Thermal inactivation of Byssochlamys nivea in pineapple nectar combined with preliminary high pressure treatments

Byssochlamys nivea is a thermal resistant filamentous fungi and potential micotoxin producer. Recent studies have verified the presence of ascospores of such microorganism in samples of pineapple nectars. Although the majority of filamentous fungi have limited heat resistance and are easily destroyed by heat, Byssochlamys nivea ascospores have shown high thermal resistance. The aim of this work was to evaluate the application of linear and Weibull models on thermal inactivation (70, 80 and 90ºC) of Byssochlamys nivea ascospores in pineapple nectar after pretreatment with high pressure (550MPa or 650MPa during 15min). Following the treatments, survival curves were built up for each processing temperature and adjusted for both models. It was observed that survival curves at 90°C after high pressure pretreatment at 550 MPa/15 min did not fit well to linear and Weibull models. For all the other treatments, the Weibull model presented a better fit. At 90ºC without pressure treatment, the Weibull model also showed a better adjustment, having a larger R2 and a smaller RMSE. Regarding the process effectiveness, a 5-log reduction (t5), as recommended for pasteurization, was only achieved for Byssochlamys nivea ascospores presented in pineapple nectar at 90ºC/10.7 min with previous high pressure treatment of 650 MPa for 15 min. Considering the high intensity and energy demanding process with possibly product damage, other preventive and alternative treatments are being investigated

Two-Dimensional Hydrodynamics of Pre-Core Collapse: Oxygen Shell Burning

By direct hydrodynamic simulation, using the Piecewise Parabolic Method (PPM) code PROMETHEUS, we study the properties of a convective oxygen burning shell in a SN 1987A progenitor star prior to collapse. The convection is too heterogeneous and dynamic to be well approximated by one-dimensional diffusion-like algorithms which have previously been used for this epoch. Qualitatively new phenomena are seen. The simulations are two-dimensional, with good resolution in radius and angle, and use a large (90-degree) slice centered at the equator. The microphysics and the initial model were carefully treated. Many of the qualitative features of previous multi-dimensional simulations of convection are seen, including large kinetic and acoustic energy fluxes, which are not accounted for by mixing length theory. Small but significant amounts of carbon-12 are mixed non-uniformly into the oxygen burning convection zone, resulting in hot spots of nuclear energy production which are more than an order of magnitude more energetic than the oxygen flame itself. Density perturbations (up to 8%) occur at the `edges' of the convective zone and are the result of gravity waves generated by interaction of penetrating flows into the stable region. Perturbations of temperature and electron fraction at the base of the convective zone are of sufficient magnitude to create angular inhomogeneities in explosive nucleosynthesis products, and need to be included in quantitative estimates of yields. Combined with the plume-like velocity structure arising from convection, the perturbations will contribute to the mixing of nickel-56 throughout supernovae envelopes. Runs of different resolution, and angular extent, were performed to test the robustness of theseComment: For mpeg movies of these simulations, see http://www.astrophysics.arizona.edu/movies.html Submitted to the Astrophysical Journa

Gravity Waves in the Sun

We present numerical simulations of penetrative convection and gravity wave excitation in the Sun. Gravity waves are self-consistently generated by a convective zone overlying a radiative interior. We produce power spectra for gravity waves in the radiative region as well as estimates for the energy flux of gravity waves below the convection zone. We calculate a peak energy flux in waves below the convection zone to be three orders of magnitude smaller than previous estimates for m=1. The simulations show that the linear dispersion relation is a good approximation only deep below the convective-radiative boundary. Both low frequency propagating gravity waves as well as higher frequency standing modes are generated; although we find that convection does not continually drive the standing g-mode frequencies.Comment: 22 pages, 14 figures, submitted to MNRA

An integrin-targeted photoactivatable Pt(IV) complex as a selective anticancer pro-drug: synthesis and photoactivation studies

A new anticancer agent based on the conjugation of a photoactivatable Pt(IV) pro-drug to a cyclic RGD-containing peptide is described. Upon visible light irradiation, phototoxicity was induced preferentially in SK-MEL-28 melanoma cancer cells overexpressing alphaVbeta3 integrin compared to control DU-145 human prostate carcinoma cells

Numerical Simulations of Penetration and Overshoot in the Sun

We present numerical simulations of convective overshoot in a two-dimensional model of the solar equatorial plane. The simulated domain extends from 0.001 R_sun to 0.93 R_sun, spanning both convective and radiative regions. We show that convective penetration leads to a slightly extended, mildly subadiabatic temperature gradient beneath the convection zone below which there is a rapid transition to a strongly subadiabatic region. A slightly higher temperature is maintained in the overshoot region by adiabatic heating from overshooting plumes. This enhanced temperature may partially account for the sound speed discrepancy between the standard solar model and helioseismology. Simulations conducted with tracer particles suggest that a fully mixed region exists down to at least 0.687 R_sun.Comment: 24 pages, 8 figures, submitted to Ap

Synthetic lethal interaction of cetuximab with MEK1/2 inhibition in NRAS-mutant metastatic colorectal cancer

KRAS mutations are an established predictor of lack of response to EGFR-targeted therapies in patients with metastatic colorectal cancer (mCRC). However, little is known about the role of the rarer NRAS mutations as a mechanism of primary resistance to the anti-EGFR monoclonal antibody cetuximab in wild-type KRAS mCRC. Using isogenic mCRC cells with a heterozygous knock-in of the NRAS activating mutation Q61K, we aimed to elucidate the mechanism(s) by which mutant NRAS blocks cetuximab from inhibiting mCRC growth. NRASQ61K/+ cells were refractory to cetuximab-induced growth inhibition. Pathway-oriented proteome profiling revealed that cetuximab-unresponsive ERK1/2 phosphorylation was the sole biomarker distinguishing cetuximab-refractory NRASQ61K/+ from cetuximab-sensitive NRAS+/+ cells. We therefore employed four representative MEK1/2 inhibitors (binimetinib, trametinib, selumetinib, and pimasertib) to evaluate the therapeutic value of MEK/ERK signaling in cetuximab-refractory NRAS mutation-induced mCRC. Co-treatment with an ineffective dose of cetuximab augmented, up to more than 1,300-fold, the cytotoxic effects of pimasertib against NRASQ61K/+ cells. Simultaneous combination of MEK1/2 inhibitors with cetuximab resulted in extremely high and dose-dependent synthetic lethal effects, which were executed, at least in part, by exacerbated apoptotic cell death. Dynamic monitoring of real-time cell growth rates confirmed that cetuximab synergistically sensitized NRASQ61K/+ cellsto MEK1/2 inhibition. Our discovery of a synthetic lethal interaction of cetuximab in combination with MEK1/2 inhibition for the NRAS mutant subgroup of mCRC underscores the importance of therapeutic intervention both in the MEK-ERK and EGFR pathways to achieve maximal therapeutic efficacy against NRAS-mutant mCRC tumors

Analysis of the shearing instability in nonlinear convection and magnetoconvection

Numerical experiments on two-dimensional convection with or without a vertical magnetic field reveal a bewildering variety of periodic and aperiodic oscillations. Steady rolls can develop a shearing instability, in which rolls turning over in one direction grow at the expense of rolls turning over in the other, resulting in a net shear across the layer. As the temperature difference across the fluid is increased, two-dimensional pulsating waves occur, in which the direction of shear alternates. We analyse the nonlinear dynamics of this behaviour by first constructing appropriate low-order sets of ordinary differential equations, which show the same behaviour, and then analysing the global bifurcations that lead to these oscillations by constructing one-dimensional return maps. We compare the behaviour of the partial differential equations, the models and the maps in systematic two-parameter studies of both the magnetic and the non-magnetic cases, emphasising how the symmetries of periodic solutions change as a result of global bifurcations. Much of the interesting behaviour is associated with a discontinuous change in the leading direction of a fixed point at a global bifurcation; this change occurs when the magnetic field is introduced