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Sökning: WFRF:(Harper J)

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531.
  • Nehme, Ralda, et al. (författare)
  • The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia
  • 2022
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • It is unclear how the 22q11.2 deletion predisposes to psychiatric disease. To study this, we generated induced pluripotent stem cells from deletion carriers and controls and utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Here, we show that upon differentiation into neural progenitor cells, the deletion acted in trans to alter the abundance of transcripts associated with risk for neurodevelopmental disorders including autism. In excitatory neurons, altered transcripts encoded presynaptic factors and were associated with genetic risk for schizophrenia, including common and rare variants. To understand how the deletion contributed to these changes, we defined the minimal protein-protein interaction network that best explains gene expression alterations. We found that many genes in 22q11.2 interact in presynaptic, proteasome, and JUN/FOS transcriptional pathways. Our findings suggest that the 22q11.2 deletion impacts genes that may converge with psychiatric risk loci to influence disease manifestation in each deletion carrier.
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532.
  • O Gorman, Eamon, 1984, et al. (författare)
  • ALMA and VLA reveal the lukewarm chromospheres of the nearby red supergiants Antares and Betelgeuse
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 638
  • Tidskriftsartikel (refereegranskat)abstract
    • We first present spatially resolved ALMA and VLA continuum observations of the early-M red supergiant Antares to search for the presence of a chromosphere at radio wavelengths. We resolve the free-free emission of the Antares atmosphere at 11 unique wavelengths between 0.7 mm (ALMA band 8) and 10 cm (VLA S band). The projected angular diameter is found to continually increase with increasing wavelength, from a low of 50.7 mas at 0.7 mm up to a diameter of 431 mas at 10 cm, which corresponds to 1.35 and 11.6 times the photospheric angular diameter, respectively. All four ALMA measurements show that the shape of the atmosphere is elongated, with a flattening of 15% at a similar position angle. The disk-averaged gas temperature of the atmosphere initially rises from a value of 2700 K at 1.35 R∗ (i.e., 0.35 R∗ above the photosphere) to a peak value of 3800 K at ∼2.5 R∗, after which it then more gradually decreases to 1650 K at 11.6 R∗. The rise in gas temperature between 1.35 R∗ and ∼2.5 R∗ is evidence for a chromospheric temperature rise above the photosphere of a red supergiant. We detect a clear change in the spectral index across the sampled wavelength range, with the flux density Sν ν1.42 between 0.7 mm and 1.4 cm, which we associate with chromosphere-dominated emission, while the flux density Sν ν0.8 between 4.3 cm and 10 cm, which we associate with wind-dominated emission. We show that the Antares MOLsphere is transparent at our observed wavelengths, and the lukewarm chromosphere that we detect is therefore real and not just an average of the cool MOLsphere and hot ultraviolet emitting gas. We then perform nonlocal thermal equilibrium modeling of the far-ultraviolet radiation field of another early-M red supergiant, Betelgeuse, and find that an additional hot (i.e., > 7000 K) chromospheric photoionization component with a much smaller filling factor must also exist throughout the chromospheres of these stars.
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533.
  • Oji, Vinzenz, et al. (författare)
  • Revised nomenclature and classification of inherited ichthyoses : Results of the First Ichthyosis Consensus Conference in Sorèze 2009
  • 2010
  • Ingår i: The Journal of American Academy of Dermatology. - : Elsevier BV. - 0190-9622 .- 1097-6787. ; 63:4, s. 607-641
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Inherited ichthyoses belong to a large, clinically and etiologically heterogeneous group of mendelian disorders of cornification, typically involving the entire integument. Over the recent years, much progress has been made defining their molecular causes. However, there is no internationally accepted classification and terminology. OBJECTIVE: We sought to establish a consensus for the nomenclature and classification of inherited ichthyoses. METHODS: The classification project started at the First World Conference on Ichthyosis in 2007. A large international network of expert clinicians, skin pathologists, and geneticists entertained an interactive dialogue over 2 years, eventually leading to the First Ichthyosis Consensus Conference held in Sorèze, France, on January 23 and 24, 2009, where subcommittees on different issues proposed terminology that was debated until consensus was reached. RESULTS: It was agreed that currently the nosology should remain clinically based. "Syndromic" versus "nonsyndromic" forms provide a useful major subdivision. Several clinical terms and controversial disease names have been redefined: eg, the group caused by keratin mutations is referred to by the umbrella term, "keratinopathic ichthyosis"-under which are included epidermolytic ichthyosis, superficial epidermolytic ichthyosis, and ichthyosis Curth-Macklin. "Autosomal recessive congenital ichthyosis" is proposed as an umbrella term for the harlequin ichthyosis, lamellar ichthyosis, and the congenital ichthyosiform erythroderma group. LIMITATIONS: As more becomes known about these diseases in the future, modifications will be needed. CONCLUSION: We have achieved an international consensus for the classification of inherited ichthyosis that should be useful for all clinicians and can serve as reference point for future research.
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534.
  • Pavey, S, et al. (författare)
  • Microarray expression profiling in melanoma reveals a BRAF mutation signature
  • 2004
  • Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 23:23, s. 4060-4067
  • Tidskriftsartikel (refereegranskat)abstract
    • We have used microarray gene expression pro. ling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase ( MAPK) activation ( either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.
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535.
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536.
  • Rohlmann, Patrick, et al. (författare)
  • Tribochemistry of imidazolium and phosphonium bis(oxalato)borate ionic liquids: Understanding the differences
  • 2023
  • Ingår i: Tribology International. - : Elsevier Ltd. - 0301-679X .- 1879-2464. ; 181
  • Tidskriftsartikel (refereegranskat)abstract
    • Lubrication properties of imidazolium and phosphonium bis(oxalato)borate ionic liquids (ILs) are compared in a reciprocating sliding contact at 80 °C and 140 °C. Both the influence of the alkyl chain length and the cation architecture on friction, wear and lubricant breakdown are investigated. Imidazolium ILs showed lower friction than phosphonium ILs though only phosphonium-based ILs reduced wear. A longer alkyl chain reduced friction only in the case of the imidazolium-based ILs. Analysis of the wear scars was consistent with chemical breakdown solely of the anion. Chemical changes in the ILs after the tribotests were more pronounced for imidazolium-based ILs, and comparison of breakdown and tribofilm formation implicated catalysis by the imidazolium center, which, in turn, had a strong dependence on the surface self-assembly.
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537.
  • Ryde, Nils, et al. (författare)
  • Systematic trend of water vapour absorption in red giant atmospheres revealed by high resolution TEXES 12 mu m spectra
  • 2015
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 573
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The structures of the outer atmospheres of red giants are very complex. Recent interpretations of a range of different observations have led to contradictory views of these regions. It is clear, however, that classical model photospheres are inadequate to describe the nature of the outer atmospheres. The notion of large optically thick molecular spheres around the stars (MOLspheres) has been invoked in order to explain spectro-interferometric observations and low-and high-resolution spectra. On the other hand high-resolution spectra in the mid-IR do not easily fit into this picture because they rule out any large sphere of water vapour in LTE surrounding red giants. Aims. In order to approach a unified scenario for these outer regions of red giants, more empirical evidence from different diagnostics are needed. Our aim here is to investigate high-resolution, mid-IR spectra for a range of red giants, spanning spectral types from early K to mid M. We want to study how the pure rotational lines of water vapour change with effective temperature, and whether we can find common properties that can put new constraints on the modelling of these regions, so that we can gain new insights. Methods. We have recorded mid-IR spectra at 12.2-12.4 mu m at high spectral resolution of ten well-studied bright red giants, with TEXES mounted on the IRTF on Mauna Kea. These stars span effective temperatures from 3450 K to 4850 K. Results. We find that all red giants in our study cooler than 4300 K, spanning a wide range of effective temperatures (down to 3450 K), show water absorption lines stronger than expected and none are detected in emission, in line with what has been previously observed for a few stars. The strengths of the lines vary smoothly with spectral type. We identify several spectral features in the wavelength region that are undoubtedly formed in the photosphere. From a study of water-line ratios of the stars, we find that the excitation temperatures, in the line-forming regions, are several hundred Kelvin lower than expected from a classical photospheric model. Conclusions. All stars in our sample show several photospheric features in their 12 mu m spectra, which can be modelled with a classical model photosphere. However, in all stars showing water-vapour lines (stars cooler than similar to 4300 K), the water lines are found to be much deeper than expected. The line ratios of these pure-rotational lines reveal low excitation temperatures. This could either be due to lower temperatures than expected in the outer regions of the photospheres caused by for example extra cooling, or due to non-LTE level populations, affecting the source function and line opacities, but this needs further investigation. We have demonstrated that these diagnostically interesting water lines are a general feature of red giants across spectral types, and we argue for a general explanation of their formation rather than explanations requiring specific properties, such as dust. Since the water lines are neither weak (filled in by emission) nor do they appear in emission, as predicted by LTE MOLsphere models in their simplest forms, the evidence of the existence of such large optically-thick, molecular spheres enshrouding the stars is weakened. It is still a challenge to find a unifying picture of the outer regions of the atmospheres of red giants, but we have presented new empirical evidence that needs to be taken into account and explained in any model of these regions.
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538.
  • Ryde, Nils, et al. (författare)
  • Water Vapor on Supergiants : The 12 μm TEXES Spectra of μ Cephei
  • 2006
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 645:1, s. 652-658
  • Tidskriftsartikel (refereegranskat)abstract
    • Several recent papers have argued for warm, semidetached, molecular layers surrounding red giant and supergiant stars, a concept known as a MOLsphere. Spectroscopic and interferometric analyses have often corroborated this general picture. Here we present high-resolution spectroscopic data of pure rotational lines of water vapor at 12 mu m for the supergiant mu Cep. This star has often been used to test the concept of molecular layers around supergiants. Given the prediction of an isothermal, optically thick water vapor layer in local thermodynamic equilibrium around the star ( MOLsphere), we expected the 12 mu m lines to be in emission or at least in absorption but filled in by emission from the molecular layer around the star. Our data, however, show the contrary; we find definite absorption. Thus, our data do not easily fit into the suggested isothermal MOLsphere scenario. The 12 mu m lines, therefore, put new, strong constraints on the MOLsphere concept and on the nature of water seen in signatures across the spectra of early M supergiants. We also find that the absorption is even stronger than that calculated from a standard, spherically symmetric model photosphere without any surrounding layers. A cool model photosphere, representing cool outer layers, is, however, able to reproduce the lines, but this model does not account for water vapor emission at 6 mu m. Thus, a unified model for water vapor on mu Cep appears to be lacking. It does seem necessary to model the underlying photospheres of these supergiants in their whole complexity. The strong water vapor lines clearly reveal inadequacies of classical model atmospheres.
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