Hydrocarbon molar water solubility predicts NMDA vs. GABAA receptor modulation.

BackgroundMany anesthetics modulate 3-transmembrane (such as NMDA) and 4-transmembrane (such as GABAA) receptors. Clinical and experimental anesthetics exhibiting receptor family specificity often have low water solubility. We hypothesized that the molar water solubility of a hydrocarbon could be used to predict receptor modulation in vitro.MethodsGABAA (α1β2γ2s) or NMDA (NR1/NR2A) receptors were expressed in oocytes and studied using standard two-electrode voltage clamp techniques. Hydrocarbons from 14 different organic functional groups were studied at saturated concentrations, and compounds within each group differed only by the carbon number at the ω-position or within a saturated ring. An effect on GABAA or NMDA receptors was defined as a 10% or greater reversible current change from baseline that was statistically different from zero.ResultsHydrocarbon moieties potentiated GABAA and inhibited NMDA receptor currents with at least some members from each functional group modulating both receptor types. A water solubility cut-off for NMDA receptors occurred at 1.1 mM with a 95% CI = 0.45 to 2.8 mM. NMDA receptor cut-off effects were not well correlated with hydrocarbon chain length or molecular volume. No cut-off was observed for GABAA receptors within the solubility range of hydrocarbons studied.ConclusionsHydrocarbon modulation of NMDA receptor function exhibits a molar water solubility cut-off. Differences between unrelated receptor cut-off values suggest that the number, affinity, or efficacy of protein-hydrocarbon interactions at these sites likely differ

A Contraction Theory Approach to Stochastic Incremental Stability

We investigate the incremental stability properties of It\^o stochastic dynamical systems. Specifically, we derive a stochastic version of nonlinear contraction theory that provides a bound on the mean square distance between any two trajectories of a stochastically contracting system. This bound can be expressed as a function of the noise intensity and the contraction rate of the noise-free system. We illustrate these results in the contexts of stochastic nonlinear observers design and stochastic synchronization.Comment: 23 pages, 2 figure

Life cycle assessment of intensive striped catfish farming in the Mekong Delta for screening hotspots as input to environmental policy and research agenda

Purpose Intensive striped catfish production in the Mekong Delta has, in recent years, raised environmental concerns. We conducted a stakeholder-based screening life cycle assessment (LCA) of the intensive farming system to determine the critical environmental impact and their causative processes in producing striped catfish. Additional to the LCA, we assessed water use and flooding hazards in the Mekong Delta. Materials and methods The goal and scope of the LCA were defined in a stakeholder workshop. It was decided there to include all processes up to the exit-gate of the fish farm in the inventory and to focus life cycle impact assessment on global warming, acidification, eutrophication, human toxicity, and marine (MAET) and freshwater aquatic ecotoxicity (FWET). A survey was used to collect primary inventory data from 28 farms on fish grow-out, and from seven feed mills. Hatching and nursing of striped catfish fingerlings were not included in the assessment due to limited data availability and low estimated impact. Average feed composition for all farms had to be applied due to limitation of budget and data availability. Results and discussion Feed ingredient production, transport and milling dominated most of the impact categories in the LCA except for eutrophication and FWET. Most feed ingredients were produced outside Vietnam, and the impact of transport was important. Because of the screening character of this LCA, generic instead of specific inventory data were used for modelling feed ingredient production. However, the use of generic data is unlikely to have affected the main findings, given the dominance of feed production in all impact categories. Of the feed ingredients, rice bran contributed the most to global warming and acidification, while wheat bran contributed the most to eutrophication. The dominance of both was mainly due to the amounts used. Fishmeal production, transport and energy contributed the most to MAET. The biggest impacts of grow-out farming in Vietnam are on eutrophication and FWET. Water nutrient discharge from grow-out farming was high but negligible compared with the natural nutrient content of the Mekong River. The discharge from all grow-out farms together hardly modified river water quality compared with that before sector expansion. Conclusions Feed production, i.e. ingredient production and transport and milling, remains the main contributor to most impact categories. It contributes indirectly to eutrophication and FWET through the pond effluents. The environmental impact of Pangasius grow-out farming can be reduced by effectively managing sludge and by using feeds with lower feed conversion ratio and lower content of fishery products in the feed. To consider farm variability, a next LCA of aquaculture should enlist closer collaboration from several feed-milling companies and sample farms using their feeds. Future LCAs should also preferably collect specific instead of generic inventory data for feed ingredient production, and include biodiversity and primary production as impact categories

Collapse dynamics of copolymers in a poor solvent: Influence of hydrodynamic interactions and chain sequence

We investigate the dynamics of the collapse of a single copolymer chain, when the solvent quality is suddenly quenched from good to poor. We employ Brownian dynamics simulations of a bead-spring chain model and incorporate fluctuating hydrodynamic interactions via the Rotne-Prager-Yamakawa tensor. Various copolymer architectures are studied within the framework of a two-letter HP model, where monomers of type H (hydrophobic) attract each other, while all interactions involving P (polar or hydrophilic) monomers are purely repulsive. The hydrodynamic interactions are found to assist the collapse. Furthermore, the chain sequence has a strong influence on the kinetics and on the compactness and energy of the final state. The dynamics is typically characterised by initial rapid cluster formation, followed by coalescence and final rearrangement to form the compact globule. The coalescence stage takes most of the collapse time, and its duration is particularly sensitive to the details of the architecture. Long blocks of type P are identified as the main bottlenecks to find the globular state rapidly.Comment: 25 pages, 13 figures, Submitted to Macromolecule

CP asymmetry and branching ratio of B -> pi pi

We investigate the branching ratios and CP asymmetries of the B -> pi pi processes measured in B factory experiments. Fits to the experimental data of this process indicate a large ratio of color-suppressed (C) to color-allowed (T) tree contributions. We investigate whether the large C/T can be explained within the QCD based model computation with i) a large effect from the end-point singularity or with ii) large final-state-interaction phase between two different isospin amplitudes. We show that the current experimental data do not exclude either possibility but we may be able to distinguish these two effects in future measurements of direct CP asymmetry of B -> pi^0 pi^0.Comment: 8 pages, 10 figure