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- Imanishi, T., et al.
(author)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Journal article (peer-reviewed)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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- Pirozhkov, A. S., et al.
(author)
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Diagnostic of laser contrast using target reflectivity
- 2009
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 94:24
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Journal article (peer-reviewed)abstract
- Using three different laser systems, we demonstrate a convenient and simple plasma based diagnostic of the contrast of high-power short-pulse lasers. The technique is based on measuring the specular reflectivity from a solid target. The reflectivity remains high even at relativistic intensities above 10(19) W/cm(2) in the case of a high-contrast prepulse-free laser. On the contrary, the specular reflectivity drops with increasing intensities in the case of systems with insufficient contrast due to beam breakup and increased absorption caused by preplasma.
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- Izumi, T., et al.
(author)
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ALMA OBSERVATIONS OF THE SUBMILLIMETER DENSE MOLECULAR GAS TRACERS IN THE LUMINOUS TYPE-1 ACTIVE NUCLEUS OF NGC 7469
- 2015
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 811:1, s. Article Number: 39-
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Journal article (peer-reviewed)abstract
- We present Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 1 observations of the central kiloparsec region of the luminous type. 1 Seyfert galaxy NGC 7469 with unprecedented high resolution (0.'' 5x0.'' 4 = 165 x 132 pc) at submillimeter wavelengths. Utilizing the wide. bandwidth of ALMA, we simultaneously obtained HCN(4-3), HCO+(4-3), CS(7-6), and partially CO(3-2) line maps, as well as the 860 mu m continuum. The region consists of the central similar to 1 '' component and the surrounding starburst ring with a radius of similar to 1.'' 5-2.'' 5. Several structures connect these components. Except for CO(3-2), these dense gas tracers are significantly concentrated toward the central similar to 1 '', suggesting their suitability to probe the nuclear regions of galaxies. Their spatial distribution resembles well those of centimeter and mid-infrared continuum emissions, but it is anticorrelated with the optical one, indicating the existence of dust-obscured star formation. The integrated intensity ratios of HCN(4-3)/HCO+(4-3) and HCN(4-3)/CS(7-6) are higher at the active galactic nucleus (AGN) position than at the starburst ring, which is consistent with our previous findings (submillimeter-HCN enhancement). However, the HCN(4-3)/HCO+(4-3) ratio at the AGN position of NGC 7469 (1.11 +/- 0.06) is almost half of the corresponding value of the low-luminosity type. 1 Seyfert galaxy NGC 1097 (2.0 +/- 0.2), despite the more than two orders of magnitude higher X-ray luminosity of NGC 7469. But the ratio is comparable to that of the close vicinity of the AGN of NGC 1068 (similar to 1.5). Based on these results, we speculate that some heating mechanisms other than X-ray (e.g., mechanical heating due to an AGN jet) can contribute significantly for shaping the chemical composition in NGC 1097.
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- Izumi, T., et al.
(author)
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SUBMILLIMETER-HCN DIAGRAM FOR ENERGY DIAGNOSTICS IN THE CENTERS OF GALAXIES
- 2016
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 818:1
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Journal article (peer-reviewed)abstract
- Compiling data from literature and the Atacama Large Millimeter/submillimeter Array archive, we show enhanced HCN(4-3)/HCO+(4-3) and/or HCN(4-3)/CS(7-6) integrated intensity ratios in circumnuclear molecular gas around active galactic nuclei (AGNs) compared to those in starburst (SB) galaxies (submillimeter HCN. enhancement). The number of sample galaxies is significantly increased from our previous work. We expect that this feature could potentially be an extinction-free energy diagnostic tool of nuclear regions of galaxies. Non-LTE radiative transfer modelings of the above molecular emission lines involving both collisional and radiative excitation, as well as a photon trapping effect, were conducted to investigate the cause of the high line ratios in AGNs. As a result, we found that enhanced abundance ratios of HCN to HCO+ and HCN to CS in AGNs as compared to SB galaxies by a factor of a few to even greater than or similar to 10 are a plausible explanation for the submillimeter HCN. enhancement. However, a counterargument of a systematically higher gas density in AGNs than in SB galaxies can also be a plausible scenario. Although we cannot fully distinguish. these two scenarios at this moment owing to an insufficient amount of multi-transition, multi-species data, the former scenario is indicative of abnormal chemical composition in AGNs. Regarding the actual mechanism to realize the composition, we suggest that it is difficult with conventional gas-phase X-ray-dominated region ionization models to reproduce the observed high line ratios. We might have to take into account other mechanisms such as neutral-neutral reactions that are efficiently activated in high-temperature environments and/or mechanically heated regions to further understand the high line ratios in AGNs.
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- Martin, S., et al.
(author)
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Multimolecule ALMA observations toward the Seyfert 1 galaxy NGC 1097
- 2015
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 573
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Journal article (peer-reviewed)abstract
- Context. The nearby Sy 1 galaxy NGC 1097 represents an ideal laboratory for exploring the molecular chemistry in the surroundings of an active galactic nucleus (AGN). Aims. Exploring the distribution of different molecular species allows us to understand the physical processes affecting the interstellar medium both in the AGN vicinity and in the outer star forming molecular ring. Methods. We carried out 3 mm ALMA observations that include seven different molecular species, namely HCN, HCO+, CCH, CS, HNCO, SiO, HC3N, and SO, as well as the C-13 isotopologues of the first two. Spectra were extracted from selected positions and all species were imaged over the central 2 kpc (similar to 30 '') of the galaxy at a resolution of similar to 2.2 '' x 1.5 '' (150 pc x 100 pc). Results. HCO+ and CS appear to be slightly enhanced in the star forming ring. CCH shows the largest variations across NGC 1097 and is suggested to be a good tracer of both obscured and early stage star formation. HNCO, SiO, and HC3N are significantly enhanced in the inner circumnuclear disk surrounding the AGN. Conclusions. Differences in the molecular abundances are observed between the star forming ring and the inner circumnuclear disk. We conclude that the HCN/HCO+ and HCN/CS differences observed between AGN-dominated and starburst (SB) galaxies are not due to a HCN enhancement due to X-rays, but rather this enhancement is produced by shocked material at distances of 200 pc from the AGN. Additionally, we claim that lower HCN/CS is a combination of a small underabundance of CS in AGNs, together with excitation effects, where a high density gas component (similar to 10(6) cm(-3)) may be more prominent in SB galaxies. However, the most promising are the differences found among the dense gas tracers that, at our modest spatial resolution, seem to outline the physical structure of the molecular disk around the AGN. In this picture, HNCO probes the well-shielded gas in the disk, surrounding the dense material moderately exposed to the X-ray radiation traced by HC3N. Finally SiO might be the innermost molecule in the disk structure.
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- Curran, S.J., et al.
(author)
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On the absence of molecular absorption in high-redshift millimetre-band searches
- 2011
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 416:3, s. 2143-2153
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Journal article (peer-reviewed)abstract
- We have undertaken a search for millimetre-waveband absorption (through the CO and HCO(+) rotational transitions) in the host galaxies of reddened radio sources (z = 0.405-1.802). Despite the colour selection (optical-near-infrared colours of V - K greater than or similar to 5 in all but one source), no absorption was found in any of the eight quasars for which the background continuum flux was detected. On the basis of the previous (mostly intervening) H(2) and OH detections, the limits reached here and in some previous surveys should be deep enough to detect molecular absorption according to their V - K colours. However, our survey makes the assumption that the reddening is associated with dust close to the emission redshift of the quasar and that the narrow millimetre component of this emission is intercepted by the compact molecular cores. By using the known millimetre absorbers to define the colour depth and comparing this with the ultraviolet luminosities of the sources, we find that, even if these assumptions are valid, only 12 of the 40 objects (mainly from this work) are potentially detectable. This is assuming an excitation temperature of T(x) = 10 K at z = 0, with the number decreasing with increasing temperatures (to zero detectable at T(x) greater than or similar to 100 K).
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- Lazorova, Lucia, et al.
(author)
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Structural Features Determining the Intestinal Epithelial Permeability and Efflux of Novel HIV-1 Protease Inhibitors
- 2011
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In: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 100:9, s. 3763-3772
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Journal article (peer-reviewed)abstract
- The primary aim of this study was to identify structural features that alter the intestinal epithelial permeability and efflux in a series of novel HIV-1 protease inhibitors (PIs). Eleven PIs were selected containing a tertiary alcohol in a transition-state mimicking scaffold, in which two substituents (R1 and R2) were varied systematically. Indinavir was selected as a reference compound. The apical-to-basolateral permeability was investigated in 2/4/A1 and Caco-2 monolayers. In addition, the basolateral-to-apical permeability was investigated in the Caco-2 monolayers and the efflux ratios were calculated. The absence of active drug transport processes in 2/4/A1 cells allowed identification and modeling of structural elements affecting the passive permeability. For instance, small aromatic R1 substituents and a small (bromo-) R2 substituent were associated with a high passive permeability. Efflux studies in Caco-2 cells indicated that amide-substituted neutral hydrophobic amino acids, such as valine and leucine, in the R1 position, reduced the apical-to-basolateral transport and enhanced the efflux. We conclude that our investigation revealed structural features that alter the intestinal epithelial permeability and efflux in the series of PIs and hope that these results can contribute to the synthesis of PIs with improved permeability and limited efflux properties.
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