Pathway and ontology analysis: emerging approaches connecting transcriptome data and clinical endpoints.

The increasing use of gene expression profiling offers great promise in clinical research into disease biology and its treatment. Along with the ability to measure changing expression levels in thousands of genes at once, comes the challenge of analyzing and interpreting the vast sets of data generated. Analysis tools are evolving rapidly to meet such challenges. The next step is to interpret observed changes in terms of the biological properties or relationships underlying them. One powerful approach is to make associations between the genes that are under investigation and well-known biochemical or signaling pathways, and further to assess the significance of such associations. Similarly, genes can be mapped to standardized biological categories via an ontology resource. We discuss these approaches and several web-based resources and tools designed to facilitate such analyses. This information can be used to facilitate understanding and to help design more focused experiments for validating the relevance and importance of these biological pathways and processes in human disease and therapeutics.

Understanding normal modes of proteins

In order to obtain accurate normal modes of proteins, which is a prerequisite for detailed analyses in a variety of vibrational spectroscopic techniques, reliable conformation-dependent force fields are required. We discuss the use of empirical polypeptide force fields for this purpose, since they have generally been quite successful in reproducing spectra of synthetic polypeptides. Although their limitations are motivating our development of a spectroscopically determined force field (SDFF), empirical force fields can still provide important insights into the normal modes of proteins. We illustrate this by calculations on deoxymyoglobin. Together with ab initio dipole derivatives, amide I and amide II IR band profiles have been computed. These, together with the eigenvectors, show how helix irregularity and force constant variation can influence the delocalization of displacements in the mode, and the shape and breadth of observed bands. The influence of rigid peptide group geometry on the low-frequency density-of-states is also examined.

Measurement of the in-medium K0 inclusive cross section in pi(-) -induced reactions at 1.15 GeV/c.

The K0 meson production by pi(-) mesons of 1.15 GeV/c momentum on C, Al, Cu, Sn, and Pb nuclear targets was measured with the FOPI spectrometer at the Schwer-Ionen-Synchrotron accelerator of GSI. Inclusive production cross sections and the momentum distributions of K0 mesons are compared to scaled elementary production cross sections and to predictions of theoretical models describing the in-medium production of kaons. The data represent a new reference for those models, which are widely used for interpretation of the strangeness production in heavy-ion collisions. The presented results demonstrate the sensitivity of the kaon production to the reaction amplitudes inside nuclei and point to the existence of a repulsive KN potential of 20+/-5 MeV at normal nuclear matter density.

Infrared amide I' band of the coiled coil.

The Fourier transform infrared (FTIR) spectra of several coiled-coil proteins have been shown to possess unusual features in the amide I' region. Band maxima occur in the vicinity of 1630 cm-1, with component bands at higher frequency. This is well below the observed band at 1650 cm-1 found in standard alpha-helical polypeptides such as poly-L-alanine. Normal mode calculations on models of the coiled-coil structure have been performed to investigate this issue. We find that the observed band profile can be reproduced with very small random variation on the phi, psi of tropomyosin. We believe that the shift to lower frequency is due to additional hydrogen bonding of the solvent accessible backbone CO groups to water.

Azimuthal dependence of collective expansion for symmetric heavy-ion collisions.

Detailed studies of the azimuthal dependence of the mean fragment and flow energies in the Au+Au and Xe+CsI systems are reported as a function of incident energy and centrality. Comparisons between data and model calculations show that the flow energy values along different azimuthal directions could be viewed as snapshots of the fireball expansion with different exposure times. For the same number of participating nucleons more transversally elongated participant shapes from the heavier system produce less collective transverse energy. Good agreement with Boltzmann-Uehling-Uhlenbeck calculations is obtained for a soft nuclear equation of state.

Nuclear stopping from 0.09A to 1.93A GeV and its correlation to flow.

We present a complete systematics (excitation functions and system-size dependences) of global stopping and side flow for heavy ion reactions in the energy range between 0.09A and 1.93A GeV. For the heaviest system, Au+Au, we observe a plateau of maximal stopping extending from about 0.2A to 0.8A GeV with a fast drop on both sides. The degree of stopping, which is shown to remain significantly below the expectations of a full stopping scenario, is found to be highly correlated to the amount of side flow.