Molecular and Genetic Determinants of Glioma Cell Invasion.

A diffusely invasive nature is a major obstacle in treating a malignant brain tumor, "diffuse glioma", which prevents neurooncologists from surgically removing the tumor cells even in combination with chemotherapy and radiation. Recently updated classification of diffuse gliomas based on distinct genetic and epigenetic features has culminated in a multilayered diagnostic approach to combine histologic phenotypes and molecular genotypes in an integrated diagnosis. However, it is still a work in progress to decipher how the genetic aberrations contribute to the aggressive nature of gliomas including their highly invasive capacity. Here we depict a set of recent discoveries involving molecular genetic determinants of the infiltrating nature of glioma cells, especially focusing on genetic mutations in receptor tyrosine kinase pathways and metabolic reprogramming downstream of common cancer mutations. The specific biology of glioma cell invasion provides an opportunity to explore the genotype-phenotype correlation in cancer and develop novel glioma-specific therapeutic strategies for this devastating disease

Time domain Einstein-Podolsky-Rosen correlation

We experimentally demonstrate creation and characterization of Einstein-Podolsky-Rosen (EPR) correlation between optical beams in the time domain. The correlated beams are created with two independent continuous-wave optical parametric oscillators and a half beam splitter. We define temporal modes using a square temporal filter with duration $T$ and make time-resolved measurement on the generated state. We observe the correlations between the relevant conjugate variables in time domain which correspond to the EPR correlation. Our scheme is extendable to continuous variable quantum teleportation of a non-Gaussian state defined in the time domain such as a Schr\"odinger cat-like state.Comment: 4 pages, 4 figure

Towards a realistic estimation of the powering performance of a ship with a gate rudder system

This paper presents an investigation on the scale effects associated with the powering performance of a Gate Rudder System (GRS) which was recently introduced as a novel energy-saving propulsion and maneuvring device. This new system was applied for the first time on a 2400 GT domestic container ship, and full-scale sea trials were conducted successfully in Japan, in 2017. The trials confirmed the superior powering and maneuvring performance of this novel system. However, a significant discrepancy was also noticed between the model test-based performance predictions and the full-scale measurements. The discrepancy was in the power-speed data and also in the maneuvring test data when these data were compared with the data of her sister container ship which was equipped with a conventional flap rudder. Twelve months after the delivery of the vessel with the gate rudder system, the voyage data revealed a surprisingly more significant difference in the powering performance based on the voyage data. The aim of this paper, therefore, is to take a further step towards an improved estimation of the powering performance of ships with a GRS with a specific emphasis on the scale effect issues associated with a GRS. More specifically, this study investigated the scale effects on the powering performance of a gate rudder system based on the analyses of the data from two tank tests and full-scale trials with the above-mentioned sister ships. The study focused on the corrections for the scale effects, which were believed to be associated with the drag and lift characteristics of the gate rudder blades due to the low Reynolds number experienced in model tests combined with the unique arrangement of this rudder and propulsion system. Based on the appropriate semi-empirical approaches that support model test and full-scale data, this study verified the scale effect phenomenon and presented the associated correction procedure. Also, this study presented an enhanced methodology for the powering performance prediction of a ship driven by a GRS implementing the proposed scale effect correction. The predicted powering performance of the subject container vessel with the GRS presented an excellent agreement with the full-scale trials data justifying the claimed scale effect and associated correction procedure, as well as the proposed enhanced methodology for the practical way of predicting the powering performance of a ship with the GRS

Optimizing Conical Intersections of Solvated Molecules: The Combined Spin-Flip Density Functional Theory/Effective Fragment Potential Method

Solvent effects on a potential energy surface crossing are investigated by optimizing a conical intersection (CI) in solution. To this end, the analytic energy gradient has been derived and implemented for the collinear spin-flip density functional theory (SFDFT) combined with the effective fragment potential (EFP) solvent model. The new method is applied to the azomethane-water cluster and the chromophore of green fluorescent protein in aqueous solution. These applications illustrate not only dramatic changes in the CI geometries but also strong stabilization of the CI in a polar solvent. Furthermore, the CI geometries obtained by the hybrid SFDFT/EFP scheme reproduce those by the full SFDFT, indicating that the SFDFT/EFP method is an efficient and promising approach for understanding nonadiabatic processes in solution

The Distance to the Galactic Center Derived From Infrared Photometry of Bulge Red Clump Stars

On the basis of the near infrared observations of bulge red clump stars near the Galactic center, we have determined the galactocentric distance to be R_0 = 7.52 +- 0.10 (stat) +- 0.35 (sys) kpc. We observed the red clump stars at |l| < 1.0 deg and 0.7 deg < |b| < 1.0 deg with the IRSF 1.4 m telescope and the SIRIUS camera in the H and Ks bands. After extinction and population corrections, we obtained (m - M)_0 = 14.38 +- 0.03 (stat) +- 0.10 (sys). The statistical error is dominated by the uncertainty of the intrinsic local red clump stars' luminosity. The systematic error is estimated to be +- 0.10 including uncertainties in extinction and population correction, zero-point of photometry, and the fitting of the luminosity function of the red clump stars. Our result, R_0 = 7.52 kpc, is in excellent agreement with the distance determined geometrically with the star orbiting the massive black hole in the Galactic center. The recent result based on the spatial distribution of globular clusters is also consistent with our result. In addition, our study exhibits that the distance determination to the Galactic center with the red clump stars, even if the error of the population correction is taken into account, can achieve an uncertainty of about 5%, which is almost the same level as that in recent geometrical determinations.Comment: 14 pages, 4 figures, accepted by Ap

Age of the Universe in the Cardassian Model

The age of the universe is obtained in a subset of Cardassian models by using WMAP data. Cardassian expansion is a modification to the Friedmann equation that allows the universe to be flat, matter dominated, and accelerating, without a vacuum component. Since this model changes the evolution of the universe, we should not a priori expect the Cardassian age to be the same as the WMAP Friedmann derived result of 13.7 +/- 0.2 Gyrs. However, in the subset of Cardassian models we consider, we discover that the age of the universe varies from 13.4 - 13.8 Gyr over the range of parameter space we explore, a result close to that of the standard Lambda Cold Dark Matter model. The Hubble constant h, which may also vary in these models, likewise varies little from the Friedmann result.Comment: 11 pages, two eps figures. v2: clarified choice of parameters, other minor changes. v3: added references, other changes to match version to be published in JCA

Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector.

A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellularly by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvIII and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients