Light 1-+ exotics: molecular resonances

Highlights in the search for nonconventional (non qqbar) meson states are the pi_1(1400) and pi_1(1600) exotic candidates. Should they exist, mounting theoretical arguments suggest that they are tetraquark molecular resonances excitable by meson rescattering. We report a new tetraquark calculation within a model field theory approximation to Quantum Chromodynamics in the Coulomb gauge supporting this conjecture. We also strengthen this claim by consistently contrasting results with exotic state predictions for hybrid (q qbar g) mesons within the same theoretical framework. Our findings confirm that molecular-like configurations involving two color singlets (a resonance, not a bound state) are clearly favored over hybrid or color-exotic tetraquark meson (q qbar q qbar atoms) formation. Finally, to assist needed further experimental searches we document a useful off-plane correlator for establishing the structure of these exotic systems along with similar, but anticipated much narrower, states that should exist in the charmonium and bottomonium spectra.Comment: 12 pages, 8 figure

Physical Interactions Driving the Activation/Inhibition of Calcium/Calmodulin Dependent Protein Kinase II

CaMKII is a protein kinase whose function is regulated by the binding of the Calcium/Calmodulin complex (Ca2+ /CaM). It is a major player in the Long Term Potentiation process where it acts as a molecular switch, oscillating between inhibited and active conformations. The mechanism for the switching is thought to be initiated by Ca2+/CaM binding, which allows the trans-phosphorylation of a subunit of CaMKII by a neighboring kinase, leading to the active state of the system. A combination of all-atom and coarse-grained MD simulations with free energy calculations, led us to reveal an interplay of electrostatic forces exerted by Ca2+/CaM on CaMKII, which initiate the activation process. The highly electrically charged Ca2+/CaM neutralizes basic regions in the linker domain of CaMKII, facilitating its opening and consequent activation. The emerging picture of CaMKII's behavior highlights the preponderance of electrostatic interactions, which are modulated by the presence of Ca2+/CaM and the phosphorylation of key sites.Fil: Asciutto, Eliana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; ArgentinaFil: Pantano, Sergio. Universidad Nacional de San Martín; Argentina. Instituto Pasteur de Montevideo; UruguayFil: General, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentin

Chiral phase transition in a covariant nonlocal NJL model

The properties of the chiral phase transition at finite temperature and chemical potential are investigated within a nonlocal covariant extension of the Nambu-Jona-Lasinio model based on a separable quark-quark interaction. We consider both the situation in which the Minkowski quark propagator has poles at real energies and the case where only complex poles appear. In the literature, the latter has been proposed as a realization of confinement. In both cases, the behaviour of the physical quantities as functions of T and μis found to be quite similar. In particular, for low values of T the chiral transition is always of first order and, for finite quark masses, at certain "end point" the transition turns into a smooth crossover. In the chiral limit, this "end point" becomes a "tricritical" point. Our predictions for the position of these points are similar, although somewhat smaller, than previous estimates. Finally, the relation between the deconfining transition and chiral restoration is also discussed.Instituto de Física La Plat

Franck-Condon principle for heavy-quark hadron decays

The Franck-Condon principle governing molecular electronic transitions is utilized to study heavy-quark hadron decays. This provides a direct assessment of the wavefunction of the parent hadron if the momentum distribution of the open-flavor decay products is measured. Model-independent results include an experimental distinction between quarkonium and exotica (hybrids, tetraquarks...), an off-plane correlator signature for tetraquarks and a direct probe of the sea quark orbital wavefunction relevant in the discussion of 3S_1 or 3P_0 decay mechanisms.Comment: Prepared for the Workshop on Scalar Mesons and Related Topics, Lisbon, 11-16 Feburary 200

Pl1 peptide engages acidic surfaces on tumor-associated fibronectin and tenascin isoforms to trigger cellular uptake

Tumor extracellular matrix (ECM) is a high-capacity target for the precision delivery of affinity ligand-guided drugs and imaging agents. Recently, we developed a PL1 peptide (sequence: PPRRGLIKLKTS) for systemic targeting of malignant ECM. Here, we map the dynamics of PL1 binding to its receptors Fibronectin Extra Domain B (FN-EDB) and Tenascin C C-isoform (TNC-C) by computational modeling and cell-free binding studies on mutated receptor proteins, and study cellular binding and internalization of PL1 nanoparticles in cultured cells. Molecular dynamics simulation and docking analysis suggested that the engagement of PL1 peptide with both receptors is primarily driven by electrostatic interactions. Substituting acidic amino acid residues with neutral amino acids at predicted PL1 binding sites in FN-EDB (D52N-D49N-D12N) and TNC-C (D39N-D45N) resulted in the loss of binding of PL1 nanoparticles. Remarkably, PL1-functionalized nanoparticles (NPs) were not only deposited on the target ECM but bound the cells and initiated a robust cellular uptake via a pathway resembling macropinocytosis. Our studies establish the mode of engagement of the PL1 peptide with its receptors and suggest applications for intracellular delivery of nanoscale payloads. The outcomes of this work can be used for the development of PL1-derived peptides with improved stability, affinity, and specificity for precision targeting of the tumor ECM and malignant cells.Fil: Lingasamy, Prakash. University of Tartu; EstoniaFil: Põnograjeva, Kristina. University of Tartu; EstoniaFil: Kopanchuk, Sergei. University of Tartu; EstoniaFil: Tobi, Allan. University of Tartu; EstoniaFil: Rinken, Ago. University of Tartu; EstoniaFil: General, Ignacio. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Asciutto, Eliana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; ArgentinaFil: Teesalu, Tambet. University of Tartu; Estoni

Coulomb gauge approach to scalar hadrons

The Coulomb gauge model, involving an effective QCD Hamiltonian in the Coulomb gauge, is applied to scalar hadrons. Mass predictions are presented for both conventional q-qbar meson and q-qbar-q-qbar tetra-quark states. Mixing matrix elements between these states were also computed and diagonalized to provide a reasonable description of the scalar spectrum below 2 GeV.Comment: Prepared for the Workshop on Scalar Mesons and Related Topics, Lisbon, 11-16 Feburary 200

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a “driver” phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine–substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.Fil: Lui, Vivian Wai Yan. University of Pittsburgh; Estados UnidosFil: Peyser, Noah D.. University of Pittsburgh; Estados UnidosFil: Ng, Patrick Kwok-Shing. University Of Texas Md Anderson Cancer Center;Fil: Hritz, Jozef. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados Unidos. Masaryk University; República ChecaFil: Zeng, Yan. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Lu, Yiling. University Of Texas Md Anderson Cancer Center;Fil: Li, Hua. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Wang, Lin. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Gilbert, Breean R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: General, Ignacio. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Bahar, Ivet. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Ju, Zhenlin. University Of Texas Md Anderson Cancer Center;Fil: Wang, Zhenghe. Case Western Reserve University; Estados UnidosFil: Pendleton, Kelsey P.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Xiao, Xiao. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Du, Yu. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Vries, John K.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Hammerman, Peter S.. Harvard Medical School; Estados UnidosFil: Garraway, Levi A.. Harvard Medical School; Estados UnidosFil: Mills, Gordon B.. University Of Texas Md Anderson Cancer Center;Fil: Johnson, Daniel E.. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Grandis, Jennifer R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados Unido

Lloyd's

Resumen: Estudio de la originalidad e influencia en la actividad aseguradora de la Corporación Lloid’s Underwriters, analizando su psicología, su historia y las características de las operaciones contratadas, los Lloid’s Underwriters y los Lloid’s Brokers

Acércate a Europa

La idea de Europa es muy antigua. También lo es la historia de la unidad europea. Sin embargo, el proyecto que más ha profundizado en la integración de Europa no surgió hasta después de la Segunda Guerra Mundial con la Declaración Schuman, la Comunidad Económica del Carbón y del Acero (CECA) y en 1957 con la Comunidad Europea de la Energía Atómica -CEEA o EURATOM- y con la Comunidad Económica Europea, actual Unión Europea. El camino ha sido largo y complicado