radical. Studies were conducted on a series of drug resistant mouse cell lines, selected by a step-wise procedure for increasing levels of resistance to the cytotoxic effects of hydroxyurea. Each successive drug selection step leading to the isolation of highly resistant cells was accompanied by stable elevations in cellular resistance and ribonucleotide reductase activity. The drug resistant cell lines exhibited gene amplification of the M2 gene, elevated M2 mRNA, and M2 protein. In addition to M2 gene amplification, posttranscriptional modulation also occurred during the drug selection. Studies of the biosynthesis rates with exogenously added iron suggest a role for iron in regulating the level of M2 protein when cells are cultured in the presence of hydroxyurea. The hydroxyurea-inactivated ribonucleotide reductase protein M2 has a destabilized iron centre, which readily releases iron. Altered expression of ferritin appears to be required for the development of hydroxyurea resistance in nammalian cells. The results show an interesting relationship between the expressions of ribonucleotide reductase and ferritin. The phorbol ester tumor promoter, TPA, is also able to alter the expression of M2. TPA was able to induce M2 mRNA levels transiently up to 18-fold within 1/2 hour. This rapid and large elevation of ribonucleotide reductase suggests that the enzyme may play a role in tumor promotion. Studies of the M2 promoter region were undertaken to better understand the mechanism of TPA induction of M2.
The role of RNase H2 in processing ribonucleotides incorporated during DNA replication.

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Williams, Jessica S; Gehle, Daniel B; Kunkel, Thomas A

2017-05-01

Saccharomyces cerevisiae RNase H2 resolves RNA-DNA hybrids formed during transcription and it incises DNA at single ribonucleotides incorporated during nuclear DNA replication. To distinguish between the roles of these two activities in maintenance of genome stability, here we investigate the phenotypes of a mutant of yeast RNase H2 (rnh201-RED; ribonucleotide excision defective) that retains activity on RNA-DNA hybrids but is unable to cleave single ribonucleotides that are stably incorporated into the genome. The rnh201-RED mutant was expressed in wild type yeast or in a strain that also encodes a mutant allele of DNA polymerase ε (pol2-M644G) that enhances ribonucleotide incorporation during DNA replication. Similar to a strain that completely lacks RNase H2 (rnh201Δ), the pol2-M644G rnh201-RED strain exhibits replication stress and checkpoint activation. Moreover, like its null mutant counterpart, the double mutant pol2-M644G rnh201-RED strain and the single mutant rnh201-RED strain delete 2-5 base pairs in repetitive sequences at a high rate that is topoisomerase 1-dependent. The results highlight an important role for RNase H2 in maintaining genome integrity by removing single ribonucleotides incorporated during DNA replication. Published by Elsevier B.V.
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Introduction to IBS

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... Day Art of IBS Gallery Contact Us Search Introduction to IBS Details What is IBS? Last Updated: ... tax-deductible donation. Make Donation What is IBS? Introduction to IBS Symptoms of IBS What Causes IBS? ...
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Removal of misincorporated ribonucleotides from prokaryotic genomes: an unexpected role for nucleotide excision repair.

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Alexandra Vaisman

2013-11-01

Full Text Available Stringent steric exclusion mechanisms limit the misincorporation of ribonucleotides by high-fidelity DNA polymerases into genomic DNA. In contrast, low-fidelity Escherichia coli DNA polymerase V (pol V has relatively poor sugar discrimination and frequently misincorporates ribonucleotides. Substitution of a steric gate tyrosine residue with alanine (umuC_Y11A reduces sugar selectivity further and allows pol V to readily misincorporate ribonucleotides as easily as deoxynucleotides, whilst leaving its poor base-substitution fidelity essentially unchanged. However, the mutability of cells expressing the steric gate pol V mutant is very low due to efficient repair mechanisms that are triggered by the misincorporated rNMPs. Comparison of the mutation frequency between strains expressing wild-type and mutant pol V therefore allows us to identify pathways specifically directed at ribonucleotide excision repair (RER. We previously demonstrated that rNMPs incorporated by umuC_Y11A are efficiently removed from DNA in a repair pathway initiated by RNase HII. Using the same approach, we show here that mismatch repair and base excision repair play minimal back-up roles in RER in vivo. In contrast, in the absence of functional RNase HII, umuC_Y11A-dependent mutagenesis increases significantly in ΔuvrA, uvrB5 and ΔuvrC strains, suggesting that rNMPs misincorporated into DNA are actively repaired by nucleotide excision repair (NER in vivo. Participation of NER in RER was confirmed by reconstituting ribonucleotide-dependent NER in vitro. We show that UvrABC nuclease-catalyzed incisions are readily made on DNA templates containing one, two, or five rNMPs and that the reactions are stimulated by the presence of mispaired bases. Similar to NER of DNA lesions, excision of rNMPs proceeds through dual incisions made at the 8(th phosphodiester bond 5' and 4(th-5(th phosphodiester bonds 3' of the ribonucleotide. Ribonucleotides misinserted into DNA can therefore be
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Characterization of a cultured human T-cell line with genetically altered ribonucleotide reductase activity. Model for immunodeficiency.

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Waddell, D; Ullman, B

1983-04-10

From human CCRF-CEM T-cells growing in continuous culture, we have selected, isolated, and characterized a clonal cell line, APHID-D2, with altered ribonucleotide reductase activity. In comparative growth rate experiments, the APHID-D2 cell line is less sensitive than the parental cell line to growth inhibition by deoxyadenosine in the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase. The APHID-D2 cell line has elevated levels of all four dNTPs. The resistance of the APHID-D2 cell line to growth inhibition by deoxyadenosine and the abnormal dNTP levels can be explained by the fact that the APHID-D2 ribonucleotide reductase, unlike the parental ribonucleotide reductase, is not normally sensitive to inhibition by dATP. These results suggest that the allosteric site of ribonucleotide reductase which binds both dATP and ATP is altered in the APHID-D2 line. The isolation of a mutant clone of human T-cells which contains a ribonucleotide reductase that has lost its normal sensitivity to dATP and which is resistant to deoxyadenosine-mediated growth inhibition suggests that a primary pathogenic target of accumulated dATP in lymphocytes from patients with adenosine deaminase deficiency may be the cellular ribonucleotide reductase.
5,6-Dihydro-5-aza-2’-deoxycytidine potentiates the anti-HIV-1 activity of ribonucleotide reductase inhibitors

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Rawson, Jonathan M.; Heineman, Richard H.; Beach, Lauren B.; Martin, Jessica L.; Schnettler, Erica K.; Dapp, Michael J.; Patterson, Steven E.; Mansky, Louis M.

2013-01-01

The nucleoside analog 5,6-dihydro-5-aza-2’-deoxycytidine (KP-1212) has been investigated as a first-in-class lethal mutagen of human immunodeficiency virus type-1 (HIV-1). Since a prodrug monotherapy did not reduce viral loads in Phase II clinical trials, we tested if ribonucleotide reductase inhibitors (RNRIs) combined with KP-1212 would improve antiviral activity. KP-1212 potentiated the activity of gemcitabine and resveratrol and simultaneously increased the viral mutant frequency. G-to-C ...
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Mutations at Several Loci Cause Increased Expression of Ribonucleotide Reductase in Escherichia coli

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Feeney, Morgan Anne; Ke, Na

2012-01-01

Production of deoxyribonucleotides for DNA synthesis is an essential and tightly regulated process. The class Ia ribonucleotide reductase (RNR), the product of the nrdAB genes, is required for aerobic growth of Escherichia coli. In catalyzing the reduction of ribonucleotides, two of the cysteines of RNR become oxidized, forming a disulfide bond. To regenerate active RNR, the cell uses thioredoxins and glutaredoxins to reduce the disulfide bond. Strains that lack thioredoxins 1 and 2 and glutaredoxin 1 do not grow because RNR remains in its oxidized, inactive form. However, suppressor mutations that lead to RNR overproduction allow glutaredoxin 3 to reduce sufficient RNR for growth of these mutant strains. We previously described suppressor mutations in the dnaA and dnaN genes that had such effects. Here we report the isolation of new mutations that lead to increased levels of RNR. These include mutations that were not known to influence production of RNR previously, such as a mutation in the hda gene and insertions in the nrdAB promoter region of insertion elements IS1 and IS5. Bioinformatic analysis raises the possibility that IS element insertion in this region represents an adaptive mechanism in nrdAB regulation in E. coli and closely related species. We also characterize mutations altering different amino acids in DnaA and DnaN from those isolated before. PMID:22247510
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HLA Class Ib Molecules and Immune Cells in Pregnancy and Preeclampsia

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Djurisic, Snezana; Hviid, Thomas Vauvert F

2014-01-01

Despite decades of research, the highly prevalent pregnancy complication preeclampsia, "the disease of theories," has remained an enigma. Indeed, the etiology of preeclampsia is largely unknown. A compiling amount of studies indicates that the pathological basis involves a complex array of geneti...... of HLA-G, and, in some studies, with preeclampsia. In this review, a genetic contribution from the mother, the father, and the fetus, together with the presence and function of various immune cells of relevance in pregnancy are reviewed in relation to HLA-G and preeclampsia....... predisposition and immunological maladaptation, and that a contribution from the mother, the father, and the fetus is likely to be important. The Human Leukocyte Antigen (HLA)-G is an increasing focus of research in relation to preeclampsia. The HLA-G molecule is primarily expressed by the extravillous...... trophoblast cells lining the placenta together with the two other HLA class Ib molecules, HLA-E and HLA-F. Soluble isoforms of HLA-G have been detected in the early endometrium, the matured cumulus-oocyte complex, maternal blood of pregnant women, in umbilical cord blood, and lately, in seminal plasma. HLA...
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Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms

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Nestoras, Konstantinos; Mohammed, Asma Hadi; Schreurs, Ann-Sofie

2010-01-01

The correct levels of deoxyribonucleotide triphosphates and their relative abundance are important to maintain genomic integrity. Ribonucleotide reductase (RNR) regulation is complex and multifaceted. RNR is regulated allosterically by two nucleotide-binding sites, by transcriptional control, and...
Clinical evaluation of enalapril maleate and furosemide usage in dogs with degenerative myxomatous mitral valve, CHF functional class Ib

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Rodrigo P. Franco

2011-09-01

Full Text Available Degenerative myxomatous mitral valve (DMMV is a heart disease of high incidence in small animal clinical medicine, affecting mainly older dogs and small breeds. Thus, a scientific investigation was performed in order to evaluate the clinical use of the medicines furosemide and enalapril maleate in dogs with this disease in CHF functional class Ib before and after the treatment was established. For this purpose 16 dogs with the given valve disease were used, separated into two groups: the first received furosemide (n=8 and the second received enalapril maleate (n=8 throughout 56 days. The dogs were evaluated in four stages (T0, T14, T28 and T56 day in relation to clinical signs, hematological, biochemical and serum assessment, which included serum angiotensin converting enzyme (ACE and aldosterone, as well as radiography, electrocardiography, Doppler-echocardiography and blood pressure. The results regarding the clinical, hematological and serum chemistry evaluations revealed no significant changes in both groups, but significant reductions in the values of ACE and aldosterone in the group receiving enalapril maleate were verified. The radiographic examination revealed reductions of VHS values and variable Pms wave of the electrocardiogram in both groups, but no changes in blood pressure values were identified. The echocardiogram showed a significant decrease of the variables LVDd/s in the studied groups and the FS% in animals that received only enalapril. Therefore, analysis of results showed that monotherapy based on enalapril maleate showed better efficiency of symptoms control in patients with CHF functional class Ib.
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DNA damage induction of ribonucleotide reductase.

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Elledge, S J; Davis, R W

1989-01-01

RNR2 encodes the small subunit of ribonucleotide reductase, the enzyme that catalyzes the first step in the pathway for the production of deoxyribonucleotides needed for DNA synthesis. RNR2 is a member of a group of genes whose activities are cell cycle regulated and that are transcriptionally induced in response to the stress of DNA damage. An RNR2-lacZ fusion was used to further characterize the regulation of RNR2 and the pathway responsible for its response to DNA damage. beta-Galactosidas...
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Cervical Cancer Stage IB

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... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IB Add to My Pictures View /Download : ... 1613x1200 View Download Large: 3225x2400 View Download Title: Cervical Cancer Stage IB Description: Stage IB1 and IB2 cervical ...
IBS Diet

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HLA class Ib molecules and immune cells in pregnancy and preeclampsia

Directory of Open Access Journals (Sweden)

Snezana eDjurisic

2014-12-01

Full Text Available Despite decades of research, the highly prevalent pregnancy complication preeclampsia, ‘the disease of theories’, has remained an enigma. Indeed, the etiology of preeclampsia is largely unknown. A compiling amount of studies indicate that the pathological basis involves a complex array of genetic predisposition and immunological maladaptation, and that a contribution from the mother, the father and the fetus is likely to be important. The Human Leukocyte Antigen (HLA –G is an increasing focus of research in relation to preeclampsia. The HLA-G molecule is primarily expressed by the extravillous trophoblast cells lining the placenta together with the two other HLA class Ib molecules, HLA-E and HLA-F. Soluble isoforms of HLA-G have been detected in the early endometrium, the matured cumulus-oocyte complex, maternal blood of pregnant women, in umbilical cord blood, and lately, in seminal plasma. HLA-G is believed to be involved in modulating immune responses in the context of vascular remodeling during pregnancy as well as in dampening potential harmful immune attacks raised against the semi-allogeneic fetus. In addition, HLA-G genetic variants are associated with both membrane-bound and soluble forms of HLA-G, and, in some studies, with preeclampsia. In this review, a genetic contribution from the mother, the father and the fetus, together with the presence and function of various immune cells of relevance in pregnancy, are reviewed in relation to HLA-G and preeclampsia.
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How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors.

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Aziz, Imran; Törnblom, Hans; Palsson, Olafur S; Whitehead, William E; Simrén, Magnus

2018-06-08

The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with ≥2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis.
[Validation of the IBS-SSS].

Science.gov (United States)

Betz, C; Mannsdörfer, K; Bischoff, S C

2013-10-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterised by abdominal pain, associated with stool abnormalities and changes in stool consistency. Diagnosis of IBS is based on characteristic symptoms and exclusion of other gastrointestinal diseases. A number of questionnaires exist to assist diagnosis and assessment of severity of the disease. One of these is the irritable bowel syndrome - severity scoring system (IBS-SSS). The IBS-SSS was validated 1997 in its English version. In the present study, the IBS-SSS has been validated in German language. To do this, a cohort of 60 patients with IBS according to the Rome III criteria, was compared with a control group of healthy individuals (n = 38). We studied sensitivity and reproducibility of the score, as well as the sensitivity to detect changes of symptom severity. The results of the German validation largely reflect the results of the English validation. The German version of the IBS-SSS is also a valid, meaningful and reproducible questionnaire with a high sensitivity to assess changes in symptom severity, especially in IBS patients with moderate symptoms. It is unclear if the IBS-SSS is also a valid questionnaire in IBS patients with severe symptoms because this group of patients was not studied. © Georg Thieme Verlag KG Stuttgart · New York.

Medications (for IBS)

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Full Text Available ... the lack of effective treatment for the overall improvement of multiple symptoms in IBS patients. However, new ... IFFGD Our Mission Awareness Activities Advocacy Activities Research Leadership Industry Council Contact us IBS Treatment Working With ...
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Full Text Available ... by a physician who specializes in motility or stress-related gastrointestinal disorders. More complex medication regimens, and ... IBS Medications Probiotics and Antibiotics Psychological Treatments Understanding Stress Cognitive Behavioral Therapy Relaxation Techniques for IBS Take ...
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Full Text Available ... the lack of effective treatment for the overall improvement of multiple symptoms in IBS patients. However, new ... effective in treating IBS in multi-center, high quality clinical trials. These are prescription medications intended for ...
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Full Text Available ... in IBS Sleep and Irritable Bowel Syndrome Gynecological Aspects of Irritable Bowel Syndrome Symptom Diary Testing in ... in IBS Sleep and Irritable Bowel Syndrome Gynecological Aspects of Irritable Bowel Syndrome Symptom Diary Testing in ...
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Full Text Available ... Diet Complementary or Alternative Treatments Medications Psychological Treatments Online Studies News You Can Use Living With IBS ... Diet Complementary or Alternative Treatments Medications Psychological Treatments Online Studies News You Can Use Living With IBS ...
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Full Text Available ... Agents Antidepressant Medications Newer IBS Medications Probiotics and Antibiotics Pharmacologic, or drug, therapy is best used in ... Agents Antidepressant Medications Newer IBS Medications Probiotics and Antibiotics Psychological Treatments Understanding Stress Cognitive Behavioral Therapy Relaxation ...
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Full Text Available ... IBS Medications Probiotics and Antibiotics Psychological Treatments Understanding Stress Cognitive Behavioral Therapy Relaxation Techniques for IBS Take Part in Online Studies Working With Your Doctor Successful relationships with healthcare providers are an important part of ...
Medications (for IBS)

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Full Text Available ... have limited benefit for treating IBS. In some persons they relieve abdominal pain or discomfort, usually if ... Anti-anxiety medications – can be helpful for some people with IBS, mainly those with emotional distress. There ...
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Full Text Available ... Tips on Finding a Doctor Doctor Visit Worksheet Words to Know Changing Doctors IBS Symptom Treatments IBS ... arises requiring an expert’s care. © Copyright 1998-2018 International Foundation for Functional Gastrointestinal Disorders, Inc. (IFFGD). All ...
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Full Text Available ... Global Treatments IBS Diet What to Do and What to Avoid Foods That Cause Cramping and Diarrhea Foods that Cause ... 12 Week Elimination Diet for IBS Rice-Based Foods Low-FODMAP Diet What Are FODMAPs? Effects of FODMAPs on the Gut ...
IBS Treatment Options

Science.gov (United States)

... 01 July 2017 Print A short bout of abdominal pain and diarrhea or constipation now and then is not unusual. But long-term or recurring symptoms are not normal. They may signal irritable bowel syndrome (IBS) – and are generally treatable. IBS Treatments Depend ...
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Full Text Available ... Global Treatments IBS Diet What to Do and What to Avoid Foods That Cause Cramping and Diarrhea Foods that Cause Gas and Bloating Dietary Fiber 12 Week Elimination Diet for IBS Rice-Based Foods Low-FODMAP Diet What Are FODMAPs? Effects of FODMAPs on the Gut ...
Classification of ulnar triangular fibrocartilage complex tears. A treatment algorithm for Palmer type IB tears.

Science.gov (United States)

Atzei, A; Luchetti, R; Garagnani, L

2017-05-01

The classical definition of 'Palmer Type IB' triangular fibrocartilage complex tear, includes a spectrum of clinical conditions. This review highlights the clinical and arthroscopic criteria that enable us to categorize five classes on a treatment-oriented classification system of triangular fibrocartilage complex peripheral tears. Class 1 lesions represent isolated tears of the distal triangular fibrocartilage complex without distal radio-ulnar joint instability and are amenable to arthroscopic suture. Class 2 tears include rupture of both the distal triangular fibrocartilage complex and proximal attachments of the triangular fibrocartilage complex to the fovea. Class 3 tears constitute isolated ruptures of the proximal attachment of the triangular fibrocartilage complex to the fovea; they are not visible at radio-carpal arthroscopy. Both Class 2 and Class 3 tears are diagnosed with a positive hook test and are typically associated with distal radio-ulnar joint instability. If required, treatment is through reattachment of the distal radio-ulnar ligament insertions to the fovea. Class 4 lesions are irreparable tears due to the size of the defect or to poor tissue quality and, if required, treatment is through distal radio-ulnar ligament reconstruction with tendon graft. Class 5 tears are associated with distal radio-ulnar joint arthritis and can only be treated with salvage procedures. This subdivision of type IB triangular fibrocartilage complex tear provides more insights in the pathomechanics and treatment strategies. II.
IBS for non-gaussian distributions

International Nuclear Information System (INIS)

Fedotov, A.; Sidorin, A.O.; Smirnov, A.V.

2010-01-01

In many situations distribution can significantly deviate from Gaussian which requires accurate treatment of IBS. Our original interest in this problem was motivated by the need to have an accurate description of beam evolution due to IBS while distribution is strongly affected by the external electron cooling force. A variety of models with various degrees of approximation were developed and implemented in BETACOOL in the past to address this topic. A more complete treatment based on the friction coefficient and full 3-D diffusion tensor was introduced in BETACOOL at the end of 2007 under the name 'local IBS model'. Such a model allowed us calculation of IBS for an arbitrary beam distribution. The numerical benchmarking of this local IBS algorithm and its comparison with other models was reported before. In this paper, after briefly describing the model and its limitations, they present its comparison with available experimental data.
topIb, a phylogenetic hallmark gene of Thaumarchaeota encodes a functional eukaryote-like topoisomerase IB.

Science.gov (United States)

Dahmane, Narimane; Gadelle, Danièle; Delmas, Stéphane; Criscuolo, Alexis; Eberhard, Stephan; Desnoues, Nicole; Collin, Sylvie; Zhang, Hongliang; Pommier, Yves; Forterre, Patrick; Sezonov, Guennadi

2016-04-07

Type IB DNA topoisomerases can eliminate torsional stresses produced during replication and transcription. These enzymes are found in all eukaryotes and a short version is present in some bacteria and viruses. Among prokaryotes, the long eukaryotic version is only observed in archaea of the phylum Thaumarchaeota. However, the activities and the roles of these topoisomerases have remained an open question. Here, we demonstrate that all available thaumarchaeal genomes contain a topoisomerase IB gene that defines a monophyletic group closely related to the eukaryotic enzymes. We show that the topIB gene is expressed in the model thaumarchaeon Nitrososphaera viennensis and we purified the recombinant enzyme from the uncultivated thaumarchaeon Candidatus Caldiarchaeum subterraneum. This enzyme is active in vitro at high temperature, making it the first thermophilic topoisomerase IB characterized so far. We have compared this archaeal type IB enzyme to its human mitochondrial and nuclear counterparts. The archaeal enzyme relaxes both negatively and positively supercoiled DNA like the eukaryotic enzymes. However, its pattern of DNA cleavage specificity is different and it is resistant to camptothecins (CPTs) and non-CPT Top1 inhibitors, LMP744 and lamellarin D. This newly described thermostable topoisomerases IB should be a promising new model for evolutionary, mechanistic and structural studies. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
6 Tips: IBS and Complementary Health Practices

Science.gov (United States)

... health practice for IBS, here are 6 tips: Hypnotherapy (hypnosis). This practice involves the power of suggestion by ... IBS. According to reviews of the scientific literature, hypnotherapy may be a helpful treatment for managing IBS ...

Caracemide, a site-specific irreversible inhibitor of protein R1 of Escherichia coli ribonucleotide reductase

DEFF Research Database (Denmark)

Larsen, I. K.; Cornett, Claus; Karlsson, M.

1992-01-01

The anticancer drug caracemide, N-acetyl-N,O-di(methylcarbamoyl)hydroxylamine, and one of its degradation products, N-acetyl-O-methylcarbamoyl-hydroxylamine, were found to inhibit the enzyme ribonucleotide reductase of Escherichia coli by specific interaction with its larger component protein R1....
Treatment of cancer of cervix stages IB1 and IB2 in the Hospital Calderon Guardia (2000-2003)

International Nuclear Information System (INIS)

Saenz, Oscar; Picans, Serafin

2004-01-01

The types of treatment applied in patients with stages of cancer of cervix IB1 and IB2, your evolution and prognosis were determined. Different methods of treatment were compared. It was a prospective descriptive and observational study of the patients of Servicio de Ginecologia Oncologica of the Hospital Calderon Guardia, San Jose, Costa Rica. It was carried out from August 2000 to November 2002. The study included all female patients with proved histological diagnosis of cervical cancer IB1 and IB2. All of them had pre-operative studies: plate of thorax, abdomen ultrasound, computerized axial tomography of pelvis and abdomen, at least received primary treatment (surgery) and the following monitoring. The statistical analysis was realized with chi-square evidences, through epi-info software. Of 24 patients only 19 got complete information. It was found a 22% of patients with positives adenopatias to level of histological study with a ganglionic compromise of 32% in general form, a 36% in the stages IB1 and a 25% in stages IB2. Of all the patients that presented ganglionic metastasis illness, did not get to show with the computerized axial tomography and it is concluded that TAC is a bad method for detection of the microscopic metastasis illness, or at least to 2 cm. None of the patients in stages IB1 presented relapse data in the observed period, founding a 100% of survival to 24 months. The patients in stages IB2 presented relapses, with a 75% of survival [es
IBS SURVEY 2010: DRIVERS, BARRIERS AND CRITICAL SUCCESS FACTORS IN ADOPTING INDUSTRIALISED BUILDING SYSTEM (IBS CONSTRUCTION BY G7 CONTRACTORS IN MALAYSIA

Directory of Open Access Journals (Sweden)

KAMARUL ANUAR MOHAMAD KAMAR

2014-08-01

Full Text Available The industrialised building system (IBS survey has become an essential tool for ensuring the IBS Roadmap (2003 to 2010 meets its goals and target. As part of the process review survey, it also records the trend achievement of Malaysia in the usage of IBS in the building construction industry. The first and second IBS surveys were published in 2003 and 2005, respectively. Afterward, the IBS Roadmap’s midterm review was conducted. The third and the most recent IBS surveys were conducted in 2008 and 2010, respectively. This paper aims to highlight a part of the IBS survey report in 2010, which has been conducted to measure the drivers, barriers and the critical success factors of G7 contractors in adopting IBS construction. G7 is a Construction Industry Development Board contractor grade that can apply tender without limit. The importance of this paper is that it guides the policy and implementation strategy of IBS by G7 contractors. The survey shows that the acceptance, adoption, and deployment of IBS in the Malaysian construction industry are still low and do not address the persisting problems, such as productivity, dependency on foreign workers and high level of construction wastage.
TSH elevations as the first laboratory evidence for pseudohypoparathyroidism type Ib (PHP-Ib).

Science.gov (United States)

Molinaro, Angelo; Tiosano, Dov; Takatani, Rieko; Chrysis, Dionisios; Russell, William; Koscielniak, Nikolas; Kottler, Marie-Laure; Agretti, Patrizia; De Marco, Giuseppina; Ahtiainen, Petteri; Christov, Marta; Mäkitie, Outi; Tonacchera, Massimo; Jüppner, Harald

2015-05-01

Hypocalcemia and hyperphosphatemia because of resistance toward parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib). In this rare disorder, which is caused by GNAS methylation changes, resistance can occur toward other hormones, such as thyroid-stimulating hormone (TSH), that mediate their actions through G protein-coupled receptors. However, these additional laboratory abnormalities are usually not recognized until PTH-resistant hypocalcemia becomes clinically apparent. We now describe four pediatric patients, first diagnosed with subclinical or overt hypothyroidism between the ages of 0.2 and 15 years, who developed overt PTH-resistance 3 to 20 years later. Although anti-thyroperoxidase (anti-TPO) antibodies provided a plausible explanation for hypothyroidism in one of these patients, this and two other patients revealed broad epigenetic GNAS abnormalities, which included loss of methylation (LOM) at exons AS, XL, and A/B, and gain of methylation at exon NESP55; ie, findings consistent with PHP-Ib. LOM at GNAS exon A/B alone led in the fourth patient to the identification of a maternally inherited 3-kb STX16 deletion, a well-established cause of autosomal dominant PHP-Ib. Although GNAS methylation changes were not detected in additional pediatric and adult patients with subclinical hypothyroidism (23 pediatric and 39 adult cases), hypothyroidism can obviously be the initial finding in PHP-Ib patients. One should therefore consider measuring PTH, along with calcium and phosphate, in patients with unexplained hypothyroidism for extended periods of time to avoid hypocalcemia and associated clinical complications. © 2014 American Society for Bone and Mineral Research.
IBS and Non-GI Functional Disorders

Science.gov (United States)

... of IBS patients have at least one coexisting somatic symptom and many IBS patients meet diagnostic criteria ... up-to-date on the latest news, stories, tips, research highlights, and more! Sign up for eNewsletter: ...
Inactivation of Lactobacillus leichmannii ribonucleotide reductase by 2',2'-difluoro-2'-deoxycytidine 5'-triphosphate: adenosylcobalamin destruction and formation of a nucleotide-based radical.

Science.gov (United States)

Lohman, Gregory J S; Gerfen, Gary J; Stubbe, Joanne

2010-02-23

Ribonucleotide reductase (RNR, 76 kDa) from Lactobacillus leichmannii is a class II RNR that requires adenosylcobalamin (AdoCbl) as a cofactor. It catalyzes the conversion of nucleoside triphosphates to deoxynucleotides and is 100% inactivated by 1 equiv of 2',2'-difluoro-2'-deoxycytidine 5'-triphosphate (F(2)CTP) in cytidine, characterized by mass spectrometry and NMR spectroscopy, indicating the trapped nucleotide had lost both of its fluorides and gained an oxygen. High-field ENDOR studies with [1'-(2)H]F(2)CTP from the reaction quenched at 30 s revealed a radical that is nucleotide-based. The relationship between this radical and the trapped cytidine analogue provides insight into the nonalkylative pathway for RNR inactivation relative to the alkylative pathway.
Endocannabinoid and cannabinoid-like fatty acid amide levels correlate with pain-related symptoms in patients with IBS-D and IBS-C: a pilot study.

Directory of Open Access Journals (Sweden)

Jakub Fichna

Full Text Available AIMS: Irritable bowel syndrome (IBS is a functional gastrointestinal (GI disorder, associated with alterations of bowel function, abdominal pain and other symptoms related to the GI tract. Recently the endogenous cannabinoid system (ECS was shown to be involved in the physiological and pathophysiological control of the GI function. The aim of this pilot study was to investigate whether IBS defining symptoms correlate with changes in endocannabinoids or cannabinoid like fatty acid levels in IBS patients. METHODS: AEA, 2-AG, OEA and PEA plasma levels were determined in diarrhoea-predominant (IBS-D and constipation-predominant (IBS-C patients and were compared to healthy subjects, following the establishment of correlations between biolipid contents and disease symptoms. FAAH mRNA levels were evaluated in colonic biopsies from IBS-D and IBS-C patients and matched controls. RESULTS: Patients with IBS-D had higher levels of 2AG and lower levels of OEA and PEA. In contrast, patients with IBS-C had higher levels of OEA. Multivariate analysis found that lower PEA levels are associated with cramping abdominal pain. FAAH mRNA levels were lower in patients with IBS-C. CONCLUSION: IBS subtypes and their symptoms show distinct alterations of endocannabinoid and endocannabinoid-like fatty acid levels. These changes may partially result from reduced FAAH expression. The here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.
Paternal uniparental isodisomy of the entire chromosome 20 as a molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib).

Science.gov (United States)

Bastepe, Murat; Altug-Teber, Ozge; Agarwal, Chhavi; Oberfield, Sharon E; Bonin, Michael; Jüppner, Harald

2011-03-01

Pseudohypoparathyoridism type Ib (PHP-Ib) typically defines the presence of end-organ resistance to parathyroid hormone in the absence of Albright's hereditary osteodystrophy. Patients affected by this disorder present with imprinting defects in the complex GNAS locus. Microdeletions within STX16 or GNAS have been identified in familial cases with PHP-Ib, but the molecular cause of the GNAS imprinting defects in sporadic PHP-Ib cases remains poorly defined. We now report a case with sporadic PHP-Ib for whom a SNPlex analysis revealed loss of the maternal GNAS allele. Further analysis of the entire genome with a 100K SNP chip identified a paternal uniparental isodisomy affecting the entire chromosome 20 without evidence for another chromosomal abnormality. Our findings explain the observed GNAS methylation changes and the patient's hormone resistance, and furthermore suggest that chromosome 20 harbors, besides GNAS, no additional imprinted region that contributes to the clinical and laboratory phenotype. Copyright © 2010 Elsevier Inc. All rights reserved.
Studies of ribonucleotide reductase in crucian carp-an oxygen dependent enzyme in an anoxia tolerant vertebrate.

Directory of Open Access Journals (Sweden)

Guro K Sandvik

Full Text Available The enzyme ribonucleotide reductase (RNR catalyzes the conversion of ribonucleotides to deoxyribonucleotides, the precursors for DNA. RNR requires a thiyl radical to activate the substrate. In RNR of eukaryotes (class Ia RNR, this radical originates from a tyrosyl radical formed in reaction with oxygen (O(2 and a ferrous di-iron center in RNR. The crucian carp (Carassius carassius is one of very few vertebrates that can tolerate several months completely without oxygen (anoxia, a trait that enables this fish to survive under the ice in small ponds that become anoxic during the winter. Previous studies have found indications of cell division in this fish after 7 days of anoxia. This appears nearly impossible, as DNA synthesis requires the production of new deoxyribonucleotides and therefore active RNR. We have here characterized RNR in crucian carp, to search for adaptations to anoxia. We report the full-length sequences of two paralogs of each of the RNR subunits (R1i, R1ii, R2i, R2ii, p53R2i and p53R2ii, obtained by cloning and sequencing. The mRNA levels of these subunits were measured with quantitative PCR and were generally well maintained in hypoxia and anoxia in heart and brain. We also report maintained or increased mRNA levels of the cell division markers proliferating cell nuclear antigen (PCNA, brain derived neurotrophic factor (BDNF and Ki67 in anoxic hearts and brains. Electron paramagnetic resonance (EPR measurements on in vitro expressed crucian carp R2 and p53R2 proteins gave spectra similar to mammalian RNRs, including previously unpublished human and mouse p53R2 EPR spectra. However, the radicals in crucian carp RNR small subunits, especially in the p53R2ii subunit, were very stable at 0°C. A long half-life of the tyrosyl radical during wintertime anoxia could allow for continued cell division in crucian carp.
Medications (for IBS)

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Full Text Available ... Agents Antidepressant Medications Newer IBS Medications Probiotics and Antibiotics Psychological Treatments Understanding Stress Cognitive Behavioral Therapy Relaxation Techniques for ...
TSH elevations as the first laboratory evidence for pseudohypoparathyroidism type Ib (PHP-Ib)†

Science.gov (United States)

Molinaro, Angelo; Tiosano, Dov; Takatani, Rieko; Chrysis, Dionisios; Russell, William; Koscielniak, Nikolas; Kottler, Marie-Laure; Agretti, Patrizia; De Marco, Giuseppina; Ahtiainen, Petteri; Christov, Marta; Mäkitie, Outi; Tonacchera, Massimo; Jüppner, Harald

2014-01-01

Hypocalcemia and hyperphosphatemia because of resistance towards parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib). In this rare disorder that is caused by GNAS methylation changes, resistance can occur towards other hormones, such as thyroid-stimulating hormone (TSH), that mediate their actions through G protein-coupled receptors. However, these additional laboratory abnormalities are usually not recognized until PTH-resistant hypocalcemia becomes clinically apparent. We now describe four pediatric patients, first diagnosed with subclinical or overt hypothyroidism between the ages of 0.2 and 15 years, who developed overt PTH-resistance 3-20 years later. Although anti-TPO antibodies provided a plausible explanation for hypothyroidism in one of these patients, this and two other patients revealed broad epigenetic GNAS abnormalities, which included loss of methylation (LOM) at exons AS, XL and A/B, and gain of methylation at exon NESP55, i.e. findings consistent with PHP-Ib. LOM at GNAS exon A/B alone led in the fourth patient to the identification of a maternally inherited 3-kb STX16 deletion, a well-established cause of autosomal dominant PHP-Ib. Although GNAS methylation changes were not detected in additional pediatric and adult patients with subclinical hypothyroidism (23 pediatric and 39 adult cases), hypothyroidism can obviously be the initial finding in PHP-Ib patients. One should therefore consider measuring PTH, along with calcium and phosphate, in patients with unexplained hypothyroidism for extended periods of time to avoid hypocalcemia and associated clinical complications. PMID:25403028
TSH elevations as the first laboratory evidence for pseudohypoparathyroidism type Ib (PHP-Ib)†

OpenAIRE

Molinaro, Angelo; Tiosano, Dov; Takatani, Rieko; Chrysis, Dionisios; Russell, William; Koscielniak, Nikolas; Kottler, Marie-Laure; Agretti, Patrizia; De Marco, Giuseppina; Ahtiainen, Petteri; Christov, Marta; Mäkitie, Outi; Tonacchera, Massimo; Jüppner, Harald

2015-01-01

Hypocalcemia and hyperphosphatemia because of resistance towards parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib). In this rare disorder that is caused by GNAS methylation changes, resistance can occur towards other hormones, such as thyroid-stimulating hormone (TSH), that mediate their actions through G protein-coupled receptors. However, these additional laboratory abnormalities are...
More negative self-esteem and inferior coping strategies among patients diagnosed with IBS compared with patients without IBS--a case-control study in primary care.

Science.gov (United States)

Grodzinsky, Ewa; Walter, Susanna; Viktorsson, Lisa; Carlsson, Ann-Kristin; Jones, Michael P; Faresjö, Åshild

2015-01-28

Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder, that affects approximately 10% of the general population and the majority are diagnosed in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to investigate the psychosocial constructs of self-esteem and sense of coherence among IBS patients compared to non-IBS patients in primary care. A case-control study in primary care setting among IBS patients meeting the ROME III criteria (n = 140) compared to controls i.e. non-IBS patients (n = 213) without any present or previous gastrointestinal complaints. The data were collected through self-reported questionnaires of psychosocial factors. IBS-patients reported significantly more negative self-esteem (p IBS-cases were also less likely to report 'good' health status (p IBS patients remained statistically significant (p = 0.02), as did the lower scores for sense of coherence among IBS cases (p = 0.04). The more frequently reported negative self-esteem and inferior coping strategies among IBS patients found in this study suggest the possibility that psychological therapies might be helpful for these patients. However these data do not indicate the causal direction of the observed associations. More research is therefore warranted to determine whether these psychosocial constructs are more frequent in IBS patients.
The IB Diploma and UK University Degree Qualifications

Science.gov (United States)

Frank-Gemmill, Gerda

2013-01-01

In recent years the International Baccalaureate (IB) Diploma has become widely accepted as a university-entry qualification in the UK, but there has been little quantitative research into the achievements of IB students at degree level. This study investigates IB students from one selective independent school who entered UK universities between…
Integrated Baseline Bystem (IBS) Version 1.03: Models guide

Energy Technology Data Exchange (ETDEWEB)

1993-01-01

The Integrated Baseline System)(IBS), operated by the Federal Emergency Management Agency (FEMA), is a system of computerized tools for emergency planning and analysis. This document is the models guide for the IBS and explains how to use the emergency related computer models. This document provides information for the experienced system user, and is the primary reference for the computer modeling software supplied with the system. It is designed for emergency managers and planners, and others familiar with the concepts of computer modeling. Although the IBS manual set covers basic and advanced operations, it is not a complete reference document set. Emergency situation modeling software in the IBS is supported by additional technical documents. Some of the other IBS software is commercial software for which more complete documentation is available. The IBS manuals reference such documentation where necessary.
Medications (for IBS)

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Full Text Available ... IBS Medications Probiotics and Antibiotics Psychological ... With Your Doctor Successful relationships with healthcare providers are an important part of managing life with a long-term digestive disorder. Working with ...
Experience with IBS-suppression lattice in RHIC

International Nuclear Information System (INIS)

Litvinenko, V.N.; Luo, Y.; Ptitsyn, V.; Satogata, T.; Tepikian, S.; Bai, M.; Bruno, D.; Cameron, P.; Connolly, R.; Della Penna, A.; Drees, A.; Fedotov, A.; Ganetis, G.; Hoff, L.; Louie, W.; Malitsky, N.; Marr, G.; Marusic, A.; Montag, C.; Pilat, F.; Roser, T.; Trbojevic, D.; Tsoupas, N.

2008-01-01

An intra-beam scattering (IBS) is the limiting factor of the luminosity lifetime for RHIC operating with heavy ions. In order to suppress the IBS we designed and implemented new lattice with higher betatron tunes. This lattice had been developed during last three years and had been used for gold ions in yellow ring of the RHIC during d-Au part of the RHIC Run-8. The use of this lattice allowed both significant increases in the luminosity lifetime and the luminosity levels via reduction of beta-stars in the IPS. In this paper we report on the development, the tests and the performance of IBS-suppression lattice in RHIC, including the resulting increases in the peak and the average luminosity. We also report on our plans for future steps with the IBS suppression
Medications (for IBS)

Medline Plus

Full Text Available ... Read more about antidiarrheal agents. Anti-anxiety medications – can be helpful for some people with IBS, mainly those with emotional distress. There are also effective medications available that relieve ...
Expression, purification, crystallization and preliminary X-ray analysis of ORF60, the small subunit (R2) of ribonucleotide reductase from Kaposi’s sarcoma-associated herpesvirus (KSHV)

International Nuclear Information System (INIS)

Gurmu, Daniel; Dahlroth, Sue-Li; Haas, Juergen; Nordlund, Pär; Erlandsen, Heidi

2010-01-01

Crystals of the R2 subunit from the oncovirus Kaposi’s sarcoma-associated γ-herpesvirus (KSHV) were obtained by the use of in situ proteolysis. The crystals diffracted to 2.0 Å resolution and belonged to space group P2 1 . Ribonucleotide reductase (RNR) is responsible for converting ribonucleotides to deoxyribonucleotides, which are the building blocks of DNA. The enzyme is present in all life forms as well as in some large DNA viruses such as herpesviruses. The α-herpesviruses and γ-herpesviruses encode two class Ia RNR subunits, R1 and R2, while the β-herpesvirus subfamily only encode an inactive R1 subunit. Here, the crystallization of the R2 subunit of RNR encoded by the ORF60 gene from the oncovirus Kaposi’s sarcoma-associated γ-herpesvirus (KSHV) is reported. These are the first crystals of a viral R2 subunit; the use of in situ proteolysis with chymotrypsin and the addition of hexamine cobalt(III) chloride that were necessary to obtain crystals are described. Optimization of the crystallization conditions yielded crystals that diffracted to 2.0 Å resolution. The crystals belonged to space group P2 1 , with unit-cell parameters a = 63.9, b = 71.2, c = 71.8 Å, α = 90, β = 106.7, γ = 90°. The data set collected was 95.3% complete, with an R merge of 9.6%. There are two molecules in the asymmetric unit, corresponding to a solvent content of 43.4%
Platelet Glycoprotein Ib-IX and Malignancy

Science.gov (United States)

2010-09-01

provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin - rich network produced by coagulation...process and can initiate the formation of a platelet - rich thrombus by tethering the platelet to a thrombogenic surface. Several ligands binding to GP Ib... Platelet Glycoprotein Ib-IX and Malignancy PRINCIPAL INVESTIGATOR: Jerry Ware, Ph.D

A CMMS Expert using BIM for IBS Building Maintenance

Directory of Open Access Journals (Sweden)

Hamzah Noraini

2016-01-01

Full Text Available In the IBS building maintenance, the conventional methods to the project delivery and its failure to form effective communication channel between complementary knowledge on IBS construction and related members that is conducted in the sequential manner has resulted in ineffectiveness for managing building maintenance, where a paradigm shift within the IBS traditional approach is necessary. The research results described are concerned with i an integrated system to record, diagnose and analyse information for IBS building maintenance to detect patent or latent defect, select an effective repair method, provide appropriate planning decision and reduce risks of defect throughout the building lifetime. ii building a decision making support in diagnosis in IBS building maintenance based on robust data collection about concrete defects and causes including in the selection of a durable replacement design and material or the proper rehabilitation method. The system development was based on analysis of number of interviews and case studies conducted with professional engineers working in IBS building maintenance departments. The paper concludes that implementing a CMMS Expert using BIM can help improve the performance of IBS building design, construction and maintenance operations.
Medications (for IBS)

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Full Text Available ... be taken on a more long-term basis. These include low dose antidepressant agents or the relatively ... IBS in multi-center, high quality clinical trials. These are prescription medications intended for specific use under ...
Medications (for IBS)

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Full Text Available ... Beth Israel Deaconess Medical Center, Boston, MA. Last modified on February 23, 2015 at 12:18:55 ... Dietary Fiber 12 Week Elimination Diet for IBS Rice-Based Foods Low-FODMAP Diet What Are FODMAPs? ...
Medications (for IBS)

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Full Text Available ... for some people with IBS, mainly those with emotional distress. There are also effective medications available that ... not linked to depression, but rather likely to effects on the brain and the gut. Antidepressant medications ...
Medications (for IBS)

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Full Text Available ... have limited benefit for treating IBS. In some persons they relieve abdominal pain or discomfort, usually if ... Summary The effectiveness of various agents differs between individuals. A medication regimen must be carefully chosen by ...
Medications (for IBS)

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Full Text Available ... He or she can help you monitor quality, effectiveness, possible interactions with other medicines you may be ... Read more about newer IBS medications. Summary The effectiveness of various agents differs between individuals. A medication ...
Medications (for IBS)

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Full Text Available ... Newer IBS Medications Probiotics and Antibiotics Pharmacologic, or drug, therapy is best used in irritable bowel syndrome ( ... limited by prescription only. It might be a drug or a supplement; manufactured or "natural." It might ...
Medications (for IBS)

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Full Text Available ... Newer IBS Medications Probiotics and Antibiotics Pharmacologic, or drug, therapy is best used in irritable bowel syndrome ( ... take for a therapeutic effect counts as a medicine. It can be readily available over-the-counter, ...
Medications (for IBS)

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Full Text Available ... Help You? IFFGD is a nonprofit education and research organization. Our mission is to inform, assist, and ... About IFFGD Our Mission Awareness Activities Advocacy Activities Research Leadership Industry Council Contact us IBS Treatment Working ...
Medications (for IBS)

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Full Text Available ... for some people with IBS, mainly those with emotional distress. There are also effective medications available that ... This Article Help You? IFFGD is a nonprofit education and research organization. Our mission is to inform, ...
Medications (for IBS)

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Full Text Available ... effective medications available that relieve the pain and improve the changes in bowel habit. They may need ... effective in treating IBS in multi-center, high quality clinical trials. These are prescription medications intended for ...
Medications (for IBS)

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Full Text Available ... J. Lembo, MD, Instructor of Medicine, Harvard Medical School; Division of Gastroenterology, Beth Israel Deaconess Medical Center, ... About IFFGD Our Mission Awareness Activities Advocacy Activities Research Leadership Industry Council Contact us IBS Treatment Working ...
Medications (for IBS)

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Full Text Available ... do not respond to physician counseling and dietary manipulations. What's a medication? Anything you take for a ... Psychological Treatments Understanding Stress Cognitive Behavioral Therapy Relaxation Techniques for IBS Take Part in Online Studies Working ...
Medications (for IBS)

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Full Text Available ... You? IFFGD is a nonprofit education and research organization. Our mission is to inform, assist, and support ... IFFGD Our Mission Awareness Activities Advocacy Activities Research Leadership Industry Council Contact us IBS Treatment Working With ...
Medications (for IBS)

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Full Text Available ... MA. Last modified on February 23, 2015 at 12:18:55 PM Treatment Understanding and Managing Pain ... Foods that Cause Gas and Bloating Dietary Fiber 12 Week Elimination Diet for IBS Rice-Based Foods ...
Medications (for IBS)

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Full Text Available ... depression, but rather likely to effects on the brain and the gut. Antidepressant medications can reduce the intensity of pain signals going from gut to brain. Read more about antidepressant medications. Newer IBS-Targeted ...
Medications (for IBS)

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Full Text Available ... discomfort, usually if the symptoms occur soon after eating. Examples include dicyclomine (Bentyl), and hyoscyamine (Levsin). Read ... treatment of IBS symptoms is not linked to depression, but rather likely to effects on the brain ...
Medications (for IBS)

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Full Text Available ... severe symptoms which do not respond to physician counseling and dietary manipulations. What's a medication? Anything you ... Therapy Relaxation Techniques for IBS Take Part in Online Studies Working With Your Doctor Successful relationships with ...
Medications (for IBS)

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Full Text Available ... it. He or she can help you monitor quality, effectiveness, possible interactions with other medicines you may ... effective in treating IBS in multi-center, high quality clinical trials. These are prescription medications intended for ...
Medications (for IBS)

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Full Text Available ... your doctor about it. He or she can help you monitor quality, effectiveness, possible interactions with other ... effectively treat multiple symptoms of IBS. Laxatives – can help treat symptoms of constipation. Laxatives should be used ...

Medications (for IBS)

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Full Text Available ... include bran or psyllium. Anticholinergics/Antispasmodics – have limited benefit for treating IBS. In some persons they relieve ... This Article Help You? IFFGD is a nonprofit education and research organization. Our mission is to inform, ...
Medications (for IBS)

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Full Text Available ... of constipation. Laxatives should be used under the supervision of a physician. Read more about laxatives. Bulking ... medications intended for specific use under a doctor’s supervision. Read more about newer IBS medications. Summary The ...
Medications (for IBS)

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Full Text Available ... treatment of IBS symptoms is not linked to depression, but rather likely to effects on the brain ... problem arises requiring an expert’s care. © Copyright 1998-2018 International Foundation for Functional Gastrointestinal Disorders, Inc. (IFFGD). ...
Medications (for IBS)

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Full Text Available ... IFFGD Our Mission Awareness Activities Advocacy Activities Research Leadership Industry Council Contact us IBS Treatment Working With ... doctor. We advise seeing a physician whenever a health problem arises requiring an expert’s care. © Copyright 1998- ...
Medications (for IBS)

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Full Text Available ... treatment of IBS symptoms is not linked to depression, but rather likely to effects on the brain ... whenever a health problem arises requiring an expert’s care. © Copyright 1998-2018 International Foundation for Functional Gastrointestinal ...
Medications (for IBS)

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Full Text Available ... IFFGD Our Mission Awareness Activities Advocacy Activities Research Leadership Industry Council Contact us IBS Treatment Working With ... We advise seeing a physician whenever a health problem arises requiring an expert’s care. © Copyright 1998-2018 ...
Functional Expression of a DNA-Topoisomerase IB from Cryptosporidium parvum

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César Ordóñez

2009-01-01

Full Text Available Cryptosporidium parvum, one of the most important causative organisms of human diarrheas during childhood, contains a monomeric DNA-topoisomerase IB (CpTopIB in chromosome 7. Heterologous expression of CpTopIB gene in a budding yeast strain lacking this activity proves that the cryptosporidial enzyme is functional in vivo. The enzymatic activity is comprised in a single polypeptide, which contains all the structural features defining a fully active TopIB. Relaxation activity of the yeast extracts was detected only when CpTopIB ORF was expressed in a yeast expression system showing time and protein dependence under steady state kinetic conditions. The susceptibility of CpTopIB-transformed yeast to the irreversible inhibitor camptothecin and its water-soluble derivatives (topotecan and SN-38 was assessed.
Identification of ribonucleotide reductase mutation causing temperature-sensitivity of herpes simplex virus isolates from whitlow by deep sequencing.

Science.gov (United States)

Daikoku, Tohru; Oyama, Yukari; Yajima, Misako; Sekizuka, Tsuyoshi; Kuroda, Makoto; Shimada, Yuka; Takehara, Kazuhiko; Miwa, Naoko; Okuda, Tomoko; Sata, Tetsutaro; Shiraki, Kimiyasu

2015-06-01

Herpes simplex virus 2 caused a genital ulcer, and a secondary herpetic whitlow appeared during acyclovir therapy. The secondary and recurrent whitlow isolates were acyclovir-resistant and temperature-sensitive in contrast to a genital isolate. We identified the ribonucleotide reductase mutation responsible for temperature-sensitivity by deep-sequencing analysis.
Medications (for IBS)

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Full Text Available ... include bran or psyllium. Anticholinergics/Antispasmodics – have limited benefit for treating IBS. In some persons they relieve abdominal pain or discomfort, usually if the symptoms occur soon after eating. Examples include dicyclomine (Bentyl), and hyoscyamine (Levsin). Read ...
Exclusion of the GNAS locus in PHP-Ib patients with broad GNAS methylation changes: evidence for an autosomal recessive form of PHP-Ib?

Science.gov (United States)

Fernández-Rebollo, Eduardo; Pérez de Nanclares, Guiomar; Lecumberri, Beatriz; Turan, Serap; Anda, Emma; Pérez-Nanclares, Gustavo; Feig, Denice; Nik-Zainal, Serena; Bastepe, Murat; Jüppner, Harald

2011-08-01

Most patients with autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry maternally inherited microdeletions upstream of GNAS that are associated with loss of methylation restricted to GNAS exon A/B. Only few AD-PHP-Ib patients carry microdeletions within GNAS that are associated with loss of all maternal methylation imprints. These epigenetic changes are often indistinguishable from those observed in patients affected by an apparently sporadic PHP-Ib form that has not yet been defined genetically. We have now investigated six female patients affected by PHP-Ib (four unrelated and two sisters) with complete or almost complete loss of GNAS methylation, whose healthy children (11 in total) showed no epigenetic changes at this locus. Analysis of several microsatellite markers throughout the 20q13 region made it unlikely that PHP-Ib is caused in these patients by large deletions involving GNAS or by paternal uniparental isodisomy or heterodisomy of chromosome 20 (patUPD20). Microsatellite and single-nucleotide variation (SNV) data revealed that the two affected sisters share their maternally inherited GNAS alleles with unaffected relatives that lack evidence for abnormal GNAS methylation, thus excluding linkage to this locus. Consistent with these findings, healthy children of two unrelated sporadic PHP-Ib patients had inherited different maternal GNAS alleles, also arguing against linkage to this locus. Based on our data, it appears plausible that some forms of PHP-Ib are caused by homozygous or compound heterozygous mutation(s) in an unknown gene involved in establishing or maintaining GNAS methylation. Copyright © 2011 American Society for Bone and Mineral Research.
Integrals for IBS and Beam Cooling

International Nuclear Information System (INIS)

Burov, A.

2005-01-01

Simulation of beam cooling usually requires performing certain integral transformations every time step or so, which is a significant burden on the CPU. Examples are the dispersion integrals (Hilbert transforms) in the stochastic cooling, wake fields and IBS integrals. An original method is suggested for fast and sufficiently accurate computation of the integrals. This method is applied for the dispersion integral. Some methodical aspects of the IBS analysis are discussed
Medications (for IBS)

Medline Plus

Full Text Available ... of a physician. Read more about laxatives. Bulking agents – provided they relieve and don’t worsen symptoms, can ease stool passage. Examples include bran or psyllium. Anticholinergics/Antispasmodics – have limited benefit for treating IBS. In some persons they relieve ...
Patient educational media preferences for information about irritable bowel syndrome (IBS).

Science.gov (United States)

Halpert, Albena; Dalton, Christine B; Palsson, Olafur; Morris, Carolyn; Hu, Yuming; Bangdiwala, Shrikant; Hankins, Jane; Norton, Nancy; Drossman, Douglas A

2008-12-01

To identify the educational media preferences of patients with irritable bowel syndrome (IBS). The IBS-Patient Education Questionnaire (PEQ) was administered to a national sample of IBS patients. Frequencies of item endorsements were compared and meaningful clinical differences were used to identify differences among subgroups. 1,242 patients completed the survey, mean age 39.3 years, 85% female, IBS duration 6.9 years, 79% had seen an MD for IBS within 6 months, and 92.6% used the web for medical information. The most desired source of education was "my doctor" (68%), followed by Internet (62%) and brochure (45%). Notably, patients favored an increase in use of media in the future (past vs. future): doctor (43 vs. 68%); Internet (36 vs. 62%); and brochures (26 vs. 45%). IBS patients expect more education than they have received. Understanding IBS patients' learning preferences can be highly valuable in the development or implementation of educational interventions.
Methyl-hydroxylamine as an efficacious antibacterial agent that targets the ribonucleotide reductase enzyme.

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Esther Julián

Full Text Available The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme.
Methyl-hydroxylamine as an efficacious antibacterial agent that targets the ribonucleotide reductase enzyme.

Science.gov (United States)

Julián, Esther; Baelo, Aida; Gavaldà, Joan; Torrents, Eduard

2015-01-01

The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR) is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA) in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme.
Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand.

Science.gov (United States)

Yasukawa, Takehiro; Reyes, Aurelio; Cluett, Tricia J; Yang, Ming-Yao; Bowmaker, Mark; Jacobs, Howard T; Holt, Ian J

2006-11-15

Using two-dimensional agarose gel electrophoresis, we show that mitochondrial DNA (mtDNA) replication of birds and mammals frequently entails ribonucleotide incorporation throughout the lagging strand (RITOLS). Based on a combination of two-dimensional agarose gel electrophoretic analysis and mapping of 5' ends of DNA, initiation of RITOLS replication occurs in the major non-coding region of vertebrate mtDNA and is effectively unidirectional. In some cases, conversion of nascent RNA strands to DNA starts at defined loci, the most prominent of which maps, in mammalian mtDNA, in the vicinity of the site known as the light-strand origin.
Incorporation of deoxyribonucleotides and ribonucleotides by a dNTP-binding cleft mutated reverse transcriptase in hepatitis B virus core particles

International Nuclear Information System (INIS)

Kim, Hee-Young; Kim, Hye-Young; Jung, Jaesung; Park, Sun; Shin, Ho-Joon; Kim, Kyongmin

2008-01-01

Our recent observation that hepatitis B virus (HBV) DNA polymerase (P) might initiate minus-strand DNA synthesis without primer [Kim et al., (2004) Virology 322, 22-30], raised a possibility that HBV P protein may have the potential to function as an RNA polymerase. Thus, we mutated Phe 436, a bulky amino acid with aromatic side chain, at the putative dNTP-binding cleft in reverse transcriptase (RT) domain of P protein to smaller amino acids (Gly or Val), and examined RNA polymerase activity. HBV core particles containing RT dNTP-binding cleft mutant P protein were able to incorporate 32 P-ribonucleotides, but not HBV core particles containing wild type (wt), priming-deficient mutant, or RT-deficient mutant P proteins. Since all the experiments were conducted with core particles isolated from transfected cells, our results indicate that the HBV RT mutant core particles containing RT dNTP-binding cleft mutant P protein could incorporate both deoxyribonucleotides and ribonucleotides in replicating systems
Quality of life in patients with Irritable Bowel Syndrome (IBS), assessed using the IBS-Quality of Life (IBS-QOL) measure after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide: results of an international prospective observational cohort study in Poland, Egypt, Mexico and China.

Science.gov (United States)

Hou, Xiaohua; Chen, Shengliang; Zhang, Yali; Sha, Weihong; Yu, Xiaofeng; Elsawah, Hesham; Afifi, Afifi Fahmy; El-Khayat, Hisham Raafat; Nouh, Alaa; Hassan, Mohamed Fathalla; Fatah, Ayman Abdel; Rucker Joerg, Isabel; Sánchez Núñez, Juan Manuel; Osthoff Rueda, Rodolfo; Jurkowska, Grazyna; Walczak, Michal; Malecka-Panas, Ewa; Linke, Krzysztof; Hartleb, Marek; Janssen-van Solingen, Gwendolyn

2014-11-01

Irritable Bowel Syndrome (IBS) has a substantial impact on health-related quality of life (HR-QoL) but high-quality data pre- and post-treatment using the IBS-Quality of Life (IBS-QOL) measure are limited. The objective of this study was to evaluate the changes from baseline of the IBS-QOL scores, symptom scores and health economic data in IBS patients, after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide. This was a prospective observational cohort study in patients with IBS, diagnosed using the Rome III criteria in four countries (Poland, Egypt, Mexico and China). A total of 607 patients were enrolled. At baseline, the IBS-QOL total scores were 52.0 in Poland, 48.9 in Egypt, 51.9 in Mexico, 76.4 in China and 56.4 overall. Increases in IBS-QOL total score were statistically significant at Weeks 4 and 8 overall and in each country (overall: 11.8 at Week 4, 24.3 at Week 8; p < 0.001). Improvements were shown in all IBS-QOL subscales and scores. Symptoms and health economic outcomes were improved. Furthermore, the favourable safety profile of these treatments was confirmed in this study. This study demonstrated that IBS patients have a substantially reduced HR-QoL and that treatment with mebeverine hydrochloride or pinaverium bromide improved HR-QoL.
Randomised controlled trial of mesalazine in IBS.

Science.gov (United States)

Barbara, Giovanni; Cremon, Cesare; Annese, Vito; Basilisco, Guido; Bazzoli, Franco; Bellini, Massimo; Benedetti, Antonio; Benini, Luigi; Bossa, Fabrizio; Buldrini, Paola; Cicala, Michele; Cuomo, Rosario; Germanà, Bastianello; Molteni, Paola; Neri, Matteo; Rodi, Marcello; Saggioro, Alfredo; Scribano, Maria Lia; Vecchi, Maurizio; Zoli, Giorgio; Corinaldesi, Roberto; Stanghellini, Vincenzo

2016-01-01

Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. ClincialTrials.gov number, NCT00626288. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
The Insight of Industrialised Building System (IBS By Bumiputera Construction Players

Directory of Open Access Journals (Sweden)

Muhammad W. M. N. W.

2016-01-01

Full Text Available The term Industrialised Building System (IBS is widely recognised by construction players in Malaysia since its first implementation since 1960s for IBS pilot projects of Pekeliling Flats and Rifle Range Flats. The aim for the implementation is to promote better system in delivering construction end-products which offers efficiency and effectiveness. At the same time, Bumiputera construction players are the majority of parties in construction industry especially in Small and Medium Enterprises (SMEs. Therefore, the purpose of this paper is to identify the perception and awareness of IBS implementation among Bumiputera players. It is found that, Bumiputera construction players have sound knowledge on the IBS and optimistic towards further implementation for future projects. Nonetheless, issues on payment methods and coordination of IBS project delivery are found to be the negative perceptions which are considered as hindrance for Bumiputera construction players’ involvement in IBS project.

Pseudohypoparathyroidism type Ib associated with novel duplications in the GNAS locus.

Directory of Open Access Journals (Sweden)

Gustavo Perez-Nanclares

Full Text Available Pseudohypoparathyroidism type 1b (PHP-Ib is characterized by renal resistance to PTH (and, sometimes, a mild resistance to TSH and absence of any features of Albright's hereditary osteodystrophy. Patients with PHP-Ib suffer of defects in the methylation pattern of the complex GNAS locus. PHP-Ib can be either sporadic or inherited in an autosomal dominant pattern. Whereas familial PHP-Ib is well characterized at the molecular level, the genetic cause of sporadic PHP-Ib cases remains elusive, although some molecular mechanisms have been associated with this subtype.The aim of the study was to investigate the molecular and imprinting defects in the GNAS locus in two unrelated patients with PHP-Ib.We have analyzed the GNAS locus by direct sequencing, Methylation-Specific Multiplex Ligation-dependent Probe Amplification, microsatellites, Quantitative Multiplex PCR of Short Fluorescent fragments and array-Comparative Genomic Hybridization studies in order to characterize two unrelated families with clinical features of PHP-Ib.We identified two duplications in the GNAS region in two patients with PHP-Ib: one of them, comprising ∼ 320 kb, occurred 'de novo' in the patient, whereas the other one, of ∼ 179 kb in length, was inherited from the maternal allele. In both cases, no other known genetic cause was observed.In this article, we describe the to-our-knowledge biggest duplications reported so far in the GNAS region. Both are associated to PHP-Ib, one of them occurring 'de novo' and the other one being maternally inherited.
Comparative study to develop a single method for retrieving wide class of recombinant proteins from classical inclusion bodies.

Science.gov (United States)

Padhiar, Arshad Ahmed; Chanda, Warren; Joseph, Thomson Patrick; Guo, Xuefang; Liu, Min; Sha, Li; Batool, Samana; Gao, Yifan; Zhang, Wei; Huang, Min; Zhong, Mintao

2018-03-01

The formation of inclusion bodies (IBs) is considered as an Achilles heel of heterologous protein expression in bacterial hosts. Wide array of techniques has been developed to recover biochemically challenging proteins from IBs. However, acquiring the active state even from the same protein family was found to be an independent of single established method. Here, we present a new strategy for the recovery of wide sub-classes of recombinant protein from harsh IBs. We found that numerous methods and their combinations for reducing IB formation and producing soluble proteins were not effective, if the inclusion bodies were harsh in nature. On the other hand, different practices with mild solubilization buffers were able to solubilize IBs completely, yet the recovery of active protein requires large screening of refolding buffers. With the integration of previously reported mild solubilization techniques, we proposed an improved method, which comprised low sarkosyl concentration, ranging from 0.05 to 0.1% coupled with slow freezing (- 1 °C/min) and fast thaw (room temperature), resulting in greater solubility and the integrity of solubilized protein. Dilution method was employed with single buffer to restore activity for every sub-class of recombinant protein. Results showed that the recovered protein's activity was significantly higher compared with traditional solubilization/refolding approach. Solubilization of IBs by the described method was proved milder in nature, which restored native-like conformation of proteins within IBs.
Data Management Guide: Integrated Baseline System (IBS). Version 2.1

Energy Technology Data Exchange (ETDEWEB)

Bower, J.C. [Bower Software Services, Kennewick, Washington (United States); Burford, M.J.; Downing, T.R.; Moise, M.C.; Williams, J.R. [Pacific Northwest Lab., Richland, WA (United States)

1995-01-01

The Integrated Baseline System (IBS) is an emergency management planning and analysis tool that is being developed under the direction of the US Army Nuclear and Chemical Agency (USANCA). The IBS Data Management Guide provides the background, as well as the operations and procedures needed to generate and maintain a site-specific map database. Data and system managers use this guide to manage the data files and database that support the administrative, user-environment, database management, and operational capabilities of the IBS. This document provides a description of the data files and structures necessary for running the IBS software and using the site map database.
Integrated Baseline System (IBS) Version 1.03: Utilities guide

Energy Technology Data Exchange (ETDEWEB)

Burford, M.J.; Downing, T.R.; Pottier, M.C.; Schrank, E.E.; Williams, J.R.

1993-01-01

The Integrated Baseline System (IBS) is an emergency management planning and analysis tool that was developed under the direction of the Federal Emergency Management Agency (FEMA). This Utilities Guide explains how to operate utility programs that are supplied as a part of the IBS. These utility programs are chiefly for managing and manipulating various kinds of IBS data and system administration files. Many of the utilities are for creating, editing, converting, or displaying map data and other data that are related to geographic location.
Integrated Baseline System (IBS) Version 2.0: Utilities Guide

Energy Technology Data Exchange (ETDEWEB)

Burford, M.J.; Downing, T.R.; Williams, J.R. [Pacific Northwest Lab., Richland, WA (United States); Bower, J.C. [Bower Software Services, Kennewick, WA (United States)

1994-03-01

The Integrated Baseline System (IBS) is an emergency management planning and analysis tool being developed under the direction of the US Army Nuclear and Chemical Agency. This Utilities Guide explains how you can use the IBS utility programs to manage and manipulate various kinds of IBS data. These programs include utilities for creating, editing, and displaying maps and other data that are referenced to geographic location. The intended audience for this document are chiefly data managers but also system managers and some emergency management planners and analysts.
Flexibility of Supply Chain in Industrialised Building System (IBS

Directory of Open Access Journals (Sweden)

Kassim U.

2014-01-01

Full Text Available It is irrefutable that the construction industry is in need of a highly technological construction method or system for the simple aim of giving it a push it deserves. In Malaysia this technologically enhanced method is known as the Indutrialised Building System (IBS. Concerted efforts have been made for the past decade by various responsible parties especially by the government. Therefore, the IBS ‘Road Map’ 2003–2010 was introduced and now continues with the IBS ‘road map’ 2011-2015. However, its performance is still at its infancy, which target is only at an initial stage. This study seeks to identify and analyse the factor of the IBS’ system’s supply chain flexibility as a factor on the success of the system itself. It has been a suspicion that there exists a condition and situation where the supply chain is too rigid and is not flexible in fulfilling the needs and demands of the IBS development in Malaysia. This inflexible situation has brought about a broad range of problems and has stood in the way of the development of the industrialised building system, despite it being introduced since 1964, or 49 years ago. Flexibility in the IBS supply chain is very important and is associated with other industries like transportation, manufacturing industry, and others. Up until now, we have yet to discover any special studies related to the flexibility in the IBS supply chain in this country. Responding to this challenge, this research is hoped to be able to provide sufficient feedback to the solution to the IBS supply chain flexibility issue. The researcher is confident that the poor system flow of supply chain has impeded the advancement of the Industrialised Building System that has long been open to debate.
Protein kinase activity associated with the corticosteroid binder IB

International Nuclear Information System (INIS)

Vujicic, M.; Djordjevic-Markovic, R.; Radic, O.; Krstic, M.; Kanazir, D.

1997-01-01

The physiological effects elicited by glucocorticoids are mediated via glucocorticoid receptors (GR). Analysis of specific glucocorticoid binding to radioactively labelled [ 3 H] triamcinolone acetonide in rat liver cytosol and analysis by ion exchange chromatography have revealed the presence of two distinct molecular species. The major form, designated as binder II appears to correspond to the well characterized glucocorticoid receptor by virtue of its size, charge, steroid binding characteristics and ability to bind to DNA.The second form, designated as corticosteroid binder IB, is a minor binding component in the liver. The binder IB differs from the binder II receptor by virtue of its lower molecular weight and its elution in the pre gradient of DEAE-Sephadex A-50 column which retains the un activated binder II receptor complexes. We examined the kinase activity of partially purified corticosteroid binder IB. Using (γ 3 2 P) ATP we detected kinase activity associated with the IB fraction from the rat liver. This kinase phosphorylate mixed histones and and dose not phosphorylate IB protein in vitro. The kinase activity is completely inhibited by the addition of Mg 2 + ions and is partially inhibited by the addition of Ca 2 +ions. (author)
2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani.

Science.gov (United States)

Carballeira, Néstor M; Cartagena, Michelle; Sanabria, David; Tasdemir, Deniz; Prada, Christopher F; Reguera, Rosa M; Balaña-Fouce, Rafael

2012-10-01

2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC(50)=5.3±0.7μM. The potency of LdTopIB inhibition follows the trend 2-ODA>2-HDA>2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC(50)=11.0μM), but it was less effective against other protozoa, Trypanosoma cruzi (IC(50)=48.1μM) and Trypanosoma brucei rhodesiense (IC(50)=64.5μM). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA>2-HDA>2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound. Copyright © 2012 Elsevier Ltd. All rights reserved.
Migraine, fibromyalgia, and depression among people with IBS: a prevalence study

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Cabral Howard J

2006-09-01

Full Text Available Abstract Background Case descriptions suggest IBS patients are more likely to have other disorders, including migraine, fibromyalgia, and depression. We sought to examine the prevalence of these conditions in cohorts of people with and without IBS. Methods The source of data was a large U.S. health plan from January 1, 1996 though June 30, 2002. We identified all people with a medical claim associated with an ICD-9 code for IBS. A non-IBS cohort was a random sample of people with an ICD-9 code for routine medical care. In the cohorts, we identified all claims for migraine, depression, and fibromyalgia. We estimated the prevalence odds ratios (PORs of each of the three conditions using the Mantel-Haenszel method. We conducted quantitative sensitivity analyses to quantify the impact of residual confounding and in differential outcome identification. Results We identified 97,593 people in the IBS cohort, and a random sample of 27,402 people to compose the non-IBS comparison cohort. With adjustment, there was a 60% higher odds in the IBS cohort of having any one of the three disorders relative to the comparison cohort (POR 1.6, 95% CI 1.5 – 1.7. There was a 40% higher odds of depression in the IBS cohort (POR 1.4, 95% CI 1.3 – 1.4. The PORs for fibromyalgia and migraine were similar (POR for fibromyalgia 1.8, 95% CI 1.7 – 1.9; POR for migraine 1.6, 95% CI 1.4 – 1.7. Differential prevalence of an unmeasured confounder, or imperfect sensitivity or specificity of outcome detection would have impacted the observed results. Conclusion People in the IBS cohort had a 40% to 80% higher prevalence odds of migraine, fibromyalgia, and depression.
Anti-Inflammatory Activities of a Chinese Herbal Formula IBS-20 In Vitro and In Vivo

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Zhonghan Yang

2012-01-01

Full Text Available Irritable bowel syndrome (IBS is a functional bowel disorder and the etiology is not well understood. Currently there is no cure for IBS and no existing medication induces symptom relief in all patients. IBS-20 is a 20-herb Chinese medicinal formula that offers beneficial effects in patients with IBS; however, the underlying mechanisms are largely unknown. This study showed that IBS-20 potently inhibited LPS- or IFNΓ-stimulated expression of pro-inflammatory cytokines, as well as classically activated macrophage marker nitric oxide synthase 2. Similarly, IBS-20 or the component herb Coptis chinensis decreased LPS-stimulated pro-inflammatory cytokine secretion from JAWS II dendritic cells. IBS-20 or the component herbs also blocked or attenuated the IFNΓ-induced drop in transepithelial electric resistance, an index of permeability, in fully differentiated Caco-2 monolayer. Finally, the up-regulation of key inflammatory cytokines in inflamed colon from TNBS-treated mice was suppressed significantly by orally administrated IBS-20, including IFNΓ and IL-12p40. These data indicate that the anti-inflammatory activities of IBS-20 may contribute to the beneficial effects of the herbal extract in patients with IBS, providing a potential mechanism of action for IBS-20. In addition, IBS-20 may be a potential therapeutic agent against other Th1-dominant gut pathologies such as inflammatory bowel disease.
Innovative Approach for IBS Vendor Selection Problem

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Omar Mohd Faizal

2016-01-01

Full Text Available Supply chain management in Industrialised Building System (IBS construction management has significantly determined the successful of company and project performance. Due to the wide variety of criteria and vendor available, the vendor selection process for a specific project needs is becoming more difficult. The need of decision aid for vendor selection in other areas is widely discussed in previous research. However, study on vendor selection for IBS project is largely neglected. Decision Support System (DSS is proposed for this purpose. Yet, most of the DSS models are impractical since they are complicated and difficult for a layman such as project managers to use. Research indicates that the rapid development of ICT has highly potential towards simple and effective DSS. Thus, this paper highlights the importance and research approach for vendor selection in IBS project management. The study is based on Design Science Research Methodology with combination of case studies. It is anticipates that this study will yield an effective value-for-money decision making platform to manage vendor selection process.
El estudio de la Fauna Ibérica

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Ramos Sánchez, María Ángeles

2007-10-01

Full Text Available Since the beginning in 1989, Fauna Ibérica has promoted coordinated research in Taxonomy bringing together more than 100 Spanish and non-Spanish experts. The programme supported by CSIC Presidency is lead by Museo Nacional de Ciencias Naturales. As a result, 30 Fauna Ibérica monographs has been published in addition to a year average of 50-60 scientific papers describing more than 50 new species per year. IBERFAUNA, the Data Bank of the Spanish Fauna, has been created including 38.000 out of the 61.000 species estimated to live in the Iberian Peninsula and Balearic Islands. This area is confirmed as one of the most biodiverse of the European Union with more than 50 % of the European species and more than 50 % of its endemics. Among future plans, a more stable organization is proposed in order to: maintaining dichotomy paper/digital publications, increasing interactivity among taxonomists and training, developing cyber-tools to facilitate public access to the information and increasing the strength of Fauna Ibérica through collaboration with other international initiatives and other areas of knowledge.Desde su inicio en 1989, Fauna Ibérica ha impulsado la investigación coordinada de más de 100 taxónomos españoles y extranjeros. El programa, apoyado por la Presidencia del CSIC, está dirigido por el Museo Nacional de Ciencias Naturales. Como resultado, se han publicado 30 monografías de la serie Fauna Ibérica, y un promedio anual de 50-60 artículos científicos que describen más de 50 nuevas especies por año. Se ha creado el Banco de Datos, IBERFAUNA, que cuenta ya con 38.000 de las aproximadamente 61.000 especies que habitan en la Península Ibérica y Baleares. Se confirma como una de las regiones más ricas en biodiversidad de la Unión Europea, con más del 50 % de las especies y más de un 50 % de sus endemismos. Entre los planes de futuro, se propone una estructura estable para Fauna Ibérica, que mantenga la dicotomía soporte
dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development

International Nuclear Information System (INIS)

Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

2015-01-01

Highlights: • Murine NTDs were successfully induced by means of hydroxyurea (HU). • The impairment of dNTP was induced via inhibition of ribonucleotide reductase. • dNTP deficiency induced by HU caused defective DNA synthesis and repair. • Abnormal apoptosis and proliferation induced by HU affected neural tube development. - Abstract: Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis
Key factors of successful JIT integration with IBS - An overview

Science.gov (United States)

Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

2016-08-01

The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.
FRAGMENTATION ISSUE IN MALAYSIAN INDUSTRIALISED BUILDING SYSTEM (IBS PROJECTS

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MOHD NASRUN MOHD NAWI

2014-02-01

Full Text Available As a developing country, Malaysian is currently driving for implementing a new or modern construction method, the Industrialised Building System (IBS, as an alternative towards enhancing construction performance. Currently, most of the IBS project developments in Malaysia are still conducted by using the traditional construction process approach. This traditional construction process has been widely criticised for its fragmented approach to project delivery and its failure to form effective teams thus created a number of issues such as reworks, time delay, rising costs, lack of communication and coordination, and wastages. This paper through literature review aims to highlight this fragmentation issue and clarify how far it affects the process of IBS implementation. Suggestions on how an integrated approach in design and construction in order to minimise the fragmentation gaps will be concluded.
A unique set of SH3-SH3 interactions controls IB1 homodimerization

DEFF Research Database (Denmark)

Kristensen, Ole; Guenat, Sylvie; Dar, Imran

2006-01-01

Islet-brain 1 (IB1 or JIP-1) is a scaffold protein that interacts with components of the c-Jun N-terminal kinase (JNK) signal-transduction pathway. IB1 is expressed at high levels in neurons and in pancreatic beta-cells, where it controls expression of several insulin-secretory components...... reduces IB1-dependent basal JNK activity in 293T cells. Impaired dimerization also results in a reduction in glucose transporter type 2 expression and in glucose-dependent insulin secretion in pancreatic beta-cells. Taken together, these results indicate that IB1 homodimerization through its SH3 domain...
Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

Science.gov (United States)

Xu, Xiao-juan; Liu, Liang; Yao, Shu-kun

2016-01-01

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory- and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.
Reduction of the degradation activity of umami-enhancing purinic ribonucleotide supplement in miso by the targeted suppression of acid phosphatases in the Aspergillus oryzae starter culture.

Science.gov (United States)

Marui, Junichiro; Tada, Sawaki; Fukuoka, Mari; Wagu, Yutaka; Shiraishi, Yohei; Kitamoto, Noriyuki; Sugimoto, Tatsuya; Hattori, Ryota; Suzuki, Satoshi; Kusumoto, Ken-Ichi

2013-09-02

Miso (fermented soybean paste) is a traditional Japanese fermented food, and is now used worldwide. The solid-state culture of filamentous fungus, Aspergillus oryzae, grown on rice is known as rice-koji, and is important as a starter for miso fermentation because of its prominent hydrolytic enzyme activities. Recently, commercial miso products have been supplemented with purinic ribonucleotides, such as inosine monophosphate (IMP) and guanine monophosphate, to enhance the characteristic umami taste of glutamate in miso. Because the purinic ribonucleotides are degraded by enzymes such as acid phosphatases in miso, heat inactivation is required prior to the addition of these flavorings. However, heat treatment is a costly process and reduces the quality of miso. Therefore, an approach to lower acid phosphatase activities in koji culture is necessary. Transcriptional analysis using an A. oryzae KBN8048 rice-koji culture showed that eight of the 13 acid phosphatase (aph) genes were significantly down-regulated by the addition of phosphoric acid in the preparation of the culture in a concentration-dependent manner, while aphC expression was markedly up-regulated under the same conditions. The eight down-regulated genes might be under the control of the functional counterpart of the Saccharomyces cerevisiae transcriptional activator Pho4, which specifically regulates phosphatase genes in response to the ambient phosphate availability. However, the regulatory mechanism of aphC was not clear. The IMP dephosphorylation activities in rice-koji cultures of KBN8048 and the aphC deletion mutant (ΔaphC) were reduced by up to 30% and 70%, respectively, in cultures with phosphoric acid, while protease and amylase activity, which is important for miso fermentation, was minimally affected. The miso products fermented using the rice-koji cultures of KBN8048 and ΔaphC prepared with phosphoric acid had reductions in IMP dephosphorylation activity of 80% and 90%, respectively, without
Los materiales hercínicos de la cordillera ibérica en el contexto del macizo ibérico

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Liñán, E.

1988-12-01

Full Text Available The discontinuity observed between the paleozoic outcrops of the Iberian Mountains and the ones of the Iberian Massif, has been the greatest incovenient to include those ones in a general Hercynian Iberian model. Two hypothesis have been proposed to the respect. One initial hypothesis postulates the inclusion of the Iberian Mountains paleozoic racks in the West Asturian-Leonese Zone (Lotze, 1961; Julivert et al., 1974. Other one postulates a double inelusion: the occidental part of the Iberian Chaines into the West Asturian-Leonese Zone and the oriental part of the Iberian Chaines into the Cantabrian Zona (Liñán, 1983. In this work new geological data are provided for the geological conexion between Cantabrian Zone and the oriental part of the Iberian Chains; they can be summarised in three points. One of them is referred to the paralellism between the Narcea and Paracuellos antiforms. Those antiforms are divided by a tectonic accident, wich separates different Precambrian sequences. Another point deals with the close relation of the stratigraphical sequences of the Paleozoic racks between the Cantabrian region and Iberian region at both sides of the Narcea and Paracuellos antiforms. the last point refers to the study of small outcrops located in the northwest of the Iberian Chains, that show a probably more similar geological structure to the Cantabrian Zone wich was defined as a fold and thrust belt.La falta de continuidad de los afloramientos paleozoicos de la Cordillera Ibérica con los del Macizo Ibérico han venido constituyendo un serio obstáculo para la inclusión de aquéllos dentro de un esquema general para el hercínico ibérico. Dos hipótesis han sido hasta ahora planteadas: su conexión con la Zona Asturoccidental-Leonesa, o su doble conexión con esta zona y con la zona Cantábrica. En este trabajo se aportan nuevos datos geológicos que son congruentes con la prolongación tanto de la Zona Cantábrica como de la Zona
Resistance to sulfur poisoning of Ni-based alloy with coinage (IB) metals

International Nuclear Information System (INIS)

Xu, Xiaopei; Zhang, Yanxing; Yang, Zongxian

2015-01-01

Highlights: • The effects of IB metal dopants on the S poisoning features of Ni are analyzed. • IB metal dopants can modify the surface electronic structure of Ni. • IB metal dopants can increase the S tolerance of Ni at an optimized concentration. • Au is a preferred dopant to increase the resistance to sulfur poisoning of Ni. - Abstract: The poisoning effects of S atom on the (1 0 0), (1 1 0) and (1 1 1) metal surfaces of pure Ni and Ni-based alloy with IB (coinage) metals (Cu, Ag, Au) are systematically studied. The effects of IB metal dopants on the S poisoning features are analyzed combining the density functional theory (DFT) results with thermodynamics data using the ab initio atomistic thermodynamic method. It is found that introducing IB doping metals into Ni surface can shift the d-band center downward from the Fermi level and weaken the adsorption of S on the (1 0 0) and (1 1 0) surfaces, and the S tolerance ability increases in the order of Ni, Cu/Ni, Ag/Ni and Au/Ni. Nevertheless, on the (1 1 1) surface, the S tolerance ability increases in the order of Ag/Ni (or Cu/Ni), Ni, and Au/Ni. When we increase the coverage of the IB metal dopants, we found that not only Au, but Cu and Ag can increase its S tolerance. We therefore propose that alloying can increase its S tolerance and alloying with Au would be a better way to increase the resistance to sulfur poisoning of the Ni anode as compared with the pure Ni and the Ag- or, Cu-doped Ni materials.

Hydroxyurea-resistant vaccinia virus: overproduction of ribonucleotide reductase

International Nuclear Information System (INIS)

Slabaugh, M.B.; Mathews, C.K.

1986-01-01

Repeated passage of vaccinia virus in increasing concentrations of hydroxyurea followed by plaque purification resulted in the isolation of variants capable of growth in 5 mM hydroxyurea, a drug concentration which inhibited the reproduction of wild-type vaccinia virus 1000-fold. Analyses of viral protein synthesis by using [ 35 S]methionine pulse-labeling at intervals throughout the infection cycle revealed that all isolates overproduced a 34,000-molecular-weight (MW) early polypeptide. Measurement of ribonucleoside-diphosphate reductase activity after infection indicated that 4- to 10-fold more activity was induced by hydroxyurea-resistant viruses than by the wild-type virus. A two-step partial purification resulted in a substantial enrichment for the 34,000-MW protein from extracts of wild-type and hydroxyurea-resistant-virus-infected, but not mock-infected, cells. In the presence of the drug, the isolates incorporated [ 3 H]thymidine into DNA earlier and a rate substantially greater than that of the wild type, although the onset of DNA synthesis was delayed in both cases. The drug resistance trait was markedly unstable in all isolates. In the absence of selective pressure, plaque-purified isolated readily segregated progeny that displayed a wide range of resistance phenotypes. The results of this study indicate that vaccinia virus encodes a subunit of ribonucleotide reductase which is 34,000-MW early protein whose overproduction confers hydroxyurea resistance on reproducing viruses
Nonsense mutation in the glycoprotein Ibα coding sequence associated with Bernard-Soulier syndrome

International Nuclear Information System (INIS)

Ware, J.; Russell, S.R.; Vicente, V.; Scharf, R.E.; Tomer, A.; McMillian, R.; Ruggeri, Z.M.

1990-01-01

Three distinct gene products, the α and β chains of glycoprotein (GP) Ib and GP IX, constitute the platelet membrane GP Ib-IX complex, a receptor for von Willebrand factor and thrombin involved in platelet adhesion and aggregation. Defective function of the GP Ib-IX complex is the hallmark of a rare congenital bleeding disorder of still undefined pathogenesis, the Bernard-Soulier syndrome. The authors have analyzed the molecular basis of the disease in one patient in whom immunoblotting of solubilized platelets demonstrated absence of normal GP Ibα but presence of a smaller immunoreactive species. The truncated polypeptide was also present, along with normal protein, in platelets from the patient's mother and two of his four children. Genetic characterization identified a nucleotide transition changing the Trp-343 codon (TGG) to a nonsense codon (TGA). Such a mutation explains the origin of the smaller GP Ibα, which by lacking half of the sequence on the carboxyl-terminal side, including the transmembrane domain, cannot be properly inserted in the platelet membrane. Both normal and mutant codons were found in the patient, suggesting that he is a compound heterozygote with a still unidentified defect in the other GP Ibα allele. Nonsense mutation and truncated GP Ibα polypeptide were found to cosegregate in four individuals through three generations and were associated with either Bernard-Soulier syndrome or carrier state phenotype. The molecular abnormality demonstrated in this family provides evidence that defective synthesis of GP Ibα alters the membrane expression of the GP Ib-IX complex and may be responsible for Bernard-Soulier syndrome
IB Offering Certificate for Careers

Science.gov (United States)

Robelen, Erik W.

2012-01-01

The International Baccalaureate (IB) organization, best known in the United States for its prestigious two-year diploma program for juniors and seniors, will enter new terrain this fall as it formally rolls out an initiative centered on a variety of career pathways that includes engineering, culinary arts, and automotive technology. The move comes…
Structural Analysis of the Active Site Geometry of N5-Carboxyaminoimidazole Ribonucleotide Synthetase from Escherichia coli

International Nuclear Information System (INIS)

Thoden, James B.; Holden, Hazel M.; Firestine, Steven M.

2008-01-01

N 5 -Carboxyaminoimidazole ribonucleotide synthetase (N 5 -CAIR synthetase) converts 5-aminoimidazole ribonucleotide (AIR), MgATP, and bicarbonate into N 5 -CAIR, MgADP, and P i . The enzyme is required for de novo purine biosynthesis in microbes yet is not found in humans suggesting that it represents an ideal and unexplored target for antimicrobial drug design. Here we report the X-ray structures of N 5 -CAIR synthetase from Escherichia coli with either MgATP or MgADP/P i bound in the active site cleft. These structures, determined to 1.6-(angstrom) resolution, provide detailed information regarding the active site geometry before and after ATP hydrolysis. In both structures, two magnesium ions are observed. Each of these is octahedrally coordinated, and the carboxylate side chain of Glu238 bridges them. For the structure of the MgADP/P i complex, crystals were grown in the presence of AIR and MgATP. No electron density was observed for AIR, and the electron density corresponding to the nucleotide clearly revealed the presence of ADP and P i rather than ATP. The bound P i shifts by approximately 3 (angstrom) relative to the γ-phosphoryl group of ATP and forms electrostatic interactions with the side chains of Arg242 and His244. Since the reaction mechanism of N 5 -CAIR synthetase is believed to proceed via a carboxyphosphate intermediate, we propose that the location of the inorganic phosphate represents the binding site for stabilization of this reactive species. Using the information derived from the two structures reported here, coupled with molecular modeling, we propose a catalytic mechanism for N 5 -CAIR synthetase.
In silico analysis of glycinamide ribonucleotide transformylase inhibition by PY873, PY899 and DIA

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Sidra Batool

2017-09-01

Full Text Available In humans, purine de novo synthesis pathway consists of multi-functional enzymes. Nucleotide metabolism enzymes are potential drug targets for treating cancer and autoimmune diseases. Glycinamide ribonucleotide transformylase (GART is one of the most important trifunctional enzymes involved in purine synthesis. Previous studies have demonstrated the role of folate inhibitors against tumor activity. In this present study, three components of GART enzyme were targeted as receptor dataset and in silico analysis was carried out with folate ligand dataset. To accomplish the task, Autodock 4.2 was used for determining the docking compatibilities of ligand and receptor dataset. Taken together, it has been suggested that folate ligands could be potentially used as inhibitors of GART.
The International Baccalaureate (IB programme: An international gateway to higher education and beyond

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Susan E. Saxton

2014-09-01

Full Text Available The aim of this article is to present the International Baccalaureate (IB Programme and briefly outline its core components, followed by a review of what authoritative reports identify as skills for the future, esteemed by universities and the job market. There is a striking match between these skills and IB outcomes; thus, DP graduates perform well in higher education and add to the reputation of those institutions. After a review of the literature, the authors found the IB Diploma Programme has been studied in many countries by both consultants and educational agencies, and also by a wide array of universities themselves; however, there are fewer qualitative studies concerning the degree to which IB graduates display attitudes, values, and behaviours in line with the IB Learner Profile. This is why the authors stress the claims made are supported by examples of significant research, noting that there is a dearth of qualitative longitudinal studies to sufficiently substantiate the affective domain claims that currently rely more on anecdotal evidence. The authors conclude by pointing out more research is needed in order to substantiate anecdotal evidence regarding future employment success for IB Diploma Programme graduates. DOI: 10.18870/hlrc.v4i3.123
Enhanced accumulation of carotenoids in sweetpotato plants overexpressing IbOr-Ins gene in purple-fleshed sweetpotato cultivar.

Science.gov (United States)

Park, Sung-Chul; Kim, Sun Ha; Park, Seyeon; Lee, Hyeong-Un; Lee, Joon Seol; Park, Woo Sung; Ahn, Mi-Jeong; Kim, Yun-Hee; Jeong, Jae Cheol; Lee, Haeng-Soon; Kwak, Sang-Soo

2015-01-01

Sweetpotato [Ipomoea batatas (L.) Lam] is an important root crop that produces low molecular weight antioxidants such as carotenoids and anthocyanin. The sweetpotato orange (IbOr) protein is involved in the accumulation of carotenoids. To increase the levels of carotenoids in the storage roots of sweetpotato, we generated transgenic sweetpotato plants overexpressing IbOr-Ins under the control of the cauliflower mosaic virus (CaMV) 35S promoter in an anthocyanin-rich purple-fleshed cultivar (referred to as IbOr plants). IbOr plants exhibited increased carotenoid levels (up to 7-fold) in their storage roots compared to wild type (WT) plants, as revealed by HPLC analysis. The carotenoid contents of IbOr plants were positively correlated with IbOr transcript levels. The levels of zeaxanthin were ∼ 12 times elevated in IbOr plants, whereas β-carotene increased ∼ 1.75 times higher than those of WT. Quantitative RT-PCR analysis revealed that most carotenoid biosynthetic pathway genes were up-regulated in the IbOr plants, including PDS, ZDS, LCY-β, CHY-β, ZEP and Pftf, whereas LCY-ɛ was down-regulated. Interestingly, CCD1, CCD4 and NCED, which are related to the degradation of carotenoids, were also up-regulated in the IbOr plants. Anthocyanin contents and transcription levels of associated biosynthetic genes seemed to be altered in the IbOr plants. The yields of storage roots and aerial parts of IbOr plants and WT plants were not significantly different under field cultivation. Taken together, these results indicate that overexpression of IbOr-Ins can increase the carotenoid contents of sweetpotato storage roots. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Purification, crystallization and preliminary X-ray analysis of Enterococcus faecium aminoglycoside-2′′-phosphotransferase-Ib [APH(2′′)-Ib

International Nuclear Information System (INIS)

Walanj, Rupa; Young, Paul; Baker, Heather M.; Baker, Edward N.; Metcalf, Peter; Chow, Joseph W.; Lerner, Stephen; Vakulenko, Sergei; Smith, Clyde A.

2005-01-01

APH(2′′)-Ib is an enzyme responsible for high-level gentamicin resistance in E. faecium isolates. Native crystals of this enzyme have been prepared and preliminary X-ray diffraction experiments have been undertaken. Bacterial resistance to the aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, APH(2′′)-Ib, has been cloned and the protein (comprising 299 amino-acid residues) expressed in Escherichia coli, purified and crystallized in the presence of 16%(w/v) PEG 3350 and gentamicin. The crystals belong to the monoclinic space group P2 1 , with approximate unit-cell parameters a = 79.7, b = 58.8, c = 81.4 Å, β = 98.4°, and preliminary X-ray diffraction analysis is consistent with the presence of two molecules in the asymmetric unit. Synchrotron diffraction data to approximately 2.65 Å resolution were collected from a native APH(2′′)-Ib crystal at beamline BL9-2 at SSRL (Stanford, CA, USA). Selenium-substituted crystals have also been produced and structure determination is proceeding
Overcoming ICT Barriers in IBS Management Process in Malaysia Construction Industry

Directory of Open Access Journals (Sweden)

Soon Ern Peniel Ang

2017-01-01

Full Text Available As the result of government’s initiative and future outlook in uprising the awareness towards the implementation of sustainable elements in construction industries, the Industrialized Building System (IBS is one of the approaches that had been introduced as an alternative to conventional building method and produce the new strategy of reducing the waste of materials in construction. The IBS approach is actively promoted through several strategies and incentives as an alternative to conventional building methods. Extensive uptakes of modern Information Communication Technology (ICT applications are able to support the different IBS processes for effective production. However, it is argued that ICT uptake at the organizational level needs to be regularly improved. Thus, this paper fulfills the need to identify the critical barriers to ICT employment and highlighting the ICT drivers in enhancing the IBS management process. Critical barriers and drivers to ICT uptake were identified through questionnaire survey with industry stakeholders and were analyzed using mean index and critical t-value with the use of SPSS software. The critical drivers are top management support and commitment and improving the availability of the technologies. The critical drivers which were identified are significant in ensuring the enhancement of ICT implementation. Hence, any system in place should avoid the highest ranked barriers or seek to alleviate their impact by focusing on the identified drivers in order to enhance implementation of ICT in IBS process management.
Translation and validation of a Japanese version of the irritable bowel syndrome-quality of life measure (IBS-QOL-J

Directory of Open Access Journals (Sweden)

Hongo Michio

2007-03-01

Full Text Available Abstract Aims To compare quality of life (QOL for patients with irritable bowel syndrome (IBS between the U.S. and Japan, it is indispensable to develop common instruments. The IBS-QOL, which is widely used in Western countries, was translated into Japanese as there has been a lack of Japanese disease-specific QOL measures for IBS. Methods The original 34 items of the IBS-QOL were translated from English into Japanese through two independent forward translations, resolution, back translation, and resolution of differences. Forty nine patients who had GI symptoms but did not have any organic diseases (including 30 IBS patients diagnosed by Rome II criteria were recruited from Tohoku University Hospital in Sendai, Japan and completed a Japanese version of the IBS-QOL (IBS-QOL-J concomitant with a Japanese version of the IBS severity index (IBSSI-J twice within 7–14 days. Results The IBS-QOL-J demonstrated high internal consistency (Cronbach's alpha; 0.96 and high reproducibility (intraclass correlation coefficient; 0.92, p Conclusion The IBS-QOL-J is a reliable instrument to assess the disease-specific QOL for IBS. Considering cross-cultural comparison, this measure is likely to be a valuable tool to investigate the QOL in Japanese patients with IBS.
Improving the stability of alpha-conotoxin AuIB through N-to-C cyclization

DEFF Research Database (Denmark)

Armishaw, Christopher J; Jensen, Anders A; Balle, Lena D

2011-01-01

Modification of alpha-conotoxin frameworks through cyclization via an oligopeptide linker has previously been shown as an effective strategy for improving in vivo stability. We have extended this strategy by investigating cyclic analogs of alpha-conotoxin AuIB, a selective alpha3beta4 nicotinic a......-AuIB. As such, the cAuIB-2 globular isomer could constitute a useful probe for studying the role of the alpha3beta4 nicotinic acetylcholine receptor in a range of in vivo experimental paradigms....
Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio).

Science.gov (United States)

Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

2016-09-16

Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp.
La Inscripción Ibérica en escritura jonia, Serreta IX.

OpenAIRE

Silgo Gauche, Luís

1997-01-01

S’estudía una nova inscripció sobre làmina de plom, localitzada casualment en l’àrea del poblat ibèric de la Serreta (Alcoi, Cocentaina, Penàguila), en l’escriptura del qual es van emprar caracters greco-ibèrics.
Contributions of type II and Ib/c supernovae to Galactic chemical evolution

International Nuclear Information System (INIS)

Sahijpal Sandeep

2014-01-01

Type II and Ib/c supernovae (SNe II and Ib/c) have made major stellar nucleosynthetic contributions to the inventories of stable nuclides during chemical evolution of the Galaxy. A case study is performed here with the help of recently developed numerical simulations of Galactic chemical evolution in the solar neighborhood to understand the contributions of SNe II and Ib/c by comparing the stellar nucleosynthetic yields obtained by two leading groups in this field. These stellar nucleosynthetic yields differ in terms of their treatment of stellar evolution and nucleosynthesis. The formulation describing Galactic chemical evolution is developed with the recently revised solar metallicity of ∼0.014. Furthermore, the recent nucleosynthetic yields of stellar models based on the revised solar metallicity are also used. The analysis suggests that it could be difficult to explain, in a self-consistent manner, the various features associated with the elemental evolutionary trends over Galactic timescales by any single adopted stellar nucleosynthetic model that incorporates SNe II and Ib/c
Measuring IBS patient reported outcomes with an abdominal pain numeric rating scale: results from the proof cohort

Science.gov (United States)

SPIEGEL, B.; BOLUS, R.; HARRIS, L. A.; LUCAK, S.; NALIBOFF, B.; ESRAILIAN, E.; CHEY, W. D.; LEMBO, A.; KARSAN, H.; TILLISCH, K.; TALLEY, J.; MAYER, E.; CHANG, L.

2009-01-01

Background Controversy exists about how to effectively measure patient reported outcomes in IBS clinical trials. Pain numeric rating scales (NRS) are widely used in the non-IBS pain literature. The FDA has proposed using the NRS in IBS. Aim To test the psychometrics of an abdominal pain NRS in IBS. Methods We analyzed data from a longitudinal cohort of Rome III IBS subjects. At entry, subjects completed a 10-point NRS, bowel symptoms, IBS severity measurements (IBSSS, FBDSI), health related quality of life indices (IBS-QOL, EQ5D), and the worker productivity activity index (WPAI). We repeated assessments at 3 months along with a response scale to calculate the minimal clinically important difference (MCID). Results There were 277 subjects (82% women; age=42±15) at baseline and 90 at 3 months. The NRS correlated cross-sectionally with IBSSS (r=0.60; p<0.0011), FBDSI (r=0.49; p<0.0001), IBS-QOL (r=0.43; p<0.0001), EQ5D (r=0.48; p<0.0001), presenteeism (r=0.39; p<0.0001), absenteeism (r=0.17; p=0.04), and distension (r=0.46; p<0.0001), but not stool frequency or form. The MCID was 2.2 points, correlating with a 29.5% reduction over time. Conclusions An abdominal pain NRS exhibits excellent validity and can be readily interpreted with an MCID in patients with IBS. These data support the use of the NRS in IBS clinical trials. PMID:19751360
More negative self-esteem and inferior coping strategies among patients diagnosed with IBS compared with patients without IBS - a case-control study in primary care

OpenAIRE

Grodzinsky, Ewa; Walter, Susanna; Viktorsson, Lisa; Carlsson, Ann-Kristin; Jones, Michael P.; Olsen Faresjö, Ashild

2015-01-01

Background Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder,that affects approximately 10% of the general population and the majority are diagnosed in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to investigate the psychosocial constructs of self-esteem and sense of...
Microbiota, gastrointestinal infections, low-grade inflammation, and antibiotic therapy in irritable bowel syndrome (IBS: an evidence-based review

Directory of Open Access Journals (Sweden)

Max Schmulson

2014-04-01

Conclusions: Further studies are required to determine the nature of the gut microbiota in IBS and the differences in low-grade inflammation between PI-IBS and non PI-IBS. Rifaximin has shown itself to be an effective treatment for IBS, regardless of prior factors.
The role of stress in IBS symptom severity

Directory of Open Access Journals (Sweden)

Sanda Pletikosic

2016-04-01

Full Text Available Irritable bowel syndrome is regarded as a biopsychosocial disorder, the result of a complex combination of predisposing, precipitating and perpetuating factors. Personality traits, affective status and stress are some of the relevant factors contributing to lower quality of life and symptom exacerbation in IBS patients. In order to examine the role of stress in IBS symptom exacerbation, the aims of this study were to explore the relationship of daily stressful events and symptom severity in a prospective manner and to explore the roles of neuroticism, anxiety, depression and stress in the vicious circle of symptom perpetuation. A total of 49 patients with IBS reported their symptom severity and daily stressful events intensity each day for 14 consecutive days. They also completed the Big five personality inventory, the Beck Depression Inventory and the State-trait anxiety inventory. Cross-correlation analyses were performed on the time series data for daily stress and symptom severity for each participant separately. Four different patterns of relationships were found in different subgroups of participants: positive cross-correlations of symptom severity and stress intensity on the same day; higher symptom severity on days following stressful days; lower symptom severity on days following stressful days; and lower stress intensity on days following severe symptoms. Using average scores for daily stress and symptom severity, as well as scores for neuroticism, anxiety and depression, we performed a path analysis to test a model of symptom exacerbation. It showed that, on the group level, average stress intensity predicts average symptom severity. Neuroticism and anxiety were not significant predictors of symptom severity, while depression showed a marginally significant relationship with symptom severity, mediated by stress intensity. In conclusion, depression and daily stress seem to be important contributors to the vicious circle of IBS symptom
Politics and Pedagogy: Discursive Constructions in the IB "Theory of Knowledge--Guide"

Science.gov (United States)

Smith, Nigel V.; Morgan, Mandy

2010-01-01

The International Baccalaureate (IB) curriculum is increasingly popular in both national and international secondary education settings. The "Theory of knowledge" (TOK) course is cast as the prime example of the international globalised values the IB Diploma represents. This article argues that such a positioning is contested within the TOK…
Critical Success Factors for Lean Thinking in the Application of Industrialised Building System (IBS)

Science.gov (United States)

Yunus, Riduan; Noor, Siti Rahimah Mohd; Halid Abdullah, Abd; Nagapan, Sasitharan; Hamid, Abdul Rahim Abdul; Tajudin, Saiful Azhar Ahmad; Rohani Mat Jusof, Siti

2017-08-01

Productivity in the manufacturing process of building components can be increased by optimising each advantage that is available in each activity. Identification of critical success factors (CSFs) for lean thinking in the Industrialised Building System (IBS) will be able to minimise cost and reduce time needed to complete a project. The focus of lean thinking in construction is on the production process and the client’s requirement. In developing countries such as Malaysia, the integration of lean thinking in IBS applications is still low and there is a shortage of comprehensive strategies to integrate lean thinking. As key stakeholders, feedback from contractors, manufacturers, developers and the local authority will be able to help the identification of CSFs in integrating lean thinking in IBS applications. The data was collected through a questionnaire survey and analysed quantitatively. There are 31 CSFs for lean thinking in IBS which have been identified in this study. A conceptual model was developed to assist researchers in investigating the influences of CSFs for lean thinking in IBS applications. This study will assist construction players to improvise their manufacturing process in the implementation of IBS to eliminate unnecessary activities and focus instead on significant processes without generating physical and non-physical waste.

A Preliminary Review on Economies of Scale (EOS Towards Industrialized Building System (IBS Manufacturer

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Tajul Ariffin Syazwana

2017-01-01

Full Text Available Industrialized Building System (IBS is a potential technology to improve productivity of construction industry. Controlled production and minimum generation of construction waste are some of the benefits that can be achieved by replacing conventional construction with IBS. In business, IBS is giving a huge opportunity for manufacturer and supplier to expand their business while contributing to construction development. However, bad strategies will put the company in high risk due to higher initial capital for machines and equipment. Therefore, strategic planning for company’s growth, profit maximization, and enhancement of productivity is undeniable to ensure the success of business in construction industry. This preliminary paper is exploring associated factors that affect Economy of Scale (EOS and their relationships in catalyzing the IBS manufacturer especially precast concrete as the scope of study to continue their business in the construction industry. Thus, a framework of EOS is proposed to assist IBS manufacturers to ensure their company’s growth and stability, competitiveness in term of monopoly or an oligopoly, increasing productivity, leading constant returns to scale, and finally increasing the firm’s efficiency. The refined EOS’s conceptual framework is an important turning point to support the development of decision making tools for IBS manufacturer towards their stability and survival in this highly competitive industry.
The communication in industrialised building system (IBS) construction project: Virtual environment

Science.gov (United States)

Pozin, Mohd Affendi Ahmad; Nawi, Mohd Nasrun Mohd

2017-10-01

Large portion of numbers team organization in the IBS construction sector is known are being fragmented. That is contributed from a segregation of construction activity thus create team working in virtually. Virtual team are the nature when teams are working in distributed area, across culture and time. Therefore, teams can be respond to the task without relocating to the site project and settle down a problem through information and communication technology (ICT). The emergence of virtual team are carry out by advancements in communication technologies as a medium to improve project team communication in project delivery process on IBS construction. Based on literature review from previous study and data collected from interviewing, this paper aim to identified communication challenges among project team members according to current project development practices in IBS construction project. Hence, in attempt to develop effective communication through the advantages of virtual team approach for IBS construction project. In order to ensure the data is gathered comprehensively and accurately, the data was collected from project managers by using semi structured interview method. It was found that virtual team approach could be enable competitive challenges on complexity in the construction project management process.
The brachytherapy vaginal cuff boost in patients with cervix cancer IB1-IB2 that have been treated with surgery plus pelvic radiotherapy in ION SOLCA, Guayaquil Ecuador from November 1 to October 2002

International Nuclear Information System (INIS)

Gamboa, Eugenia; Falquez, Roberto

2003-01-01

To determine if the additional vaginal cuff irradiation is necessary or not in patients with cervix cancer, stages IB 1- IB 2, that has been treated previously with radical hysterectomies and pelvic radiotherapy, to get better local control and global survival versus presence of complications. We studied 54 patients from Radiation Oncology Department of ION SOLCA Guayaquil Ecuador, with cervix cancer stages IB1 - IB2, that have been treated with surgery plus pelvic radiotherapy plus or not brachytherapy. They have been divides into two arms, group one included surgery plus Rx T (radiotherapy) plus BxT (Brachytherapy), and group two included those patients with surgery plus external RxT alone. We studied, aged, histologic type, surgery type, doses and techniques of teletherapy and brachytherapy and we analyzed the presence of complications. Conclusions: The brachytherapy vaginal cuff boost in patients with cervix cancer IB1-IB2 that have been treated with surgery plus pelvic radiotherapy is not useful to get better local control and global survival in some patients carefully chosen without desfavorable factors, because this therapy represent and increase in the complication. (The author)
Integrated Baseline System (IBS) Version 2.0: Models guide

Energy Technology Data Exchange (ETDEWEB)

1994-03-01

The Integrated Baseline System (IBS) is an emergency management planning and analysis tool being developed under the direction of the US Army Nuclear and Chemical Agency. This Models Guide summarizes the IBS use of several computer models for predicting the results of emergency situations. These include models for predicting dispersion/doses of airborne contaminants, traffic evacuation, explosion effects, heat radiation from a fire, and siren sound transmission. The guide references additional technical documentation on the models when such documentation is available from other sources. The audience for this manual is chiefly emergency management planners and analysts, but also data managers and system managers.
Rendimientos del colágeno, poliornitinas (tipos: IB, IIB y IC) y colágeno mas poliornitina IB, como substratos para el cultivo de ganglios ciliares disociados de embrión de pollo

OpenAIRE

Bustos Ruiz, M.; Alcaín Tejada, F.J.; Padilla-Alvarez, F.

1981-01-01

Dissociated ciliary ganglia of 8 days embryos were cultured in heart conditioned medium, employing differents substrata types: collagen, po¬lyornithines (types: IB,IIB and IC) and collagen plus polyornithine IB. The results from neuron survival (with and without prolongations) and non neuronal cells it obtained graphically. The polyornithines mollecular weights are discussed respect inductor factors binding for conditioned medium. The type IB is better than others types (IIB y IC), but collag...
Purification, crystallization and preliminary X-ray analysis of Enterococcus faecium aminoglycoside-2′′-phosphotransferase-Ib [APH(2′′)-Ib

Energy Technology Data Exchange (ETDEWEB)

Walanj, Rupa; Young, Paul; Baker, Heather M.; Baker, Edward N.; Metcalf, Peter [Laboratory of Structural Biology, School of Biological Sciences, University of Auckland, Auckland (New Zealand); Chow, Joseph W.; Lerner, Stephen [Division of Infectious Diseases, Wayne State University School of Medicine and VA Medical Center, Detroit, Michigan 48201 (United States); Vakulenko, Sergei [Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556 (United States); Smith, Clyde A., E-mail: csmith@slac.stanford.edu [Stanford Synchrotron Radiation Laboratory, Stanford University, Menlo Park, CA 94025 (United States); Laboratory of Structural Biology, School of Biological Sciences, University of Auckland, Auckland (New Zealand)

2005-04-01

APH(2′′)-Ib is an enzyme responsible for high-level gentamicin resistance in E. faecium isolates. Native crystals of this enzyme have been prepared and preliminary X-ray diffraction experiments have been undertaken. Bacterial resistance to the aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, APH(2′′)-Ib, has been cloned and the protein (comprising 299 amino-acid residues) expressed in Escherichia coli, purified and crystallized in the presence of 16%(w/v) PEG 3350 and gentamicin. The crystals belong to the monoclinic space group P2{sub 1}, with approximate unit-cell parameters a = 79.7, b = 58.8, c = 81.4 Å, β = 98.4°, and preliminary X-ray diffraction analysis is consistent with the presence of two molecules in the asymmetric unit. Synchrotron diffraction data to approximately 2.65 Å resolution were collected from a native APH(2′′)-Ib crystal at beamline BL9-2 at SSRL (Stanford, CA, USA). Selenium-substituted crystals have also been produced and structure determination is proceeding.
The Significance of Coordination for Industrialised Building System (IBS) Precast Concrete in Construction Industry

OpenAIRE

Fitri Othman Mohd Khairul; Wan Muhammad Wan Mohd Nurdden; Abd Hadi Nurulhudaya; Azman Mohd Azrai

2017-01-01

IBS precast concrete is construction system which is meant to improve the conventional construction process. However IBS precast concrete projects are suffering from serious problems such as cost overrun, delays and less quality of the end product. The absence of coordination is perceived as the reason for this issue. The purpose of this paper is to review the significance of coordination for IBS precast concrete in the construction industry. It if found that the fragmentation which occurs in...
Advantages and Setbacks of Industrialized Building System (IBS) Implementation: A Case Study in Sarawak

OpenAIRE

Sing Sing Wong; Ling Kung Lau

2015-01-01

Industrialized Building System (IBS) is an innovative technique adopted to increase the efficiency, quality and productivity of projects. However, these advantages are proven mainly for projects located in urban areas only. IBS is not a common practice for projects located in rural areas. Although there were studies about IBS in Malaysia about its advantages and setbacks, these studies were focusing on projects located in urban areas located in West Malaysia only. Hence, this paper aids to cl...
Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

DEFF Research Database (Denmark)

Pless, Stephan Alexander; Galpin, Jason D; Frankel, Adam

2011-01-01

Cardiac sodium channels are established therapeutic targets for the management of inherited and acquired arrhythmias by class I anti-arrhythmic drugs (AADs). These drugs share a common target receptor bearing two highly conserved aromatic side chains, and are subdivided by the Vaughan-Williams...
FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial.

Science.gov (United States)

McIntosh, Keith; Reed, David E; Schneider, Theresa; Dang, Frances; Keshteli, Ammar H; De Palma, Giada; Madsen, Karen; Bercik, Premysl; Vanner, Stephen

2017-07-01

To gain mechanistic insights, we compared effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms, the metabolome and the microbiome of patients with IBS. We performed a controlled, single blind study of patients with IBS (Rome III criteria) randomised to a low (n=20) or high (n=20) FODMAP diet for 3 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS). The metabolome was evaluated using the lactulose breath test (LBT) and metabolic profiling in urine using mass spectrometry. Stool microbiota composition was analysed by 16S rRNA gene profiling. Thirty-seven patients (19 low FODMAP; 18 high FODMAP) completed the 3-week diet. The IBS-SSS was reduced in the low FODMAP diet group (pmetabolome. In subsets of patients, FODMAPs modulate histamine levels and the microbiota, both of which could alter symptoms. NCT01829932. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Supply Chain Management on IBS Implementation in Klang Valley Construction Industry: Challenges and Issues

Science.gov (United States)

Azrizal Fauzi, Mohd; Hasim, Sulaiman; Awang, Anizah; Ridzuan, Ahmad Ruslan Mohd; Nur Yunus, Juzailah

2017-12-01

Industrialized Building System (IBS) is a system where the components of the building are manufactured in a factory and it will be transported to the site to form the structures. The supply chain management (SCM) is a system where the delivery flows of the IBS products from manufacturers to the site. The aim of this research is to identify the major challenges and to analyze the issues on IBS implementation in SCM in Klang Valley from the manufacturers perspective. The methodology used in this paper is based on primary data through questionnaire and interview. Questionnaires were sent to the Manufacturers. It can be concluded that this paper attempts to present more on the challenges and issues that those companies of manufacturers faced during their success journey in finding integration in their supply chain. The main contributions of this paper are integrating all the supply chain integration challenges and issues on IBS. Therefore, these contributions will be helpful for the organization of manufacturers and IBS players that establish the integration in their SCM.
Ribonucleotides Linked to DNA of Herpes Simplex Virus Type 1

Science.gov (United States)

Hirsch, Ivan; Vonka, Vladimír

1974-01-01

Cells of a continuous cell line derived from rabbit embryo fibroblasts were infected with herpes simplex type 1 virus (HSV-1) and maintained in the presence of either [5-3H]uridine or [methyl-3H]thymidine or 32PO43−. Nucleocapsids were isolated from the cytoplasmic fraction, partially purified, and treated with DNase and RNase. From the pelleted nucleocapsids, DNA was extracted and purified by centrifugation in sucrose and cesium sulfate gradients. The acid-precipitable radioactivity of [5-3H]uridine-labeled DNA was partially susceptible to pancreatic RNase and alkaline treatment; the susceptibility to the enzyme decreased with increasing salt concentration. No drop of activity of DNA labeled with [3H]thymidine was observed either after RNase or alkali treatment. Base composition analysis of [5-3H]uridine-labeled DNA showed that the radioactivity was recovered as uracil and cytosine. In the cesium sulfate gradient, the purified [5-3H]uridine-labeled DNA banded at the same position as the 32P-labeled DNA. The present data tend to suggest that ribonucleotide sequences are present in HSV DNA, that they are covalently attached to the viral DNA, and that they can form double-stranded structures. PMID:4364894
Topoisomerase IB of Deinococcus radiodurans resolves guanine ...

Indian Academy of Sciences (India)

2015-11-28

Nov 28, 2015 ... All the oligonucleotides men- tioned here were ... further reactions with DraTopoIB were carried out at 37°C ... of G4 DNA moves faster than unfolded and intermolecular .... for its action on intramolecular G4 DNA structure was.
Development and validation of the irritable bowel syndrome scale under the system of quality of life instruments for chronic diseases QLICD-IBS: combinations of classical test theory and generalizability theory.

Science.gov (United States)

Lei, Pingguang; Lei, Guanghe; Tian, Jianjun; Zhou, Zengfen; Zhao, Miao; Wan, Chonghua

2014-10-01

This paper is aimed to develop the irritable bowel syndrome (IBS) scale of the system of Quality of Life Instruments for Chronic Diseases (QLICD-IBS) by the modular approach and validate it by both classical test theory and generalizability theory. The QLICD-IBS was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, and quantitative statistical procedures. One hundred twelve inpatients with IBS were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability, and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, t tests and also G studies and D studies of generalizability theory analysis. Multi-trait scaling analysis, correlation, and factor analyses confirmed good construct validity and criterion-related validity when using SF-36 as a criterion. Test-retest reliability coefficients (Pearson r and intra-class correlation (ICC)) for the overall score and all domains were higher than 0.80; the internal consistency α for all domains at two measurements were higher than 0.70 except for the social domain (0.55 and 0.67, respectively). The overall score and scores for all domains/facets had statistically significant changes after treatments with moderate or higher effect size standardized response mean (SRM) ranging from 0.72 to 1.02 at domain levels. G coefficients and index of dependability (Ф coefficients) confirmed the reliability of the scale further with more exact variance components. The QLICD-IBS has good validity, reliability, responsiveness, and some highlights and can be used as the quality of life instrument for patients with IBS.
SYMPOSIUM REPORT: An Evidence-Based Approach to IBS and CIC: Applying New Advances to Daily Practice

Science.gov (United States)

Chey, William D.

2017-01-01

Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regularly publishes reviews on IBS and CIC therapies. The most recent of these reviews was published by the ACG Task Force on the Management of Functional Bowel Disorders in 2014. The key objective of this review was to evaluate the efficacy of therapies for IBS or CIC compared with placebo or no treatment in randomized controlled trials. Evidence-based approaches to managing diarrhea-predominant IBS include dietary measures, such as a diet low in gluten and fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs); loperamide; antispasmodics; peppermint oil; probiotics; tricyclic antidepressants; alosetron; eluxadoline, and rifaximin. Evidence-based approaches to managing constipation-predominant IBS and CIC include fiber, stimulant laxatives, polyethylene glycol, selective serotonin reuptake inhibitors, lubiprostone, and guanylate cyclase agonists. With the growing evidence base for IBS and CIC therapies, it has become increasingly important for clinicians to assess the quality of evidence and understand how to apply it to the care of individual patients. PMID:28729815
The sweet potato IbMYB1 gene as a potential visible marker for sweet potato intragenic vector system.

Science.gov (United States)

Kim, Cha Young; Ahn, Young Ock; Kim, Sun Ha; Kim, Yun-Hee; Lee, Haeng-Soon; Catanach, Andrew S; Jacobs, Jeanne M E; Conner, Anthony J; Kwak, Sang-Soo

2010-07-01

MYB transcription factors play important roles in transcriptional regulation of many secondary metabolites including anthocyanins. We cloned the R2R3-MYB type IbMYB1 complementary DNAs from the purple-fleshed sweet potato (Ipomoea batatas L. cv Sinzami) and investigated the expression patterns of IbMYB1 gene with IbMYB1a and IbMYB1b splice variants in leaf and root tissues of various sweet potato cultivars by reverse transcription-polymerase chain reaction. The transcripts of IbMYB1 were predominantly expressed in the purple-fleshed storage roots and they were also detectable in the leaf tissues accumulating anthocyanin pigments. In addition, transcript levels of IbMYB1 gene were up-regulated by treatment with methyl jasmonate or salicylic acid in leaf and root tissues of cv. White Star. To set up the intragenic vector system in sweet potato, we first evaluated the utilization of the IbMYB1 gene as a visible selectable marker. The IbMYB1a was transiently expressed in tobacco leaves under the control of a constitutive cauliflower mosaic virus 35S promoter, a root-specific and sucrose-inducible sporamin promoter, and an oxidative stress-inducible sweet potato anionic peroxidase2 promoter. We also showed that overexpression of IbMYB1a induced massive anthocyanin pigmentation in tobacco leaves and up-regulated the transcript levels of the structural genes in anthocyanin biosynthetic pathway. Furthermore, high-performance liquid chromatography analysis revealed that the expression of IbMYB1a led to production of cyanidin as a major core molecule of anthocyanidins in tobacco leaves. These results suggest that the IbMYB1 gene can be applicable to a visible marker for sweet potato transformation with intragenic vectors, as well as the production of anthocyanin as important nutritive value in other plant species.
Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhengming; Zhou, Jun; Zhang, Yingtao [Developmental Therapeutics Program, Karmanos Cancer Institute, Detroit, MI (United States); Bepler, Gerold, E-mail: beplerg@karmanos.org [Developmental Therapeutics Program, Karmanos Cancer Institute, Detroit, MI (United States)

2011-09-23

Highlights: {yields} Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. {yields} The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. {yields} The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. {yields} C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. {yields} The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy. -- Abstract: Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its function is indispensible in cell proliferation and DNA repair. It also serves as a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'-difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic explanation remains to be determined. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90 kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change resulting from covalent labeling by gemcitabine. It is specific to gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable in human tumor xenografts in mice treated with gemcitabine. Among mutations of seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the conformational change, while N427A, C787A, and C790A diminished it. C444A was unique since it was able to alter the conformation even in absence of gemcitabine treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine-induced conformational change of RRM1, and this stabilized RRM1
Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

International Nuclear Information System (INIS)

Chen, Zhengming; Zhou, Jun; Zhang, Yingtao; Bepler, Gerold

2011-01-01

Highlights: → Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. → The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. → The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. → C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. → The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy. -- Abstract: Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its function is indispensible in cell proliferation and DNA repair. It also serves as a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'-difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic explanation remains to be determined. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90 kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change resulting from covalent labeling by gemcitabine. It is specific to gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable in human tumor xenografts in mice treated with gemcitabine. Among mutations of seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the conformational change, while N427A, C787A, and C790A diminished it. C444A was unique since it was able to alter the conformation even in absence of gemcitabine treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine-induced conformational change of RRM1, and this stabilized RRM1 conformation has the potential to serve as a specific
The ties that bind: perceived social support, stress, and IBS in severely affected patients.

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Lackner, J M; Brasel, A M; Quigley, B M; Keefer, L; Krasner, S S; Powell, C; Katz, L A; Sitrin, M D

2010-08-01

This study assessed the association between social support and the severity of irritable bowel syndrome (IBS) symptoms in a sample of severely affected IBS patients recruited to an NIH-funded clinical trial. In addition, we examined if the effects of social support on IBS pain are mediated through the effects on stress. Subjects were 105 Rome II diagnosed IBS patients (F = 85%) who completed seven questionnaires which were collected as part of a pretreatment baseline assessment. Partial correlations were conducted to clarify the relationships between social support and clinically relevant variables with baseline levels of psychopathology, holding constant number of comorbid medical diseases, age, gender, marital status, ethnicity, and education. Analyses indicated that social support was inversely related to IBS symptom severity. Social support was positively related with less severe pain. A similar pattern of data was found for perceived stress but not quality of life impairment. Regression analyses examined if the effects of social support on pain are mediated by stress. The effects of social support on bodily pain were mediated by stress such that the greater the social support the less stress and the less pain. This effect did not hold for symptom severity, quality of life, or psychological distress. This study links the perceived adequacy of social support to the global severity of symptoms of IBS and its cardinal symptom (pain). It also suggests that the mechanism by which social support alleviates pain is through a reduction in stress levels.
The Significance of Coordination for Industrialised Building System (IBS Precast Concrete in Construction Industry

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Fitri Othman Mohd Khairul

2017-01-01

Full Text Available IBS precast concrete is construction system which is meant to improve the conventional construction process. However IBS precast concrete projects are suffering from serious problems such as cost overrun, delays and less quality of the end product. The absence of coordination is perceived as the reason for this issue. The purpose of this paper is to review the significance of coordination for IBS precast concrete in the construction industry. It if found that the fragmentation which occurs in the construction industry requires continuity of coordination due to the construction activities are intertwined in nature. Coordination is designated to assist stakeholders in completing and complementing each other with the paramount focus of achieving the objective. Proper coordination is required in delivering the desired construction product at the ideal time, cost and quality. As for the findings, the significance of coordination for IBS precast concrete can be seen through the precast concrete construction phases which consist of planning; design; manufacturing; transportation and installation/construction. These phases are meant to complement construction process with the purpose to reduce issues of fragmentation and enhance IBS precast concrete project delivery.

Critical ICT-Inhibiting Factors on IBS Production Management Processes in the Malaysia Construction Industry

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Ern, Peniel Ang Soon; Kasim, Narimah; Hamid, Zuhairi Abd; Chen, Goh Kai

2017-10-01

Industrialized Building System (IBS) is one of the approaches that had been introduced as an alternative to conventional building method where it becomes the new strategy of enhancing the sustainable construction in current industries while spearheading a huge advancement of benefits with green constructions into the existing industries. The IBS approach is actively promoted through several strategies and incentives as an alternative to conventional building methods. Extensive uptakes of modern Information Communication Technology (ICT) applications are able to support the different IBS processes for effective production. However, it is argued that ICT uptake at the organisational level is still in its infancy. This raises the importance to identify critical inhibitors which are inhibing the effective uptake of ICT in the IBS production management process. Critical inhibitors to ICT uptake were identified through questionnaire survey with the IBS industry stakeholders. The mean index and critical t-values are generated with the use of the quantitative tool, Statistical Package for Social Sciences (SPSS). The top ten priority ranked inhibitors reflect the Cost, People and Process elements to ICT uptake. High costs in acquiring the technologies and resistance to change were some main concerns from the findings.
Klinefelter's Syndrome with Seizure, Pseudohypoparathyroidism Type Ib and Multiple Endocrine Dysfunctions

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Chwen-Yi Yang

2005-12-01

Full Text Available Klinefelter's syndrome is rarely associated with hypocalcemia, especially pseudohypoparathyroidism (PHP type Ib. We describe a case of Klinefelter's syndrome associated with seizure, PHP type Ib and multiple endocrine dysfunctions. A 19-year-old Taiwanese male was admitted due to seizures with loss of consciousness. He had been diagnosed with Klinefelter's syndrome with seizure disorder and hypocalcemia 3 months previously. Physical examination revealed eunuchoidism but no osteodystrophy, while laboratory data revealed severe hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone. Chromosomal study showed 47, XXY. Osteoporosis was found on chest and abdominal radiography. Dense calcification in the cerebrum and cerebellum was shown on brain computed tomography and magnetic resonance imaging. Elevation of the patient's serum calcium level was noted after vitamin D and calcium carbonate supplements were given. Klinefelter's syndrome is rarely associated with PHP type Ib; our patient's hypocalcemia improved after long-term aggressive treatment.
Development of a Rhizoctonia solani AG1-IB Specific Gene Model Enables Comparative Genome Analyses between Phytopathogenic R. solani AG1-IA, AG1-IB, AG3 and AG8 Isolates.

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Daniel Wibberg

Full Text Available Rhizoctonia solani, a soil-born plant pathogenic basidiomycetous fungus, affects various economically important agricultural and horticultural crops. The draft genome sequence for the R. solani AG1-IB isolate 7/3/14 as well as a corresponding transcriptome dataset (Expressed Sequence Tags--ESTs were established previously. Development of a specific R. solani AG1-IB gene model based on GMAP transcript mapping within the eukaryotic gene prediction platform AUGUSTUS allowed detection of new genes and provided insights into the gene structure of this fungus. In total, 12,616 genes were recognized in the genome of the AG1-IB isolate. Analysis of predicted genes by means of different bioinformatics tools revealed new genes whose products potentially are involved in degradation of plant cell wall components, melanin formation and synthesis of secondary metabolites. Comparative genome analyses between members of different R. solani anastomosis groups, namely AG1-IA, AG3 and AG8 and the newly annotated R. solani AG1-IB genome were performed within the comparative genomics platform EDGAR. It appeared that only 21 to 28% of all genes encoded in the draft genomes of the different strains were identified as core genes. Based on Average Nucleotide Identity (ANI and Average Amino-acid Identity (AAI analyses, considerable sequence differences between isolates representing different anastomosis groups were identified. However, R. solani isolates form a distinct cluster in relation to other fungi of the phylum Basidiomycota. The isolate representing AG1-IB encodes significant more genes featuring predictable functions in secondary metabolite production compared to other completely sequenced R. solani strains. The newly established R. solani AG1-IB 7/3/14 gene layout now provides a reliable basis for post-genomics studies.
BUSINESS STRATEGY OF LARGE CONTRACTORS IN ADOPTING INDUSTRIALISED BUILDING SYSTEM (IBS: THE MALAYSIAN CASE

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FRANKY AMBON

2012-12-01

Full Text Available Industrialised Building System (IBS is the term coined by the government and industry in Malaysia to represent the construction industry and the application of prefabrication method in building construction. The purpose of this exploratory research paper is to highlight business strategy being pursued by large Malaysian contractors in adopting IBS. The paper uses case study as research method. The analysis is based primarily on cross-case analysis and pattern matching technique. The paper observes contractors which involved in IBS are part of larger holding companies in a corporate set-up include design and manufacturing subsidiaries. The companies positioned themselves as one-stop total solution provider for IBS and offer a wider range of services from design, production, and installation to clients. To become competitive and able to create total solution, contractors need to establish cluster and consortium of integrated project team by creating a partnership when and where it is needed. A vendor development programme modelled along the lines of the development of automotive industry should also be established. Future empirical studies should extensively examine these areas, especially the development of business model for contractors. The availability of this model could help to accelerate the uptake of IBS among contractors.
Towards Integrated Team Practice: A Case of Malaysian Industrialised Building System (IBS Construction Projects

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Mohd Nawi Mohd Nasrun

2014-01-01

Full Text Available Problems associated with fragmentation in the traditional construction process, such as isolation of professionals, lack of co-ordination between design and construction, and the sequential manner of its processes, has impacted on construction performance leading to a lack of integration, wastage, low productivity and efficiency. Integrated team practice is perceived as paramount. Unfortunately, there has a limitation of study focus on the dimension of fully integrated team especially for Malaysian Industrialised Building System (IBS projects. Accordingly, this research paper explores and identifies the dimension of fully integrated team from the traditional approach and conduct a validation process for implementing it in Malaysian IBS projects. The research presented uses interviews case study to obtain qualitative data. It was found that the dimension of fully integrated team from the traditional construction process could apply to the Malaysian IBS projects. Suggestions on how an integrated team practice in IBS design and construction process in order to minimise the fragmentation gaps will be concluded.
Travel Tips Help IBS Sufferers Enjoy Their Vacations

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... can feel more in control when traveling." IFFGD's travel tips include: Allow enough time in the morning to get to the airport ... Heartache 2004-0929 Norton Honored 2004-0525 IBS Travel Tips ... Real World 2001-1119 Heartburn or Heart Attack Commentary ...
Deoxynucleoside Salvage in Fission Yeast Allows Rescue of Ribonucleotide Reductase Deficiency but Not Spd1-Mediated Inhibition of Replication

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Oliver Fleck

2017-04-01

Full Text Available In fission yeast, the small, intrinsically disordered protein S-phase delaying protein 1 (Spd1 blocks DNA replication and causes checkpoint activation at least in part, by inhibiting the enzyme ribonucleotide reductase, which is responsible for the synthesis of DNA. The CRL4Cdt2 E3 ubiquitin ligase mediates degradation of Spd1 and the related protein Spd2 at S phase of the cell cycle. We have generated a conditional allele of CRL4Cdt2, by expressing the highly unstable substrate-recruiting protein Cdt2 from a repressible promoter. Unlike Spd1, Spd2 does not regulate deoxynucleotide triphosphate (dNTP pools; yet we find that Spd1 and Spd2 together inhibit DNA replication upon Cdt2 depletion. To directly test whether this block of replication was solely due to insufficient dNTP levels, we established a deoxy-nucleotide salvage pathway in fission yeast by expressing the human nucleoside transporter human equilibrative nucleoside transporter 1 (hENT1 and the Drosophila deoxynucleoside kinase. We present evidence that this salvage pathway is functional, as 2 µM of deoxynucleosides in the culture medium is able to rescue the growth of two different temperature-sensitive alleles controlling ribonucleotide reductase. However, salvage completely failed to rescue S phase delay, checkpoint activation, and damage sensitivity, which was caused by CRL4Cdt2 inactivation, suggesting that Spd1—in addition to repressing dNTP synthesis—together with Spd2, can inhibit other replication functions. We propose that this inhibition works at the point of the replication clamp proliferating cell nuclear antigen, a co-factor for DNA replication.
iB1350 no.3. Passive double confinement and SA population dose evaluation for the iB1350

International Nuclear Information System (INIS)

Sato, Takashi; Matsumoto, Keiji; Hosomi, Kenji; Iwasaki, Ryuji

2017-01-01

iB1350 stands for an innovative, intelligent and inexpensive BWR 1350. It is the first Generation III.7 reactor after the Fukushima Daiichi accident. The iB1350 uses the Mark W containment and the in-containment filtered venting system (IFVS). The Mark W containment is made of reinforced concrete and has double cylinder FP barriers. There are also IC/iPCCS pools, a fuel pool and a dryer separator (DS) pool on the top slab of the containment. These pools work as water seal for FP leakage through the top slab. Most FP such as CsI are scrubbed in the pools. The containment head is also submerged in the reactor well pool. The pool water works as shielding for radiation from the reactor core during normal operation and water seal for FP scrubbing during a severe accident. The base mat concrete is covered with the S/P and the core catcher that is also submerged with corium flooding water during an accident. Therefore, the Mark W containment has passive double confinement barriers for FP. Moreover, the IFVS works as in-containment filtered venting system that scrubs FP from the wet well (WW) and the dry well (DW). The filtered venting tank is arranged in the outer well (OW) of the Mark W containment. Even noble gases and organic iodine going through the filtered venting system are still confined inside the containment and never released directly to the environment. The IFVS uses the innovative passive containment cooling system (iPCCS) as the pre-stage heat removal system. The iPCCS has a normal open suction line from the WW. Therefore, FP are scrubbed in the S/P at first and then vented into the filtered venting tank. After the DW suction line of the iPCCS is opened all the steam is cooled and condensed in the heat exchanger. Most FP are trapped in the condensate and returned into the WW through the condensate return line of the iPCCS. Therefore, the Mark W containment has excellent FP double confinement barriers and the in-containment filtered venting system that enable
Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials.

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Lindfors, Perjohan; Unge, Peter; Arvidsson, Patrik; Nyhlin, Henry; Björnsson, Einar; Abrahamsson, Hasse; Simrén, Magnus

2012-02-01

Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units. The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year. We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (Phypnotherapy group than in the control group (Phypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers.
Genetic recombination and Cryptosporidium hominis virulent subtype IbA10G2.

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Li, Na; Xiao, Lihua; Cama, Vitaliano A; Ortega, Ynes; Gilman, Robert H; Guo, Meijin; Feng, Yaoyu

2013-10-01

Little is known about the emergence and spread of virulent subtypes of Cryptosporidium hominis, the predominant species responsible for human cryptosporidiosis. We conducted sequence analyses of 32 genetic loci of 53 C. hominis specimens isolated from a longitudinally followed cohort of children living in a small community. We identified by linkage disequilibrium and recombination analyses only limited genetic recombination, which occurred exclusively within the 60-kDa glycoprotein gene subtype IbA10G2, a predominant subtype for outbreaks in industrialized nations and a virulent subtype in the study community. Intensive transmission of virulent subtype IbA10G2 in the study area might have resulted in genetic recombination with other subtypes. Moreover, we identified selection for IbA10G2 at a 129-kb region around the 60-kDa glycoprotein gene in chromosome 6. These findings improve our understanding of the origin and evolution of C. hominis subtypes and the spread of virulent subtypes.
Validity, reliability, and factor analysis of Persian version of quality of life questionnaire for irritable bowel syndrome (IBS-QOL-34

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Nasrine Masaeli

2013-01-01

Full Text Available Background: Quality of life (QOL improvement is the main objective of treating patients with irritable bowel syndrome (IBS. This study aimed to assess the validity, reliability, and factor analysis of IBS-QOL-34 questionnaire as a common transcultural instrument for Iranian IBS patients. Materials and Methods: Two hundred and forty patients with IBS (based on gastroenterologists′ diagnosis according to ROM III criteria were referred to Digestive Health Clinic in Psychosomatic Research Center have been selected in this study. Aside with IBS-QOL-34, MOS 36-item short-form health survey (SF-36 and IBS severity index (IBSSI questionnaires were completed by the cases for determination of correlation coefficients; the data were analyzed using descriptive statistics, factor analysis, Cronbach′s alpha, Pearson correlation coefficient by Statistical Package for Social Sciences (SPSS software, version 18. Results: Total reliability of the questionnaire was reported by using Cronbach′s alpha as 0.95, ranging from 0.65 to 0.90. Correlation coefficients of concurrent implementation of IBS-QOL with SF-36 and IBSSI resulted in −0.61 and 0.64, respectively. Exploratory factor analysis using varimax rotation identified eight principle components, which will determine QOL at 67% variance. Conclusion: According to the results, IBS-QOL-34 questionnaire has good psychometric properties in the research community and can be safely used as a valid tool to assess QOL of patients with IBS for healthcare and therapeutic purposes.
Detergent-Resistant Membrane Microdomains Facilitate Ib Oligomer Formation and Biological Activity of Clostridium perfringens Iota-Toxin

National Research Council Canada - National Science Library

Hale, Martha

2004-01-01

...) were extracted with cold Triton X-100. Western blotting revealed that Ib oligomers localized in DRMs extracted from Vero, but not MRC-5, cells while monomeric Ib was detected in the detergent-soluble fractions of both cell types...
Expression of the sweetpotato R2R3-type IbMYB1a gene induces anthocyanin accumulation in Arabidopsis.

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Chu, Hyosub; Jeong, Jae Cheol; Kim, Wook-Jin; Chung, Dong Min; Jeon, Hyo Kon; Ahn, Young Ock; Kim, Sun Ha; Lee, Haeng-Soon; Kwak, Sang-Soo; Kim, Cha Young

2013-06-01

R2R3-type MYB transcription factors (TFs) play important roles in transcriptional regulation of anthocyanins. The R2R3-type IbMYB1 is known to be a key regulator of anthocyanin biosynthesis in the storage roots of sweetpotato. We previously showed that transient expression of IbMYB1a led to anthocyanin pigmentation in tobacco leaves. In this article, we generated transgenic Arabidopsis plants expressing the IbMYB1a gene under the control of CaMV 35S promoter, and the sweetpotato SPO and SWPA2 promoters. Overexpression of IbMYBa in transgenic Arabidopsis produced strong anthocyanin pigmentation in seedlings and generated a deep purple color in leaves, stems and seeds. Reverse transcription-polymerase chain reaction analysis showed that IbMYB1a expression induced upregulation of several structural genes in the anthocyanin biosynthetic pathway, including 4CL, CHI, F3'H, DFR, AGT, AAT and GST. Furthermore, overexpression of IbMYB1a led to enhanced expression of the AtTT8 (bHLH) and PAP1/AtMYB75 genes. high-performance liquid chromatography analysis revealed that IbMYB1a expression led to the production of cyanidin as a major core molecule of anthocyanidins in Arabidopsis, as occurs in the purple leaves of sweetpotato (cv. Sinzami). This result shows that the IbMYB1a TF is sufficient to induce anthocyanin accumulation in seedlings, leaves, stems and seeds of Arabidopsis plants. Copyright © Physiologia Plantarum 2012.
TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse and rat sensory neurons.

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Marie E Barabas

Full Text Available Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J DRG neurons. Approximately 80% of all small-diameter (<27 µm neurons from lumbar 1-6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79% or cinnamaldehyde (84% were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81% cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66% of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2-4% responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter responded to AITC (6% or cinnamaldehyde (4%, confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is
TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons

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Stucky, Cheryl L.

2012-01-01

Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J) DRG neurons. Approximately 80% of all small-diameter (neurons from lumbar 1–6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79%) or cinnamaldehyde (84%) were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81%) cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66%) of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2–4%) responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter) responded to AITC (6%) or cinnamaldehyde (4%), confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is functionally expressed
Learning Negotiation Policies Using IB3 and Bayesian Networks

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Nalepa, Gislaine M.; Ávila, Bráulio C.; Enembreck, Fabrício; Scalabrin, Edson E.

This paper presents an intelligent offer policy in a negotiation environment, in which each agent involved learns the preferences of its opponent in order to improve its own performance. Each agent must also be able to detect drifts in the opponent's preferences so as to quickly adjust itself to their new offer policy. For this purpose, two simple learning techniques were first evaluated: (i) based on instances (IB3) and (ii) based on Bayesian Networks. Additionally, as its known that in theory group learning produces better results than individual/single learning, the efficiency of IB3 and Bayesian classifier groups were also analyzed. Finally, each decision model was evaluated in moments of concept drift, being the drift gradual, moderate or abrupt. Results showed that both groups of classifiers were able to effectively detect drifts in the opponent's preferences.
Reduced responses of submucous neurons from irritable bowel syndrome patients to a cocktail containing histamine, serotonin, TNFα and tryptase (IBS-cocktail

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Daniela eOstertag

2015-12-01

Full Text Available Background & Aims:Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS. Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC.Methods:Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase and TNF-α (IBS-cocktail was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Results:Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P=0.097 or P=0.448. However, the neuronal response after application of the IBS-cocktail was significantly decreased (P=0.039 independent of whether diarrhea (n=12, constipation (n=5 or bloating (n=5 was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P=0.019 when compared to incubation with HC supernatant.Conclusion:We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.
A new method using insert-based systems (IBS) to improve cell behavior study on flexible and rigid biomaterials.

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Grenade, Charlotte; Moniotte, Nicolas; Rompen, Eric; Vanheusden, Alain; Mainjot, Amélie; De Pauw-Gillet, Marie-Claire

2016-12-01

In vitro studies about biomaterials biological properties are essential screening tests. Yet cell cultures encounter difficulties related to cell retention on material surface or to the observation of both faces of permeable materials. The objective of the present study was to develop a reliable in vitro method to study cell behavior on rigid and flexible/permeable biomaterials elaborating two specific insert-based systems (IBS-R and IBS-F respectively). IBS-R was designed as a specific cylindrical polytetrafluoroethylene (PTFE) system to evaluate attachment, proliferation and morphology of human gingival fibroblasts (HGFs) on grade V titanium and lithium disilicate glass-ceramic discs characteristics of dental prostheses. The number of cells, their covering on discs and their morphology were determined from MTS assays and microscopic fluorescent images after 24, 48 and 72 h. IBS-F was developed as a two components system to study HGFs behavior on guided bone regeneration polyester membranes. The viability and the membrane barrier effect were evaluated by metabolic MTS assays and by scanning electron microscopy. IBS-R and IBS-F were shown to promote (1) easy and rapid handling; (2) cell retention on biomaterial surface; (3) accurate evaluation of the cellular proliferation, spreading and viability; (4) use of non-toxic material. Moreover IBS-F allowed the study of the cell migration through degradable membranes, with an access to both faces of the biomaterial and to the bottom of culture wells for medium changing.
The impact of abuse and mood on bowel symptoms and health-related quality of life in irritable bowel syndrome (IBS).

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Kanuri, N; Cassell, B; Bruce, S E; White, K S; Gott, B M; Gyawali, C P; Sayuk, G S

2016-10-01

Irritable bowel syndrome (IBS) is a common abdominal pain disorder without an organic explanation. Abuse histories (physical, sexual, emotional) are prevalent in IBS. While abuse relates to mood disorders (depression and anxiety) also common in IBS, the influence of abuse on gastrointestinal (GI) symptoms and health-related quality of life (HRQOL) and its independence from psychological symptom comorbidity has not been studied. Consecutive GI outpatients completed the ROME III Research Diagnostic Questionnaire and questionnaires on trauma (Life-Stress Questionnaire), mood (Beck Depression/Anxiety Inventories), somatic symptoms (PHQ-12), and HRQOL (SF-36). Current GI symptom severity and bother were assessed using 10-cm Visual Analog Scales. 272 ROME-defined IBS (47.6 ± 0.9 years, 81% female) and 246 non-FGID (51.6 ± 1.0 years, 65% female) subjects participated. IBS patients reported greater rates of physical, sexual, and emotional abuse (p IBS with abuse. Abuse effects were additive, with greater IBS symptom severity and poorer HRQOL noted in cases with multiple forms of abuse. Mediation analyses suggested that abuse effects on GI symptoms and HRQOL were partially mediated by mood. Abuse experiences common among IBS sufferers are associated with reports of greater GI symptoms and poorer HRQOL, particularly in those with multiple forms of abuse; this relationship may be partially mediated by concomitant mood disturbances. © 2016 John Wiley & Sons Ltd.
Invasive cervical carcinoma (stage IB-IIB): assessment with MR imaging

International Nuclear Information System (INIS)

Sironi, S.; Del Maschio, A.; Belloni, C.; Taccagni, L.

1990-01-01

In patients with cervical carcinoma the selection of the optimal therapy depends on the precise preoperative assessment of the extent of disease. Currently, decisions regarding the management of these patients are made on the basis of clinical (FIGO) staging that has 50% mean error rate. To investigate the value of MR imaging in staging patients with invasive cervical cancer, we performed 25 MR examinations on 23 patients with histologic diagnosis of cervical cancer. All patients were clinically considered as having stage IB or IIB disease and underwent radical hysterectomy, providing specimens for pathologic correlation. The overall accuracy of MR imaging in staging cervical carcinoma (stage IB-IIB) was 78.1%. MR imaging seems to be the most reliable preoperative modality for staging invasive cervical cancer

A fluorimetric readout reporting the kinetics of nucleotide-induced human ribonucleotide reductase oligomerization.

Science.gov (United States)

Fu, Yuan; Lin, Hongyu; Wisitpitthaya, Somsinee; Blessing, William A; Aye, Yimon

2014-11-24

Human ribonucleotide reductase (hRNR) is a target of nucleotide chemotherapeutics in clinical use. The nucleotide-induced oligomeric regulation of hRNR subunit α is increasingly being recognized as an innate and drug-relevant mechanism for enzyme activity modulation. In the presence of negative feedback inhibitor dATP and leukemia drug clofarabine nucleotides, hRNR-α assembles into catalytically inert hexameric complexes, whereas nucleotide effectors that govern substrate specificity typically trigger α-dimerization. Currently, both knowledge of and tools to interrogate the oligomeric assembly pathway of RNR in any species in real time are lacking. We therefore developed a fluorimetric assay that reliably reports on oligomeric state changes of α with high sensitivity. The oligomerization-directed fluorescence quenching of hRNR-α, covalently labeled with two fluorophores, allows for direct readout of hRNR dimeric and hexameric states. We applied the newly developed platform to reveal the timescales of α self-assembly, driven by the feedback regulator dATP. This information is currently unavailable, despite the pharmaceutical relevance of hRNR oligomeric regulation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Prevalence of mood and anxiety disorder in self reported irritable bowel syndrome (IBS). An epidemiological population based study of women.

Science.gov (United States)

Mykletun, Arnstein; Jacka, Felice; Williams, Lana; Pasco, Julie; Henry, Margaret; Nicholson, Geoffrey C; Kotowicz, Mark A; Berk, Michael

2010-08-05

Irritable bowel syndrome (IBS) is commonly regarded as a functional disorder, and is hypothesized to be associated with anxiety and depression. This evidence mainly rests on population-based studies utilising self-report screening instruments for psychopathology. Other studies applying structured clinical interviews are generally based on small clinical samples, which are vulnerable to biases. The extant evidence base for an association between IBS and psychopathology is hence not conclusive. The aim of this study was therefore to re-examine the hypothesis using population-based data and psychiatric morbidity established with a structured clinical interview. Data were derived from a population-based epidemiological study (n = 1077). Anxiety and mood disorders were established using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP) and the General Health Questionnaire (GHQ-12). Current and lifetime IBS was self-reported. Hypertension and diabetes were employed as comparison groups as they are expected to be unrelated to mental health. Current IBS (n = 69, 6.4%) was associated with an increased likelihood of current mood and/or anxiety disorders (OR = 2.62, 95%CI 1.49 - 4.60). Half the population reporting a lifetime IBS diagnosis also had a lifetime mood or anxiety disorder. Exploratory analyses demonstrated an increased prevalence of IBS across most common anxiety and mood disorders, the exception being bipolar disorder. The association with IBS and symptoms load (GHQ-12) followed a curved dose response pattern. In contrast, hypertension and diabetes were consistently unrelated to psychiatric morbidity. IBS is significantly associated with anxiety and mood disorders. This study provides indicative evidence for IBS as a disorder with a psychosomatic aspect.
Prevalence of mood and anxiety disorder in self reported irritable bowel syndrome (IBS. An epidemiological population based study of women

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Mykletun Arnstein

2010-08-01

Full Text Available Abstract Background Irritable bowel syndrome (IBS is commonly regarded as a functional disorder, and is hypothesized to be associated with anxiety and depression. This evidence mainly rests on population-based studies utilising self-report screening instruments for psychopathology. Other studies applying structured clinical interviews are generally based on small clinical samples, which are vulnerable to biases. The extant evidence base for an association between IBS and psychopathology is hence not conclusive. The aim of this study was therefore to re-examine the hypothesis using population-based data and psychiatric morbidity established with a structured clinical interview. Methods Data were derived from a population-based epidemiological study (n = 1077. Anxiety and mood disorders were established using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP and the General Health Questionnaire (GHQ-12. Current and lifetime IBS was self-reported. Hypertension and diabetes were employed as comparison groups as they are expected to be unrelated to mental health. Results Current IBS (n = 69, 6.4% was associated with an increased likelihood of current mood and/or anxiety disorders (OR = 2.62, 95%CI 1.49 - 4.60. Half the population reporting a lifetime IBS diagnosis also had a lifetime mood or anxiety disorder. Exploratory analyses demonstrated an increased prevalence of IBS across most common anxiety and mood disorders, the exception being bipolar disorder. The association with IBS and symptoms load (GHQ-12 followed a curved dose response pattern. In contrast, hypertension and diabetes were consistently unrelated to psychiatric morbidity. Conclusions IBS is significantly associated with anxiety and mood disorders. This study provides indicative evidence for IBS as a disorder with a psychosomatic aspect.
[Synthesis of exo-β-glucosaminidase BY FUNGUS Penicillium sp. IB-37-2].

Science.gov (United States)

Aktuganov, G E; Galimzyanova, N F; Teregulova, G A; Melentjev, A I

2016-01-01

A new strain Penicillium sp. IB-37-2, which actively hydrolyzes chitosan (SD ∼80–85%) but possesses low activity against colloidal chitin, was isolated. The fungus was observed to have a high level chitosanase biosynthesis (1.5–3.0 U/mL) during submerged cultivation at 28°C, with a pH of 3.5–7.0 and 220 rpm in nutrient media containing chitosan or chitin from shells of crabs. Purification of the chitosanase enzyme complex from Penicillium sp. IB-37-2 by ultrafiltration and hydrophobic chromatography, followed by denaturing electrophoresis, revealed two predominant proteins with molecular weights of 89 and 41 kDa. The purified enzyme complex demonstrated maximal activity (maximal rate of hydrolysis of dissolved chitosan) and stability at 50–55°C and a pH of 3.5–4.0. The enzyme preparation also hydrolyzed laminarin, β-(1,3)-(1,4)-glycan, and colloidal chitin. Exohydrolysis of chitosan by the preparation isolated from Penicillium sp. IB-37-2 resulted in the formation of single product, D-glucosamine.
Al-Shāṭibīs sufismekritik:

DEFF Research Database (Denmark)

Riexinger, Martin Thomas

2016-01-01

The faqīh (Islamic legal scholar) al-Shāṭibī (d. 1388) from Granada is primarily known for his innovative approach within the field of legal theory (uṣūl al-fiqh). However, he dedicated much attention to the criticism of sufism. But like other Islamic scholars who opposed Sufism he did...
BK polyomavirus genotypes Ia and Ib1 exhibit different biological properties in renal transplant recipients.

Science.gov (United States)

Varella, Rafael B; Zalona, Ana Carolina J; Diaz, Nuria C; Zalis, Mariano G; Santoro-Lopes, Guilherme

2018-01-02

BK polyomavirus (BKV) is an opportunist agent associated with nephropathy (BKVAN) in 1-10% of kidney transplant recipients. BKV is classified into genotypes or subgroups according to minor nucleotidic variations with unknown biological implications. Studies assessing the possible association between genotypes and the risk of BKVAN in kidney transplant patients have presented conflicting results. In these studies, genotype Ia, which is highly prevalent in Brazil, was less frequently found and, thus, comparative data on the biological properties of this genotype are lacking. In this study, BKV Ia and Ib1 genotypes were compared according to their viral load, genetic evolution (VP1 and NCCR) - in a cohort of renal transplant recipients. The patients infected with Ia (13/23; 56.5%) genotype exhibited higher viral loads in urine [>1.4 log over Ib1 (10/23; 43.5%); p=0.025]. In addition, genotype Ia was associated with diverse mutations at VP1 loops and sites under positive selection outside loops, which were totally absent in Ib1. Although the number of viremic patients was similar, the three patients who had BK nephropathy (BKVAN) were infected with Ia genotype. NCCR architecture (ww or rr) were not distinctive between Ia and Ib1 genotypes. Ia genotype, which is rare in other published BKV cohorts, presented some diverse biological properties in transplanted recipients in comparison to Ib1. Copyright © 2017 Elsevier B.V. All rights reserved.
Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis

International Nuclear Information System (INIS)

Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.; Murphy, W.H.

1978-01-01

The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log 10 PD 50 values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplanted Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain
A new method using insert-based systems (IBS) to improve cell behavior study on flexible and rigid biomaterials

OpenAIRE

Grenade, Charlotte; Moniotte, Nicolas; Rompen, Eric; Vanheusden, Alain; Mainjot, Amélie; De Pauw-Gillet, Marie-Claire

2016-01-01

In vitro studies about biomaterials biological properties are essential screening tests. Yet cell cultures encounter difficulties related to cell retention on material surface or to the observation of both faces of permeable materials. The objective of the present study was to develop a reliable in vitro method to study cell behavior on rigid and flexible/permeable biomaterials elaborating two specific insert-based systems (IBS-R and IBS-F respectively). IBS-R was designed as a specific cylin...
Platelet apoptosis by cld-induced glycoportein Ibα clustering

DEFF Research Database (Denmark)

van der Wal, Dianne E; Du, V X; Lo, KS

2010-01-01

Summary Background: Cold-storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα-distribution indicative of receptor clustering and initiates thromboxane A2-formation. GPIbα is associated with 14-3-3 proteins, which contribute to GPIbα-signaling and in nucleated cells...
Proteomics analysis of IBS-D with spleen and kidney yang deficiency

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Yijie Li

2017-01-01

Conclusion: These data suggest that SKYD/IBS-D pathophysiology likely involves inflammation, cell growth, apoptosis, stress granule formation, immune activation, loss of epithelial cell integrity, and visceral hypersensitivity.
MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1

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Qiuke Hou

2017-12-01

Full Text Available Background/Aims: Irritable bowel syndrome with diarrhoea (IBS-D is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii verify in vitro whether occludin (OCLN and zonula occludens 1 (ZO1/TJP1 were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. Methods: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. Results: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further
EVALUATION OF LOW URINARY TRACT SYMPTOMS AND ERECTILE FUNCTION IN MEN WITH IRRITABLE BOWEL SYNDROME(IBS

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Dogan Atilgan

2014-06-01

Conclusion: IBS, is a major health problem with serious psychosocial side effects and significantly reduces patients quality of life. LUTS and ED may be seen frequently in patients with IBS. Therefore, during menagement of these patients multydiciplinary assesment should be kept in mind. [J Contemp Med 2014; 4(2.000: 64-68
Enhanced mutagenicity of low doses of alkylating agents and UV-light by inhibition of ribonucleotide reductase

International Nuclear Information System (INIS)

Jenssen, D.

1986-01-01

Monofunctional alkylating agents and UV-light are potent inducers of gene mutations in mammalian cells. Most data on these agent are supporting the idea that 0/sup 6/-alkylguanine is the dominating lesion responsible for the mutations induced by the alkylating agents and thymine-dimers in the case of UV-light. However, little is known about the mutagenic fate of these lesions during the replicative process. This is an essential issue to investigate not the least because of quantitative aspects. By investigating the factors affecting the mutagenic yield of these lesions, they hope to get further information on the mechanisms(s) involved. To study this, a system was applied which involves synchronized V79 Chinese hamster cells and inhibitors of the replication process. By applying hydroxyurea (HU), as inhibitor of the ribonucleotide reductase (RNR) step in DNA synthesis, the effect of nucleotide pool imbalance has been studied at the HGPRT-locus using V79 Chinese hamster cells
Motivational Factors on Adopting Modular Coordination Concept in Industrialized Building System (IBS

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Yunus Riduan

2016-01-01

Full Text Available Modular coordination (MC is recognized as a tool towards rationalization and industrialization. The implementation of MC concept in the design stage may improve the constructability and construction time. However, the implementation of MC in Industrialized Building System (IBS implementation is still low compare to other developed countries such as the United Kingdom, Sweden and Japan. This paper examined the interrelationship between motivational factors of stakeholders in adopting MC concept using Interpretative Structural Modeling (ISM. Questionnaire survey was engaged in this study to identify significant motivational factors. Then, semi-structure interviews were used to collect qualitative data. ISM was adopted to build relationship between factors and develop an initial model to promote the adoption of MC in IBS construction. Seven (7 significant motivational factors were identified in this research namely 1 ‘stakeholder’s commitment’, 2 ‘reduce site disruption’, 3 ‘increase productivity’, 4 ‘high skilled workers’, 5 ‘site sustainability (environment, economy and social benefits’ 6 ‘standardization’ and 7 ‘enabling ‘open building’ concept’. The result using Matrice d’Impacts Croises Multiplication Applique an Clasment (MICMAC shows that there are three factors can be categorized as Independent / Driving Factors namely ‘stakeholder’s commitment’, ‘standardization’ and ‘enabling “open building” concept’. These factors should be explored in details to enhance the adoption of IBS in Malaysia. The findings provide a very good platform for a further research in formulating an efficient solution to promote MC concept adoption among the stakeholders. This scenario will improve the deliverables of IBS construction and eliminate negative perception in its implementation.
A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D.

Science.gov (United States)

Eswaran, Shanti L; Chey, William D; Han-Markey, Theresa; Ball, Sarah; Jackson, Kenya

2016-12-01

There has been an increasing interest in the role of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) in irritable bowel syndrome (IBS). We report results from the first randomized controlled trial of the low FODMAP diet in US adults with IBS and diarrhea (IBS-D). The objectives were to compare the efficacy of the low FODMAP diet vs. a diet based upon modified National Institute for Health and Care Excellence guidelines (mNICE) on overall and individual symptoms in IBS-D patients. This was a single-center, randomized-controlled trial of adult patients with IBS-D (Rome III) which compared 2 diet interventions. After a 2-week screening period, eligible patients were randomized to a low FODMAP or mNICE diet for 4 weeks. The primary end point was the proportion of patients reporting adequate relief of IBS-D symptoms ≥50% of intervention weeks 3-4. Secondary outcomes included a composite end point which required response in both abdominal pain (≥30% reduction in mean daily pain score compared with baseline) and stool consistency (decrease in mean daily Bristol Stool Form of ≥1 compared with baseline), abdominal pain and stool consistency responders, and other key individual IBS symptoms assessed using daily questionnaires. After screening, 92 subjects (65 women, median age 42.6 years) were randomized. Eighty-four patients completed the study (45 low FODMAP, 39 mNICE). Baseline demographics, symptom severity, and nutrient intake were similar between groups. Fifty-two percent of the low FODMAP vs. 41% of the mNICE group reported adequate relief of their IBS-D symptoms (P=0.31). Though there was no significant difference in the proportion of composite end point responders (P=0.13), the low FODMAP diet resulted in a higher proportion of abdominal pain responders compared with the mNICE group (51% vs. 23%, P=0.008). Compared with baseline scores, the low FODMAP diet led to greater reductions in average daily scores of abdominal pain, bloating
Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

Science.gov (United States)

Melis, D; Balivo, F; Della Casa, R; Romano, A; Taurisano, R; Capaldo, B; Riccardi, G; Monsurrò, M R; Parenti, G; Andria, G

2008-12-01

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.
Cell death in response to antimetabolites directed at ribonucleotide reductase and thymidylate synthase

Science.gov (United States)

Asuncion Valenzuela, Malyn M; Castro, Imilce; Gonda, Amber; Diaz Osterman, Carlos J; Jutzy, Jessica M; Aspe, Jonathan R; Khan, Salma; Neidigh, Jonathan W; Wall, Nathan R

2015-01-01

New agent development, mechanistic understanding, and combinatorial partnerships with known and novel modalities continue to be important in the study of pancreatic cancer and its improved treatment. In this study, known antimetabolite drugs such as gemcitabine (ribonucleotide reductase inhibitor) and 5-fluorouracil (thymidylate synthase inhibitor) were compared with novel members of these two drug families in the treatment of a chemoresistant pancreatic cancer cell line PANC-1. Cellular survival data, along with protein and messenger ribonucleic acid expression for survivin, XIAP, cIAP1, and cIAP2, were compared from both the cell cytoplasm and from exosomes after single modality treatment. While all antimetabolite drugs killed PANC-1 cells in a time- and dose-dependent manner, neither family significantly altered the cytosolic protein level of the four inhibitors of apoptosis (IAPs) investigated. Survivin, XIAP, cIAP1, and cIAP2 were found localized to exosomes where no significant difference in expression was recorded. This inability for significant and long-lasting expression may be a reason why pancreatic cancer lacks responsiveness to these and other cancer-killing agents. Continued investigation is required to determine the responsibilities of these IAPs in their role in chemoresistance in pancreatic adenocarcinoma. PMID:25767396
Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: a retrospective analysis

International Nuclear Information System (INIS)

Zhang, Fan; Cheng, Yi-Kan; Li, Wen-Fei; Guo, Rui; Chen, Lei; Sun, Ying; Mao, Yan-Ping; Zhou, Guan-Qun; Liu, Xu; Liu, Li-Zhi; Lin, Ai-Hua; Tang, Ling-Long; Ma, Jun

2015-01-01

To assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT). We retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT. Greatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3–57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT. Level Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation
A Measure of Suffering in relation to Anxiety and Quality of Life in IBS Patients: Preliminary Results

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Sanda Pletikosić Tončić

2017-01-01

Full Text Available Irritable bowel syndrome (IBS is a chronic gastrointestinal (GI disorder with a severe impact on quality of life (QoL. We explored the relationship of a visual measure of suffering, the PRISM-RII, with quality of life (QoL and anxiety measures in IBS patients. Participants were 44 IBS patients who completed several questionnaires and kept a symptom diary for two weeks. The measures used were PRISM-RII (self-illness separation (SIS; illness perception measure (IPM; IBS-36 (IBS health related QoL; SF-36 (physical and mental health related QoL; State-Trait Anxiety Inventory (STAI-T; Visceral Sensitivity Index (VSI; GI-specific anxiety; and a symptom diary. SIS was negatively correlated to VSI, while IPM was negatively correlated to SIS and the physical component of SF-36 and positively to VSI and symptom severity. We found significant differences between participants who perceive their illness as small and those who perceive it as medium in SIS, symptom severity, VSI, and the mental component of SF-36. Participants, who perceived their illness as small, represented their illness as more distant, showed lower average symptom severity, and had lower GI-specific anxiety and higher QoL. The results indicate that IPM and SIS can be useful in discriminating patients with more prominent psychological difficulties and QoL impairment.
Nereididae (Annelida, Polychaeta colectados en las campañas “Fauna II, III, IV” (Proyecto “Fauna Ibérica” y catálogo de las especies conocidas para el ámbito ibérico

Directory of Open Access Journals (Sweden)

Núñez, Jorge

2002-06-01

Full Text Available A check-list of 19 polychaetes species belonging to the family Nereididae is made, from the material collected during the Cruises “Fauna Ibérica II, III and IV”. Of these, data on the sampling stations are given. As a result of the identification of nereidid specimens, three new records for the Iberian Peninsula were found, Ceratonereis vittata Langerhans, 1884, Neanthes rubicunda (Ehlers, 1864 and Nereis perivisceralis Claparède, 1864. An updated catalogue is also presented, with the 36 nereidid species known for the Iberian Peninsula.

Se confecciona una lista de 19 especies de poliquetos pertenecientes a la familia Nereididae, a partir del material colectado en las campañas oceanográficas “Fauna Ibérica II, III y IV”. De éstas, se aportan datos sobre las estaciones de muestreo. De todo el material identificado son nuevas citas para la Península Ibérica tres especies: Ceratonereis vittata Langerhans, 1884, Neanthes rubicunda (Ehlers, 1864 y Nereis perivisceralis Claparède, 1864. También se aporta un catálogo actualizado de los neréididos conocidos para la Península Ibérica compuesto por 36 especies.

Reports of "satisfactory relief" by IBS patients receiving usual medical care are confounded by baseline symptom severity and do not accurately reflect symptom improvement.

Science.gov (United States)

Whitehead, William E; Palsson, Olafur S; Levy, Rona L; Feld, Andrew D; VonKorff, Michael; Turner, Marsha

2006-05-01

Treatment trials for irritable bowel syndrome (IBS) usually define a responder as a patient who reports satisfactory relief or adequate relief of symptoms at the end of the trial. However, these measures have not been adequately validated. (1) Compare a binary satisfactory relief measure to alternative ways of defining a treatment responder. (2) Determine whether baseline IBS symptom severity or psychological distress influence the sensitivity of these outcome measures. A total of 350 patients (81% females, average age 50 yr) who had a medical diagnosis of IBS and satisfied Rome II criteria, were recruited from Group Health Cooperative of Puget Sound. At baseline the Irritable Bowel Severity Scale (IBSS) was used to assess symptom severity and to classify patients as mild, moderate, or severe. Psychological distress and IBS-specific quality of life (IBS-QOL) were also assessed. After 6 months treatment with standard medical care, IBSS and IBS-QOL were reassessed, and patients were asked whether they had experienced satisfactory relief and whether they were somewhat or markedly better. Initial severity of IBS significantly affected the proportion who reported satisfactory relief (mild, 72%; moderate, 53%; severe, 44%) and the proportion who were somewhat or markedly better (mild, 62%; moderate, 44%; severe, 38%), but did not affect the proportion with a 50% reduction in symptoms (mild, 26%; moderate, 25%; severe, 23%). Although mild patients were the most likely to report satisfactory relief, they showed no average decrease in symptom severity or improvement in IBS-QOL. Conversely, severe patients, who were the least likely to report satisfactory relief, had the largest reductions in IBS symptom severity and the largest improvements in IBS-QOL. Psychological distress had no significant effect on the responder rate after adjusting for IBS symptom severity. These data from a descriptive study suggest that satisfactory relief is confounded with initial IBS symptom
Neuroimmune interactions at different intestinal sites are related to abdominal pain symptoms in children with IBS.

Science.gov (United States)

Di Nardo, G; Barbara, G; Cucchiara, S; Cremon, C; Shulman, R J; Isoldi, S; Zecchi, L; Drago, L; Oliva, S; Saulle, R; Barbaro, M R; Stronati, L

2014-02-01

Neuroimmune interactions and inflammation have been proposed as factors involved in sensory-motor dysfunction and symptom generation in adult irritable bowel syndrome (IBS) patients. In children with IBS and healthy controls, we measured ileocolonic mast cell infiltration and fecal calprotectin and evaluated the relationships between these parameters and abdominal pain symptoms and stooling pattern. Irritable bowel syndrome patients diagnosed according to Pediatric Rome III criteria and healthy controls kept a 2-week pain/stooling diary. Ileocolonic mucosal mast cells (MC) and MC in close proximity to nerve fibers (MC-NF) were identified immunohistochemically and quantified. Fecal calprotectin concentration was measured. 21 IBS patients and 10 controls were enrolled. The MC-NF count was significantly higher in the ileum (p = 0.01), right colon (p = 0.04), and left colon (p Abdominal pain intensity score correlated with ileal MC count (r(s) = 0.47, p = 0.030) and right colon MC-NF count (r(s) = 0.52, p = 0.015). In addition, children with IBS with >3 abdominal pain episodes/week had greater ileal (p = 0.002) and right colonic (p = 0.01) MC counts and greater ileal (p = 0.05) and right colonic (p = 0.016) MC-NF counts than children with less frequent pain. No relationship was found between MC and MC-NF and fecal calprotectin or stooling pattern. Mast cells-nerve fibers counts are increased in the ileocolonic mucosa of children with IBS. Mast cells and MC-NF counts are related to the intensity and frequency of abdominal pain. © 2013 John Wiley & Sons Ltd.
Phenotyping of subjects for large scale studies on patients with IBS

NARCIS (Netherlands)

Boeckxstaens, G. E.; Drug, V.; Dumitrascu, D.; Farmer, A. D.; Hammer, J.; Hausken, T.; Niesler, B.; Pohl, D.; Pojskic, L.; Polster, A.; Simren, M.; Goebel-Stengel, M.; van Oudenhove, L.; Vassallo, M.; Wensaas, K.-A.; Aziz, Q.; Houghton, L. A.

2016-01-01

Background Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity,
STRATEGI PEMASARAN TERHADAP PENJUALAN PRODUK TABUNGAN IB HASANAH DI PT. BANK NEGARA INDONESIA SYARIAH KANTOR CABANG JAKARTA BARAT

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Raden Ajeng Entaresmen

2017-02-01

Full Text Available BNI Syariah branch office in West Jakarta has one of funding products that Savings iB Hasanah useful for pure investment vehicles Shariah compliance, where customers can make deposits and withdrawals of cash very easily. In marketing this product, BNI Syariah use 2 pattern to implement a marketing strategy that intensification patterns for customers who already have a product BNI Syariah and extension patterns for prospective customers at other banks that have not used that product at BNI Syariah. Besides, in general BNI Syariah has some marketing strategies that include 9P is Process, People, Product, Price, Place, Promotion, Partners, Presentation, and Passion. Employees who are experts in marketing their products to barriers such as the lack of make Savings iB Hasanah customers, how to services and lack of staff was quick to respond, competition between conventional banks and Islamic banks BNI Syariah office supplies in some areas. Keywords : Marketing strategy, Savings iB Hasanah, Product marketing barriers savings iB Hasanah
Prevalence of quinolone resistance determinant qnrA6 among broad- and extended-spectrum beta-lactam-resistant Proteus mirabilis and Morganella morganii clinical isolates with sul1-type class 1 integron association in a Tunisian Hospital.

Science.gov (United States)

Mahrouki, Sihem; Perilli, Mariagrazia; Bourouis, Amel; Chihi, Hela; Ferjani, Mustapha; Ben Moussa, Mohamed; Amicosante, Gianfranco; Belhadj, Omrane

2013-08-01

The aim of this study was to investigate the prevalence and the emergence of plasmid-mediated quinolone resistance among broad-spectrum beta-lactam-resistant Proteus mirabilis and Morganella morganii clinical isolates recovered in the Military Hospital in Tunisia. Of 200 strains examined, 50 exhibited resistance to quinolones. Quinolone resistance determinants (qnr and aac(6')-Ib-cr) were characterized by multiplex PCR and sequencing. Chromosomal quinolone resistance mutations in the quinolone resistance-determining region (QRDR) and class 1 integron characterization were analysed by PCR and sequencing. The clonal relationship between the isolates was studied by pulsed-field gel electrophoresis (PFGE). Fourteen isolates harboured qnrA6 and among them 8 (57%) were extended-spectrum beta-lactamase (ESBL) producers, whilst 12 (85%) isolates harboured blaDHA-1. Mutations in the QRDR were detected in gyrA (Ser83Ile, Glu87Lys), gyrB (Ser464Phe), and parC (Ser80Ile). qnrA6 and blaDHA-1 genes were found embedded in complex sul1-type class 1 integrons. A gene cassette carrying aac(6')-Ib-cr was found located in the class 1 integron upstream of the qacEΔ1 gene. According to the PFGE analysis, the isolates were clonally unrelated. This is the first description in North Africa of class 1 integrons carrying blaDHA-1, qnrA6 gene, and aac(6')-Ib-cr determinants in clinical strains of Proteus mirabilis and Morganella morganii.
Colm Tóibín and Post-Nationalist Ireland: Redefining Family Through Alterity

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José Carregal-Romero

2012-03-01

Full Text Available In nationalist Ireland, definitions of family have traditionally followed a hetero-normative and sexist pattern whereby husbands and wives fulfilled deeply unequal roles. Moreover, the notion of family has been too often idealized as a site of peace and unconditional love, its members being united by unbreakable bonds of mutual affection. In Colm Tóibín’s fiction, “traditional” families tend to be dysfunctional and the relations between their members become strained because of emotional distance, regrets and distrust. However, Tóibín’s protagonists do find their sense of home and domesticity outside the traditional parameters of family. In this regard, this paper intends to analyze the manner in which Tóibín de-stabilizes canonical definitions through his revisionist agenda and his inscription of alternative forms of family. In order to shed light on these points, I shall refer to his novels The South (1990, The Heather Blazing (1992, The Blackwater Lightship (1999 and his short stories “A Long Winter” (Mothers and Sons, 2006, “Two Women” and “The Street” (The Empty Family, 2010.
Revisión de epigrafía Ibérica turolense

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Ignacio SIMÓN CORNAGO

2012-07-01

Full Text Available El objetivo de este artículo es revisar varias inscripciones ibéricas procedentes de tres yacimientos de la provincia de Teruel: un grafito grabado sobre un adobe de San Antonio de Calaceite, recuperado en las excavaciones de Juan Cabré y que se conserva en el Museo Arqueológico de Barcelona; una posible inscripción bilingüe de Azaila, incisa sobre un pequeño canto rodado, actualmente perdido y que presenta una notable similitud con otro descubierto en La Moleta dels Frares (Castellón; y, finalmente, dos estelas de La Iglesuela del Cid, reutilizadas como material de construcción en la ermita de Nuestra Señora del Cid, donde también se conservan una tercera inscripción ibérica y un conjunto de epígrafes latinos.
Descending pain modulation in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

Science.gov (United States)

Chakiath, Rosemary J; Siddall, Philip J; Kellow, John E; Hush, Julia M; Jones, Mike P; Marcuzzi, Anna; Wrigley, Paul J

2015-12-10

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. While abdominal pain is a dominant symptom of IBS, many sufferers also report widespread hypersensitivity and present with other chronic pain conditions. The presence of widespread hypersensitivity and extra-intestinal pain conditions suggests central nervous dysfunction. While central nervous system dysfunction may involve the spinal cord (central sensitisation) and brain, this review will focus on one brain mechanism, descending pain modulation. We will conduct a comprehensive search for the articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2015, that report on any aspect of descending pain modulation in irritable bowel syndrome. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and, if possible, a meta-analysis will be carried out. The systematic review outlined in this protocol aims to summarise current knowledge regarding descending pain modulation in IBS. PROSPERO CRD42015024284.
Intensi Berwirausaha Pada Pelajar Kelas Ekstrakurikuler Kewirausahaan SMAK St. Louis 1 Di Surabaya [The Entrepreneurship Intentions of Entrepreneurship Students in Extracurricular Classes at SMAK St. Louis 1 in Surabaya

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Gregorius Romaryo Tanubun

2016-10-01

Full Text Available The purpose of this research is to understand: (1 the influence of family on entrepreneur intention; (2 the impact of entrepreneurial study on entrepreneur intention; and (3 the difference in entrepreneurial intention among an entrepreneurial class of students at SMAK St. Louis 1 in Surabaya. The population of this research is students of an entrepreneurial class at SMAK St. Louis 1 in Surabaya. The sampling technique used is census with 40 respondents as samples. This research is a quantitative research with multiple regression method and independent samples t-test with SPSS 23 as analysis tool. The findings of this research indicate that: (1 family variable (K reacts significantly negative towards entrepreneurial intention (IB, (2 entrepreneurial education variable (PK reacts significantly towards entrepreneurial intention (IB, and (3 no difference is found between men and women.
A review on the current issues and barriers of Industrialised Building System (IBS) adoption in Malaysia’s construction industry

Science.gov (United States)

Amin, M. A. Mohd; Abas, N. H.; Shahidan, S.; Rahmat, M. H.; Suhaini, N. A.; Nagapan, S.; Rahim, R. Abdul

2017-11-01

Malaysia considers the construction industry as one of the main contributors to its Gross Domestic Product (GDP). However, there are some unresolved issues arising from the ongoing and widespread adoption of the conventional method of construction such as the resultant fragmentation of the industry itself; delays in production and delivery time of unnecessary wastages and lack of sustainability practice. Malaysian Government has been continuously encouraging the industry to use, partly or if not wholly, the Industrialized Building System (IBS), which is considered to be an important part of sustainable construction initiative. IBS was introduced to Malaysia as the solution to issues related to dependencies of foreign workers, raising demand for affordable accommodations and improving image, quality and productivity of construction industry. However, the IBS adoption in Malaysia remains low. This paper presents the review of the current issues and barriers of IBS adoption in Malaysian construction industry.
Regulation of Small Mitochondrial DNA Replicative Advantage by Ribonucleotide Reductase in Saccharomyces cerevisiae

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Elliot Bradshaw

2017-09-01

Full Text Available Small mitochondrial genomes can behave as selfish elements by displacing wild-type genomes regardless of their detriment to the host organism. In the budding yeast Saccharomyces cerevisiae, small hypersuppressive mtDNA transiently coexist with wild-type in a state of heteroplasmy, wherein the replicative advantage of the small mtDNA outcompetes wild-type and produces offspring without respiratory capacity in >95% of colonies. The cytosolic enzyme ribonucleotide reductase (RNR catalyzes the rate-limiting step in dNTP synthesis and its inhibition has been correlated with increased petite colony formation, reflecting loss of respiratory function. Here, we used heteroplasmic diploids containing wild-type (rho+ and suppressive (rho− or hypersuppressive (HS rho− mitochondrial genomes to explore the effects of RNR activity on mtDNA heteroplasmy in offspring. We found that the proportion of rho+ offspring was significantly increased by RNR overexpression or deletion of its inhibitor, SML1, while reducing RNR activity via SML1 overexpression produced the opposite effects. In addition, using Ex Taq and KOD Dash polymerases, we observed a replicative advantage for small over large template DNA in vitro, but only at low dNTP concentrations. These results suggest that dNTP insufficiency contributes to the replicative advantage of small mtDNA over wild-type and cytosolic dNTP synthesis by RNR is an important regulator of heteroplasmy involving small mtDNA molecules in yeast.
In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria.

Science.gov (United States)

Simonetti, Oriana; Cirioni, Oscar; Ghiselli, Roberto; Orlando, Fiorenza; Silvestri, Carmela; Mazzocato, Susanna; Kamysz, Wojciech; Kamysz, Elzbieta; Provinciali, Mauro; Giacometti, Andrea; Guerrieri, Mario; Offidani, Annamaria

2014-05-01

The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections. Copyright © 2014 Elsevier Inc. All rights reserved.
Comparison of breath testing with fructose and high fructose corn syrups in health and IBS.

Science.gov (United States)

Skoog, S M; Bharucha, A E; Zinsmeister, A R

2008-05-01

Although incomplete fructose absorption has been implicated to cause gastrointestinal symptoms, foods containing high fructose corn syrup (HFCS) contain glucose. Glucose increases fructose absorption in healthy subjects. Our hypothesis was that fructose intolerance is less prevalent after HFCS consumption compared to fructose alone in healthy subjects and irritable bowel syndrome (IBS). Breath hydrogen levels and gastrointestinal symptoms were assessed after 40 g of fructose (12% solution) prepared either in water or as HFCS, administered in double-blind randomized order on 2 days in 20 healthy subjects and 30 patients with IBS. Gastrointestinal symptoms were recorded on 100-mm Visual Analogue Scales. Breath hydrogen excretion was more frequently abnormal (P fructose (68%) than HFCS (26%) in controls and patients. Fructose intolerance (i.e. abnormal breath test and symptoms) was more prevalent after fructose than HFCS in healthy subjects (25% vs. 0%, P = 0.002) and patients (40% vs. 7%, P = 0.062). Scores for several symptoms (e.g. bloating r = 0.35) were correlated (P fructose but not HFCS; in the fructose group, this association did not differ between healthy subjects and patients. Symptoms were not significantly different after fructose compared to HFCS. Fructose intolerance is more prevalent with fructose alone than with HFCS in health and in IBS. The prevalence of fructose intolerance is not significantly different between health and IBS. Current methods for identifying fructose intolerance should be modified to more closely reproduce fructose ingestion in daily life.
Short Stories, Novels and Spain. An Interview With Colm Tóibín

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José-Francisco Fernández Sánchez

2009-03-01

Full Text Available Colm Tóibín (Enniscorthy, 1955 is the author of five novels, The South (1990, The Heather Blazing (1992, The Story of the Night (1996, The Blackwater Lightship(1999 and The Master (2004. This last novel won the IMPAC Dublin Literary Award, the Los Angeles Times Novel of the Year, the Prix du Meilleur Livre Etranger for the best foreign novel published in 2005 in France, and it was shortlisted for the Man Booker Prize. Colm Tóibín has a long career in journalism and was the editor of the magazine Magill from 1982 to 1985. He is also the author of several non-fiction books, including Homage to Barcelona (1990 and The Sign of the Cross: Travels in Catholic Europe (1994. He edited The Penguin Book of Irish Fiction (1999 and has recently published his first book of short stories,Mothers and Sons (2006. Colm Tóibín attended the 10th International Conference on the Short Story in English, held at University College Cork on 19-21 June 2008, where this interview took place.
Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis. [X radiation, mice

Energy Technology Data Exchange (ETDEWEB)

Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.; Murphy, W.H.

1978-12-01

The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log/sub 10/PD/sub 50/ values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplanted Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain.
[Abdominal spasms, meteorism, diarrhea: fructose intolerance, lactose intolerance or IBS?].

Science.gov (United States)

Litschauer-Poursadrollah, Margaritha; El-Sayad, Sabine; Wantke, Felix; Fellinger, Christina; Jarisch, Reinhart

2012-12-01

Meteorism, abdominal spasms, diarrhea, casually obstipation, flatulence and nausea are symptoms of fructose malabsorption (FIT) and/or lactose intolerance (LIT), but are also symptoms of irritable bowel syndrome (IBS). Therefore these diseases should be considered primarily in patients with digestive complaints. For diagnosis an H(2)-breath test is used.In 1,935 patients (526 m, 1,409 f) a fructose intolerance test and in 1,739 patients (518 m,1,221 f) a lactose intolerance test was done.FIT is found more frequently than LIT (57 versus 52 % in adults (p intolerance (HIT). Headache (ca. 10 %), fatigue (ca. 5 %) and dizziness (ca. 3 %) may occur after the test, irrespective whether the test was positive or negative.In more than 2/3 of patients a diet reduced in fructose or lactose may lead to improvement or remission of these metabolic disorders. IBS, which is often correlated with FIT (183/221 patients = 83 %), can be improved by relevant but also not relevant diets indicating that irritable bowel disease seems to be caused primarily by psychological disorders.
Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.

Science.gov (United States)

Francavilla, Ruggiero; Piccolo, Maria; Francavilla, Antonio; Polimeno, Lorenzo; Semeraro, Francesco; Cristofori, Fernanda; Castellaneta, Stefania; Barone, Michele; Indrio, Flavia; Gobbetti, Marco; De Angelis, Maria

2018-04-23

The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD). About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; Psymptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.
[Using a multicomponent functional food in IBS patients with constipation a comparative controlled study].

Science.gov (United States)

Pilipenko, V I; Teplyuk, D A; Shakhovskaya, A K; Isakov, V A; Vorobyova, V M; Vorobyova, I S; Sarkisyan, V A; Kochetkova, A A; Mikheeva, G A; Yudina, A V

2016-01-01

Irritable bowel syndrome (IBS) is highly prevalent functional gastrointestinal disorder associated with decrease in quality of life and a high social cost. Diet is one of several therapeutic options in IBS treatment; therefore the development and clinical evaluation of innovative functional food for IBS patients are actual. Instant drink containing 4 g inulin, 4 mg menthol and 2 mg of pyridoxine (in daily dose) has been evaluated. 49 patients 18-68 (41.5±16.5) years old fulfilling the Rome III criteria for IBS-C were randomly assigned into two groups: one received standard diet plus two drinks per day for 2 weeks and control group received standard diet. Response to therapy was recorded daily using Likert scale of abdominal pain, bloating and feeling of incomplete bowel emptying, frequency of bowel movement, Bristol stool scale, and quality of life was assessed by IBSQoL questionnaire before and after the treatment. The consumption of the drink with inulin and menthol contributed to a significant positive effect on the stool parameters (from 0.91±0.73 to 1.12±0.45 bowel movements per day in stool frequency, p=0.05, from 2.68±1.63 to 3.43±1.27 index Bristol scale, p=0.05), reduced the severity of abdominal pain (from 1.78±0.58 to 1.47?0.61 Likert scale points, p=0.05), bloating (from 2.22±0.83 to 1.53±0.71 points ofLikertscale,p= 0.01) and a sense of incomplete bowelemptying (from 2.22 ± 0.88 to 1.61± 0.81 points of Likert scale, p=0.001), as well as increased the quality of life (from 75.3± 12.0 to 83.3±6.7%, p=0.05), but a significant part of patients (10 of 25) complained the appearance of heartburn after the start of the treatment. In conclusion, the consumption of the functional drink containing inulin, menthol and pyridoxine is associated with improve in stool parameters, abdominal pain, Bristol scale index and increase in quality of life in patients with IBS-C, but produce noticeable heartburn. Changes in functional drink composition are needed to
Effects on gastrointestinal transit and antroduodenojejunal manometry after gut-directed hypnotherapy in irritable bowel syndrome (IBS).

Science.gov (United States)

Lindfors, Perjohan; Törnblom, Hans; Sadik, Riadh; Björnsson, Einar S; Abrahamsson, Hasse; Simrén, Magnus

2012-12-01

Gut-directed hypnotherapy is an effective treatment in irritable bowel syndrome (IBS) but little is known about the mechanisms of action. In this study we aimed to investigate the effects on gastrointestinal motility when treating IBS with gut-directed hypnotherapy. We randomized 90 patients with IBS, refractory to standard management to receive gut-directed hypnotherapy 1 h/week for 12 weeks or supportive treatment for the same time period. Eighty-one subjects (40 hypnotherapy, 41 controls) could be evaluated by one or more of the following investigations, both before and after the intervention: gastric emptying time, small bowel transit time, colonic transit time, and antroduodenojejunal manometry. No significant differences in gastric emptying time, small bowel transit time, or colonic transit time was found when comparing the baseline and post-intervention measurements in the hypnotherapy group or in the control group. The same was true concerning the results of the antroduodenojejunal manometry. However, there was a numerical trend toward a higher number of migrating motor complexes at manometry and an accelerated gastric emptying time after hypnotherapy that did not reach statistical significance. In this study, we were not able to find evidence for long-standing effects on gastrointestinal motility as a mediator of the effects on IBS when treating the condition with gut-directed hypnotherapy. Further research to understand the mechanism of action is needed.
Current job situation of the alumni from IBS Groningen -2017

NARCIS (Netherlands)

Liefers, Jan

2017-01-01

Our main question is: what is the current job situation of the alumni from IBS Groningen? The sub questions are: •How many students graduated in the various years? •What are the most popular jobs? •Where do alumni work and what is the career path? •What is their highest degree? •What companies

Trino IB ameliorates the oxidative stress of cryptorchidism in the rat ...

African Journals Online (AJOL)

The study examined the effect of Trino IB, a mixture of oleuropein and -lipoic acid, on the plasma concentration of g-glutamyl transpeptidase (GGT), malondialdehyde (MDA), sperm count and apoptotic degeneration of testicular germ cells in experimentally induced cryptorchidism in adult male rats. Oral administration of ...
′Belonging without Belonging′: Colm Tóibín′s Dialogue with the Past

DEFF Research Database (Denmark)

Bøss, Michael

2005-01-01

It is argued that Tóibín is not the typical 'revisionist' intellectual that some have made him into, but a humanist and a sort of in-between, making a virtue of his own ambivalences towards notions of tradition, community and nationhood. The essay makes an analysis of these ambivalences with refe......It is argued that Tóibín is not the typical 'revisionist' intellectual that some have made him into, but a humanist and a sort of in-between, making a virtue of his own ambivalences towards notions of tradition, community and nationhood. The essay makes an analysis of these ambivalences...
Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB-IIIB

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Magdalena Franc

2015-02-01

Full Text Available Introduction : The aim of the present study was to evaluate the profile of VEGF-C gene expression in particular stages of cervical cancer (IB-IIIB and to estimate the correlation between VEGF-C mRNA quantity profile and clinical stage. Material and methods : Material for molecular analysis consisted of cervical cancer tissue specimens collected from 38 women (10, 15, 13 cases were classified as IB, IIB and IIIB, respectively. The control group was composed of normal cervical tissues collected from 10 women who underwent hysterectomy for non-oncological reasons. The number of VEGF-C mRNA copies in particular groups was estimated by the reverse transcription quantitative polymerase chain reaction (RT-qPCR method. Results: In the control group the average number of mRNA copies was 134 ± 36 (median: 106, in a group with stage IB it was 16 077 ± 7090 (median: 580, for stage IIB – 35 019 ± 8945 (median: 40 870. The highest number of mRNA VEGF-C copies was derived in a group of patients with cervical cancer of stage IIIB. The average quantity was 56 155 ± 12 470, whereas median 55 981. A statistically significantly higher level of VEGF-C gene expression was disclosed in cervical cancer specimens with stage IIB and IIIB than in the control group. In stage IIIB, the VEGF-C gene expression was significantly higher than in specimens derived from individuals in stage IB. Conclusions : In squamous cell carcinoma of the uterine cervix of stage IB-IIIB genes involved in lymphangiogenesis, especially VEGF-C , are expressed, which expression increases as the clinical stage of cervical cancer is higher.
Ribonucleotide Reductase Inhibitors: A New Look at an Old Target for Radiosensitization

International Nuclear Information System (INIS)

Chapman, Tobias R.; Kinsella, Timothy J.

2012-01-01

Ribonucleotide reductase (RR), the rate limiting enzyme in the synthesis and repair of DNA, has been studied as a target for inhibition in the treatment of cancer for many years. While some researchers have focused on RR inhibitors as chemotherapeutic agents, particularly in hematologic malignancies, some of the most promising data has been generated in the field of radiosensitization. Early pre-clinical studies demonstrated that the addition of the first of these drugs, hydroxyurea, to ionizing radiation (IR) produced a synergistic effect in vitro, leading to a large number of clinical studies in the 1970–1980s. These studies, mainly in cervical cancer, initially produced a great deal of interest, leading to the incorporation of hydroxyurea in the treatment protocols of many institutions. However, over time, the conclusions from these studies have been called into question and hydroxyurea has been replaced in the standard of care of cervical cancer. Over the last 10 years, a number of well-done pre-clinical studies have greatly advanced our understanding of RR as a target. Those advances include the elucidation of the role of p53R2 and our understanding of the temporal relationship between the delivery of IR and the response of RR. At the same time, new inhibitors with increased potency and improved binding characteristics have been discovered, and pre-clinical and early clinical data look promising. Here we present a comprehensive review of the pre-clinical and clinical data in the field to date and provide some discussion of future areas of research.
Ribonucleotide Reductase Inhibitors: A New Look at an Old Target for Radiosensitization

Energy Technology Data Exchange (ETDEWEB)

Chapman, Tobias R. [Tufts University School of Medicine, Boston, MA (United States); Kinsella, Timothy J., E-mail: tkinsella@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI (United States)

2012-01-04

Ribonucleotide reductase (RR), the rate limiting enzyme in the synthesis and repair of DNA, has been studied as a target for inhibition in the treatment of cancer for many years. While some researchers have focused on RR inhibitors as chemotherapeutic agents, particularly in hematologic malignancies, some of the most promising data has been generated in the field of radiosensitization. Early pre-clinical studies demonstrated that the addition of the first of these drugs, hydroxyurea, to ionizing radiation (IR) produced a synergistic effect in vitro, leading to a large number of clinical studies in the 1970–1980s. These studies, mainly in cervical cancer, initially produced a great deal of interest, leading to the incorporation of hydroxyurea in the treatment protocols of many institutions. However, over time, the conclusions from these studies have been called into question and hydroxyurea has been replaced in the standard of care of cervical cancer. Over the last 10 years, a number of well-done pre-clinical studies have greatly advanced our understanding of RR as a target. Those advances include the elucidation of the role of p53R2 and our understanding of the temporal relationship between the delivery of IR and the response of RR. At the same time, new inhibitors with increased potency and improved binding characteristics have been discovered, and pre-clinical and early clinical data look promising. Here we present a comprehensive review of the pre-clinical and clinical data in the field to date and provide some discussion of future areas of research.
INTEGRAL FIELD SPECTROSCOPY OF SUPERNOVA EXPLOSION SITES: CONSTRAINING THE MASS AND METALLICITY OF THE PROGENITORS. I. TYPE Ib AND Ic SUPERNOVAE

Energy Technology Data Exchange (ETDEWEB)

Kuncarayakti, Hanindyo; Maeda, Keiichi [Kavli Institute for the Physics and Mathematics of the Universe (WPI), Todai Institutes for Advanced Study, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8583 (Japan); Doi, Mamoru; Morokuma, Tomoki; Hashiba, Yasuhito [Institute of Astronomy, Graduate School of Science, The University of Tokyo, 2-21-1 Osawa, Mitaka, Tokyo 181-0015 (Japan); Aldering, Greg [Physics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720 (United States); Arimoto, Nobuo [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-0015 (Japan); Pereira, Rui [CNRS/IN2P3, Institut de Physique Nucleaire de Lyon, 4 Rue Enrico Fermi, F-69622 Villeurbanne Cedex (France); Usuda, Tomonori, E-mail: hanindyo.kuncarayakti@ipmu.jp [Subaru Telescope, National Astronomical Observatory of Japan, 650 North A' ohoku Place, Hilo, HI 96720 (United States)

2013-08-01

Integral field spectroscopy of 11 Type Ib/Ic supernova (SN Ib/Ic) explosion sites in nearby galaxies has been obtained using UH88/SNIFS and Gemini-N/GMOS. The use of integral field spectroscopy enables us to obtain both spatial and spectral information about the explosion site, enabling the identification of the parent stellar population of the SN progenitor star. The spectrum of the parent population provides metallicity determination via strong-line method and age estimation obtained via comparison with simple stellar population models. We adopt this information as the metallicity and age of the SN progenitor, under the assumption that it was coeval with the parent stellar population. The age of the star corresponds to its lifetime, which in turn gives the estimate of its initial mass. With this method we were able to determine both the metallicity and initial (zero-age main sequence) mass of the progenitor stars of SNe Ib and Ic. We found that on average SN Ic explosion sites are more metal-rich and younger than SN Ib sites. The initial mass of the progenitors derived from parent stellar population age suggests that SN Ic has more massive progenitors than SN Ib. In addition, we also found indication that some of our SN progenitors are less massive than {approx}25 M{sub Sun }, indicating that they may have been stars in a close binary system that have lost their outer envelope via binary interactions to produce SNe Ib/Ic, instead of single Wolf-Rayet stars. These findings support the current suggestions that both binary and single progenitor channels are in effect in producing SNe Ib/Ic. This work also demonstrates the power of integral field spectroscopy in investigating SN environments and active star-forming regions.
The Gut-Brain Axis and the Microbiome: Clues to Pathophysiology and Opportunities for Novel Management Strategies in Irritable Bowel Syndrome (IBS

Directory of Open Access Journals (Sweden)

Eamonn M.M. Quigley

2018-01-01

Full Text Available Irritable bowel syndrome (IBS is one of the most common of all medical disorders worldwide and, while for some it represents no more than a nuisance, for others it imposes significant negative impacts on daily life and activities. IBS is a heterogeneous disorder and may well have a number of causes which may lie anywhere from the external environment to the contents of the gut lumen and from the enteric neuromuscular apparatus and the gut immune system to the central nervous system. Consequently, the paradigm of the gut-brain axis, which includes the participation of these various factors, has proven a useful model to assist clinicians and patients alike in understanding the genesis of symptoms in IBS. Now, given the widespread interest in the gut microbiome in health and disease, in general, reports of disordered enteric bacterial communities in IBS, and experimental data to indicate that components of the gut microbiota can influence brain morphology and function, as well as behavior and cognition, this concept has been extended to encompass the microbiota-gut-brain axis. The implications of this novel concept to the assessment and management of IBS will be explored in this review.
Long‐Term Monitoring of a Geosynthetic Reinforced Soil Integrated Bridge System (GRS‐IBS)

Science.gov (United States)

2017-11-01

The geosynthetic reinforced soil integrated bridge system (GRS-IBS) is an innovative alternative to conventional bridge technology that utilizes closely spaced layers of geosynthetic reinforcement and compacted granular fill material to provide direc...
Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma.

Science.gov (United States)

Hung, Jung-Jyh; Wu, Yu-Chung; Chou, Teh-Ying; Jeng, Wen-Juei; Yeh, Yi-Chen; Hsu, Wen-Hu

2016-04-01

The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Deoxynucleoside salvage in fission yeast allows rescue of ribonucleotide reductase deficiency but not Spd1-mediated inhibition of replication

DEFF Research Database (Denmark)

Fleck, Oliver; Fahnøe, Ulrik; Løvschal, Katrine Vyff

2017-01-01

In fission yeast, the small, intrinsically disordered protein S-phase delaying protein 1 (Spd1) blocks DNA replication and causes checkpoint activation at least in part, by inhibiting the enzyme ribonucleotide reductase, which is responsible for the synthesis of DNA. The CRL4(Cdt2) E3 ubiquitin...... ligase mediates degradation of Spd1 and the related protein Spd2 at S phase of the cell cycle. We have generated a conditional allele of CRL4(Cdt2), by expressing the highly unstable substrate-recruiting protein Cdt2 from a repressible promoter. Unlike Spd1, Spd2 does not regulate deoxynucleotide...... triphosphate (dNTP) pools; yet we find that Spd1 and Spd2 together inhibit DNA replication upon Cdt2 depletion. To directly test whether this block of replication was solely due to insufficient dNTP levels, we established a deoxy-nucleotide salvage pathway in fission yeast by expressing the human nucleoside...
HF-EPR, Raman, UV/VIS light spectroscopic, and DFT studies of the ribonucleotide reductase R2 tyrosyl radical from Epstein-Barr virus.

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Ane B Tomter

Full Text Available Epstein-Barr virus (EBV belongs to the gamma subfamily of herpes viruses, among the most common pathogenic viruses in humans worldwide. The viral ribonucleotide reductase small subunit (RNR R2 is involved in the biosynthesis of nucleotides, the DNA precursors necessary for viral replication, and is an important drug target for EBV. RNR R2 generates a stable tyrosyl radical required for enzymatic turnover. Here, the electronic and magnetic properties of the tyrosyl radical in EBV R2 have been determined by X-band and high-field/high-frequency electron paramagnetic resonance (EPR spectroscopy recorded at cryogenic temperatures. The radical exhibits an unusually low g₁-tensor component at 2.0080, indicative of a positive charge in the vicinity of the radical. Consistent with these EPR results a relatively high C-O stretching frequency associated with the phenoxyl radical (at 1508 cm⁻¹ is observed with resonance Raman spectroscopy. In contrast to mouse R2, EBV R2 does not show a deuterium shift in the resonance Raman spectra. Thus, the presence of a water molecule as a hydrogen bond donor moiety could not be identified unequivocally. Theoretical simulations showed that a water molecule placed at a distance of 2.6 Å from the tyrosyl-oxygen does not result in a detectable deuterium shift in the calculated Raman spectra. UV/VIS light spectroscopic studies with metal chelators and tyrosyl radical scavengers are consistent with a more accessible dimetal binding/radical site and a lower affinity for Fe²⁺ in EBV R2 than in Escherichia coli R2. Comparison with previous studies of RNR R2s from mouse, bacteria, and herpes viruses, demonstrates that finely tuned electronic properties of the radical exist within the same RNR R2 Ia class.
Determination of total ribonucleotide pool in plant materials by high-pH anion-exchange high-performance liquid chromatography following extraction with potassium hydroxide.

Science.gov (United States)

Riondet, Christophe; Morel, Sylvain; Alcaraz, Gérard

2005-06-10

A new, improved method that only requires a potassium hydroxide extraction procedure is presented for the analysis of a full nucleotide pool in plant materials. Quantification was performed by high-pH anion-exchange chromatography (HPAEC) with UV detection after a potassium hydroxide extraction, and allowed the quantification of 13 linear ribonucleotides in a single run. The method has been validated by comparison of six extraction methods and also by measurement of the intracellular nucleotide levels of three plant species (cell cultures and leaves). The evolution of the nucleotide pool of Nicotiana tabacum cell culture during growth has also been measured, and showed an increase in the pool until the fifth day, where the growth rate reaches a maximum, after which a decrease was observed.
Effectiveness of postoperative radiation therapy in stage IB cervical cancer with residual disease

International Nuclear Information System (INIS)

Herman, J.; Perez-Tamayo, C.; Komaki, R.U.; Terada, K.; Roberts, J.A.; Morley, G.W.; Greenberg, M.; Mattingly, R.; Hopkins, M.

1987-01-01

Twenty-one patients with stage IB cervical cancer were treated with radical hysterectomy, pelvic lymph node dissection, and pelvic radiation therapy to approximately 5,090 rad. Patients were divided into two groups: group I, nine patients with involved parametria or positive margins at surgery; group II, 12 patients with metastatic pelvic lymph nodes. Patients in group I had an actuarial survival of 40% at 5 years and 20% at 10 years; patients in group II had an actuarial survival of 67% at 5 and 10 years (.01 < P < .05). The overall actuarial survival was 55% at 5 years and 43% at 10 years. Thus, patients with stage IB disease and involved parametrium or surgical margins do poorly. Alternative forms of therapy should be considered when this disease picture is clinically suspected preoperatively
Using the skin protective lotion IB1 as a substitute for chemical protective gloves.

Science.gov (United States)

Ophir, Nimrod; Milk, Nadav; Mayer, Talia; Ravfogel, Shaul; Yavnai, Nirit; Eisenkraft, Arik; Kadar, Tamar; Kassirer, Michael; Rosman, Yossi

2016-10-01

We aimed to evaluate the performance of medical personnel in using the IB1 topical protective lotion on their hands and wrists together with standard disposable medical gloves, compared to standard-issued medical chemical protective gloves. This randomized cross-over study included 144 medical personnel. Primary endpoints were time-to-completion of autoinjection; success rate, number of attempts, and time-to-achieve successful endotracheal intubation; time-to-achieve satisfactory tube fixation; time-to-draw and inject the content of an ampoule; and the total time-to-perform all medical procedures. Secondary endpoints included the subjective assessment of convenience to perform these four procedures with each protective measure. Mean time was significantly shorter using IB1 compared to chemical protective gloves for tube fixation, ampoule drawing, and the total time-to-perform all procedures (58.6±22.7 seconds vs. 71.7±29.7; 31.5±21.8 vs. 38.2±19.4; 137.4±56.1 vs. 162.5±63.6, respectively; Pgloves (Pgloves significantly shorten the time-to-perform medical procedures requiring fine motor dexterities and is subjectively more convenient than chemical protective gloves. IB1 should be considered as an appropriate alternative for medical teams in a chemical event. Copyright © 2016 Elsevier Inc. All rights reserved.
A framework of initiatives for successful application of life cycle costing (LCC in industrialised building system (IBS in Malaysian construction industry

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Shamsuddin Siti Mazzuana

2017-01-01

Full Text Available Industrialised Building System (IBS contributes a great shift in sustainable construction and benefits the society. Previous studies have proven in general that one of the hindrances in promoting sustainable in IBS, is a high cost for any pre-cast material specifically thus effected the overall cost. The introduction of Life Cycle Costing (LCC leads into providing a better and comprehensive cost estimation, including projecting actual cost to operate the building, hence providing a better baseline for decision making. The lacking application of LCC in IBS is still in trivial impact, therefore, this paper presents a framework which produced by expressing the successful initiatives of LCC and IBS in Malaysia construction industry. The framework developed based on findings from the extensive literature reviews, 164 responded questionnaires, and 19 expert opinions, which has three sections: Strategy Development, System Development and the last part is Decision Level. Aspects of objectivity, practicality, reliability, completeness that were likely to be implemented in the Malaysian construction industry were used. There are significant opinions on the usefulness and completeness of the proposed framework in providing a comprehensive cost estimates which helps much in deciding to carry out IBS or remain with a traditional construction method.
Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life.

Science.gov (United States)

Böhn, Lena; Störsrud, Stine; Törnblom, Hans; Bengtsson, Ulf; Simrén, Magnus

2013-05-01

Despite the fact that food and diet are central issues, that concern patients with irritable bowel syndrome (IBS), the current understanding about the association between the intake of certain foods/food groups and the gastrointestinal (GI) symptom pattern, psychological symptoms, and quality of life is poor. The aim of this study was to determine which food groups and specific food items IBS patients report causing GI symptoms, and to investigate the association with GI and psychological symptoms and quality of life. We included 197 IBS patients (mean age 35 (18-72) years; 142 female subjects) who completed a food questionnaire in which they specified symptoms from 56 different food items or food groups relevant to food intolerance/allergy. The patients also completed questionnaires to assess depression and general anxiety (Hospital Anxiety and Depression), GI-specific anxiety (Visceral Sensitivity Index), IBS symptoms (IBS-Severity Scoring System), somatic symptoms (Patient Health Questionnaire-15), and quality of life (Irritable Bowel Syndrome Quality of Life Questionnaire). In all, 84% of the studied population reported symptoms related to at least one of the food items surveyed. Symptoms related to intake of food items with incompletely absorbed carbohydrates were noted in 138 (70%) patients; the most common were dairy products (49%), beans/lentils (36%), apple (28%), flour (24%), and plum (23%). Of these, 58% experienced GI symptoms from foods rich in biogenic amines, such as wine/beer (31%), salami (22%), and cheese (20%). Histamine-releasing foods, such as milk (43%), wine/beer (31%), and pork (21%), were also considered causes of symptoms in IBS patients. GI symptoms were also frequently reported after intake of fried and fatty foods (52%). With increasing IBS symptom severity, patients reported more food items responsible for their GI symptoms (P=0.004), and this was also found in patients with more severe somatic symptoms (Psleep (r=-0.25; P=0
Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS.

LENUS (Irish Health Repository)

Wilcz-Villega, E

2013-11-29

Increased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and claudin (CLD)-1 and associations with IBS symptoms.
Diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) and immunoblot (IB) for the detection of antibodies against Neospora caninum in milk from dairy cows.

Science.gov (United States)

Chatziprodromidou, I P; Apostolou, T

2018-04-01

The aim of the study was to estimate the sensitivity and specificity of enzyme-linked immunosorbent assay (ELISA) and immunoblot (IB) for detecting antibodies of Neospora caninum in dairy cows, in the absence of a gold standard. The study complies with STRADAS-paratuberculosis guidelines for reporting the accuracy of the test. We tried to apply Bayesian models that do not require conditional independence of the tests under evaluation, but as convergence problems appeared, we used Bayesian methodology, that does not assume conditional dependence of the tests. Informative prior probability distributions were constructed, based on scientific inputs regarding sensitivity and specificity of the IB test and the prevalence of disease in the studied populations. IB sensitivity and specificity were estimated to be 98.8% and 91.3%, respectively, while the respective estimates for ELISA were 60% and 96.7%. A sensitivity analysis, where modified prior probability distributions concerning IB diagnostic accuracy applied, showed a limited effect in posterior assessments. We concluded that ELISA can be used to screen the bulk milk and secondly, IB can be used whenever needed.
Diverse regulation of retinal pigment epithelium phagocytosis of photoreceptor outer segments by calcium-independent phospholipase A₂, group VIA and secretory phospholipase A₂, group IB

DEFF Research Database (Denmark)

Zhan, Chen; Wang, Jinmei; Kolko, Miriam

2012-01-01

PURPOSE: To investigate the roles of the phospholipases A(2) (PLA(2)) subtypes, iPLA(2)-VIA and sPLA(2)-IB in retinal pigment epithelium (RPE) phagocytosis of photoreceptor outer segments (POS) and to explore a possible interaction between sPLA(2)-IB and iPLA(2)-VIA in the RPE. METHODS: To explore...... the role of iPLA(2)-VIA in RPE phagocytosis of POS, experiments with iPLA(2)-VIA vector transfection, iPLA(2)-VIA(-/-) knockout (KO) mice, and iPLA(2)-VIA inhibition by bromoenol lactone (BEL) were done. Exogenous addition of sPLA(2)-IB was used to investigate the role of sPLA(2)-IB in RPE phagocytosis....... A Luciferase Reporter Vector containing the iPLA(2)-VIA promoter was used to study the effects of sPLA(2)-IB on the iPLA(2)-VIA promoter. RESULTS: ARPE-19 and primary mouse RPE cells transfected with iPLA(2)-VIA showed increased phagocytosis. Phagocytosis was reduced in primary mouse RPE inhibited with BEL...
Web and Internet-based Capabilities (IbC) Policies - U.S. Department of

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&IIC DCIO IE DCIO R&A DCIO CS In the News Library Contact us Web and Internet-based Capabilities (IbC) Policies Army Navy Air Force Marine Corps General DoD Internet Services and Internet-Based ) Information Collection under the Paperwork Reduction Act (PRA) (OMB Memo) Internet Domain Name and Internet

Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy

International Nuclear Information System (INIS)

Calais, G.; Le Floch, O.; Chauvet, B.; Reynaud-Bougnoux, A.; Bougnoux, P.

1989-01-01

In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor
The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS and Wheat-Sensitive Irritable Bowel Syndrome (IBS: An Update

Directory of Open Access Journals (Sweden)

Carlo Catassi

2017-11-01

Full Text Available Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS. New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion.
Vicente Blasco Ibáñez (1867-1928: viaje por Oriente y Egipto

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Lara Peinado, Federico

2005-04-01

Full Text Available Con este artículo se pretende rememorar los viajes efectuados a Turquía (1907 y años después al país del Nilo (1924 por el famoso novelista Vicente Blasco Ibáñez (1867-1928. Sus impresiones, la historia de los países visitados, la descripción de sus ciudades y paisajes tomaron cuerpo en las obras tituladas Oriente y La vuelta al mundo de un novelista. Blasco Ibáñez supo resumir la historia de Constantinopla así como la de Egipto -especialmente su antigüedad- con sencillas palabras, sin tecnicismos, haciendo llegar al lector el impacto que le causaron monumentos y ambientes de la ciudad turca en un caso, y las pirámides, tumbas y el paisaje nilotico en otro, además de introducirlo en el alma de sus gentes.…
Using "Competing Visions of Human Rights" in an International IB World School

Science.gov (United States)

Tolley, William J.

2013-01-01

William Tolley, a teaching fellow with the Choices Program, is the Learning and Innovation Coach and head of history at the International School of Curitiba, Brazil (IB). He writes in this article that he has found that the "Competing Visions of Human Rights" teaching unit, developed by Brown University's Choices Program, provides a…
Prevalence of mood and anxiety disorder in self reported irritable bowel syndrome (IBS). An epidemiological population based study of women

OpenAIRE

Mykletun, Arnstein; Jacka, Felice; Williams, Lana; Pasco, Julie; Henry, Margaret; Nicholson, Geoffrey C.; Kotowicz, Mark A.; Berk, Michael

2010-01-01

Abstract Background Irritable bowel syndrome (IBS) is commonly regarded as a functional disorder, and is hypothesized to be associated with anxiety and depression. This evidence mainly rests on population-based studies utilising self-report screening instruments for psychopathology. Other studies applying structured clinical interviews are generally based on small clinical samples, which are vulnerable to biases. The extant evidence base for an association between IBS and psychopathology is h...
Gastrointestinal (GI) permeability correlates with trait anxiety and urinary norepinephrine/creatinine (CR)ratio in children with functional abdominal pain (FAP)and irritable bowel syndrome (IBS) but not in controls

Science.gov (United States)

FAP and IBS affect 10–15% of school age children and bear many similarities to irritable bowel syndrome (IBS) in adults (e.g., functional pain, visceral hyperalgesia). Animal models of IBS have suggested a relationship between neonatal stress/anxiety and increased GI permeability later in life. We h...
Dinosaurios de la Península Ibérica

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Sanz, J. L.

2006-12-01

Full Text Available Body fossils of the Iberian Peninsula dinosaurs are very relevant for the knowledge of several aspects of the evolutionary history of the group, and, in addition, for the interpretation of the distribution of many of its components, due to the geographic situation of the Iberian Peninsula. Almost all of the groups of dinosaurs are represented in the Iberian Peninsula record: ornithopods, thyreophorans, theropods and sauropods. These groups are present, mainly, in the transit Jurassic-Cretaceous (Kimmeridigian- Berriasian, the upper part of the Lower Cretaceous (Barremian-Aptian and in the end of the Upper Cretaceous (Campanian-Masstrichtian. Ornithischian dinosaurs are represented by thyreophorans such as the stegosaurians Dacentrurus and Stegosaurus, the ankylosaurs Dracopelta, Polacanthus and Struthiosaurus, and ornithopods like hypsilophodontids, basal iguanodontians (Rhabdodon, dryosaurids, camptosaurids (Draconyx and Camptosaurus, iguanodontids (Iguanodon and hadrosaurids (Pararhabdodon. Some Incertae sedis and taxa in process of description are present too. Sauropods are represented by taxa related to Neosauropoda (Lourinhasaurus, Dinheirosaurus, Galveosaurus and Losillasaurus and titanosauriforms (Aragosaurus, Lusotitan and Lirainosaurus. In addition, new forms are still in description, like the sauropods of Riodeva (Teruel, Peñarroya de Tastavins (Teruel and Morella (Castellón. Theropods are represented by the ceratosaurian Ceratosaurus, the spinosauroid Torvosaurus, the carnosaurs Lourinhanosaurus and Allosaurus, the tyrannosaurid Aviatyrannis, the ornithomimosaur Pelecanimimus, and the avian-theropods Iberomesornis, Concornis, Eoalulavis and Noguerornis. Nevertheless, theropods diversity is more abundant as it shows the great variability of teeth morphotypes identified.registro de restos directos de dinosaurios en la Península Ibérica ha mostrado, en los últimos años, que puede ser muy relevante para el conocimiento de distintos
IbM PENYUSUNAN PENILAIAN AUTENTIK BAGI GURU SEKOLAH DI PONPES DARUL FIKRI BAWEN

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Joko Siswanto

2015-09-01

Full Text Available Abstract Low motivation of teachers in implementing authentic assessment becomes the basis for IbM team to carry out extension activities. Authentic assessment has actually been around a long time, but this issue arose when the curriculum was launched in 2013. During this time, most of the teachers at school in the field only make an assessment test course, not many people touched assessment tests that are written. Through activities of IbM Authentic Assessment Preparation Training for Teachers of Pesantren Darul Fikri Bawen, participants are expected to conduct a written assessment, performance assessment, product assessment projects, portfolio assessment, and manage the mark using computer-based process. Prior to socialization, teachers must first take pretest and post test. Pre test shows an average score of 89.65 while the average of post-test scores shows 97.6. During the activities, the participants felt helped and gave a positive response to organized similar activities. Keywords: Preparation, Assessment Authentic, Darul Fikri Boarding School Teacher
IB2d: a Python and MATLAB implementation of the immersed boundary method.

Science.gov (United States)

Battista, Nicholas A; Strickland, W Christopher; Miller, Laura A

2017-03-29

The development of fluid-structure interaction (FSI) software involves trade-offs between ease of use, generality, performance, and cost. Typically there are large learning curves when using low-level software to model the interaction of an elastic structure immersed in a uniform density fluid. Many existing codes are not publicly available, and the commercial software that exists usually requires expensive licenses and may not be as robust or allow the necessary flexibility that in house codes can provide. We present an open source immersed boundary software package, IB2d, with full implementations in both MATLAB and Python, that is capable of running a vast range of biomechanics models and is accessible to scientists who have experience in high-level programming environments. IB2d contains multiple options for constructing material properties of the fiber structure, as well as the advection-diffusion of a chemical gradient, muscle mechanics models, and artificial forcing to drive boundaries with a preferred motion.
Avasõnad / Mats Estonius, Toomas Hendrik Ilves, Eduardo Ibáñes, Uffe A. Baslev

Index Scriptorium Estoniae

2010-01-01

Konverentsi avasõnad laususid Tallinna Ülikooli prorektor Mats Estonius, Eesti Vabariigi president Toomas Hendrik Ilves, Hispaania Kuningriigi suursaadik Eestis Eduardo Ibáñes, Taani Kuningriigi suursaadik Eestis Uffe A. Baslev
Influence of microstructure on laser damage threshold of IBS coatings

International Nuclear Information System (INIS)

Stolz, C.J.; Genin, F.Y.; Kozlowski, M.R.; Long, D.; Lalazari, R.; Wu, Z.L.; Kuo, P.K.

1996-01-01

Ion-beam sputtering (IBS) coatings were developed for the laser gyro industry to meet significantly different requirements than those of fusion lasers. Laser gyro mirrors are small ( 26 J/cm 2 at 1,064 nm with 3-ns pulses). As part of the National Ignition Facility (NIF) coating development effort, IBS coatings are being studied to explore the possible benefits of this technology to NIF optics. As an initial step to achieving the NIF size and damage threshold requirements, the coating process is being scaled to uniformly coat a 20 x 40 cm 2 area with reduced spectral, reflected wavefront, and laser damage threshold requirements. Here, multilayer coatings deposited by ion-beam sputtering with amorphous layers were found to have lower damage thresholds at 1,064 nm than similar coatings with crystalline layers. Interestingly, at higher fluences the damage was less severe for the amorphous coatings. The magnitude of the difference in damage thresholds between the two different microstructures was strongly influenced by the size of the tested area. To better understand the microstructure effects, single layers of HfO 2 with different microstructures were studied using transmission electron microscopy, ellipsometry, and a photothermal deflection technique. Since the laser damage initiated at defects, the influence of thermal diffusivity on thermal gradients in nodular defects is also presented
Poor Prognostic Factors in Patients with Malignant Pleural Mesothelioma Classified as Pathological Stage IB According to the Eighth Edition TNM Classification.

Science.gov (United States)

Takuwa, Teruhisa; Hashimoto, Masaki; Kuroda, Ayumi; Nakamura, Akifumi; Nakamichi, Toru; Fukuda, Akihiro; Matsumoto, Seiji; Kondo, Nobuyuki; Hasegawa, Seiki

2018-04-03

The change in TNM classification of malignant pleural mesothelioma (MPM) between the seventh and eighth edition classifications has resulted in the downstaging of many advanced-stage patients into pathological stage IB. Many mesotheliomas without lymph node metastasis have been classified as stage IB in the eighth edition classification. Stage IB mesotheliomas comprised a heterogeneous group with different prognosis. It is necessary to clarify the prognostic factors in this group. Between September 2009 and August 2016, a total of 89 patients with MPM underwent curative intent surgery [pleurectomy decortication n = 57 (64.1%), extrapleural pneumonectomy n = 32 (35.9%)] at our institution. Of these, 40 were reclassified as stage IB according to the eighth edition TNM classification. Independent unfavorable prognostic factors were identified by univariate analyses using the log-rank test and Cox proportional hazards regression models. Three independent significant factors were identified that indicated an unfavorable prognosis: a nonepithelioid subtype, lymphovascular invasion, and preoperative forced expiratory volume in 1 s (FEV1) < 2000 ml. Patients with no, one, and two of these risk factors showed 3-year overall survival probabilities of 94.7, 62.5, and 0%, respectively. The 3-year survival of patients with one factor did not differ significantly from that of patients with stage III MPM, whereas that of patients with two factors was significantly shorter (p = 0.015). Independent poor prognostic factors for patients with stage IB MPM patients, allowing subgroups with poorer and more favorable prognoses to be identified. This should help personalize decisions on adjuvant chemotherapy.
Enhanced salt stress tolerance in transgenic potato plants expressing IbMYB1, a sweet potato transcription factor.

Science.gov (United States)

Cheng, Yu-Jie; Kim, Myoung-Duck; Deng, Xi-Ping; Kwak, Sang-Soo; Chen, Wei

2013-12-01

IbMYB1, a transcription factor (TF) for R2R3-type MYB TFs, is a key regulator of anthocyanin biosynthesis during storage of sweet potatoes. Anthocyanins provide important antioxidants of nutritional value to humans, and also protect plants from oxidative stress. This study aimed to increase transgenic potatoes' (Solanum tuberosum cv. LongShu No.3) tolerance to environmental stress and enhance their nutritional value. Transgenic potato plants expressing IbMYB1 genes under the control of an oxidative stress-inducible peroxidase (SWPA2) promoter (referred to as SM plants) were successfully generated through Agrobacterium-mediated transformation. Two representative transgenic SM5 and SM12 lines were evaluated for enhanced tolerance to salinity, UV-B rays, and drought conditions. Following treatment of 100 mM NaCl, seedlings of SM5 and SM12 lines showed less root damage and more shoot growth than control lines expressing only an empty vector. Transgenic potato plants in pots treated with 400 mM NaCl showed high amounts of secondary metabolites, including phenols, anthocyanins, and flavonoids, compared with control plants. After treatment of 400 mM NaCl, transgenic potato plants also showed high DDPH radical scavenging activity and high PS II photochemical efficiency compared with the control line. Furthermore, following treatment of NaCl, UV-B, and drought stress, the expression levels of IbMYB1 and several structural genes in the flavonoid biosynthesis such as CHS, DFR, and ANS in transgenic plants were found to be correlated with plant phenotype. The results suggest that enhanced IbMYB1 expression affects secondary metabolism, which leads to improved tolerance ability in transgenic potatoes.
Overexpression of the IbMYB1 gene in an orange-fleshed sweet potato cultivar produces a dual-pigmented transgenic sweet potato with improved antioxidant activity.

Science.gov (United States)

Park, Sung-Chul; Kim, Yun-Hee; Kim, Sun Ha; Jeong, Yu Jeong; Kim, Cha Young; Lee, Joon Seol; Bae, Ji-Yeong; Ahn, Mi-Jeong; Jeong, Jae Cheol; Lee, Haeng-Soon; Kwak, Sang-Soo

2015-04-01

The R2R3-type protein IbMYB1 is a key regulator of anthocyanin biosynthesis in the storage roots of sweet potato [Ipomoea batatas (L.) Lam]. Previously, we demonstrated that IbMYB1 expression stimulated anthocyanin pigmentation in tobacco leaves and Arabidopsis. Here, we generated dual-pigmented transgenic sweet potato plants that accumulated high levels of both anthocyanins and carotenoids in a single sweet potato storage root. An orange-fleshed cultivar with high carotenoid levels was transformed with the IbMYB1 gene under the control of either the storage root-specific sporamin 1 (SPO1) promoter or the oxidative stress-inducible peroxidase anionic 2 (SWPA2) promoter. The SPO1-MYB transgenic lines exhibited higher anthocyanin levels in storage roots than empty vector control (EV) or SWPA2-MYB plants, but carotenoid content was unchanged. SWPA2-MYB transgenic lines exhibited higher levels of both anthocyanin and carotenoids than EV plants. Analysis of hydrolyzed anthocyanin extracts indicated that cyanidin and peonidin predominated in both overexpression lines. Quantitative reverse transcription-polymerase chain reaction analysis demonstrated that IbMYB1 expression in both IbMYB1 transgenic lines strongly induced the upregulation of several genes in the anthocyanin biosynthetic pathway, whereas the expression of carotenoid biosynthetic pathway genes varied between transgenic lines. Increased anthocyanin levels in transgenic plants also promoted the elevation of proanthocyanidin and total phenolic levels in fresh storage roots. Consequently, all IbMYB1 transgenic plants displayed much higher antioxidant activities than EV plants. In field cultivations, storage root yields varied between the transgenic lines. Taken together, our results indicate that overexpression of IbMYB1 is a highly promising strategy for the generation of transgenic plants with enhanced antioxidant capacity. © 2014 Scandinavian Plant Physiology Society.
Modeling and control simulation of the China CLEAR-IB

International Nuclear Information System (INIS)

Yan, Shoujun; Wan, Jiashuang; Wang, Pengfei; Fang, Huawei; Sun, Changyi; Zhao, Fuyu

2014-01-01

Highlights: • A model for the reactor for CLEAR-IB was developed. • A PI controller was designed to control the power. • A control strategy was adopted to control the water enthalpy of air cooler. • Dynamic simulation of the whole system was performed. - Abstract: To investigate the dynamic and control characteristics of the plant, a model for the main components of the reactor and the most relevant interactions among them is developed. The system comprises of the primary system with lead bismuth eutectic (LBE) as the coolant, the secondary circuit with steam water mixture as the coolant and the associated air cooling system for an effective rejection of thermal power to the environment as a final heat sink. A Proportional-Integral (PI) controller is designed to keep the power following the set value as quickly as possible. To keep outlet coolant of air coolers and inlet coolant of HXs being saturated water, a control strategy based on a simultaneous feed-forward and feedback scheme has been adopted. Based on the developed model and control strategy, dynamic simulation of the whole system in the cases of step changes of external source and load is performed. The simulation results show that the proposed model is accurate enough to describe the dynamic behaviors of the plant in spite of its simplicity. It has also been demonstrated that the developed controllers for the CLEAR-IB can provide superior reactor control capabilities due to the efficiency of the control strategy adopted
El Cortijo del Ahorcado (Baeza, Jaén : estudio de los restos arquitectónicos de época ibérica

Directory of Open Access Journals (Sweden)

María del Rosario Lucas Pellicer

1988-01-01

Full Text Available Las investigaciones dedicadas en los últimos años a la arqueología del mundo ibérico han contribuido notablemente a ampliar los conocimientos sobre la arquitectura funeraria y sobre los relieves y esculturas vinculados a excepcionales monumentos erigidos en honor a los difuntos. La publicación de M. Almagro Gorbea Arquitectura y Sociedad en la Cultura Ibérica, aparecida en 1983, es, junto con otros trabajos más recientes, buena prueba de los logros alcanzados. Basta contrastar las actuales teorías y la documentación hoy disponible con la síntesis que sobre arte ibérico trazara García y Bellido en 1953, para hacernos una idea cabal del progreso alcanzado en los últimos años.
Climatología de las depresiones térmicas en la Península Ibérica

OpenAIRE

Portela Lozano, María Adelaida

1994-01-01

Este trabajo tiene como principal objetivo el estudio de un sistema meteorológico característico en los meses de primavera y verano sobre la península ibérica: la depresión térmica ibérica. Aunque su existencia es bien conocida y ha sido considerada en las clasificaciones climatológicas de los tipos de tiempo, no se había realizado ningún tipo de análisis mas detallado, como el que se presenta en este trabajo, debido a su leve repercusión sobre la predicción del tiempo realizada a partir de l...
Una interpretación socioeconómica del bronce final en el sudoeste de la Península Ibérica

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Barceló, Juan A.

1992-12-01

Full Text Available In this paper, I have tried to study socioeconomic transformations in the Southwestern Iberian Peninsula during the Late Bronze Age. This case study gives interesting information to verify some of the theoretical constructs used to give meaning to the Passage from “Tribal” or Subsistence Economies to Social Stratification. We can say that in Southwestern Iberian during the Late Bronze Age, the introduction of a foreign technology and the beginnings of new exchange networks caused deep transformations in the Social Order, that had great significance in the passage to a Class-Society.

En este artículo pretendo estudiar las transformaciones socioeconómicas en el Sudoeste de la Península Ibérica durante el Bronce Final o Bronce Reciente -los dos términos son sinónimos en este trabajo-. Se trata del análisis de un caso histórico específico que proporciona interesante información para la ulterior verificación de algunas de las Teorías usadas para interpretar la transición de las economías de subsistencia «Tribales» a la Estratificación Social. He intentado demostrar que en el Sudoeste de la Península Ibérica durante el Bronce Final, la introducción de una tecnología foránea (el auténtico bronce y el inicio de nuevas redes de intercambio causaron una profunda transformación del Orden Social, que tuvo una gran relevancia en la transición hacia la Sociedad de Clases.
The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.

Science.gov (United States)

Staudacher, Heidi M; Whelan, Kevin

2017-08-01

There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%-80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
30 CFR 57.22202 - Main fans (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Main fans (I-A, I-B, I-C, II-A, III, V-A, and V... Main fans (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). (a) Main fans shall be— (1) Installed on the... mines, provided with an automatic signal device to give an alarm when the fan stops. The signal device...

Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Shu-xia Guo

2016-09-01

Full Text Available Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP TaqIB polymorphism (rs708272, the risk of developing composite ischemic cardiovascular disease (CVD and the concentration of high-density lipoprotein cholesterol (HDL-C, but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians.
Puñales de antenas en territorio ibérico

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Emeterio CUADRADO

2009-10-01

Full Text Available Así como en la zona peninsular ocupada por los iberos históricos encontramos la falcata como su espada peculiar, en las Mesetas y otros lugares del país, habitados por los invasores Célticos, hallamos en la segunda Edad del Hierro, la de antenas. La introducción de espadas de la Tene, que debe comenzar en el s. IV a. J. C, se hace más intensa en el mundo ibérico que en el céltico.
Knowledge-Based Energy Damage Model for Evaluating Industrialised Building Systems (IBS Occupational Health and Safety (OHS Risk

Directory of Open Access Journals (Sweden)

Abas Nor Haslinda

2016-01-01

Full Text Available Malaysia’s construction industry has been long considered hazardous, owing to its poor health and safety record. It is proposed that one of the ways to improve safety and health in the construction industry is through the implementation of ‘off-site’ systems, commonly termed ‘industrialised building systems (IBS’ in Malaysia. This is deemed safer based on the risk concept of reduced exposure, brought about by the reduction in onsite workers; however, no method yet exists for determining the relative safety of various construction methods, including IBS. This study presents a comparative evaluation of the occupational health and safety (OHS risk presented by different construction approaches, namely IBS and traditional methods. The evaluation involved developing a model based on the concept of ‘argumentation theory’, which helps construction designers integrate the management of OHS risk into the design process. In addition, an ‘energy damage model’ was used as an underpinning framework. Development of the model was achieved through three phases, namely Phase I – knowledge acquisitaion, Phase II – argument trees mapping, and Phase III – validation of the model. The research revealed that different approaches/methods of construction projects carried a different level of energy damage, depending on how the activities were carried out. A study of the way in which the risks change from one construction process to another shows that there is a difference in the profile of OHS risk between IBS construction and traditional methods.Therefore, whether the option is an IBS or traditional approach, the fundamental idea of the model is to motivate construction designers or decision-makers to address safety in the design process and encourage them to examine carefully the probable OHS risk variables surrounding an action, thus preventing accidents in construction.
Analysis of HgI2 and PbI2 crystals and detectors by particle-induced x-ray emission (PIXE) and ion backscattering spectroscopy (IBS)

International Nuclear Information System (INIS)

Bench, G.S.; Heikkinen, D.W.; Antolak, A.J.; Morse, D.H.; Pontau, A.E.; James, R.B.; David, D.C.; Burger, A.; Van Den Berg, L.

1993-03-01

The Ion Micro-Analysis Group (IMAG) in Livermore conducts quantitative trace elemental analysis with PIXE and depth profiling with IBS using an MeV ion microbeam. The system has the capability to produce two-dimensional trace element and IBS images. PIXE analyses have been conducted on HgI 2 and PbI 2 crystals and detector materials in order to identify and quantify near surface trace contaminants. IBS measurements have been conducted to investigate elemental depth distributions in various materials. The results of measurements on several different samples are reported and a discussion of factors affecting quantitative in vacuo microanalysis of these materials is presented
Influencia de los procesos tectónicos y volcánicos en la morfología de los márgenes continentales ibéricos

OpenAIRE

Maestro, A.; Bohoyo, F.; López-Martínez, J.; Acosta, J.; Gómez-Ballesteros, M.; Llave, E.; Muñoz, A.; Terrinha, P.; Dominguez, M.; Fernández-Sáez, F.

2015-01-01

Los márgenes continentales ibéricos son mayoritariamente de tipo pasivo, si bien, el sector septentrional ha actuado durante algunas etapas de su evolución geológica como un margen activo, y la zona meridional puede considerarse como un margen transformante que corresponde al límite entre las placas Ibérica y Africana y que también actuó como margen activo. Los diferentes tipos, orígenes e intensidades de los procesos endógenos que han afectado a los márgenes ibéricos han dado lugar al desarr...
Adjuvant postoperative radiation therapy following simple hysterectomy and radical hysterectomy in stage IB cancer of the cervix: Analysis of risk factors and patterns of failure

International Nuclear Information System (INIS)

Kim, R.Y.; Weppelmann, B.; Sanford, S.P.; Salter, M.M.; Brascho, D.J.

1986-01-01

Between 1969 and 1980, 242 cases of stage IB cancer of the cervix were referred to the department of radiation oncology for curative radiation therapy. In 186 cases treatment was with radiation therapy alone. In 56 cases treatment included adjuvant postoperative radiation therapy; a minimum follow-up of 5 years has been carried out in this group. In 17 cases radiation therapy followed a simple hysterectomy for an unexpected stage IB cancer of the cervix. In 39 cases radiation therapy was given after a radical hysterectomy for stage IB cancer of the cervix because of positive margins and/or positive pelvic lymph nodes
Fission Meter Information Barrier Attribute Measurement System: Task 1 Report: Document existing Fission Meter neutron IB system

Energy Technology Data Exchange (ETDEWEB)

Kerr, P. L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-02-28

An SNM attribute Information Barrier (IB) system was developed for a 2011 US/UK Exercise. The system was modified and extensively tested in a 2013-2014 US-UK Measurement Campaign. This work demonstrated rapid deployment of an IB system for potential treaty use. The system utilizes an Ortec Fission Meter neutron multiplicity counter and custom computer code. The system demonstrates a proof-of-principle automated Pu-240 mass determination with an information barrier. After a software start command is issued, the system automatically acquires and downloads data, performs an analysis, and displays the results. This system conveys the results of a Pu mass threshold measurements in a way the does not reveal sensitive information. In full IB mode, only red/green ‘lights’ are displayed in the software. In test mode, more detailed information is displayed. The code can also read in, analyze, and display results from previously acquired or simulated data. Because the equipment is commercial-off-the-shelf (COTS), the system demonstrates a low-cost short-lead-time technology for treaty SNM attribute measurements. A deployed system will likely require integration of additional authentication and tamper-indicating technologies. This will be discussed for the project in this and future progress reports.
E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

Energy Technology Data Exchange (ETDEWEB)

Fang, Zejun [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Gong, Chaoju [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058 (China); Liu, Hong [Zhejiang Normal University – Jinhua People' s Hospital Joint Center for Biomedical Research, Jinhua, Zhejiang, 321004 (China); Zhang, Xiaomin; Mei, Lingming [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Song, Mintao [Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005 (China); Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Chen, Xiang, E-mail: sychenxiang@126.com [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China)

2015-08-21

As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and
Record of Lower Gondwana megafloral assemblage from Lower Kamthi Formation of Ib River Coalfield, Orissa, India

Energy Technology Data Exchange (ETDEWEB)

Goswami, S. [Birbal Sahni Institute of Paleobotany, Lucknow (India)

2006-03-15

Recent investigations carried out in the Ib River Coalfield, Mahanadi Master Basin, Orissa, identified some fossiliferous beds in the Lower Gondwana deposits. Two exposures of the Lower Kamthi Formation yielded diverse and abundant plant remains, which include Neomariopteris, Vertebraria, and a scale leaf along with 14 Glossopteris species otherwise mapped as Barren Measures and Upper Kamthi formations. Glossopteris indica dominates the flora (22.78%) followed by G. communis (17.72%) and G. browniana (13.92%). Based on megafloral assemblages, different beds exposed at Gopalpur and Laxamanpur Pahar are assigned here to the Lower Kamthi Formation (Late Permian). The floristic composition suggests that a warm and humid climate prevailed during the Late Permian. The status of the Kamthi Formation in the Ib River Coalfield has been redefined in the present study.
Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine.

OpenAIRE

Wessels, M R; Paoletti, L C; Rodewald, A K; Michon, F; DiFabio, J; Jennings, H J; Kasper, D L

1993-01-01

Antisera elicited by type Ia group B streptococci (GBS) contain antibodies that react with both type Ia and type Ib strains. Previous studies suggested that antibodies elicited by type Ia organisms recognized a carbohydrate antigen or epitope common to Ia and Ib strains. We now report the synthesis and immunogenicity testing of a type Ia polysaccharide-tetanus toxoid (Ia-TT) conjugate vaccine. Ia-TT elicited type Ia polysaccharide-specific immunoglobulin G antibodies in all three of the rabbi...
Welcome address / Mats Estonius, Toomas Hendrik Ilves, Eduardo Ibàñes, Uffe A. Baslev

Index Scriptorium Estoniae

2010-01-01

Läänemere strateegia konverentsi avasõnad laususid Tallinna Ülikooli teadusprorektor Mats Estonius, Eesti Vabariigi president Toomas Hendrik Ilves ((vt. ka foto lk. 21), Hispaania Kuningriigi suursaadik Eestis Eduardo Ibáñes ja Taani Kuningriigi suursaadik Eestis Uffe A. Baslev
A convenient diagnostic function test of peripheral blood neutrophils in glycogen storage disease type Ib

NARCIS (Netherlands)

Verhoeven, A.J.; Visser, G; Van Zwieten, R; Gruszczynska, B; Poll-The, DWEET; Smit, GPA

Neutrophils from patients suffering from glycogen storage disease type To (GSD-Ib) show several defects, one of which is a decreased rate of glucose utilization. In this study, we established experimental conditions to show the stimulation of the neutrophil respiratory burst by extracellular
Nitrogen aggregation in Ib type synthetic diamonds at low pressure and high-temperature annealing

International Nuclear Information System (INIS)

Kazyuchits, N.M.; Rusetskij, M.S.; Latushko, Ya.I.; Kazyuchits, V.N.; Zajtsev, A.M.

2015-01-01

A new technique for annealing of diamonds at low pressure and high temperature (LPHT) is considered. The absorption spectra of synthetic Ib diamonds are given before and after annealing. This is evident from a comparison of the spectra that nitrogen aggregation process takes place at the LPHT annealing diamond. (authors)
La República Federal de Alemania ante el fin de las dictaduras ibéricas (1974-1976): miradas entrecruzadas

OpenAIRE

Sanz Díaz, Carlos

2012-01-01

El papel protagonista de la República Federal de Alemania, por medio principalmente de su gobierno, partidos y fundaciones políticas, y sindicatos, en las transiciones ibéricas ha sido puesto de manifiesto desde los primeros estudios sobre la dimensión internacional de los cambios de régimen político en Portugal y España en 1974-1975. Este artículo pretende contribuir al conocimiento del «factor alemán» en las transiciones ibéricas subrayando la percepción que se tenía desde Bonn de la peníns...
A patient with common glycogen storage disease type Ib mutations without neutropenia or neutrophil dysfunction

NARCIS (Netherlands)

Martens, DHJ; Kuijpers, TW; Maianski, NA; Rake, JP; Smit, GPA; Visser, G

We describe a 16-year old boy with glycogen storage disease type Ib, homozygous for the common 1211-1212delCT mutation, who never experienced neutropenia, and did not suffer from frequent infections or inflammatory bowel disease. In addition, neutrophil function tests showed no abnormalities.
′Belonging without Belonging′: Colm Tóibín′s Dialogue with the Past

DEFF Research Database (Denmark)

Bøss, Michael

2005-01-01

It is argued that Tóibín is not the typical 'revisionist' intellectual that some have made him into, but a humanist and a sort of in-between, making a virtue of his own ambivalences towards notions of tradition, community and nationhood. The essay makes an analysis of these ambivalences with refe...
Comparative evaluation of microleakage in class II cavities restored with Ceram X and Filtek P-90: An in vitro study

Directory of Open Access Journals (Sweden)

Poonam Bogra

2012-01-01

Full Text Available Context: Polymerization shrinkage in composite resins is responsible for microleakage. Methacrylate-based composite resins have linear reactive groups resulting in high polymerization shrinkage. A recently introduced composite resin Filtek P90 is based on siloxanes and oxiranes which polymerize by cationic "ring opening" polymerization resulting in reduced polymerization shrinkage. Objectives: Aim of this study was to compare microleakage in class II cavities restored with a nanoceramic restorative (Ceram X and a silorane composite (Filtek P90. Materials and Methods: Standardized class II box type cavities were prepared on mesial (Groups Ia and IIa and distal (Groups Ib and IIb surfaces of twenty extracted permanent molar teeth with gingival floor ending 1 mm coronal and apical to the cementoenamel junction, respectively. The teeth in Group Ia and Ib were restored with Ceram X and Group IIa and IIb with Filtek P90. The specimens were thermocycled and microleakage evaluated. Statistical Analysis Used: The data were statistically analyzed using Wilcoxon Signed-Rank test at the 0.05 level of significance. Results: Mean microleakage score of group la and lb was 1 ± 2.260 and 2.8 ± 1.229, respectively. And that of group Ila and llb was 0.2 ± .869 and 0.3 ± .588, respectively. When groups I and II were compared, results were statistically significant (P<0.05. Conclusion: It was concluded that silorane-based composite may be a better substitute for methacrylate-based composites.
Carlos Hugo Molina Saucedo. Andrés Ibáñez, un caudillo para el siglo XXI. La Comuna de Santa Cruz de la Sierra de 1876; Andrey Schelchkov. Andrés Ibáñez y la Revolución de la Igualdad en Santa Cruz: primer ensayo de federalismo en Bolivia, 1876-1877

Directory of Open Access Journals (Sweden)

Clayton Mendonça Cunha Filho

2014-11-01

Full Text Available Carlos Hugo Molina Saucedo. Andrés Ibáñez, un caudillo para el siglo XXI. La Comuna de Santa Cruz de la Sierra de 1876Andrey Schelchkov. Andrés Ibáñez y la Revolución de la Igualdad en Santa Cruz: primer ensayo de federalismo en Bolivia, 1876-1877
Estructuras de fondo rehundido altomedievales en la Península Ibérica

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TEJERIZO GARCÍA, C.

2014-01-01

Full Text Available La presencia de estructuras de fondo rehundido en contextos arqueológicos altomedievales está ampliamente documentada en toda Europa y cuenta con una dilatada historiografía. En la Península Ibérica, asociado a la expansión urbanística, se ha podido detectar un conjunto muy significativo de estas estructuras. Sin embargo, la falta de sistematización y análisis ha llevado a algunos problemas en su detección y documentación, así como a excesos conceptuales y de interpretación. En este trabajo se realiza una recopilación analítica de las evidencias de estructuras de fondo rehundido de época altomedieval presentes en la Península Ibérica mostrando su alta complejidad y diversidad. Basado en un análisis de la evidencia disponible, y frente a las tesis etnicistas que las vinculan a la llegada de grupos alóctonos, se propone una interpretación relacionada con el desarrollo de un modo de producción campesino tras la desarticulación de la economía imperial romana.
A novel one-step real-time multiplex PCR assay to detect Streptococcus agalactiae presence and serotypes Ia, Ib, and III.

Science.gov (United States)

Furfaro, Lucy L; Chang, Barbara J; Payne, Matthew S

2017-09-01

Streptococcus agalactiae is the leading cause of early-onset neonatal sepsis. Culture-based screening methods lack the sensitivity of molecular assays and do not indicate serotype; a potentially important virulence marker. We aimed to develop a multiplex PCR to detect S. agalactiae while simultaneously identifying serotypes Ia, Ib, and III; commonly associated with infant disease. Primers were designed to target S. agalactiae serotype-specific cps genes and the dltS gene. The assay was validated with 512 vaginal specimens from pregnant women. 112 (21.9%) were dltS positive, with 14.3%, 0.9%, and 6.3% of these identified as cps Ia, Ib, and III, respectively. Our assay is a specific and sensitive method to simultaneously detect S. agalactiae and serotypes Ia, Ib, and III in a single step. It is of high significance for clinical diagnostic applications and also provides epidemiological data on serotype, information that may be important for vaccine development and other targeted non-antibiotic therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

Science.gov (United States)

Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

2015-07-01

Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.
Comparison of medical costs generated by IBS patients in primary and secondary care in the Netherlands

NARCIS (Netherlands)

Flik, Carla E.; Laan, Wijnand; Smout, Andre J. P. M.; Weusten, Bas L. A. M.; de Wit, Niek J.

2015-01-01

Background: Irritable Bowel Syndrome (IBS) is a functional somatic syndrome characterized by patterns of persistent bodily complaints for which a thorough diagnostic workup does not reveal adequate explanatory structural pathology. Detailed insight into disease-specific health-care costs is critical
Aportaciones a la flora vascular del norte de la Península Ibérica

Directory of Open Access Journals (Sweden)

Fidalgo, E., Llorente, A., Cadiñanos, J.A., Tarruella, J.

2012-01-01

Full Text Available Se citan varios taxones nuevos o interesantes de la flora vascular del norte de la Península Ibérica, concretamente de las provincias vascas de Álava, Vizcaya y Guipúzcoa y de las comunidades de Cantabria, Asturias, Castilla-León y Navarra.
Intellectually Gifted Females and Their Perspectives of Lived Experience in the AP and IB Programs

Science.gov (United States)

Vanderbrook, Carrie M.

2006-01-01

The Advanced Placement (AP) and International Baccalaureate (IB) programs serve as popular choices for many intellectually gifted high school students. This article describes an aspect of a larger study that examined 5 intellectually gifted females' perceptions of their educational experience while enrolled in one of the programs. Using the…
Sparing bilateral neck level IB in oropharyngeal carcinoma and xerostomia outcomes.

Science.gov (United States)

Tam, Moses; Riaz, Nadeem; Kannarunimit, Danita; Peña, Angela P; Schupak, Karen D; Gelblum, Daphna Y; Wolden, Suzanne L; Rao, Shyam; Lee, Nancy Y

2015-08-01

To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC). A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; Pxerostomia outcomes.
El Calloviense de los Ibérides (dominio Ibérico, España. Síntesis bioestratigráfica

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Meléndez, G.

1987-04-01

Full Text Available More than 60 Callovian geological profiles in the Iberides (between Burgos and Alicante have been studied. The Ricla (Zaragoza Callovian section as reference biostratigraphic outline has been established, documenting almost all Callovian Mesogean Zones and Subzones and many biohorizons. The others profiles in relation with the elected as reference are briefly described, standing out the scarce thickness and Upper Callovian and frequently Middle Callovian absence.Se han estudiado más de 60 perfiles geológicos de edad Calloviense en los Ibérides (entre Burgos y Alicante. El Calloviense de Ricla (Zaragoza se toma como esquema bioestratigráfico de referencia, documentándose casi todas las zonas y subzonas y muchos de los biohorizontes del Calloviense de la Mesogea. Los demás perfiles se describen sumariamente en relación al elegido como referencia, destacando su escasa potencia y la falta de Calloviense superior y frecuentemente de Calloviense medio.
A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways

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Li Zeng

2018-03-01

Full Text Available Though the detailed pathological mechanism of post-infectious irritable bowel syndrome (PI-IBS remains unclear, accumulating evidence indicates that oxidative stress and inflammation are implicated in the process of PI-IBS. Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. EphA2, a member of Eph receptor family, promotes oxidative stress and inflammatory responses via regulation of Nrf2 and NF-κB signaling pathways in various types of human diseases. Understanding the mechanisms by which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for the development of new strategies to treat PI-IBS. However, the effects of ALW-II-41-27, a novel EphA2 inhibitor on PI-IBS and the underlying molecular mechanisms have never been studied. In the present study, we showed that ALW-II-41-27 decreased gastrointestinal motility and abdominal withdrawal reflex (AWR scores, markedly reduced the levels of oxidative stress markers [4-hydroxy-2-nonenal (4-HNE, protein carbonyl, and 8-hydroxy-2-de-axyguanine (8-OHdG] and proinflammatory cytokines (TNF-α, IL-6, IL-17, and ICAM-1, and remarkably increased the level of anti-inflammatory cytokine (IL-10 in serum and colon of Trichinella spiralis-infected mice. Moreover, ALW-II-41-27 was effective in suppressing oxidative stress and inflammation in LPS-treated NCM460 colonic cells. Treatment of ALW-II-41-27 reversed the activation of NF-κB and inactivation of Nrf2 in LPS-treated NCM460 cells. Importantly, these protective effects of ALW-II-41-27 were partially inhibited by EphA2 KO and abolished by EphA2 overexpression. In conclusion, EphA2 may represent a promising therapeutic target for patients with PI-IBS and ALW-II-41-27 might function as a novel therapeutic agent for PI-IBS.
FIST/6IB1, BWR/6 System Responses to Intermediate Break in Recirculation Suction Line LINE

International Nuclear Information System (INIS)

1993-01-01

1 - Description of test facility: BWR/6-218 standard plant. A full size bundle with electrically heated rods is used to simulate the reactor core. A scaling ratio of 1/624 is applied in the design of the system components. Key features of the FIST facility include: (1) Full height test vessel and internals; (2) correctly scaled fluid volume distribution; (3) simulation of ECCS, S/RV, and ADS; (4) level trip capability; (5) heated feedwater supply system, which provides the capability for steady state operation. 2 - Description of test: Test 6IB1 investigates system responses to an intermediate break in the recirculation suction line. BWR system licensing evaluations for various size recirculation break LOCA's indicates that a break size of about 0.2 sq.ft., without LPCS operation, is the highest PCT case for the intermediate break LOCA. Test 6IB1 simulates this event
Invasive cervical carcinoma (Stages IB-IIB)

International Nuclear Information System (INIS)

Sironi, S.; Zanello, A.; Rodighiero, M.G.; Vanzulli, A.; Del Maschio, A.; Taccagni, G.L.; Belloni, C.

1991-01-01

In the patients with invasive cervical carcinoma, the accurate assessment of parametrial invasion greatly affects the therapeutic choice between surgery and radiation therapy. As a matter of fact, surgery is usually performed only in the patients with carcinoma confined to the cervix, whereas those with parametrial involvement, or more advanced stages, are treated with radiation therapy. This prospective study was aimed at investigating the comparative adequecy of CT and MR imaging in assessing parametrial status in the patients with invasive cervical cancer. Twenty-one consecutive patients, with histologic diagnosis of cervical carcinoma, were investigated. All of them were clinically considered as having invasive cervical cancer (FIGO stage IB-IIB) and subsequently underwent surgery. In all cases, detailed histology of the parametrium was obtained. Pathological data were compared with CT and MR findings in all cases. As for assessing parametrial involvement by cancer, CT had 62% accuracy, 63% sensitivity, and 60% specificity, versus MR imaging 81% accuracy, 69% sensitivity, and 80% specificify. Therefore, MR imaging appears to be superior to CT in assessing the parametrial status of patients with invasive cervical carcinoma; the method yields valuable information for treatment planning
Aportaciones coloniales a las creencias funerarias ibéricas

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Joaquín García Raya

1999-01-01

Full Text Available La «mediterraneidad» de la península ibérica ha producido una serie de contactos con otros pueblos de esta cuenca, atraídos por su riqueza minera o como recurso a la colmatación de sus territorios de origen, lo cual produjo una traslación de ritos funerarios, cuya lectura arqueológica ha significado interpretaciones erróneas básicas.The "Mediterranean style» of the Iberian Península has given way to a series of contacts wth otherpeoples fron this valley, attracted by its mining richness and as an option tgo the overcrowding of their native territories. This brought about the implantation of funeral ceremonies, who archaelogical reading has meant false interpretations.
Srinagarind Hospital experience in concurrent chemoradiation for 100 patients with stage IB2 to IVA uterine cervical cancer

International Nuclear Information System (INIS)

Tangsiriwatthana, T.; Chumworathayi, B.; Yuenyao, P.; Luanratanakorn, S.; Pattamadilok, J.

2007-01-01

The aim of this study was to determine responses, acute adverse effects, and survival outcomes of women with stage IB2 to IVA treated with weekly cisplatin concurrent with pelvic irradiation at Srinagarind Hospital. The medical records of 100 women with cervical cancer stage IB2 to IVA who were treated with weekly cisplatin 40 mg/m 2 concurrent with pelvic radiotherapy at Srinagarind Hospital between January 2003 and June 2006 were reviewed and analyzed. During the study period, 100 women were eligible for analysis, with a mean age of 46 years (range 24-60 years). Distribution according to International Federation of Gynecology and Obstetrics (FIGO) staging was IB2 1.0%, IIB 47.0%, IIIB 51.0%, and IVA 1.0%, respectively. A total of 86 patients received five or more cycles of weekly cisplatin. Grade 3 and 4 hematologic toxicities were found in 6.0%. The overall response rate was 97.0%. Complete response was achieved in 86 patients (86.0%) and partial response in 11 patients (11.0%). Stable disease was found in 1 patient (1.0%) but no progressive disease was found. Progression-free survival and overall survival rate were 69.6% and 96.1%, respectively. Weekly cisplatin (40 mg/m 2 ) concurrent with pelvic irradiation for locally advanced cervical cancer was effective with acceptable toxicity in Thai women. (author)
MicroRNA modulation induced by AICA ribonucleotide in J1 mouse ES cells.

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Xiaoyan Shi

Full Text Available ES cells can propagate indefinitely, maintain self-renewal, and differentiate into almost any cell type of the body. These properties make them valuable in the research of embryonic development, regenerative medicine, and organ transplantation. MicroRNAs (miRNAs are considered to have essential functions in the maintenance and differentiation of embryonic stem cells (ES cells. It was reported that, strong external stimuli, such as a transient low-pH and hypoxia stress, were conducive to the formation of induced pluripotent stem cells (iPS cells. AICA ribonucleotide (AICAR is an AMP-activated protein kinase activator, which can let cells in the state of energy stress. We have demonstrated that AICAR can maintain the pluripotency of J1 mouse ES cells through modulating protein expression in our previous research, but its effects on ES cell miRNA expression remain unknown. In this study, we conducted small RNA high-throughput sequencing to investigate AICAR influence on J1 mouse ES cells by comparing the miRNA expression patterns of the AICAR-treated cells and those without treatment. The result showed that AICAR can significantly modulate the expression of multiple miRNAs, including those have crucial functions in ES cell development. Some differentially expressed miRNAs were selected and confirmed by real-time PCR. For the differently expressed miRNAs identified, further study was conducted regarding the pluripotency and differentiation associated miRNAs with their targets. Moreover, miR-134 was significantly down-regulated after AICAR treatment, and this was suggested to be directly associated with the up-regulated pluripotency markers, Nanog and Sox2. Lastly, Myc was significantly down-regulated after AICAR treatment; therefore, we predicted miRNAs that may target Myc and identified that AICAR induced up-regulation of miR-34a, 34b, and 34c can repress Myc expression in J1 mouse ES cells. Taken together, our study provide a new mechanism for
HLA-G in human reproduction

DEFF Research Database (Denmark)

Hviid, Thomas Vauvert F

2005-01-01

The non-classical human leukocyte antigen (HLA) class Ib genes, HLA-E, -G and -F, are located on chromosome 6 in the human major histocompatibility complex (MHC). HLA class Ib antigens resemble the HLA class Ia antigens in many ways, but several major differences have been described. This review ...... transplantation and in inflammatory or autoimmune disease, and of HLA-G in an evolutionary context, are also briefly examined....
iB1350 no.1. A generation III.7 reactor after the Fukushima Daiichi accident

International Nuclear Information System (INIS)

Sato, Takashi; Matsumoto, Keiji; Hosomi, Kenji; Kojima, Yoshihiro; Taguchi, Keisuke

2017-01-01

iB1350 stands for an innovative, intelligent and inexpensive BWR 1350. It is the first generation III.7 reactor after the Fukushima Daiichi accident. It has incorporated lessons learned from the Fukushima Daiichi accident and WENRA safety objectives. It has innovative safety to cope with devastating natural disasters including a giant earthquake, a large tsunami and a monster hurricane. The iB1350 can survive passively such devastation and a very prolonged SBO without any support from the outside of a site up to 7 days even preventing core melt. It, however, is based on the well-established proven ABWR design. The NSSS is exactly the same as that of the current ABWR. As for safety design, it has a double cylinder RCCV (Mark W containment) and in-depth hybrid safety systems (IDHS). The Mark W containment has double FP confinement barriers and the in-containment filtered venting system (IFVS) that enable passively no emergency evacuation outside the immediate vicinity of the plant for a SA. It has a large volume to hold hydrogen, an innovative core catcher (iCC), a passive flooding system and an innovative passive containment cooling system (iPCCS) establishing passively practical elimination of containment failure even in a long term. The IDHS consists of 4 division active safety systems for a DBA, 2 division active safety systems for a SA and built-in passive safety systems (BiPSS) consisting of an isolation condenser (IC) and the iPCCS for a SA. While the conventional PCCS can never cool the S/P, the iPCCS can automatically cool the S/P directly even in a DBA LOCA. That makes it possible for the iB1350 to optimize the active safety systems for a DBA. Sato came up with several optimized configurations of the IDHS that are expected to achieve further cost reduction and enhance its reliability resulting from passive feature of the iPCCS. The IC/iPCCS pool has enough capacity for 7 day grace period. The IC/iPCCS heat exchangers, the core and the spent fuel pool are
Regulators of ribonucleotide reductase inhibit Ty1 mobility in saccharomyces cerevisiae

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O'Donnell John P

2010-11-01

Full Text Available Abstract Background Ty1 is a long terminal repeat retrotransposon of Saccharomyces cerevisiae, with a replication cycle similar to retrovirus replication. Structurally, Ty1 contains long terminal repeat (LTR regions flanking the gag and pol genes that encode for the proteins that enable Ty1 mobility. Reverse transcriptase produces Ty1 complementary (cDNA that can either be integrated back into the genome by integrase or recombined into the yeast genome through homologous recombination. The frequency of Ty1 mobility is temperature sensitive, with optimum activity occurring at 24-26°C. Results In this study, we identified two host genes that when deleted allow for high temperature Ty1 mobility: RFX1 and SML1. The protein products of these genes are both negative regulators of the enzyme ribonucleotide reductase, a key enzyme in regulating deoxyribonucleotide triphosphate (dNTP levels in the cell. Processing of Ty1 proteins is defective at high temperature, and processing is not improved in either rfx1 or sml1 deletion strains. Ty1 mobility at high temperature is mediated by homologous recombination of Ty1 cDNA to Ty1 elements within the yeast genome. We quantified cDNA levels in wild type, rfx1 and sml1 deletion background strains at different temperatures. Southern blot analysis demonstrated that cDNA levels were not markedly different between the wild type and mutant strains as temperatures increased, indicating that the increased Ty1 mobility is not a result of increased cDNA synthesis in the mutant strains. Homologous recombination efficiency was increased in both rfx1 and sml1 deletion strains at high temperatures; the rfx1 deletion strain also had heightened homologous recombination efficiency at permissive temperatures. In the presence of the dNTP reducing agent hydroxyurea at permissive temperatures, Ty1 mobility was stimulated in the wild type and sml1 deletion strains but not in the rfx1 deletion strain. Mobility frequency was greatly
Class I self-splicing introns are found in the T-even bacteriophage family

International Nuclear Information System (INIS)

Chu, F.K.; Maley, F.; Maley, G.F.

1987-01-01

The thymidylate synthase gene (td) and ribonucleotide reductase B2 subunit gene (nrdB) EMBO both of bacteriophage T4 in origin, are procaryotic intron-containing protein-encoding genes. To screen for other procaryotic introns, southern hybridization analysis of several procaryotic genomes was carried out, using T4 phage td DNA restriction fragments and synthetic oligodeoxynucleotides defining strategic td exon and intron regions. Furthermore, the labeling pattern of total RNA with [α- 32 P]GTP, a typical reaction of self-splicing RNAs (class I), was examined. Experimental data implicate multiple self-splicing introns only in the T-even phages: five (1, 0.9, 0.83, 0.75 and 0.6 kb) in T4 and three (1, 0.9 and 0.75 kb) each in T2 and T6 phages. Northern hybridization analysis of total RNA extracted from T-even phage-infected cells confirms that the 1 kb RNA from each phage is in fact the excised intron segment from the precursor RNA transcribed from an intron-containing td gene in each case. This RNA cyclizes to form a contiguous circular molecule. The 0.6 kb RNA is most likely the T4 phage nrdB intron which seems to be absent from the corresponding gene in T2 and T6. The remaining RNA species are candidates for other self-splicing introns in these phages
Mida kujutab endast IB õppekava? / Toomas Kruusimägi, Anu Parts, Karl Hendrik Thomson ; intervjueerinud Raivo Juurak

Index Scriptorium Estoniae

Kruusimägi, Toomas, 1962-

2010-01-01

Uuest rahvusvahelisest International Baccalaureate'i (IB) õppekavast ja selle rakendamisest Tallinna Inglise Kolledži 11. klassis alates möödunud aastast räägivad kooli direktor Toomas Kruusimägi, õppedirektor Anu Parts ning õpilane Karl Hendrik Thomson
TINGKAT KEPUASAN PENGGUNA APLIKASI INTERSYSTEM BUSINESS SOLUTION (IBS PADA PT CITAJAYA INFINITE SYSTEM

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Anderes Gui

2009-05-01

Full Text Available Use of applications to assist business processes to be completed faster, saat have been very widely adopted by companies so that good performance yang applications and meet the needs of users will be very important. The purpose of this research is to find the application user expectations Intersystem Business Solution (IBS in PT Citajaya Infinite System and find out how the performance of these applications after implemented so that will be generated an output, which form the level of satisfaction from the use of applications by managers and employees at the company. Data collection methods used were observation, interviews, and questionnaires. Manual methods used in data processing, Microsoft Excel 2003, and SPSS version 13.0. While the analysis method using gap analysis to determine the scale and range of satisfaction levels. So, one conclusion that can be drawn from this study is the performance of this application is sufficient to meet user expectations.Keywords: level of satisfaction, users, IBS applicationABSTRAKPenggunaan aplikasi untuk membantu proses bisnis agar menjadi lebih cepat diselesaikan, saat ini sudah sangat banyak diterapkan oleh perusahaan-perusahaan sehingga kinerja aplikasi yang baik dan memenuhi kebutuhan dari pengguna akan sangat penting sekali. Tujuan dari penelitian ini adalah untuk mencari harapan pengguna aplikasi Intersystem Business Solution (IBS pada PT Citajaya Infinite System dan mengetahui bagaimana kinerja aplikasi ini setelah diimplementasikan sehingga akan dihasilkan sebuah output, yang berupa tingkat kepuasan dari penggunaan aplikasi oleh para manajer dan karyawan di perusahaan tersebut. Metode pengumpulan data yang digunakan adalah observasi, wawancara, dan kuesioner. Metode pengolahan datanya menggunakan manual, Microsoft Excel 2003, dan SPSS versi 13.0. Sedangkan metode analisisnya menggunakan gap analysis dan rentang skala untuk menentukan tingkat kepuasan. Jadi, salah satu simpulan yang dapat diambil
Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib

NARCIS (Netherlands)

Correia, Catherine E.; Bhattacharya, Kaustuv; Lee, Philip J.; Shuster, Jonathan J.; Theriaque, Douglas W.; Shankar, Meena N.; Smit, G. Peter A.; Weinstein, David A.

2008-01-01

Background: Type I glycogen storage disease (GSD) is caused by a deficiency of glucose-6-phosphatase resulting in severe fasting hypoglycemia. Objective: We compared the efficacy of a new modified starch with the currently used cornstarch therapy in patients with type Ia and Ib GSD. Design: This was
Necrópolis Ibérica de «El Cigarralejo» : estudio osteológico (comparado con los ajuares

Directory of Open Access Journals (Sweden)

M. Santonja Alonso

1993-01-01

Full Text Available Se expone detalladamente la «historia» osteológica de 187 cremados de la Necrópolis Ibérica de «El Cigarralejo»: sexo, edad, medidas de epífisis y grosores de pared en ios fragmentos más frecuentes, paleontología que presentan, sus interrogantes y conclusiones. Igualmente, sobre la identificación de las tumbas dobles y de las infantiles.The osteologic «history» of 187 cremations from the «Necrópolis Ibérica de el Cigarralejo» is expounded in detall: sex, age, epiphysis, measurements, thickness of the most frequent pieces, and palaeopathology features, as well as some and conclusions. At the same time, it will deal with Children's and double graves Identification.

Impactos, vulnerabilidad y adaptación al Cambio Climático en los bosques ibéricos.

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Asier Herrero

2017-01-01

Full Text Available Se han registrado numerosos impactos relacionados con el cambio climático en los bosques ibéricos que pueden cambiar la composición, estructura y funcionamiento de los mismos. Es importante considerar que los efectos del cambio climático interactúan comúnmente con otros motores de cambio, dificultando de esta manera la cuantificación de la contribución del cambio climático en los impactos observados. Entre los impactos registrados encontramos alteraciones fisiológicas, fenológicas, demográficas y de distribución, las cuales a su vez pueden provocar cambios en la composición, estructura y funcionamiento de los ecosistemas forestales ibéricos. A medida que el cambio climático avance, y las condiciones climáticas se alejen cada vez más de las actuales, se espera un aumento de los impactos observados. En este contexto, se hace necesario evaluar correctamente la vulnerabilidad de poblaciones, especies y ecosistemas frente al cambio climático futuro para poder diseñar y aplicar medidas de adaptación eficaces que minimicen los impactos y favorezcan el proceso de ajuste a las nuevas condiciones. La aplicación de las medidas de adaptación debe enmarcarse en una gestión adaptativa y anticipadora, que fomente la colaboración activa entre todos los actores involucrados en la gestión e investigación de los bosques ibéricos.
Jinetes en Grecia y sus ecos en la cultura ibérica

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Domínguez Monedero, Adolfo J.

2005-12-01

Full Text Available The uses of the horse in Greece are reviewed from the Mycenaean until Late Classical times in order to trace its development as a military weapon. Besides, the social projection of the use of the horse in Greece is also addressed, as well as the development of equestrian contests which served also as a means of stressing the social status of the leading groups within the Greek poleis. In a final chapter the possible reflections of the uses of the horse in Greece in the Iberian world are also considered, although the possible relationships are confined mainly to iconographical loans from Greek prototypes to some Iberian artistic manifestations.

Se pasa revista a los usos del caballo en Grecia desde época micénica hasta el final del Clasicismo a fin de observar su desarrollo como arma militar. Además, se estudia también la proyección social del uso del caballo en Grecia así como el desarrollo de competiciones ecuestres que sirvieron también como medio de exhibir el estatus social de los grupos dirigentes de las poleis griegas. En el capítulo final se consideran también los posibles ecos de los usos del caballo en Grecia en el mundo ibérico, aunque estas posibles relaciones se limitan sobre todo a préstamos iconográficos de modelos griegos a algunas manifestaciones artísticas ibéricas.
Ribonucleotide reductase as a drug target against drug resistance Mycobacterium leprae: A molecular docking study.

Science.gov (United States)

Mohanty, Partha Sarathi; Bansal, Avi Kumar; Naaz, Farah; Gupta, Umesh Datta; Dwivedi, Vivek Dhar; Yadava, Umesh

2018-06-01

Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aimed to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy. The study was conducted by retrieving RNR of M. leprae from GenBank. A molecular 3D model of M. leprae was predicted using homology modelling and validated. A total of 325 characters were included in the analysis. The predicted 3D model of RNR showed that the ϕ and φ angles of 251 (96.9%) residues were positioned in the most favoured regions. It was also conferred that 18 α-helices, 6 β turns, 2 γ turns and 48 helix-helix interactions contributed to the predicted 3D structure. Virtual screening of Food and Drug Administration approved drug molecules recovered 1829 drugs of which three molecules, viz., lincomycin, novobiocin and telithromycin, were taken for the docking study. It was observed that the selected drug molecules had a strong affinity towards the modelled protein RNR. This was evident from the binding energy of the drug molecules towards the modelled protein RNR (-6.10, -6.25 and -7.10). Three FDA-approved drugs, viz., lincomycin, novobiocin and telithromycin, could be taken for further clinical studies to find their efficacy against drug resistant leprosy. Copyright © 2018 Elsevier B.V. All rights reserved.
La memoria del último exilio español en la escritura de tres mujeres: Victoria Kent, Dolores Ibárruri y Carmen Parga

Directory of Open Access Journals (Sweden)

Bettina Pacheco

2011-11-01

Full Text Available Resumo: Este artigo realiza uma breve análise de três obras de testemunhos do exílio escritas por mulheres: Victoria Kent, destacada advogada socialista cromprometida com o governo da República Espanhola; Dolores Ibárruri, a mítica Pasionária; e Carmen Parga, republicana exilada na Rússia e México. As três dão sua visão, a sua maneira e através da escrita, sobre o drama vivido oferecendo sua concepção particular do exílio. Antes de entrar nas obras aludidas, examina-se brevemente as duas concepções sobre a dramática experiência do exilado que Cláudio Guillén reconheceu na escrita dos clássicos: Ovídio e Plutarco.Palavras-chave: Literatura comparada; literatura espanhola; Victoria Kent; Dolores Ibárruri; Carmen Parga; literatura latina; Ovídio; Plutarco; exílio.Resumen: Este artículo realiza um somero análisis de três obras testimoniales del exílio escritas por mujeres: Victoria Kent, destacada abogada socialista comprometida com el gobierno de la República Española; Dolores Ibárruri, la mítica Pasionaria; y Carmen Parga, republicana exiliada en Rusía y México. Las tres dan su visión, a su manera y a través de la escritura, sobre el drama vivido ofreciendo su concepción particular del exílio. Antes de entrar en las obras aludidas, se examina brevemente las dos concepiones sobre la dramática experiencia del exilado que Cláudio Guillén há reconocido em la escritura de dos clássicos: Ovídio y Plutarco.Palabras-clave: Literatura comparada; literatura española; Victoria Kent; Dolores Ibárruri; Carmen Parga; literatura latina; Ovídio; Plutarco; exílio.Keywords: Comparative literature; Spanish literature; Victoria Kent; Dolores Ibárruri; Carmen Parga; latin literature; Ovid; Plutarch; exile.
H+ -pyrophosphatase IbVP1 promotes efficient iron use in sweet potato [Ipomoea batatas (L.) Lam.].

Science.gov (United States)

Fan, Weijuan; Wang, Hongxia; Wu, Yinliang; Yang, Nan; Yang, Jun; Zhang, Peng

2017-06-01

Iron (Fe) deficiency is one of the most common micronutrient deficiencies limiting crop production globally, especially in arid regions because of decreased availability of iron in alkaline soils. Sweet potato [Ipomoea batatas (L.) Lam.] grows well in arid regions and is tolerant to Fe deficiency. Here, we report that the transcription of type I H + -pyrophosphatase (H + -PPase) gene IbVP1 in sweet potato plants was strongly induced by Fe deficiency and auxin in hydroponics, improving Fe acquisition via increased rhizosphere acidification and auxin regulation. When overexpressed, transgenic plants show higher pyrophosphate hydrolysis and plasma membrane H + -ATPase activity compared with the wild type, leading to increased rhizosphere acidification. The IbVP1-overexpressing plants showed better growth, including enlarged root systems, under Fe-sufficient or Fe-deficient conditions. Increased ferric precipitation and ferric chelate reductase activity in the roots of transgenic lines indicate improved iron uptake, which is also confirmed by increased Fe content and up-regulation of Fe uptake genes, e.g. FRO2, IRT1 and FIT. Carbohydrate metabolism is significantly affected in the transgenic lines, showing increased sugar and starch content associated with the increased expression of AGPase and SUT1 genes and the decrease in β-amylase gene expression. Improved antioxidant capacities were also detected in the transgenic plants, which showed reduced H 2 O 2 accumulation associated with up-regulated ROS-scavenging activity. Therefore, H + -PPase plays a key role in the response to Fe deficiency by sweet potato and effectively improves the Fe acquisition by overexpressing IbVP1 in crops cultivated in micronutrient-deficient soils. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.
Rapid detection of AAC(6')-Ib-cr production using a MALDI-TOF MS strategy.

Science.gov (United States)

Pardo, C-A; Tan, R N; Hennequin, C; Beyrouthy, R; Bonnet, R; Robin, F

2016-12-01

Plasmid-mediated quinolone resistance mechanisms have become increasingly prevalent among Enterobacteriaceae strains since the 1990s. Among these mechanisms, AAC(6')-Ib-cr is the most difficult to detect. Different detection methods have been developed, but they require expensive procedures such as Sanger sequencing, pyrosequencing, polymerase chain reaction (PCR) restriction, or the time-consuming phenotypic method of Wachino. In this study, we describe a simple matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method which can be easily implemented in clinical laboratories that use the MALDI-TOF technique for bacterial identification. We tested 113 strains of Enterobacteriaceae, of which 64 harbored the aac(6')-Ib-cr gene. We compared two MALDI-TOF strategies, which differed by their norfloxacin concentration (0.03 vs. 0.5 g/L), and the method of Wachino with the PCR and sequencing strategy used as the reference. The MALDI-TOF strategy, performed with 0.03 g/L norfloxacin, and the method of Wachino yielded the same high performances (Se = 98 %, Sp = 100 %), but the turnaround time of the MALDI-TOF strategy was faster (<5 h), simpler, and inexpensive (<1 Euro). Our study shows that the MALDI-TOF strategy has the potential to become a major method for the detection of many different enzymatic resistance mechanisms.
Purification, characterization and end product analysis of dextran degrading endodextranase from Bacillus licheniformis KIBGE-IB25.

Science.gov (United States)

Zohra, Rashida Rahmat; Aman, Afsheen; Ansari, Asma; Haider, Muhammad Samee; Qader, Shah Ali Ul

2015-07-01

Degradation of high molecular weight dextran for obtaining low molecular weight dextran is based on the hydrolysis using chemical and enzymatic methods. Current research study focused on production, purification and characterization of dextranase from a newly isolated strain of Bacillus licheniformis KIBGE-IB25. Dextranase was purified up to 36 folds with specific activity of 1405 U/mg and molecular weight of 158 kDa. It was found that enzyme performs optimum cleavage of dextran (5000 Da, 0.5%) at 35 °C in 15 min at pH 4.5 with a Km and Vmax of 0.374 mg/ml and 182 μmol/min, respectively. Relative amino acid composition analysis of purified enzyme suggested the presence of higher number of hydrophobic, acidic and glycosylation promoting amino acids. The N-terminal sequence of dextranase KIBGE-IB25 was AYTVTLYLQG. It exhibited distinct amino acid sequence yet shared some inherent characteristics with glycosyl hydrolases (GH) family 49 and also testified the presence of O-glycosylation at N-terminal end. Copyright © 2015 Elsevier B.V. All rights reserved.
Estilo desornamentado, arquitetura-chã: alguns aspectos do renascimento na Península Ibérica

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Andrea Buchidid Loewen

2011-12-01

Full Text Available En el siglo 16, en la Península Ibérica, la asimilación del romano dale impulsión a una corriente arquitectónica en la cual un clasicismo progresivo e la desnudez decorativa anuncian la llegada del llamado Renacimiento. A despecho de sus peculiaridades, tanto el estilo-chão portugués cuanto el desornamentado español se sostienen sobre doctrinas arquitectónicas de origen itálica. Traídas sea por los artífices que estuvieran en tales tierras - o por los arquitectos desde allá llamados a trabajar en la Península - sea por los tratados de arquitectura importados y, más tarde, traducidos al castellano y al portugués, tales doctrinas alimentaran todavía la publicación de otras significativas obras de sistematización teórica, como la sagrediana Medidas del romano. Esto artículo discute tales aspectos del Renacimiento en la Península Ibérica.
`Science to the Glory of God'. The Popular Science Magazine Ibérica and its Coverage of Radioactivity, 1914-1936

Science.gov (United States)

Herran, Néstor

2012-03-01

This paper provides a first approach to the history of Ibérica, one of the most important popular science magazines published in Spain before the Civil War. Founded in 1914 by members of the Society of Jesus based at the Ebro Observatory, Ibérica reached a weekly circulation of about 10,000 in the mid 1920s, and was instrumental in extending science education in Jesuit education facilities and in developing a "reactionary modernist" culture that embraced Catholicism and modernisation. By focusing on its coverage of radioactivity and the radium industry, the article aims to examine the magazine's popularising style and ideology, and to determine its role in the debates regarding the cultural value of science in the first decades of twentieth century Spain.
MULTI-WAVELENGTH OBSERVATIONS OF SUPERNOVA 2011ei: TIME-DEPENDENT CLASSIFICATION OF TYPE IIb AND Ib SUPERNOVAE AND IMPLICATIONS FOR THEIR PROGENITORS

International Nuclear Information System (INIS)

Milisavljevic, Dan; Margutti, Raffaella; Soderberg, Alicia M.; Chomiuk, Laura; Sanders, Nathan E.; Pignata, Giuliano; Bufano, Filomena; Fesen, Robert A.; Parrent, Jerod T.; Parker, Stuart; Mazzali, Paolo; Pian, Elena; Pickering, Timothy; Buckley, David A. H.; Crawford, Steven M.; Gulbis, Amanda A. S.; Hettlage, Christian; Hooper, Eric; Nordsieck, Kenneth H.; O'Donoghue, Darragh

2013-01-01

We present X-ray, UV/optical, and radio observations of the stripped-envelope, core-collapse supernova (SN) 2011ei, one of the least luminous SNe IIb or Ib observed to date. Our observations begin with a discovery within ∼1 day of explosion and span several months afterward. Early optical spectra exhibit broad, Type II-like hydrogen Balmer profiles that subside rapidly and are replaced by Type Ib-like He-rich features on a timescale of one week. High-cadence monitoring of this transition suggests absorption attributable to a high-velocity (∼> 12, 000 km s –1 ) H-rich shell, which is likely present in many Type Ib events. Radio observations imply a shock velocity of v ≈ 0.13 c and a progenitor star average mass-loss rate of M-dot ∼1.4×10 -5 M sun yr -1 (assuming wind velocity v w = 10 3 km s –1 ). This is consistent with independent constraints from deep X-ray observations with Swift-XRT and Chandra. Overall, the multi-wavelength properties of SN 2011ei are consistent with the explosion of a lower-mass (3-4 M ☉ ), compact (R * ∼ 11 cm), He-core star. The star retained a thin hydrogen envelope at the time of explosion, and was embedded in an inhomogeneous circumstellar wind suggestive of modest episodic mass loss. We conclude that SN 2011ei's rapid spectral metamorphosis is indicative of time-dependent classifications that bias estimates of the relative explosion rates for Type IIb and Ib objects, and that important information about a progenitor star's evolutionary state and mass loss immediately prior to SN explosion can be inferred from timely multi-wavelength observations.
MULTI-WAVELENGTH OBSERVATIONS OF SUPERNOVA 2011ei: TIME-DEPENDENT CLASSIFICATION OF TYPE IIb AND Ib SUPERNOVAE AND IMPLICATIONS FOR THEIR PROGENITORS

Energy Technology Data Exchange (ETDEWEB)

Milisavljevic, Dan; Margutti, Raffaella; Soderberg, Alicia M.; Chomiuk, Laura; Sanders, Nathan E. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Pignata, Giuliano; Bufano, Filomena [Departamento de Ciencias Fisicas, Universidad Andres Bello, Avda. Republica 252, Santiago (Chile); Fesen, Robert A.; Parrent, Jerod T. [Department of Physics and Astronomy, Dartmouth College, 6127 Wilder Lab, Hanover, NH 03755 (United States); Parker, Stuart [Parkdale Observatory, 225 Warren Road, RDl Oxford, Canterbury 7495 (New Zealand); Mazzali, Paolo [Max-Planck-Institut fuer Astrophysik, Karl-Schwarzschild-Strasse 1, D-85748 Garching (Germany); Pian, Elena [Kavli Institute for Theoretical Physics, Kohn Hall, University of California at Santa Barbara, Santa Barbara, CA 93106-4030 (United States); Pickering, Timothy; Buckley, David A. H.; Crawford, Steven M.; Gulbis, Amanda A. S.; Hettlage, Christian [South African Astronomical Observatory, P.O. Box 9, Observatory 7935, Cape Town (South Africa); Hooper, Eric; Nordsieck, Kenneth H. [Department of Astronomy, University of Wisconsin, Madison, WI 53706 (United States); O' Donoghue, Darragh, E-mail: dmilisav@cfa.harvard.edu [Southern African Large Telescope, P.O. Box 9, Observatory 7935, Cape Town (South Africa); and others

2013-04-10

We present X-ray, UV/optical, and radio observations of the stripped-envelope, core-collapse supernova (SN) 2011ei, one of the least luminous SNe IIb or Ib observed to date. Our observations begin with a discovery within {approx}1 day of explosion and span several months afterward. Early optical spectra exhibit broad, Type II-like hydrogen Balmer profiles that subside rapidly and are replaced by Type Ib-like He-rich features on a timescale of one week. High-cadence monitoring of this transition suggests absorption attributable to a high-velocity ({approx}> 12, 000 km s{sup -1}) H-rich shell, which is likely present in many Type Ib events. Radio observations imply a shock velocity of v Almost-Equal-To 0.13 c and a progenitor star average mass-loss rate of M-dot {approx}1.4 Multiplication-Sign 10{sup -5} M{sub sun} yr{sup -1} (assuming wind velocity v{sub w} = 10{sup 3} km s{sup -1}). This is consistent with independent constraints from deep X-ray observations with Swift-XRT and Chandra. Overall, the multi-wavelength properties of SN 2011ei are consistent with the explosion of a lower-mass (3-4 M{sub Sun }), compact (R{sub *} {approx}< 1 Multiplication-Sign 10{sup 11} cm), He-core star. The star retained a thin hydrogen envelope at the time of explosion, and was embedded in an inhomogeneous circumstellar wind suggestive of modest episodic mass loss. We conclude that SN 2011ei's rapid spectral metamorphosis is indicative of time-dependent classifications that bias estimates of the relative explosion rates for Type IIb and Ib objects, and that important information about a progenitor star's evolutionary state and mass loss immediately prior to SN explosion can be inferred from timely multi-wavelength observations.
Comparison of breath testing with fructose and high fructose corn syrups in health and IBS

OpenAIRE

Skoog, S. M.; Bharucha, A. E.; Zinsmeister, A. R.

2008-01-01

Although incomplete fructose absorption has been implicated to cause gastrointestinal symptoms, foods containing high fructose corn syrup (HFCS) contain glucose. Glucose increases fructose absorption in healthy subjects. Our hypothesis was that fructose intolerance is less prevalent after HFCS consumption compared to fructose alone in healthy subjects and irritable bowel syndrome (IBS). Breath hydrogen levels and gastrointestinal symptoms were assessed after 40 g of fructose (12% solution) pr...
Quantifying women's stated benefit-risk trade-off preferences for IBS treatment outcomes.

Science.gov (United States)

Johnson, F Reed; Hauber, A Brett; Ozdemir, Semra; Lynd, Larry

2010-01-01

The Food and Drug Administration, currently, is exploring quantitative benefit-risk methods to support regulatory decision-making. A scientifically valid method for assessing patients' benefit-risk trade-off preferences is needed to compare risks and benefits in a common metric. The study aims to quantify the maximum acceptable risk (MAR) of treatment-related adverse events (AEs) that women with diarrhea-predominant irritable bowel syndrome (IBS) are willing to accept in exchange for symptom relief. A stated-choice survey was used to elicit trade-off preferences among constructed treatment profiles, each defined by symptom severity and treatment-related AEs. Symptom attributes included frequency of abdominal pain and discomfort, frequency of diarrhea, and frequency of urgency. AE attributes included frequency of mild-to-moderate constipation and the risk of four possible serious AEs. A Web-enabled survey was administered to 589 female US residents at least 18 years of age with a self-reported diagnosis of diarrhea-predominant IBS. Preference weights and MAR were estimated using mixed-logit methods. SUBJECTS were willing to accept higher risks of serious AEs in return for treatments offering better symptom control. For an improvement from the lowest to the highest of four benefit levels, subjects were willing to tolerate a 2.65% increase in impacted-bowel risk, but only a 1.34% increase in perforated-bowel risk. Variation in MARs across AE types is consistent with the relative seriousness of the AEs. Stated-preference methods offer a scientifically valid approach to quantifying benefit-risk trade-off preferences that can be used to inform regulatory decision-making.
Prácticas rituales ibéricas en La Cueva del Sapo (Chiva, Valencia: más allá del caliciforme

Directory of Open Access Journals (Sweden)

Sonia MACHAUSE LÓPEZ

2015-01-01

Full Text Available Se presentan los resultados del estudio interdisciplinar del yacimiento ibérico de la Cueva del Sapo (Chiva, Valencia. Las características del conjunto estudiado muestran un contexto ritual que sería frecuentado entre los SS. V-II a. C. La diversidad cronológica y material así como el volumen de restos indican la existencia de varias actividades rituales intermitentes, no generalizadas y que se suceden en el tiempo. Nos acercamos a ellas a través de la presencia de restos de fauna, con escasas evidencias de consumo que reflejan un ritual principal en torno a la figura del ciervo, huesos humanos sin incinerar con marcas que demuestran un tratamiento concreto del cadáver ligado a un complejo ritual funerario en época ibérica y otros materiales –cerámicas, metales y carbones– que también son pruebas de una actividad ritual en la cueva, cuyas características difieren de los criterios tradicionales establecidos para las cuevas con materiales ibéricos. Todos estos factores nos hacen replantearnos la definición tradicional, todavía vigente, para este tipo de contextos rituales, cargada en algunas ocasiones de excesivas generalizaciones.
Haches, diptongos y otros detalles de alguna importancia: notas sobre numerales (proto)vascos y comparación vasco-ibérica (con un apéndice sobre 'hiri' y otro sobre 'bat'-'bi')

OpenAIRE

Lacarra Andrinua, Joseba Andoni

2010-01-01

Trabajo desarrollado dentro del proyecto Monumenta Linguae Vasconum III (FFI2008-04516) del MICIN y del GIC: IT-486-10 del GV. [ES] Analizamos las propuestas sobre numerales vasco-ibéricos de Orduña (2005) y Ferrer i Jané (2009) desde el punto de vista de la gramática histórica vasca. Además de la inexistencia de correspondencias vasco-ibéricas ni de reconstrucción alguna de la protolengua vasco-ibérica (hecho reconocido por los propios autores), las supuestas similitudes presentadas no...
MODEL PENGUKURAN KINERJA INTELLECTUAL CAPITAL DENGAN IB-VAIC DI PERBANKAN SYARIAH

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Ihyaul Ulum

2013-06-01

Full Text Available The aim of this study is to develop a measurement of intellectual capital performance of Indonesian syariah banking by modifying the Pulic’s model that popular with the name of VAIC (value added intellectual coefficient. This study was done by documentation and focus group discussion with some financial accounting experts and public accountants. The result show that the main formula to measure IC performance of syariah banking is not too different with Pulic model, it was: iB-VAIC™ = iB-VACA + IB-VAHU + iB-STVA. The different one is the accounts to develop VA. VA in Pulic model was constructed by total revenue, while in iB-VAIC, VA was constructed from syariah activities.
Unlocking the Sugar ‘Steric Gate’ of DNA Polymerases†

Science.gov (United States)

Brown, Jessica A.; Suo, Zucai

2011-01-01

To maintain genomic stability, ribonucleotide incorporation during DNA synthesis is controlled predominantly at the DNA polymerase level. A steric clash between the 2′-hydroxyl of an incoming ribonucleotide and a bulky active site residue, known as the ‘steric gate’, establishes an effective mechanism for most DNA polymerases to selectively insert deoxyribonucleotides. Recent kinetic, structural, and in vivo studies have illuminated novel features about ribonucleotide exclusion and the mechanistic consequences of ribonucleotide misincorporation on downstream events, such as the bypass of a ribonucleotide in a DNA template and the subsequent extension of the DNA lesion bypass product. These important findings are summarized in this review article. PMID:21226515
IbM PENGEMBANGAN POTENSI LOKAL POSDAYA DURIAN JAYA MENUJU DESA WISATA DI KELURAHAN BUBAKAN, KEC. MIJEN, KOTA SEMARANG

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Rasiman .

2015-09-01

Full Text Available Abstract ?é?á Based on the data analysis of monograph in Bubakan Village, whichhas various kinds of?é?á potential local resources (e.q:fruits, plants vegetable and cattle, Posdaya Durian Jayaas a partner of IbM, has some potential activities that can be developed?é?á as pioneer of potential local tourist resort intheareaofBubakanvillage. The present activities of the Posdaya are divided into several fields:a.Education;b.Health;c.Entrepreneurship; andd.Environment Care. Those localpotentialresources were still needed serious managerial development in accordance todesign a new local tourist resort. The IbM activities in RW02 Bubakan aimed at 1 making cat fish abon and various food from flourmocaf, 2 conducting a seminar with village officials, community leaders, and the group Posdaya to design a?é?á tourist village. 3 socializing about?é?á nutrients forchildren in Posyandu ?óÔé¼?ôMawar Dua?óÔé¼?Ø. Keyword: local potential resources, Posdaya Durian Jaya, local tourist resort
IX Simposio Ibérico sobre Nutrición Mineral de las Plantas

OpenAIRE

Abadía Bayona, Javier

2003-01-01

Del 10 al 13 de Septiembre de 2002 se celebró el IX Simposio Ibérico sobre Nutrición Mineral de las Plantas en el Campus de Aula Dei de Zaragoza. El Simposio se realizó bajo los auspicios de la Sociedad Española de Fisiología Vegetal, el Consejo Superior de Investigaciones Científicas (CSIC), el Instituto Agronómico Mediterráneo de Zaragoza-Centro Internacional de Altos Estudios Agronómicos Mediterráneos (CIHEAM-IAMZ), la Asociación Internacional para la Optimización de...
An appraisal of the Permian palaeobiodiversity and geology of the Ib-River Basin, eastern coastal area, India

Science.gov (United States)

Goswami, Shreerup; Saxena, Anju; Singh, Kamal Jeet; Chandra, Shaila; Cleal, Christopher J.

2018-05-01

The Ib-River Basin situated in the east coastal area of India, in Odisha State is a south-eastern part of the Mahanadi Master Basin. A large number of plant macrofossils belonging to the Glossopteris flora were described and documented between 2006 and 2010 from various localities of the Barakar and Lower Kamthi formations of this basin. The floral components representing leaves, roots and fructifications in these assemblages belong to the Lycopodiales, Equisetales, Sphenophyllales, Filicales, Cordaitales, Cycadales, Ginkgoales, Coniferales and Glossopteridales. In the present study, all the available data pertaining to the biological remains, petrological analyses as well as the geology of this basin are reviewed and analyzed to deduce and reconstruct the biostratigraphy, palaeoclimate, palaeoenvironment and the landscape of this basin during Permian time in general and during the deposition of Barakar (Artinskian - Kungurian) and Lower Kamthi (Lopingian) formations in particular. The floral composition suggests the prevalence of a temperate climate with a slight change from warm moist to warm dry conditions during the deposition of the Barakar Formation and warm and humid during the deposition of Lower Kamthi sediments. Distribution of various plant groups in the Barakar and Lower Kamthi formations have been shown to depict the biodiversity trends. Vegetational reconstructions during the deposition of the Barakar and Lower Kamthi formations around the Ib-River Basin have also been attempted based on all the fossil records from this area. The status of unclassified Barakar and Kamthi formations has been redefined. Apart from megafloristics, the palynology of the basin is also discussed. Possible marine incursions and marine marginal environment in the Ib-Basin during Permian are overtly summarized on the basis of records of acritarchs, typical marine ichnofossils and evidences of wave activity in Lower Gondwana sediments of this Basin.

IB-MECA, an Adenosine A(3) Receptor Agonist, Does Not Influence Survival of Lethally gamma-Irradiated Mice

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

2012-01-01

Roč. 61, č. 6 (2012), s. 649-654 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/08/0158; GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : Mouse * IB-MECA * Adenosine A(3) receptor agonist Subject RIV: BO - Biophysics Impact factor: 1.531, year: 2012
Una nueva forma en la cerámica ibérica de San Miguel de Liria (Valencia

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Domingo FLETCHER VALLS

2009-10-01

Full Text Available En la campaña de excavaciones llevadas a cabo en 1941, en el ya célebre poblado ibérico de San Miguel de Liria (Valencia, la Edeta de los textos clásicos, la suerte nos deparó, entre los abundantísimos materiales cerámicos, en el departamento señalado con el número 61, el hallazgo de un vaso de gran tamaño, fragmentado por la presión de las tierras, pero, afortunadamente, completo, lo que ha permitido su completa restauración, comprobándose una vez reconstruido, que se trata de una vasija de galbo único hasta la fecha, no sólo entre los múltiples que nos ha proporcionado este yacimiento sino en todo el conjunto de cerámicas ibéricas que conocemos, por lo que juzgamos de interés dar noticias de ia misma, anticipándonos a la completa publicación que de los vasos de este poblado tenemos en prensa.
TRAC-PF1/MOD1 independent assessment: Semiscale Mod-2A intermediate break test S-IB-3

International Nuclear Information System (INIS)

Kmetyk, L.N.

1986-02-01

The TRAC-PF1/MOD1 independent assessment project at Sandia National Laboratories is part of an overall effort funded by the NRC to determine the ability of various system codes to predict the detailed thermal/hydraulic response of light water reactors during accident and off-normal conditions. The TRAC code is being assessed at SNLA against test data from various integral and separate effects test facilities. As part of this assessment matrix, an intermediate break test (S-IB-3), performed at the Semiscale Mod-2A facility, has been analyzed. Using an input model with a 3-D VESSEL component, the vessel and downcomer inventories during 3-IB-3 were generally well predicted, but the core heatup was underpredicted compared to data. An equivalent calculation with an all 1-D input model ran about twice as fast as our basecase analysis using a 3-D VESSEL in the input model, but the results of the two calculations diverged significantly for many parameters of interest, with the 3-D VESSEL model results in better agreement with data. 22 refs., 100 figs
Hyper production of cellulose degrading endo (1,4 β-d-glucanase from Bacillus licheniformis KIBGE-IB2

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Asad Karim

2015-04-01

Full Text Available Cellulase hydrolyzes β (1,4 glycosidic linkages of cellulose polymer to soluble sugar. An extracellular enzyme production by Bacillus licheniformis KIBGE-IB2 (GenBank accession No. GU216259 was studied under various environmental conditions. Maximum enzyme production was measured in the liquid fermentation medium after 48 h, containing (gL−1, CMC, 5.0; peptone, 15.0; yeast extract, 15.0; CaCl2·2H2O, 0.001; FeSO4·7H2O, 0.001; K2HPO4, 5.0; NaH2PO4, 5.0 and MgSO4·7H2O, 1.0. The optimal pH and temperature for enzyme production was found to be 6.0 and 37°C, respectively. It was also found that beside soluble sugars, a significant amount of enzyme production was obtained when biomass (wheat bran and orange peel were examined as a sole carbon source. The current findings indicate that endo (1,4 β-d-glucanase from B. licheniformis KIBGE-IB2 can be beneficial for commercial purpose.
iPTF13bvn: The first evidence of a binary progenitor for a type Ib supernova

Energy Technology Data Exchange (ETDEWEB)

Bersten, Melina C.; Folatelli, Gastón; Nomoto, Ken' ichi; Quimby, Robert [Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8583 (Japan); Benvenuto, Omar G. [Facultad de Ciencias Astronómicas y Geofísicas, Universidad Nacional de La Plata, Paseo del Bosque S/N, B1900FWA La Plata (Argentina); Kuncarayakti, Hanindyo [Millennium Institute of Astrophysics, Casilla 36-D, Santiago (Chile); Srivastav, Shubham; Anupama, G. C.; Sahu, Devendra K., E-mail: melina.bersten@ipmu.jp [Indian Institute of Astrophysics, Koramangala, Bangalore 560034 (India)

2014-10-01

The recent detection in archival Hubble Space Telescope images of an object at the location of supernova (SN) iPTF13bvn may represent the first direct evidence of the progenitor of a Type Ib SN. The object's photometry was found to be compatible with a Wolf-Rayet pre-SN star mass of ≈11 M {sub ☉}. However, based on hydrodynamical models, we show that the progenitor had a pre-SN mass of ≈3.5 M {sub ☉} and that it could not be larger than ≈8 M {sub ☉}. We propose an interacting binary system as the SN progenitor and perform evolutionary calculations that are able to self-consistently explain the light curve shape, the absence of hydrogen, and the pre-SN photometry. We further discuss the range of allowed binary systems and predict that the remaining companion is a luminous O-type star of significantly lower flux in the optical than the pre-SN object. A future detection of such a star may be possible and would provide the first robust identification of a progenitor system for a Type Ib SN.
Specific alteration of rhythm in temperature-stressed rats possess features of abdominal pain in IBS patients

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Yasuo Itomi

2015-09-01

Full Text Available It is known that specific alteration of rhythm in temperature (SART stress produces somatic pain. However, it remains to be investigated whether SART stress induces visceral pain. In this study, we investigated the visceral hypersensitivity in the SART stress model by pharmacological tools and heterotopical nociception. Four-week-old Sprague–Dawley rats were exposed to repeated cold stress. Visceral pain was measured by visceromotor response to colorectal distension, and the effects of alosetron and duloxetine on visceral pain were investigated in SART rats. Heterotopical nociception was given by capsaicin injection into the left forepaw to induce diffuse noxious inhibitory controls (DNIC. SART stress induced visceral hypersensitivity that was sustained at minimum for one week. In pharmacological analysis, alosetron and duloxetine improved SART stress-induced visceral hypersensitivity. Heterotopical nociception induced DNIC in normal conditions, but was disrupted in SART rats. On the other hand, RMCP-II mRNA in distal colon was not affected by SART stress. In conclusion, SART rats exhibit several features of visceral pain in IBS, and may be a useful model for investigating the central modification of pain control in IBS.
Genomic Characterization of Two Novel SAR11 Isolates From the Red Sea, Including the First Strain of the SAR11 Ib clade

KAUST Repository

Jimenez Infante, Francy M.

2017-06-22

The SAR11 clade (Pelagibacterales) is a diverse group that forms a monophyletic clade within the Alphaproteobacteria, and constitutes up to one third of all prokaryotic cells in the photic zone of most oceans. Pelagibacterales are very abundant in the warm and highly saline surface waters of the Red Sea, raising the question of adaptive traits of SAR11 populations in this water body and warmer oceans through the world. In this study, two pure cultures were successfully obtained from surface waters on the Red Sea, one isolate of subgroup Ia and one of the previously uncultured SAR11 Ib lineage. The novel genomes were very similar to each other and to genomes of isolates of SAR11 subgroup Ia (Ia pan-genome), both in terms of gene content and synteny. Among the genes that were not present in the Ia pan-genome, 108 (RS39, Ia) and 151 genes (RS40, Ib) were strain-specific. Detailed analyses showed that only 51 (RS39, Ia) and 55 (RS40, Ib) of these strain-specific genes had not reported before on genome fragments of Pelagibacterales. Further analyses revealed the potential production of phosphonates by some SAR11 members and possible adaptations for oligotrophic life, including pentose sugar utilization and adhesion to marine particulate matter.
Genomic Characterization of Two Novel SAR11 Isolates From the Red Sea, Including the First Strain of the SAR11 Ib clade

KAUST Repository

Jimenez Infante, Francy M.; Ngugi, David; Vinu, Manikandan; Blom, Jochen; Alam, Intikhab; Bajic, Vladimir B.; Stingl, Ulrich

2017-01-01

The SAR11 clade (Pelagibacterales) is a diverse group that forms a monophyletic clade within the Alphaproteobacteria, and constitutes up to one third of all prokaryotic cells in the photic zone of most oceans. Pelagibacterales are very abundant in the warm and highly saline surface waters of the Red Sea, raising the question of adaptive traits of SAR11 populations in this water body and warmer oceans through the world. In this study, two pure cultures were successfully obtained from surface waters on the Red Sea, one isolate of subgroup Ia and one of the previously uncultured SAR11 Ib lineage. The novel genomes were very similar to each other and to genomes of isolates of SAR11 subgroup Ia (Ia pan-genome), both in terms of gene content and synteny. Among the genes that were not present in the Ia pan-genome, 108 (RS39, Ia) and 151 genes (RS40, Ib) were strain-specific. Detailed analyses showed that only 51 (RS39, Ia) and 55 (RS40, Ib) of these strain-specific genes had not reported before on genome fragments of Pelagibacterales. Further analyses revealed the potential production of phosphonates by some SAR11 members and possible adaptations for oligotrophic life, including pentose sugar utilization and adhesion to marine particulate matter.
Magmatismo alcalino del Triásico Superior (Noriense) en el extremo NO de la Rama Aragonesa de la Cordillera Ibérica: Modelo de emplazamiento en relación con fallas sin-sedimentarias

OpenAIRE

Sanz, Tomás; Lago San José, Marceliano; Gil Imaz, Andrés; Pocoví Juan, Andrés; Galé, Carlos

2012-01-01

A través de un estudio lito-estratigráfico y tectónico se pretende deducir el contexto estructural en el que se desarrolló el magmatismo alcalino del Triásico Superior, para el margen nor-occidental de la Rama Aragonesa de la Cordillera Ibérica (Sierra del Moncayo). La reactivación del rift Ibérico y el emplazamiento de al menos dos sills en área estudiada, pudo tener lugar a través de la apertura de un número reducido de fallas normales, con orientación actual Ibérica (NO-S...
Moluscos Poliplacóforos del litoral atlántico del sur de la Península Ibérica

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Carmona Zalvide, M. P.

2000-12-01

Full Text Available In this paper, an updated check-list of the polyplacophoran species from Sagres (Portugal to Strait of Gibraltar is present. Twenty taxa are recorded in this area: Lepidopleurus cajetanus, Leptochiton cancellatus, Leptochiton algesirensis, Leptochiton scabridus, Callochiton septemvalvis, Callochiton euplaeae, Lepidochitona cinerea, Lepidochitona corrugata, Lepidochitona canariensis, Lepidochitona monterosatoi, Lepidochitona kaasi, Lepidochitona severianoi, Chaetopleura angulata, Ischnochiton rissoi, Chiton olivaceus, Chiton corallinus, Chiton phaesolinus, Acanthochitona fascicularis and Acanthochitona crinita. From these species, Lepidochitona canariensis, L simrothi, Callochiton septemvalvis and Lepidochitona monterosatoi amplify their geographical distribution to Southern Atlantic coast of southern Iberian Peninsula.

Se aporta el catálogo de los Moluscos Poliplacóforos de las costas atlánticas del sur de la Península Ibérica, desde Sagres (Portugal hasta Gibraltar. Se cita un total de 20 taxones (Lepidopleurus cajetanus, Leptochiton cancellatus, Leptochiton algesirensis, Leptochiton scabridus, Callochiton septemvalvis, Callochiton euplaeae, Lepidochitona cinerea, Lepidochitona corrugata, Lepidochitona canariensis, Lepidochitona monterosatoi, Lepidochitona kaasi, Lepidochitona severianoi, Chaetopleura angulata, Ischnochiton rissoi, Chiton olivaceus, Chiton corallinus, Chiton phaesolinus, Acanthochitona fascicularis y Acanthochitona crinita todos ellos pertenecientes al dominio litoral. La captura de Lepidochitona canariensis y L. simrothi en aguas atlánticas ibéricas constituye la primera cita para el suratlántico ibérico. A su vez se amplía la distribución a esta zona de Callochiton septemvalvis y de Lepidochitona monterosatoi.
Art, Politics and Memory: a Conversation with Colm Tóibín

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Claudia Luppino

2013-03-01

Full Text Available The participation to a literary festival in Florence gave the interviewer the occasion to meet one of the most prolific and best loved Irish writers of our days. In what immediately took the shape and flavour of an informal and multifarious conversation – more than a strictly academic interview – Colm Tóibín, thus, shed an insightful light on his aesthetic beliefs and practice, but also on his political views, interest in current affairs and the impact of autobiography on his fiction. His relationship with John McGahern, one of the greatest twentieth-century Irish novelists, was also thoroughly addressed.
OC5 Project Phase Ib: Validation of Hydrodynamic Loading on a Fixed, Flexible Cylinder for Offshore Wind Applications

DEFF Research Database (Denmark)

Robertson, Amy N.; Wendt, Fabian; Jonkman, Jason M.

2016-01-01

at the Danish Hydraulic Institute (DHI) with support from the Technical University of Denmark (DTU). The first phase of OC5 examined two simple cylinder structures (Phase Ia and Ib) to focus on validation of hydrodynamic models used in the various tools before moving on to more complex offshore wind systems...
A randomised clinical trial (RCT) of a symbiotic mixture in patients with irritable bowel syndrome (IBS): effects on symptoms, colonic transit and quality of life.

Science.gov (United States)

Cappello, Carmelina; Tremolaterra, Fabrizio; Pascariello, Annalisa; Ciacci, Carolina; Iovino, Paola

2013-03-01

The aim of this study is to test in a double-blinded, randomised placebo-controlled study the effects of a commercially available multi-strain symbiotic mixture on symptoms, colonic transit and quality of life in irritable bowel syndrome (IBS) patients who meet Rome III criteria. There is only one other double-blinded RCT on a single-strain symbiotic mixture in IBS. This is a double-blinded, randomised placebo-controlled study of a symbiotic mixture (Probinul, 5 g bid) over 4 weeks after 2 weeks of run-in. The primary endpoints were global satisfactory relief of abdominal flatulence and bloating. Responders were patients who reported at least 50 % of the weeks of treatment with global satisfactory relief. The secondary endpoints were change in abdominal bloating, flatulence, pain and urgency by a 100-mm visual analog scale, stool frequency and bowel functions on validated adjectival scales (Bristol Scale and sense of incomplete evacuation). Pre- and post-treatment colonic transit time (Metcalf) and quality of life (SF-36) were assessed. Sixty-four IBS patients (symbiotic n = 32, 64 % females, mean age 38.7 ± 12.6 years) were studied. This symbiotic mixture reduced flatulence over a 4-week period of treatment (repeated-measures analysis of covariance, p symbiotic group. This symbiotic mixture has shown a beneficial effect in decreasing the severity of flatulence in IBS patients, a lack of adverse events and a good side-effect profile; however, it failed to achieve an improvement in global satisfactory relief of abdominal flatulence and bloating. Further studies are warranted.
Organ-Specific and Age-Dependent Expression of Insulin-like Growth Factor-I (IGF-I) mRNA Variants: IGF-IA and IB mRNAs in the Mouse

OpenAIRE

Ohtsuki, Takashi; Otsuki, Mariko; Murakami, Yousuke; Maekawa, Tetsuya; Yamamoto, Takashi; Akasaka, Koji; Takeuchi, Sakae; Takahashi, Sumio

2005-01-01

Insulin-like growth factor-I (IGF-I) gene generates several IGF-I mRNA variants by alternative splicing. Two promoters are present in mouse IGF-I gene. Each promoter encodes two IGF-I mRNA variants (IGF-IA and IGF-IB mRNAs). Variants differ by the presence (IGF-IB) or absence (IGF-IA) of a 52-bp insert in the E domain-coding region. Functional differences among IGF-I mRNAs, and regulatory mechanisms for alternative splicing of IGF-I mRNA are not yet known. We analyzed the expression of mouse ...
A Universidade na cidade : urbanismo e arquitectura universitários na Península Ibérica da Idade Média e da Primeira Idade Moderna

OpenAIRE

Lobo, Rui

2010-01-01

Tese de Doutoramento em Arquitectura (Teoria e História da Arquitectura), apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra A dissertação visa analisar os processos de implantação urbana das universidades ibéricas ao longo dos primeiros quatro séculos do fenómeno universitário na Península. Visa igualmente esclarecer o desenvolvimento dos modelos tipológicos da arquitectura universitária ibérica, tanto colégios como edifícios-sede das escolas. Analisa-...
Las copas tipo Cástulo en la Península Ibérica

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Sánchez, Carmen

1992-12-01

Full Text Available The Castulo cup is one of the most common black glaze Attic forms in the Iberian Peninsula from the Atlantic coast to Ampurias. Their date in the Iberian Peninsula is some years later than that proposed for Athens. They did not appear till some years after the second half of the 5th c. B.C. Their production probably continued until the first quarter of the 4th century B.C. They are almost fixed in their form for about a century, but some differences in the outside decoration and the underside of the foot can be pointed out. Two main types are proposed for the second half of the 5th century and the first quarter of the 4th century B.C. The differences in date compared with those found at Athens can be explained as an adaptation of the workshops to the demands of Iberian customers. Athen's artisans continued making Castulo cups for export at a time when in Athens they did not use them any more, because the stemless cup had been replaced by the popular kantharoi and cup-kantharoi.

La copa Cástulo es una de las formas áticas de barniz negro más abundante en los yacimientos peninsulares desde la costa atlántica hasta Ampurias. Su cronología es en la Península Ibérica algo posterior a la propuesta para Atenas. No aparecen hasta algo después de mediados del siglo V y probablemente se continúan fabricando hasta el primer cuarto del IV a. C. No experimentan durante casi un siglo de producción ninguna variación formal, sin embargo sí se pueden ver diferencias en el tratamiento de la decoración exterior y del fondo externo. Se proponen aquí fundamentalmente dos tipos de la segunda mitad del siglo V y primer cuarto del IV a. C. La diferencia cronológica con las halladas en Atenas se explica como una adaptación de los talleres áticos a la demanda de los clientes ibéricos. Los artesanos atenienses continúan fabricando copas Cástulo para la exportación cuando en Atenas se han dejado ya de utilizar las copas de pie bajo al ser
La habitación sagrada de la ciudad ibérica de La Serreta

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Grau, Ignacio

2008-12-01

Full Text Available In this paper a department with probable sacred functions in the Iberian settlement of La Serreta (Alcoi-Cocentaina- Penàguila, Alicante is analyzed. In this room an exceptional material record was found that includes some of the better examples of the so-called narrative figured pottery style, the image of a nurse goddess in terracotta, imported vessels and specialized metal instruments. This outstanding ensemble allows us to define this space as a singular deposit and a representative room with possible religious functions, which formed the back bone of the complex social and political relationships of the Iberian oppidum at the end of the 3rd cent. B.C.En el siguiente artículo se analiza un departamento con probables funciones sagradas en el asentamiento ibérico de La Serreta (Alcoi-Cocentaina-Penàguila, Alicante. En esta habitación se recuperó un excepcional conjunto material que incluye algunos de los mejores ejemplos de cerámica con decoración figurada de estilo narrativo, una plaqueta de terracota que representa una divinidad nutricia, vajilla de importación e instrumental especializado de orfebre. Las características de este destacado conjunto nos llevan a definir el espacio como un depósito singular y una habitación representativa con posibles funciones religiosas que contribuiría a articular las complejas relaciones sociales y políticas del oppidum ibérico a finales del s. III a.C.
Beneficial effects of bio-controlling agent Bacillus cereus IB311 on the agricultural crop production and its biomass optimization through response surface methodology

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GOUTAM BANERJEE

2017-10-01

Full Text Available ABSTRACT Disease in agricultural field is a big problem that causes a massive loss in production. In this present investigation, we have reported a soil-borne bacterium Bacillus cereus IB311 which is antagonistic to plant pathogens (Pseudomonas syringae and Agrobacterium tumefaciens, and could make a substantial contribution to the prevention of plant diseases. To prove the practical application, the strain was directly applied in agricultural field. The results demonstrated that B. cereus IB311 has increased the production (20% and 26% in term of average pod number per plant, average seed number per pod, and seed yield per experimental plot in ground nut (Arachis hypogaea var. Koushal, G201 and sesame (Sesamum indicum var. Kanak, respectively. To reduce the production cost, the biomass production was optimized through response surface methodology (RSM. Interactions of three variables (glucose, beef extract and inoculum were studied using Central Composite Design. According to our analysis, optimum production of Bacillus cereus IB311 (5.383 µg/ mL may be obtained at glucose 1.985%, beef extract 1.615% and inoculums size 0.757%. Therefore, we strongly believe that the application of this strain in agricultural field as bio-controlling agent will definitely enhance the production yield and will reduce the disease risk.
Sintaxis espacial en el oppidum ibérico. Reflexiones sobre los modelos espaciales y sociales

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Grau Mira, Ignasi

2015-12-01

Full Text Available In this paper we propose an approach to the analysis based on the space syntax applied to the domestic space of the societies of Iron Age in the central region of Mediterranean Iberia. In the first section, the importance of setting the houses to understand the Iberian society is introduced. Secondly, an analysis of some examples of Mediterranean central area is developed, in which we identify two clearly defined spatial models. Finally these models are related to the aggregation of households to make up the Iberian communities.En el presente trabajo realizamos un aproximación mediante el análisis basado en la sintaxis espacial aplicado al espacio doméstico de las sociedades de la edad del Hierro de la franja central de la Iberia Mediterránea, entre los siglos VI y III a. C. En una primera sección se introduce la importancia de la configuración de las casas para comprender la sociedad ibérica. A continuación seleccionamos algunos ejemplos de la mitad meridional del País Valenciano para realizar nuestro análisis. Se identifican de dos modelos espaciales claramente definidos. Por último se relacionan estos esquemas constructivos con los procesos de agregación de unidades familiares para constituir las comunidades ibéricas.
Genomic characterization of two novel SAR11 isolates from the Red Sea, including the first strain of the SAR11 Ib clade.

Science.gov (United States)

Jimenez-Infante, Francy; Ngugi, David Kamanda; Vinu, Manikandan; Blom, Jochen; Alam, Intikhab; Bajic, Vladimir B; Stingl, Ulrich

2017-07-01

The SAR11 clade (Pelagibacterales) is a diverse group that forms a monophyletic clade within the Alphaproteobacteria, and constitutes up to one third of all prokaryotic cells in the photic zone of most oceans. Pelagibacterales are very abundant in the warm and highly saline surface waters of the Red Sea, raising the question of adaptive traits of SAR11 populations in this water body and warmer oceans through the world. In this study, two pure cultures were successfully obtained from surface waters on the Red Sea: one isolate of subgroup Ia and one of the previously uncultured SAR11 Ib lineage. The novel genomes were very similar to each other and to genomes of isolates of SAR11 subgroup Ia (Ia pan-genome), both in terms of gene content and synteny. Among the genes that were not present in the Ia pan-genome, 108 (RS39, Ia) and 151 genes (RS40, Ib) were strain specific. Detailed analyses showed that only 51 (RS39, Ia) and 55 (RS40, Ib) of these strain-specific genes had not reported before on genome fragments of Pelagibacterales. Further analyses revealed the potential production of phosphonates by some SAR11 members and possible adaptations for oligotrophic life, including pentose sugar utilization and adhesion to marine particulate matter. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dorvilleidos (Polychaeta, Dorvilleidae recolectados durante el proyecto “Fauna Ibérica” y catálogo de las especies íbero-baleares

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Núñez, J.

2013-12-01

Full Text Available A check-list of Dorvilleids (Eunicida, Dorvilleidae species collected during the oceanographic cruises “Fauna Ibérica II, III and IV” is presented. A total of 6 genera and 9 species were identified, including the first record from the littoral of Iberian Peninsula of Iphitime paguri Fage & Legendre, a species commensal of crustaceans. An updated catalogue of recorded dorvilleids from the Iberian Peninsula and Balearic islands is presented. This catalogue comprises 7 genera and 22 species. An appendix with data (locality, coordinates and seabed substrate of each sampling station is provided.Se elabora un listado de las especies de dorvilleidos (Eunicida, Dorvilleidae a partir de muestras recogidas durante las campañas oceanográficas “Fauna Ibérica II, III y IV” que agrupa un total de 6 géneros y 9 especies. A partir del material estudiado, se cita por primera vez para el litoral de la península Ibérica la especie comensal de crustáceos: Iphitime paguri Fage & Legendre, 1934. También se incluye un catálogo actualizado de los dorvilleidos conocidos para el ámbito íbero-balear, compuesto por 7 géneros y 22 especies. Por último, se presenta un apéndice con datos abióticos para cada estación: localidad, coordenadas, profundidad y tipo de sustrato.
The effects of age on treatment and outcomes in women with stages IB1-IIB cervical cancer.

Science.gov (United States)

Roque, Dario R; Cronin, Beth; Robison, Katina; Lopes, Vrishali; Rizack, Tina; Dizon, Don S

2013-10-01

Age may affect the treatment choice and subsequent outcome in elderly patients with cervical cancer. Given the potential for cure with either surgery or chemoradiation in early stage disease, we aimed to determine whether a patient's age influenced treatment received and the ensuing outcome. We identified 303 patients with stages IB1-IIB cervical carcinoma treated at our institution between 2000 and 2010, who were divided into two groups based on age at time of diagnosis: stage at presentation, and grade. Women ≥ 65 years of age were less likely to receive primary surgical management (p=0.03). Age did not influence disease-specific or all-cause mortality. However, women over 65 years who underwent primary surgery were at significantly increased risk of all-cause mortality compared to younger women (HR 6.53, 95% CI: 2.57-16.6). Age appears to influence treatment received by patients with stages IB1-IIB cervical cancer. Although there was no difference in cancer-specific mortality stratified by type of treatment received, surgery was associated with a 6.5-fold increased risk of all-cause mortality among women 65 years or over. © 2013.
Saccharomyces boulardii CNCM I-745 supplementation reduces gastrointestinal dysfunction in an animal model of IBS

OpenAIRE

Brun, Paola; Scarpa, Melania; Marchiori, Chiara; Sarasin, Gloria; Caputi, Valentina; Porzionato, Andrea; Giron, Maria Cecilia; Palù, Giorgio; Castagliuolo, Ignazio

2017-01-01

Background We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure. Methods Mice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S. boulardii (107 CFU/day...
The Rhizoctonia solani AG1-IB (isolate 7/3/14 transcriptome during interaction with the host plant lettuce (Lactuca sativa L..

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Bart Verwaaijen

Full Text Available The necrotrophic pathogen Rhizoctonia solani is one of the most economically important soil-borne pathogens of crop plants. Isolates of R. solani AG1-IB are the major pathogens responsible for bottom-rot of lettuce (Lactuca sativa L. and are also responsible for diseases in other plant species. Currently, there is lack of information regarding the molecular responses in R. solani during the pathogenic interaction between the necrotrophic soil-borne pathogen and its host plant. The genome of R. solani AG1-IB (isolate 7/3/14 was recently established to obtain insights into its putative pathogenicity determinants. In this study, the transcriptional activity of R. solani AG1-IB was followed during the course of its pathogenic interaction with the host plant lettuce under controlled conditions. Based on visual observations, three distinct pathogen-host interaction zones on lettuce leaves were defined which covered different phases of disease progression on tissue inoculated with the AG1-IB (isolate 7/3/14. The zones were defined as: Zone 1-symptomless, Zone 2-light brown discoloration, and Zone 3-dark brown, necrotic lesions. Differences in R. solani hyphae structure in these three zones were investigated by microscopic observation. Transcriptional activity within these three interaction zones was used to represent the course of R. solani disease progression applying high-throughput RNA sequencing (RNA-Seq analysis of samples collected from each Zone. The resulting three transcriptome data sets were analyzed for their highest expressed genes and for differentially transcribed genes between the respective interaction zones. Among the highest expressed genes was a group of not previously described genes which were transcribed exclusively during early stages of interaction, in Zones 1 and 2. Previously described importance of up-regulation in R. solani agglutinin genes during disease progression could be further confirmed; here, the corresponding genes
The Rhizoctonia solani AG1-IB (isolate 7/3/14) transcriptome during interaction with the host plant lettuce (Lactuca sativa L.).

Science.gov (United States)

Verwaaijen, Bart; Wibberg, Daniel; Kröber, Magdalena; Winkler, Anika; Zrenner, Rita; Bednarz, Hanna; Niehaus, Karsten; Grosch, Rita; Pühler, Alfred; Schlüter, Andreas

2017-01-01

The necrotrophic pathogen Rhizoctonia solani is one of the most economically important soil-borne pathogens of crop plants. Isolates of R. solani AG1-IB are the major pathogens responsible for bottom-rot of lettuce (Lactuca sativa L.) and are also responsible for diseases in other plant species. Currently, there is lack of information regarding the molecular responses in R. solani during the pathogenic interaction between the necrotrophic soil-borne pathogen and its host plant. The genome of R. solani AG1-IB (isolate 7/3/14) was recently established to obtain insights into its putative pathogenicity determinants. In this study, the transcriptional activity of R. solani AG1-IB was followed during the course of its pathogenic interaction with the host plant lettuce under controlled conditions. Based on visual observations, three distinct pathogen-host interaction zones on lettuce leaves were defined which covered different phases of disease progression on tissue inoculated with the AG1-IB (isolate 7/3/14). The zones were defined as: Zone 1-symptomless, Zone 2-light brown discoloration, and Zone 3-dark brown, necrotic lesions. Differences in R. solani hyphae structure in these three zones were investigated by microscopic observation. Transcriptional activity within these three interaction zones was used to represent the course of R. solani disease progression applying high-throughput RNA sequencing (RNA-Seq) analysis of samples collected from each Zone. The resulting three transcriptome data sets were analyzed for their highest expressed genes and for differentially transcribed genes between the respective interaction zones. Among the highest expressed genes was a group of not previously described genes which were transcribed exclusively during early stages of interaction, in Zones 1 and 2. Previously described importance of up-regulation in R. solani agglutinin genes during disease progression could be further confirmed; here, the corresponding genes exhibited
IbM BAGI GURU MATEMATIKA SMPDI KABUPATEN KENDAL

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Rasiman .

2015-07-01

Full Text Available Abstract Community service activities for this, intended for junior high school mathematics teachers, especially in MGMPs Kendal in support of Curriculum 2013. The 2013 curriculum is implemented in stages beginning in school year 2013-2014 through the implementation is limited, especially for schools that are ready to implement it. In the academic year of 2013/2014, Curriculum 2013 implemented on a limited basis for Class I and IV Elementary / Madrasah Ibtida'iyah (SD / MI, Class VII School SMP / MTs (SMP / MTs, and Class X High School / School SMK / Madrasah Aliyah (SMA / SMK / MA / MAK. In the academic year of 2015/2016 is expected toCurriculum 2013 has been implemented in the whole class I to Class XII. For that we consider necessary the holding of training activities and workshops preparation of lesson plans and training curriculum in 2013 based learning media creation software GeoGebra useful for teachers of Mathematics junior in Kendal. The method used is the training and workshops with a target output of each participant design a lesson plan curriculum in 2013 and the manufacture of Mathematics instructional media with the help of software GeoGebra. Keywords: Curriculum 2013, GeoGebra
La distribución de las zigenas (Lepidoptera, Zygaenidae ibéricas: una consecuencia del efecto península

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Martín Cano, J.

2003-12-01

Full Text Available The distribution of the burnets of the genus Zygaena in the Iberian Peninsula has been analysed. The method used has been the comparison of species densities in grids of equal area. Geographical, physical and climatic factors have been used as independent variables. The most relevant variables for the burnet species densities are the geographical longitude and the distance to the Pyrenees. The second most important factor is altitude and finally other variables as soil type and climatic irregularity. The resulting model is very similar to that of the Iberian butterflies, and, similarly to this group, it can be related to a marked peninsular effect. A parsimony analysis highlights the importance of the oriental part of the Iberian Peninsula as a biogeographical corridor for these species.

Se ha analizado la distribución de las especies del género Zygaena presentes en la Península Ibérica. El método empleado ha sido el análisis de la densidad de especies en cuadrículas de igual superficie. Como variables independientes se han utilizado factores geográficos, físicos y climáticos. Los más relevantes para la densidad de especies de zigenas son la longitud geográfica y la distancia a Pirineos. En segundo lugar está la altitud, y finalmente otros factores como el tipo de suelo y la irregularidad pluviométrica. El modelo resultante es muy parecido al que presentan las mariposas ibéricas, y al igual que en éstas, puede asignarse a un marcado efecto península. El análisis de parsimonia pone de manifiesto la importancia de la parte oriental de la Península Ibérica como corredor biogeográfico para estas especies.
Randomized study of preoperative radiation and surgery or irradiation alone in the treatment of Stage IB and IIA carcinoma of the uterine cervix

International Nuclear Information System (INIS)

Perez, C.A.; Camel, H.M.; Kao, M.S.; Askin, F.

1980-01-01

A prospective randomized study in selected patients with Stage IB and IIA carcinoma of the uterine cervix was carried out. Patients were randomized to be treated with 1) irradiation alone consisting of 1000 rad whole pelvis, additional 4000 rads to the parametria with a step wedge midline block, and two intracavitary insertions for 7500 mgh; and 2) irradiation and surgery, consisting of 2000 rad whole pelvis irradiation, one intracavitary insertion for 5000 to 6000 mgh followed in two to six weeks later by a radical hysterectomy with pelvic lymphadenectomy. The five-year, tumor-free actuarial survival for Stage IB patients treated with radiation was 87% and with preoperative radiation and surgery 82%. In Stage IIA, the actuarial five-year survival NED was 57% for the irradiation alone group and 71% for the patients treated with preoperative radiation and radical hysterectomy. Major complications of therapy were slightly higher in the patients trated with radiation alone (9.4%, consisting of one recto-vaginal fistula and one vesico-vaginal fistula and a combined recto-vesico-vaginal fistula in another patient). In the preoperative radiation group, only two ureteral strictures (4.1%) were noted. The present study shows no significant difference in therapeutic results or morbidity for invasive carcinoma of the uterine cervix Stage IB or IIA treated with irradiation alone or combined with a radical hysterectomy
IB-LBM study on cell sorting by pinched flow fractionation.

Science.gov (United States)

Ma, Jingtao; Xu, Yuanqing; Tian, Fangbao; Tang, Xiaoying

2014-01-01

Separation of two categories of cells in pinched flow fractionation(PFF) device is simulated by employing IB-LBM. The separation performances at low Reynolds number (about 1) under different pinched segment widths, flow ratios, cell features, and distances between neighboring cells are studied and the results are compared with those predicted by the empirical formula. The simulation indicates that the diluent flow rate should approximate to or more than the flow rate of particle solution in order to get a relatively ideal separation performance. The discrepancy of outflow position between numerical simulation and the empirical prediction enlarges, when the cells become more flexible. Too short distance between two neighboring cells could lead to cell banding which would result in incomplete separation, and the relative position of two neighboring cells influences the banding of cells. The present study will probably provide some new applications of PFF, and make some suggestions on the design of PFF devices.
Therapeutic Results of Surgery and Radiation Therapy in Younger Patients with Stage IB Cervical Cancer

International Nuclear Information System (INIS)

Huh, Gil Cha; Yang, Kwang Mo; Suh, Hyun Suk; Kim, Yong Bong; Lee, Eung Soo; Park, Sung Kwan

1995-01-01

Purpose : To evaluate the prognostic importance of age in patients with Stage IB cervical cancer, we examined the relationship between age and survival in patients. Methods and materials : Retrospective analysis was performed on 107 patients were treated with surgery followed by postoperative radiotherapy or radiation alone between October 1983 and August 1993 and 28 patients with Stage IB cervical cancer treated with surgery alone between January 1989 and August 1993 at Inje University Seoul Paik Hospital. Patients ranged in age from 26 to 74 (median 48) and were followed for a median period of 39 months. Patients were divided into two groups; Group A comprising 32 patients with≤age 40 and Group B comprising 75 patients with>age 40. Both Group A and Group B patients were comparable with respect to all covariables studied. Results : The overall 5-year survival and the disease free 5-year survival for the 107 patients studied were 85.2% and 82.1% respectively. The overall survival for group A and Group B was 92% and 83%, respectively(p>0.05). The disease free 5-year survival for Group A and Group B was 82.3% and 82.6%, respectively(p>0.05). There was no difference in both local and distant failure in Group A and Group B. Conclusion : On the basis of the this analysis it is concluded that age alone is a poor indicator of prognosis and should not be used as an indication for adjuvant treatment
Assessment and analysis of noise levels in and around Ib river coalfield, Orissa, India.

Science.gov (United States)

Mohapatra, Haraprasad; Goswami, Shreerup

2012-05-01

Heavy earth moving machineries, different capacities of dumpers and loaders, blasting and drilling make the mining environment noisy. A study was carried out to assess the noise level in different opencast projects in and around Belpahar and Brajarajnagar areas of Ib river coalfield. Noise assessment was carried out in various residential, commercial and industrial places. The noise levels, especially L(eq) values of different wheel loaders, dumpers, shovel and crusher units were also assessed and were more than permissible limit (90dB) in some of their operating conditions. Sound ressure level measurements while drilling into coal and overburden at Lakhanpur opencast project yielded noise levels (L(eq)) of 81.33 to 96.2 dB. Thus, these L(eq) values of drilling machines in most of the operating conditions were above permissible limit. The average noise intensities (6 a.m.-10 p.m.: 51.6-60.875dB and 10 p.m.-6 a.m.: 42.6-49.8dB) and L(eq) values (6 a.m.-10 p.m.: 50.9-67.0dB and 10 p.m.-6 a.m.: 40.8-53.3dB) during both day and night time of the residential areas around the Ib river coalfield were in close proximity or beyond the permissible limit. The L(eq) values at some of the commercial and industrial places were beyond (6 a.m.-10 p.m.: 61.6-88.3 dB and 10 p.m.-6 a.m.: 55.4-64.8dB) permissible limit. However, in most of the cases, the L(max) noise values were more (6 a.m.-10 p.m.: 68.5-91.4 dB and 10 p.m.-6 a.m.: 69.3-76.4dB) than the permissible limit. Analysis of variance was also computed for heavy earth moving machineries in different operating conditions and also for different residential, commercial and industrial places to infer the level of significance. The difference of noise intensity produced by different wheel loaders at Lakhanpur and Lilari opencast projects, drilling machines at Lakhanpur opencast project, 50 tons capacity dumpers at various conditions of Ib river coalfield within the same operating condition was significant at both 5% and 1% levels
Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D Symptoms in an Opioid-Receptor Dependent Manner.

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Chunqiu Chen

Full Text Available Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI tract and cortical neurons using animal models and in vitro tests.The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D symptoms. Then the opioid antagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons.In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR and delta- (DOR opioid receptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons.Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions.
Resumen de tesis. Patrones de distribución de la biodiversidad de mamíferos de la Península Ibérica: pasado, presente y futuro

OpenAIRE

Morales Barbero, Jennifer

2017-01-01

[ES] Las biotas contemporáneas son el resultado acumulativo de una serie de complejas interacciones entre las propiedades de los organismos y las condiciones de su entorno sucedidas a lo largo del desarrollo de la vida en la Tierra. Por tanto, la distribución y evolución de las especies, incluidos los mamíferos de la Península Ibérica, no es azarosa, sino que sigue patrones que responden a diferentes factores contemporáneos y pasados. La Península Ibérica es un destacado punto caliente de...
Is There "Space" for International Baccalaureate? A Case Study Exploring Space and the Adoption of the IB Middle Year Programme

Science.gov (United States)

Monreal, Timothy

2016-01-01

Henri Lefebvre (1991) wrote, "[representational] space is alive: it speaks" (p. 42). This article explores how we might "listen" to space in education by examining the role of space in one school's decision to adopt the International Baccalaureate's Middle Years Programme [IB MYP]. It builds upon recent scholarship that applies…
Risk strata-based therapy and outcome in stage Ib-IIa carcinoma cervix: single-centre ten-year experience.

Science.gov (United States)

Kundargi, Rajshekar S; Guruprasad, B; Rathod, Praveen Shankar; Shakuntala, Pn; Shobha, K; Pallavi, Vr; Uma Devi, K; Bafna, Ud

2013-01-01

To review the outcome of stage (Ib, IIa), cervical cancer patients were primarily treated with radical hysterectomy and risk-based postoperative therapy. Between January 2001 and December 2011, 601 cases underwent surgery followed by tailored therapy. Patients were classified into low risk (pelvic lymph node negative, tumour less than 4 cm, no evidence of lympho-vascular invasion, less than one-third of thickness of surgical stoma involved), intermediate risk (positive lympho-vascular space invasion, tumour size more than 4 cm, and deep invasion of cervical stroma), and high risk (pelvic lymph node involved, positive parametrial, or vaginal margins) groups. Postoperative adju-vant therapy in the form of radiotherapy alone to those with intermediate risk and chemo-radiotherapy to those with high risk was given to patients. The median follow-up was 60 months. The majority of patients had intermediate risk. The overall event-free survival (EFS) at five years was 74.37%, with EFS of 86.5% in those from the low-risk group, 73% in those from the intermediate-risk group, and 64% in those from the high-risk group. In conclusion, risk strata-based adjuvant postoperative therapy is able to provide a favourable outcome in patients with stage Ib-IIa cervical cancer with a nearly 11% improvement in survival compared with historical control.
Synthesis and conformational properties of oligonucleotides incorporating 2'-O-phosphorylated ribonucleotides as structural motifs of pre-tRNA splicing intermediates.

Science.gov (United States)

Tsuruoka, H; Shohda, K; Wada, T; Sekine, M

2000-11-03

To synthesize oligonucleotides containing 2'-O-phosphate groups, four kinds of ribonucleoside 3'-phosphoramidite building blocks 6a-d having the bis(2-cyano-1,1-dimethylethoxy)thiophosphoryl (BCMETP) group were prepared according to our previous phosphorylation procedure. These phosphoramidite units 6a-d were not contaminated with 3'-regioisomers and were successfully applied to solid-phase synthesis to give oligodeoxyuridylates 15, 16 and oligouridylates 21, 22. Self-complementary Drew-Dickerson DNA 12mers 24-28 replaced by a 2'-O-phosphorylated ribonucleotide at various positions were similarly synthesized. In these syntheses, it turned out that KI(3) was the most effective reagent for oxidative desulfurization of the initially generated thiophosphate group to the phosphate group on polymer supports. Without using this conversion step, a tridecadeoxyuridylate 17 incorporating a 2'-O-thiophosphorylated uridine derivative was also synthesized. To investigate the effect of the 2'-phosphate group on the thermal stability and 3D-structure of DNA(RNA) duplexes, T(m) measurement of the self-complementary oligonucleotides obtained and MD simulation of heptamer duplexes 33-36 were carried out. According to these analyses, it was suggested that the nucleoside ribose moiety phosphorylated at the 2'-hydroxyl function predominantly preferred C2'-endo to C3'-endo conformation in DNA duplexes so that it did not significantly affect the stability of the DNA duplex. On the other hand, the 2'-modified ribose moiety was expelled to give a C3'-endo conformation in RNA duplexes so that the RNA duplexes were extremely destabilized.
Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase.

Science.gov (United States)

Iman, Maryam; Khansefid, Zeynab; Davood, Asghar

2016-01-01

Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of hydroxyurea in RNR inhibition as anticancer agent. The binding affinity of hydroxyurea and compound III to RNR was studied by docking method. The docking study was performed for the crystal structure of human RNR with the radical scavenger Hydroxyurea and its oxidized form to inhibit the human RNR. hydroxyurea and compound III bind at the active site with Tyr-176, which are essential for free radical formation. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2. To confirm the binding mode of inhibitors, the molecular dynamics (MD) simulations were performed using GROMACS 4.5.5, based upon the docked conformation of inhibitors. Both of the studied compounds stayed in the active site. The results of MD simulations confirmed the binding mode of ligands, accuracy of docking and the reliability of active conformations which were obtained by AutoDock. MD studies confirm our proposed mechanism in which compound III reacts with the active site residues specially Tyr-176, and inhibits the radical generation and subsequently inhibits the RNR enzyme.
Irritable bowel s yn drome

African Journals Online (AJOL)

2009-01-29

Jan 29, 2009 ... antidepressants have been assessed in placebo-controlled trials and found to be superior to placebo in controlling IBS pain.9. The lowest effective dose should be used. Unfortunately these drugs may aggravate constipation and should be used with caution in IBS-C. Other classes of antidepressant,.
Geir Hønneland, Russia and the Arctic: Environment, Identity and Foreign Policy & Leif Christian Jensen, International Relations in the Arctic: Norway and the Struggle for Power in the New North (London/New York: IB Tauris, 2016

Directory of Open Access Journals (Sweden)

Romain Chuffart

2017-03-01

Full Text Available A review of the books: Geir Hønneland, Russia and the Arctic: Environment, Identity and Foreign Policy (London/New York: IB Tauris, 2016; and Leif Christian Jensen, International Relations in the Arctic: Norway and the Struggle for Power in the New North (London/New York: IB Tauris, 2016
Fragmentation of the CRISPR-Cas Type I-B signature protein Cas8b.

Science.gov (United States)

Richter, Hagen; Rompf, Judith; Wiegel, Julia; Rau, Kristina; Randau, Lennart

2017-11-01

CRISPR arrays are transcribed into long precursor RNA species, which are further processed into mature CRISPR RNAs (crRNAs). Cas proteins utilize these crRNAs, which contain spacer sequences that can be derived from mobile genetic elements, to mediate immunity during a reoccurring virus infection. Type I CRISPR-Cas systems are defined by the presence of different Cascade interference complexes containing large and small subunits that play major roles during target DNA selection. Here, we produce the protein and crRNA components of the Type I-B CRISPR-Cas complex of Clostridium thermocellum and Methanococcus maripaludis. The C. thermocellum Cascade complexes were reconstituted and analyzed via size-exclusion chromatography. Activity of the heterologous M. maripaludis CRISPR-Cas system was followed using phage lambda plaques assays. The reconstituted Type-I-B Cascade complex contains Cas7, Cas5, Cas6b and the large subunit Cas8b. Cas6b can be omitted from the reconstitution protocol. The large subunit Cas8b was found to be represented by two tightly associated protein fragments and a small C-terminal Cas8b segment was identified in recombinant complexes and C. thermocellum cell lysate. Production of Cas8b generates a small C-terminal fragment, which is suggested to fulfill the role of the missing small subunit. A heterologous, synthetic M. maripaludis Type I-B system is active in E. coli against phage lambda, highlighting a potential for genome editing using endogenous Type-I-B CRISPR-Cas machineries. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

The lignan niranthin poisons Leishmania donovani topoisomerase IB and favours a Th1 immune response in mice

OpenAIRE

Chowdhury, Sayan; Mukherjee, Tulika; Mukhopadhyay, Rupkatha; Mukherjee, Budhaditya; Sengupta, Souvik; Chattopadhyay, Sharmila; Jaisankar, Parasuraman; Roy, Syamal; Majumder, Hemanta K

2012-01-01

Niranthin, a lignan isolated from the aerial parts of the plant Phyllanthus amarus, exhibits a wide spectrum of pharmacological activities. In the present study, we have shown for the first time that niranthin is a potent anti-leishmanial agent. The compound induces topoisomerase I-mediated DNA–protein adduct formation inside Leishmania cells and triggers apoptosis by activation of cellular nucleases. We also show that niranthin inhibits the relaxation activity of heterodimeric type IB topois...
Single nucleotide polymorphisms in BMPR-IB and STAT5B genes and their association with growth and reproductive traits in chicken

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Shahram Niknafs

2014-04-01

Full Text Available The aim of the current study was to investigate the association of G4533815A SNP in STAT5B and A287G SNP in BMPR-IB genes with growth and reproduction related traits in chicken. A sample of 205 individuals from breeding station of Mazandaran native chicken population was selected randomly. All of the individuals were genotyped for both SNPs using PCR-RFLP technique. Marker-trait association analyses were performed using estimated breeding value of the traits as dependent variable in GLM procedure of SAS 9.1. Results suggested that breeding value least square means for genotypes of G4533815A SNP is significantly differed from each other for traits of body weight at 8 and 12 weeks (P<0.01. In the case of BMPR-IB gene, no significant difference was found. In conclusion, STAT5B gene may be associated with body growth in chicken and may be considered in Marker Assisted Selection program to improve chicken growth performance.
The ladies of Moixent in the plastic context and in Iberian society | Las «damitas» de Moixent en el contexto de la plástica y la sociedad ibérica

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María Isabel Izquierdo Peraile

2001-12-01

Full Text Available Notre objectif dans ce travail est de proposer une nouvelle valorisation des hauts-reliefs sculptés en blocs architectoniques connus comme les «damitas» («petites dames», qui se trouvaient dans un empierré tumulaire de la nécropole ibérique du Corral de Saus (Moixent, Valencia. Nous proposons une lecture différente, axée sur le genre, de ces figures dans le contexte des représentations féminines et juvéniles de la plastique ibérique, ainsi que leur compréhension dans la société qui crée ces images. | Nuestro objetivo en este trabajo es plantear un nueva valoración de los altorrelieves esculpidos en bloques arquitectónicos conocidos como las «damitas», procedentes de un empedrado tumular de la necrópolis ibérica del Corral de Saus (Moixent, Valencia. Proponemos una lectura distinta, en clave de género, de estas figuras en el contexto de las representaciones femeninas y juveniles de la plástica ibérica, así como su comprensión en la sociedad que genera estas imágenes.
Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

Science.gov (United States)

Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

2016-02-01

ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International
A common central engine for long gamma-ray bursts and Type Ib/c supernovae

Science.gov (United States)

Sobacchi, E.; Granot, J.; Bromberg, O.; Sormani, M. C.

2017-11-01

Long-duration, spectrally soft gamma-ray bursts (GRBs) are associated with Type Ic core collapse (CC) supernovae (SNe), and thus arise from the death of massive stars. In the collapsar model, the jet launched by the central engine must bore its way out of the progenitor star before it can produce a GRB. Most of these jets do not break out, and are instead 'choked' inside the star, as the central engine activity time, te, is not long enough. Modelling the long-soft GRB duration distribution assuming a power-law distribution for their central engine activity times, ∝ t_e^{-α } for te > tb, we find a steep distribution (α ∼ 4) and a typical GRB jet breakout time of tb ∼ 60s in the star's frame. The latter suggests the presence of a low-density, extended envelope surrounding the progenitor star, similar to that previously inferred for low-luminosity GRBs. Extrapolating the range of validity of this power law below what is directly observable, to te < tb, by only a factor of ∼4-5 produces enough events to account for all Type Ib/c SNe. Such extrapolation is necessary to avoid fine-tuning the distribution of central engine activity times with the breakout time, which are presumably unrelated. We speculate that central engines launching relativistic jets may operate in all Type Ib/c SNe. In this case, the existence of a common central engine would imply that (i) the jet may significantly contribute to the energy of the SN; (ii) various observational signatures, like the asphericity of the explosion, could be directly related to jet's interaction with the star.
El asentamiento orientalizante e ibérico antiguo de "La Rábita", Guardamar del Segura (Alicante. Avance de las excavaciones 1996-1998

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Azuar, Rafael

1998-12-01

Full Text Available [es] Al sur de la desembocadura del río Segura, la excavación de La Rábita califal ha revelado la existencia, en el mismo lugar, de un establecimiento de época Orientalizante/Protoibérica e Ibérica Antigua. El hábitat, cuya historia empieza probablemente a finales del siglo VIII o en tomo al 700 a.C., en un momento que se puede fijar hacia el 600 a.C., fue rodeado de una potente muralla que incluye una superficie de 1,5 Ha. El asentamiento ha sido un lugar de intercambios intensos con el mundo orientalizante y fenicio-occidental. [fr] L´établissement orientalisant et ibérique ancien de "La Rábita", Guardamar del Segura (Alicante, Espagne. Campagnes de fouilles, 1996-1998. Au sud de l´embouchure du Segura, la fouille de La Rábita califale a révélé l´existence, au même emplacement, d'un établissement d'époque Orientalisante/Protoibérique et Ibérique Ancienne. L'habitat dont l'histoire commence probablement à la fin du VIIIe siècle ou aux environ de 700 avant J.-C.a été, à un moment que l´on peut situer autour de 600, entouré d'une puissante enceinte; il est alors vaste de 1,5 hectares. L'établissement a été un lieu d'échanges actifs avec le monde orientalisant et phénicien d'Occident.
The Interstitial Status of Irish Gayness in Colm Tóibín’s The Blackwater Lightship and The Master

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José M. Yebra

2014-03-01

Full Text Available This paper explores the liminal status of Irish gayness in the aftermath of its decriminalization in 1993. Colm Tóibín’s The Blackwater Lightship (1999 tries to reconcile Irish Catholicism and traditional family with new models of Irishness. Declan, the protagonist of the novel, goes back home when he is about to die of AIDS. His return reveals a dysfunctional family which only his disease brings together. His grandmother, mother and sister mourn Declan’s corpse-like body. Making reference to Julia Kristeva’s concepts of “abjection” and “the chora” (1982, 1984, I contend that the hero’s disease is a necessary sacrifice for the family and Ireland as a whole to resurface. The second part of the paper addresses Tóibín’s The Master (2004, whose fictional Henry James counterbalances Declan’s overt homosexuality and AIDS-related death. The Master delves into James’s hybridity as a closeted American of Irish descent opposed to Oscar Wilde’s flamboyant gay Irishness. The restraint of the former and the traumatic downfall of the latter make up the late-Victorian framework through which Declan’s late-twentieth-century sacrifice becomes meaningful.
Unlocking the Sugar ‘Steric Gate’ of DNA Polymerases†

OpenAIRE

Brown, Jessica A.; Suo, Zucai

2011-01-01

To maintain genomic stability, ribonucleotide incorporation during DNA synthesis is controlled predominantly at the DNA polymerase level. A steric clash between the 2′-hydroxyl of an incoming ribonucleotide and a bulky active site residue, known as the ‘steric gate’, establishes an effective mechanism for most DNA polymerases to selectively insert deoxyribonucleotides. Recent kinetic, structural, and in vivo studies have illuminated novel features about ribonucleotide exclusion and the mechan...
Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies.

Science.gov (United States)

Couto, Ana Rita; Parreira, Bruna; Thomson, Russell; Soares, Marta; Power, Deborah M; Stankovich, Jim; Armas, Jácome Bruges; Brown, Matthew A

2017-01-01

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P =0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4 , were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients ( P =0.03). Four variants were identified in LEMD3 , and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified.
Risk model in stage IB1-IIB cervical cancer with positive node after radical hysterectomy

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Chen Z

2016-05-01

Full Text Available Zhilan Chen,1,2,* Kecheng Huang,1,* Zhiyong Lu,1,3 Song Deng,1,4 Jiaqiang Xiong,1 Jia Huang,1 Xiong Li,5 Fangxu Tang,1 Zhihao Wang,6 Haiying Sun,1 Lin Wang,1 Shasha Zhou,1 Xiaoli Wang,1 Yao Jia,1 Ting Hu,1 Juan Gui,7 Dongyi Wan,1 Ding Ma,1 Shuang Li,1 Shixuan Wang11Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Techonology, Wuhan, 2Department of Obstetrics and Gynecology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 3Hubei Key Laboratory of Embryonic Stem Cell Research, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, 4Department of Obstetrics and Gynecology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 5Department of Obstetrics and Gynecology, Wuhan Central Hospital, Wuhan, 6Department of Pathology and Pathophysiology, Key Laboratory of Ministry of Education of China for Neurological Disorders, Huazhong University of Science and Techonology, Wuhan, 7Department of Obstetrics and Gynecology, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workAbstract: The purpose of this study was to identify risk factors in patients with surgically treated node-positive IB1-IIB cervical cancer and to establish a risk model for disease-free survival (DFS and overall survival (OS. A total of 170 patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment for node-positive International Federation of Gynaecology and Obstetrics (FIGO stage IB1-IIB cervical cancer from January 2002 to December 2008 were retrospectively analyzed. Five published risk models were evaluated in this population. The variables, including common iliac lymph node metastasis and parametrial invasion, were independent predictors of outcome in a multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk
Crystal structure of a copper-transporting PIB-type ATPase

DEFF Research Database (Denmark)

Gourdon, Pontus Emanuel; Liu, Xiang-Yu; Skjørringe, Tina

2011-01-01

Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu(+)-ATPase, ......Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu...
Emporion y las mutaciones de la arquitectura ibérica a la primera Edad de Hierro

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Pierre MORET

2009-12-01

Full Text Available RESUMEN: A partir de las recientes excavaciones de la palaia polis de Empúries, se discute la posibilidad de influjos cruzados entre arquitecturas griega e indígena durante la primera Edad de Hierro en el Languedoc y costas orientales de la península Ibérica.ABSTRACT: Recent excavations at the palaia polis of Emporion (Empúries, Spain give way to a discussion about possible cross-influences between greek domestic architecture and native architecture in Western Languedoc and along the eastern coast of the Iberian Peninsula.
Preoperatively Assessable Clinical and Pathological Risk Factors for Parametrial Involvement in Surgically Treated FIGO Stage IB-IIA Cervical Cancer.

Science.gov (United States)

Canaz, Emel; Ozyurek, Eser Sefik; Erdem, Baki; Aldikactioglu Talmac, Merve; Yildiz Ozaydin, Ipek; Akbayir, Ozgur; Numanoglu, Ceyhun; Ulker, Volkan

2017-10-01

Determining the risk factors associated with parametrial involvement (PMI) is of paramount importance to decrease the multimodality treatment in early-stage cervical cancer. We investigated the preoperatively assessable clinical and pathological risk factors associated with PMI in surgically treated stage IB1-IIA2 cervical cancer. A retrospective cohort study of women underwent Querleu-Morrow type C hysterectomy for cervical cancer stage IB1-IIA2 from 2001 to 2015. All patients underwent clinical staging examination under anesthesia by the same gynecological oncologists during the study period. Evaluated variables were age, menopausal status, body mass index, smoking status, FIGO (International Federation of Obstetrics and Gynecology) stage, clinically measured maximal tumor diameter, clinical presentation (exophytic or endophytic tumor), histological type, tumor grade, lymphovascular space invasion, clinical and pathological vaginal invasion, and uterine body involvement. Endophytic clinical presentation was defined for ulcerative tumors and barrel-shaped morphology. Two-dimensional transvaginal ultrasonography was used to measure tumor dimensions. Of 127 eligible women, 37 (29.1%) had PMI. On univariate analysis, endophytic clinical presentation (P = 0.01), larger tumor size (P PMI. In multivariate analysis endophytic clinical presentation (odds ratio, 11.34; 95% confidence interval, 1.34-95.85; P = 0.02) and larger tumor size (odds ratio, 32.31; 95% confidence interval, 2.46-423.83; P = 0.008) were the independent risk factors for PMI. Threshold of 31 mm in tumor size predicted PMI with 71% sensitivity and 75% specificity. We identified 18 patients with tumor size of more than 30 mm and endophytic presentation; 14 (77.7%) of these had PMI. Endophytic clinical presentation and larger clinical tumor size (>3 cm) are independent risk factors for PMI in stage IB-IIA cervical cancer. Approximately 78% of the patients with a tumor size of more than 3 cm and endophytic
La Industria Cárnica del Porcino Ibérico en Jabugo (Huelva, España, 1997-2016

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Francisco Javier García-Delgado

2017-12-01

Full Text Available El municipio de Jabugo es uno de los más importantes en la transformación del cerdo ibérico. En las últimas décadas el sector ha sufrido una transformación, con procesos de concentración, relocalización y posicionamiento entre sus empresas. Como resultado de ello, las grandes industrias han salido fortalecidas, y la Denominación de Origen Protegida “Jabugo” aparece como una oportunidad para el sector.
MULTI-PERSON DECISION FOR SUSTAINABLE DESIGN ON IBS FLOOR SYSTEM SELECTION

Directory of Open Access Journals (Sweden)

Christiono Utomo

2013-05-01

Full Text Available Selecting a design solution (choice problem is one of the natures of design decision. If the problem is more complex and involves multi participants, decision aid is necessary. This paper discusses the nature of group judgment and negotiation on multi-criteria decision-making methodologies. It presents a conceptual model of negotiation support in a multi-person decision on building floor system selection. Decision technique (AHP was applied for decision process in a satisfying options and game theory for coalition formation. An n-person cooperative game is represented by a set of all players. The proposed coalition formation model enables each agent to select individually or coalition. It improves the value of building system decision. It further emphasizes the importance of performance evaluation in the design process and value-based decision. The support model can be extended to an automated negotiation and in different building system selection with proper modification. Keywords: Multi-person, design decision, IBS, floor system selection.
En torno a un Grafito Ibérico de Fuenvich (Requena

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Carmen ARANEGUI

2009-10-01

Full Text Available RESUMEN: Se trata de un grafito realizado en caracteres del tipo «levantino» de uso común desde La Contestania a la Galia Narbonense. Consta de un solo letrero que hay que juzgar como ibérico. Ha sido escrito sobre una pátera. El grafito podría ser un nombre personal. Por haber aparecido en un asentamiento ibero-romano, hay que considerarlo dentro del proceso de romanización (siglo I a. C, fecha en que se data el grafito.ABSTRACT: It's about a graffito, executed with printings of a «levantino» type of a common use from the Contestania until the Galia Narbonense. It's formed of a single sign which we have to judge as Iberian. It has been written on a patera. The graffito could be a personal name. Because it appeared on an Iberian-roman site we must consider the graffito as belonging to the time of the romanisation process, i.e., first century B. C.
Semantic Analysis of Virtual Classes and Nested Classes

DEFF Research Database (Denmark)

Madsen, Ole Lehrmann

1999-01-01

Virtual classes and nested classes are distinguishing features of BETA. Nested classes originated from Simula, but until recently they have not been part of main stream object- oriented languages. C++ has a restricted form of nested classes and they were included in Java 1.1. Virtual classes...... classes and parameterized classes have been made. Although virtual classes and nested classes have been used in BETA for more than a decade, their implementation has not been published. The purpose of this paper is to contribute to the understanding of virtual classes and nested classes by presenting...
HLA-G in human reproduktion: aspects of genetics, function, and pregnancy complications

DEFF Research Database (Denmark)

Hviid, TVF

2006-01-01

-G polymorphism, the possible significance of this polymorphism in respect to HLA-G function and certain complications of pregnancy (such as pre-eclampsia and recurrent spontaneous abortions (RSA)) are discussed together with possible importance to IVF. Finally, aspects of a possible role of HLA-G in organ...... transplantation and in inflammatory or autoimmune disease, and of HLA-G in an evolutionary context, are also briefly examined......The non-classical human leukocyte antigen (HLA) class Ib genes, HLA-E, -G and -F, are located on chromosome 6 in the human major histocompatibility complex (MHC). HLA class Ib antigens resemble the HLA class Ia antigens in many ways, but several major differences have been described. This review...
Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

Science.gov (United States)

Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng

2015-01-01

Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron’s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4− Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374
Class 1 and 2 integrons, sul resistance genes and antibiotic resistance in Escherichia coli isolated from Dongjiang River, South China

International Nuclear Information System (INIS)

Su Haochang; Ying Guangguo; Tao Ran; Zhang Ruiquan; Zhao Jianliang; Liu Yousheng

2012-01-01

Antibiotic susceptibility, detection of sul gene types and presence of class 1, 2 and 3 integrons and gene cassettes using PCR assays were investigated in 3456 Escherichia coli isolates obtained from 38 sampling sites of the Dongjiang River catchment in the dry and wet seasons. 89.1% of the isolates were resistant and 87.5% showed resistance to at least three antibiotics. sul2 was detected most frequently in 89.2% of 1403 SXT-resistant isolates. The presence of integrons (class 1 and 2) was frequently observed (82.3%) while no class 3 integron was found. In these integrons, 21 resistance genes of 14 gene cassette arrays and 10 different families of resistance genes were identified. Three gene cassette arrays, aac(6')-Ib-cr-aar-3-dfrA27-aadA16, aacA4-catB3-dfrA1 and aadA2-lnuF, were detected for the first time in surface water. The results showed that bacterial resistance in the catchment was seriously influenced by human activities, especially discharge of wastewater. Highlights: ► Antibiotic resistance was investigated for a river catchment of southern China. ► 87.5% of E coli isolates showed resistance to at least three antibiotics. ► The presence of integrons (class 1 and 2) was frequently observed (82.3%). ► Bacterial resistance in the catchment was seriously influenced by human activities. - Bacterial resistance to antibiotics in a catchment is related to the discharge of wastewater into the aquatic environment.

Biochemical Characterization of Mycobacterium smegmatis RnhC (MSMEG_4305), a Bifunctional Enzyme Composed of Autonomous N-Terminal Type I RNase H and C-Terminal Acid Phosphatase Domains.

Science.gov (United States)

Jacewicz, Agata; Shuman, Stewart

2015-08-01

Mycobacterium smegmatis encodes several DNA repair polymerases that are adept at incorporating ribonucleotides, which raises questions about how ribonucleotides in DNA are sensed and removed. RNase H enzymes, of which M. smegmatis encodes four, are strong candidates for a surveillance role. Here, we interrogate the biochemical activity and nucleic acid substrate specificity of M. smegmatis RnhC, a bifunctional RNase H and acid phosphatase. We report that (i) the RnhC nuclease is stringently specific for RNA:DNA hybrid duplexes; (ii) RnhC does not selectively recognize and cleave DNA-RNA or RNA-DNA junctions in duplex nucleic acid; (iii) RnhC cannot incise an embedded monoribonucleotide or diribonucleotide in duplex DNA; (iv) RnhC can incise tracts of 4 or more ribonucleotides embedded in duplex DNA, leaving two or more residual ribonucleotides at the cleaved 3'-OH end and at least one or two ribonucleotides on the 5'-PO4 end; (v) the RNase H activity is inherent in an autonomous 140-amino-acid (aa) N-terminal domain of RnhC; and (vi) the C-terminal 211-aa domain of RnhC is an autonomous acid phosphatase. The cleavage specificity of RnhC is clearly distinct from that of Escherichia coli RNase H2, which selectively incises at an RNA-DNA junction. Thus, we classify RnhC as a type I RNase H. The properties of RnhC are consistent with a role in Okazaki fragment RNA primer removal or in surveillance of oligoribonucleotide tracts embedded in DNA but not in excision repair of single misincorporated ribonucleotides. RNase H enzymes help cleanse the genome of ribonucleotides that are present either as ribotracts (e.g., RNA primers) or as single ribonucleotides embedded in duplex DNA. Mycobacterium smegmatis encodes four RNase H proteins, including RnhC, which is characterized in this study. The nucleic acid substrate and cleavage site specificities of RnhC are consistent with a role in initiating the removal of ribotracts but not in single-ribonucleotide surveillance. Rnh
Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis.

Science.gov (United States)

Ford, Alexander C; Chey, William D; Talley, Nicholas J; Malhotra, Ashish; Spiegel, Brennan M R; Moayyedi, Paul

2009-04-13

Individuals with irritable bowel syndrome (IBS) report abdominal pain, bloating, and diarrhea, symptoms similar to those in celiac disease. Studies suggest that the prevalence of celiac disease is increased in individuals with IBS; however, evidence is conflicting, and current guidelines do not always recommend screening for celiac disease in these individuals. We conducted a systematic review and meta-analysis to estimate prevalence of celiac disease in unselected adults who met diagnostic criteria for IBS. MEDLINE (1950 to May 31, 2008) and EMBASE (1980 to May 31, 2008) were searched. Case series and case-control studies that used serologic tests for celiac disease were eligible for inclusion. Prevalence of positive serologic indications of celiac disease and biopsy-proved celiac disease were extracted and pooled for all studies and were compared between cases and controls using an odds ratio and 95% confidence interval. Fourteen studies were identified comprising 4204 individuals, of whom 2278 (54%) met diagnostic criteria for IBS. Pooled prevalence of positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease were 4.0% (95% confidence interval, 1.7-7.2), 1.63% (0.7-3.0), and 4.1% (1.9-7.0), respectively. Pooled odds ratios (95% confidence intervals) for positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS compared with controls without IBS were 3.40 (1.62-7.13), 2.94 (1.36-6.35), and 4.34 (1.78-10.6). Prevalence of biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS was more than 4-fold that in controls without IBS.
Presenting a Model Based on Fuzzy Application to Optimize the Time of IBS Projects in Gas Refineries

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Naderpour Abbas

2017-01-01

Full Text Available Nowadays, the construction industry has started to embrace IBS as a method of attaining better construction quality and productivity and reducing risks related to occupational safety and health. The built of pre-fabricated component in factories reduces many problems related to lack of purposing uncertainty in scheduling calculation and time management of projects. In the case of using IBS method for managing time in projects, former studies such as Allan Tay’s research, indicates that this method can save up at least 29% of overall completion period versus the conventional method. But beside mentioned advantages of this technical method, the projects could be optimized more and more in scheduling calculations. This issue is critical in gas refineries, since special parameters such as risk of spreading poison H2S gas and mandatory of performing projects in short time period events such as maintenance overhauls demands to perform projects in optimum time. Custom scheduling calculation of project planning uses the Critical Path Method (CPM as a tool for Planning Project’s activities. The researches of this paper’s authors indicated that Fuzzy Critical Path Method (FCPM is the best technique to manage the uncertainty in project scheduling and can save up the construction project’s time versus the custom methods. This paper aims to present a model based on fuzzy application in CPM calculations to optimize the time of Industrial Building System.
Vertebrados marinos del neógeno del suroeste de la Península Ibérica

OpenAIRE

Toscano Grande, Antonio

2016-01-01

Esta Tesis Doctoral aborda el estudio de los vertebrados marinos presentes en las formaciones del Mioceno y Plioceno del SO de la Cuenca del Guadalquivir en la provincia de Huelva, sus aspectos evolutivos e implicaciones paleoecológicas. Los resultados obtenidos permiten definir con mayor resolución la evolución de los ecosistemas litorales y marinos del SO de la Península Ibérica durante el Neógeno superior. Durante esta época, las dos principales vías de comunicación entre el océano Atlánti...
The high-frequency ESR spectra of the syntetic diamond and nanodiamonds type Ib at low temperature

International Nuclear Information System (INIS)

Khatsko, E.; Kobets, M.; Dergachev, K.; Kulbickas, A.; Rasteniene, L.; Vaisnoras, R.

2013-01-01

The ESR absorption spectra of nonirradiated and irradiated (by electrons with an energy of 2 MeV) bulk diamond and nanodiamond powder of type Ib have been studied at a wide range of frequencies (70-20 GHz) and temperature (4.2-0 K) by ESR method. It is shown, that in the ESR spectrum of bulk diamond absorption lines of ion nickel catalyst Ni +a nd a paramagnetic single center of the nitrogen N 0 is observed. Absorption lines of the paramagnetic centers with dangling bonds on the nanodiamond surface (surface defects) in the ESR spectra are obtained.
Aportaciones al conocimiento faunístico de los géneros Limnebius Leach, 1815 y Ochthebius Leach, 1815 en la Península Ibérica (Coleoptera, Hydraenidae

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Delgado, J. A.

2007-12-01

Full Text Available New records on the distributional range of 3 species of the genus Limnebius Leach and 9 species of Ochthebius Leach belonging to the subgenera Asiobates Thomson and Ochthebius Leach in the Iberian Peninsula are given. Three new records are specially relevant to the knowledge of the Iberian hydraenid fauna: Ochthebius (Asiobates bicolon Germar, 1824, collected in the provinces of Soria and Cuenca, which represent the first confirmed records for this species in Spain, Ochthebius (Asiobates figueroi Garrido, 1990 reported for Cuenca and, finally, the confirmation of the presence in the Iberian Peninsula of Ochthebius (Ochthebius pusillus Stephens, 1835.Se amplía el conocimiento del área de distribución de 3 especies de Limnebius Leach y 9 especies de Ochthebius Leach de los subgéneros Asiobates Thomson y Ochthebius Leach en la Península Ibérica. Entre estas citas destacan las capturas en las provincias de Cuenca y Soria de Ochthebius (Asiobates bicolon Germar, 1824 que suponen el primer registro ibérico de la especie y de Ochthebius (Asiobates figueroi Garrido, 1990 en la provincia de Cuenca. Igualmente se confirma la presencia en la Península Ibérica de Ochthebius (Ochthebius pusillus Stephens, 1835.
Diseño y desarrollo del Plan de Igualdad en Bonduelle Ibérica S.A.U

OpenAIRE

HIGINO BLAZQUEZ, ANNABELLE

2015-01-01

[ES] El objeto del proyecto es elaborar un plan de igualdad en Bonduelle Ibérica S.A.U. mediante un diagnóstico de situación, analizar la política estratégica en materia de Igualdad de la empresa y proponer acciones y medidas asociadas a dicha política para la toma de decisiones de la Alta Dirección, así como los indicadores clave de seguimiento definidos para los ejes principales en materia de igualdad. Paralelamente, se presentan los procedimientos de control interno de es...
Iberos, públicos y cultura de masas. El pasado ibérico en el imaginario colectivo valenciano

OpenAIRE

Vizcaíno Estevan, Antonio

2015-01-01

La presente investigación plantea analizar de qué maneras el pasado ibérico ha sido imaginado, percibido y utilizado por la sociedad valenciana desde la concesión del Estatuto de Autonomía (1982) hasta la actualidad (2012). El propósito, siguiendo los principios de la Arqueología Pública, es ahondar en los significados que el pasado y el patrimonio tienen en el presente, así como examinar su papel en los procesos de construcción identitaria, especialmente los referidos a las identidades de ba...
Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib : Results of the European Study on Glycogen Storage Disease Type I

NARCIS (Netherlands)

Visser, G; Rake, JP; Fernandes, J; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Smit, GPA

Objective: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. Method: As part of a collaborative European Study on GSD type I, a retrospective registry was established in
Rice gene SDL/RNRS1, encoding the small subunit of ribonucleotide reductase, is required for chlorophyll synthesis and plant growth development.

Science.gov (United States)

Qin, Ran; Zeng, Dongdong; Liang, Rong; Yang, Chengcong; Akhter, Delara; Alamin, Md; Jin, Xiaoli; Shi, Chunhai

2017-09-05

A new mutant named sdl (stripe and drooping leaf) was characterized from indica cultivar Zhenong 34 by ethylmethane sulfonate (EMS) mutagenesis. The mutant sdl exhibited development defects including stripe and drooping leaf, dwarfism and deformed floral organs. The gene SDL was found allelic to RNRS1 by map-based cloning, which was homologous to Arabidopsis TSO2 encoding the small subunit of ribonucleotide reductase. The gDNA sequencing results of sdl in mutant showed that there was a repetitive sequence insertion of 138-bp at the 475 th bp in the exon. The redundant sequence was conserved in SDL homologous proteins, which contained the active site (tyrosine), as well as two amino acids glutamate and histidine involved in the binding of iron. There were fewer chloroplasts and grana lamellas in sdl leaf compared with those of wild-type. Additionally, the stripe leaves of sdl seedlings were highly sensitive to temperature, since the chlorophyll content was increased with the temperature rising. The drooping leaf of sdl might be resulted from the disappearance of vascular bundles and mesophyll cells in both leaf midrib and lateral veins. Fittingly to the phenotypes of mutant sdl, the expression levels of genes associated with photosynthesis and chlorophyll synthesis were found to be down- or up-regulated at different temperatures in mutant sdl. Also, the transcriptional levels of genes related to plant height and floral organ formation showed obvious differences between wild-type and sdl. The "SDL/RNRS1" was, hence, required for the chlorophyll biosynthesis and also played pleiotropic roles in the regulation of plant development. Copyright © 2017. Published by Elsevier B.V.
Lack of a peroxiredoxin suppresses the lethality of cells devoid of electron donors by channelling electrons to oxidized ribonucleotide reductase.

Science.gov (United States)

Boronat, Susanna; Domènech, Alba; Carmona, Mercè; García-Santamarina, Sarela; Bañó, M Carmen; Ayté, José; Hidalgo, Elena

2017-06-01

The thioredoxin and glutaredoxin pathways are responsible of recycling several enzymes which undergo intramolecular disulfide bond formation as part of their catalytic cycles such as the peroxide scavengers peroxiredoxins or the enzyme ribonucleotide reductase (RNR). RNR, the rate-limiting enzyme of deoxyribonucleotide synthesis, is an essential enzyme relying on these electron flow cascades for recycling. RNR is tightly regulated in a cell cycle-dependent manner at different levels, but little is known about the participation of electron donors in such regulation. Here, we show that cytosolic thioredoxins Trx1 and Trx3 are the primary electron donors for RNR in fission yeast. Unexpectedly, trx1 transcript and Trx1 protein levels are up-regulated in a G1-to-S phase-dependent manner, indicating that the supply of electron donors is also cell cycle-regulated. Indeed, genetic depletion of thioredoxins triggers a DNA replication checkpoint ruled by Rad3 and Cds1, with the final goal of up-regulating transcription of S phase genes and constitutive RNR synthesis. Regarding the thioredoxin and glutaredoxin cascades, one combination of gene deletions is synthetic lethal in fission yeast: cells lacking both thioredoxin reductase and cytosolic dithiol glutaredoxin. We have isolated a suppressor of this lethal phenotype: a mutation at the Tpx1-coding gene, leading to a frame shift and a loss-of-function of Tpx1, the main client of electron donors. We propose that in a mutant strain compromised in reducing equivalents, the absence of an abundant and competitive substrate such as the peroxiredoxin Tpx1 has been selected as a lethality suppressor to favor RNR function at the expense of the non-essential peroxide scavenging function, to allow DNA synthesis and cell growth.
Lack of a peroxiredoxin suppresses the lethality of cells devoid of electron donors by channelling electrons to oxidized ribonucleotide reductase.

Directory of Open Access Journals (Sweden)

Susanna Boronat

2017-06-01

Full Text Available The thioredoxin and glutaredoxin pathways are responsible of recycling several enzymes which undergo intramolecular disulfide bond formation as part of their catalytic cycles such as the peroxide scavengers peroxiredoxins or the enzyme ribonucleotide reductase (RNR. RNR, the rate-limiting enzyme of deoxyribonucleotide synthesis, is an essential enzyme relying on these electron flow cascades for recycling. RNR is tightly regulated in a cell cycle-dependent manner at different levels, but little is known about the participation of electron donors in such regulation. Here, we show that cytosolic thioredoxins Trx1 and Trx3 are the primary electron donors for RNR in fission yeast. Unexpectedly, trx1 transcript and Trx1 protein levels are up-regulated in a G1-to-S phase-dependent manner, indicating that the supply of electron donors is also cell cycle-regulated. Indeed, genetic depletion of thioredoxins triggers a DNA replication checkpoint ruled by Rad3 and Cds1, with the final goal of up-regulating transcription of S phase genes and constitutive RNR synthesis. Regarding the thioredoxin and glutaredoxin cascades, one combination of gene deletions is synthetic lethal in fission yeast: cells lacking both thioredoxin reductase and cytosolic dithiol glutaredoxin. We have isolated a suppressor of this lethal phenotype: a mutation at the Tpx1-coding gene, leading to a frame shift and a loss-of-function of Tpx1, the main client of electron donors. We propose that in a mutant strain compromised in reducing equivalents, the absence of an abundant and competitive substrate such as the peroxiredoxin Tpx1 has been selected as a lethality suppressor to favor RNR function at the expense of the non-essential peroxide scavenging function, to allow DNA synthesis and cell growth.
40 CFR 90.404 - Test procedure overview.

Science.gov (United States)

2010-07-01

... mode and five power modes at one speed (rated or intermediate). The test cycle for Class I-A, III, IV... measurement device. The exhaust gases generated during engine operation are sampled either raw or dilute and... fuel consumption. For Phase 2 Class I-B, Class I, and Class II natural gas fueled engines the test is...
La historia de la esclavitud y la historia medieval de la Península Ibérica

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William D. (Jr. Phillips

2010-01-01

Full Text Available La historia de la esclavitud en la Península Ibérica ha despertado un gran interés e inspirado un gran número de publicaciones en las últimas décadas. La esclavitud fue una constante a lo largo de los periodos antiguo y medieval, hasta nuestros días. Sin embargo, al mismo tiempo, era escasa en número y sus porcentajes reducidos respecto al número total de la población. En la mayor parte de los periodos, los esclavos suponían menos de un 5% de la población total, aunque en algunas ciudades era a veces superior, llegando a suponer hasta un 25%. El origen de los esclavos podía variar, desde los hijos de madres esclavas, a los cautivos de guerra que no habían conseguido rescatarse, o esclavos importados a la Península Ibérica por mercaderes. Este último grupo varió en su composición a lo largo del tiempo, e incluía esclavos europeos, del Próximo Oriente, del Magreb y de África Subsahariana. A partir del siglo XVI y hasta el XVIII, aparecen también en la documentación unos cuantos esclavos americanos y asiáticos. Hasta la fecha, los estudios se han basado en aquellos documentos de venta que proporcionaban información sobre los esclavos. Más recientemente, la documentación procedente de casos legales, cofradías religiosas y por los propios esclavos han cobrado importancia. Las nuevas tendencias dentro de los estudios sobre la esclavitud investigan las relaciones entre raza —concepto definido y analizado de muy distintas formas— y esclavitud, y el creciente reconocimiento del enorme peso de la esclavitud femenina. Las historias de estas mujeres y de sus hijos, que crecieron como esclavos, se convertirán probablemente en uno de los temas clave de estos nuevos enfoques.The history of slavery in the Península Ibérican Peninsula has generated great interest and many publications over the last several decades. Slavery was a constant presence from ancient through medieval to early modern times. At the same time, though, it
Class prediction for high-dimensional class-imbalanced data

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Lusa Lara

2010-10-01

Full Text Available Abstract Background The goal of class prediction studies is to develop rules to accurately predict the class membership of new samples. The rules are derived using the values of the variables available for each subject: the main characteristic of high-dimensional data is that the number of variables greatly exceeds the number of samples. Frequently the classifiers are developed using class-imbalanced data, i.e., data sets where the number of samples in each class is not equal. Standard classification methods used on class-imbalanced data often produce classifiers that do not accurately predict the minority class; the prediction is biased towards the majority class. In this paper we investigate if the high-dimensionality poses additional challenges when dealing with class-imbalanced prediction. We evaluate the performance of six types of classifiers on class-imbalanced data, using simulated data and a publicly available data set from a breast cancer gene-expression microarray study. We also investigate the effectiveness of some strategies that are available to overcome the effect of class imbalance. Results Our results show that the evaluated classifiers are highly sensitive to class imbalance and that variable selection introduces an additional bias towards classification into the majority class. Most new samples are assigned to the majority class from the training set, unless the difference between the classes is very large. As a consequence, the class-specific predictive accuracies differ considerably. When the class imbalance is not too severe, down-sizing and asymmetric bagging embedding variable selection work well, while over-sampling does not. Variable normalization can further worsen the performance of the classifiers. Conclusions Our results show that matching the prevalence of the classes in training and test set does not guarantee good performance of classifiers and that the problems related to classification with class
La cerámica pintada de tradición indígena en las áreas ibéricas de la Hispania romana

OpenAIRE

Abascal Palazón, Juan Manuel

1992-01-01

Contribución a un workshop de la Societat Catalana d'Arqueologia que tuvo lugar en 1992 en Barcelona. Análisis global de la producción de cerámica pintada de época romana en la costa mediterránea de la Península Ibérica.
La Torre Portal y el Portal Torreado en las fortificaciones ibéricas. Estudio de las entradas Norte y Oeste de la Bastida de les Alcusses (Moixent, Valéncia

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Enrique Díes Cusí

2005-01-01

Full Text Available En este trabajo presentamos dos estructuras halladas en el poblado ibérico de La Bastida de les Alcusses durante la campaña de excavación de 1998. Se trata de dos entradas (la Oeste y la Norte que presentan la particularidad de ser edificios en sí mismos, si bien de factura diversa. Estos edificios se describen y se estudian constructivamente, analizando la posibilidad de que se trate de dos Portales, uno de ellos una Torre Portal y el otro un Portal Torreado, de larga tradición en la arquitectura oriental y, creemos, con paralelos en la arquitectura ibérica.
Structure and expression of MHC class Ib genes of the central M region in rat and mouse: M4, M5, and M6.

Science.gov (United States)

Lambracht-Washington, Doris; Moore, Yuki F; Wonigeit, Kurt; Lindahl, Kirsten Fischer

2008-04-01

The M region at the telomeric end of the murine major histocompatibility complex (MHC) contains class I genes that are highly conserved in rat and mouse. We have sequenced a cosmid clone of the LEW rat strain (RT1 haplotype) containing three class I genes, RT1.M6-1, RT1.M4, and RT1.M5. The sequences of allelic genes of the BN strain (RT1n haplotype) were obtained either from cDNAs or genomic clones. For the coding parts of the genes few differences were found between the two RT1 haplotypes. In LEW, however, only RT1.M5 and RT1.M6 have open reading frames; whereas in BN all three genes were intact. In line with the findings in BN, transcription was found for all three rat genes in several tissues from strain Sprague Dawley. Protein expression in transfectants could be demonstrated for RT1.M6-1 using the monoclonal antibody OX18. By sequencing of transcripts obtained by RT-PCR, a second, transcribed M6 gene, RT1.M6-2, was discovered, which maps next to RT1.M6-1 outside of the region covered by the cosmid. In addition, alternatively spliced forms for RT1.M5 and RT1.M6 were detected. Of the orthologous mouse genes, H2-M4, H2-M5, and H2-M6, only H2-M5 has an open reading frame. Other important differences between the corresponding parts of the M region of the two species are insertion of long LINE repeats, duplication of RT1.M6, and the inversion of RT1.M5 in the rat. This demonstrates substantial evolutionary dynamics in this region despite conservation of the class I gene sequences themselves.
Comparison of the binding properties of the mushroom Marasmius oreades lectin and Griffonia simplicifolia I-B isolectin to alphagalactosyl carbohydrate antigens in the surface phase

DEFF Research Database (Denmark)

Kirkeby, Svend; Winter, Harry C; Goldstein, Irwin J

2004-01-01

The binding of two alpha-galactophilic lectins, Marasmius oreades agglutinin (MOA), and Griffonia simplicifolia I isolectin B(4) (GS I-B(4)) to neoglycoproteins and natural glycoproteins were compared in a surface phase assay. Neoglycoproteins carrying various alpha-galactosylated glycans and lam...
Trascendencia del tema del Labrador en la cerámica ibérica de la provincia de Teruel

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María Rosario LUCAS PELLICER

2009-10-01

Full Text Available En 1981 tras comparar sucintamente las figuraciones vasculares de las distintas áreas ibéricas, formulaba tímidamente la hipótesis de que los personajes del círculo de Azaila guardaban relación con el sistema trifuncional indoeuropeo defendido por Dumezil. El hombre con el arado representaría la tercera función cuya competencia se extiende a la fertilidad de la naturaleza (riqueza y abundancia de frutos, ganados y cosechas y a su renovación (juventud.

Dependent Classes

DEFF Research Database (Denmark)

Gasiunas, Vaidas; Mezini, Mira; Ostermann, Klaus

2007-01-01

of dependent classes and a machine-checked type soundness proof in Isabelle/HOL [29], the first of this kind for a language with virtual classes and path-dependent types. [29] T.Nipkow, L.C. Poulson, and M. Wenzel. Isabelle/HOL -- A Proof Assistant for Higher-Order Logic, volume 2283 of LNCS, Springer, 2002......Virtual classes allow nested classes to be refined in subclasses. In this way nested classes can be seen as dependent abstractions of the objects of the enclosing classes. Expressing dependency via nesting, however, has two limitations: Abstractions that depend on more than one object cannot...... be modeled and a class must know all classes that depend on its objects. This paper presents dependent classes, a generalization of virtual classes that expresses similar semantics by parameterization rather than by nesting. This increases expressivity of class variations as well as the flexibility...
A geochemical evaluation of the Ash Sha'ib mineral prospect, Asir quadrangle, Kingdom of Saudi Arabia

Science.gov (United States)

Allcott, Glenn H.

1970-01-01

The mineralized zone at the remotely located Ash Sha'ib ancient mine contains only a small tonnage of moderately low grade sulfide- bearing rock. Based on present data the gross value of the deposit, with a value of $25.00 or more per ton, is $20,000,000. A belt of metasedimentary rocks, intruded by gabbro to the south and granite to the north, was the host for fissure vein-replacement type mineralization. Most of the mineralization is in a siliceous dolomite transected by fissures. The main sulfide mineral is sphalerite, but minor amounts of chalcopyrlte and argentlferous galena contribute to the value of the mineralized sections.
Retrospective case-control study of surgical treatment of stage IB-IIA cervical carcinomas after neoadjuvant radiotherapy

International Nuclear Information System (INIS)

Cigriejiene, V. M.; Kajenas, S.; Balnys, M.; Mikuckaite, L.

2004-01-01

To evaluate if preoperative radiotherapy influences course of operation (radical hysterectomy and lymphadenectomy) and postoperative period in series of stage IB-IIA cervical carcinomas. Retrospective comparative study was performed. During the study we analyzed 101 case histories of patients who underwent radical type II hysterectomy with lymphadenectomy in Kaunas University of Medicine Hospital and Kaunas Hospital of Oncology between 1995 and 2002. Mean operation time was shorter, hemoglobin and hematocrit values after operation were better, stay in hospital was longer, demand for narcotic analgetics was bigger, function of ovaries was maintained more rarely (p 0.05). In our study, preoperative radiotherapy did not seem to complicate course of radical hysterectomy. (author)
Characterization of hydroxyurea (HYU) S49 T lymphoma cells

International Nuclear Information System (INIS)

Albert, D.A.; Gudas, L.J.

1986-01-01

This paper tests the hypotheses that in vivo ribonucleotide reductase activity and consequent deoxyribonucleoside triphosphate production is rate-limited by the availability of M2 activity. The authors selected and characterized cell lines with variable resistance to hydroxyurea and comparing them with wild type S49 T-lymphoma cells. Ribonucleotide reductase assay was measured and in the process C 14-CDP was added in the final volume of assay mixture. It is shown that hydroxourea reversibly binds to the tyrosine radical of the M2 subunit of ribonucleotide reductase that is required for catalytic activity
Typing of multiple single-nucleotide polymorphisms using ribonuclease cleavage of DNA/RNA chimeric single-base extension primers and detection by MALDI-TOF mass spectrometry

DEFF Research Database (Denmark)

Mengel-From, Jonas; Sanchez Sanchez, Juan Jose; Børsting, Claus

2005-01-01

A novel single-base extension (SBE) assay using cleavable and noncleavable SBE primers in the same reaction mix is described. The cleavable SBE primers consisted of deoxyribonucleotides and one ribonucleotide (hereafter denoted chimeric primers), whereas the noncleavable SBE primers consisted....... A ribonuclease mix was developed to specifically cleave the chimeric primers, irrespective of the base of the ribonucleotide, whereas standard primers without a ribonucleotide were unaffected by the ribonuclease treatment. The SBE products were analyzed in linear mode using a matrix-assisted laser desorption...... containing 9 chimeric primers and 8 standard primers....
Diverse gene cassettes in class 1 integrons of facultative oligotrophic bacteria of River Mahananda,West Bengal, India.

Directory of Open Access Journals (Sweden)

Ranadhir Chakraborty

Full Text Available BACKGROUND: In this study a large random collection (n=2188 of facultative oligotrophic bacteria, from 90 water samples gathered in three consecutive years (2007-2009 from three different sampling sites of River Mahananda in Siliguri, West Bengal, India, were investigated for the presence of class 1 integrons and sequences of the amplification products. METHODOLOGY/PRINCIPAL FINDINGS: Replica plating method was employed for determining the antibiotic resistance profile of the randomly assorted facultative oligotrophic isolates. Genomic DNA from each isolate was analyzed by PCR for the presence of class 1 integron. Amplicons were cloned and sequenced. Numerical taxonomy and 16S rRNA gene sequence analyses were done to ascertain putative genera of the class 1 integron bearing isolates. Out of 2188 isolates, 1667 (76.19% were antibiotic-resistant comprising of both single-antibiotic resistance (SAR and multiple-antibiotic resistant (MAR, and 521 (23.81% were sensitive to all twelve different antibiotics used in this study. Ninety out of 2188 isolates produced amplicon(s of varying sizes from 0.15 to 3.45 KB. Chi-square (χ(2 test revealed that the possession of class 1 integron in sensitive, SAR and MAR is not equally probable at the 1% level of significance. Diverse antibiotic-resistance gene cassettes, aadA1, aadA2, aadA4, aadA5, dfrA1, dfrA5, dfrA7, dfrA12, dfrA16, dfrA17, dfrA28, dfrA30, dfr-IIe, blaIMP-9, aacA4, Ac-6'-Ib, oxa1, oxa10 and arr2 were detected in 64 isolates. The novel cassettes encoding proteins unrelated to any known antibiotic resistance gene function were identified in 26 isolates. Antibiotic-sensitive isolates have a greater propensity to carry gene cassettes unrelated to known antibiotic-resistance genes. The integron-positive isolates under the class Betaproteobacteria comprised of only two genera, Comamonas and Acidovorax of family Comamonadaceae, while isolates under class Gammaproteobacteria fell under the families
Analysis of the vegetation of the sandstone ridges (Ib land type of the north-eastern parts of the Mapungubwe National Park, Limpopo Province, South Africa

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Albie R. Gotze

2008-12-01

Full Text Available The establishment of the Mapungubwe National Park has been an objective of several conservationists for many years. The ultimate objective is that this park should become a major component of a Transfrontier National Park shared by Botswana, Zimbabwe and South Africa. The aim of this study was to identify, classify and describe the plant communities present in the Ib land type of the park. Sampling was done by means of the Braun-Blanquet method. A total of 48 stratified random relevés were sampled in the Ib land type. All relevé data were imported into a TURBOVEG database, after which the numerical classification technique TWINSPAN was used as a first approximation. Subsequently, Braun-Blanquet procedures were used to refine data and a phytosociological table was constructed, using the visual editor, MEGATAB. Two plant communities and several subcommunities and variants were identified and described from the phytosociological table.
Spectroscopic Evidence for a H Bond Network at Y356 Located at the Subunit Interface of Active E. coli Ribonucleotide Reductase.

Science.gov (United States)

Nick, Thomas U; Ravichandran, Kanchana R; Stubbe, JoAnne; Kasanmascheff, Müge; Bennati, Marina

2017-07-18

The reaction catalyzed by E. coli ribonucleotide reductase (RNR) composed of α and β subunits that form an active α2β2 complex is a paradigm for proton-coupled electron transfer (PCET) processes in biological transformations. β2 contains the diferric tyrosyl radical (Y 122 ·) cofactor that initiates radical transfer (RT) over 35 Å via a specific pathway of amino acids (Y 122 · ⇆ [W 48 ] ⇆ Y 356 in β2 to Y 731 ⇆ Y 730 ⇆ C 439 in α2). Experimental evidence exists for colinear and orthogonal PCET in α2 and β2, respectively. No mechanistic model yet exists for the PCET across the subunit (α/β) interface. Here, we report unique EPR spectroscopic features of Y 356 ·-β, the pathway intermediate generated by the reaction of 2,3,5-F 3 Y 122 ·-β2/CDP/ATP with wt-α2, Y 731 F-α2, or Y 730 F-α2. High field EPR (94 and 263 GHz) reveals a dramatically perturbed g tensor. [ 1 H] and [ 2 H]-ENDOR reveal two exchangeable H bonds to Y 356 ·: a moderate one almost in-plane with the π-system and a weak one. DFT calculation on small models of Y· indicates that two in-plane, moderate H bonds (r O-H ∼1.8-1.9 Å) are required to reproduce the g x value of Y 356 · (wt-α2). The results are consistent with a model, in which a cluster of two, almost symmetrically oriented, water molecules provide the two moderate H bonds to Y 356 · that likely form a hydrogen bond network of water molecules involved in either the reversible PCET across the subunit interface or in H + release to the solvent during Y 356 oxidation.
IB4(+) nociceptors mediate persistent muscle pain induced by GDNF.

Science.gov (United States)

Alvarez, Pedro; Chen, Xiaojie; Bogen, Oliver; Green, Paul G; Levine, Jon D

2012-11-01

Skeletal muscle is a well-known source of glial cell line-derived neurotrophic factor (GDNF), which can produce mechanical hyperalgesia. Since some neuromuscular diseases are associated with both increased release of GDNF and intense muscle pain, we explored the role of GDNF as an endogenous mediator in muscle pain. Intramuscularly injected GDNF induced a dose-dependent (0.1-10 ng/20 μl) persistent (up to 3 wk) mechanical hyperalgesia in the rat. Once hyperalgesia subsided, injection of prostaglandin E(2) at the site induced a prolonged mechanical hyperalgesia (>72 h) compared with naïve rats (vibration increased muscle GDNF levels at 24 h, a time point where rats also exhibited marked muscle hyperalgesia. Intrathecal antisense oligodeoxynucleotides to mRNA encoding GFRα1, the canonical binding receptor for GDNF, reversibly inhibited eccentric exercise- and mechanical vibration-induced muscle hyperalgesia. Finally, electrophysiological recordings from nociceptors innervating the gastrocnemius muscle in anesthetized rats, revealed significant increase in response to sustained mechanical stimulation after local GDNF injection. In conclusion, these data indicate that GDNF plays a role as an endogenous mediator in acute and induction of chronic muscle pain, an effect likely to be produced by GDNF action at GFRα1 receptors located in IB4(+) nociceptors.
Class size versus class composition

DEFF Research Database (Denmark)

Jones, Sam

Raising schooling quality in low-income countries is a pressing challenge. Substantial research has considered the impact of cutting class sizes on skills acquisition. Considerably less attention has been given to the extent to which peer effects, which refer to class composition, also may affect...... bias from omitted variables, the preferred IV results indicate considerable negative effects due to larger class sizes and larger numbers of overage-for-grade peers. The latter, driven by the highly prevalent practices of grade repetition and academic redshirting, should be considered an important...
Social Class Dialogues and the Fostering of Class Consciousness

Science.gov (United States)

Madden, Meredith

2015-01-01

How do critical pedagogies promote undergraduate students' awareness of social class, social class identity, and social class inequalities in education? How do undergraduate students experience class consciousness-raising in the intergroup dialogue classroom? This qualitative study explores undergraduate students' class consciousness-raising in an…
Zen law and features of liquidus-solidus curves in binary state diagrams based on elements VIIIA and IB of the periodic table

Science.gov (United States)

Potekaev, A. I.; Kondratyuk, A. A.; Porobova, S. A.; Klopotov, A. A.; Markova, T. N.; Kakushkin, Yu A.; Klopotov, V. D.

2016-11-01

The paper presents the analysis of binary state diagrams based on elements VIIIA and IB of the periodic table and crystal geometry parameters of solid solutions and intermetallic compositions. The analysis shows an explicit correlation between the type of the evolution of phase diagrams classified by Lebedev depending on the nature of atomic volume deviations observed in solid solutions and intermetallic compounds from Zen law.
Introducción a los problemas del arte esquemático de la Península Ibérica

Directory of Open Access Journals (Sweden)

Francisco JORDÁ CERDÁ

2009-10-01

Full Text Available Los que, bien por las necesidades de la investigación, bien por las de orden didáctico y pedagógico, han tenido que aproximarse al conocimiento del arte rupestre esquemático de la Península Ibérica, se han encontrado con todo caudal de elementos artísticoreligiosos, en el que a un amplio repertorio tipológico se une una gran variedad temática y una diversidad de técnicas de representación.
Describing three-class task performance: three-class linear discriminant analysis and three-class ROC analysis

Science.gov (United States)

He, Xin; Frey, Eric C.

2007-03-01

Binary ROC analysis has solid decision-theoretic foundations and a close relationship to linear discriminant analysis (LDA). In particular, for the case of Gaussian equal covariance input data, the area under the ROC curve (AUC) value has a direct relationship to the Hotelling trace. Many attempts have been made to extend binary classification methods to multi-class. For example, Fukunaga extended binary LDA to obtain multi-class LDA, which uses the multi-class Hotelling trace as a figure-of-merit, and we have previously developed a three-class ROC analysis method. This work explores the relationship between conventional multi-class LDA and three-class ROC analysis. First, we developed a linear observer, the three-class Hotelling observer (3-HO). For Gaussian equal covariance data, the 3- HO provides equivalent performance to the three-class ideal observer and, under less strict conditions, maximizes the signal to noise ratio for classification of all pairs of the three classes simultaneously. The 3-HO templates are not the eigenvectors obtained from multi-class LDA. Second, we show that the three-class Hotelling trace, which is the figureof- merit in the conventional three-class extension of LDA, has significant limitations. Third, we demonstrate that, under certain conditions, there is a linear relationship between the eigenvectors obtained from multi-class LDA and 3-HO templates. We conclude that the 3-HO based on decision theory has advantages both in its decision theoretic background and in the usefulness of its figure-of-merit. Additionally, there exists the possibility of interpreting the two linear features extracted by the conventional extension of LDA from a decision theoretic point of view.
Social affiliation in same-class and cross-class interactions.

Science.gov (United States)

Côté, Stéphane; Kraus, Michael W; Carpenter, Nichelle C; Piff, Paul K; Beermann, Ursula; Keltner, Dacher

2017-02-01

Historically high levels of economic inequality likely have important consequences for relationships between people of the same and different social class backgrounds. Here, we test the prediction that social affiliation among same-class partners is stronger at the extremes of the class spectrum, given that these groups are highly distinctive and most separated from others by institutional and economic forces. An internal meta-analysis of 4 studies (N = 723) provided support for this hypothesis. Participant and partner social class were interactively, rather than additively, associated with social affiliation, indexed by affiliative behaviors and emotions during structured laboratory interactions and in daily life. Further, response surface analyses revealed that paired upper or lower class partners generally affiliated more than average-class pairs. Analyses with separate class indices suggested that these patterns are driven more by parental income and subjective social class than by parental education. The findings illuminate the dynamics of same- and cross-class interactions, revealing that not all same-class interactions feature the same degree of affiliation. They also reveal the importance of studying social class from an intergroup perspective. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
A Novel Mechanism of Sugar Selection Utilized by a Human X-family DNA Polymerase†

Science.gov (United States)

Brown, Jessica A.; Fiala, Kevin A.; Fowler, Jason D.; Sherrer, Shanen M.; Newmister, Sean A.; Dyum, Wade W.; Suo, Zucai

2009-01-01

During DNA synthesis, most DNA polymerases and reverse transcriptases select against ribonucleotides via a steric clash between the ribose 2′-hydroxyl group and the bulky side chain of an active site residue. Here, we demonstrated that human DNA polymerase λ used a novel sugar selection mechanism to discriminate against ribonucleotides, whereby the ribose 2′-hydroxyl group was excluded mostly by a backbone segment and slightly by the side chain of Y505. Such a steric clash was further demonstrated to be dependent on the size and orientation of the substituent covalently attached at the ribonucleotide C2′ position. PMID:19900463
Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible new twist on smallpox therapy.

Science.gov (United States)

Osheroff, Neil

2006-10-01

Smallpox is a serious and highly contagious disease that is caused by the variola virus. It is one of the most severe infectious human diseases known, with mortality rates as high as 30%. A successful worldwide vaccination program led to the eradication of smallpox in 1980. However, the high transmission rate of variola virus, coupled with the deadly nature of smallpox, makes this virus a potentially devastating weapon for bioterrorism. Currently, there is no specific treatment for smallpox. However, a recent article on the structure of a variola topoisomerase IB-DNA complex provides an intriguing starting point for the rational design of drugs with potential activity against smallpox.
Exportación de jamón ibérico envasado al vacío a Hong Kong

OpenAIRE

Batres Martínez, Jaime; Da Corte Dos Ramos, Sara M.; Doblas Martínez, Alejandro; Mancera Carmona, Lucía; Ramírez Sotomayor, Pilar

2014-01-01

La siguiente operación de comercio exterior trata sobre la exportación de jamón ibérico envasado al vacío desde España a Hong Kong, un producto gourmet de alto prestigio con gran reconocimiento a nivel mundial. Ésta se articula a través de la intermediación de VENSPA TRADE AGENTS S.L., una sociedad constituida por los integrantes de este proyecto que pone en contacto al exportador del producto, Dehesas del Múrtiga S.L., con el importador en Hong Kong, The Spanish Pantry HK Limited. Esto compo...
Estrategias de migración del género Acrocephalus en la Península Ibérica

OpenAIRE

Andueza Osés, Miren

2014-01-01

El objetivo de esta tesis es profundizar en el conocimiento de las estrategias migratorias de las aves del género Acrocephalus, el carricero común A. scirpaceus y el carricerín común A. shoenobaenus, durante la migración de otoño en la Península Ibérica. Su estudio se aborda a dos niveles: por un lado, la organización espacial de la migración a nivel peninsular y por otro el comportamiento en las áreas de descanso. A nivel peninsular, se observa que los carriceros que pasaron por la zona oest...
A phase Ia/Ib clinical trial of metronomic chemotherapy based on a mathematical model of oral vinorelbine in metastatic non-small cell lung cancer and malignant pleural mesothelioma: rationale and study protocol

International Nuclear Information System (INIS)

Elharrar, Xavier; Barbolosi, Dominique; Ciccolini, Joseph; Meille, Christophe; Faivre, Christian; Lacarelle, Bruno; André, Nicolas; Barlesi, Fabrice

2016-01-01

Metronomic oral vinorelbine is effective in metastatic NSCLC and malignant pleural mesothelioma, but all the studies published thus far were based upon a variety of empirical and possibly suboptimal schedules, with inconsistent results. Mathematical modelling showed by simulation that a new metronomic protocol could lead to a better safety and efficacy profile. This phase Ia/Ib trial was designed to confirm safety (phase Ia) and evaluate efficacy (phase Ib) of a new metronomic oral vinorelbine schedule. Patients with metastatic NSCLC or malignant pleural mesothelioma in whom standard treatments failed and who exhibited ECOG performance status 0–2 and adequate organ function will be eligible. Our mathematical PK-PD model suggested an alternative weekly D1, D2 and D4 schedule (named Vinorelbine Theoretical Protocol) with a respective dose of 60, 30 and 60 mg. Trial recruitment will be two-staged, as 12 patients are planned to participate in phase Ia to confirm safety and consolidate the calibration of the model parameters. Depending on the phase Ia results and after a favourable decision from a consultative committee, the extension phase (phase Ib) will be an efficacy study including 20 patients who will receive the Optimal Vinorelbine Theoretical Protocol. The primary endpoint is the tolerance (assessed by CTC v4.0) for the phase Ia and the objective response according to RECIST 1.1 for phase Ib. An ancillary study on circulating angiogenesis biomarkers will be a subproject of the trial. This ongoing trial is the first to prospectively test a mathematically optimized schedule in metronomic chemotherapy. As such, this trial can be considered as a proof-of-concept study demonstrating the feasibility to run a computational-driven protocol to ensure an optimal efficacy/toxicity balance in patients with cancer

A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours

NARCIS (Netherlands)

C.M.L. Herpen (Carla); F.A.L.M. Eskens (Ferry); M.J.A. de Jonge (Maja); I.M.E. Desar (Ingrid); L. Hooftman (Leon); E. Bone (Elisabeth); J.N.H. Timmerbonte (Johanna); J. Verweij (Jaap)

2010-01-01

textabstractBackground: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with
COP9 signalosome: a provider of DNA building blocks

DEFF Research Database (Denmark)

Nielsen, Olaf

2003-01-01

In fission yeast, the COP9 signalosome is required to activate ribonucleotide reductase for DNA synthesis. This is mediated via the ubiquitin ligase Pcu4, activation of which leads to degradation of the scaffold protein Spd1, which anchors the small ribonucleotide reductase subunit in the nucleus...
Exploring social class: voices of inter-class couples.

Science.gov (United States)

McDowell, Teresa; Melendez-Rhodes, Tatiana; Althusius, Erin; Hergic, Sara; Sleeman, Gillian; Ton, Nicky Kieu My; Zimpfer-Bak, A J

2013-01-01

Social class is not often discussed or examined in-depth in couple and family therapy research and literature even though social class shapes familial relationships and is considered an important variable in marital satisfaction. In this qualitative study, we explored the perceptions of eight couples who made lasting commitments across class lines by asking them about the impact of their social class backgrounds on their relationships. Three categories of themes emerged including: (a) differences and similarities in values and attitudes toward education, work, money, and class awareness/classism, (b) relationship issues involving families of origin, friends, and class-based couple conflict, and (c) differences in economic resources, social capital and privileges/opportunities. Implications for assessment and treatment of couples are included. © 2012 American Association for Marriage and Family Therapy.
Progesterone and DNA Damage Encourage Uterine Cell Proliferation and Decidualization through Up-regulating Ribonucleotide Reductase 2 Expression during Early Pregnancy in Mice*

Science.gov (United States)

Lei, Wei; Feng, Xu-Hui; Deng, Wen-Bo; Ni, Hua; Zhang, Zhi-Rong; Jia, Bo; Yang, Xin-Ling; Wang, Tong-Song; Liu, Ji-Long; Su, Ren-Wei; Liang, Xiao-Huan; Qi, Qian-Rong; Yang, Zeng-Ming

2012-01-01

Embryo implantation into the maternal uterus is a crucial step for the successful establishment of mammalian pregnancy. Following the attachment of embryo to the uterine luminal epithelium, uterine stromal cells undergo steroid hormone-dependent decidualization, which is characterized by stromal cell proliferation and differentiation. The mechanisms underlying steroid hormone-induced stromal cell proliferation and differentiation during decidualization are still poorly understood. Ribonucleotide reductase, consisting of two subunits (RRM1 and RRM2), is a rate-limiting enzyme in deoxynucleotide production for DNA synthesis and plays an important role in cell proliferation and tumorgenicity. Based on our microarray analysis, Rrm2 expression was significantly higher at implantation sites compared with interimplantation sites in mouse uterus. However, the expression, regulation, and function of RRM2 in mouse uterus during embryo implantation and decidualization are still unknown. Here we show that although both RRM1 and RRM2 expression are markedly induced in mouse uterine stromal cells undergoing decidualization, only RRM2 is regulated by progesterone, a key regulator of decidualization. Further studies showed that the induction of progesterone on RRM2 expression in stromal cells is mediated by the AKT/c-MYC pathway. RRM2 can also be induced by replication stress and DNA damage during decidualization through the ATR/ATM-CHK1-E2F1 pathway. The weight of implantation sites and deciduoma was effectively reduced by specific inhibitors for RRM2. The expression of decidual/trophoblast prolactin-related protein (Dtprp), a reliable marker for decidualization in mice, was significantly reduced in deciduoma and steroid-induced decidual cells after HU treatment. Therefore, RRM2 may be an important effector of progesterone signaling to induce cell proliferation and decidualization in mouse uterus. PMID:22403396
A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours.

NARCIS (Netherlands)

Herpen, C.M.L. van; Eskens, F.A.; Jonge, M. de; Desar, I.M.E.; Hooftman, L.; Bone, E.A.; Timmer-Bonte, J.N.H.; Verweij, J.

2010-01-01

BACKGROUND: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS:
Atypical antipsychotics as a possible treatment option for irritable bowel syndrome.

Science.gov (United States)

Pae, Chi-Un; Lee, Soo-Jung; Han, Changsu; Patkar, Ashwin A; Masand, Prakash S

2013-05-01

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder (FGID) that is characterised by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits. Although the pathophysiology of IBS is not fully understood, it is believed that psychiatric comorbidities are highly common in such patients. A variety of psychotropic medications are widely used in the treatment of IBS, particularly older antidepressants such as tricyclic antidepressants (TCAs). With the advent of newer antidepressant classes with better safety and tolerability compared with TCAs, such as serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), clinicians now have more advanced treatment options for treating IBS. Additionally, some atypical antipsychotics (AAs) have recently received approval for treatment of major depressive disorder (MDD). Some AAs may have potentials based on their pharmacodynamic profile and proven benefit for mood symptoms, pain, anxiety and sleep disturbances. This article describes the potential rationale, clinical data and practical aspects involved in the use of AAs for patients with IBS. Atypical antipsychotics (AAs) may have a role in the treatment of irritable bowel syndrome (IBS) based on the currently available findings, although there is no clear evidence, and a number of clinical issues to be addressed in the use of AAs for the treatment of IBS.
Astronomy in Denver: The polarization evolution of the luminous Type Ib SN 2012au

Science.gov (United States)

Hoffman, Jennifer L.; DeKlotz, Sophia; Cooper, Kevin; Slay, Hannah; Williams, George Grant; Supernova Spectropolarimetry Project (SNSPOL)

2018-06-01

We present an analysis of the spectropolarimetric behavior of the Type Ib SN 2012au over the first 315 days of its evolution. Our data were obtained by the Supernova Spectropolarimetry Project using the CCD Imaging/Spectropolarimeter (SPOL) at the 61" Kuiper, the 90" Bok, and the 6.5-m MMT telescopes. SN 2012au was a very energetic, luminous, and slowly evolving event that may represent an intermediate case between normal core-collapse supernovae and the enigmatic superluminous supernovae. Strong, time-variable line polarization signatures, particularly in the He Il λ5876 line, support previous hypotheses of an asymmetric explosion and allow us to trace detailed structures within the supernova ejecta as they change over time. We compare the polarimetric evolution of the continuum and emission lines in SN 2012au and compare its behavior with that of other bright and polarimetrically variable supernovae.
Class impressions : Higher social class elicits lower prosociality

NARCIS (Netherlands)

Van Doesum, Niels J.; Tybur, Joshua M.; Van Lange, Paul A.M.

2017-01-01

Social class predicts numerous important life outcomes and social orientations. To date, literature has mainly examined how an individual's own class shapes interactions with others. But how prosocially do people treat others they perceive as coming from lower, middle, or higher social classes?
Treatment of bulky stage IB and IIB cervical cancers with outpatient neutron brachytherapy, external pelvic radiation and extrafascial hysterectomy

International Nuclear Information System (INIS)

Van Nagell, J.R.; Maruyama, Y.; Yoneda, J.; Donaldson, E.S.; Hanson, M.B.; Gallion, H.H.; Powell, D.E.; Kryscio, R.J.

1986-01-01

From January, 1977, to December, 1982, twenty-nine patients with bulky (>4 cms diameter) Stage IB or IIB cervical cancer were treated at the University of Kentucky Medical Center by a combination of out-patient neutron brachytherapy (Cf-252) and external pelvic radiation followed by extrafascial hysterectomy. Residual tumor was present in the hysterectomy specimens of 25 per cent. Complications during and following radiation therapy and surgery were minimal and included vaginal stenosis, proctitis, and hemorrhagic cystitis. The mean duration of hospitalization for surgery in these patients was 6.6 days (range 5-15 days) and postoperative morbidity was low. No patient required blood transfusion. Four patients developed urinary tract infections and two had superficial wound separations. Following treatment, patients were seen at monthly intervals for one year, every three months for two years, and every six months thereafter. No patient has been lost to follow-up. Two patients (7 per cent) developed tumor recurrence and have died of disease (1 of distant metastases; 1 local). The remaining 27 patients (93 per cent) are alive and well with no evidence of disease 24-89 months (mean 48 months) after therapy. No radiogenic fistulae or bowel obstruction were observed. These preliminary results suggest that the combination of outpatient neutron brachytherapy, external pelvic radiation, and extrafascial hysterectomy for patients with Stage IB and IIB cervical cancer is well tolerated. Complications associated with this treatment regimen have been minimal, and the recurrence rate is low. The duration of intracavitary neutron brachytherapy was short, and outpatient therapy was well received by patients
Anexo: Fibras de lino en las piletas del poblado ibérico del Coll del Moro (Gandesa, Terra Alta: estudio paleoetnobotánico

Directory of Open Access Journals (Sweden)

Alonso i Martínez, Natàlia

1994-12-01

Full Text Available In this paper we offer the results of research on flax fibres discovered in water-bassins of the Iberian settlement of Coll del Moro (Gandesa, Spain

En el presente estudio presentamos los resultados obtenidos en las investigaciones realizadas sobre la funcionalidad de las piletas del poblado ibérico del Coll del Moro (Gandesa, en las cuales detectamos una importante presencia de fibras de lino.
RxClass

Data.gov (United States)

U.S. Department of Health & Human Services — The RxClass Browser is a web application for exploring and navigating through the class hierarchies to find the RxNorm drug members associated with each class....
Marinbiologisk optegnelse i NUḪBAT AL-DAHR FĪ ʿAǦ ʾIB AL-BARR WA-AL-BAḤR

OpenAIRE

Provencal, Philippe

2014-01-01

I det arabiske geografiske værk NUḪBAT AL-DAHR FĪ ʿAǦ ʾIB AL-BARR WA-AL-BAḤR (færdigskrevet mellem 1324 og 1327) fra omtales seks dyr fra Adenbugten. Det dreje sig om savrokke, kuglefisk, pilrokke, pindsvinefisk og hvalhaj. Det sidste dyr har ikke kunnet bestemmes. Artiklen bringer en oversættelse af optegnelsen til engelsk samt både en filologisk som en biologisk kommentar. The aim of this article is to present a medieval Arabic report regarding sixanimals from the Gulf of Aden, to provid...
Los animales representados en el arte rupestre de la Península Ibérica. Frecuencias de los mismos

Directory of Open Access Journals (Sweden)

Jesús Altuna

2002-01-01

Full Text Available Se trata de recuentos de los animales figurados en el arte parietal paleolítico de la Península Ibérica, considerados tanto en su conjunto y comparados con el de Perigord y el Pirineos Francés, como en las diversas regiones de la misma Península, incluidos los sitios protugueses. Tanto la primera comparación como la consideración por separado de los animales representados en las diversas regiones peninsulares, muestra diferencias notables. Por fin se recuentan las figuras animales de todos los sitios del País Vasco, tanto peninsular como continental.
Determining mutations in G6PC and SLC37A4 genes in a sample of Brazilian patients with glycogen storage disease types Ia and Ib

Directory of Open Access Journals (Sweden)

Marcelo Paschoalete Carlin

2013-01-01

Full Text Available Glycogen storage disease (GSD comprises a group of autosomal recessive disorders characterized by deficiency of the enzymes that regulate the synthesis or degradation of glycogen. Types Ia and Ib are the most prevalent; while the former is caused by deficiency of glucose-6-phosphatase (G6Pase, the latter is associated with impaired glucose-6-phosphate transporter, where the catalytic unit of G6Pase is located. Over 85 mutations have been reported since the cloning of G6PC and SLC37A4 genes. In this study, twelve unrelated patients with clinical symptoms suggestive of GSDIa and Ib were investigated by using genetic sequencing of G6PC and SLC37A4 genes, being three confirmed as having GSD Ia, and two with GSD Ib. In seven of these patients no mutations were detected in any of the genes. Five changes were detected in G6PC, including three known point mutations (p.G68R, p.R83C and p.Q347X and two neutral mutations (c.432G > A and c.1176T > C. Four changes were found in SLC37A4: a known point mutation (p.G149E, a novel frameshift insertion (c.1338_1339insT, and two neutral mutations (c.1287G > A and c.1076-28C > T. The frequency of mutations in our population was similar to that observed in the literature, in which the mutation p.R83C is also the most frequent one. Analysis of both genes should be considered in the investigation of this condition. An alternative explanation to the negative results in this molecular study is the possibility of a misdiagnosis. Even with a careful evaluation based on laboratory and clinical findings, overlap with other types of GSD is possible, and further molecular studies should be indicated.
Type Families with Class, Type Classes with Family

DEFF Research Database (Denmark)

Serrano, Alejandro; Hage, Jurriaan; Bahr, Patrick

2015-01-01

Type classes and type families are key ingredients in Haskell programming. Type classes were introduced to deal with ad-hoc polymorphism, although with the introduction of functional dependencies, their use expanded to type-level programming. Type families also allow encoding type-level functions......, now as rewrite rules. This paper looks at the interplay of type classes and type families, and how to deal with shortcomings in both of them. Furthermore, we show how to use families to simulate classes at the type level. However, type families alone are not enough for simulating a central feature...... of type classes: elaboration, that is, generating code from the derivation of a rewriting. We look at ways to solve this problem in current Haskell, and propose an extension to allow elaboration during the rewriting phase....
La aristocracia ibérica ante la romanización. Ideología y espacios funerarios en Marroquíes Bajos (Jaén)

OpenAIRE

Serrano Peña, José Luis; Molinos Molinos, Manuel

2011-01-01

Presentamos el estudio de las necrópolis de un asentamiento periurbano de la ciudad romana de Aurgi (Jaén), en el que, a través del estudio formal e ideológico de los espacios funerarios, planteamos una situación concreta de perduración de las tradiciones ibéricas en el contexto de la romanización en el Alto Guadalquivir.
Feedback reliability calculation for an iterative block decision feedback equalizer

OpenAIRE

Huang, G; Nix, AR; Armour, SMD

2009-01-01

A new class of iterative block decision feedback equalizer (IB-DFE) was pioneered by Chan and Benvenuto. Unlike the conventional DFE, the IB-DFE is optimized according to the reliability of the feedback (FB) symbols. Since the use of the training sequence (TS) for feedback reliability (FBR) estimation lowers the bandwidth efficiency, FBR estimation without the need for additional TS is of considerable interest. However, prior FBR estimation is limited in the literature to uncoded M-ary phases...
La fauna exótica en la Península Ibérica : apuntes para el estudio del coleccionismo animal en el Medievo hispánico

Directory of Open Access Journals (Sweden)

Dolores Carmen Morales Muñiz

2000-01-01

Full Text Available Por sus especiales circunstancias, la península ibérica gozó de privilegiadas condiciones para proveerse de fauna exótica Este artículo examina el papel desempeñado por esa fauna en la España medieval especialmente su contribución al desarrollo de los zoológicos. Secundariamente se contempla la introducción de especies autóctonas en la península ibérica y los motivos de su permanencia y/o desaparición actual.Probably due to its strategic geographical position, the Iberían península has enjoyed a privileged condltion in terms of fluxes of exotic faunas througfiout history. This paper reviews the role played by exotic faunas in Medieval Spain, in particular with reference to the creation of zoos and zoological parks at large. In addition, a brief consideration is made about aspects related to the introductions of autochtonous species at various places of the iberían territory itself as well as extinction events of certain taxa or stocks.
Binary phase diagrams based on elements VIIIA and IB periods of the D.I. Mendeleev’s table and features of crystallographic parameters

Science.gov (United States)

Potekaev, A. I.; Klopotov, A. A.; Porobova, S. A.; Klopotov, V. D.; Markova, T. N.; Imanaliev, M. I.

2017-01-01

The data obtained as a result of the analysis of crystallogeometric parameters and the structure of state diagrams of binary systems from elements VIIIA and IB periods of the D.I. Mendeleev’s table are presented. It is shown that the classification of the evolution of phase diagrams of binary systems by types, proposed by T.A. Lebedev, correlates with features of concentration dependences of the deviation of atomic volumes in solid solutions from Zen law.
Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems.

Science.gov (United States)

Sherlock, Madeline E; Sudarsan, Narasimhan; Breaker, Ronald R

2018-05-21

Riboswitches are noncoding portions of certain mRNAs that bind metabolite, coenzyme, signaling molecule, or inorganic ion ligands and regulate gene expression. Most known riboswitches sense derivatives of RNA monomers. This bias in ligand chemical composition is consistent with the hypothesis that widespread riboswitch classes first emerged during the RNA World, which is proposed to have existed before proteins were present. Here we report the discovery and biochemical validation of a natural riboswitch class that selectively binds guanosine tetraphosphate (ppGpp), a widespread signaling molecule and bacterial "alarmone" derived from the ribonucleotide GTP. Riboswitches for ppGpp are predicted to regulate genes involved in branched-chain amino acid biosynthesis and transport, as well as other gene classes that previously had not been implicated to be part of its signaling network. This newfound riboswitch-alarmone partnership supports the hypothesis that prominent RNA World signaling pathways have been retained by modern cells to control key biological processes. Copyright © 2018 the Author(s). Published by PNAS.

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