332 research outputs found
Study of sea ice in the Sea of Okhotsk and its influence on the Oyashio current
The author has identified the following significant results. Two photographic techniques were applied to Skylab S190A multispectral pictures for extracting oceanic patterns at the sea surface separately from cloud patterns. One is the image-masking technique and another a stereographic analysis. The extracted oceanic patterns were interpreted as areas where the amount, or the concentration of phytoplankton was high by utilizing surface data of water temperature, ocean current by GEK, and microplankton
PERFORMANCE AND FLOW CHARACTERISTICS OF NOZZLES FOR INITIALLY SUBCOOLED HOT WATER (INFLUENCE OF TURBULENCE AND DECOMPRESSION RATE)
The purpose of this study was to improve the performance characteristics of a convergent-divergent nozzle for flashing expansion of initially subcooled hot water. The slip between the vapor and liquid along the divergent passage and the maximum nonequilibrium pressure drop at the nozzle throat(this is related to the thermal nonequilibrium) cause a decline in the nozzle efficiency. To decrease the maximum pressure drop,a nozzle with thin wires just upstream of the throat and a nozzle with a smaller convergent angle were manufactured and tested. Initially subcooled hot water at an inlet pressure of 0.47MPa and inlet temperatures of 409.9 to 421.8K (inlet subcoolings of 0.9-12.9K) were used with the nozzle back pressures ranging from 5 to 101.3kPa. The following results were attained:(1)the maximum nonequilibrium pressure drop at the throat decreased and the thrust coefficient increased by 10οΌ
; (2)the thrust coefficient was found to be independent of the inlet subcooling and exit stream-expansion ratio; (3)a correlation between the ratio of the exit pressure to the inlet pressure and the appropriate exit stream-expansion ratio was obtained empirically;and (4)the critical flow rate was found to be lower than that for an ordinary convergent-divergent nozzle
Elastin is Localised to the Interfascicular Matrix of Energy Storing Tendons and Becomes Increasingly Disorganised With Ageing
Tendon is composed of fascicles bound together by the interfascicular matrix (IFM). Energy storing tendons are more elastic and extensible than positional tendons; behaviour provided by specialisation of the IFM to enable repeated interfascicular sliding and recoil. With ageing, the IFM becomes stiffer and less fatigue resistant, potentially explaining why older tendons become more injury-prone. Recent data indicates enrichment of elastin within the IFM, but this has yet to be quantified. We hypothesised that elastin is more prevalent in energy storing than positional tendons, and is mainly localised to the IFM. Further, we hypothesised that elastin becomes disorganised and fragmented, and decreases in amount with ageing, especially in energy storing tendons. Biochemical analyses and immunohistochemical techniques were used to determine elastin content and organisation, in young and old equine energy storing and positional tendons. Supporting the hypothesis, elastin localises to the IFM of energy storing tendons, reducing in quantity and becoming more disorganised with ageing. These changes may contribute to the increased injury risk in aged energy storing tendons. Full understanding of the processes leading to loss of elastin and its disorganisation with ageing may aid in the development of treatments to prevent age related tendinopathy
Highly Pathogenic Avian Influenza Virus H5N1 Infects Alveolar Macrophages without Virus Production or Excessive TNF-Alpha Induction
Highly pathogenic avian influenza virus (HPAIV) of the subtype H5N1 causes severe, often fatal pneumonia in humans. The pathogenesis of HPAIV H5N1 infection is not completely understood, although the alveolar macrophage (AM) is thought to play an important role. HPAIV H5N1 infection of macrophages cultured from monocytes leads to high percentages of infection accompanied by virus production and an excessive pro-inflammatory immune response. However, macrophages cultured from monocytes are different from AM, both in phenotype and in response to seasonal influenza virus infection. Consequently, it remains unclear whether the results of studies with macrophages cultured from monocytes are valid for AM. Therefore we infected AM and for comparison macrophages cultured from monocytes with seasonal H3N2 virus, HPAIV H5N1 or pandemic H1N1 virus, and determined the percentage of cells infected, virus production and induction of TNF-alpha, a pro-inflammatory cytokine. In vitro HPAIV H5N1 infection of AM compared to that of macrophages cultured from monocytes resulted in a lower percentage of infected cells (up to 25% vs up to 84%), lower virus production and lower TNF-alpha induction. In vitro infection of AM with H3N2 or H1N1 virus resulted in even lower percentages of infected cells (up to 7%) than with HPAIV H5N1, while virus production and TNF-alpha induction were comparable. In conclusion, this study reveals that macrophages cultured from monocytes are not a good model to study the interaction between AM and these influenza virus strains. Furthermore, the interaction between HPAIV H5N1 and AM could contribute to the pathogenicity of this virus in humans, due to the relative high percentage of infected cells rather than virus production or an excessive TNF-alpha induction
OSIRISv1.2: A named entity recognition system for sequence variants of genes in biomedical literature
<p>Abstract</p> <p>Background</p> <p>Single Nucleotide Polymorphisms, among other type of sequence variants, constitute key elements in genetic epidemiology and pharmacogenomics. While sequence data about genetic variation is found at databases such as dbSNP, clues about the functional and phenotypic consequences of the variations are generally found in biomedical literature. The identification of the relevant documents and the extraction of the information from them are hampered by the large size of literature databases and the lack of widely accepted standard notation for biomedical entities. Thus, automatic systems for the identification of citations of allelic variants of genes in biomedical texts are required.</p> <p>Results</p> <p>Our group has previously reported the development of OSIRIS, a system aimed at the retrieval of literature about allelic variants of genes <url>http://ibi.imim.es/osirisform.html</url>. Here we describe the development of a new version of OSIRIS (OSIRISv1.2, <url>http://ibi.imim.es/OSIRISv1.2.html</url>) which incorporates a new entity recognition module and is built on top of a local mirror of the MEDLINE collection and HgenetInfoDB: a database that collects data on human gene sequence variations. The new entity recognition module is based on a pattern-based search algorithm for the identification of variation terms in the texts and their mapping to dbSNP identifiers. The performance of OSIRISv1.2 was evaluated on a manually annotated corpus, resulting in 99% precision, 82% recall, and an F-score of 0.89. As an example, the application of the system for collecting literature citations for the allelic variants of genes related to the diseases intracranial aneurysm and breast cancer is presented.</p> <p>Conclusion</p> <p>OSIRISv1.2 can be used to link literature references to dbSNP database entries with high accuracy, and therefore is suitable for collecting current knowledge on gene sequence variations and supporting the functional annotation of variation databases. The application of OSIRISv1.2 in combination with controlled vocabularies like MeSH provides a way to identify associations of biomedical interest, such as those that relate SNPs with diseases.</p
Tumour-derived CSF2/granulocyte macrophage colony stimulating factor controls myeloid cell accumulation and progression of gliomas
BACKGROUND: Malignant tumours release factors, which attract myeloid cells and induce their polarisation to pro-invasive, immunosuppressive phenotypes. Brain-resident microglia and peripheral macrophages accumulate in the tumour microenvironment of glioblastoma (GBM) and induce immunosuppression fostering tumour progression. Macrophage colony stimulating factors (CSFs) control the recruitment of myeloid cells during peripheral cancer progression, but it is disputable, which CSFs drive their accumulation in gliomas. METHODS: The expression of CSF2 (encoding granulocyte-macrophage colony stimulating factor) was determined in TCGA datasets and five human glioma cell lines. Effects of stable CSF2 knockdown in glioma cells or neutralising CSF2 or receptor CSF2RΞ± antibodies on glioma invasion were tested in vitro and in vivo. RESULTS: CSF2 knockdown or blockade of its signalling reduced microglia-dependent glioma invasion in microglia-glioma co-cultures. CSF2-deficient human glioma cells encapsulated in cell-impermeable hollow fibres and transplanted to mouse brains, failed to attract microglia, but stimulated astrocyte recruitment. CSF2-depleted gliomas were smaller, attracted less microglia and macrophages, and provided survival benefit in tumour-bearing mice. Apoptotic microglia/macrophages were detected in CSF2-depleted tumours. CONCLUSIONS: CSF2 is overexpressed in a subset of mesenchymal GBMs in association with high immune gene expression. Tumour-derived CSF2 attracts, supports survival and induces pro-tumorigenic polarisation of microglia and macrophages
Adherent Human Alveolar Macrophages Exhibit a Transient Pro-Inflammatory Profile That Confounds Responses to Innate Immune Stimulation
Alveolar macrophages (AM) are thought to have a key role in the immunopathogenesis of respiratory diseases. We sought to test the hypothesis that human AM exhibit an anti-inflammatory bias by making genome-wide comparisons with monocyte derived macrophages (MDM). Adherent AM obtained by bronchoalveolar lavage of patients under investigation for haemoptysis, but found to have no respiratory pathology, were compared to MDM from healthy volunteers by whole genome transcriptional profiling before and after innate immune stimulation. We found that freshly isolated AM exhibited a marked pro-inflammatory transcriptional signature. High levels of basal pro-inflammatory gene expression gave the impression of attenuated responses to lipopolysaccharide (LPS) and the RNA analogue, poly IC, but in rested cells pro-inflammatory gene expression declined and transcriptional responsiveness to these stimuli was restored. In comparison to MDM, both freshly isolated and rested AM showed upregulation of MHC class II molecules. In most experimental paradigms ex vivo adherent AM are used immediately after isolation. Therefore, the confounding effects of their pro-inflammatory profile at baseline need careful consideration. Moreover, despite the prevailing view that AM have an anti-inflammatory bias, our data clearly show that they can adopt a striking pro-inflammatory phenotype, and may have greater capacity for presentation of exogenous antigens than MDM
Elastogenic Protein Expression of a Highly Elastic Murine Spinal Ligament: The Ligamentum Flavum
Spinal ligaments, such as the ligamentum flavum (LF), are prone to degeneration and iatrogenic injury that can lead to back pain and nerve dysfunction. Repair and regeneration strategies for these tissues are lacking, perhaps due to limited understanding of spinal ligament formation, the elaboration of its elastic fibers, maturation and homeostasis. Using immunohistochemistry and histology, we investigated murine LF elastogenesis and tissue formation from embryonic to mature postnatal stages. We characterized the spatiotemporal distribution of the key elastogenic proteins tropoelastin, fibrillin-1, fibulin-4 and lysyl oxidase. We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth. Elastic fibers were first detected histologically at postnatal day (P) 7, the earliest stage at which tropoelastin and fibulin-4 stained intensely. From P7 to P28, elastic fibers grew in diameter and became straighter along the axis. The growth of elastic fibers coincided with intense staining of tropoelastin and fibulin-4 staining, possibly supporting a chaperone role for fibulin-4. These expression patterns correlated with reported skeletal and behavioral changes during murine development. This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues
HIV-1 Nef Targets MHC-I and CD4 for Degradation Via a Final Common Ξ²-COPβDependent Pathway in T Cells
To facilitate viral infection and spread, HIV-1 Nef disrupts the surface
expression of the viral receptor (CD4) and molecules capable of presenting HIV
antigens to the immune system (MHC-I). To accomplish this, Nef binds to the
cytoplasmic tails of both molecules and then, by mechanisms that are not well
understood, disrupts the trafficking of each molecule in different ways.
Specifically, Nef promotes CD4 internalization after it has been transported to
the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal
transport of MHC-I from the TGN to the cell surface. Despite these differences
in initial intracellular trafficking, we demonstrate that MHC-I and CD4 are
ultimately found in the same Rab7+ vesicles and are both
targeted for degradation via the activity of the Nef-interacting protein,
Ξ²-COP. Moreover, we demonstrate that Nef contains two separable
Ξ²-COP binding sites. One site, an arginine (RXR) motif in the N-terminal
Ξ± helical domain of Nef, is necessary for maximal MHC-I degradation. The
second site, composed of a di-acidic motif located in the C-terminal loop domain
of Nef, is needed for efficient CD4 degradation. The requirement for redundant
motifs with distinct roles supports a model in which Nef exists in multiple
conformational states that allow access to different motifs, depending upon
which cellular target is bound by Nef
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