Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy

Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy. We explored two strategies: 1) transient blockade of autophagy with chloroquine (CQ), which blocks fusion of autophagosomes and lysosomes during ADR treatment, and 2) permanent inhibition of autophagy by a stable knockdown of ATG5 (ATG5KD), which inhibits the formation of autophagosomes in MMC during and after ADR treatment. We found that while CQ prolonged tumor dormancy, but that stable knockdown of autophagy resulted in early escape from dormancy and recurrence. Interestingly, ATG5KD MMC contained an increased frequency of ADR-induced polyploid-like cells and rendered MMC resistant to immunotherapy. On the other hand, a transient blockade of autophagy did not affect the sensitivity of MMC to immunotherapy. Our observations suggest that while chemotherapy-induced autophagy may facilitate tumor relapse, cell-intrinsic autophagy delays tumor relapse, in part, by inhibiting the formation of polyploid-like tumor dormancy

Evolution of Our Understanding of Myeloid Regulatory Cells: From MDSCs to Mregs

The term myeloid-derived suppressor cells (MDSCs) was first suggested in 2007 in order to reflect the origin and function of myeloid cells during immunosuppression in cancer and other pathologic conditions. Emerging evidence suggests that MDSCs suppress CTL and Th1 responses in malignant diseases while they regulate effective immune responses in parasitic and helminth infections as well as Th17 inflammatory response during autoimmune diseases. Based on these data, the term myeloid regulatory cells (Mregs) more accurately reflects their function and interactions with different cells of the immune system during diseased conditions. Here, we provide evidence on the multifaceted function of Mregs during diseased state

On the peak-to-average power of OFDM signals based on oversampling

Orthogonal frequency-division multiplexing (OFDM) introduces large amplitude variations in time, which can result in significant signal distortion in the presence of nonlinear amplifiers. We introduce a new bound for the peak of the continuous envelope of an OFDM signal, based on the maximum of its corresponding oversampled sequence; it is shown to be very tight as the oversampling rate increases. The bound is then used to derive a closed-form probability upper bound for the complementary cumulative distribution function of the peak-to-mean envelope power ratio of uncoded OFDM signals for sufficiently large numbers of subcarriers. As another application of the bound for oversampled sequences, we propose tight relative error bounds for computation of the peak power using two main methods: the oversampled inverse fast Fourier transform and the method introduced for coded systems based on minimum distance decoding of the code

Morphological instability of the solid-liquid interface in crystal growth under supercooled liquid film flow and natural convection airflow

Ring-like ripples on the surface of icicles are an example of morphological instability of the ice-water interface during ice growth under supercooled water film flow. The surface of icicles is typically covered with ripples of about 1 cm in wavelength, and the wavelength appears to be almost independent of external temperature, icicle radius, and volumetric water flow rate. One side of the water layer consists of the water-air surface and growing ice is the other. This is one of the more complicated moving phase boundary problems with two interfaces. A recent theoretical work [K. Ueno, Phys. Rev. E 68, (2003) 021603] to address the underlying instability that produces ripples is based on the assumption of the absence of airflow around icicles. In this paper, we extend the previous theoretical framework to include a natural convection airflow ahead of the water-air surface and consider whether the effect of natural convection airflow on the wavelength of ripples produced on an ice surface is essential or not.Comment: 19 pages, 5 figure

Branch Flow Model: Relaxations and Convexification—Part II

We propose a branch flow model for the analysis and optimization of mesh as well as radial networks. The model leads to a new approach to solving optimal power flow (OPF) that consists of two relaxation steps. The first step eliminates the voltage and current angles and the second step approximates the resulting problem by a conic program that can be solved efficiently. For radial networks, we prove that both relaxation steps are always exact, provided there are no upper bounds on loads. For mesh networks, the conic relaxation is always exact but the angle relaxation may not be exact, and we provide a simple way to determine if a relaxed solution is globally optimal. We propose convexification of mesh networks using phase shifters so that OPF for the convexified network can always be solved efficiently for an optimal solution. We prove that convexification requires phase shifters only outside a spanning tree of the network and their placement depends only on network topology, not on power flows, generation, loads, or operating constraints. Part I introduces our branch flow model, explains the two relaxation steps, and proves the conditions for exact relaxation. Part II describes convexification of mesh networks, and presents simulation results

Linear stability analysis in inhomogeneous equilibrium configurations

We propose a novel method to find local plane-wave solutions of the linearized equations of motion of relativistic hydrodynamics in inhomogeneous equilibrium configurations, i.e., when a fluid in equilibrium is rigidly moving with nonzero thermal vorticity. Our method is based on extending the conserved currents to the tangent bundle, using a type of Wigner transformation. The Wigner-transformed conserved currents can then be Fourier-transformed into the cotangent bundle to obtain the dispersion relations for the space-time dependent eigenfrequencies. We show that the connection between the stability of hydrodynamics and the evolution of plane waves is not as straightforward as in the homogeneous case, namely, it is restricted to the equilibrium-preserving directions in the cotangent bundle. We apply this method to Mueller-Israel-Stewart (MIS) theory and show that the interplay between the bulk viscous pressure and the shear-stress tensor with acceleration and rotation leads to novel modes, as well as modifications of the already known ones. We conclude that, within the domain of applicability, i.e., when boundary effects are negligible and the vorticity is not too large, MIS theory is stable and causal, with the same stability and causality conditions as for homogeneous equilibrium configurations.Comment: 29 pages, 2 figure

Branch Flow Model: Relaxations and Convexification (Parts I, II)

We propose a branch flow model for the anal- ysis and optimization of mesh as well as radial networks. The model leads to a new approach to solving optimal power flow (OPF) that consists of two relaxation steps. The first step eliminates the voltage and current angles and the second step approximates the resulting problem by a conic program that can be solved efficiently. For radial networks, we prove that both relaxation steps are always exact, provided there are no upper bounds on loads. For mesh networks, the conic relaxation is always exact but the angle relaxation may not be exact, and we provide a simple way to determine if a relaxed solution is globally optimal. We propose convexification of mesh networks using phase shifters so that OPF for the convexified network can always be solved efficiently for an optimal solution. We prove that convexification requires phase shifters only outside a spanning tree of the network and their placement depends only on network topology, not on power flows, generation, loads, or operating constraints. Part I introduces our branch flow model, explains the two relaxation steps, and proves the conditions for exact relaxation. Part II describes convexification of mesh networks, and presents simulation results.Comment: A preliminary and abridged version has appeared in IEEE CDC, December 201

New class of exact solutions to Einstein-Maxwell-dilaton theory on four-dimensional Bianchi type IX geometry

We construct new classes of cosmological solution to the five dimensional Einstein-Maxwell-dilaton theory, that are non-stationary and almost conformally regular everywhere. The base geometry for the solutions is the four-dimensional Bianchi type IX geometry. In the theory, the dilaton field is coupled to the electromagnetic field and the cosmological constant term, with two different coupling constants. We consider all possible solutions with different values of the coupling constants, where the cosmological constant takes any positive, negative or zero values. In the ansatzes for the metric, dilaton and electromagnetic fields, we consider dependence on time and two spatial directions. We also consider a special case of the Bianchi type IX geometry, in which the geometry reduces to that of Eguchi-Hanson type II geometry and find a more general solution to the theory.Comment: 38 pages, 15 figures, two new appendices added, typos correcte