Are animal models of addiction useful?

Background: Preclinical research involving non-human animals has made important contributions to our understanding of risk-factors for addiction, neuroadaptations that follow chronic drug exposure, and to the development of some efficacious pharmacotherapies for addiction. Despite these contributions, we argue that animal models of addiction have impeded progress in our understanding of addiction and its treatment in humans. Argument: First of all, the majority of pharmacological treatments that were initially developed using animal models have failed to prove effective for the treatment of addiction in humans, resulting in a huge waste of resources. Secondly, we demonstrate that prevailing animal models that portray addiction as a disorder of compulsion and habit cannot be reconciled with observations that psychoactive drug use in humans is a goal-directed operant behaviour that remains under the control of its consequences, even in people who are addicted. Thirdly, addiction may be a uniquely human phenomenon that is dependent on language, which necessarily limits the validity of animal models. Finally, we argue that addicted brains must be understood as one component of broader networks of symptoms and environmental and social factors that are impossible to model in laboratory animals. Conclusions: A case can be made that animal models of addiction have not served us well in understanding and treating addiction in humans. It is important to reconsider some widely-held beliefs about the nature of addictive behaviour in humans that have arisen from the zeal to translate observations of laboratory animals

Type soundness for dependent object types (DOT)

Scala's type system unifies aspects of ML modules, object-oriented, and functional programming. The Dependent Object Types (DOT) family of calculi has been proposed as a new theoretic foundation for Scala and similar expressive languages. Unfortunately, type soundness has only been established for restricted subsets of DOT. In fact, it has been shown that important Scala features such as type refinement or a subtyping relation with lattice structure break at least one key metatheoretic property such as environment narrowing or invertible subtyping transitivity, which are usually required for a type soundness proof. The main contribution of this paper is to demonstrate how, perhaps surprisingly, even though these properties are lost in their full generality, a rich DOT calculus that includes recursive type refinement and a subtyping lattice with intersection types can still be proved sound. The key insight is that subtyping transitivity only needs to be invertible in code paths executed at run time, with contexts consisting entirely of valid runtime objects, whereas inconsistent subtyping contexts can be permitted for code that is never executed

Quantum Films Adsorbed on Graphite: Third and Fourth Helium Layers

Using a path-integral Monte Carlo method for simulating superfluid quantum films, we investigate helium layers adsorbed on a substrate consisting of graphite plus two solid helium layers. Our results for the promotion densities and the dependence of the superfluid density on coverage are in agreement with experiment. We can also explain certain features of the measured heat capacity as a function of temperature and coverage.Comment: 13 pages in the Phys. Rev. two-column format, 16 Figure

Unconventional carrier-mediated ferromagnetism above room temperature in ion-implanted (Ga, Mn)P:C

Ion implantation of Mn ions into hole-doped GaP has been used to induce ferromagnetic behavior above room temperature for optimized Mn concentrations near 3 at.%. The magnetism is suppressed when the Mn dose is increased or decreased away from the 3 at.% value, or when n-type GaP substrates are used. At low temperatures the saturated moment is on the order of one Bohr magneton, and the spin wave stiffness inferred from the Bloch-law T^3/2 dependence of the magnetization provides an estimate Tc = 385K of the Curie temperature that exceeds the experimental value, Tc = 270K. The presence of ferromagnetic clusters and hysteresis to temperatures of at least 330K is attributed to disorder and proximity to a metal-insulating transition.Comment: 4 pages, 4 figures (RevTex4

‘Superbull’ males : what role do they play and what drives their appearance within the Doryteuthis gahi Patagonian Shelf population?

This work was funded by the Falkland Islands Government. Thanks are due to FCT/MCTES for financial support to CESAM (UID/AMB/50017/2019) through national funds and ERDF co-financing, under the Partnership Agreement for the PT2020 and Compete 2020 programs. This work was funded by the Falkland Islands Government. The study was conducted using E.U. Copernicus Marine Service Information. We are grateful to the scientific observers from the Falkland Islands fisheries department for sample collection and to the director of fisheries, John Barton, for supporting this work.Peer reviewedPublisher PD

Dehydration mechanism of a small molecular solid: 5-nitrouracil hydrate

Previous studies of the dehydration of 5-nitrouracil (5NU) have resulted in it being classified as a ‘‘channel hydrate’’ in which dehydration proceeds principally by the exit of the water molecules along channels in the structure. We have re-examined this proposal and found that in fact there are no continuous channels in the 5NU structure that would contribute to such a mechanism. Product water molecules would be immediately trapped in unlinked voids in the crystal structure and would require some additional mechanism to break loose from the crystal. Through a detailed structural analysis of the macro and micro structure of the 5NU as it dehydrates, we have developed a model for the dehydration process based on the observed development of structural defects in the 5NU crystal and the basic crystallography of the material. The model was tested against standard kinetic measurements and found to present a satisfactory account of kinetic observations, thus defining the mechanism. Overall, the study shows the necessity of complementing standard kinetic studies with a parallel macro and micro examination of the dehydrating material when evaluating the mechanisms of dehydration and decomposition processes

Cosmic antiprotons as a probe for supersymmetric dark matter?

The flux of cosmic ray antiprotons from neutralino annihilations in the galactic halo is computed for a large sample of models in the MSSM (the Minimal Supersymmetric extension of the Standard Model). We also revisit the problem of estimating the background of low-energy cosmic ray induced secondary antiprotons, taking into account their subsequent interactions (and energy loss) and the presence of nuclei in the interstellar matter. We consider a two-zone diffusion model, with and without a galactic wind. We find that, given the uncertainties in the background predictions, there is no need for a primary (exotic) component to explain present data. However, allowing for a signal by playing with the uncertainties in the background estimate, we discuss the characteristic features of the supersymmetric models which give a satisfactory description of the data. We point out that in some cases the optimal kinetic energy to search for a signal from supersymmetric dark matter is above several GeV, rather than the traditional sub-GeV region. The large astrophysical uncertainties involved do not, one the other hand, allow the exclusion of any of the MSSM models we consider, on the basis of data. We present besides numerical results also convenient parameterizations of the antiproton yields of all `basic' two-body final states. We also give examples of the yield and differential energy spectrum for a set of supersymmetric models with high rates. We also remark that it is difficult to put a limit on the antiproton lifetime from present measurements, since the injection of antiprotons from neutralino annihilation can compensate the loss from decay.Comment: 22 pages, 11 figures, uses emulateapj.st

A Calculus of Bounded Capacities

Resource control has attracted increasing interest in foundational research on distributed systems. This paper focuses on space control and develops an analysis of space usage in the context of an ambient-like calculus with bounded capacities and weighed processes, where migration and activation require space. A type system complements the dynamics of the calculus by providing static guarantees that the intended capacity bounds are preserved throughout the computation

Tracking and imaging gamma ray experiment (TIGRE) for 1 to 100 MEV gamma ray astronomy

A large international collaboration from the high energy astrophysics community has proposed the Tracking and Imaging Gamma Ray Experiment (TIGRE) for future space observations. TIGRE will image and perform energy spectroscopy measurements on celestial sources of gamma rays in the energy range from 1 to 100 MeV. This has been a difficult energy range experimentally for gamma ray astronomy but is vital for the future considering the recent exciting measurements below 1 and above 100 MeV. TIGRE is both a double scatter Compton and gamma ray pair telescope with direct imaging of individual gamma ray events. Multi‐layers of Si strip detectors are used as Compton and pair converters CsI(Tl) scintillation detectors are used as a position sensitive calorimeter. Alternatively, thick GE strip detectors may be used for the calorimeter. The Si detectors are able to track electrons and positrons through successive Si layers and measure their directions and energy losses. Compton and pair events are completely reconstructed allowing each event to be imaged on the sky. TIGRE will provide an order‐of‐magnitude improvement in discrete source sensitivity in the 1 to 100 MeV energy range and determine spectra with excellent energy and excellent angular resolutions. It’s wide field‐of‐view of π sr permits observations of the entire sky for extended periods of time over the life of the mission