Stress-Induced Cocaine Seeking Requires a Beta-2 Adrenergic Receptor-Regulated Pathway from the Ventral Bed Nucleus of the Stria Terminalis That Regulates CRF Actions in the Ventral Tegmental Area

The ventral bed nucleus of the stria terminalis (vBNST) has been implicated in stress-induced cocaine use. Here we demonstrate that, in the vBNST, corticotropin releasing factor (CRF) is expressed in neurons that innervate the ventral tegmental area (VTA), a site where the CRF receptor antagonist antalarmin prevents the reinstatement of cocaine seeking by a stressor, intermittent footshock, following intravenous self-administration in rats. The vBNST receives dense noradrenergic innervation and expresses β adrenergic receptors (ARs). Footshock-induced reinstatement was prevented by bilateral intra-vBNST injection of the β-2 AR antagonist, ICI-118,551, but not the β-1 AR antagonist, betaxolol. Moreover, bilateral intra-vBNST injection of the β-2 AR agonist, clenbuterol, but not the β-1 agonist, dobutamine, reinstated cocaine seeking, suggesting that activation of vBNST β-2 AR is both necessary for stress-induced reinstatement and sufficient to induce cocaine seeking. The contribution of a β-2 AR-regulated vBNST-to-VTA pathway that releases CRF was investigated using a disconnection approach. Injection of ICI-118,551 into the vBNST in one hemisphere and antalarmin into the VTA of the contralateral hemisphere prevented footshock-induced reinstatement, whereas ipsilateral manipulations failed to attenuate stress-induced cocaine seeking, suggesting that β-2 AR regulate vBNST efferents that release CRF into the VTA, activating CRF receptors, and promoting cocaine use. Last, reinstatement by clenbuterol delivered bilaterally into the vBNST was prevented by bilateral vBNST pretreatment with antalarmin, indicating that β-2 AR-mediated actions in the vBNST also require local CRF receptor activation. Understanding the processes through which stress induces cocaine seeking should guide the development of new treatments for addiction

Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes

ESID: A Visual Analytics Tool to Epidemiological Emergencies

Visual analysis tools can help illustrate the spread of infectious diseases and enable informed decisions on epidemiology and public health issues. To create visualisation tools that are intuitive, easy to use, and effective in communicating information, continued research and development focusing on user-centric and methodological design models is extremely important. As a contribution to this topic, this paper presents the design and development of the visual analytics application ESID (Epidemiological Scenarios for Infectious Diseases). The goal of ESID is to provide a platform for rapid assessment of the most effective interventions for infectious disease control. ESID provides spatial-temporal analysis, forecasting, comparison of simulations, interactive filters, and accessibility options. In its current form, it shows the simulations of a hybrid graph-equation-based model as introduced in for infection control. The model can be stratified for different age groups and takes into account the properties of the infectious disease as well as human mobility and contact behaviour.Comment: 6 pages, 5 images and 1 table, Eurovis workshop on visual analytics (EuroVA) 202

A strategy to characterize the LISA-Pathfinder cold gas thruster system

The cold gas micro-propulsion system that will be used during the LISA-Pathfinder mission will be one of the most important component used to ensure the "free-fall" of the enclosed test masses. In this paper we present a possible strategy to characterize the effective direction and amplitude gain of each of the 6 thrusters of this system

In-flight thermal experiments for LISA pathfinder: simulating temperature noise at the inertial sensors

Thermal Diagnostics experiments to be carried out on board LISA Pathfinder (LPF) will yield a detailed characterisation of how temperature fluctuations affect the LTP (LISA Technology Package) instrument performance, a crucial information for future space based gravitational wave detectors as the proposed eLISA. Amongst them, the study of temperature gradient fluctuations around the test masses of the Inertial Sensors will provide as well information regarding the contribution of the Brownian noise, which is expected to limit the LTP sensitivity at frequencies close to 1 mHz during some LTP experiments. In this paper we report on how these kind of Thermal Diagnostics experiments were simulated in the last LPF Simulation Campaign (November, 2013) involving all the LPF Data Analysis team and using an end-to-end simulator of the whole spacecraft. Such simulation campaign was conducted under the framework of the preparation for LPF operations

Free-flight experiments in LISA Pathfinder

The LISA Pathfinder mission will demonstrate the technology of drag-free test masses for use as inertial references in future space-based gravitational wave detectors. To accomplish this, the Pathfinder spacecraft will perform drag-free flight about a test mass while measuring the acceleration of this primary test mass relative to a second reference test mass. Because the reference test mass is contained within the same spacecraft, it is necessary to apply forces on it to maintain its position and attitude relative to the spacecraft. These forces are a potential source of acceleration noise in the LISA Pathfinder system that are not present in the full LISA configuration. While LISA Pathfinder has been designed to meet it's primary mission requirements in the presence of this noise, recent estimates suggest that the on-orbit performance may be limited by this `suspension noise'. The drift-mode or free-flight experiments provide an opportunity to mitigate this noise source and further characterize the underlying disturbances that are of interest to the designers of LISA-like instruments. This article provides a high-level overview of these experiments and the methods under development to analyze the resulting data.Comment: 13 pages, 5 figures. Accepted to Journal Of Physics, Conference Series. Presented at 10th International LISA Symposium, May 2014, Gainesville, FL, US

The LISA pathfinder mission

ISA Pathfinder (LPF), the second of the European Space Agency's Small Missions for Advanced Research in Technology (SMART), is a dedicated technology validation mission for future spaceborne gravitational wave detectors, such as the proposed eLISA mission. LISA Pathfinder, and its scientific payload - the LISA Technology Package - will test, in flight, the critical technologies required for low frequency gravitational wave detection: it will put two test masses in a near-perfect gravitational free-fall and control and measure their motion with unprecedented accuracy. This is achieved through technology comprising inertial sensors, high precision laser metrology, drag-free control and an ultra-precise micro-Newton propulsion system. LISA Pathfinder is due to be launched in mid-2015, with first results on the performance of the system being available 6 months thereafter. The paper introduces the LISA Pathfinder mission, followed by an explanation of the physical principles of measurement concept and associated hardware. We then provide a detailed discussion of the LISA Technology Package, including both the inertial sensor and interferometric readout. As we approach the launch of the LISA Pathfinder, the focus of the development is shifting towards the science operations and data analysis - this is described in the final section of the paper

State space modelling and data analysis exercises in LISA Pathfinder

LISA Pathfinder is a mission planned by the European Space Agency to test the key technologies that will allow the detection of gravitational waves in space. The instrument on-board, the LISA Technology package, will undergo an exhaustive campaign of calibrations and noise characterisation campaigns in order to fully describe the noise model. Data analysis plays an important role in the mission and for that reason the data analysis team has been developing a toolbox which contains all the functionalities required during operations. In this contribution we give an overview of recent activities, focusing on the improvements in the modelling of the instrument and in the data analysis campaigns performed both with real and simulated data.Comment: Plenary talk presented at the 9th International LISA Symposium, 21-25 May 2012, Pari

A noise simulator for eLISA: migrating LISA pathfinder knowledge to the eLISA mission

We present a new technical simulator for the eLISA mission, based on state space modeling techniques and developed in MATLAB. This simulator computes the coordinate and velocity over time of each body involved in the constellation, i.e. the spacecraft and its test masses, taking into account the different disturbances and actuations. This allows studying the contribution of instrumental noises and system imperfections on the residual acceleration applied on the TMs, the latter reflecting the performance of the achieved free-fall along the sensitive axis. A preliminary version of the results is presented

Disentangling the magnetic force noise contribution in LISA pathfinder

Magnetically-induced forces on the inertial masses on-board LISA Pathfinder are expected to be one of the dominant contributions to the mission noise budget, accounting for up to 40%. The origin of this disturbance is the coupling of the residual magnetization and susceptibility of the test masses with the environmental magnetic field. In order to fully understand this important part of the noise model, a set of coils and magnetometers are integrated as a part of the diagnostics subsystem. During operations a sequence of magnetic excitations will be applied to precisely determine the coupling of the magnetic environment to the test mass displacement using the on-board magnetometers. Since no direct measurement of the magnetic field in the test mass position will be available, an extrapolation of the magnetic measurements to the test mass position will be carried out as a part of the data analysis activities. In this paper we show the first results on the magnetic experiments during an end- to-end LISA Pathfinder simulation, and we describe the methods under development to map the magnetic field on-board