Biogenesis of HLA Ligand Presentation in Immune Cells Upon Activation Reveals Changes in Peptide Length Preference.

Induction of an effective tumor immunity is a complex process that includes the appropriate presentation of the tumor antigens, activation of specific T cells, and the elimination of malignant cells. Potent and efficient T cell activation is dependent on multiple factors, such as timely expression of co-stimulatory molecules, the differentiation state of professional antigen presenting cells (e.g., dendritic cells; DCs), the functionality of the antigen processing and presentation machinery (APPM), and the repertoire of HLA class I and II-bound peptides (termed immunopeptidome) presented to T cells. So far, how molecular perturbations underlying DCs maturation and differentiation affect the in vivo cross-presented HLA class I and II immunopeptidomes is largely unknown. Yet, this knowledge is crucial for further development of DC-based immunotherapy approaches. We applied a state-of-the-art sensitive MS-based immunopeptidomics approach to characterize the naturally presented HLA-I and -II immunopeptidomes eluted from autologous immune cells having distinct functional and biological states including CD14 <sup>+</sup> monocytes, immature DC (ImmDC) and mature DC (MaDC) monocyte-derived DCs and naive or activated T and B cells. We revealed a presentation of significantly longer HLA peptides upon activation that is HLA allotype specific. This was apparent in the self-peptidome upon cell activation and in the context of presentation of exogenously loaded antigens, suggesting that peptide length is an important feature with potential implications on the rational design of anti-cancer vaccines

Distribution of graph-distances in Boltzmann ensembles of RNA secondary structures

Large RNA molecules often carry multiple functional domains whose spatial arrangement is an important determinant of their function. Pre-mRNA splicing, furthermore, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium therefore provides useful information on the overall shape of the molecule can provide insights into the interplay of its functional domains. Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between arbitrary nucleotides can be computed in polynomial time by means of dynamic programming. A naive implementation would yield recursions with a very high time complexity of O(n^11). Although we were able to reduce this to O(n^6) for many practical applications a further reduction seems difficult. We conclude, therefore, that sampling approaches, which are much easier to implement, are also theoretically favorable for most real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Uniqueness Theorem for Generalized Maxwell Electric and Magnetic Black Holes in Higher Dimensions

Based on the conformal energy theorem we prove the uniqueness theorem for static higher dimensional electrically and magnetically charged black holes being the solution of Einstein (n-2)-gauge forms equations of motion. Black hole spacetime contains an asymptotically flat spacelike hypersurface with compact interior and non-degenerate components of the event horizon.Comment: 7 pages, RevTex, to be published in Phys.Rev.D1

On the `Stationary Implies Axisymmetric' Theorem for Extremal Black Holes in Higher Dimensions

All known stationary black hole solutions in higher dimensions possess additional rotational symmetries in addition to the stationary Killing field. Also, for all known stationary solutions, the event horizon is a Killing horizon, and the surface gravity is constant. In the case of non-degenerate horizons (non-extremal black holes), a general theorem was previously established [gr-qc/0605106] proving that these statements are in fact generally true under the assumption that the spacetime is analytic, and that the metric satisfies Einstein's equation. Here, we extend the analysis to the case of degenerate (extremal) black holes. It is shown that the theorem still holds true if the vector of angular velocities of the horizon satisfies a certain "diophantine condition," which holds except for a set of measure zero.Comment: 30pp, Latex, no figure

Nonequilibrium phase transitions induced by multiplicative noise: effects of self-correlation

A recently introduced lattice model, describing an extended system which exhibits a reentrant (symmetry-breaking, second-order) noise-induced nonequilibrium phase transition, is studied under the assumption that the multiplicative noise leading to the transition is colored. Within an effective Markovian approximation and a mean-field scheme it is found that when the self-correlation time of the noise is different from zero, the transition is also reentrant with respect to the spatial coupling D. In other words, at variance with what one expects for equilibrium phase transitions, a large enough value of D favors disorder. Moreover, except for a small region in the parameter subspace determined by the noise intensity and D, an increase in the self-correlation time usually preventsthe formation of an ordered state. These effects are supported by numerical simulations.Comment: 15 pages. 9 figures. To appear in Phys.Rev.

Isotopic composition of fragments in multifragmentation of very large nuclear systems: effects of the chemical equilibrium

Studies on the isospin of fragments resulting from the disassembly of highly excited large thermal-like nuclear emitting sources, formed in the ^{197}Au + ^{197}Au reaction at 35 MeV/nucleon beam energy, are presented. Two different decay systems (the quasiprojectile formed in midperipheral reactions and the unique source coming from the incomplete fusion of projectile and target in the most central collisions) were considered; these emitting sources have the same initial N/Z ratio and excitation energy (E^* ~= 5--6 MeV/nucleon), but different size. Their charge yields and isotopic content of the fragments show different distributions. It is observed that the neutron content of intermediate mass fragments increases with the size of the source. These evidences are consistent with chemical equilibrium reached in the systems. This fact is confirmed by the analysis with the statistical multifragmentation model.Comment: 9 pages, 4 ps figure

Isotopic Scaling of Heavy Projectile Residues from the collisions of 25 MeV/nucleon 86Kr with 124Sn, 112Sn and 64Ni, 58Ni

The scaling of the yields of heavy projectile residues from the reactions of 25 MeV/nucleon 86Kr projectiles with 124Sn,112Sn and 64Ni, 58Nitargets is studied. Isotopically resolved yield distributions of projectile fragments in the range Z=10-36 from these reaction pairs were measured with the MARS recoil separator in the angular range 2.7-5.3 degrees. The velocities of the residues, monotonically decreasing with Z down to Z~26-28, are employed to characterize the excitation energy. The yield ratios R21(N,Z) for each pair of systems are found to exhibit isotopic scaling (isoscaling), namely, an exponential dependence on the fragment atomic number Z and neutron number N. The isoscaling is found to occur in the residue Z range corresponding to the maximum observed excitation energies. The corresponding isoscaling parameters are alpha=0.43 and beta=-0.50 for the Kr+Sn system and alpha=0.27 and beta=-0.34 for the Kr+Ni system. For the Kr+Sn system, for which the experimental angular acceptance range lies inside the grazing angle, isoscaling was found to occur for Z<26 and N<34. For heavier fragments from Kr+Sn, the parameters vary monotonically, alpha decreasing with Z and beta increasing with N. This variation is found to be related to the evolution towards isospin equilibration and, as such, it can serve as a tracer of the N/Z equilibration process. The present heavy-residue data extend the observation of isotopic scaling from the intermediate mass fragment region to the heavy-residue region. Such high-resolution mass spectrometric data can provide important information on the role of isospin in peripheral and mid-peripheral collisions, complementary to that accessible from modern large-acceptance multidetector devices.Comment: 8 pages, 6 figures, submitted to Phys. Rev.

Collective modes of asymmetric nuclear matter in Quantum HadroDynamics

We discuss a fully relativistic Landau Fermi liquid theory based on the Quantum Hadro-Dynamics ($QHD$) effective field picture of Nuclear Matter ({\it NM}). From the linearized kinetic equations we get the dispersion relations of the propagating collective modes. We focus our attention on the dynamical effects of the interplay between scalar and vector channel contributions. A beautiful ``mirror'' structure in the form of the dynamical response in the isoscalar/isovector degree of freedom is revealed, with a complete parallelism in the role respectively played by the compressibility and the symmetry energy. All that strongly supports the introduction of an explicit coupling to the scalar-isovector channel of the nucleon-nucleon interaction. In particular we study the influence of this coupling (to a $\delta$-meson-like effective field) on the collective response of asymmetric nuclear matter ($ANM$). Interesting contributions are found on the propagation of isovector-like modes at normal density and on an expected smooth transition to isoscalar-like oscillations at high baryon density. Important ``chemical'' effects on the neutron-proton structure of the mode are shown. For dilute $ANM$ we have the isospin distillation mechanism of the unstable isoscalar-like oscillations, while at high baryon density we predict an almost pure neutron wave structure of the propagating sounds.Comment: 18 pages (LATEX), 8 Postscript figures, uses "epsfig

Accuracy and Stability of Computing High-Order Derivatives of Analytic Functions by Cauchy Integrals

High-order derivatives of analytic functions are expressible as Cauchy integrals over circular contours, which can very effectively be approximated, e.g., by trapezoidal sums. Whereas analytically each radius r up to the radius of convergence is equal, numerical stability strongly depends on r. We give a comprehensive study of this effect; in particular we show that there is a unique radius that minimizes the loss of accuracy caused by round-off errors. For large classes of functions, though not for all, this radius actually gives about full accuracy; a remarkable fact that we explain by the theory of Hardy spaces, by the Wiman-Valiron and Levin-Pfluger theory of entire functions, and by the saddle-point method of asymptotic analysis. Many examples and non-trivial applications are discussed in detail.Comment: Version 4 has some references and a discussion of other quadrature rules added; 57 pages, 7 figures, 6 tables; to appear in Found. Comput. Mat