27,041 research outputs found
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
An economic impact study and analysis of the economies of Gibraltar and the Campo de Gibraltar
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
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