Identification and characterization of murine DNAM-1 (CD226) and its poliovirus receptor family ligands

The leukocyte adhesion molecule DNAM-1 (CD226) is a member of the immunoglobulin superfamily and constitutively expressed on the majority of CD4+ and CD8+ T lymphocytes, natural killer (NK) cells, monocytes/macrophages, and a subset of B lymphocytes. The poliovirus receptor (PVR; CD155) and its family member nectin 2 (CD112) have recently been identified as the ligands for DNAM-1. Interaction of DNAM-1 with the ligands induces NK cell- and CD8+ T cell-mediated cytotoxicity and cytokine secretion. However, in vivo function of the receptor-ligand interaction has remained unclear. Here, we identified murine DNAM-1 and PVR homologues that physically and functionally bind each other. We demonstrated that ligand binding of murine DNAM-1 induced a costimulatory signal in antigen-specific CD8+ T cells. These results should provide a useful animal model to explore a role of DNAM-1 in immune responses in vivo.     

Simultaneous determination of 6beta-hydroxycortisol and cortisol in human urine by liquid chromatography with ultraviolet absorbance detection for phenotyping the CYP3A activity determined by the cortisol 6beta-hydroxylation clearance

This study describes a high-performance liquid chromatographic (HPLC) method for the simultaneous determination of 6beta-hydroxycortisol (6beta-OHF) and cortisol in human urine using either methylprednisolone or beclomethasone as internal standard. Separation was achieved on a reversed-phase phenyl column by a gradient elution of 0.05 M KH(2)PO(4)-0.01 M CH(3)COOH (pH 3.77) and 0.05 M KH(2)PO(4)-0.01 M CH(3)COOH with acetonitrile (4:6, v/v). 6beta-Hydroxycortisol and cortisol were monitored by UV absorption at 239 nm. The lower quantitation limits of the present HPLC method were 21.5 ng/ml for 6beta-OHF and 5.0 ng/ml for cortisol in urine. The within-day reproducibilities in the amounts of 6beta-OHF and cortisol determined were in good agreement with the actual amounts added, the relative error being less than 1.59%. The inter-assay precisions (R.S.D. values) were less than 7.91% for 6beta-OHF and cortisol. The method was compared with the GC/MS method by measuring 6beta-OHF in the same urine samples. A good correlation was found between the amounts determined by the two methods. The regression equations for the HPLC (y) and GC/MS (x) methods were: y=1.0701x+17.389 (r=0.9772) for methylprednisolone as internal standard and y=1.0827x+6.1364 (r=0.9794) for beclomethasone as internal standard.     

Quantum simulation of nanosized materials: 100 years of mystery is solved

Application of alpha-oscillator theory to quantum electrodynamics (QED) solves the mystery (as Feynman said) of the double-slit phenomenon involved in the foundation of quantum mechanics (QM). Even if with the same initial condition given, different spots on the screen can be predicted deterministically with no introduction of hidden variables. The general proof has already been published in Ref. [3] and “what is new in this paper” is the concrete numerical algorithm of the extended normal mode technique in section “Concrete numerical algorithm of the extended normal mode technique” and concrete trajectory of one electron in section “Current of one electron”. The interference pattern is similar to, but cannot be reproduced quantitatively by, that of QM wave function, contrary to many-years-anticipation: a new prediction, awaiting experimental test over and above the Bohr–Einstein gedanken experiment. QED paves the way for the new generic quantitative theory of electronic structure and dynamics over and above QM. Alpha-oscillator theory presents new aspects of QED from basic physics to material sciences with mathematical rigor. Quantum simulation of nanosized materials is a realization of the new-generation quantum theory. A new era of quantum simulation of nanosized materials is realized. Correct theory of the double-slit phenomenon is QED. Correct quantum theoretical view of the double-slit phenomenon is relativistic quantum field theory (QFT).     

Annual cycle of circulations in Lake Biwa, part 1: model validation

We perform a series of model studies of the physical environment in Lake Biwa. In part 1, provided here, we formulate and validate a numerical model which consists of three-dimensional momentum and continuity equations for a Boussinesq fluid under the hydrostatic approximation in a rotating frame, the advective–diffusive equation for water temperature, and the full nonlinear equation of state for freshwater. Water motion is driven by heat flux and wind forcing which are evaluated from the time series of meteorological parameters observed at weather stations around and on the lake using bulk formulae. This model for the first time accurately simulates the annual and interannual variations found in observed water temperature and velocity fields in the 2004–2006 hindcast experiment. A current system of cyclonic (counterclockwise) and anticyclonic (clockwise) circular gyres appears above the seasonal thermocline during a stratified season, and a bottom flow appears along the eastern slope to sink cold dense water from the shallow eastern region to the deep lake bottom during an unstratified season. Full overturning of the water column during winter causes bottom water temperature to change interannually depending on the severity of winter. These successful results endorse the benefits of the model when investigating the physical environment of the lake over longer timescales.     

Quantitative analysis of hemin-induced neutrophil extracellular trap formation and effects of hydrogen peroxide on this phenomenon

Formation of neutrophil extracellular traps (NETs) can perpetuate sterile inflammation; thus, it is important to clarify their pathophysiological characteristics. Free heme, derived via hemolysis, is a major contributor to organ damage, and reportedly induces neutrophil activation as well as reactive oxygen species (ROS) production and NET formation. For this study, we examined hemin (Fe³⁺ -protoporphyrin IX)-induced NET formation quantitatively in vitro as well as the effects of oxidative stress.NETs formed in vitro from cultured neutrophils were quantitatively detected by using nuclease treatment and Sytox Green, a nucleic acid stain. Hemin-induced NET production was found to be in a dose-dependent manner, NADPH oxidase-dependent and toll-like receptor (TLR)-4 independent. Additionally, the iron molecule in the porphyrin ring was considered essential for the formation of NETs. In the presence of low concentrations of hydrogen peroxide, low concentrations of hemin-induced NETs were enhanced, unlike those of phorbol myristate acetate (PMA)-induced NETs.Quantitative analysis of NET formation may prove to be a useful tool for investigating NET physiology, and hemin could function as a possible therapeutic target for hemolysis-related events.