312 research outputs found

    Paleomagnetism and astronomically induced cyclicity of the Armantes section; a Miocene continental red sequence in the Calatayud-Daroca basin (Central Sapin)

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    The Armantes section is a red-bed sequence consisting of a regular altemation (10 m scale) of reddish silts and pink/white limestones.In between these limestones, a smaller-scale bedding (2-3 m scale) is intercalated, characterised by varying carbonate content and related differences in erosion resistance. An earlier correlation of the magnetic polarity sequence of the Armantes section to the geomagnetic polarity time scale (GPTS) suggested a periodicity of 111 kyr for the large-scale cyclicity (Krijgsman et al., 1994b). The carbonate, gamma-ray and susceptibility records indicate that 4 to 5 small-scale cycles are developed in one large-scale cycle, showing that the small-scale cyclicity is related to precession and thus caused by climate forcing. We suggest that the precipitation of the carbonates is most likely related to rising ground-water levels and an increase of evaporation. This implies that the thick limestone beds would correlate to eccentricity maxima and the smaller-scale limestone beds to precession minima. Rock magnetic experiments show that the NRM in the Armantes section results from the presence of hematite and magnetite/maghemite.The relative contribution of hematite is strongly related to the lithology. Hematite is the dominant carrier in the limestones, while in the silts magnetite/maghemite prevail

    A unique protein profile of peripheral neutrophils from COPD patients does not reflect cytokine-induced protein profiles of neutrophils in vitro

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    Contains fulltext : 96603.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Inflammation, both local and systemic, is a hallmark of chronic obstructive pulmonary disease (COPD). Inflammatory mediators such as TNFalpha and GM-CSF are secreted by lung epithelium, alveolar macrophages and other inflammatory cells and are thought to be important contributors in the pathogenesis of COPD. Indeed, neutrophils are activated by these cytokines and these cells are one of the major inflammatory cell types recruited to the pulmonary compartment of COPD patients. Furthermore, these inflammatory mediators are found in the peripheral blood of COPD patients and, therefore, we hypothesized that TNFalpha/GM-CSF-induced protein profiles can be found in peripheral neutrophils of COPD patients. METHODS: Using fluorescence 2-dimensional difference gel electrophoresis we investigated differentially regulated proteins in peripheral neutrophils from COPD patients and healthy age-matched control subjects. Furthermore, protein profiles from COPD patients were compared with those of neutrophils of healthy age-matched controls that were stimulated with TNFalpha and/or GM-CSF in vitro. Protein gels were compared using DeCyder 7.0 software. RESULTS: We identified 7 significantly regulated protein spots between peripheral neutrophils from COPD patients and age-matched healthy control subjects. Stimulation of peripheral neutrophils with TNFalpha, GM-CSF or TNFalpha + GM-CSF in vitro resulted in 13, 20 and 22 regulated protein spots, respectively. However, these cytokine-induced protein differences did not correspond with the protein differences found in neutrophils from COPD patients. CONCLUSION: These results show that neutrophils from COPD patients have a unique protein profile compared to neutrophils from healthy age-matched controls. Furthermore, the neutrophil profiles of COPD patients do not reflect putative dominant signals induced by TNFalpha, GM-CSF or their combination. Our results indicate that systemic neutrophil responses in COPD patients are caused by a unique but subtle interplay between multiple inflammatory signals

    Post-Eocene coupled oroclines in the Talesh (NW Iran): paleomagnetic constraints

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    The Talesh Mountains (NW Iran) witnessed a long deformation history from the Triassic Cimmerian orogeny to the ongoing Arabia-Eurasia collision. This protracted multi-stage deformation has generated a remarkably curved orogen with a puzzling kinematic and deformational history. In this study, we investigate the origin of the Talesh curvature through paleomagnetic analyses on rocks of Paleozoic, Mesozoic and Cenozoic age. Our results indicate that at least two major, large-scale, vertical-axis-rotations took place since the Late Cretaceous: 1) a pre-Eocene 73° ± 17° clockwise rotation and 2) post-Eocene differential rotations that formed the Z-shaped mountain belt within a crustal-scale shear zone. The latter involved an increasing amount of clockwise (CW) rotation from south (16°) to north (48°). The orocline formation likely started during the Oligocene where an approximately east-west oriented mountain belt was buckled by the Arabia-Eurasia collision, with Arabia acting as a rigid indenter and the South Caspian basin as a rigid backstop. We hypothesise that the NE-SW oriented Aras and Lahijan fault zones, inherited from transform faults related to the Mesozoic opening of the Caspian-Black Sea back-arc, accommodated the coupled orocline formation

    Analysis of paleomagnetic data: a tribute to Hans Zijderveld. Introduction

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43920/1/11288_2004_Article_147505.pd

    Dissecting distinct proteolytic activities of FMDV Lpro implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression

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    Author summary Outbreaks of the picornavirus foot-and-mouth disease virus (FMDV) have significant consequences for animal health and product safety and place a major economic burden on the global livestock industry. Understanding how this notorious animal pathogen suppresses the antiviral type I interferon (IFN-alpha/beta) response may help to develop countermeasures to control FMDV infections. FMDV suppresses the IFN-alpha/beta response through the activity of its Leader protein (L-pro), a protease that can cleave host cell proteins. L(pro)was also shown to have deubiquitinase and deISGylase activity, raising the possibility that L(pro)suppresses IFN-alpha/beta by removing ubiquitin and/or ISG15, two posttranslational modifications that can regulate the activation, interactions and localization of (signaling) proteins. Here, we show that TBK1 and MAVS, two signaling proteins that are important for activation of IFN-alpha/beta gene transcription, are cleaved by L-pro. By generating L(pro)mutants lacking either of these two activities, we demonstrate that L-pro's ability to cleave signaling proteins, but not its deubiquitination/deISGylase activity, correlates with suppression of IFN-beta gene transcription. The type I interferon response is an important innate antiviral pathway. Recognition of viral RNA by RIG-I-like receptors (RLRs) activates a signaling cascade that leads to type I interferon (IFN-alpha/beta) gene transcription. Multiple proteins in this signaling pathway (e.g. RIG-I, MDA5, MAVS, TBK1, IRF3) are regulated by (de)ubiquitination events. Most viruses have evolved mechanisms to counter this antiviral response. The leader protease (L-pro) of foot-and-mouth-disease virus (FMDV) has been recognized to reduce IFN-alpha/beta gene transcription; however, the exact mechanism is unknown. The proteolytic activity of L(pro)is vital for releasing itself from the viral polyprotein and for cleaving and degrading specific host cell proteins, such as eIF4G and NF-kappa B. In addition, L(pro)has been demonstrated to have deubiquitination/deISGylation activity. L-pro's deubiquitination/deISGylation activity and the cleavage/degradation of signaling proteins have both been postulated to be important for reduced IFN-alpha/beta gene transcription. Here, we demonstrate that TBK1, the kinase that phosphorylates and activates the transcription factor IRF3, is cleaved by L(pro)in FMDV-infected cells as well as in cells infected with a recombinant EMCV expressing L-pro.In vitrocleavage experiments revealed that L(pro)cleaves TBK1 at residues 692-694. We also observed cleavage of MAVS in HeLa cells infected with EMCV-L-pro, but only observed decreasing levels of MAVS in FMDV-infected porcine LFPK alpha V beta 6 cells. We set out to dissect L-pro's ability to cleave RLR signaling proteins from its deubiquitination/deISGylation activity, to determine their relative contributions to the reduction of IFN-alpha/beta gene transcription. The introduction of specific mutations, of which several were based on the recently published structure of L(pro)in complex with ISG15, allowed us to identify specific amino acid substitutions that separate the different proteolytic activities of L-pro. Characterization of the effects of these mutations revealed that L-pro's ability to cleave RLR signaling proteins but not its deubiquitination/deISGylation activity correlates with the reduced IFN-beta gene transcription

    Dielectric material options for integrated capacitors

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    Future MIM capacitor generations will require significantly increased specific capacitances by utilization of high-k dielectric materials. In order to achieve high capacitance per chip area, these dielectrics have to be deposited in three-dimensional capacitor structures by ALD or AVD (atomic vapor deposition) process techniques. In this study eight dielectric materials, which can be deposited by these techniques and exhibit the potential to reach k-values of over 50 were identified, prepared and characterized as single films and stacked film systems. To primarily focus on a material comparison, preliminary processes were used for film deposition on planar test devices. Measuring leakage current density versus the dielectric constant k shows that at low voltages (=1 V) dielectrics with k-values up to 100 satisfy the typical leakage current density specification o
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