Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer

Metabolic remodeling is now widely regarded as a hallmark of cancer, but it is not clear whether individual metabolic strategies are frequently exploited by many tumours. Here we compare messenger RNA profiles of 1,454 metabolic enzymes across 1,981 tumours spanning 19 cancer types to identify enzymes that are consistently differentially expressed. Our meta-analysis recovers established targets of some of the most widely used chemotherapeutics, including dihydrofolate reductase, thymidylate synthase and ribonucleotide reductase, while also spotlighting new enzymes, such as the mitochondrial proline biosynthetic enzyme PYCR1. The highest scoring pathway is mitochondrial one-carbon metabolism and is centred on MTHFD2. MTHFD2 RNA and protein are markedly elevated in many cancers and correlated with poor survival in breast cancer. MTHFD2 is expressed in the developing embryo, but is absent in most healthy adult tissues, even those that are proliferating. Our study highlights the importance of mitochondrial compartmentalization of one-carbon metabolism in cancer and raises important therapeutic hypotheses

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): first annual report†

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) was founded on 10 December 2009 with the initiative of Roland Hetzer (Deutsches Herzzentrum Berlin, Berlin, Germany) and Jan Gummert (Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Germany) with 15 other founding international members. It aims to promote scientific research to improve care of end-stage heart failure patients with ventricular assist device or a total artificial heart as long-term mechanical circulatory support. Likewise, the organization aims to provide and maintain a registry of device implantation data and long-term follow-up of patients with mechanical circulatory support. Hence, EUROMACS affiliated itself with Dendrite Clinical Systems Ltd to offer its members a software tool that allows input and analysis of patient clinical data on a daily basis. EUROMACS facilitates further scientific studies by offering research groups access to any available data wherein patients and centres are anonymized. Furthermore, EUROMACS aims to stimulate cooperation with clinical and research institutions and with peer associations involved to further its aims. EUROMACS is the only European-based Registry for Patients with Mechanical Circulatory Support with rapid increase in institutional and individual membership. Because of the expeditious data input, the European Association for Cardiothoracic Surgeons saw the need to optimize the data availability and the significance of the registry to improve care of patients with mechanical circulatory support and its potential contribution to scientific intents; hence, the beginning of their alliance in 2012. This first annual report is designed to provide an overview of EUROMACS' structure, its activities, a first data collection and an insight to its scientific contribution

Event-by-Event Fluctuations in Particle Multiplicities and Transverse Energy Produced in 158.A GeV Pb+Pb collisions

Event-by-event fluctuations in the multiplicities of charged particles and photons, and the total transverse energy in 158$\cdot A$ GeV Pb+Pb collisions are studied for a wide range of centralities. For narrow centrality bins the multiplicity and transverse energy distributions are found to be near perfect Gaussians. The effect of detector acceptance on the multiplicity fluctuations has been studied and demonstrated to follow statistical considerations. The centrality dependence of the charged particle multiplicity fluctuations in the measured data has been found to agree reasonably well with those obtained from a participant model. However for photons the multiplicity fluctuations has been found to be lower compared to those obtained from a participant model. The multiplicity and transverse energy fluctuations have also been compared to those obtained from the VENUS event generator.Comment: To appear in Physical Review C; changes : more detailed discussion on errors and few figures modifie

Particle density fluctuations

Event-by-event fluctuations in the multiplicities of charged particles and photons at SPS energies are discussed. Fluctuations are studied by controlling the centrality of the reaction and rapidity acceptance of the detectors. Results are also presented on the event-by-event study of correlations between the multiplicity of charged particles and photons to search for DCC-like signals.Comment: Talk presented at Quark Matter 2002, Nantes, Franc

Azimuthal Anisotropy of Photon and Charged Particle Emission in Pb+Pb Collisions at 158 A GeV/c

The azimuthal distributions of photons and charged particles with respect to the event plane are investigated as a function of centrality in Pb + Pb collisions at 158 A GeV/c in the WA98 experiment at the CERN SPS. The anisotropy of the azimuthal distributions is characterized using a Fourier analysis. For both the photon and charged particle distributions the first two Fourier coefficients are observed to decrease with increasing centrality. The observed anisotropies of the photon distributions compare well with the expectations from the charged particle measurements for all centralities.Comment: 8 pages and 6 figures. The manuscript has undergone a major revision. The unwanted correlations were enhanced in the random subdivision method used in the earlier version. The present version uses the more established method of division into subevents separated in rapidity to minimise short range correlations. The observed results for charged particles are in agreement with results from the other experiments. The observed anisotropy in photons is explained using flow results of pions and the correlations arising due to the decay of the neutral pion

Interferometry of Direct Photons in Central 280Pb+208Pb Collisions at 158A GeV

Two-particle correlations of direct photons were measured in central 208Pb+208Pb collisions at 158 AGeV. The invariant interferometric radii were extracted for 100<K_T<300 MeV/c and compared to radii extracted from charged pion correlations. The yield of soft direct photons, K_T<300 MeV/c, was extracted from the correlation strength and compared to theoretical calculations.Comment: 5 pages, 4 figure

Suppression of High-p_T Neutral Pion Production in Central Pb+Pb Collisions at sqrt{s_NN} = 17.3 GeV Relative to p+C and p+Pb Collisions

Neutral pion transverse momentum spectra were measured in p+C and p+Pb collisions at sqrt{s_NN} = 17.4 GeV at mid-rapidity 2.3 < eta_lab < 3.0 over the range 0.7< p_T < 3.5 GeV/c. The spectra are compared to pi0 spectra measured in Pb+Pb collisions at sqrt{s_NN} = 17.3 GeV in the same experiment. For a wide range of Pb+Pb centralities (N_part < 300) the yield of pi0's with p_T > 2 GeV/c is larger than or consistent with the p+C or p+Pb yields scaled with the number of nucleon-nucleon collisions (N_coll), while for central Pb+Pb collisions with N_part > 350 the pi0 yield is suppressed.Comment: 5 pages, 4 figure

Search for DCC in 158A GeV Pb+Pb Collisions

A detailed analysis of the phase space distributions of charged particles and photons have been carried out using two independent methods. The results indicate the presence of nonstatistical fluctuations in localized regions of phase space.Comment: Talk at the PANIC99 Conference, June 9-16, 199

Present Status and Future of DCC Analysis

Disoriented Chiral Condensates (DCC) have been predicted to form in high energy heavy ion collisions where the approximate chiral symmetry of QCD has been restored. This leads to large imbalances in the production of charged to neutral pions. Sophisticated analysis methods are being developed to disentangle DCC events out of the large background of events with conventionally produced particles. We present a short review of current analysis methods and future prospects.Comment: 12 pages, 5 figures. Invited talk presented at the 13th International Conference on Ultrarelativistic Nucleus-Nucleus Collisions (Quark Matter 97), Tsukuba, Japan, 1-5 Dec 199

Central Pb+Pb Collisions at 158 A GeV/c Studied by Pion-Pion Interferometry

Two-particle correlations have been measured for identified negative pions from central 158 AGeV Pb+Pb collisions and fitted radii of about 7 fm in all dimensions have been obtained. A multi-dimensional study of the radii as a function of kT is presented, including a full correction for the resolution effects of the apparatus. The cross term Rout-long of the standard fit in the Longitudinally CoMoving System (LCMS) and the vl parameter of the generalised Yano-Koonin fit are compatible with 0, suggesting that the source undergoes a boost invariant expansion. The shapes of the correlation functions in Qinv and Qspace have been analyzed in detail. They are not Gaussian but better represented by exponentials. As a consequence, fitting Gaussians to these correlation functions may produce different radii depending on the acceptance of the experimental setup used for the measurement.Comment: 13 pages including 10 figure