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

About the holographic pseudo-Goldstone boson

Pseudo-Goldstone bosons in 4D strongly coupled theories have a dual description in terms of 5D gauge theories in warped backgrounds. We introduce systematic methods of computing the pseudo-Goldstone potential for an arbitrary warp factor in 5D. When applied to electroweak symmetry breaking, our approach clarifies the relation of physical observables to geometrical quantities in five dimensions.Comment: 16 page

Detection of Anomalous Reactor Activity Using Antineutrino Count Rate Evolution Over the Course of a Reactor Cycle

This paper analyzes the sensitivity of antineutrino count rate measurements to changes in the fissile content of civil power reactors. Such measurements may be useful in IAEA reactor safeguards applications. We introduce a hypothesis testing procedure to identify statistically significant differences between the antineutrino count rate evolution of a standard 'baseline' fuel cycle and that of an anomalous cycle, in which plutonium is removed and replaced with an equivalent fissile worth of uranium. The test would allow an inspector to detect anomalous reactor activity, or to positively confirm that the reactor is operating in a manner consistent with its declared fuel inventory and power level. We show that with a reasonable choice of detector parameters, the test can detect replacement of 73 kg of plutonium in 90 days with 95% probability, while controlling the false positive rate at 5%. We show that some improvement on this level of sensitivity may be expected by various means, including use of the method in conjunction with existing reactor safeguards methods. We also identify a necessary and sufficient daily antineutrino count rate to achieve the quoted sensitivity, and list examples of detectors in which such rates have been attained.Comment: 9 pages, 7 figures, submitted to J. Appl. Phy