Differential effects on membrane permeability and viability of human keratinocyte cells undergoing very low intensity megasonic fields

Among different therapeutic applications of Ultrasound (US), transient membrane sonoporation (SP) - a temporary, non-lethal porosity, mechanically induced in cell membranes through US exposure - represents a compelling opportunity towards an efficient and safe drug delivery. Nevertheless, progresses in this field have been limited by an insufficient understanding of the potential cytotoxic effects of US related to the failure of the cellular repair and to the possible activation of inflammatory pathway. In this framework we studied the in vitro effects of very low-intensity US on a human keratinocyte cell line, which represents an ideal model system of skin protective barrier cells which are the first to be involved during medical US treatments. Bioeffects linked to US application at 1 MHz varying the exposure parameters were investigated by fluorescence microscopy and fluorescence activated cell sorting. Our results indicate that keratinocytes undergoing low US doses can uptake drug model molecules with size and efficiency which depend on exposure parameters. According to sub-cavitation SP models, we have identified the range of doses triggering transient membrane SP, actually with negligible biological damage. By increasing US doses we observed a reduced cells viability and an inflammatory gene overexpression enlightening novel healthy relevant strategies

Identification of the TeV Gamma-ray Source ARGO J2031+4157 with the Cygnus Cocoon

The extended TeV gamma-ray source ARGO J2031+4157 (or MGRO J2031+41) is positionally consistent with the Cygnus Cocoon discovered by $Fermi$-LAT at GeV energies in the Cygnus superbubble. Reanalyzing the ARGO-YBJ data collected from November 2007 to January 2013, the angular extension and energy spectrum of ARGO J2031+4157 are evaluated. After subtracting the contribution of the overlapping TeV sources, the ARGO-YBJ excess map is fitted with a two-dimensional Gaussian function in a square region of $10^{\circ}\times 10^{\circ}$, finding a source extension $\sigma_{ext}$= 1$^{\circ}$.8$\pm$0$^{\circ}$.5. The observed differential energy spectrum is $dN/dE =(2.5\pm0.4) \times 10^{-11}(E/1 TeV)^{-2.6\pm0.3}$ photons cm$^{-2}$ s$^{-1}$ TeV$^{-1}$, in the energy range 0.2-10 TeV. The angular extension is consistent with that of the Cygnus Cocoon as measured by $Fermi$-LAT, and the spectrum also shows a good connection with the one measured in the 1-100 GeV energy range. These features suggest to identify ARGO J2031+4157 as the counterpart of the Cygnus Cocoon at TeV energies. The Cygnus Cocoon, located in the star-forming region of Cygnus X, is interpreted as a cocoon of freshly accelerated cosmic rays related to the Cygnus superbubble. The spectral similarity with Supernova Remnants indicates that the particle acceleration inside a superbubble is similar to that in a SNR. The spectral measurements from 1 GeV to 10 TeV allows for the first time to determine the possible spectrum slope of the underlying particle distribution. A hadronic model is adopted to explain the spectral energy distribution.Comment: 16 pages, 3 figures, has been accepted by ApJ for publicatio

4MOST Consortium Survey 3: Milky Way Disc and Bulge Low-Resolution Survey (4MIDABLE-LR)

The mechanisms of the formation and evolution of the Milky Way are encoded in the orbits, chemistry and ages of its stars. With the 4MOST MIlky way Disk And BuLgE Low-Resolution Survey (4MIDABLE-LR) we aim to study kinematic and chemical substructures in the Milky Way disc and bulge region with samples of unprecedented size out to larger distances and greater precision than conceivable with Gaia alone or any other ongoing or planned survey. Gaia gives us the unique opportunity for target selection based almost entirely on parallax and magnitude range, hence increasing the efficiency in sampling larger Milky Way volumes with well-defined and effective selection functions. Our main goal is to provide a detailed chrono-chemo-kinematical extended map of our Galaxy and the largest Gaia follow-up down to $G = 19$ magnitudes (Vega). The complex nature of the disc components (for example, large target densities and highly structured extinction distribution in the Milky Way bulge and disc area), prompted us to develop a survey strategy with five main sub-surveys that are tailored to answer the still open questions about the assembly and evolution of our Galaxy, while taking full advantage of the Gaia data.Comment: Part of the 4MOST issue of The Messenger, published in preparation of 4MOST Community Workshop, see http://www.eso.org/sci/meetings/2019/4MOST.htm

Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate

Hen egg-white lysozyme (HEWL) was the first enzyme to have its three-dimensional structure determined by X-ray diffraction techniques(1). A catalytic mechanism, featuring a long-lived oxo-carbenium-ion intermediate, was proposed on the basis of model-building studies(2). The `Phillips' mechanism is widely held as the paradigm for the catalytic mechanism of beta -glycosidases that cleave glycosidic linkages with net retention of configuration of the anomeric centre. Studies with other retaining beta -glycosidases, however, provide strong evidence pointing to a common mechanism for these enzymes that involves a covalent glycosyl-enzyme intermediate, as previously postulated(3). Here we show, in three different cases using electrospray ionization mass spectrometry, a catalytically competent covalent glycosyl-enzyme intermediate during the catalytic cycle of HEWL. We also show the three-dimensional structure of this intermediate as determined by Xray diffraction. We formulate a general catalytic mechanism for all retaining beta -glycosidases that includes substrate distortion, formation of a covalent intermediate, and the electrophilic migration of C1 along the reaction coordinate

Quantized Black Holes, Their Spectrum and Radiation

Under quite natural general assumptions, the following results are obtained. The maximum entropy of a quantized surface is demonstrated to be proportional to the surface area in the classical limit. The general structure of the horizon spectrum is found. The discrete spectrum of thermal radiation of a black hole Under quite natural general assumptions, the following results are obtained. The maximum entropy of a quantized surface is demonstrated to be proportional to the surface area in the classical limit. The general structure of the horizon spectrum is found. The discrete spectrum of thermal radiation of a black hole fits the Wien profile. The natural widths of the lines are much smaller than the distances between them. The total intensity of the thermal radiation is estimated. In the special case of loop quantum gravity, the value of the Barbero -- Immirzi parameter is found. Different values for this parameter, obtained under additional assumption that the horizon is described by a U(1) Chern -- Simons theory, are demonstrated to be in conflict with the firmly established holographic bound.Comment: 15 pages, content of few talks given at conferences this summe

Near-threshold production of omega mesons in the pn -> d omega reaction

The first measurement of the p n -> d omega total cross section has been achieved at mean excess energies of Q = 28 and 57 MeV by using a deuterium cluster-jet target. The momentum of the fast deuteron was measured in the ANKE spectrometer at COSY-Juelich and that of the slow "spectator" proton p(sp) from the p d -> p(sp) d omega reaction in a silicon telescope placed close to the target. The cross sections lie above those measured for p p -> p p omega but seem to be below theoretical predictions.Comment: 7 pages, 8 figures; second approach to describe the background has been added; results changed insignificantly, EPJ in pres

Observation of the TeV gamma-ray source MGRO J1908+06 with ARGO-YBJ

The extended gamma ray source MGRO J1908+06, discovered by the Milagro air shower detector in 2007, has been observed for about 4 years by the ARGO-YBJ experiment at TeV energies, with a statistical significance of 6.2 standard deviations. The peak of the signal is found at a position consistent with the pulsar PSR J1907+0602. Parametrizing the source shape with a two-dimensional Gauss function we estimate an extension \sigma = 0.49 \pm 0.22 degrees, consistent with a previous measurement by the Cherenkov Array H.E.S.S.. The observed energy spectrum is dN/dE = 6.1 \pm 1.4 \times 10^-13 (E/4 TeV)^{-2.54 \pm 0.36} photons cm^-2 s^-1 TeV^-1, in the energy range 1-20 TeV. The measured gamma ray flux is consistent with the results of the Milagro detector, but is 2-3 times larger than the flux previously derived by H.E.S.S. at energies of a few TeV. The continuity of the Milagro and ARGO-YBJ observations and the stable excess rate observed by ARGO-YBJ along 4 years of data taking support the identification of MGRO J1908+06 as the steady powerful TeV pulsar wind nebula of PSR J1907+0602, with an integrated luminosity above 1 TeV about 1.8 times the Crab Nebula luminosity.Comment: 6 pages, accepted for pubblication by ApJ. Replaced to correct the author lis

From toothpick legs to dropping vaginas: Gender and sexuality in Joan Rivers' stand-up comedy performance

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 Intellect.This article employs sociocultural analysis to examine Joan Rivers’ stand-up comedy performances in order to reveal how she successfully operates in a sphere of artistic expression that has been, and continues to be, male-dominated. The analysis uncovers how Rivers’ stand-up comedy performance involves a complex combination of elements and how it fuses features that are regarded as ‘traditionally masculine’, such as aggression, with features frequently used by other female stand-up comedians, such as self-deprecating comedy and confessional comedy. Furthermore, the analysis exposes the complex ways in which constructions of gender and sexuality are negotiated and re-negotiated in Rivers’ stand-up comedy performance, and illustrates how dominant ideological identity constructions can be simultaneously reinforced and subverted within the same comic moment