GALEX, Optical and IR Light Curves of MQ Dra: UV Excesses at Low Accretion Rates

Ultraviolet light curves constructed from NUV and FUV detectors on GALEX reveal large amplitude variations during the orbital period of the Low Accretion Rate Polar MQ Dra (SDSSJ1553+55). This unexpected variation from a UV source is similar to that seen and discussed in the Polar EF Eri during its low state of accretion, even though the accretion rate in MQ Dra is an order of magnitude lower than even the low state of EF Eri. The similarity in phasing of the UV and optical light curves in MQ Dra imply a similar location for the source of light. We explore the possibilities of hot spots and cyclotron emission with simple models fit to the UV, optical and IR light curves of MQ Dra. To match the GALEX light curves with a single temperature circular hot spot requires different sizes of spots for the NUV and FUV, while a cyclotron model that can produce the optical harmonics with a magnetic field near 60 MG requires multipoles with fields > 200 MG to match the UV fluxes.Comment: accepted for ApJ; 15 pages, 7 tables, 8 fig

Epistasis not needed to explain low dN/dS

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a phenomenon known as epistasis. In a recent letter to Nature, Breen et al. (2012) argued that epistasis must be "pervasive throughout protein evolution" because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS) is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al. assumed that all amino acids observed in a protein alignment at any particular position have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis. Furthermore, for all nuclear and chloroplast genes in the Breen et al. dataset, we show that the observed dN/dS values and the observed patterns of amino acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.Comment: This manuscript is in response to "Epistasis as the primary factor in molecular evolution" by Breen et al. Nature 490, 535-538 (2012

Investigation of routes and funnels in protein folding by free energy functional methods

We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can lower the free energy barrier to folding. Correlating stronger contact energies with entropically likely contacts of a given native structure lowers the barrier, and anticorrelating the energies has the reverse effect. Designing in relatively mild energetic heterogeneity can eliminate the barrier completely at the transition temperature. Sequences with native energies tuned to fold uniformly, as well as sequences tuned to fold by a single or a few routes, are rare. Sequences with weak native energetic heterogeneity are more common; their folding kinetics is more strongly determined by properties of the native structure. Sequences with different distributions of stability throughout the protein may still be good folders to the same structure. A measure of folding route narrowness is introduced which correlates with rate, and which can give information about the intrinsic biases in ordering due to native topology. This theoretical framework allows us to systematically investigate the coupled effects of energy and topology in protein folding, and to interpret recent experiments which investigate these effects.Comment: 12 pages, 1 figure, to appear in Proc. Natl. Acad. Sc

GALEX and Optical Light Curves of WX LMi, SDSSJ103100.5+202832.2 and SDSSJ121209.31+013627.7

{\it GALEX} near ultraviolet (NUV) and far-ultraviolet (FUV) light curves of three extremely low accretion rate polars show distinct modulations in their UV light curves. While these three systems have a range of magnetic fields from 13 to 70 MG, and of late type secondaries (including a likely brown dwarf in SDSSJ121209.31+013627.7), the accretion rates are similar, and the UV observations imply some mechanism is operating to create enhanced emission zones on the white dwarf. The UV variations match in phase to the two magnetic poles viewed in the optical in WX LMi and to the single poles evident in the optical in SDSSJ1212109.31+013627.7 and SDSSJ103100.55+202832.2. Simple spot models of the UV light curves show that if hot spots are responsible for the UV variations, the temperatures are on the order of 10,000-14,000K. For the single pole systems, the size of the FUV spot must be smaller than the NUV and in all cases, the geometry is likely more complicated than a simple circular spot.Comment: 29 pages, 4 tables, 10 figures, Astrophysical Journal, accepte

Continuation-Passing C: compiling threads to events through continuations

In this paper, we introduce Continuation Passing C (CPC), a programming language for concurrent systems in which native and cooperative threads are unified and presented to the programmer as a single abstraction. The CPC compiler uses a compilation technique, based on the CPS transform, that yields efficient code and an extremely lightweight representation for contexts. We provide a proof of the correctness of our compilation scheme. We show in particular that lambda-lifting, a common compilation technique for functional languages, is also correct in an imperative language like C, under some conditions enforced by the CPC compiler. The current CPC compiler is mature enough to write substantial programs such as Hekate, a highly concurrent BitTorrent seeder. Our benchmark results show that CPC is as efficient, while using significantly less space, as the most efficient thread libraries available.Comment: Higher-Order and Symbolic Computation (2012). arXiv admin note: substantial text overlap with arXiv:1202.324

Protein structures and optimal folding emerging from a geometrical variational principle

Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is found that, irrespective of the sequence, the native state of a protein has exceedingly large number of conformations with a given amount of structural overlap compared to other compact artificial backbones; moreover the conformational entropies of unrelated proteins of the same length are nearly equal at any given stage of folding. These results are suggestive of an extremality principle underlying protein evolution, which, in turn, is shown to be associated with the emergence of secondary structures.Comment: Revtex, 5 pages, 5 postscript figure

Mean-Field HP Model, Designability and Alpha-Helices in Protein Structures

Analysis of the geometric properties of a mean-field HP model on a square lattice for protein structure shows that structures with large number of switch backs between surface and core sites are chosen favorably by peptides as unique ground states. Global comparison of model (binary) peptide sequences with concatenated (binary) protein sequences listed in the Protein Data Bank and the Dali Domain Dictionary indicates that the highest correlation occurs between model peptides choosing the favored structures and those portions of protein sequences containing alpha-helices.Comment: 4 pages, 2 figure

The Calcitonin and Glucocorticoids Combination: Mechanistic Insights into Their Class-Effect Synergy in Experimental Arthritis

PMCID: PMC3564948This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Age-Correlated Gene Expression in Normal and Neurodegenerative Human Brain Tissues

Human brain aging has received special attention in part because of the elevated risks of neurodegenerative disorders such as Alzheimer's disease in seniors. Recent technological advances enable us to investigate whether similar mechanisms underlie aging and neurodegeneration, by quantifying the similarities and differences in their genome-wide gene expression profiles.We have developed a computational method for assessing an individual's "physiological brain age" by comparing global mRNA expression datasets across a range of normal human brain samples. Application of this method to brains samples from select regions in two diseases--Alzheimer's disease (AD, superior frontal gyrus), frontotemporal lobar degeneration (FTLD, in rostral aspect of frontal cortex ∼BA10)--showed that while control cohorts exhibited no significant difference between physiological and chronological ages, FTLD and AD exhibited prematurely aged expression profiles.This study establishes a quantitative scale for measuring premature aging in neurodegenerative disease cohorts, and it identifies specific physiological mechanisms common to aging and some forms of neurodegeneration. In addition, accelerated expression profiles associated with AD and FTLD suggest some common mechanisms underlying the risk of developing these diseases