Understanding diversity of human innate immunity receptors: analysis of surface features of leucine-rich repeat domains in NLRs and TLRs.

BackgroundThe human innate immune system uses a system of extracellular Toll-like receptors (TLRs) and intracellular Nod-like receptors (NLRs) to match the appropriate level of immune response to the level of threat from the current environment. Almost all NLRs and TLRs have a domain consisting of multiple leucine-rich repeats (LRRs), which is believed to be involved in ligand binding. LRRs, found also in thousands of other proteins, form a well-defined "horseshoe"-shaped structural scaffold that can be used for a variety of functions, from binding specific ligands to performing a general structural role. The specific functional roles of LRR domains in NLRs and TLRs are thus defined by their detailed surface features. While experimental crystal structures of four human TLRs have been solved, no structure data are available for NLRs.ResultsWe report a quantitative, comparative analysis of the surface features of LRR domains in human NLRs and TLRs, using predicted three-dimensional structures for NLRs. Specifically, we calculated amino acid hydrophobicity, charge, and glycosylation distributions within LRR domain surfaces and assessed their similarity by clustering. Despite differences in structural and genomic organization, comparison of LRR surface features in NLRs and TLRs allowed us to hypothesize about their possible functional similarities. We find agreement between predicted surface similarities and similar functional roles in NLRs and TLRs with known agonists, and suggest possible binding partners for uncharacterized NLRs.ConclusionDespite its low resolution, our approach permits comparison of molecular surface features in the absence of crystal structure data. Our results illustrate diversity of surface features of innate immunity receptors and provide hints for function of NLRs whose specific role in innate immunity is yet unknown

Circular dichroism at equal energy sharing in photo-double-ionization of He

Interference between dipole and quadrupole transition amplitudes in photo-double-ionization of He by an elliptically polarized vuv photon is shown to induce circular dichroism in the case of equal energy sharing. The magnitude of this retardation-induced dichroic effect is estimated and its impact on the nondipole asymmetries of the triply differential cross section is demonstrated

Correlation, nondipole, and entanglement effects in atomic and spin-based systems

This dissertation deals with two different fields of physics, therefore it comprises two different parts. The first part contains three chapters and describes theoretical studies of one of the most fundamental processes in atomic physics, the one-photon double ionization of a He atom. This process represents a prototype for the complete breakup (by absorption of a single photon) of a bound system of three particles, interacting in both the initial (bound) and final (continuum) states by long-range Coulomb interactions. In Chapter 2, electron correlations and the physical mechanisms of the double ionization process are studied by analyzing the fully-differential cross sections within the electric-dipole approximation and within the framework of lowest-order perturbation theory in the interelectron interaction. Chapter 3 is devoted to studies of the influence of nondipole effects (i.e., of the spatial inhomogeneity of the light wave) on the double photoionization process by analyzing the fully-differential cross sections. In Chapter 4, the angle-integrated cross sections for double ionization are analyzed, and two kinds of model-independent parametrizations for such cross sections are derived. The second part of the dissertation (Chapter 5) presents an independent piece of theoretical research at the interface between condensed matter physics and the rapidly developing field of quantum computing and quantum information. This part analyzes entanglement properties of eigenstates of a pair of interacting mesoscopic magnetic quantum dots. Such nanodots are proposed as promising candidates for scalable quantum registers (qubits) designed for storing and manipulating quantum states in a solid state quantum computer. The results presented in Chapters 2, 3, and 5 have been published, while those in Chapter 4 are currently under preparation for submission

Perturbative calculation of the triply differential cross section for photo-double-ionization of He

Single-photon, two-electron ionization of He is analyzed, taking into account electron correlation using lowest-order perturbation theory and including all individual electron angular momenta in the final two-electron continuum. Perturbative account of electron correlation in the final state, which describes the so-called TS-1 mechanism of double photoionization, combined with a variational account of electron screening, is found to provide results for the triply differential cross section at an excess energy of 20 eV that are in excellent agreement with both absolute experimental data and results of non-perturbative calculations, for all kinematics of the process in which the TS-1 mechanism is expected to dominate