A Pointing Solution for the Medium Size Telescopes for the Cherenkov Telescope Array

An important aspect of the calibration of the Cherenkov Telescope Array is the pointing, which enables an exact alignment of each telescope and therefore allows to transform a position in the sky to a point in the plane of the Cherenkov camera and vice versa. The favoured approach for the pointing calibration of the medium size telescopes (MST) is the installation of an optical CCD-camera in the dish of the telescope that captures the position of the Cherenkov camera and of the stars in the night sky simultaneously during data taking. The adaption of this approach is presented in this proceeding.Comment: 6 pages, 9 figures, Proceedings of the 6th International Symposium on High-Energy Gamma-Ray Astronomy (Gamma2016

Capability of Cherenkov Telescopes to Observe Ultra-fast Optical Flares

The large optical reflector (~ 100 m^2) of a H.E.S.S. Cherenkov telescope was used to search for very fast optical transients of astrophysical origin. 43 hours of observations targeting stellar-mass black holes and neutron stars were obtained using a dedicated photometer with microsecond time resolution. The photometer consists of seven photomultiplier tube pixels: a central one to monitor the target and a surrounding ring of six pixels to veto background events. The light curves of all pixels were recorded continuously and were searched offline with a matched-filtering technique for flares with a duration of 2 us to 100 ms. As expected, many unresolved (500 us) background events originating in the earth's atmosphere were detected. In the time range 3 to 500 us the measurement is essentially background-free, with only eight events detected in 43 h; five from lightning and three presumably from a piece of space debris. The detection of flashes of brightness ~ 0.1 Jy and only 20 us duration from the space debris shows the potential of this setup to find rare optical flares on timescales of tens of microseconds. This timescale corresponds to the light crossing time of stellar-mass black holes and neutron stars.Comment: Accepted for publication in Astroparticle Physics, 8 pages, 9 figures, 1 tabl

Observations of the Crab Nebula with H.E.S.S. Phase II

The High Energy Stereoscopic System (H.E.S.S.) phase I instrument was an array of four $100\,\mathrm{m}^2$ mirror area Imaging Atmospheric Cherenkov Telescopes (IACTs) that has very successfully mapped the sky at photon energies above $\sim 100\,$GeV. Recently, a $600\,\mathrm{m}^2$ telescope was added to the centre of the existing array, which can be operated either in standalone mode or jointly with the four smaller telescopes. The large telescope lowers the energy threshold for gamma-ray observations to several tens of GeV, making the array sensitive at energies where the Fermi-LAT instrument runs out of statistics. At the same time, the new telescope makes the H.E.S.S. phase II instrument. This is the first hybrid IACT array, as it operates telescopes of different size (and hence different trigger rates) and different field of view. In this contribution we present results of H.E.S.S. phase II observations of the Crab Nebula, compare them to earlier observations, and evaluate the performance of the new instrument with Monte Carlo simulations.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherland

Targeting Astrocytes Ameliorates Neurologic Changes in a Mouse Model of Alzheimer\u27s Disease

Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer\u27s disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically activated phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific Gfa2 promoter to target hippocampal astrocytes in APP/PS1 mice. AAV-Gfa2 vectors drove the expression of VIVIT, a peptide that interferes with the immune/inflammatory calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway, shown by our laboratory and others to orchestrate biochemical cascades leading to astrocyte activation. After several months of treatment with Gfa2-VIVIT, APP/PS1 mice exhibited improved cognitive and synaptic function, reduced glial activation, and lower amyloid levels. The results confirm a deleterious role for activated astrocytes in AD and lay the groundwork for exploration of other novel astrocyte-based therapies

The roles of inflammation and immune mechanisms in Alzheimer's disease

AbstractThe Alzheimer's Association's Research roundtable met in April 2015 to explore the role of neuroinflammatory mechanisms in the progression of Alzheimer's disease (AD). The ability of innate immune cells, particularly microglia and astrocytes, to mediate neuroinflammation in AD has been implicated as a significant contributor to disease pathogenesis. Adaptive immunity, which plays an important role in responding to injury and some diseases of the central nervous system, may contribute to neuroinflammation in AD as well. Communication between the central and peripheral immune systems may also be important in AD. An increased understanding of the physiology of the innate immune system may aid the identification of new therapeutic targets or mechanisms. The development of predictive animal models and translatable neuroinflammation biomarkers for AD would also facilitate the advancement of novel treatments for innate immunity. Important challenges impeding the advancement of new therapeutic agents and strategies to overcome them were discussed

Challenges and Considerations Related to Studying Dementia in Blacks/African Americans

Blacks/African Americans have been reported to be ~2–4 times more likely to develop clinical Alzheimer’s disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic groups. We encourage neuroscientists to consider shifting away from using biologic determination to interpret data, and work instead toward a paradigm of incorporating both biological and socio-environmental factors known to affect health outcomes with the goal of understanding and improving dementia treatments for Blacks/African Americans and other underserved populations

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective p38αMAPK Inhibitor that Attenuates Disease Progression in Alzheimer\u27s Disease Mouse Models

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, pursuit of the neurotherapeutic hypothesis requires kinase isoform selective inhibitors with appropriate neuropharmacology features. Synaptic dysfunction disorders offer a potential for enhanced pharmacological efficacy due to stress-induced activation of p38αMAPK in both neurons and glia, the interacting cellular components of the synaptic pathophysiological axis, to be modulated. We report a novel isoform selective p38αMAPK inhibitor, MW01-18-150SRM (=MW150), that is efficacious in suppression of hippocampal-dependent associative and spatial memory deficits in two distinct synaptic dysfunction mouse models. A synthetic scheme for biocompatible product and positive outcomes from pharmacological screens are presented. The high-resolution crystallographic structure of the p38αMAPK/MW150 complex documents active site binding, reveals a potential low energy conformation of the bound inhibitor, and suggests a structural explanation for MW150\u27s exquisite target selectivity. As far as we are aware, MW150 is without precedent as an isoform selective p38MAPK inhibitor or as a kinase inhibitor capable of modulating in vivo stress related behavior

Calibration Strategy of the Cherenkov Telescope Array

The construction of the Cherenkov Telescope Array is expected to start soon. We will present the baseline methods and their extensions currently foreseen to calibrate the observatory. These are bound to achieve the strong requirements on allowed systematic uncertainties for the reconstructed gamma-ray energy and flux scales, as well as on the pointing resolution, and on the overall duty cycle of the observatory. Onsite calibration activities are designed to include a robust and efficient calibration of the telescope cameras, and various methods and instruments to achieve calibration of the overall optical throughput of each telescope, leading to both inter-telescope calibration and an absolute calibration of the entire observatory. One important aspect of the onsite calibration is a correct understanding of the atmosphere above the telescopes, which constitutes the calorimeter of this detection technique. It is planned to be constantly monitored with state-of-the-art instruments to obtain a full molecular and aerosol profile up to the stratosphere. In order to guarantee the best use of the observation time, in terms of usable data, an intelligent scheduling system is required, which gives preference to those sources and observation programs that can cope with the given atmospheric conditions, especially if the sky is partially covered by clouds, or slightly contaminated by dust. Ceilometers in combination with all-sky-cameras are plannned to provide the observatory with a fast, online and full-sky knowledge of the expected conditions for each pointing direction. For a precise characterization of the adopted observing direction, wide-field optical telescopes and Raman Lidars are planned to provide information about the height-resolved and wavelength-dependent atmospheric extinction, throughout the field-of-view of the cameras