Low-Temperature Enhancement of Semi-annihilation and the AMS-02 Positron Anomaly

Semi-annihilation is a generic feature of particle dark matter that is most easily probed by cosmic ray experiments. We explore models where the semi-annihilation cross section is enhanced at late times and low temperatures by the presence of an s-channel resonance near threshold. The relic density is then sensitive to the evolution of the dark matter temperature, and we compute expressions for the associated Boltzmann equation valid in general semi-annihilating models. At late times, a self-heating effect warms the dark matter, allowing number-changing processes to remain effective long after kinetic decoupling of the dark and visible sectors. This allows the semi-annihilation signal today to be enhanced by up to five orders of magnitude over the thermal relic cross section. As a case study, we apply this to a dark matter explanation of the positron excess seen by AMS-02. We see that unlike annihilating dark matter, our model has no difficulty fitting the data while also giving the correct relic density. However, constraints from the CMB and $\gamma$-rays from the galactic centre do restrict the preferred regions of parameter space.Comment: 32 pages, 5 figures; minor update

Two-Dimensional Pursuit-Evasion in a Compact Domain with Piecewise Analytic Boundary

In a pursuit-evasion game, a team of pursuers attempt to capture an evader. The players alternate turns, move with equal speed, and have full information about the state of the game. We consider the most restictive capture condition: a pursuer must become colocated with the evader to win the game. We prove two general results about pursuit-evasion games in topological spaces. First, we show that one pursuer has a winning strategy in any CAT(0) space under this restrictive capture criterion. This complements a result of Alexander, Bishop and Ghrist, who provide a winning strategy for a game with positive capture radius. Second, we consider the game played in a compact domain in Euclidean two-space with piecewise analytic boundary and arbitrary Euler characteristic. We show that three pursuers always have a winning strategy by extending recent work of Bhadauria, Klein, Isler and Suri from polygonal environments to our more general setting.Comment: 21 pages, 6 figure

Should the democrats move to the left on economic policy?

Could John Kerry have gained votes in the 2004 Presidential election by more clearly distinguishing himself from George Bush on economic policy? At first thought, the logic of political preferences would suggest not: the Republicans are to the right of most Americans on economic policy, and so in a one-dimensional space with party positions measured with no error, the optimal strategy for the Democrats would be to stand infinitesimally to the left of the Republicans. The median voter theorem suggests that each party should keep its policy positions just barely distinguishable from the opposition. In a multidimensional setting, however, or when voters vary in their perceptions of the parties' positions, a party can benefit from putting some daylight between itself and the other party on an issue where it has a public-opinion advantage (such as economic policy for the Democrats). We set up a plausible theoretical model in which the Democrats could achieve a net gain in votes by moving to the left on economic policy, given the parties' positions on a range of issue dimensions. We then evaluate this model based on survey data on voters' perceptions of their own positions and those of the candidates in 2004. Under our model, it turns out to be optimal for the Democrats to move slightly to the right but staying clearly to the left of the Republicans' current position on economic issues.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS150 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org). With Correction

Solution Structures of \u3cem\u3eMycobacterium tuberculosis\u3c/em\u3e Thioredoxin C and Models of Intact Thioredoxin System Suggest New Approaches to Inhibitor and Drug Design

Here, we report the NMR solution structures of Mycobacterium tuberculosis (M. tuberculosis) thioredoxin C in both oxidized and reduced states, with discussion of structural changes that occur in going between redox states. The NMR solution structure of the oxidized TrxC corresponds closely to that of the crystal structure, except in the C-terminal region. It appears that crystal packing effects have caused an artifactual shift in the α4 helix in the previously reported crystal structure, compared with the solution structure. On the basis of these TrxC structures, chemical shift mapping, a previously reported crystal structure of the M. tuberculosis thioredoxin reductase (not bound to a Trx) and structures for intermediates in the E. coli thioredoxin catalytic cycle, we have modeled the complete M. tuberculosis thioredoxin system for the various steps in the catalytic cycle. These structures and models reveal pockets at the TrxR/TrxC interface in various steps in the catalytic cycle, which can be targeted in the design of uncompetitive inhibitors as potential anti-mycobacterial agents, or as chemical genetic probes of function

NMR Dynamics Investigation of Ligand-Induced Changes of Main and Side-Chain Arginine N-H’s in Human Phosphomevalonate Kinase

Phosphomevalonate kinase (PMK) catalyzes phosphoryl transfer from adenosine triphosphate (ATP) to mevalonate 5-phosphate (M5P) on the pathway for synthesizing cholesterol and other isoprenoids. To permit this reaction, its substrates must be brought proximal, which would result in a significant and repulsive buildup of negative charge. To facilitate this difficult task, PMK contains 17 arginines and eight lysines. However, the way in which this charge neutralization and binding is achieved, from a structural and dynamics perspective, is not known. More broadly, the role of arginine side-chain dynamics in binding of charged substrates has not been experimentally defined for any protein to date. Herein we report a characterization of changes to the dynamical state of the arginine side chains in PMK due to binding of its highly charged substrates, ATP and M5P. These studies were facilitated by the use of arginine-selective labeling to eliminate spectral overlap. Model-free analysis indicated that while substrate binding has little effect on the arginine backbone dynamics, binding of either substrate leads to significant rigidification of the arginine side chains throughout the protein, even those that are \u3e8 Å from the binding site. Such a global rigidification of arginine side chains is unprecedented and suggests that there are long-range electrostatic interactions of sufficient strength to restrict the motion of arginine side chains on the picosecond-to-nanosecond time scale. It will be interesting to see whether such effects are general for arginine residues in proteins that bind highly charged substrates, once additional studies of arginine side-chain dynamics are reported

Integrated economic-hydrologic water modeling at the basin scale: the Maipo river basin

Increasing competition for water across sectors increases the importance of the river basin as the appropriate unit of analysis to address the challenges facing water resources management; and modeling at this scale can provide essential information for policymakers in their resource allocation decisions. This paper introduces an integrated economic-hydrologic modeling framework that accounts for the interactions between water allocation, farmer input choice, agricultural productivity, nonagricultural water demand, and resource degradation in order to estimate the social and economic gains from improvement in the allocation and efficiency of water use. The model is applied to the Maipo River Basin in Chile. Economic benefits to water use are evaluated for different demand management instruments, including markets in tradable water rights, based on production and benefit functions with respect to water for the agricultural and urban-industrial sectors.Resource allocation., Water resources development Chile., Chile.,

A combined in vitro / in vivo selection for polymerases with novel promoter specificities

BACKGROUND: The DNA-dependent RNA polymerase from T7 bacteriophage (T7 RNAP) has been extensively characterized, and like other phage RNA polymerases it is highly specific for its promoter. A combined in vitro / in vivo selection method has been developed for the evolution of T7 RNA polymerases with altered promoter specificities. Large (10(3) – 10(6)) polymerase libraries were made and cloned downstream of variant promoters. Those polymerase variants that can recognize variant promoters self-amplify both themselves and their attendent mRNAs in vivo. Following RT / PCR amplification in vitro, the most numerous polymerase genes are preferentially cloned and carried into subsequent rounds of selection. RESULTS AND CONCLUSIONS: A T7 RNA polymerase library that was randomized at three positions was cloned adjacent to a T3-like promoter sequence, and a 'specialist' T7 RNA polymerase was identified. A library that was randomized at a different set of positions was cloned adjacent to a promoter library in which four positions had been randomized, and 'generalist' polymerases that could utilize a variety of T7 promoters were identified, including at least one polymerase with an apparently novel promoter specificity. This method may have applications for evolving other polymerase variants with novel phenotypes, such as the ability to incorporate modified nucleotides