Optimizing Abstract Abstract Machines

The technique of abstracting abstract machines (AAM) provides a systematic approach for deriving computable approximations of evaluators that are easily proved sound. This article contributes a complementary step-by-step process for subsequently going from a naive analyzer derived under the AAM approach, to an efficient and correct implementation. The end result of the process is a two to three order-of-magnitude improvement over the systematically derived analyzer, making it competitive with hand-optimized implementations that compute fundamentally less precise results.Comment: Proceedings of the International Conference on Functional Programming 2013 (ICFP 2013). Boston, Massachusetts. September, 201

More Bang For Your Buck: Quorum-Sensing Capabilities Improve the Efficacy of Suicidal Altruism

Within the context of evolution, an altruistic act that benefits the receiving individual at the expense of the acting individual is a puzzling phenomenon. An extreme form of altruism can be found in colicinogenic E. coli. These suicidal altruists explode, releasing colicins that kill unrelated individuals, which are not colicin resistant. By committing suicide, the altruist makes it more likely that its kin will have less competition. The benefits of this strategy rely on the number of competitors and kin nearby. If the organism explodes at an inopportune time, the suicidal act may not harm any competitors. Communication could enable organisms to act altruistically when environmental conditions suggest that that strategy would be most beneficial. Quorum sensing is a form of communication in which bacteria produce a protein and gauge the amount of that protein around them. Quorum sensing is one means by which bacteria sense the biotic factors around them and determine when to produce products, such as antibiotics, that influence competition. Suicidal altruists could use quorum sensing to determine when exploding is most beneficial, but it is challenging to study the selective forces at work in microbes. To address these challenges, we use digital evolution (a form of experimental evolution that uses self-replicating computer programs as organisms) to investigate the effects of enabling altruistic organisms to communicate via quorum sensing. We found that quorum-sensing altruists killed a greater number of competitors per explosion, winning competitions against non-communicative altruists. These findings indicate that quorum sensing could increase the beneficial effect of altruism and the suite of conditions under which it will evolve.Comment: 8 pages, 8 figures, ALIFE '14 conferenc

Missing data in randomized controlled trials testing palliative interventions pose a significant risk of bias and loss of power: a systematic review and meta-analyses

Objectives To assess the risk posed by missing data (MD) to the power and validity of trials evaluating palliative interventions. Study Design and Setting A systematic review of MD in published randomized controlled trials (RCTs) of palliative interventions in participants with life-limiting illnesses was conducted, and random-effects meta-analyses and metaregression were performed. CENTRAL, MEDLINE, and EMBASE (2009-2014) were searched with no language restrictions. Results One hundred and eight RCTs representing 15,560 patients were included. The weighted estimate for MD at the primary endpoint was 23.1% (95% confidence interval [CI] 19.3, 27.4). Larger MD proportions were associated with increasing numbers of questions/tests requested (odds ratio [OR] , 1.19; 95% CI 1.05, 1.35) and with longer study duration (OR, 1.09; 95% CI 1.02, 1.17). Meta-analysis found evidence of differential rates of MD between trial arms, which varied in direction (OR, 1.04; 95% CI 0.90, 1.20; I 2 35.9, P = 0.001). Despite randomization, MD in the intervention arms (vs. control) were more likely to be attributed to disease progression unrelated to the intervention (OR, 1.31; 95% CI 1.02, 1.69). This was not the case for MD due to death (OR, 0.92; 95% CI 0.78, 1.08). Conclusion The overall proportion and differential rates and reasons for MD reduce the power and potentially introduce bias to palliative care trials

HAT-P-7: A Retrograde or Polar Orbit, and a Third Body

We show that the exoplanet HAT-P-7b has an extremely tilted orbit, with a true angle of at least 86 degrees with respect to its parent star's equatorial plane, and a strong possibility of retrograde motion. We also report evidence for an additional planet or companion star. The evidence for the unparalleled orbit and the third body is based on precise observations of the star's apparent radial velocity. The anomalous radial velocity due to rotation (the Rossiter-McLaughlin effect) was found to be a blueshift during the first half of the transit and a redshift during the second half, an inversion of the usual pattern, implying that the angle between the sky-projected orbital and stellar angular momentum vectors is 182.5 +/- 9.4 degreees. The third body is implicated by excess radial-velocity variation of the host star over 2 yr. Some possible explanations for the tilted orbit are a close encounter with another planet, the Kozai effect, and resonant capture by an inward-migrating outer planet.Comment: ApJ Letters, in press [7 pages

PtrA is required for coordinate regulation of gene expression during phosphate stress in a marine Synechococcus

Previous microarray analyses have shown a key role for the two-component system PhoBR (SYNW0947, SYNW0948) in the regulation of P transport and metabolism in the marine cyanobacterium Synechococcus sp. WH8102. However, there is some evidence that another regulator, SYNW1019 (PtrA), probably under the control of PhoBR, is involved in the response to P depletion. PtrA is a member of the cAMP receptor protein transcriptional regulator family that shows homology to NtcA, the global nitrogen regulator in cyanobacteria. To define the role of this regulator, we constructed a mutant by insertional inactivation and compared the physiology of wild-type Synechcococcus sp. WH8102 with the ptrA mutant under P-replete and P-stress conditions. In response to P stress the ptrA mutant failed to upregulate phosphatase activity. Microarrays and quantitative RT-PCR indicate that a subset of the Pho regulon is controlled by PtrA, including two phosphatases, a predicted phytase and a gene of unknown function psip1 (SYNW0165), all of which are highly upregulated during P limitation. Electrophoretic mobility shift assays indicate binding of overexpressed PtrA to promoter sequences upstream of the induced genes. This work suggests a two-tiered response to P depletion in this strain, the first being PhoB-dependent induction of high-affinity PO4 transporters, and the second the PtrA-dependent induction of phosphatases for scavenging organic P. The levels of numerous other transcripts are also directly or indirectly influenced by PtrA, including those involved in cell-surface modification, metal uptake, photosynthesis, stress responses and other metabolic processes, which may indicate a wider role for PtrA in cellular regulation in marine picocyanobacteria

Variability within individuals of plasma ionic magnesium concentrations

BACKGROUND: With the invention of the ion-selective electrode (ISE), ionic magnesium (iMg) is a common blood assay. This could be advantageous, as iMg is the biologically active form of Mg. There is some evidence that iMg has considerable within subject variability. RESULTS: Individual ranges averaged .08 mmol/L (range .05 to .14). Coefficients of variation (CV) ranged from 3% to 7% (mean 4%) while analytical variation was determined to be 2.3%. Biological variability thus accounts for almost half of the variability, which is clinically significant, as 9 of the 13 subjects recorded at least one value below a reference range of .46 – .60 mmol/L. A significant within-day variation (p < .001) was noted, with differences between 7:00 and 10:00 as well as 10:00 and 22:00. Between day variations were not significant (p = .56). CONCLUSIONS: A plausible explanation of this data is that iMg has a circadian rhythm. Thus, cautious interpretation of single iMg values is warranted until future research determines the nature of iMg variability