Cocaine Addiction as a Homeostatic Reinforcement Learning Disorder

Drug addiction implicates both reward learning and homeostatic regulation mechanisms of the brain. This has stimulated 2 partially successful theoretical perspectives on addiction. Many important aspects of addiction, however, remain to be explained within a single, unified framework that integrates the 2 mechanisms. Building upon a recently developed homeostatic reinforcement learning theory, the authors focus on a key transition stage of addiction that is well modeled in animals, escalation of drug use, and propose a computational theory of cocaine addiction where cocaine reinforces behavior due to its rapid homeostatic corrective effect, whereas its chronic use induces slow and long-lasting changes in homeostatic setpoint. Simulations show that our new theory accounts for key behavioral and neurobiological features of addiction, most notably, escalation of cocaine use, drug-primed craving and relapse, individual differences underlying dose-response curves, and dopamine D2-receptor downregulation in addicts. The theory also generates unique predictions about cocaine self-administration behavior in rats that are confirmed by new experimental results. Viewing addiction as a homeostatic reinforcement learning disorder coherently explains many behavioral and neurobiological aspects of the transition to cocaine addiction, and suggests a new perspective toward understanding addiction

Neutron Star Mergers Are the Dominant Source of the r-process in the Early Evolution of Dwarf Galaxies

There are many candidate sites of the r-process: core-collapse supernovae (including rare magnetorotational core-collapse supernovae), neutron star mergers, and neutron star/black hole mergers. The chemical enrichment of galaxies---specifically dwarf galaxies---helps distinguish between these sources based on the continual build-up of r-process elements. This technique can distinguish between the r-process candidate sites by the clearest observational difference---how quickly these events occur after the stars are created. The existence of several nearby dwarf galaxies allows us to measure robust chemical abundances for galaxies with different star formation histories. Dwarf galaxies are especially useful because simple chemical evolution models can be used to determine the sources of r-process material. We have measured the r-process element barium with Keck/DEIMOS medium-resolution spectroscopy. We present the largest sample of barium abundances (almost 250 stars) in dwarf galaxies ever assembled. We measure [Ba/Fe] as a function of [Fe/H] in this sample and compare with existing [alpha/Fe] measurements. We have found that a large contribution of barium needs to occur at more delayed timescales than core-collapse supernovae in order to explain our observed abundances, namely the significantly more positive trend of the r-process component of [Ba/Fe] vs. [Fe/H] seen for [Fe/H] <~ -1.6 when compared to the [Mg/Fe] vs. [Fe/H] trend. We conclude that neutron star mergers are the most likely source of r-process enrichment in dwarf galaxies at early times.Comment: Accepted to ApJ on 2018 October 2

Conformal invariance in 2-dimensional discrete field theory

A discretized massless wave equation in two dimensions, on an appropriately chosen square lattice, exactly reproduces the solutions of the corresponding continuous equations. We show that the reason for this exact solution property is the discrete analog of conformal invariance present in the model, and find more general field theories on a two-dimensional lattice that exactly solve their continuous limit equations. These theories describe in general non-linearly coupled bosonic and fermionic fields and are similar to the Wess-Zumino-Witten model.Comment: 18 pages, RevTeX, 2 figures included; revision of title and introductio

Levinson's theorem and higher degree traces for Aharonov-Bohm operators

We study Levinson type theorems for the family of Aharonov-Bohm models from different perspectives. The first one is purely analytical involving the explicit calculation of the wave-operators and allowing to determine precisely the various contributions to the left hand side of Levinson's theorem, namely those due to the scattering operator, the terms at 0-energy and at infinite energy. The second one is based on non-commutative topology revealing the topological nature of Levinson's theorem. We then include the parameters of the family into the topological description obtaining a new type of Levinson's theorem, a higher degree Levinson's theorem. In this context, the Chern number of a bundle defined by a family of projections on bound states is explicitly computed and related to the result of a 3-trace applied on the scattering part of the model.Comment: 33 page

Security of Quantum Bit-String Generation

We consider the cryptographic task of bit-string generation. This is a generalisation of coin tossing in which two mistrustful parties wish to generate a string of random bits such that an honest party can be sure that the other cannot have biased the string too much. We consider a quantum protocol for this task, originally introduced in Phys. Rev. A {\bf 69}, 022322 (2004), that is feasible with present day technology. We introduce security conditions based on the average bias of the bits and the Shannon entropy of the string. For each, we prove rigorous security bounds for this protocol in both noiseless and noisy conditions under the most general attacks allowed by quantum mechanics. Roughly speaking, in the absence of noise, a cheater can only bias significantly a vanishing fraction of the bits, whereas in the presence of noise, a cheater can bias a constant fraction, with this fraction depending quantitatively on the level of noise. We also discuss classical protocols for the same task, deriving upper bounds on how well a classical protocol can perform. This enables the determination of how much noise the quantum protocol can tolerate while still outperforming classical protocols. We raise several conjectures concerning both quantum and classical possibilities for large n cryptography. An experiment corresponding to the scheme analysed in this paper has been performed and is reported elsewhere.Comment: 16 pages. No figures. Accepted for publication in Phys. Rev. A. A corresponding experiment is reported in quant-ph/040812

Macrocyclic cyanocobalamin (vitamin B12) as a homogeneous electrocatalyst for water oxidation under neutral conditions

Highly water-soluble cyanocobalamin (also known as vitamin B-12) is the most structurally macrocyclic complex comprising cobalt in the center of a corrin ring. Interestingly, it acts as a robust electrocatalyst in water oxidation at similar to 0.58 V overpotential with a faradaic efficiency of 97.50% under neutral buffered conditions. The catalyst is impressively stable even after long-term bulk electrolysis, and homogeneous in nature, as established by a series of experiments and characterization techniques

Fluctuations of the partial filling factors in competitive RSA from binary mixtures

Competitive random sequential adsorption on a line from a binary mix of incident particles is studied using both an analytic recursive approach and Monte Carlo simulations. We find a strong correlation between the small and the large particle distributions so that while both partial contributions to the fill factor fluctuate widely, the variance of the total fill factor remains relatively small. The variances of partial contributions themselves are quite different between the smaller and the larger particles, with the larger particle distribution being more correlated. The disparity in fluctuations of partial fill factors increases with the particle size ratio. The additional variance in the partial contribution of smaller particle originates from the fluctuations in the size of gaps between larger particles. We discuss the implications of our results to semiconductor high-energy gamma detectors where the detector energy resolution is controlled by correlations in the cascade energy branching process.Comment: 19 pages, 8 figure

Synthesis and evaluation of N⁶-substituted apioadenosines as potential adenosine A₃ receptor modulators

Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A(3)AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of beta-D-apio-D-furano- and alpha-D-apio-L-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N-6 of beta-D-apio-D-furanoadenosine afforded an A(3)AR antagonist (10c, K = 0.98 mu M), while a similar modification of an alpha-D-apio-L-furanoadenosine gave rise to a partial agonist (11c, K-i = 3.07 mu M). The structural basis for this difference was examined by docking to an A(3)AR model; the antagonist lacked a crucial interaction with Thr94