Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions.

Glucose is vital for life, serving as both a source of energy and carbon building block for growth. When glucose is limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss of glucose, we performed nutrient-sensitized genome-wide genetic screens and a PRISM growth assay across 482 cancer cell lines. We report that catabolism of uridine from the medium enables the growth of cells in the complete absence of glucose. While previous studies have shown that uridine can be salvaged to support pyrimidine synthesis in the setting of mitochondrial oxidative phosphorylation deficiency <sup>1</sup> , our work demonstrates that the ribose moiety of uridine or RNA can be salvaged to fulfil energy requirements via a pathway based on: (1) the phosphorylytic cleavage of uridine by uridine phosphorylase UPP1/UPP2 into uracil and ribose-1-phosphate (R1P), (2) the conversion of uridine-derived R1P into fructose-6-P and glyceraldehyde-3-P by the non-oxidative branch of the pentose phosphate pathway and (3) their glycolytic utilization to fuel ATP production, biosynthesis and gluconeogenesis. Capacity for glycolysis from uridine-derived ribose appears widespread, and we confirm its activity in cancer lineages, primary macrophages and mice in vivo. An interesting property of this pathway is that R1P enters downstream of the initial, highly regulated steps of glucose transport and upper glycolysis. We anticipate that 'uridine bypass' of upper glycolysis could be important in the context of disease and even exploited for therapeutic purposes

Supersymmetric Unification Without Low Energy Supersymmetry And Signatures for Fine-Tuning at the LHC

The cosmological constant problem is a failure of naturalness and suggests that a fine-tuning mechanism is at work, which may also address the hierarchy problem. An example -- supported by Weinberg's successful prediction of the cosmological constant -- is the potentially vast landscape of vacua in string theory, where the existence of galaxies and atoms is promoted to a vacuum selection criterion. Then, low energy SUSY becomes unnecessary, and supersymmetry -- if present in the fundamental theory -- can be broken near the unification scale. All the scalars of the supersymmetric standard model become ultraheavy, except for a single finely tuned Higgs. Yet, the fermions of the supersymmetric standard model can remain light, protected by chiral symmetry, and account for the successful unification of gauge couplings. This framework removes all the difficulties of the SSM: the absence of a light Higgs and sparticles, dimension five proton decay, SUSY flavor and CP problems, and the cosmological gravitino and moduli problems. High-scale SUSY breaking raises the mass of the light Higgs to about 120-150 GeV. The gluino is strikingly long lived, and a measurement of its lifetime can determine the ultraheavy scalar mass scale. Measuring the four Yukawa couplings of the Higgs to the gauginos and higgsinos precisely tests for high-scale SUSY. These ideas, if confirmed, will demonstrate that supersymmetry is present but irrelevant for the hierarchy problem -- just as it has been irrelevant for the cosmological constant problem -- strongly suggesting the existence of a fine-tuning mechanism in nature.Comment: Typos and equations fixed, references adde

Search for Sub-TeV Gamma Rays Coincident with BATSE Gamma Ray Bursts

Project GRAND is a 100m x 100m air shower array of proportional wire chambers (PWCs). There are 64 stations each with eight 1.29 m^2 PWC planes arranged in four orthogonal pairs placed vertically above one another to geometrically measure the angles of charged secondaries. A steel plate above the bottom pair of PWCs differentiates muons (which pass undeflected through the steel) from non-penetrating particles. FLUKA Monte Carlo studies show that a TeV gamma ray striking the atmosphere at normal incidence produces 0.23 muons which reach ground level where their angles and identities are measured. Thus, paradoxically, secondary muons are used as a signature for gamma ray primaries. The data are examined for possible angular and time coincidences with eight gamma ray bursts (GRBs) detected by BATSE. Seven of the GRBs were selected because of their good acceptance by GRAND and high BATSE Fluence. The eighth GRB was added due to its possible coincident detection by Milagrito. For each of the eight candidate GRBs, the number of excess counts during the BATSE T90 time interval and within plus or minus five degrees of BATSE's direction was obtained. The highest statistical significance reported in this paper (2.7 sigma) is for the event that was predicted to be the most likely to be observed (GRB 971110).Comment: To be presented at the XXVIII International Cosmic Ray Conference, Tsukuba, Japa

Multiscale magnetic underdense regions on the solar surface: Granular and Mesogranular scales

The Sun is a non-equilibrium dissipative system subjected to an energy flow which originates in its core. Convective overshooting motions create temperature and velocity structures which show a temporal and spatial evolution. As a result, photospheric structures are generally considered to be the direct manifestation of convective plasma motions. The plasma flows on the photosphere govern the motion of single magnetic elements. These elements are arranged in typical patterns which are observed as a variety of multiscale magnetic patterns. High resolution magnetograms of quiet solar surface revealed the presence of magnetic underdense regions in the solar photosphere, commonly called voids, which may be considered a signature of the underlying convective structure. The analysis of such patterns paves the way for the investigation of all turbulent convective scales from granular to global. In order to address the question of magnetic structures driven by turbulent convection at granular and mesogranular scales we used a "voids" detection method. The computed voids distribution shows an exponential behavior at scales between 2 and 10 Mm and the absence of features at 5-10 Mm mesogranular scales. The absence of preferred scales of organization in the 2-10 Mm range supports the multiscale nature of flows on the solar surface and the absence of a mesogranular convective scale

VFISV: Very Fast Inversion of the Stokes Vector for the Helioseismic and Magnetic Imager

In this paper we describe in detail the implementation and main properties of a new inversion code for the polarized radiative transfer equation (VFISV: Very Fast inversion of the Stokes vector). VFISV will routinely analyze pipeline data from the Helioseismic and Magnetic Imager (HMI) on-board of the Solar Dynamics Observatory (SDO). It will provide full-disk maps (4096$\times$4096 pixels) of the magnetic field vector on the Solar Photosphere every 10 minutes. For this reason VFISV is optimized to achieve an inversion speed that will allow it to invert 16 million pixels every 10 minutes with a modest number (approx. 50) of CPUs. Here we focus on describing a number of important details, simplifications and tweaks that have allowed us to significantly speed up the inversion process. We also give details on tests performed with data from the spectropolarimeter on-board of the Hinode spacecraft.Comment: 23 pages, 9 figures (2 color). Submitted for publication to Solar Physic

Analytical, experimental and numerical study of a graded honeycomb structure under in-plane impact load with low velocity

Given the significance of energy absorption in various industries, light shock absorbers such as honeycomb structure under in-plane and out-of-plane loads have been in the core of attention. The purpose of this research is the analyses of graded honeycomb structure (GHS) behaviour under in-plane impact loading and its optimisation. Primarily, analytical equations for plateau stress and specific energy are represented, taking power hardening model (PHM) and elastic–perfectly plastic model (EPPM) into consideration. For the validation and comparison of acquired analytical equations, the energy absorption of a GHS made of five different aluminium grades is simulated in ABAQUS/CAE. In order to validate the numerical simulation method in ABAQUS, an experimental test has been conducted as the falling a weight with low velocity on a GHS. Numerical results retain an acceptable accordance with experimental ones with a 5.4% occurred error of reaction force. For a structure with a specific kinetic energy, the stress–strain diagram is achieved and compared with the analytical equations obtained. The maximum difference between the numerical and analytical plateau stresses for PHM is 10.58%. However, this value has been measured to be 38.78% for EPPM. In addition, the numerical value of absorbed energy is compared to that of analytical method for two material models. The maximum difference between the numerical and analytical absorbed energies for PHM model is 6.4%, while it retains the value of 48.08% for EPPM. Based on the conducted comparisons, the numerical and analytical results based on PHM are more congruent than EPPM results. Applying sequential quadratic programming method and genetic algorithm, the ratio of structure mass to the absorbed energy is minimised. According to the optimisation results, the structure capacity of absorbing energy increases by 18% compared to the primary model

Gamma Ray Bursts as Probes of Quantum Gravity

Gamma ray bursts (GRBs) are short and intense pulses of $\gamma$-rays arriving from random directions in the sky. Several years ago Amelino-Camelia et al. pointed out that a comparison of time of arrival of photons at different energies from a GRB could be used to measure (or obtain a limit on) possible deviations from a constant speed of light at high photons energies. I review here our current understanding of GRBs and reconsider the possibility of performing these observations.Comment: Lectures given at the 40th winter school of theretical physics: Quantum Gravity and Phenomenology, Feb. 2004 Polan

Realising the Olympic dream: vision, support and challenge

The sporting arena is replete with examples and anecdotes of great inspirational coaches that have led teams to success, often in the face of adversity and against seemingly better opponents. The role of the coach in developing and motivating athletes has also been the focus of much research in sport psychology (e.g., Challaduria 1990; Smith & Smoll, 2007). Despite the ease with which one readily accepts that coaches can be inspirational, the sport coaching literature is somewhat devoid of research on inspirational coaches and the effects of such coaches on athletic success. The purpose of the current paper is to theoretically delineate the inspirational effects of coaches in sport. Given the relative paucity of inspiration-related research in sport we draw upon contemporary theories of leadership from organisational and military psychology (e.g., transformational and charismatic leadership theories). We propose a sport-specific model of leadership that centres around the vision, support, and challenge meta-cognitive model developed by Arthur and Hardy in military contexts. The model posits that �great� coaches inspire their athletes by: (a) creating an inspirational vision of the future; (b) providing the necessary support to achieve the vision; and (c) providing the challenge to achieve the vision. The underlying proposition is that the vision provides meaning and direction for followers� effort. That is, the vision serves as the beacon around which all the sweat, pain and sacrifice involved in achieving success at the highest level in sport is directed. At the heart of this model is the notion that athletes can achieve their dreams provided they are inspired to do so; this is because all other things being equal the person who is motivated to practice longer and train harder will ultimately be the best. The current paper will delineate the coach�s role in inspiring the athlete to train harder and longer

Fermi acceleration in astrophysical jets

We consider the acceleration of energetic particles by Fermi processes (i.e., diffusive shock acceleration, second order Fermi acceleration, and gradual shear acceleration) in relativistic astrophysical jets, with particular attention given to recent progress in the field of viscous shear acceleration. We analyze the associated acceleration timescales and the resulting particle distributions, and discuss the relevance of these processes for the acceleration of charged particles in the jets of AGNs, GRBs and microquasars, showing that multi-component powerlaw-type particle distributions are likely to occur.Comment: 6 pages, one figure; based on talk at "The multimessenger approach to unidentified gamma-ray sources", Barcelona/Spain, July 2006; accepted for publication in Astrophysics and Space Scienc