Identification of atropine-and P2X1 receptor antagonist-reistant, neurogenic contractions of the urinary bladder

Acetylcholine and ATP are excitatory cotransmitters in parasympathetic nerves. We used P2X1 receptor antagonists to further characterize the purinergic component of neurotransmission in isolated detrusor muscle of guinea pig urinary bladder. In the presence of atropine (1 μm) and prazosin (100 nm), pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) (0.1–100 μm) and suramin (1–300 μm) inhibited contractions evoked by 4 Hz nerve stimulation in a concentration-dependent manner (IC50 of 6.9 and 13.4 μm, respectively). Maximum inhibition was 50–60%, which was unaffected by coadministration of the ectonucleotidase inhibitor ARL67156 (6-N,N-diethyl-d-β,γ-dibromomethyleneATP) (100 μm). The remaining responses were abolished by tetrodotoxin (1 μm). PPADS and suramin also reduced contractions to exogenous ATP (300 μm) by 40–50%, but abolished those to the P2X1 agonist α,β-methyleneATP (α,β-meATP) (1 μm). The P2X1 antagonists reactive blue 2, NF279 (8,8′-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)] bis-1,3,5-naphthalenetrisulfonic acid), MRS2159 (pyridoxal-α5-phosphate-6-phenylazo-4′-carboxylic acid) (100 μm), and NF449 [4,4′,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid] (3 μm) abolished contractions to α,β-meATP (1 μm; n = 4–5), but only reduced contractions evoked by 4 Hz nerve stimulation by ∼40–60% (n = 4–6) and ATP by 30–60% (n = 4–7). However, prolonged exposure to α,β-meATP (50 μm) abolished contractions evoked by all three stimuli (n = 5–12). PPADS (100 μm) and suramin (300 μm) reduced the peak neurogenic contraction of the mouse urinary bladder to 30–40% of control. At the same concentrations, the P2X1 antagonists abolished the nonadrenergic, purinergic component of neurogenic contractions in the guinea pig vas deferens (n = 4–5). Thus, P2X1 receptor antagonists inhibit, but do not abolish, the noncholinergic component of neurogenic contractions of guinea pig and mouse urinary bladder, indicating a second mode of action of neuronally released ATP. This has important implications for treatment of dysfunctional urinary bladder, for which this atropine- and P2X1 antagonist-resistant site represents a novel therapeutic target

Quantum interference of electromagnetic fields from remote quantum memories

We observe quantum, Hong-Ou-Mandel, interference of fields produced by two remote atomic memories. High-visibility interference is obtained by utilizing the finite atomic memory time in four-photon delayed coincidence measurements. Interference of fields from remote atomic memories is a crucial element in protocols for scalable generation of multi-node remote qubit entanglement.Comment: 4 pages, 3 figure

Computing the Loewner driving process of random curves in the half plane

We simulate several models of random curves in the half plane and numerically compute their stochastic driving process (as given by the Loewner equation). Our models include models whose scaling limit is the Schramm-Loewner evolution (SLE) and models for which it is not. We study several tests of whether the driving process is Brownian motion. We find that just testing the normality of the process at a fixed time is not effective at determining if the process is Brownian motion. Tests that involve the independence of the increments of Brownian motion are much more effective. We also study the zipper algorithm for numerically computing the driving function of a simple curve. We give an implementation of this algorithm which runs in a time O(N^1.35) rather than the usual O(N^2), where N is the number of points on the curve.Comment: 20 pages, 4 figures. Changes to second version: added new paragraph to conclusion section; improved figures cosmeticall

Remarks on geometric entropy

The recently discussed notion of geometric entropy is shown to be related to earlier calculations of thermal effects in Rindler space. The evaluation is extended to de Sitter space and to a two-dimensional black hole.Comment: 7p.,uses jyTeX,MUTP/94/

Generating Interpretable Fuzzy Controllers using Particle Swarm Optimization and Genetic Programming

Autonomously training interpretable control strategies, called policies, using pre-existing plant trajectory data is of great interest in industrial applications. Fuzzy controllers have been used in industry for decades as interpretable and efficient system controllers. In this study, we introduce a fuzzy genetic programming (GP) approach called fuzzy GP reinforcement learning (FGPRL) that can select the relevant state features, determine the size of the required fuzzy rule set, and automatically adjust all the controller parameters simultaneously. Each GP individual's fitness is computed using model-based batch reinforcement learning (RL), which first trains a model using available system samples and subsequently performs Monte Carlo rollouts to predict each policy candidate's performance. We compare FGPRL to an extended version of a related method called fuzzy particle swarm reinforcement learning (FPSRL), which uses swarm intelligence to tune the fuzzy policy parameters. Experiments using an industrial benchmark show that FGPRL is able to autonomously learn interpretable fuzzy policies with high control performance.Comment: Accepted at Genetic and Evolutionary Computation Conference 2018 (GECCO '18

Improved analyses of changes and uncertainties in sea surface temperature measured in situ sice the mid-nineteenth century: The HadSST2 dataset

A new flexible gridded dataset of sea surface temperature (SST) since 1850 is presented and its uncertainties are quantified. This analysis [the Second Hadley Centre Sea Surface Temperature dataset (HadSST2)] is based on data contained within the recently created International Comprehensive Ocean–Atmosphere Data Set (ICOADS) database and so is superior in geographical coverage to previous datasets and has smaller uncertainties. Issues arising when analyzing a database of observations measured from very different platforms and drawn from many different countries with different measurement practices are introduced. Improved bias corrections are applied to the data to account for changes in measurement conditions through time. A detailed analysis of uncertainties in these corrections is included by exploring assumptions made in their construction and producing multiple versions using a Monte Carlo method. An assessment of total uncertainty in each gridded average is obtained by combining these bias-correction-related uncertainties with those arising from measurement errors and undersampling of intragrid box variability. These are calculated by partitioning the variance in grid box averages between real and spurious variability. From month to month in individual grid boxes, sampling uncertainties tend to be most important (except in certain regions), but on large-scale averages bias-correction uncertainties are more dominant owing to their correlation between grid boxes. Changes in large-scale SST through time are assessed by two methods. The linear warming between 1850 and 2004 was 0.52° ± 0.19°C (95% confidence interval) for the globe, 0.59° ± 0.20°C for the Northern Hemisphere, and 0.46° ± 0.29°C for the Southern Hemisphere. Decadally filtered differences for these regions over this period were 0.67° ± 0.04°C, 0.71° ± 0.06°C, and 0.64° ± 0.07°C

Oblique Parameter Constraints on Large Extra Dimensions

We consider the Kaluza-Klein scenario in which gravity propagates in the $4+n$ dimensional bulk of spacetime and the Standard Model particles are confined to a 3-brane. We calculate the gauge boson self-energy corrections arising from the exchange of virtual gravitons and present our results in the $STU$-formalism. We find that the new physics contributions to $S$, $T$ and $U$ decouple in the limit that the string scale $M_S$ goes to infinity. The oblique parameters constrain the lower limit on $M_S$. Taking the quantum gravity cutoff to be $M_S$, $S$-parameter constraints impose $M_S>1.55$ TeV for $n=2$ at the 1$\sigma$ level. $T$-parameter constraints impose $M_S>1.25 (0.75)$ TeV for $n=3 (6)$.Comment: Version to appear in PR

Mott transition in lattice boson models

We use mathematically rigorous perturbation theory to study the transition between the Mott insulator and the conjectured Bose-Einstein condensate in a hard-core Bose-Hubbard model. The critical line is established to lowest order in the tunneling amplitude.Comment: 20 page

Identification of proteins in the postsynaptic density fraction by mass spectrometry

Our understanding of the organization of postsynaptic signaling systems at excitatory synapses has been aided by the identification of proteins in the postsynaptic density (PSD) fraction, a subcellular fraction enriched in structures with the morphology of PSDs. In this study, we have completed the identification of most major proteins in the PSD fraction with the use of an analytical method based on mass spectrometry coupled with searching of the protein sequence databases. At least one protein in each of 26 prominent protein bands from the PSD fraction has now been identified. We found 7 proteins not previously known to be constituents of the PSD fraction and 24 that had previously been associated with the PSD by other methods. The newly identified proteins include the heavy chain of myosin-Va (dilute myosin), a motor protein thought to be involved in vesicle trafficking, and the mammalian homolog of the yeast septin protein cdc10, which is important for bud formation in yeast. Both myosin-Va and cdc10 are threefold to fivefold enriched in the PSD fraction over brain homogenates. Immunocytochemical localization of myosin-Va in cultured hippocampal neurons shows that it partially colocalizes with PSD-95 at synapses and is also diffusely localized in cell bodies, dendrites, and axons. Cdc10 has a punctate distribution in cell bodies and dendrites, with some of the puncta colocalizing with PSD-95. The results support a role for myosin-Va in transport of materials into spines and for septins in the formation or maintenance of spines