| 1. |
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| 2. |
- Bonifacio, P., et al.
(author)
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First stars XII. Abundances in extremely metal-poor turnoff stars, and comparison with the giants
- 2009
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 501:2, s. 519-530
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Journal article (peer-reviewed)abstract
- Context. The detailed chemical abundances of extremely metal-poor (EMP) stars are key guides to understanding the early chemical evolution of the Galaxy. Most existing data, however, treat giant stars that may have experienced internal mixing later. Aims. We aim to compare the results for giants with new, accurate abundances for all observable elements in 18 EMP turno. stars. Methods. VLT/UVES spectra at R similar to 45 000 and S/N similar to 130 per pixel (lambda lambda 330-1000 nm) are analysed with OSMARCS model atmospheres and the TURBOSPECTRUM code to derive abundances for C, Mg, Si, Ca, Sc, Ti, Cr, Mn, Co, Ni, Zn, Sr, and Ba. Results. For Ca, Ni, Sr, and Ba, we find excellent consistency with our earlier sample of EMP giants, at all metallicities. However, our abundances of C, Sc, Ti, Cr, Mn and Co are similar to 0.2 dex larger than in giants of similar metallicity. Mg and Si abundances are similar to 0.2 dex lower (the giant [Mg/Fe] values are slightly revised), while Zn is again similar to 0.4 dex higher than in giants of similar [Fe/H] (6 stars only). Conclusions. For C, the dwarf/giant discrepancy could possibly have an astrophysical cause, but for the other elements it must arise from shortcomings in the analysis. Approximate computations of granulation (3D) effects yield smaller corrections for giants than for dwarfs, but suggest that this is an unlikely explanation, except perhaps for C, Cr, and Mn. NLTE computations for Na and Al provide consistent abundances between dwarfs and giants, unlike the LTE results, and would be highly desirable for the other discrepant elements as well. Meanwhile, we recommend using the giant abundances as reference data for Galactic chemical evolution models.
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| 3. |
- Richards, Stephen, et al.
(author)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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In: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Journal article (peer-reviewed)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 4. |
- Sivarani, T., et al.
(author)
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First stars X. The nature of three unevolved carbon-enhanced metal-poor stars
- 2006
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In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 459:1, s. 125-135
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Journal article (peer-reviewed)abstract
- Context. On the order of 20% of the very metal-poor stars in the Galaxy exhibit large carbon enhancements. It is important to establish which astrophysical sites and processes are responsible for the elemental abundance patterns of this early Galactic population. Aims. We seek to understand the nature of the progenitors of three main-sequence turnoff Carbon-Enhanced Metal-Poor (CEMP) stars, CS 31080-095, CS 22958-042, and CS 29528-041, based on a detailed abundance analysis. Methods. From high-resolution VLT/UVES spectra (R similar to 43 000), we determine abundances or upper limits for Li, C, N, O, and other important elements, as well as C-12/C-13 isotopic ratios. Results. All three stars have -3.30 <= [Fe/H]<= -2.85 and moderate to high CNO abundances. CS 22958-042 is one of the most carbon-rich CEMP stars known ([C/Fe] = +3.2), while CS 29528-041 (one of the few N-enhanced metal-poor stars known) is one of the most nitrogen rich ([N/Fe] = +3.0). Oxygen is very high in CS 31080-095 ([O/Fe] = +2.35) and in CS 22958-042 ([O/Fe] = +1.35). All three stars exhibit [Sr/Fe] < 0; Ba is not detected in CS 22958-042 ([Ba/Fe] < -0.53),but it is moderately enhanced ([Ba/Fe] similar to 1) in the other two stars. CS 22958-042 displays one of the largest sodium overabundances yet found in CEMP stars ([Na/Fe] = +2.8). CS 22958-042 has C-12/C-13 = 9, similar to most other CEMP stars without enhanced neutron-capture elements, while C-12/C-13 = 40 in CS 31080-095. CS 31080-095 and CS 29528-041 have A(Li) similar to 1.7, below the Spite Plateau, while Li is not detected in CS 22958-042. Conclusions. CS 22958-042 is a CEMP-no star, but the other two stars are in no known class of CEMP star and thus either constitute a new class or are a link between the CEMP-no and CEMP-s classes, adding complexity to the abundance patterns for CEMP stars. We interpret the abundance patterns in our stars to imply that current models for the presumed AGB binary progenitors lack an extra-mixing process, similar to those apparently operating in RGB stars.
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| 5. |
- Spite, M., et al.
(author)
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First stars IX - Mixing in extremely metal-poor giants. Variation of the C-12/C-13, [Na/Mg] and [Al/Mg] ratios
- 2006
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In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 455:1, s. 291-301
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Journal article (peer-reviewed)abstract
- Context. Extremely metal-poor (EMP) stars preserve a fossil record of the composition of the ISM when the Galaxy formed. It is crucial, however, to verify whether internal mixing has modified their surface composition, especially in the giants where most elements can be studied. Aims. We aim to understand the CNO abundance variations found in some, but not all EMP field giants analysed earlier. Mixing beyond the first dredge-up of standard models is required, and its origin needs clarification. Methods. The C-12/C-13 ratio is the most robust diagnostic of deep mixing, because it is insensitive to the adopted stellar parameters and should be uniformly high in near-primordial gas. We have measured C-12 and C-13 abundances in 35 EMP giants (including 22 with [Fe/H] < -3.0) from high-quality VLT/UVES spectra analysed with LTE model atmospheres. Correlations with other abundance data are used to study the depth of mixing. Results. The C-12/C-13 ratio is found to correlate with [C/Fe] (and Li/H), and clearly anti-correlate with [N/Fe], as expected if the surface abundances are modified by CNO processed material from the interior. Evidence for such deep mixing is observed in giants above log L/L-circle dot = 2.6, brighter than in less metal-poor stars, but matching the bump in the luminosity function in both cases. Three of the mixed stars are also Na- and Al-rich, another signature of deep mixing, but signatures of the ON cycle are not clearly seen in these stars. Conclusions. Extra mixing processes clearly occur in luminous RGB stars. They cannot be explained by standard convection, nor in a simple way by rotating models. The Na- and Al-rich giants could be AGB stars themselves, but an inhomogeneous early ISM or pollution from a binary companion remain possible alternatives.
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| 6. |
- Spite, M, et al.
(author)
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First stars VI - Abundances of C, N, O, Li, and mixing in extremely metal-poor giants. Galactic evolution of the light elements
- 2005
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In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 430:2, s. 655-668
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Journal article (peer-reviewed)abstract
- We have investigated the poorly-understood origin of nitrogen in the early Galaxy by determining N abundances from the NH band at 336 nm in 35 extremely metal-poor halo giants, with carbon and oxygen abundances from Cayrel et al. (2004, A&A, 416, 1117), using high-quality ESO VLT/UVES spectra (30 of our 35 stars are in the range -4.1 <[Fe/H] < -2.7 and 22 stars have [Fe/H] < -3.0). N abundances derived both from the NH band and from the CN band at 389 nm for 10 stars correlate well, but show a systematic difference of 0.4 dex, which we attribute to uncertainties in the physical parameters of the NH band (line positions, gf values, dissociation energy, etc.). Because any dredge-up of CNO processed material to the surface may complicate the interpretation of CNO abundances in giants, we have also measured the surface abundance of lithium in our stars as a diagnostic of such mixing. Our sample shows a clear dichotomy between two groups of stars. The first group shows evidence of C to N conversion through CN cycling and strong Li dilution, a signature of mixing; these stars are generally more evolved and located on the upper Red Giant Branch (RGB) or Horizontal Branch (HB). The second group has [N/Fe] < 0.5, shows no evidence for C to N conversion, and Li is only moderately diluted; these stars belong to the lower RGB and we conclude that their C and N abundances are very close to those of the gas from which they formed in the early Galaxy, they are called "unmixed stars". The [O/Fe] and [(C+N)/Fe] ratios are the same in the two groups, confirming that the differences between them are caused by dredge-up of CN-processed material in the first group, with negligible contributions from the O-N cycle. The "unmixed" stars reflect the abundances in the early Galaxy: the [C/Fe] ratio is constant (about + 0.2 dex) and the [C/Mg] ratio is close to solar at low metallicity, favouring a high C production by massive zero-metal supernovae. The [N/Fe] and [N/Mg] ratios scatter widely. Their mean values in each metallicity bin decrease with increasing metallicity, but this trend could be a statistical effect. The larger values of these ratios define a flat upper plateau ([N/Mg] = 0.0, [N/Fe] = + 0.1), which could reflect higher values within a wide range of yields of zero-metal SNe II. Alternatively, by analogy with the DLAs, the lower abundances ([N/Mg] = -1.1, [N/Fe] = -0.7) could reflect generally low yields from the first SNe II, the other stars being N enhanced by winds of massive Asymptotic Giant Branch (AGB) stars. Since all the stars show clear [alpha/Fe] enhancements, they were formed before any significant enrichment of the Galactic gas by SNe Ia, and their composition should reflect the yields of the first SNe II. However, if massive AGB stars or AGB supernovae evolved more rapidly than SNe Ia and contaminated the ISM, our stars would also reflect the yields of these AGB stars. At present it cannot be decided whether primary N is produced primarily in SNe II or in massive AGB stars, or in both. The stellar N abundances and [N/O] ratios are compatible with those found in Damped Lyman-alpha (DLA) systems. They extend the well-known DLA "plateau" at [N/O] approximate to -0.8 to lower metallicities, albeit with more scatter; no star is found below the putative "low [N/alpha] plateau" at [N/O] approximate to -1.55 in DLAs.
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| 7. |
- Ainsworth, Elizabeth A., et al.
(author)
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Next generation of elevated [CO2] experiments with crops: a critical investment for feeding the future world
- 2008
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In: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 31:9, s. 1317-1324
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Journal article (peer-reviewed)abstract
- A rising global population and demand for protein-rich diets are increasing pressure to maximize agricultural productivity. Rising atmospheric [CO2] is altering global temperature and precipitation patterns, which challenges agricultural productivity. While rising [CO2] provides a unique opportunity to increase the productivity of C-3 crops, average yield stimulation observed to date is well below potential gains. Thus, there is room for improving productivity. However, only a fraction of available germplasm of crops has been tested for CO2 responsiveness. Yield is a complex phenotypic trait determined by the interactions of a genotype with the environment. Selection of promising genotypes and characterization of response mechanisms will only be effective if crop improvement and systems biology approaches are closely linked to production environments, that is, on the farm within major growing regions. Free air CO2 enrichment (FACE) experiments can provide the platform upon which to conduct genetic screening and elucidate the inheritance and mechanisms that underlie genotypic differences in productivity under elevated [CO2]. We propose a new generation of large-scale, low-cost per unit area FACE experiments to identify the most CO2-responsive genotypes and provide starting lines for future breeding programmes. This is necessary if we are to realize the potential for yield gains in the future.
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| 8. |
- Francois, Olivier, et al.
(author)
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Demographic history of European populations of Arabidopsis thaliana
- 2008
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 4:5, s. e1000075-
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Journal article (peer-reviewed)abstract
- The model plant species Arabidopsis thaliana is successful at colonizing land that has recently undergone human-mediated disturbance. To investigate the prehistoric spread of A. thaliana, we applied approximate Bayesian computation and explicit spatial modeling to 76 European accessions sequenced at 876 nuclear loci. We find evidence that a major migration wave occurred from east to west, affecting most of the sampled individuals. The longitudinal gradient appears to result from the plant having spread in Europe from the east ~10,000 years ago, with a rate of westward spread of ~0.9 km/year. This wave-of-advance model is consistent with a natural colonization from an eastern glacial refugium that overwhelmed ancient western lineages. However, the speed and time frame of the model also suggest that the migration of A. thaliana into Europe may have accompanied the spread of agriculture during the Neolithic transition.
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| 9. |
- Giraud, Antoine, et al.
(author)
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Dissecting the genetic components of adaptation of Escherichia coli to the mouse gut
- 2008
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 4:1
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Journal article (peer-reviewed)abstract
- While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.
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| 10. |
- Hibbett, D. S., et al.
(author)
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A higher-level phylogenetic classification of the Fungi
- 2007
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In: Mycological Research. - : Elsevier BV. - 0953-7562 .- 1469-8102. ; 111, s. 509-547
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Journal article (peer-reviewed)abstract
- A comprehensive phylogenetic classification of the kingdom Fungi is proposed, with reference to recent molecular phylogenetic analyses, and with input from diverse members of the fungal taxonomic community. The classification includes 195 taxa, down to the level of order, of which 16 are described or validated here: Dikarya subkingdom nov.; Chytridiomycota, Neocallimastigomycota phyla nov.; Monoblepharidomycetes, Neocallimastigomycetes class. nov.; Eurotiomycetidae, Lecarioromycetidae, Mycocaliciomycetidae subclass. nov.; Acarosporales, Corticiales, Baeomycetales, Candelariales, Gloeophyllales, Melanosporales, Trechisporales, Umbilicariales ords. nov. The clade containing Ascomycota and Basidiomycota is classified as subkingdom Dikarya, reflecting the putative synapomorphy of dikaryotic hyphae. The most dramatic shifts in the classification relative to previous works concern the groups that have traditionally been included in the Chytridiomycota and Zygomycota. The Chytridiomycota is retained in a restricted sense, with Blastocladiomycota and Neocallimastigomycota representing segregate phyla of flagellated Fungi. Taxa traditionally placed in Zygomycota are distributed among Glomeromycota and several subphyla incertae sedis, including Mucoromycotina, Entomophthoromycotina, Kickxellomycotina, and Zoopagomycotiria. Microsporidia are included in the Fungi, but no further subdivision of the group is proposed. Several genera of 'basal' Fungi of uncertain position are not placed in any higher taxa, including Basidiobolus, Caulochytrium, Olpidium, and Rozella. (c) 2007 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
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| 11. |
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| 12. |
- Jeppsson, Jan-Olof, et al.
(author)
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Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: I. Analyte definition and proposal of a candidate reference method.
- 2007
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In: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; 45:4, s. 558-562
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Journal article (peer-reviewed)abstract
- An alcohol-associated change in the serum transferrin glycoform pattern, carbohydrate-deficient transferrin (CDT), is used as a biomarker of chronic moderate to heavy alcohol consumption. A current limitation in CDT analysis is the lack of standardization, which hampers clinical and analytical comparison between studies. This situation prompted initiation of a Working Group (WG) on CDT Standardization under the auspices of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The standardization work aims to define and validate the analyte, select a reference method, work out procedures for the production of reference materials, and make suggestions for the clinical usage of CDT. The first recommendation of the WG is that disialotransferrin should be the primary target molecule for CDT measurement and the single analyte on which CDT standardization is based. It is further recommended that HPLC should be the analytical principle considered as the basis of an interim reference method until a suitable mass spectrometric reference method is established. In clinical use, CDT should be expressed in a relative amount (% CDT), to compensate for variations in the total transferrin concentration.
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| 13. |
- Kervyn, Matthieu, et al.
(author)
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Voluminous lava flows at Oldoinyo Lengai in 2006 : chronology of events and insights into the shallow magmatic system
- 2008
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In: Bulletin of Volcanology. - : Springer Science and Business Media LLC. - 0258-8900 .- 1432-0819. ; 70:9, s. 1069-1086
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Journal article (peer-reviewed)abstract
- The largest natrocarbonatite lava flow eruption ever documented at Oldoinyo Lengai, NW Tanzania, occurred from March 25 to April 5, 2006, in two main phases. It was associated with hornito collapse, rapid extrusion of lava covering a third of the crater and emplacement of a 3-km long compound rubbly pahoehoe to blocky aa-like flow on the W flank. The eruption was followed by rapid enlargement of a pit crater. The erupted natrocarbonatite lava has high silica content (3% SiO2). The eruption chronology is reconstructed from eyewitness and news media reports and Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data, which provide the most reliable evidence to constrain the eruption’s onset and variations in activity. The eruption products were mapped in the field and the total erupted lava volume estimated at 9.2 +/- 3.0x10(5) m(3). The event chronology and field evidence are consistent with vent construct instability causing magma mixing and rapid extrusion from shallow reservoirs. It provides new insights into and highlights the evolution of the shallow magmatic system at this unique natrocarbonatite volcano.
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| 14. |
- Magnusson, Alf, 1958, et al.
(author)
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Characterization of diesel model fuel sprays impinging on a temperature controlled wall using rapid thermocouples and PDPA (Phase Doppler Particle Analyzer)
- 2008
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In: Ilass Europe 2008.
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Conference paper (other academic/artistic)abstract
- Spray-wall interaction has been found to influence therate of heat release and the formation of emissions in DI diesel engines. Experimental and numerical studies of sprays impinging on a wall have shown that the heat transfer and droplet size and velocity distributions vary when there is a change of such parameters as wall temperature, air temperature, injection pressure and distance to the wall. The objective of this work is to experimentally study how the surface temperature of a wall and different air temperatures affect the properties of an impinging spray of a two--component model fuel (IDEA) that consists of 70 % n-decane and 30 % 1-methylnaphthalene using rapid thermocouples and a phase doppler particle analyzer (PDPA). The experiments were carried out in the high-pressure, high-temperature (HP/HT) spray rig at Chalmers. Air temperatures were chosen to achieve both evaporating and non-evaporating conditions of the fuel. The air pressure was adjusted to give the same density for all cases. A standard common rail system controlled by a solenoid valve together with a single-hole nozzle was used for two different fuel injection pressures.
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| 15. |
- Moali, C, et al.
(author)
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Substrate-specific modulation of a multisubstrate proteinase - C-terminal processing of fibrillar procollagens is the only BMP-1-dependent activity to be enhanced by PCPE-1
- 2005
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In: Journal of Biological Chemistry. - 1083-351X. ; 280:25, s. 24188-24194
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Journal article (peer-reviewed)abstract
- Members of the bone morphogenetic protein-1/tolloid (BMP-1/Tld) family of metalloproteinases, also known as procollagen C-proteinases (PCPs), control multiple biological events ( including matrix assembly, cross-linking, cell adhesion/migration and pattern formation) through enzymatic processing of several extracellular substrates. PCP activities on fibrillar procollagens can be stimulated by another family of extracellular proteins, PCP enhancers (PCPE-1, PCPE-2), which lack intrinsic enzymatic activity. While PCPs have multiple substrates, the extent to which PCPEs is involved in the processing of proteins other than fibrillar procollagens is unknown. In the experiments reported here, PCPE-1 was found to have no effect on the in vitro BMP-1 processing of procollagen VII, the procollagen V N-propeptide, the laminin 5 gamma 2 chain, osteoglycin, prolysyl oxidase, or chordin. In contrast, PCPE-1 enhanced C-terminal processing of human fibrillar procollagen III but only when this substrate was in its native, disulfide-bonded conformation. Surprisingly, processing of procollagen III continued to be enhanced when essentially all the triple-helical region was removed. These and previous results (Ricard-Blum, S., Bernocco, S., Font, B., Moali, C., Eichenberger, D., Farjanel, J., Burchardt, E. R., van der Rest, M., Kessler, E., and Hulmes, D. J. S. ( 2002) J. Biol. Chem. 277, 33864 - 33869; Bernocco, S., Steiglitz, B. M., Svergun, D. I., Petoukhov, M. V., Ruggiero, F., Ricard- Blum, S., Ebel, C., Geourjon, C., Deleage, G., Font, B., Eichenberger, D., Greenspan, D. S., and Hulmes, D. J. S. ( 2003) J. Biol. Chem. 278, 7199 - 7205) indicate that the mechanism of PCPE-1 action involves recognition sites in both the C-propeptide domain and in the C-telopeptide region of the procollagen molecule. PCPEs therefore define a new class of extracellular adaptor proteins that stimulate proteinase activity in a substrate-specific manner, thereby providing a new target for the selective regulation of PCP activity on fibrillar procollagen substrates.
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| 16. |
- Smith, Peter B., et al.
(author)
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Demographic Effects on the Use of Vertical Sources of Guidance by Managers in Widely Differing Cultural Contexts
- 2005
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In: International Journal of Cross Cultural Management. - : Sage Publications. - 1470-5958 .- 1741-2838. ; 5:1, s. 5-26
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Journal article (peer-reviewed)abstract
- Data provided by 7380 middle managers from 60 nations are used to determine whether demographic variables are correlated with managers’ reliance on vertical sources of guidance in different nations and whether these correlations differ depending on national culture characteristics. Significant effects of Hofstede’s national culture scores, age, gender, organization ownership and department function are found. After these main effects have been discounted, significant although weak interactions are found, indicating that demographic effects are stronger in individualist, low power distance nations than elsewhere. Significant non-predicted interaction effects of uncertainty avoidance and masculinity-femininity are also obtained. The implications for theory and practice of the use of demographic attributes in understanding effective management procedures in various parts of the world are discussed.
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| 17. |
- Sorbe, Bengt, et al.
(author)
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Intravaginal brachytherapy in FIGO stage I low-risk endometrial cancer : a controlled randomized study
- 2009
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In: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 19:5, s. 873-878
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Journal article (peer-reviewed)abstract
- The purpose of the study was to compare postoperative vaginal irradiation with surgery alone in low-risk International Federation of Gynecology and Obstetrics (FIGO) stage IA-IB endometrial carcinoma. The study was a prospective, randomized trial of 645 evaluable low-risk endometrial carcinoma patients from 6 European gynecologic cancer centers. All tumors were in FIGO stage IA-IB, of endometrioid histological type, and FIGO grade 1-2. High-dose-rate afterloading equipments (iridium [Ir] 192 or cobalt [co] 60) were used at 5 centers, and low-dose-rate (LDR) afterloading equipment (cesium [Cs] 137) at 1 center. Perspex vaginal applicators or ovoids were normally used, and the dose was specified at 5 mm from the surface of the applicator. Three to 6 fractions (3.0-8.0 Gy) were given, and the overall treatment time was 4 to 15 days. A total of 319 patients were treated with surgery plus vaginal irradiation (treatment group), and 326 patients with surgery alone (control group).Twenty-six recurrences (4.0%) were recorded in the complete series. The locoregional recurrence rate was 2.6%, whereas distant metastases occurred in 1.4%. The rate of vaginal recurrences was 1.2% in the treatment group versus 3.1% in the control group. The difference was not statistically significant (P = 0.114). Side effects were few and mild (grade 1-2). Dysuria, frequency, and incontinence were slightly more common after vaginal irradiation (2.8% vs 0.6%, respectively). Late intestinal problems were few and similar in the 2 groups. The conclusions were that the impact of postoperative brachytherapy on even the locoregional recurrence rate seems to be limited in patients with low-risk endometrial carcinoma. The overall recurrence rate and survival were similar in the 2 groups.
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| 18. |
- van Meurs, Joyce B, et al.
(author)
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Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.
- 2008
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In: JAMA : the journal of the American Medical Association. - Chicago : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 299:11, s. 1277-90
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Journal article (peer-reviewed)abstract
- CONTEXT: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. OBJECTIVE: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. DESIGN AND SETTING: Prospective, multicenter, collaborative study of individual-level data on 37,534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. MAIN OUTCOME MEASURES: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. RESULTS: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25,052 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 x 10(-8)), as was the Val1330 allele (n = 24,812; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 x 10(-9)). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2 (P = 3.8 x 10(-5)) and 8 mg/cm2 (P = 5.0 x 10(-6)) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20,096 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31,435 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6 Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments. CONCLUSIONS: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10(-7)] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis.
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