Excitation of stellar p-modes by turbulent convection: 1. Theoretical formulation

Stochatic excitation of stellar oscillations by turbulent convection is investigated and an expression for the power injected into the oscillations by the turbulent convection of the outer layers is derived which takes into account excitation through turbulent Reynolds stresses and turbulent entropy fluctuations. This formulation generalizes results from previous works and is built so as to enable investigations of various possible spatial and temporal spectra of stellar turbulent convection. For the Reynolds stress contribution and assuming the Kolmogorov spectrum we obtain a similar formulation than those derived by previous authors. The entropy contribution to excitation is found to originate from the advection of the Eulerian entropy fluctuations by the turbulent velocity field. Numerical computations in the solar case in a companion paper indicate that the entropy source term is dominant over Reynold stress contribution to mode excitation, except at high frequencies.Comment: 14 pages, accepted for publication in A&

Splice variants in apoptotic pathway

Elimination of superfluous or mutated somatic cells is provided by various mechanisms including apoptosis, and deregulation of apoptotic signaling pathways contributes to oncogenesis. 40 years have passed since the term “apoptosis” was introduced by Kerr et al. in 1972; among the programmed cell death, a variety of therapeutic strategies especially targeting apoptotic pathways have been investigated. Alternative precursor messenger RNA splicing, by which the process the exons of pre-mRNA are spliced in different arrangements to produce structurally and functionally distinct mRNA and proteins, is another field in progress, and it has been recognized as one of the most important mechanisms that maintains genomic and functional diversity. A variety of apoptotic genes are regulated through alternative pre-mRNA splicing as well, some of which have important functions as pro-apoptotic and anti-apoptotic factors. In this article we summarized splice variants of some of the apoptotic genes including BCL2L1, BIRC5, CFLAR, and MADD, as well as the regulatory mechanisms of alternative splicing of these genes. If the information of the apoptosis and aberrant splicing in each of malignancies is integrated, it will become possible to target proper variants for apoptosis, and the trans-elements themselves can become specific targets of cancer therapy as well. This article is part of a Special Issue entitled “Apoptosis: Four Decades Later”

On the possible existence of short-period g-mode instabilities powered by nuclear burning shells in post-AGB H-deficient (PG1159-type) stars

We present a pulsational stability analysis of hot post-AGB H-deficient pre-white dwarf stars with active He-burning shells. The stellar models employed are state-of-the-art equilibrium structures representative of PG1159 stars derived from the complete evolution of the progenitor stars. On the basis of fully nonadiabatic pulsation computations, we confirmed theoretical evidence for the existence of a separate PG1159 instability strip in the $\log T_{\rm eff} - \log g$ diagram characterized by short-period $g$-modes excited by the $\epsilon$-mechanism. This instability strip partially overlaps the already known GW Vir instability strip of intermediate/long period $g$-modes destabilized by the classical $\kappa$-mechanism acting on the partial ionization of C and/or O in the envelope of PG1159 stars. We found that PG1159 stars characterized by thick He-rich envelopes and located inside this overlapping region could exhibit both short and intermediate/long periods simultaneously. we study the particular case of VV 47, a pulsating planetary nebula nucleus that has been reported to exhibit a series of unusually short pulsation periods. We found that the long periods exhibited by VV 47 can be readily explained by the classical $\kappa$-mechanism, while the observed short-period branch below $\approx 300$ s could correspond to modes triggered by the He-burning shell through the $\epsilon$-mechanism, although more observational work is needed to confirm the reality of these short-period modes. Were the existence of short-period $g$-modes in this star convincingly confirmed by future observations, VV 47 could be the first known pulsating star in which both the $\kappa$-mechanism and the $\epsilon$-mechanism of mode driving are simultaneously operating.Comment: 9 pages, 5 figures, 2 tables. To be published in The Astrophysical Journa

MEK inhibitors cobimetinib and trametinib, regressed a gemcitabine-resistant pancreatic-cancer patient-derived orthotopic xenograft (PDOX).

A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p.o., 14 consecutive days, n = 7); carfilzomib (2 mg/kg, i.v., twice a week for 2 weeks, n = 7); bortezomib (1 mg/kg, i.v., twice a week for 2 weeks, n = 7); MK-1775 (20 mg/kg, p.o., 14 consecutive days, n = 7); BEZ-235 (45 mg/kg, p.o., 14 consecutive days, n = 7); vorinostat (50 mg/kg, i.p., 14 consecutive days, n = 7). Only the MEK inhibitors, cobimetinib and trametinib, regressed tumor growth, and they were more significantly effective than other therapies (p < 0.0001, respectively), thereby demonstrating the precision of the PDOX models of PDAC and its potential for individualizing pancreatic-cancer therapy

Crustal Oscillations of Slowly Rotating Relativistic Stars

We study low-amplitude crustal oscillations of slowly rotating relativistic stars consisting of a central fluid core and an outer thin solid crust. We estimate the effect of rotation on the torsional toroidal modes and on the interfacial and shear spheroidal modes. The results compared against the Newtonian ones for wide range of neutron star models and equations of state.Comment: 15 page

High-efficacy targeting of colon-cancer liver metastasis with Salmonella typhimurium A1-R via intra-portal-vein injection in orthotopic nude-mouse models.

Liver metastasis is the main cause of colon cancer-related death and is a recalcitrant disease. We report here the efficacy and safety of intra-portal-vein (iPV) targeting of Salmonella typhimurium A1-R on colon cancer liver metastasis in a nude-mouse orthotopic model. Nude mice with HT29 human colon cancer cells, expressing red fluorescent protein (RFP) (HT29-RFP), growing in the liver were administered S. typhimurium A1-R by either iPV (1×104 colony forming units (CFU)/100 μl) or, for comparison, intra-venous injection (iv; 5×107 CFU/100 μl). Similar amounts of bacteria were delivered to the liver with the two doses, indicating that iPV delivery is 5×103 times more efficient than iv delivery. Treatment efficacy was evaluated by tumor fluorescent area (mm2) and total fluorescence intensity. Tumor fluorescent area and fluorescence intensity highly correlated (p<0.0001). iPV treatment was more effective compared to both untreated control and iv treatment (p<0.01 and p<0.05, respectively with iPV treatment with S. typhimurium arresting metastatic growth). There were no significant differences in body weight between all groups. The results of this study suggest that S. typhimurium A1-R administered iPV has potential for peri-operative adjuvant treatment of colon cancer liver metastasis

Vemurafenib-resistant BRAF-V600E-mutated melanoma is regressed by MEK-targeting drug trametinib, but not cobimetinib in a patient-derived orthotopic xenograft (PDOX) mouse model.

Melanoma is a recalcitrant disease. The present study used a patient-derived orthotopic xenograft (PDOX) model of melanoma to test sensitivity to three molecularly-targeted drugs and one standard chemotherapeutic. A BRAF-V600E-mutant melanoma obtained from the right chest wall of a patient was grown orthotopically in the right chest wall of nude mice to establish a PDOX model. Two weeks after implantation, 50 PDOX nude mice were divided into 5 groups: G1, control without treatment; G2, vemurafenib (VEM) (30 mg/kg); G3; temozolomide (TEM) (25 mg/kg); G4, trametinib (TRA) (0.3 mg/kg); and G5, cobimetinib (COB) (5 mg/kg). Each drug was administered orally, daily for 14 consecutive days. Tumor sizes were measured with calipers twice a week. On day 14 from initiation of treatment, TRA, an MEK inhibitor, was the only agent of the 4 tested that caused tumor regression (P < 0.001 at day 14). In contrast, another MEK inhibitor, COB, could slow but not arrest growth or cause regression of the melanoma. First-line therapy TEM could slow but not arrest tumor growth or cause regression. The patient in this study had a BRAF-V600E-mutant melanoma and would be considered to be a strong candidate for VEM as first-line therapy, since VEM targets this mutation. However, VEM was not effective. The PDOX model thus helped identify the very-high efficacy of TRA against the melanoma PDOX and is a promising drug for this patient. These results demonstrate the powerful precision of the PDOX model for cancer therapy, not achievable by genomic analysis alone

The chaotic behavior of the black hole system GRS 1915+105

A modified non-linear time series analysis technique, which computes the correlation dimension $D_2$, is used to analyze the X-ray light curves of the black hole system GRS 1915+105 in all twelve temporal classes. For four of these temporal classes $D_2$ saturates to $\approx 4-5$ which indicates that the underlying dynamical mechanism is a low dimensional chaotic system. Of the other eight classes, three show stochastic behavior while five show deviation from randomness. The light curves for four classes which depict chaotic behavior have the smallest ratio of the expected Poisson noise to the variability ($< 0.05$) while those for the three classes which depict stochastic behavior is the highest ($> 0.2$). This suggests that the temporal behavior of the black hole system is governed by a low dimensional chaotic system, whose nature is detectable only when the Poisson fluctuations are much smaller than the variability.Comment: Accepted for publication in Astrophysical Journa

Excitation of stellar oscillations by gravitational waves: hydrodynamic model and numerical results for the Sun

Starting from a general relativistic framework a hydrodynamic formalism is derived that yields the mean-square amplitudes and rms surface velocities of normal modes of non-relativistic stars excited by arbitrary gravitational wave (GW) radiation. In particular, stationary GW fields are considered and the resulting formulae are evaluated for two general types of GW radiation: radiation from a particular astrophysical source (e.g., a binary system) and a stochastic background of gravitational waves (SBGW). Expected sources and signal strengths for both types of GW radiation are reviewed and discussed. Numerical results for the Sun show that low-order quadrupolar g modes are excited more strongly than p modes by orders of magnitude. Maximal rms surface velocities in the case of excitation by astrophysical sources are found to be v {\le} 10^(-8) mm/s, assuming GW strain amplitudes of h {\le} 10^(-20). It is shown that current models for an SBGW produced by cosmic strings, with Omega_GW ~ 10^(-8)-10^(-5) in the frequency range of solar g modes, are able to produce maximal solar g-mode rms surface velocities of 10^(-5)-10^(-3) mm/s. This result lies close to or within the amplitude range of 10^(-3)-1 mm/s expected from excitation by turbulent convection, which is currently considered to be responsible for stellar g-mode excitation. It is concluded that studying g-mode observations of stars other than the Sun, in which excitation by GWs could be even more effective due to different stellar structures, might provide a new method to either detect GWs or to deduce a significant direct upper limit on an SBGW at intermediate frequencies between the pulsar bound and the bounds from interferometric detectors on Earth.Comment: 20 pages, 5 figure

Inclusion of turbulence in solar modeling

The general consensus is that in order to reproduce the observed solar p-mode oscillation frequencies, turbulence should be included in solar models. However, until now there has not been any well-tested efficient method to incorporate turbulence into solar modeling. We present here two methods to include turbulence in solar modeling within the framework of the mixing length theory, using the turbulent velocity obtained from numerical simulations of the highly superadiabatic layer of the sun at three stages of its evolution. The first approach is to include the turbulent pressure alone, and the second is to include both the turbulent pressure and the turbulent kinetic energy. The latter is achieved by introducing two variables: the turbulent kinetic energy per unit mass, and the effective ratio of specific heats due to the turbulent perturbation. These are treated as additions to the standard thermodynamic coordinates (e.g. pressure and temperature). We investigate the effects of both treatments of turbulence on the structure variables, the adiabatic sound speed, the structure of the highly superadiabatic layer, and the p-mode frequencies. We find that the second method reproduces the SAL structure obtained in 3D simulations, and produces a p-mode frequency correction an order of magnitude better than the first method.Comment: 10 pages, 12 figure