Characterizing disease states from topological properties of transcriptional regulatory networks

BACKGROUND: High throughput gene expression experiments yield large amounts of data that can augment our understanding of disease processes, in addition to classifying samples. Here we present new paradigms of data Separation based on construction of transcriptional regulatory networks for normal and abnormal cells using sequence predictions, literature based data and gene expression studies. We analyzed expression datasets from a number of diseased and normal cells, including different types of acute leukemia, and breast cancer with variable clinical outcome. RESULTS: We constructed sample-specific regulatory networks to identify links between transcription factors (TFs) and regulated genes that differentiate between healthy and diseased states. This approach carries the advantage of identifying key transcription factor-gene pairs with differential activity between healthy and diseased states rather than merely using gene expression profiles, thus alluding to processes that may be involved in gene deregulation. We then generalized this approach by studying simultaneous changes in functionality of multiple regulatory links pointing to a regulated gene or emanating from one TF (or changes in gene centrality defined by its in-degree or out-degree measures, respectively). We found that samples can often be separated based on these measures of gene centrality more robustly than using individual links. We examined distributions of distances (the number of links needed to traverse the path between each pair of genes) in the transcriptional networks for gene subsets whose collective expression profiles could best separate each dataset into predefined groups. We found that genes that optimally classify samples are concentrated in neighborhoods in the gene regulatory networks. This suggests that genes that are deregulated in diseased states exhibit a remarkable degree of connectivity. CONCLUSION: Transcription factor-regulated gene links and centrality of genes on transcriptional networks can be used to differentiate between cell types. Transcriptional network blueprints can be used as a basis for further research into gene deregulation in diseased states

Unilateral contact dermatitis of the breast caused by amyl nitrites (poppers)

Non peer reviewe

Relativistic Kinetic Equations for Electromagnetic, Scalar and Pseudoscalar Interactions

We derive the kinetic equations for both the covariant and equal-time Wigner functions of Dirac particles with electromagnetic, scalar and pseudoscalar interactions. We emphasize the constraint equations for the spinor components in the equal-time formulation.Comment: 12 pages, no figures, revte

Robust energy harvesting from walking vibrations by means of nonlinear cantilever beams

In the present work we examine how mechanical nonlinearity can be appropriately utilized to achieve strong robustness of performance in an energy harvesting setting. More specifically, for energy harvesting applications, a great challenge is the uncertain character of the excitation. The combination of this uncertainty with the narrow range of good performance for linear oscillators creates the need for more robust designs that adapt to a wider range of excitation signals. A typical application of this kind is energy harvesting from walking vibrations. Depending on the particular characteristics of the person that walks as well as on the pace of walking, the excitation signal obtains completely different forms. In the present work we study a nonlinear spring mechanism that is composed of a cantilever wrapping around a curved surface as it deflects. While for the free cantilever, the force acting on the free tip depends linearly on the tip displacement, the utilization of a contact surface with the appropriate distribution of curvature leads to essentially nonlinear dependence between the tip displacement and the acting force. The studied nonlinear mechanism has favorable mechanical properties such as low frictional losses, minimal moving parts, and a rugged design that can withstand excessive loads. Through numerical simulations we illustrate that by utilizing this essentially nonlinear element in a 2 degrees-of-freedom (DOF) system, we obtain strongly nonlinear energy transfers between the modes of the system. We illustrate that this nonlinear behavior is associated with strong robustness over three radically different excitation signals that correspond to different walking paces. To validate the strong robustness properties of the 2DOF nonlinear system, we perform a direct parameter optimization for 1DOF and 2DOF linear systems as well as for a class of 1DOF and 2DOF systems with nonlinear springs similar to that of the cubic spring that are physically realized by the cantilever–surface mechanism. The optimization results show that the 2DOF nonlinear system presents the best average performance when the excitation signals have three possible forms. Moreover, we observe that while for the linear systems the optimal performance is obtained for small values of the electromagnetic damping, for the 2DOF nonlinear system optimal performance is achieved for large values of damping. This feature is of particular importance for the system׳s robustness to parasitic damping.Massachusetts Institute of Technology. Naval Engineering Education Center. (Grant 3002883706)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374)MIT Energy Initiativ

Particle Production and Effective Thermalization in Inhomogeneous Mean Field Theory

As a toy model for dynamics in nonequilibrium quantum field theory we consider the abelian Higgs model in 1+1 dimensions with fermions. In the approximate dynamical equations, inhomogeneous classical (mean) Bose fields are coupled to quantized fermion fields, which are treated with a mode function expansion. The effective equations of motion imply e.g. Coulomb scattering, due to the inhomogeneous gauge field. The equations are solved numerically. We define time dependent fermion particle numbers with the help of the single-time Wigner function and study particle production starting from inhomogeneous initial conditions. The particle numbers are compared with the Fermi-Dirac distribution parametrized by a time dependent temperature and chemical potential. We find that the fermions approximately thermalize locally in time.Comment: 16 pages + 6 eps figures, some clarifications and two references added, typos corrected; to appear in Phys.Rev.

The kinetic description of vacuum particle creation in the oscillator representation

The oscillator representation is used for the non-perturbative description of vacuum particle creation in a strong time-dependent electric field in the framework of scalar QED. It is shown that the method can be more effective for the derivation of the quantum kinetic equation (KE) in comparison with the Bogoliubov method of time-dependent canonical transformations. This KE is used for the investigation of vacuum creation in periodical linear and circular polarized electric fields and also in the case of the presence of a constant magnetic field, including the back reaction problem. In particular, these examples are applied for a model illustration of some features of vacuum creation of electron-positron plasma within the planned experiments on the X-ray free electron lasers.Comment: 17 pages, 3 figures, v2: a reference added; some changes in tex

Dileptons from Disoriented Chiral Condensates

Disoriented chiral condensates or long wavelength pionic oscillations and their interaction with the thermal environment can be a significant source of dileptons. We calculate the yield of such dilepton production within the linear sigma model, both in a quantal mean-field treatment and in a semi-classical approximation. We then illustrate the basic features of the dilepton spectrum in a schematic model. We find that dilepton yield with invariant mass near and below $2m_{\pi}$ due to the soft pion modes can be up to two orders of magnitude larger than the corresponding equilibrium yield.Comment: 22 pages, 8 figures, uses epsf-styl

Electrostatic pair creation and recombination in quantum plasmas

The collective production of electron-positron pairs by electrostatic waves in quantum plasmas is investigated. In particular, a semi-classical governing set of equation for a self-consistent treatment of pair creation by the Schwinger mechanism in a quantum plasma is derived.Comment: 4 pages, 3 figures, to appear in JETP Letter

Quantum scalar field in FRW Universe with constant electromagnetic background

We discuss massive scalar field with conformal coupling in Friedmann-Robertson-Walker (FRW) Universe of special type with constant electromagnetic field. Treating an external gravitational-electromagnetic background exactly, at first time the proper-time representations for out-in, in-in, and out-out scalar Green functions are explicitly constructed as proper-time integrals over the corresponding (complex) contours. The vacuum-to-vacuum transition amplitudes and number of created particles are found and vacuum instability is discussed. The mean values of the current and energy-momentum tensor are evaluated, and different approximations for them are investigated. The back reaction of the particles created to the electromagnetic field is estimated in different regimes. The connection between proper-time method and effective action is outlined. The effective action in scalar QED in weakly-curved FRW Universe (De Sitter space) with weak constant electromagnetic field is found as derivative expansion over curvature and electromagnetic field strength. Possible further applications of the results are briefly mentioned.Comment: 38 pages, LaTe