448 research outputs found
Tsunami Propagation from the Open Sea to the Coast
The tsunami generated by the Great East Japan Earthquake (GEJE) caused serious damage to the coastal areas of the Tohoku district. Numerical simulations are used to predict damage caused by tsunamis. Shallow-water equations are generally used in numerical simulations of tsunami propagation from the open sea to the coast. This research focuses on viscous shallow-water equations and attempts to generate a computational method using finite-element techniques based on the previous investigations of Kanayama and Ohtsuka (1978). First, the viscous shallow-water equation system is derived from the Navier-Stokes equations, based on the assumption of hydrostatic pressure in the direction of gravity. The derived equations have the horizontal viscosity term hereditary from the original Navier-Stokes equations. Next, a numerical finite element scheme is shown. Finally, tsunami simulations of Tohoku-Oki are shown using the above-mentioned approach. Our main concern in this chapter is how to set the boundary condition on the open boundary
Molecular cloning and analysis of zebrafish voltage-gated sodium channel beta subunit genes: implications for the evolution of electrical signaling in vertebrates
<p>Abstract</p> <p>Background</p> <p>Action potential generation in excitable cells such as myocytes and neurons critically depends on voltage-gated sodium channels. In mammals, sodium channels exist as macromolecular complexes that include a pore-forming alpha subunit and 1 or more modulatory beta subunits. Although alpha subunit genes have been cloned from diverse metazoans including flies, jellyfish, and humans, beta subunits have not previously been identified in any non-mammalian species. To gain further insight into the evolution of electrical signaling in vertebrates, we investigated beta subunit genes in the teleost <it>Danio rerio </it>(zebrafish).</p> <p>Results</p> <p>We identified and cloned single zebrafish gene homologs for beta1-beta3 (<it>zbeta1-zbeta3</it>) and duplicate genes for beta4 (<it>zbeta4.1, zbeta4.2</it>). Sodium channel beta subunit loci are similarly organized in fish and mammalian genomes. Unlike their mammalian counterparts, <it>zbeta1 </it>and <it>zbeta2 </it>subunit genes display extensive alternative splicing. Zebrafish beta subunit genes and their splice variants are differentially-expressed in excitable tissues, indicating tissue-specific regulation of <it>zbeta1-4 </it>expression and splicing. Co-expression of the genes encoding zbeta1 and the zebrafish sodium channel alpha subunit Na<sub>v</sub>1.5 in Chinese Hamster Ovary cells increased sodium current and altered channel gating, demonstrating functional interactions between zebrafish alpha and beta subunits. Analysis of the synteny and phylogeny of mammalian, teleost, amphibian, and avian beta subunit and related genes indicated that all extant vertebrate beta subunits are orthologous, that beta2/beta4 and beta1/beta3 share common ancestry, and that beta subunits are closely related to other proteins sharing the V-type immunoglobulin domain structure. Vertebrate sodium channel beta subunit genes were not identified in the genomes of invertebrate chordates and are unrelated to known subunits of the <it>para </it>sodium channel in <it>Drosophila</it>.</p> <p>Conclusion</p> <p>The identification of conserved orthologs to all 4 voltage-gated sodium channel beta subunit genes in zebrafish and the lack of evidence for beta subunit genes in invertebrate chordates together indicate that this gene family emerged early in vertebrate evolution, prior to the divergence of teleosts and tetrapods. The evolutionary history of sodium channel beta subunits suggests that these genes may have played a key role in the diversification and specialization of electrical signaling in early vertebrates.</p
Genomic analysis uncovers prognostic and immunogenic characteristics of ferroptosis for clear cell renal cell carcinoma
In this study, the characteristic patterns of ferroptosis in clear cell renal cell carcinoma (ccRCC) were systematically investigated with the interactions between ferroptosis and the tumor microenvironment (TME). On the mRNA expression profiles of 57 ferroptosis-related genes (FRGs), three ferroptosis patterns were constructed, with distinct prognosis and immune cell infiltrations (especially T cells and dendritic cells). The high ferroptosis scores were characterized by poorer prognosis, increased T cell infiltration, higher immune and stromal scores, elevated tumor mutation burden, and enhanced response to anti-CTLA4 immunotherapy. Meanwhile, the low ferroptosis scores were distinctly associated with enhanced tumor purity and amino acid and fatty acid metabolism pathways. Following validation, the ferroptosis score was an independent and effective prognostic factor. Collectively, ferroptosis could be involved in the diverse and complex TME. Evaluation of the ferroptosis patterns may heighten the comprehension about immune infiltrations in the TME, assisting oncologists to generate individualized immunotherapeutic strategies
Suzaku Observations of the North Polar Spur: Evidence for Nitrogen Enhancement
We present observations of the North Polar Spur (NPS) using the X-ray Imaging
Spectrometer (XIS) aboard the Suzaku X-ray satellite. The NPS is a large region
of enhanced soft X-ray and radio emission projected above the plane of the
Galaxy, likely produced by a series of supernovae and stellar winds from the
nearby Sco-Cen OB association. The exceptional sensitivity and spectral
resolution of the XIS below 1 keV allow unprecedented probing of low-energy
spectral lines, including CVI (0.37 keV) and NVII (0.50 keV), and we have
detected highly-ionized nitrogen toward the NPS for the first time. For this
single pointing toward the brightest 3/4 keV emission (l = 26.8 deg, b = +22.0
deg), the best-fit NPS emission model implies a hot (kT ~ 0.3 keV), collisional
ionization equilibrium (CIE) plasma with depleted C, O, Ne, Mg, and Fe
abundances of less than 0.5 solar, but an enhanced N abundance, with N/O = 4.0
+0.4,-0.5 times solar. The temperature and total thermal energy of the gas
suggest heating by one or more supernovae, while the enhanced nitrogen
abundance is best explained by enrichment from stellar material that has been
processed by the CNO cycle. Due to the time required to develop AGB stars, we
conclude that this N/O enhancement cannot be caused by the Sco-Cen OB
association, but may result from a previous enrichment episode in the solar
neighborhood.Comment: 13 pages, 10 figures, accepted for publication in PASJ (2nd Suzaku
Special Issue
Amphiphilic γ-cyclodextrin–fullerene complexes with photodynamic activity
Amphiphilic γ-cyclodextrin–fullerene 2 : 1 complexes (CLFCH complexes) were prepared by high-speed vibration milling of lipophilic tail-grafted γ-cyclodextrin (γ-CD), hydrophilic tail-grafted γ-CD and fullerene C₆₀. The transamidation of γ-CD–fullerene complexes having two amino groups with lipophilic and hydrophilic activated esters also afforded amphiphilic CLFCH complexes. Self-assemblies consisting of amphiphilic CLFCH complexes efficiently generated singlet oxygen under photoirradiation. Under visible light irradiation conditions, CLFCH complexes bearing a vitamin E moiety as a lipophilic tail showed high photodynamic activity toward cancer cells
The antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus
BACKGROUND: The increase in antibiotic resistant bacteria has led to renewed interest in development of alternative antimicrobial compounds such as antimicrobial peptides (AMPs), either naturally-occurring or synthetically-derived. Knowledge of the mode of action (MOA) of synthetic compounds mimicking the function of AMPs is highly valuable both when developing new types of antimicrobials and when predicting resistance development. Despite many functional studies of AMPs, only a few of the synthetic peptides have been studied in detail. RESULTS: We investigated the MOA of the lysine-peptoid hybrid, LP5, which previously has been shown to display antimicrobial activity against Staphylococcus aureus. At concentrations of LP5 above the minimal inhibitory concentration (MIC), the peptoid caused ATP leakage from bacterial cells. However, at concentrations close to the MIC, LP5 inhibited the growth of S. aureus without ATP leakage. Instead, LP5 bound DNA and inhibited macromolecular synthesis. The binding to DNA also led to inhibition of DNA gyrase and topoisomerase IV and caused induction of the SOS response. CONCLUSIONS: Our data demonstrate that LP5 may have a dual mode of action against S. aureus. At MIC concentrations, LP5 binds DNA and inhibits macromolecular synthesis and growth, whereas at concentrations above the MIC, LP5 targets the bacterial membrane leading to disruption of the membrane. These results add new information about the MOA of a new synthetic AMP and aid in the future design of synthetic peptides with increased therapeutic potential
The Neutralization of the Eosinophil Peroxidase Antibody Accelerates Eosinophilic Mucin Decomposition
Eosinophilic airway inflammation, complicated by bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), is difficult to treat. The disease may become refractory when eosinophilic mucin associated with eosinophil peroxidase (EPX) and autoantibodies fills in the paranasal sinus and small airway. This study investigated the functional role of an anti-EPX antibody in eosinophilic mucin of ECRS in eosinophilic airway inflammation. Eosinophilic mucin was obtained from patients with ECRS. The effects of the anti-EPX antibody on dsDNA release from eosinophils and eosinophilic mucin decomposition were evaluated. Immunofluorescence or enzyme-linked immunosorbent assays were performed to detect the anti-EPX antibody and its supernatant and serum levels in eosinophilic mucin, respectively. The serum levels of the anti-EPX antibody were positively correlated with sinus computed tomography score and fractionated exhaled nitrogen oxide. Patients with refractory ECRS had higher serum levels of the anti-EPX antibody than those without. However, dupilumab treatment decreased the serum levels of the anti-EPX antibody. Immunoglobulins (Igs) in the immunoprecipitate of mucin supernatants enhanced dsDNA release from eosinophils, whereas the neutralization of Igs against EPX stopped dsDNA release. Furthermore, EPX antibody neutralization accelerated mucin decomposition and restored corticosteroid sensitivity. Taken together, the anti-EPX antibody may be involved in the formulation of eosinophilic mucin and be used as a clinical marker and therapeutic target for intractable eosinophilic airway inflammation
ToF-SIMS analysis of carbonaceous particles in the sample catcher of the Hayabusa spacecraft
Three carbonaceous category 3 particles (RA-QD02-0180, RB-QD04-0037-01, and RB-QD04-0047-02) returned in the sample catcher from the Hayabusa spacecraft were analyzed by time of flight-secondary ion mass spectrometry (ToF-SIMS) to establish an analytical procedure for determination of their origins. By the different analytical schemes, the three particles gave distinct elemental and molecular ions, in which the organic carbons commonly appear to be associated with nitrogen, silicon, and/or fluorine. The particles could be debris of silicon rubber and fluorinated compounds and are therefore man-made artifacts rather than natural organic matter
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