Metabolomic study of the LDL receptor null mouse fed a high-fat diet reveals profound perturbations in choline metabolism that are shared with ApoE null mice

Failure to express or expression of dysfunctional low-density lipoprotein receptors (LDLR) causes familial hypercholesterolemia in humans, a disease characterized by elevated blood cholesterol concentrations, xanthomas, and coronary heart disease, providing compelling evidence that high blood cholesterol concentrations cause atherosclerosis. In this study, we used 1H nuclear magnetic resonance spectroscopy to examine the metabolic profiles of plasma and urine from the LDLR knockout mice. Consistent with previous studies, these mice developed hypercholesterolemia and atherosclerosis when fed a high-fat/cholesterol/cholate-containing diet. In addition, multivariate statistical analysis of the metabolomic data highlighted significant differences in tricarboxylic acid cycle and fatty acid metabolism, as a result of high-fat/cholesterol diet feeding. Our metabolomic study also demonstrates that the effect of high-fat/cholesterol/cholate diet, LDLR gene deficiency, and the diet-genotype interaction caused a significant perturbation in choline metabolism, notably the choline oxidation pathway. Specifically, the loss in the LDLR caused a marked reduction in the urinary excretion of betaine and dimethylglycine, especially when the mice are fed a high-fat/cholesterol/cholate diet. Furthermore, as we demonstrate that these metabolic changes are comparable with those detected in ApoE knockout mice fed the same high-fat/cholesterol/cholate diet they may be useful for monitoring the onset of atherosclerosis across animal models

The quality of monetary policy and inflation performance: globalization and its aftermath

With a few unfortunate exceptions the last three decades have seen reductions in inflation around the world to the point that many would argue that further improvements in price stability would offer only limited welfare gains. This experience is the result of many factors, some of which are country-specific. In this paper we seek to isolate one of the factors, namely, the improvement in the quality of monetary policy. There are two novel aspects to the study. Firstly, we essentially estimate a gravity-like model. Secondly, we propose generally a more exhaustive analysis of the potential role of a large number of institutional factors than has been done before. Briefly, we find that institutional factors play a role in explaining inflation relative to the US experience, which is used as the benchmark. Nevertheless, any reduction in inflation stemming from greater central bank autonomy is a feature of the 1980s and early 1990s. Thereafter, central banks in the OECD look very much alike.globalization; inflation differentials; monetary policy strategy; institutional change

Model of Transcriptional Activation by MarA in Escherichia coli

We have developed a mathematical model of transcriptional activation by MarA in Escherichia coli, and used the model to analyze measurements of MarA-dependent activity of the marRAB, sodA, and micF promoters in mar-rob- cells. The model rationalizes an unexpected poor correlation between the mid-point of in vivo promoter activity profiles and in vitro equilibrium constants for MarA binding to promoter sequences. Analysis of the promoter activity data using the model yielded the following predictions regarding activation mechanisms: (1) MarA activation of the marRAB, sodA, and micF promoters involves a net acceleration of the kinetics of transitions after RNA polymerase binding, up to and including promoter escape and message elongation; (2) RNA polymerase binds to these promoters with nearly unit occupancy in the absence of MarA, making recruitment of polymerase an insignificant factor in activation of these promoters; and (3) instead of recruitment, activation of the micF promoter might involve a repulsion of polymerase combined with a large acceleration of the kinetics of polymerase activity. These predictions are consistent with published chromatin immunoprecipitation assays of interactions between polymerase and the E. coli chromosome. A lack of recruitment in transcriptional activation represents an exception to the textbook description of activation of bacterial sigma-70 promoters. However, use of accelerated polymerase kinetics instead of recruitment might confer a competitive advantage to E. coli by decreasing latency in gene regulation.Comment: 30 pages, 2 figure

Collinearity, convergence and cancelling infrared divergences

The Lee-Nauenberg theorem is a fundamental quantum mechanical result which provides the standard theoretical response to the problem of collinear and infrared divergences. Its argument, that the divergences due to massless charged particles can be removed by summing over degenerate states, has been successfully applied to systems with final state degeneracies such as LEP processes. If there are massless particles in both the initial and final states, as will be the case at the LHC, the theorem requires the incorporation of disconnected diagrams which produce connected interference effects at the level of the cross-section. However, this aspect of the theory has never been fully tested in the calculation of a cross-section. We show through explicit examples that in such cases the theorem introduces a divergent series of diagrams and hence fails to cancel the infrared divergences. It is also demonstrated that the widespread practice of treating soft infrared divergences by the Bloch-Nordsieck method and handling collinear divergences by the Lee-Nauenberg method is not consistent in such cases.Comment: 29 pages, 17 figure

Identifications of Einstein Slew Survey sources

The status of identifications of the Einstien Slew Survey, a bright soft x-ray catalog with 550 new x-ray sources, is discussed. Possible counterparts were found for greater than 95 percent of the Slew Survey based on positional coincidences and color-color diagnostics. The survey will be fully identified via upcoming radio and optical observations

Einstein Slew Survey: Data analysis innovations

Several new methods were needed in order to make the Einstein Slew X-ray Sky Survey. The innovations which enabled the Slew Survey to be done are summarized. These methods included experimental approach to large projects, parallel processing on a LAN, percolation source detection, minimum action identifications, and rapid dissemination of the whole data base

Pathwise super-replication via Vovk's outer measure

Since Hobson's seminal paper [D. Hobson: Robust hedging of the lookback option. In: Finance Stoch. (1998)] the connection between model-independent pricing and the Skorokhod embedding problem has been a driving force in robust finance. We establish a general pricing-hedging duality for financial derivatives which are susceptible to the Skorokhod approach. Using Vovk's approach to mathematical finance we derive a model-independent super-replication theorem in continuous time, given information on finitely many marginals. Our result covers a broad range of exotic derivatives, including lookback options, discretely monitored Asian options, and options on realized variance.Comment: 18 page

Science, Measurement, and Technology Requirements for Infrared Climate Benchmark Missions

Quantifying climate change in the presence of natural variability requires highly accurate global measurements covering more than a decade. Instrument design considerations for trending terrestrial emitted radiance are described