Control of Glycolytic Flux by AMPK and p53-Mediated Signaling Pathways in Tumor Cells Adapted to Grow at Low pH

Introduction: Tumor cells grow in nutrient and oxygen deprived microenvironments and adapt to the suboptimal growth conditions by altering metabolic pathways. This adaptation process characteristically results in a tumor phenotype that displays anaerobic glycolysis, chronic acidification and aggressive tumor characteristics. Understanding the tumor cell reaction to the microenvironment is a critical factor in predicting the tumor response to hyperthermia. The glucose regulatory molecule, 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase Isoform-3 (PFKFB3), is a bifunctional enzyme central to glycolytic flux and downstream of the metabolic stress sensor AMP-activated protein kinase (AMPK), which has been shown to activate an isoform of Phosphofructokinase (PFK-2). Society for Thermal Medicine Annual Meeting April 23-26, Clearwater Beach, FL

Control of Glycolytic Flux by AMPK and p53-mediated Signaling Pathways in Tumor Cells Grown at Low pH

Introduction: Tumor cells grow in nutrient and oxygen deprived microenvironments and adapt to the suboptimal growth conditions by altering metabolic pathways. This adaptation process characteristically results in a tumor phenotype that displays upregulated Hif-1α anaerobic glycolysis, chronic acidification, reduced rate of overall protein synthesis, lower rate of cell proliferation and aggressive invasive characteristics. Most transplantable tumors exhibit a pHe of 6.7- 7.0; the DB-1 melanoma xenografts used here have a pHe=6.7. Understanding tumor cell reaction to the microenvironment is a critical factor in predicting the tumor response to radiotherapy. The glucose regulatory molecule, 6-Phosphofructo-2-Kinase/Fructose-2,6- Biphosphatase Isoform-3 (PFKFB3), is a bifunctional enzyme central to glycolytic flux and downstream of the metabolic stress sensor AMP-activated protein kinase (AMPK), which we show activates an isoform of phosphofructokinase (PFK-2). Radiation Research Society (RRS) 8th Annual Meeting September 25-29, Maui, H

Kinetic Theory of Collisionless Self-Gravitating Gases: II. Relativistic Corrections in Galactic Dynamics

In this paper we study the kinetic theory of many-particle astrophysical systems imposing axial symmetry and extending our previous analysis in Phys. Rev. D 83, 123007 (2011). Starting from a Newtonian model describing a collisionless self-gravitating gas, we develop a framework to include systematically the first general relativistic corrections to the matter distribution and gravitational potentials for general stationary systems. Then, we use our method to obtain particular solutions for the case of the Morgan & Morgan disks. The models obtained are fully analytical and correspond to the post-Newtonian generalizations of classical ones. We explore some properties of the models in order to estimate the importance of post-Newtonian corrections and we find that, contrary to the expectations, the main modifications appear far from the galaxy cores. As a by-product of this investigation we derive the corrected version of the tensor virial theorem. For stationary systems we recover the same result as in the Newtonian theory. However, for time dependent backgrounds we find that there is an extra piece that contributes to the variation of the inertia tensor.Comment: 30 pages, 8 figures. v2: Minor corrections and references added. Conclusions unchanged. v3: Version published in PR

A painless multi-level automatic goal-oriented hp-adaptive coarsening strategy for elliptic and non-elliptic problems

This work extends an automatic energy-norm $hp$-adaptive strategy based on performing quasi-optimal unrefinements to the case of non-elliptic problems and goal-oriented adaptivity. The proposed approach employs a multi-level hierarchical data structure and alternates global $h$- and $p$-refinements with a coarsening step. Thus, at each unrefinement step, we eliminate the basis functions with the lowest contributions to the solution. When solving elliptic problems using energy-norm adaptivity, the removed basis functions are those with the lowest contributions to the energy of the solution. For non-elliptic problems or goal-oriented adaptivity, we propose an upper bound of the error representation expressed in terms of an inner product of the specific equation, leading to error indicators that deliver quasi-optimal $hp$-unrefinements. This unrefinement strategy removes unneeded unknowns possibly introduced during the pre-asymptotical regime. In addition, the grids over which we perform the unrefinements are arbitrary, and thus, we can limit their size and associated computational costs. We numerically analyze our algorithm for energy-norm and goal-oriented adaptivity. In particular, we solve two-dimensional ($2$D) Poisson, Helmholtz, convection-dominated equations, and a three-dimensional ($3$D) Helmholtz-like problem. In all cases, we observe \revb{exponential} convergence rates. Our algorithm is robust and straightforward to implement; therefore, it can be easily adapted for industrial applications.BERC.2022-202

Nonadiabatic forces in ion-solid interactions: the initial stages of radiation damage

The Born-Oppenheimer approximation is the keystone for molecular dynamics simulations of radiation damage processes; however, actual materials response involves nonadiabatic energy exchange between nuclei and electrons. In this work, time dependent density functional theory is used to calculate the electronic excitations produced by energetic protons in Al. We study the influence of these electronic excitations on the interatomic forces and find that they differ substantially from the adiabatic case, revealing a nontrivial connection between electronic and nuclear stopping that is absent in the adiabatic case. These results unveil new effects in the early stages of radiation damage cascades

Identification of plasma and urinary metabolites and catabolites derived from orange juice (poly)phenols: analysis by high-performance liquid chromatography–high-resolution mass spectrometry

Orange juice is a rich source of (poly)phenols, in particular, the flavanones hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside. Following the acute consumption of 500 mL of orange juice containing 398 μmol of (poly)phenols by 12 volunteers, 0–24 h plasma and urine samples were analyzed by targeted high-performance liquid chromatography–high-resolution mass spectrometry in order to identify flavanone metabolites and phenolic acid and aromatic catabolites. A total of 19 flavanone metabolites—comprising di-O-glucuronide, O-glucuronide, O-glucuronyl-sulfate, and sulfate derivatives of hesperetin, naringenin, and eriodictyol—and 65 microbial-derived phenolic catabolites, such as phenylpropanoid, phenylpropionic, phenylacetic, benzoic, and hydroxycarboxylic acids and benzenetriol and benzoylglycine derivatives, including free phenolics and phase II sulfate, glucuronide, and methyl metabolites, were identified or partially identified in plasma and/or urine samples. The data obtained provide a detailed evaluation of the fate of orange juice (poly)phenols as they pass through the gastrointestinal tract and are absorbed into the circulatory system prior to renal excretion. Potential pathways for these conversions are proposed