Toward an Ising Model of Cancer and Beyond

Theoretical and computational tools that can be used in the clinic to predict neoplastic progression and propose individualized optimal treatment strategies to control cancer growth is desired. To develop such a predictive model, one must account for the complex mechanisms involved in tumor growth. Here we review resarch work that we have done toward the development of an "Ising model" of cancer. The review begins with a description of a minimalist four-dimensional (three in space and one in time) cellular automaton (CA) model of cancer in which healthy cells transition between states (proliferative, hypoxic, and necrotic) according to simple local rules and their present states, which can viewed as a stripped-down Ising model of cancer. This model is applied to model the growth of glioblastoma multiforme, the most malignant of brain cancers. This is followed by a discussion of the extension of the model to study the effect on the tumor dynamics and geometry of a mutated subpopulation. A discussion of how tumor growth is affected by chemotherapeutic treatment is then described. How angiogenesis as well as the heterogeneous and confined environment in which a tumor grows is incorporated in the CA model is discussed. The characterization of the level of organization of the invasive network around a solid tumor using spanning trees is subsequently described. Then, we describe open problems and future promising avenues for future research, including the need to develop better molecular-based models that incorporate the true heterogeneous environment over wide range of length and time scales (via imaging data), cell motility, oncogenes, tumor suppressor genes and cell-cell communication. The need to bring to bear the powerful machinery of the theory of heterogeneous media to better understand the behavior of cancer in its microenvironment is presented.Comment: 55 pages, 21 figures and 3 tables. To appear in Physical Biology. Added reference

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP)(1). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed(2-6). Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions(7), is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions(8,9), but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results(10,11), indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.Peer reviewe

Constraints on jet quenching in p-Pb collisions at root s(NN)=5.02 TeV measured by the event-activity dependence of semi-inclusive hadron-jet distributions

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high-transverse momentum trigger hadron in p-Pb collisions at root s(NN) = 5.02TeV. Jets are reconstructed from charged-particle tracks using the anti-k(T) algorithm with resolution parameter R = 0.2 and 0.4. A data-driven statistical approach is used to correct the uncorrelated background jet yield. Recoil jet distributions are reported for jet transverse momentum 15 < p(T,jet)(ch) < 50 GeV/c and are compared in various intervals of p-Pb event activity, based on charged-particle multiplicity and zero-degree neutral energy in the forward (Pb-going) direction. The semi-inclusive observable is self-normalized and such comparisons do not require the interpretation of p-Pb event activity in terms of collision geometry, in contrast to inclusive jet observables. These measurements provide new constraints on the magnitude of jet quenching in small systems at the LHC. In p-Pb collisions with high event activity, the average medium-induced out-of-cone energy transport for jets with R = 0.4 and 15 < p(T,jet)(ch) < 50 GeV/c is measured to be less than 0.4 GeV/c at 90% confidence, which is over an order of magnitude smaller than a similar measurement for central Pb-Pb collisions at root s(NN) = 2.76 TeV. Comparison is made to theoretical calculations of jet quenching in small systems, and to inclusive jet measurements in p-Pb collisions selected by event activity at the LHC and in d-Au collisions at RHIC.78395113CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOSem informaçãoSem informaçãoSem informaçãoAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

Insight into particle production mechanisms via angular correlations of identified particles in pp collisions at root s=7 TeV

Sem informaçãoTwo-particle angular correlations were measured in pp collisions at root s = 7 TeV for pions, kaons, protons, and lambdas, for all particle/anti-particle combinations in the pair. Data for mesons exhibit an expected peak dominated by effects associated with mini-jets and are well reproduced by general purpose Monte Carlo generators. However, for baryon-baryon and anti-baryon-anti-baryon pairs, where both particles have the same baryon number, a near-side anti-correlation structure is observed instead of a peak. This effect is interpreted in the context of baryon production mechanisms in the fragmentation process. It currently presents a challenge to Monte Carlo models and its origin remains an open question.778117Sem informaçãoSem informaçãoSem informaçãoFunded by SCOAP3

Global baryon number conservation encoded in net-proton fluctuations measured in Pb–Pb collisions at √sNN = 2.76 TeV

Experimental results are presented on event-by-event net-proton fluctuation measurements in Pb–Pb collisions at √SNN=2.76 TeV, recorded by the ALICE detector at the CERN LHC. These measurements have as their ultimate goal an experimental test of Lattice QCD (LQCD) predictions on second and higher order cumulants of net-baryon distributions to search for critical behavior near the QCD phase boundary. Before confronting them with LQCD predictions, account has to be taken of correlations stemming from baryon number conservation as well as fluctuations of participating nucleons. Both effects influence the experimental measurements and are usually not considered in theoretical calculations. For the first time, it is shown that event-by-event baryon number conservation leads to subtle long-range correlations arising from very early interactions in the collisions.publishedVersio

Measurement of the production of high-p(T) electrons from heavy-flavour hadron decays in Pb-Pb collisions at root s(NN)=2.76 TeV

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPElectrons from heavy-flavour hadron decays (charm and beauty) were measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass of energy root s(NN) = 2.76 TeV. The transverse momentum (pT) differential production yields at mid-rapidity were used to calculate the nuclear modification factor R-AA in the interval 3 < p(T) < 18 GeV/c. The R-AA shows a strong suppression compared to binary scaling of pp collisions at the same energy (up to a factor of 4) in the 10% most central Pb-Pb collisions. There is a centrality trend of suppression, and a weaker suppression (down to a factor of 2) in semi-peripheral (50-80%) collisions is observed. The suppression of electrons in this broad p(T) interval indicates that both charm and beauty quarks lose energy when they traverse the hot medium formed in Pb-Pb collisions at LHC.771467481CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informaçãoSem informaçãoSem informaçãoThe ALICE Collaboration would like to thank all its engineers and technicians for their invaluable contributions to the construction of the experiment and the CERN accelerator teams for the outstanding performance of the LHC complex. The ALICE Collaboration gratefully acknowledges the resources and support provided by all Grid centres and the Worldwide LHC Computing Grid (WLCG) collaboration. The ALICE Collaboration acknowledges the following funding agencies for their support in building and running the ALICE detector: A.I. Alikhanyan National Science Laboratory (Yerevan Physics Institute) Foundation (ANSL), State Committee of Science and World Federation of Scientists (WFS), Armenia; Austrian Academy of Sciences and Nationalstiftung für Forschung, Technologie und Entwicklung, Austria; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (Finep) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil; Ministry of Education of China (MOE of China), Ministry of Science & Technology of China (MOST of China) and National Natural Science Foundation of China (NSFC), China; Ministry of Science, Education and Sports and Croatian Science Foundation, Croatia; Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Cuba; Ministry of Education, Youth and Sports of the Czech Republic, Czech Republic; Danish National Research Foundation (DNRF), The Carlsberg Foundation and The Danish Council for Independent Research–Natural Sciences, Denmark; Helsinki Institute of Physics (HIP), Finland; Commissariat à l'Energie Atomique (CEA) and Institut National de Physique Nucléaire et de Physique des Particules (IN2P3) and Centre National de la Recherche Scientifique (CNRS), France; Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (BMBF) and GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany; Ministry of Education, Research and Religious Affairs, Greece; National Research, Development and Innovation Office, Hungary; Department of Atomic Energy, Government of India (DAE), India; Indonesian Institute of Science, Indonesia; Centro Fermi – Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi and Istituto Nazionale di Fisica Nucleare (INFN), Italy; Institute for Innovative Science and Technology, Nagasaki Institute of Applied Science (IIST), Japan Society for the Promotion of Science (JSPS) KAKENHI and Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; Consejo Nacional de Ciencia y Tecnología (CONACYT), through Fondo de Cooperación Internacional en Ciencia y Tecnología (FONCICYT) and Dirección General de Asuntos del Personal Academico (DGAPA), Mexico; Nationaal instituut voor subatomaire fysica (Nikhef), Netherlands; The Research Council of Norway, Norway; Commission on Science and Technology for Sustainable Development in the South (COMSATS), Pakistan; Pontificia Universidad Católica del Perú, Peru; Ministry of Science and Higher Education and National Science Centre, Poland; Ministry of Education and Scientific Research, Institute of Atomic Physics and Romanian National Agency for Science, Technology and Innovation, Romania; Joint Institute for Nuclear Research (JINR), Ministry of Education and Science of the Russian Federation and National Research Centre Kurchatov Institute, Russia; Ministry of Education, Science, Research and Sport of the Slovak Republic, Slovakia; National Research Foundation of South Africa, South Africa; Korea Institute of Science and Technology Information and National Research Foundation of Korea (NRF), South Korea; Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Ministerio de Ciencia e Innovacion, Spain; Knut & Alice Wallenberg Foundation (KAW) and Swedish Research Council (VR), Sweden; European Organization for Nuclear Research, Switzerland; National Science and Technology Development Agency (NSDTA), Office of the Higher Education Commission under NRU project of Thailand and Suranaree University of Technology (SUT), Thailand; Turkish Atomic Energy Agency (TAEK), Turkey; National Academy of Sciences of Ukraine, Ukraine; Science and Technology Facilities Council (STFC), United Kingdom; National Science Foundation of the United States of America (NSF) and United States Department of Energy, Office of Nuclear Physics (DOE NP), United States