Reduced GABA(B) receptor subunit expression and paired-pulse depression in a genetic model of absence seizures

Neocortical networks play a major role in the genesis of generalized spike-and-wave (SW) discharges associated with absence seizures in humans and in animal models, including genetically predisposed WAG/Rij rats. Here, we tested the hypothesis that alterations in GABAB receptors contribute to neocortical hyperexcitability in these animals. By using Real-Time PCR we found that mRNA levels for most GABAB(1) subunits are diminished in epileptic WAG/Rij neocortex as compared with age-matched non-epileptic controls (NEC), whereas GABAB(2) mRNA is unchanged. Next, we investigated the cellular distribution of GABAB(1) and GABAB(2) subunits by confocal microscopy and discovered that GABAB(1) subunits fail to localize in the distal dendrites of WAG/Rij neocortical pyramidal cells. Intracellular recordings from neocortical cells in an in vitro slice preparation demonstrated reduced paired-pulse depression of pharmacologically isolated excitatory and inhibitory responses in epileptic WAG/Rij rats as compared with NECs; moreover, paired-pulse depression in NEC slices was diminished by a GABAB receptor antagonist to a greater extent than in WAG/Rij rats further suggesting GABAB receptor dysfunction. In conclusion, our data identify changes in GABAB receptor subunit expression and distribution along with decreased paired-pulse depression in epileptic WAG/Rij rat neocortex. We propose that these alterations may contribute to neocorticalhyperexcitability and thus to SW generation in absence epilepsy

Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease

Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1-/- mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1-/- mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1-/- mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia

Flaring Behavior of the Quasar 3C~454.3 across the Electromagnetic Spectrum

We analyze the behavior of the parsec-scale jet of the quasar 3C~454.3 during pronounced flaring activity in 2005-2008. Three major disturbances propagated down the jet along different trajectories with Lorentz factors $\Gamma>$10. The disturbances show a clear connection with millimeter-wave outbursts, in 2005 May/June, 2007 July, and 2007 December. High-amplitude optical events in the $R$-band light curve precede peaks of the millimeter-wave outbursts by 15-50 days. Each optical outburst is accompanied by an increase in X-ray activity. We associate the optical outbursts with propagation of the superluminal knots and derive the location of sites of energy dissipation in the form of radiation. The most prominent and long-lasting of these, in 2005 May, occurred closer to the black hole, while the outbursts with a shorter duration in 2005 Autumn and in 2007 might be connected with the passage of a disturbance through the millimeter-wave core of the jet. The optical outbursts, which coincide with the passage of superluminal radio knots through the core, are accompanied by systematic rotation of the position angle of optical linear polarization. Such rotation appears to be a common feature during the early stages of flares in blazars. We find correlations between optical variations and those at X-ray and $\gamma$-ray energies. We conclude that the emergence of a superluminal knot from the core yields a series of optical and high-energy outbursts, and that the mm-wave core lies at the end of the jet's acceleration and collimation zone.Comment: 57 pages, 23 figures, 8 tables (submitted to ApJ

The linearity response of the Planck-LFI flight model receivers

In this paper we discuss the linearity response of the Planck-LFI receivers, with particular reference to signal compression measured on the 30 and 44 GHz channels. In the article we discuss the various sources of compression and present a model that accurately describes data measured during tests performed with individual radiomeric chains. After discussing test results we present the best parameter set representing the receiver response and discuss the impact of non linearity on in-flight calibration, which is shown to be negligible.Comment: this paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jinst; This is an author-created, un-copyedited version of an article accepted for publication in JINST. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at 10.1088/1748-0221/4/12/T12011

MOJAVE: Monitoring of Jets in Active Galactic Nuclei with VLBA Experiments. VI. Kinematics Analysis of a Complete Sample of Blazar Jets

We discuss the jet kinematics of a complete flux-density-limited sample of 135 radio-loud active galactic nuclei (AGN) resulting from a 13 year program to investigate the structure and evolution of parsec-scale jet phenomena. Our analysis is based on new 2 cm Very Long Baseline Array (VLBA) images obtained between 2002 and 2007, but includes our previously published observations made at the same wavelength, and is supplemented by VLBA archive data. In all, we have used 2424 images spanning the years 1994-2007 to study and determine the motions of 526 separate jet features in 127 jets. The data quality and temporal coverage (a median of 15 epochs per source) of this complete AGN jet sample represents a significant advance over previous kinematics surveys. In all but five AGNs, the jets appear one-sided, most likely the result of differential Doppler boosting. In general the observed motions are directed along the jet ridge line, outward from the optically thick core feature. We directly observe changes in speed and/or direction in one third of the well-sampled jet components in our survey. While there is some spread in the apparent speeds of separate features within an individual jet, the dispersion is about three times smaller than the overall dispersion of speeds among all jets. This supports the idea that there is a characteristic flow that describes each jet, which we have characterized by the fastest observed component speed. The observed maximum speed distribution is peaked at ~10c, with a tail that extends out to ~50c. This requires a distribution of intrinsic Lorentz factors in the parent population that range up to ~50. We also note the presence of some rare low-pattern speeds or even stationary features in otherwise rapidly flowing jets... (abridged)Comment: 19 pages, 10 figures, 2 tables, accepted by the Astronomical Journal; online only material is available from http://www.cv.nrao.edu/2cmVLBA/pub/MOJAVE_VI_suppl.zi

A comprehensive approach to lung function in bronchiectasis

Background: International guidelines recommend simple spirometry for bronchiectasis patients. However, pulmonary pathophysiology of bronchiectasis is very complex and still poorly understood. Our objective was to characterize lung function in bronchiectasis and identify specific functional sub-groups. Methods: This was a multicenter, prospective, observational study enrolling consecutive adults with bronchiectasis during stable sate. Patients underwent body-plethysmography before and after acute bronchodilation testing, diffusing lung capacity (DLCO) with a 3-year follow up. Air trapping and hyperinflation were a residual volume (RV) > 120%predicted and a total lung capacity>120%predicted. Acute reversibility was: \u394FEV1 6512% and 200 mL from baseline (FEV1rev) and \u394RV 6510% reduction from baseline (RVrev). Sensitivity analyses included different reversibility cutoffs and excluded patients with concomitant asthma or chronic obstructive pulmonary disease. Results: 187 patients were enrolled (median age: 68 years; 29.4% males). Pathophysiological abnormalities often overlapped and were distributed as follows: air trapping (70.2%), impaired DLCO (55.7%), airflow obstruction (41.1%), hyperinflation (15.7%) and restriction (8.0%). 9.7% of patients had normal lung function. RVrev (17.6%) was more frequent than FEV1rev (4.3%). Similar proportions were found after multiple sensitivity analyses. Compared with non-reversible patients, patients with RVrev had more severe obstruction (mean(SD) FEV1%pred: 83.0% (24.4) vs 68.9% (26.2); P = 0.02) and air trapping (RV%pred, 151.9% (26.6) vs 166.2% (39.9); P = 0.028). Conclusions: Spirometry alone does not encompass the variety of pathophysiological characteristics in bronchiectasis. Air trapping and diffusion impairment, not airflow obstruction, represent the most common functional abnormalities. RVrev is related to worse lung function and might be considered in bronchiectasis\u2019 workup and for patients\u2019 functional stratification

Multiwavelength Observations of the Gamma-Ray Blazar PKS 0528+134 in Quiescence

We present multiwavelength observations of the ultraluminous blazar-type radio loud quasar PKS 0528+134 in quiescence during the period July to December 2009. Significant flux variability on a time scale of several hours was found in the optical regime, accompanied by a weak trend of spectral softening with increasing flux. We suggest that this might be the signature of a contribution from the accretion disk at the blue end of the optical spectrum. The optical flux is weakly polarized with rapid variations of the degree and direction of polarization, while the polarization of the 43 GHz radio core remains steady. Optical spectropolarimetry suggests a trend of increasing degree of polarization with increasing wavelength, providing additional evidence for an accretion disc contribution towards the blue end of the optical spectrum. We constructed four SEDs indicating that even in the quiescent state, the bolometric luminosity of PKS 0528+134 is dominated by its gamma-ray emission. A leptonic single-zone jet model produced acceptable fits to the SEDs with contributions to the high-energy emission from synchrotron self-Compton radiation and Comptonization of direct accretion disk emission. Fit parameters close to equipartition were obtained. The moderate variability on long time scales implies the existence of on-going particle acceleration, while the observed optical polarization variability seems to point towards a turbulent acceleration process. Turbulent particle acceleration at stationary features along the jet therefore appears to be a viable possibility for the quiescent state of PKS 0528+134.Comment: Accepted for Publication in The Astrophysical Journal. - Acknowledgement adde

Thermal susceptibility of the Planck-LFI receivers

This paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jinst . This paper describes the impact of the Planck Low Frequency Instrument front end physical temperature fluctuations on the output signal. The origin of thermal instabilities in the instrument are discussed, and an analytical model of their propagation and impact on the receivers signal is described. The experimental test setup dedicated to evaluate these effects during the instrument ground calibration is reported together with data analysis methods. Finally, main results obtained are discussed and compared to the requirements.Comment: This is an author-created, un-copyedited version of an article accepted for publication in Journal of Instrumentation. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at 10.1088/1748-0221/4/12/T1201

Planck pre-launch status: calibration of the Low Frequency Instrument flight model radiometers

The Low Frequency Instrument (LFI) on-board the ESA Planck satellite carries eleven radiometer subsystems, called Radiometer Chain Assemblies (RCAs), each composed of a pair of pseudo-correlation receivers. We describe the on-ground calibration campaign performed to qualify the flight model RCAs and to measure their pre-launch performances. Each RCA was calibrated in a dedicated flight-like cryogenic environment with the radiometer front-end cooled to 20K and the back-end at 300K, and with an external input load cooled to 4K. A matched load simulating a blackbody at different temperatures was placed in front of the sky horn to derive basic radiometer properties such as noise temperature, gain, and noise performance, e.g. 1/f noise. The spectral response of each detector was measured as was their susceptibility to thermal variation. All eleven LFI RCAs were calibrated. Instrumental parameters measured in these tests, such as noise temperature, bandwidth, radiometer isolation, and linearity, provide essential inputs to the Planck-LFI data analysis.Comment: 15 pages, 18 figures. Accepted for publication in Astronomy and Astrophysic