Cytosolic DNA Sensor Upregulation Accompanies DNA Electrotransfer in B16.F10 Melanoma Cells

In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFN β mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16. F10 cells in culture, IFN beta mRNA and protein levels were significantly upregulated. The mRNAs for several DNA sensors were present in these cells; DNA-dependent activator of interferon regulatory factor (DAI), DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 (DDX60), and p204 were significantly upregulated while DDX60 protein levels were coordinately upregulated. Upregulation of DNA sensors in tumors could be masked by the lower transfection efficiency compared to in vitro or to dilution by other tumor cell types. Mirroring the observation of tumor necrosis, cells underwent a significant DNA concentration-dependent decrease in proliferation and survival. Taken together, these results indicate that DNA electrotransfer may cause the upregulation of several intracellular DNA sensors in B16. F10 cells, inducing effects in vitro and potentially in vivo

Electrocatalysis in confined space

The complex interplay of restricted mass transport leading to local accumulation or depletion of educts, intermediates, products, counterions and co-ions influences the reactions at the active sites of electrocatalysts when electrodes are rough, three-dimensionally mesoporous or nanoporous. This influence is important with regard to activity, and even more to selectivity, of electrocatalytic reactions. The underlying principles are discussed based on the growing awareness of these considerations over recent years

Upregulation of DNA Sensors in B16.F10 Melanoma Spheroid Cells After Electrotransfer of pDNA

Increased expression of cytosolic DNA sensors, a category of pattern recognition receptor, after control plasmid DNA electrotransfer was observed in our previous studies on B16.F10 murine melanoma cells. This expression was correlated with the upregulation of proinflammatory cytokines and chemokines and was associated with cell death. Here, we expanded our research to include the influence of features of cells in a 3-dimensional environment, which better represents the tumors’ organization in vivo. Our results show that lower number of cells were transfected in spheroids compared to 2-dimensional cultures, that growth was delayed after electroporation alone or after electrotransfer of plasmid DNA, and that DNA sensors DDX60, DAI/ ZBP1, and p204 were upregulated 4 hours and 24 hours after electrotransfer of plasmid DNA. Moreover, the cytokines interferon β and tumor necrosis factor α were also upregulated but only 4 hours after electrotransfer of plasmid DNA. Thus, our results confirm the results obtained in 2-dimensional cell cultures demonstrating that electrotransfer of plasmid DNA to tumor cells in spheroids also upregulated cytosolic DNA sensors and cytokines

Direct and Indirect Associations of Food Insecurity, Adolescent–Parent Relationship, and Adolescent Future Orientation

This cross-sectional study on Ghanaian adolescents examined the direct and indirect associations of food insecurity, parent–adolescent relationship, and adolescent future orientation. We used structural equation modeling to examine reliability and validity of our latent constructs and our hypothesized direct and indirect relationships. Results indicated adequate fit of our measurement and structural models with the data. Results also showed a significant direct and indirect effect of food insecurity. Food insecurity was directly associated with parental connection, orientation toward success, and uncertainty about the future. Food insecurity was also indirectly associated with orientation toward success and uncertainty about the future, via parental connection. Further, higher levels of parental connection were directly associated with higher levels of orientation toward success and with lower levels of uncertainty about the future. Understanding the direct and indirect effect of food insecurity is important for the design of appropriate interventions that promote holistic and positive adolescent development

Probing non-tensorial polarizations of stochastic gravitational-wave backgrounds with ground-based laser interferometers

In a general metric theory of gravitation in four dimensions, six polarizations of a gravitational wave are allowed: two scalar and two vector modes, in addition to two tensor modes in general relativity. Such additional polarization modes appear due to additional degrees of freedom in modified theories of gravitation or theories with extra dimensions. Thus, observations of gravitational waves can be utilized to constrain the extended models of gravitation. In this paper, we investigate detectability of additional polarization modes of gravitational waves, particularly focusing on a stochastic gravitational-wave background, with laser-interferometric detectors on the Earth. We found that multiple detectors can separate the mixture of polarization modes in detector outputs, and that they have almost the same sensitivity to each polarization mode of stochastic gravitational-wave background.Comment: 18 pages, 13 figure

Six-body Light-Front Tamm-Dancoff approximation and wave functions for the massive Schwinger model

The spectrum of the massive Schwinger model in the strong coupling region is obtained by using the light-front Tamm-Dancoff (LFTD) approximation up to including six-body states. We numerically confirm that the two-meson bound state has a negligibly small six-body component. Emphasis is on the usefulness of the information about states (wave functions). It is used for identifying the three-meson bound state among the states below the three-meson threshold. We also show that the two-meson bound state is well described by the wave function of the relative motion.Comment: 19 pages, RevTeX, 7 figures are available upon request; Minor errors have been corrected; Final version to appear in Phys.Rev.

The endogenous soluble VEGF receptor-2 isoform suppresses lymph node metastasis in a mouse immunocompetent mammary cancer model

BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer. METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each injection. RESULTS: Deaths from metastasis were much lower in the pesVEGFR-2 and pEndo groups than in those of the pVec. Tumor volume was significantly lower in the pesVEGFR-2 and the pEndo groups throughout the study. Multiplicity of lymph node and lung metastatic nodules was significantly suppressed in the pesVEGFR-2 and pEndo groups. Moreover, the total number of overall metastasis including the other organs was also decreased in these groups. However, pesVEGFR-2 was not able to decrease the number of lungs, ovaries, kidneys and adrenals with metastasis as counted by unilateral or bilateral metastasis. The number of CD34+/Lyve-1⁻ blood microvessels was significantly decreased in the pEndo group, while the number of CD34⁻/Lyve-1+ lymphatic vessels was significantly decreased in the pesVEGFR-2 and pEndo groups. In addition, a significant reduction in the number of dilated lymphatic vessels containing intraluminal cancer cells was observed in the pesVEGFR-2 and pEndo groups. Levels of apoptosis were significantly increased in the pEndo group, whereas the rates of cell proliferation were significantly decreased in the pesVEGFR-2 and pEndo groups. CONCLUSIONS: Our data demonstrate that esVEGFR-2 can inhibit mainly lymph node metastasis. The antimetastatic activity of esVEGFR-2 may be of high clinical significance in the treatment of metastatic breast cancer because lymph node involvement is a most important prognostic factor in cancer patients

Dark-field transmission electron microscopy and the Debye-Waller factor of graphene

Graphene's structure bears on both the material's electronic properties and fundamental questions about long range order in two-dimensional crystals. We present an analytic calculation of selected area electron diffraction from multi-layer graphene and compare it with data from samples prepared by chemical vapor deposition and mechanical exfoliation. A single layer scatters only 0.5% of the incident electrons, so this kinematical calculation can be considered reliable for five or fewer layers. Dark-field transmission electron micrographs of multi-layer graphene illustrate how knowledge of the diffraction peak intensities can be applied for rapid mapping of thickness, stacking, and grain boundaries. The diffraction peak intensities also depend on the mean-square displacement of atoms from their ideal lattice locations, which is parameterized by a Debye-Waller factor. We measure the Debye-Waller factor of a suspended monolayer of exfoliated graphene and find a result consistent with an estimate based on the Debye model. For laboratory-scale graphene samples, finite size effects are sufficient to stabilize the graphene lattice against melting, indicating that ripples in the third dimension are not necessary.Comment: 10 pages, 4 figure

P-Process Nucleosynthesis inside Supernova-Driven Supercritical Accretion Disks

We investigate p-process nucleosynthesis in a supercritical accretion disk around a compact object of 1.4 M_solar, using the self-similar solution of an optically thick advection dominated flow. Supercritical accretion is expected to occur in a supernova with fallback material accreting onto a new-born compact object. It is found that appreciable amounts of p-nuclei are synthesized via the p-process in supernova-driven supercritical accretion disks (SSADs) when the accretion rate m_dot = M_dot c^2/(16 L_Edd) >10^5, where L_Edd is the Eddington luminosity. Abundance profiles of p-nuclei ejected from SSADs have similar feature to those of the oxygen/neon layers in Type II supernovae when the abundance of the fallback gas far from the compact object is that of the oxygen/neon layers in the progenitor. The overall abundance profile is in agreement with that of the solar system. Some p-nuclei, such as Mo, Ru, Sn, and La, are underproduced in the SSADs as in Type II supernovae. If the fallback gas is mixed with a small fraction of proton through Rayleigh-Taylor instability during the explosion, significant amounts of Mo92 are produced inside the SSADs. Ru96 and La138 are also produced when the fallback gas contains abundant proton though the overall abundance profile of p-nuclei is rather different from that of the solar system. The p-process nucleosynthesis in SSADs contributes to chemical evolution of p-nuclei, in particular Mo92, if several percents of fallback matter are ejected via jets and/or winds.Comment: 15 pages, 7 figures included, 3 tables, LaTeX emulateapj5.sty, accepted for publication by the Astronomical Journal (March, 2003

Dark-field transmission electron microscopy and the Debye-Waller factor of graphene

Graphene\u27s structure bears on both the material\u27s electronic properties and fundamental questions about long-range order in two-dimensional crystals. We present an analytic calculation of selected area electron diffraction from multilayer graphene and compare it with data from samples prepared by chemical vapor deposition and mechanical exfoliation. A single layer scatters only 0.5% of the incident electrons, so this kinematical calculation can be considered reliable for five or fewer layers. Dark-field transmission electron micrographs of multilayer graphene illustrate how knowledge of the diffraction peak intensities can be applied for rapid mapping of thickness, stacking, and grain boundaries. The diffraction peak intensities also depend on the mean-square displacement of atoms from their ideal lattice locations, which is parameterized by a Debye-Waller factor. We measure the Debye-Waller factor of a suspended monolayer of exfoliated graphene and find a result consistent with an estimate based on the Debye model. For laboratory-scale graphene samples, finite size effects are sufficient to stabilize the graphene lattice against melting, indicating that ripples in the third dimension are not necessary