Cocaine Selectively Reorganizes Excitatory Inputs to Substantia Nigra Pars Compacta Dopamine Neurons

Substantia nigra pars compacta (SNc) dopamine neurons and their targets are involved in addiction and cue-induced relapse. However, afferents onto SNc dopamine neurons themselves appear insensitive to drugs of abuse, such as cocaine, when afferents are collectively stimulated electrically. This contrasts with ventral tegmental area (VTA) dopamine neurons, whose glutamate afferents react robustly to cocaine. We used an optogenetic strategy to isolate identified SNc inputs and determine whether cocaine sensitivity in the mouse SNc circuit is conferred at the level of three glutamate afferents: dorsal raphé nucleus (DR), pedunculopontine nucleus (PPN), and subthalamic nucleus (STN). We found that excitatory afferents to SNc dopamine neurons are sensitive to cocaine in an afferent-specific manner. A single exposure to cocaine in vivo led to PPN-innervated synapses reducing the AMPA-to-NMDA receptor-mediated current ratio. In contrast to work in the VTA, this was due to increased NMDA receptor function with no change in AMPA receptor function. STN synapses showed a decrease in calcium-permeable AMPA receptors after cocaine, but no change in the AMPA-to-NMDA ratio. Cocaine also increased the release probability at DR-innervated and STN-innervated synapses, quantified by decreases in paired-pulse ratios. However, release probability at PPN-innervated synapses remained unaffected. By examining identified inputs, our results demonstrate a functional distribution among excitatory SNc afferent nuclei in response to cocaine, and suggest a compelling architecture for differentiation and separate parsing of inputs within the nigrostriatal system

Modeling DNA Structure, Elasticity and Deformations at the Base-pair Level

We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between neighboring base-pairs. The sugar-phosphate backbones are taken into account by semi-rigid harmonic springs with a non-zero spring length. The competition of these two interactions and the introduction of a simple geometrical constraint leads to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the Stack-of-Plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean squared base-pair step parameters. For the optimized model parameters we measured the critical force where the transition from B- to S-DNA occurs to be approximately $140{pN}$. We observe an overstretched S-DNA conformation with highly inclined bases that partially preserves the stacking of successive base-pairs.Comment: 15 pages, 25 figures. submitted to PR

Optical spectroscopic study of the interplay of spin and charge in NaV2O5

We investigate the temperature dependent optical properties of NaV2O5, in the energy range 4meV-4eV. The symmetry of the system is discussed on the basis of infrared phonon spectra. By analyzing the optically allowed phonons at temperatures below and above the phase transition, we conclude that a second-order change to a larger unit cell takes place below 34 K, with a fluctuation regime extending over a broad temperature range. In the high temperature undistorted phase, we find good agreement with the recently proposed centrosymmetric space group Pmmn. On the other hand, the detailed analysis of the electronic excitations detected in the optical conductivity, provides direct evidence for a charge disproportionated electronic ground-state, at least on a locale scale: A consistent interpretation of both structural and optical conductivity data requires an asymmetrical charge distribution on each rung, without any long range order. We show that, because of the locally broken symmetry, spin-flip excitations carry a finite electric dipole moment, which is responsible for the detection of direct two-magnon optical absorption processes for E parallel to the a axis. The charged-magnon model, developed to interpret the optical conductivity of NaV2O5, is described in detail, and its relevance to other strongly correlated electron systems, where the interplay of spin and charge plays a crucial role in determining the low energy electrodynamics, is discussed.Comment: Revtex, 19 pages, 16 postscript pictures embedded in the text, submitted to PRB. Find more stuff at http://www.stanford.edu/~damascel/andreaphd.html or http://www.ub.rug.nl/eldoc/dis/science/a.damascelli

Understanding the process of psychological development in youth athletes attending an intensive wrestling camp

This study used a grounded theory methodology to understand if and how psychological development in youth athletes was facilitated by an ‘intensive’ summer wrestling camp experience. The theoretical sampling approach involved 10 athlete participants of the camp, nine parents of athletes, the director of the camp, and four camp staff members, who took part in a series of interviews before, during, and after the camp. Two researchers were also embedded in the camp and attended all sessions, took detailed notes, collected camp materials, and conducted observations. Following a grounded theory analysis approach, a model is presented that outlines how youth participants’ developed psychological qualities from the coach created hallenges and adversity that were systematically designed to facilitate sport performance enhancement and life skills. Variations emerged in psychological antecedents and characteristics, how the challenging wrestling camp environment was interpreted and experienced, and how learning was transferred to sport and life domains outside of the wrestling camp. This study provided insight into a unique youth sport context that was able to simultaneously develop psychological qualities to be used as sport performance enhancement and life skills

Balloon Measurements of Cosmic Ray Muon Spectra in the Atmosphere along with those of Primary Protons and Helium Nuclei over Mid-Latitude

We report here the measurements of the energy spectra of atmospheric muons and of the cosmic ray primary proton and helium nuclei in a single experiment. These were carried out using the MASS superconducting spectrometer in a balloon flight experiment in 1991. The relevance of these results to the atmospheric neutrino anomaly is emphasized. In particular, this approach allows uncertainties caused by the level of solar modulation, the geomagnetic cut-off of the primaries and possible experimental systematics to be decoupled in the comparison of calculated fluxes of muons to measured muon fluxes. The muon observations cover the momentum and depth ranges of 0.3-40 GeV/c and 5-886 g/cmsquared, respectively. The proton and helium primary measurements cover the rigidity range from 3 to 100 GV, in which both the solar modulation and the geomagnetic cut-off affect the energy spectra at low energies.Comment: 31 pages, including 17 figures, simplified apparatus figure, to appear in Phys. Rev.

Scale-free memory model for multiagent reinforcement learning. Mean field approximation and rock-paper-scissors dynamics

A continuous time model for multiagent systems governed by reinforcement learning with scale-free memory is developed. The agents are assumed to act independently of one another in optimizing their choice of possible actions via trial-and-error search. To gain awareness about the action value the agents accumulate in their memory the rewards obtained from taking a specific action at each moment of time. The contribution of the rewards in the past to the agent current perception of action value is described by an integral operator with a power-law kernel. Finally a fractional differential equation governing the system dynamics is obtained. The agents are considered to interact with one another implicitly via the reward of one agent depending on the choice of the other agents. The pairwise interaction model is adopted to describe this effect. As a specific example of systems with non-transitive interactions, a two agent and three agent systems of the rock-paper-scissors type are analyzed in detail, including the stability analysis and numerical simulation. Scale-free memory is demonstrated to cause complex dynamics of the systems at hand. In particular, it is shown that there can be simultaneously two modes of the system instability undergoing subcritical and supercritical bifurcation, with the latter one exhibiting anomalous oscillations with the amplitude and period growing with time. Besides, the instability onset via this supercritical mode may be regarded as "altruism self-organization". For the three agent system the instability dynamics is found to be rather irregular and can be composed of alternate fragments of oscillations different in their properties.Comment: 17 pages, 7 figur

The First VERITAS Telescope

The first atmospheric Cherenkov telescope of VERITAS (the Very Energetic Radiation Imaging Telescope Array System) has been in operation since February 2005. We present here a technical description of the instrument and a summary of its performance. The calibration methods are described, along with the results of Monte Carlo simulations of the telescope and comparisons between real and simulated data. The analysis of TeV $\gamma$-ray observations of the Crab Nebula, including the reconstructed energy spectrum, is shown to give results consistent with earlier measurements. The telescope is operating as expected and has met or exceeded all design specifications.Comment: Accepted by Astroparticle Physic

Effective Functional Form of Regge Trajectories

We present theoretical arguments and strong phenomenological evidence that hadronic Regge trajectories are essentially nonlinear and can be well approximated, for phenomenological purposes, by a specific square-root form.Comment: 29 pages, LaTeX. Published versio

Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy

Acute myeloid leukemia (AML) is a malignancy of immature progenitor cells. AML differentiation therapies trigger leukemia maturation and can induce remission, but relapse is prevalent and its cellular origin is unclear. Here we describe high resolution analysis of differentiation therapy response and relapse in a mouse AML model. Triggering leukemia differentiation in this model invariably produces two phenotypically distinct mature myeloid lineages in vivo. Leukemia-derived neutrophils dominate the initial wave of leukemia differentiation but clear rapidly and do not contribute to residual disease. In contrast, a therapyinduced population of mature AML-derived eosinophil-like cells persists during remission, often in extramedullary organs. Using genetic approaches we show that restricting therapy induced leukemia maturation to the short-lived neutrophil lineage markedly reduces relapse rates and can yield cure. These results indicate that relapse can originate from therapy resistant mature AML cells, and suggest differentiation therapy combined with targeted eradication of mature leukemia-derived lineages may improve disease outcome.Steven Ngo, Ethan P. Oxley, Margherita Ghisi, Maximilian M. Garwood, Mark D. McKenzie, Helen L. Mitchell, Peter Kanellakis, Olivia Susanto, Michael J. Hickey, Andrew C. Perkins, Benjamin T. Kile, Ross A. Dickin