Temperature Dependence of the Relative Rates of Chlorination and Hydrolysis of N2O5 in NaCl-Water Solutions.

We have measured the temperature dependence of the ClNO2 product yield in competition with hydrolysis following N2O5 uptake to aqueous NaCl solutions. For NaCl-D2O solutions spanning 0.0054 M to 0.21 M, the ClNO2 product yield decreases on average by only 43 % from 5 to 25 C. Less reproducible measurements at 0.54 M and 2.4 M NaCl also fall within this range. The ratio of the rate constants for chlorination and hydrolysis of N2O5 in D2O is determined on average to be 1150±90 at 25 C up to 0.21 M NaCl, favoring chlorination. This ratio is observed to decrease significantly at the two highest concentrations. An Arrhenius analysis reveals that the activation energy for hydrolysis is just 3.0±1.5 kJ/mol larger than for chlorination up to 0.21 M, indicating that Cl- and D2O attack on N2O5 have similar energetic barriers despite the differences in charge and complexity of these reactants. In combination with the measured pre-exponential ratio favoring chlorination of {300\ }_{-200}^{+400}, we conclude that the strong preference of N2O5 to undergo chlorination over hydrolysis is driven by dynamic and entropic, rather than enthalpic, factors. Molecular dynamics simulations elucidate the distinct solvation between strongly hydrated Cl- and the hydrophobically solvated N2O5. Combining this molecular picture with the Arrhenius analysis implicates the role of water in mediating interactions between such distinctly solvated species and suggests a role for diffusion limitations on the chlorination reaction

Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria.

The oligosaccharyl transferase (OST) protein complex mediates the N-linked glycosylation of substrate proteins in the endoplasmic reticulum (ER), which regulates stability, activity, and localization of its substrates. Although many OST substrate proteins have been identified, the physiological role of the OST complex remains incompletely understood. Here we show that the OST complex in C. elegans is crucial for ER protein homeostasis and defense against infection with pathogenic bacteria Pseudomonas aeruginosa (PA14), via immune-regulatory PMK-1/p38 MAP kinase. We found that genetic inhibition of the OST complex impaired protein processing in the ER, which in turn up-regulated ER unfolded protein response (UPRER). We identified vitellogenin VIT-6 as an OST-dependent glycosylated protein, critical for maintaining survival on PA14. We also showed that the OST complex was required for up-regulation of PMK-1 signaling upon infection with PA14. Our study demonstrates that an evolutionarily conserved OST complex, crucial for ER homeostasis, regulates host defense mechanisms against pathogenic bacteria

Web 2.0 OLAP: From data cubes to tag clouds

Increasingly, business projects are ephemeral. New Business Intelligence tools must support ad-lib data sources and quick perusal. Meanwhile, tag clouds are a popular community-driven visualization technique. Hence, we investigate tag-cloud views with support for OLAP operations such as roll-ups, slices, dices, clustering, and drill-downs. As a case study, we implemented an application where users can upload data and immediately navigate through its ad hoc dimensions. To support social networking, views can be easily shared and embedded in other Web sites. Algorithmically, our tag-cloud views are approximate range top-k queries over spontaneous data cubes. We present experimental evidence that iceberg cuboids provide adequate online approximations. We benchmark several browser-oblivious tag-cloud layout optimizations

Mitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response

Abstract Accumulating evidence indicates that mitochondria play crucial roles in immunity. However, the role of the mitochondrial Krebs cycle in immunity remains largely unknown, in particular at the organism level. Here we show that mitochondrial aconitase, ACO-2, a Krebs cycle enzyme that catalyzes the conversion of citrate to isocitrate, inhibits immunity against pathogenic bacteria in C. elegans. We find that the genetic inhibition of aco-2 decreases the level of oxaloacetate. This increases the mitochondrial unfolded protein response, subsequently upregulating the transcription factor ATFS-1, which contributes to enhanced immunity against pathogenic bacteria. We show that the genetic inhibition of mammalian ACO2 increases immunity against pathogenic bacteria by modulating the mitochondrial unfolded protein response and oxaloacetate levels in cultured cells. Because mitochondrial aconitase is highly conserved across phyla, a therapeutic strategy targeting ACO2 may eventually help properly control immunity in humans