High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.

PURPOSE: To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients. DESIGN: Retrospective clinical and molecular genetic study. METHODS: Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot. RESULTS: We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1-0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families. CONCLUSIONS: The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0%-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases, which could be underdiagnosed

Acoustic and optical variations during rapid downward motion episodes in the deep north-western Mediterranean Sea

An Acoustic Doppler Current Profiler (ADCP) was moored at the deep-sea site of the ANTARES neutrino telescope near Toulon, France, thus providing a unique opportunity to compare high-resolution acoustic and optical observations between 70 and 170 m above the sea bed at 2475 m. The ADCP measured downward vertical currents of magnitudes up to 0.03 m s-1 in late winter and early spring 2006. In the same period, observations were made of enhanced levels of acoustic reflection, interpreted as suspended particles including zooplankton, by a factor of about 10 and of horizontal currents reaching 0.35 m s-1. These observations coincided with high light levels detected by the telescope, interpreted as increased bioluminescence. During winter 2006 deep dense-water formation occurred in the Ligurian subbasin, thus providing a possible explanation for these observations. However, the 10-20 days quasi-periodic episodes of high levels of acoustic reflection, light and large vertical currents continuing into the summer are not direct evidence of this process. It is hypothesized that the main process allowing for suspended material to be moved vertically later in the year is local advection, linked with topographic boundary current instabilities along the rim of the 'Northern Current'.Comment: 30 pages, 7 figure

The ANTARES Telescope Neutrino Alert System

The ANTARES telescope has the capability to detect neutrinos produced in astrophysical transient sources. Potential sources include gamma-ray bursts, core collapse supernovae, and flaring active galactic nuclei. To enhance the sensitivity of ANTARES to such sources, a new detection method based on coincident observations of neutrinos and optical signals has been developed. A fast online muon track reconstruction is used to trigger a network of small automatic optical telescopes. Such alerts are generated for special events, such as two or more neutrinos, coincident in time and direction, or single neutrinos of very high energy.Comment: 17 pages, 9 figures submitted to Astroparticle Physic

Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction

OBJECTIVE: OPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1 patients. METHODS: Twenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Patients underwent neuro-ophthalmological examinations. Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Twenty patients underwent 2-D proton spectroscopic imaging. RESULTS: Brain imaging disclosed abnormalities in 12 patients. Cerebellar atrophy mainly involving the vermis was observed in almost a quarter of the patients; other abnormalities included unspecific white matter hypersignal, hemispheric cortical atrophy, and lactate peak. Neurological examination disclosed one patient with a transient right hand motor deficit and ENT examination revealed hearing impairment in 6 patients. Patients with abnormal MRI were characterized by: (i) an older age (ii) more severe visual impairment with chronic visual acuity deterioration, and (iii) more frequent associated deafness. CONCLUSIONS: Our results demonstrate that brain imaging abnormalities are common in OPA1 patients, even in those with normal neurological examination. Lactate peak, cerebellar and cortical atrophies are consistent with the mitochondrial dysfunction related to OPA1 mutations and might result from widespread neuronal degeneration

Time calibration of the ANTARES neutrino telescope

The ANTARES deep-sea neutrino telescope comprises a three-dimensional array of photomultipliers to detect the Cherenkov light induced by upgoing relativistic charged particles originating from neutrino interactions in the vicinity of the detector. The large scattering length of light in the deep sea facilitates an angular resolution of a few tenths of a degree for neutrino energies exceeding 10 TeV. In order to achieve this optimal performance, the time calibration procedures should ensure a relative time calibration between the photomultipliers at the level of similar to 1 ns. The methods developed to attain this level of precision are described

The positioning system of the ANTARES Neutrino Telescope

The ANTARES neutrino telescope, located 40km off the coast of Toulon in the Mediterranean Sea at a mooring depth of about 2475m, consists of twelve detection lines equipped typically with 25 storeys. Every storey carries three optical modules that detect Cherenkov light induced by charged secondary particles (typically muons) coming from neutrino interactions. As these lines are flexible structures fixed to the sea bed and held taut by a buoy, sea currents cause the lines to move and the storeys to rotate. The knowledge of the position of the optical modules with a precision better than 10cm is essential for a good reconstruction of particle tracks. In this paper the ANTARES positioning system is described. It consists of an acoustic positioning system, for distance triangulation, and a compass-tiltmeter system, for the measurement of the orientation and inclination of the storeys. Necessary corrections are discussed and the results of the detector alignment procedure are described

A method for detection of muon induced electromagnetic showers with the ANTARES detector

The primary aim of ANTARES is neutrino astronomy with upward going muons created in charged current muon neutrino interactions in the detector and its surroundings. Downward going muons are background for neutrino searches. These muons are the decay products of cosmic-ray collisions in the Earth's atmosphere far above the detector. This paper presents a method to identify and count electromagnetic showers induced along atmospheric muon tracks with the ANTARES detector. The method is applied to both cosmic muon data and simulations and its applicability to the reconstruction of muon event energies is demonstrated.Comment: 20 pages, 7 figure

Performance of the front-end electronics of the ANTARES neutrino telescope

ANTARES is a high-energy neutrino telescope installed in the Mediterranean Sea at a depth of 2475 m. It consists of a three-dimensional array of optical modules, each containing a large photomultiplier tube. A total of 2700 front-end ASICs named Analogue Ring Samplers (ARS) process the phototube signals, measure their arrival time, amplitude and shape as well as perform monitoring and calibration tasks. The ARS chip processes the analogue signals from the optical modules and converts information into digital data. All the information is transmitted to shore through further multiplexing electronics and an optical link. This paper describes the performance of the ARS chip; results from the functionality and characterization tests in the laboratory are summarized and the long-term performance in the apparatus is illustrated.Comment: 20 pages, 22 figures, published in Nuclear Instruments and Methods

Measurement of the Group Velocity of Light in Sea Water at the ANTARES Site

The group velocity of light has been measured at eight different wavelengths between 385 nm and 532 nm in the Mediterranean Sea at a depth of about 2.2 km with the ANTARES optical beacon systems. A parametrisation of the dependence of the refractive index on wavelength based on the salinity, pressure and temperature of the sea water at the ANTARES site is in good agreement with these measurements.Comment: 14 pages, 5 figure

Search for neutrino emission from gamma-ray flaring blazars with the ANTARES telescope

The ANTARES telescope is well-suited to detect neutrinos produced in astrophysical transient sources as it can observe a full hemisphere of the sky at all times with a high duty cycle. Radio-loud active galactic nuclei with jets pointing almost directly towards the observer, the so-called blazars, are particularly attractive potential neutrino point sources. The all-sky monitor LAT on board the Fermi satellite probes the variability of any given gamma-ray bright blazar in the sky on time scales of hours to months. Assuming hadronic models, a strong correlation between the gamma-ray and the neutrino fluxes is expected. Selecting a narrow time window on the assumed neutrino production period can significantly reduce the background. An unbinned method based on the minimization of a likelihood ratio was applied to a subsample of data collected in 2008 (61 days live time). By searching for neutrinos during the high state periods of the AGN light curve, the sensitivity to these sources was improved by about a factor of two with respect to a standard time-integrated point source search. First results on the search for neutrinos associated with ten bright and variable Fermi sources are presented.The authors acknowledge the financial support of the funding agencies: Centre National de la Recherche Scientifique (CNRS), Commissariat a l'energie atomique et aux energies alternatives (CEA), Agence National de la Recherche (ANR), Commission Europeenne (FEDER fund and Marie Curie Program), Region Alsace (contrat CPER), Region Provence-Alpes-Cote d'Azur, Departement du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium fur Bildung und Forschung (BMBF), Germany; Istituto Nazionale di Fisica Nucleare (INFN), Italy; Stichting voor Fundamenteel Onderzoek der Materie (FOM), Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; Council of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, Russia; National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia e Innovacion (MICINN), Prometeo of Generalitat Valenciana and MultiDark, Spain. We also acknowledge the technical support of Werner, AIM and Foselev Marine for the sea operation and the CC-IN2P3 for the computing facilities.Adrián Martínez, S.; Al Samarai, I.; Albert, A.; André, M.; Anghinolfi, M.; Anton, G.; Anvar, S.... (2012). Search for neutrino emission from gamma-ray flaring blazars with the ANTARES telescope. Astroparticle Physics. 36(1):204-210. https://doi.org/10.1016/j.astropartphys.2012.06.001S20421036