181 research outputs found

    Data report: logging while drilling data analysis of Leg 171A, a multivariate statistical approach

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    In the northern Barbados accretionary wedge, several Deep Sea Drilling Project (DSDP) and Ocean Drilling Program (ODP) legs (DSDP Leg 78 and ODP Legs 110, 156, and 171A) targeted the décollement and the seaward extension of the décollement, the proto-décollement. During Leg 171A, the logging while drilling (LWD) technique was used to determine the physical properties variations along a profile across the deformation front. Because of the unstable borehole conditions in accretionary wedges, LWD is the most effective method for the measurements of physical properties in these poorly consolidated sediments. LWD data are acquired just above the drill bit a few minutes after the formation has been drilled, yielding measurements as close to in situ conditions as possible. The large amount of LWD data and the demand for a quick, objective, and reliable evaluation calls for the application of multivariate statistical methods. The multivariate factor analysis is a method of reducing the amount of logging data while giving them a new integrated meaning with no loss of important information, resulting in factor logs that are helpful tools for further interpretation. The cluster analysis of the two or three most significant factors proved to be a useful and objective method to identify and confirm significant logging units. The main objective of the application of multivariate statistical methods in this study is twofold. First, Leg 171A was a stand-alone logging leg, where no cores were retrieved. The factor analysis was used as an objective tool for a classification of the drilled sequences based on their physical and chemical properties. The new factor logs mirror the basic processes behind the measured geophysical properties and make them easier to interpret. Second, in the succeeding cluster analysis, similar geophysical properties are grouped into one cluster, reflecting one logging unit. These objectively defined logging units can be compared to statistical electrofacies, which are helpful in differentiating lithologic characterizations. In particular for LWD measurements, the multivariate statistical methods of factor and cluster analysis are helpful tools for a fast, reliable, and objective definition of logging units, which should be considered for future legs

    Disseminated cutaneous Herpes Simplex Virus-1 in a woman with rheumatoid arthritis receiving Infliximab: A case report

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    <p>Abstract</p> <p>Introduction</p> <p>We present the case of a 49-year-old woman with a seronegative rheumatoid arthritis who developed pustular psoriasis whilst on etanercept and subsequently developed disseminated herpes simplex on infliximab.</p> <p>Case presentation</p> <p>Our patient presented with an inflammatory arthritis which failed to respond to both methotrexate and leflunomide, and sulphasalazine treatment led to side effects. She was started on etanercept but after 8 months of treatment developed scaly pustular lesions on her palms and soles typical of pustular psoriasis. Following the discontinuation of etanercept, our patient required high doses of oral prednisolone to control her inflammatory arthritis. A second biologic agent, infliximab, was introduced in addition to low-dose methotrexate and 15 mg of oral prednisolone. However, after just 3 infusions of infliximab, she was admitted to hospital with a fever, widespread itchy vesicular rash and worsening inflammatory arthritis. Fluid from skin vesicles examined by polymerase chain reaction showed Herpes Simplex Virus type 1. Blood cultures were negative and her chest X-ray was normal. Her infliximab was discontinued and she was started on acyclovir, 800 mg five times daily for 2 weeks. She made a good recovery with improvement in her skin within 48 hours.</p> <p>She continued for 2 months on a prophylactic dose of 400 mg bd. Her rheumatoid arthritis became increasingly active and a decision was made to introduce adalimumab alongside acyclovir. Acyclovir prophylaxis has been continued but the dose tapered so that she is taking only 200 mg of acyclovir on alternate days. There has been no recurrence of Herpes Simplex Virus lesions despite increasing adalimumab to 40 mg weekly 3 months after starting treatment.</p> <p>Conclusion</p> <p>We believe this to be the first reported case of widespread cutaneous Herpes Simplex Virus type 1 infection following treatment with infliximab. We discuss the clinical manifestations of Herpes Simplex Virus infections with particular emphasis on the immunosuppressed patient and the use of prophylactic acyclovir. Pustular psoriasis is now a well recognised but uncommon side effect of antitumour necrosis factor therapy and can lead to cessation of therapy, as in our patient's case.</p

    Significance of northeast-trending features in Canada Basin, Arctic Ocean

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    © The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Geochemistry, Geophysics, Geosystems 18 (2017): 4156–4178, doi:10.1002/2017GC007099.Synthesis of seismic velocity, potential field, and geological data from Canada Basin and its surrounding continental margins suggests that a northeast-trending structural fabric has influenced the origin, evolution, and current tectonics of the basin. This structural fabric has a crustal origin, based on the persistence of these trends in upward continuation of total magnetic intensity data and vertical derivative analysis of free-air gravity data. Three subparallel northeast-trending features are described. Northwind Escarpment, bounding the east side of the Chukchi Borderland, extends ∼600 km and separates continental crust of Northwind Ridge from high-velocity transitional crust in Canada Basin. A second, shorter northeast-trending zone extends ∼300 km in northern Canada Basin and separates inferred continental crust of Sever Spur from magmatically intruded crust of the High Arctic Large Igneous Province. A third northeast-trending feature, here called the Alaska-Prince Patrick magnetic lineament (APPL) is inferred from magnetic data and its larger regional geologic setting. Analysis of these three features suggests strike slip or transtensional deformation played a role in the opening of Canada Basin. These features can be explained by initial Jurassic-Early Cretaceous strike slip deformation (phase 1) followed in the Early Cretaceous (∼134 to ∼124 Ma) by rotation of Arctic Alaska with seafloor spreading orthogonal to the fossil spreading axis preserved in the central Canada Basin (phase 2). In this model, the Chukchi Borderland is part of Arctic Alaska.Funding for this work was provided in part through the Geological Survey of Canada as part of Canada’s UNCLOS Project and through the U.S. Geological Survey as part of the U.S. Extended Continental Shelf project

    Distribution of crustal types in Canada Basin, Arctic Ocean

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    © The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Tectonophysics 691, Part A (2016): 8-30, doi:10.1016/j.tecto.2016.01.038.Seismic velocities determined from 70 sonobuoys widely distributed in Canada Basin were used to discriminate crustal types. Velocities of oceanic layer 3 (6.7 -7.1 km/s), transitional (7.2-7.6 km/s) and continental crust (5.5-6.6 km/s) were used to distinguish crustal types. Potential field data supports the distribution of oceanic crust as a polygon with maximum dimensions of ~340 km (east-west) by ~590 km (north-south) and identification of the ocean-continent boundary (OCB). Paired magnetic anomalies are associated only with crust that has oceanic velocities. Furthermore, the interpreted top of oceanic crust on seismic reflection profiles is more irregular and sometimes shallower than adjacent transitional crust. The northern segment of the narrow Canada Basin Gravity Low (CBGL), often interpreted as a spreading centre, bisects this zone of oceanic crust and coincides with the location of a prominent valley in seismic reflection profiles. Data coverage near the southern segment of CBGL is sparse. Velocities typical of transitional crust are determined east of it. Extension in this region, close to the inferred pole of rotation, may have been amagmatic. Offshore Alaska is a wide zone of thinned continental crust up to 300 km across. Published longer offset refraction experiments in the Basin confirm the depth to Moho and the lack of oceanic layer 3 velocities. Further north, towards Alpha Ridge and along Northwind Ridge, transitional crust is interpreted to be underplated or intruded by magmatism related to the emplacement of the High Arctic Large Igneous Province (HALIP). Although a rotational plate tectonic model is consistent with the extent of the conjugate magnetic anomalies that occupy only a portion of Canada Basin, it does not explain the asymmetrical configuration of the oceanic crust in the deep water portion of Canada Basin, and the unequal distribution of transitional and continental crust around the basin.Funding for this work was provided through the Geological Survey of Canada as part of the Canada’s Extended Continental Slope (ECS) Program. Funding for this work was also provided in part through the U.S. Geological Survey as part of the U.S. ECS Project.2018-02-0

    Globular-shaped variable lymphocyte receptors B antibody multimerized by a hydrophobic clustering in hagfish

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    In hagfish and lampreys, two representative jawless vertebrates, the humoral immunity is directly mediated by variable lymphocyte receptors B (VLRBs). Both monomeric VLRBs are structurally and functionally similar, but their C-terminal tails differ: lamprey VLRB has a Cys-rich tail that forms disulfide-linked pentamers of dimers, contributing to its multivalency, whereas hagfish VLRB has a superhydrophobic tail of unknown structure. Here, we reveal that VLRBs obtained from hagfish plasma have a globular-shaped multimerized form (approximately 0.6 to 1.7 MDa) that is generated by hydrophobic clustering instead of covalent linkage. Electron microscopy (EM) and single-particle analysis showed that the multimerized VLRBs form globular-shaped clusters with an average diameter of 28.7 ± 2.2 nm. The presence of VLRBs in the complex was confirmed by immune-EM analysis using an anti-VLRB antibody. Furthermore, the hydrophobic hagfish C-terminus (HC) was capable of triggering multimerization and directing the cellular surface localization via a glycophosphatidylinositol linkage. Our results strongly suggest that the hagfish VLRB forms a previously unknown globular-shaped antibody. This novel identification of a structurally unusual VLRB complex may suggest that the adaptive immune system of hagfish differs from that of lamprey

    Infected Cell Protein (ICP)47 Enhances Herpes Simplex Virus Neurovirulence by Blocking the CD8+ T Cell Response

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    The herpes simplex virus (HSV) infected cell protein (ICP)47 blocks CD8+ T cell recognition of infected cells by inhibiting the transporter associated with antigen presentation (TAP). In vivo, HSV-1 replicates in two distinct tissues: in epithelial mucosa or epidermis, where the virus enters sensory neurons; and in the peripheral and central nervous system, where acute and subsequently latent infections occur. Here, we show that an HSV-1 ICP47− mutant is less neurovirulent than wild-type HSV-1 in mice, but replicates normally in epithelial tissues. The reduced neurovirulence of the ICP47− mutant was due to a protective CD8+ T cell response. When compared with wild-type virus, the ICP47− mutant expressed reduced neurovirulence in immunologically normal mice, and T cell–deficient nude mice after reconstitution with CD8+ T cells. However, the ICP47− mutant exhibited normal neurovirulence in mice that were acutely depleted of CD8+ T cells, and in nude mice that were not reconstituted, or were reconstituted with CD4+ T cells. In contrast, CD8+ T cell depletion did not increase the neurovirulence of an unrelated, attenuated HSV-1 glycoprotein (g)E− mutant. ICP47 is the first viral protein shown to influence neurovirulence by inhibiting CD8+ T cell protection

    Framework for a Protein Ontology

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    Biomedical ontologies are emerging as critical tools in genomic and proteomic research, where complex data in disparate resources need to be integrated. A number of ontologies describe properties that can be attributed to proteins. For example, protein functions are described by the Gene Ontology (GO) and human diseases by SNOMED CT or ICD10. There is, however, a gap in the current set of ontologies – one that describes the protein entities themselves and their relationships. We have designed the PRotein Ontology (PRO) to facilitate protein annotation and to guide new experiments. The components of PRO extend from the classification of proteins on the basis of evolutionary relationships to the representation of the multiple protein forms of a gene (products generated by genetic variation, alternative splicing, proteolytic cleavage, and other post-translational modifications). PRO will allow the specification of relationships between PRO, GO and other ontologies in the OBO Foundry. Here we describe the initial development of PRO, illustrated using human and mouse proteins involved in the transforming growth factor-beta and bone morphogenetic protein signaling pathways

    A Novel Cre Recombinase Imaging System for Tracking Lymphotropic Virus Infection In Vivo

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    BACKGROUND:Detection, isolation, and identification of individual virus infected cells during long term infection are critical to advance our understanding of mechanisms of pathogenesis for latent/persistent viruses. However, current approaches to study these viruses in vivo have been hampered by low sensitivity and effects of cell-type on expression of viral encoded reporter genes. We have designed a novel Cre recombinase (Cre)-based murine system to overcome these problems, and thereby enable tracking and isolation of individual in vivo infected cells. METHODOLOGY/PRINCIPAL FINDINGS:Murine gammaherpesvirus 68 (MHV-68) was used as a prototypic persistent model virus. A Cre expressing recombinant virus was constructed and characterised. The virus is attenuated both in lytic virus replication, producing ten-fold lower lung virus titres than wild type virus, and in the establishment of latency. However, despite this limitation, when the sEGFP7 mouse line containing a Cre-activated enhanced green fluorescent protein (EGFP) was infected with the Cre expressing virus, sites of latent and persistent virus infection could be identified within B cells and macrophages of the lymphoid system on the basis of EGFP expression. Importantly, the use of the sEGFP7 mouse line which expresses high levels of EGFP allowed individual virus positive cells to be purified by FACSorting. Virus gene expression could be detected in these cells. Low numbers of EGFP positive cells could also be detected in the bone marrow. CONCLUSIONS/SIGNIFICANCE:The use of this novel Cre-based virus/mouse system allowed identification of individual latently infected cells in vivo and may be useful for the study and long-term monitoring of other latent/persistent virus infections

    An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates

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    Background. Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosphila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution. Principal findings. We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3. Conclusions. These data show that the vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways
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