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The outbreak of COVID-19 has overwhelmed healthcare systems all over the world. The aim of this article is to describe the process of transforming the Vall d’Hebron University Hospital, the second largest hospital in Spain, into a COVID-19 centre coordinating response to the pandemic in its reference area.

Kainate (KA)-type glutamate receptors (KARs) are implicated in various neuropsychiatric and neurological disorders through their ionotropic and metabotropic actions. However, compared to AMPA- and NMDA-type receptor functions, many aspects of KAR biology remain incompletely understood. Our study demonstrates an important role of KARs in organizing climbing fiber (CF)-Purkinje cell (PC) synapses and synaptic plasticity in the cerebellum, independently of their ion channel or metabotropic functions. The amino-terminal domain (ATD) of the GluK4 KAR subunit binds to C1ql1, provided by CFs, and associates with Bai3, an adhesion-type G protein-coupled receptor expressed in PC dendrites. Mice lacking GluK4 exhibit no KAR-mediated responses, reduced C1ql1 and Bai3 levels, and fewer CF-PC synapses, along with impaired long-term depression and oculomotor learning. Remarkably, introduction of the ATD of GluK4 significantly improves all these phenotypes. These findings demonstrate that KARs act as synaptic scaffolds, orchestrating synapses by forming a KAR-C1ql1-Bai3 complex in the cerebellum.

La prevención de la enfermedad cardiovascular se fundamenta en la detección y control de los factores de riesgo cardiovascular (FRCV). En España existen importantes diferencias territoriales tanto en la prevalencia como en el grado de control de los FRCV. En la última década ha habido una mejora del control de la hipertensión y la dislipidemia, pero un empeoramiento de los factores de riesgo cardiometabólicos relacionados con la obesidad y la diabetes.

Altered glutamatergic neurotransmission is thought to contribute to mental disorders and neurodegenerative diseases. Copy-number variation in genes associated with glutamatergic synapses represents a source of genetic variability, possibly underlying neurological and mental disease susceptibility. The GRIK4gene encodes a high-affinity kainate receptor subunit of essentially unknown function, although de novoduplication of the 11q23.3-q24.1 locus to which it maps has been detected in autism and other disorders. To determine how changes in the dose of Grik4affect synaptic activity, we studied mice overexpressing this gene in the forebrain. A mild gain in Grik4enhances synaptic transmission, causing a persistent imbalance in inhibitory and excitatory activity and disturbing the circuits responsible for the main amygdala outputs. These changes in glutamatergic activity reverse when Grik4levels are normalized; thus, they may account for the behavioral abnormalities in disorders like autism or schizophrenia.

Context. Flat-spectrum radio sources often show a core-jet structure on pc-scales. Individual jet components reveal predominantly outward directed motion. For the BL Lac object S5 0716+714 conflicting apparent velocities have been reported in the literature. This object is an intra-day variable source and suited to investigate a possible correlation between kinematic properties and flux-density variability on different timescales.

Context. BL Lacertaeis the prototype of the blazar subclass named after it. Yet, it has occasionally shown a peculiar behaviour that has questioned a simple interpretation of its broad-band emission in terms of synchrotron plus synchrotron self-Compton (SSC) radiation.

Context. Since 2001, the radio quasar 3C 454.3has undergone a period of high optical activity, culminating in the brightest optical state ever observed, during the 2004-2005 outburst. The Whole Earth Blazar Telescope (WEBT) consortium has carried out several multifrequency campaigns to follow the source behaviour.

Aims. The Whole Earth Blazar Telescope (WEBT) consortium has been monitoring the blazar 3C 454.3from the radio to the optical bands since 2004 to study its emission variability properties.

Context. The quasar 3C 279is among the most extreme blazars in terms of luminosity and variability of flux at all wavebands. Its variations in flux and polarization are quite complex and therefore require intensive monitoring observations at multiple wavebands to characterise and interpret the observed changes.

Context.The blazar AO 0235+164was claimed to show a quasi-periodic behaviour in the radio and optical bands in the past, with the main outbursts repeating every 5–6 years. However, the predicted 2004 outburst did not occur, and further analysis suggested a longer time scale, according to which the next event would have occurred in the 2006–2007 observing season. Moreover, an extra emission component contributing to the UV and soft X-ray flux was detected, whose nature is not yet clear. An optical outburst was observed in late 2006–early 2007, which triggered a Whole Earth Blazar Telescope (WEBT) campaign as well as target of opportunity (ToO) observations by the Swift satellite.

Context.The quasar-type blazar 3C 454.3was observed to undergo an unprecedented optical outburst in spring 2005, affecting the source brightness from the near-IR to the X-ray frequencies. This was first followed by a millimetric and then by a radio outburst, which peaked in February 2006.

Context.Recent studies have shown that a remarkable share of quasars classified in the literature as gigahertz-peaked spectrum (GPS) sources and high frequency peakers (HFPs) are actually flaring flat-spectrum sources or blazars. Thus, at least among the quasar-type samples, genuine GPS sources and HFPs seem to be rare.

Aims.We present a study of variability time scales in a large sample of Active Galactic Nuclei at several frequencies between 4.8 and 230 GHz. We investigate the differences of various AGN types and frequencies and correlate the measured time scales with physical parameters such as the luminosity and the Lorentz factor. Our sample consists of both high and low polarization quasars, BL Lacertae objects and radio galaxies. The basis of this work is the 22 GHz, 37 GHz and 87 GHz monitoring data from the Metsähovi Radio Observatory spanning over 25 years. In addition, we used higher 90 GHz and 230 GHz frequency data obtained with the SEST-telescope between 1987 and 2003. Further lower frequency data at 4.8 GHz, 8 GHz and 14.5 GHz from the University of Michigan monitoring programme have been used.

Context.In spring 2005 the blazar 3C 454.3was observed in an unprecedented bright state from the near-IR to the hard X-ray frequencies. A mm outburst peaked in June–July 2005, and it was followed by a flux increase at high radio frequencies.

Aims.A huge multiwavelength campaign targeting the blazar AO 0235+164was organized by the Whole Earth Blazar Telescope (WEBT) in 2003–2005 to study the variability properties of the source.

In this letter we present the results of a wavelet analysis of the radio light curve of the BL Lac Object PKS B0048-097from the University of Michigan Radio Astronomy Observatory monitoring program at 8 GHz during twenty-five years, from 1979 to 2004. The results show a remarkable periodicity of 450–470 days in the early 1980s that changed to a ~585 day periodicity in the late 1980s to early 1990s. A less pronounced ~400 day periodicity is found after ${\sim}1995$. Very-long-baseline interferometry imaging at 15 GHz shows dramatic structural changes in the usually unresolved source between two epochs, 1995.57 and 2002.38. The pronounced northward directed jet seen in the 2002 image differs by more than 90° in direction from the source structure found in earlier epochs. These findings make PKS B0048-097a primary target for multi-wavelength observations and intensive radio monitoring to decipher the blazar-variability phenomenon.

BL Lacertaehas been the target of several observing campaigns by the Whole Earth Blazar Telescope (WEBT) collaboration and is one of the best studied blazars at all accessible wavelengths. A recent analysis of the optical and radio variability indicates that part of the radio variability is correlated with the optical light curve. Here we present an analysis of a huge VLBI data set including 108 images at 15, 22, and 43 GHz obtained between 1995 and 2004. The aim of this study is to identify the different components contributing to the single-dish radio light curves. We obtain separate radio light curves for the VLBI core and jet and show that the radio spectral index of single-dish observations can be used to trace the core variability. Cross-correlation of the radio spectral index with the optical light curve indicates that the optical variations lead the radio by about 100 days at 15 GHz. By fitting the radio time lags vs. frequency, we find that the power law is steeper than expected for a freely expanding conical jet in equipartition with energy density decreasing as the square of the distance down the jet as in the Königl model. The analysis of the historical data back to 1968 reveals that during a time range of 16 years the optical variability was reduced and its correlation with the radio emission was suppressed. There is a section of the compact radio jet where the emission is weak such that flares propagating down the jet are bright first in the core region with a secondary increase in flux about 1.0 mas from the core. This illustrates the importance of direct imaging to the interpretation of multi-wavelength light curves that can be affected by several distinct components at any given time. We discuss how the complex behaviour of the light curves and correlations can be understood within the framework of a precessing helical jet model.

Aims.We study the synchrotron flaring behaviour of the blazar 3C 279 based on an extensive dataset covering 10 years of monitoring at 19 different frequencies in the radio-to-optical range.

Context.The radio quasar 3C 454.3underwent an exceptional optical outburst lasting more than 1 year and culminating in spring 2005. The maximum brightness detected was $R=12.0$, which represents the most luminous quasar state thus far observed ($M_B \sim -31.4$).

Context.Some intra-day variable, compact extra-galactic radio sources show brightness temperatures severely exceeding 1012K, the limit set by catastrophic inverse-Compton (IC) cooling in sources of incoherent synchrotron radiation. The violation of the IC limit, actually possible under non-stationary conditions, would lead to IC avalanches in the soft-γ-ray energy band during transient periods.

Aims.The aim of this work is to identify and study spectral features in the quasar 3C 273 usually blended by its strong jet emission.

A multiwavelength campaign to observe the BL Lac object AO 0235+16($z=0.94$) was set up by the Whole Earth Blazar Telescope (WEBT) collaboration during the observing seasons 2003–2004 and 2004–2005, involving radio, near-IR and optical photometric monitoring, VLBA monitoring, optical spectral monitoring, and three pointings by the XMM-Newton satellite. Here we report on the results of the first season, which involved the participation of 24 optical and near-IR telescopes and 4 radio telescopes, as well as the first XMM-Newton pointing, which occurred on January 18–19, 2004. Unpublished data from previous epochs were also collected (from 5 optical-NIR and 3 radio telescopes), in order to fill the gap between the end of the period presented in Raiteri et al. (2001) and the start of the WEBT campaign. The contribution of the southern AGN, 2 arcsec distant from the source, is taken into account. It is found to especially affect the blue part of the optical spectrum when the source is faint. In the optical and near-IR the source has been very active in the last 3 years, although it has been rather faint most of the time, with noticeable variations of more than a magnitude over a few days. In contrast, in the radio bands it appears to have been “quiescent” since early 2000. The major radio (and optical) outburst predicted to peak around February–March 2004 (with a six month uncertainty) has not occurred yet. When comparing our results with the historical light curves, two different behaviours seem to characterize the optical outbursts: only the major events present a radio counterpart. The X-ray spectra obtained by the three EPIC detectors are well fitted by a power law with extra-absorption at $z=0.524$; the energy index in the 0.2–10 keV range is well constrained: $\alpha=0.645$±0.028 and the 1 keV flux density is 0.311 ±$0.008~\rm \mu Jy$. The analysis of the X-ray light curves reveals that no significant variations occurred during the pointing. In contrast, simultaneous dense radio monitoring with the 100 m telescope at Effelsberg shows a ~2–3% flux decrease in 6–7 h, which, if intrinsic, would imply a brightness temperature well above the Compton limit and hence a lower limit to the Doppler factor $\delta \ga 46$. We construct the broad-band spectral energy distribution of January 18–19, 2004 with simultaneous radio data from Effelsberg, optical data from the Nordic Optical Telescope (NOT), optical–UV data from the Optical Monitor onboard XMM-Newton, and X-ray data by the EPIC instruments. Particular care is taken to correct data for extinction due to both the Milky Way and the $z=0.524$absorber. The resulting SED suggests the existence of a bump in the UV spectral region.

We have combined new data from our observing campaigns and data from the literature to construct the radio continuum spectra for a sample of mostly quasar-type high peaking gigahertz-peaked spectrum (GPS) source candidates. We have also studied the spectra and variability of so called “bona fide” GPS sources and other inverted-spectrum sources from the literature. For many of our sample sources we now have data spanning over two decades, enabling us to study their long term behaviour.
Based on our earlier results we expected to find several new high peaking GPS sources. Instead we found out that even most of the “bona fide” GPS sources cease to adhere to the generic GPS source properties when using these well-sampled long term data sets.
In our sample of 35 inverted-spectrum sources from the literature only five seem to be consistent with the GPS properties, and even out of these sources two are too sparsely sampled to firmly make conclusions about their variability. Thirteen of the “bona fide” GPS sources exhibit pronounced activity, which diverges from the low variability expected from these sources. None of our new candidates turned out to have both a convex spectrum and little to no variability, but there is one variable source with a consistently convex spectrum. All the rest have flat spectra, but the upper envelope of the spectrum is clearly convex for four extremely variable sources. Similar continuum spectra with a flat lower envelope and a convex upper envelope are observed for eight previously identified inverted-spectrum sources.
According to this study the genuine quasar-type GPS sources are rare but there is a large number of highly variable sources that can have a convex spectrum peaking at high radio frequencies (up to ca. 100 GHz) during flares. Many of the GPS sources from the literature have too easily been classified as GPS sources based on too sparse data, and studying the long term variability is essential for identifying the sources with consistently convex continuum spectra.

A very detailed monitoring of a radio flare in the Seyfert I galaxy III Zw 2 with the VLA and the VLBA is presented. The relative astrometry in the VLBA observations was precise to a few μas. The spectral and spatial evolutions of the source are closely linked, and these observations allowed us to study a textbook example of a synchrotron self-absorbed jet in great detail. We observed a phase where the jet gets frustrated with neither expansion nor spectral evolution. Then the jet breaks free and starts to expand with apparent superluminal motion. This expansion is accompanied by a strong spectral evolution. The results are a good confirmation of synchrotron theory and equipartition for jets.

The Whole Earth Blazar Telescope (WEBT) collaboration has collected a large amount of optical and radio data on BL Lacertaein the last years, which, when added to literature data, allow to construct well-sampled light curves of the source from 1968 to the end of 2003. These optical and radio data are here analysed with three statistical methods designed for unevenly-sampled data trains in order to search for possible periodicities. While the main radio outbursts repeat every ~8 years, with a possible progressive stretching of the period, the evidence of an optical periodicity is much less clear. Radio light curves from 4.8 to 37 GHz are well correlated, with variations at the higher frequencies leading the lower-frequency ones by a few weeks for contiguous bands, up to a few months when considering the largest frequency separations. The radio behaviour reveals the presence of two different components, the softer-spectrum one constituting the bulk of the radio emission. On the other hand, the harder component shows itself as radio events which appear enhanced at the higher frequencies and seem to have optical counterparts. Cross-correlation between the optical light curve and radio hardness ratios indicates a radio time delay of more than 3 months. Thus, our analysis suggests a scenario where flux variations propagate towards less and less opaque regions, giving rise to related optical and hard radio events and, in more extended zones, to soft events apparently uncorrelated with the former ones.

We have carried out a multifrequency analysis of the radio variability of blazars, exploiting the data obtained during the extensive monitoring programs carried out at the University of Michigan Radio Astronomy Observatory (UMRAO, at 4.8, 8, and 14.5 GHz) and at the Metsähovi Radio Observatory (22 and 37 GHz). Two different techniques detect, in the Metsähovi light curves, evidence of periodicity at both frequencies for 5 sources (0224+671, 0945+408, 1226+023, 2200+420, and 2251+158). For the last three sources, consistent periods are found also at the three UMRAO frequencies and the Scargle (1982) method yields an extremely low false-alarm probability. On the other hand, the 22 and 37 GHz periodicities of 0224+671 and 0945+408 (which were less extensively monitored at Metsähovi and for which we get a significant false-alarm probability) are not confirmed by the UMRAO database, where some indications of ill-defined periods of about a factor of two longer are retrieved. We have also investigated the variability index, the structure function, and the distribution of intensity variations of the most extensively monitored sources. We find a statistically significant difference in the distribution of the variability index for BL Lac objects compared to flat-spectrum radio quasars (FSRQs), in the sense that the former objects are more variable. For both populations the variability index steadily increases with increasing frequency. The distribution of intensity variations also broadens with increasing frequency, and approaches a log-normal shape at the highest frequencies. We find that variability enhances by 20–30% the high frequency counts of extragalactic radio-sources at bright flux densities, such as those of the WMAP and Plancksurveys. In all objects with detected periodicity we find evidence for the existence of impulsive signals superimposed on the periodic component.

The BL Lacertae object AO 0235+16is well known for its extreme optical and radio variability. New optical and radio data have been collected in the last four years by a wide international collaboration, which confirm the intense activity of this source: on the long term, overall variations of $5\rm mag$in the Rband and up to a factor 18 in the radio fluxes were detected, while short-term variability up to $0.5\rm mag$in a few hours and $1.3\rm mag$in one day was observed in the optical band. The optical data also include the results of the Whole Earth Blazar Telescope (WEBT) first-light campaign organized in November 1997, involving a dozen optical observatories. The optical spectrum is observed to basically steepen when the source gets fainter. We have investigated the existence of typical variability time scales and of possible correlations between the optical and radio emissions by means of visual inspection and Discrete Correlation Function (DCF) analysis. On the long term, the autocorrelation function of the optical data shows a double-peaked maximum at 4100-4200 days (11.2-11.5 years), while a double-peaked maximum at 3900-4200 days (10.7-11.5 years) is visible in the radio autocorrelation functions. The existence of this similar characteristic time scale of variability in the two bands is by itself an indication of optical-radio correlation. A further analysis by means of Discrete Fourier Transform (DFT) technique and folded light curves reveals that the major radio outbursts repeat quasi-regularly with a periodicity of ~5.7 years, i.e. half the above time scale. This period is also in agreement with the occurrence of some of the major optical outbursts, but not all of them. Visual inspection and DCF analysis of the optical and radio light curves then reveal that in some cases optical outbursts seem to be simultaneous with radio ones, but in other cases they lead the radio events. Moreover, a deep inspection of the radio light curves suggests that in at least two occasions (the 1992-1993 and 1998 outbursts) flux variations at the higher frequencies may have led those at the lower ones.

We present intensive optical, infrared, and radio monitoring observations of the BL Lac object OJ 287, taken between the years 1993-1998. Two large optical outbursts were detected at the predicted times in November 1994 and December 1995. The detection of these outbursts supports the binary black hole model for OJ 287. Optical and radio polarisation observations show large variability in the degree of polarisation and position angle, very similar to those observed during the 1983/84 outburst in OJ 287. The polarisation position angles show very similar behaviour during these observations, indicating that, at least, the magnetic field orientations in radio and optical bands are related in OJ 287. Optical and infrared light curves show continuous variability in time scales ranging from tens of minutes to years. In the radio bands we have observed some of the lowest ever measured flux levels. During the first optical outburst in November 1994 the observed radio flux was very low, but during the second optical outburst radio bands also showed high flux levels. This is a puzzling observation, which can hopefully be used for discriminating between different outburst models. On top of the large outbursts OJ 287 has displayed flaring activity in time scales from days to weeks and shorter time scale flickering.

We demonstrate continuous wave (CW) terahertz generation from antennas fabricated on C^12-irradiated semi-insulating (SI) GaAs substrates. The dark current drawn by the antennas fabricated on irradiated substrates is ∼3 to 4 orders of magnitude lower compared to antennas fabricated on un-irradiated substrates, while the photocurrents decrease by only ∼1.5 orders of magnitude. This can be attributed to the strong reduction of the carrier lifetime that is 2.5 orders of magnitude, with values around τ_rec=0.2  ps. Reduced thermal heating allows for higher bias voltages to the irradiated antenna devices resulting in higher CW terahertz power, just slightly lower than that of low-temperature grown GaAs (LT GaAs)at similar excitation conditions.

We present a wide multi-wavelength database of most observations of the quasar 3C 273 obtained during the last 30 years. This database is the most complete set of observations available for an active galactic nucleus (AGN). It contains nearly 20 000 observations grouped together into 70 light curves covering 16 orders of magnitude in frequency from the radio to the γ-ray domain. The database is constituted of many previously unpublished observations and of most publicly available data gathered in the literature and on the World Wide Web (WWW). It is complete to the best of our knowledge, except in the optical (UBV) domain where we chose not to add all observations from the literature. In addition to the photometric data, we present the spectra of 3C 273 obtained by the International Ultraviolet Explorer (IUE) satellite. In the X-ray domain, we used the spectral fit parameters from the literature to construct the light curves. Apart from describing the data, we show the most representative light curves and the average spectrum of 3C 273. The database is available on the WWW in a homogeneous and clear form and we wish to update it regularly by adding new observations.

We present results from a two year intensive monitoring of BL Lac object 3C 66A (PKS 0219+428). This object was observed in outburst during these two years. It reached the brightest ever observed magnitude on V=13.59 (1.2.1995) and on K=10.59 (15.2.1994). The optical and infrared light curves are characterised by randomly distributed fast flares, lasting a few days and well defined outbursts lasting a week or two. On top of these flares we can occasionally see small amplitude microvariability. No clear correlation can be found between the spectral behaviour and the occurrence of these flares. In the radio bands 3C 66A was quite faint and very stable compared to the optical variations. The light curves will be presented with preliminary analysis and discussions on the possible causes for the observed variations.

Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, such as bone marrow, skeletal muscle, dental pulp, bone, umbilical cord and adipose tissue. MSCs are used in regenerative medicine mainly based on their capacity to differentiate into specific cell types and also as bioreactors of soluble factors that will promote tissue regeneration from the damaged tissue cellular progenitors. In addition to these regenerative properties, MSCs hold an immunoregulatory capacity, and elicit immunosuppressive effects in a number of situations. Not only are they immunoprivileged cells, due to the low expression of class II Major Histocompatibilty Complex (MHC-II) and costimulatory molecules in their cell surface, but they also interfere with different pathways of the immune response by means of direct cell-to-cell interactions and soluble factor secretion. In vitro, MSCs inhibit cell proliferation of T cells, B-cells, natural killer cells (NK) and dendritic cells (DC), producing what is known as division arrest anergy. Moreover, MSCs can stop a variety of immune cell functions: cytokine secretion and cytotoxicity of T and NK cells; B cell maturation and antibody secretion; DC maturation and activation; as well as antigen presentation. It is thought that MSCs need to be activated to exert their immunomodulation skills. In this scenario, an inflammatory environment seems to be necessary to promote their effect and some inflammation-related molecules such as tumor necrosis factor-α and interferon-γ might be implicated. It has been observed that MSCs recruit T-regulatory lymphocytes (Tregs) to both lymphoid organs and graft. There is great controversy concerning the mechanisms and molecules involved in the immunosuppressive effect of MSCs. Prostaglandin E2, transforming growth factor-β, interleukins- 6 and 10, human leukocyte antigen-G5, matrix metalloproteinases, indoleamine-2,3-dioxygenase and nitric oxide are all candidates under investigation. In vivo studies have shown many discrepancies regarding the immunomodulatory properties of MSCs. These studies have been designed to test the efficacy of MSC therapy in two different immune settings: the prevention or treatment of allograft rejection episodes, and the ability to suppress abnormal immune response in autoimmune and inflammatory diseases. Preclinical studies have been conducted in rodents, rabbits and baboon monkeys among others for bone marrow, skin, heart, and corneal transplantation, graft versus host disease, hepatic and renal failure, lung injury, multiple sclerosis, rheumatoid arthritis, diabetes and lupus diseases. Preliminary results from some of these studies have led to human clinical trials that are currently being carried out. These include treatment of autoimmune diseases such as Crohns disease, ulcerative colitis, multiple sclerosis and type 1 diabetes mellitus; prevention of allograft rejection and enhancement of the survival of bone marrow and kidney grafts; and treatment of resistant graft versus host disease. We will try to shed light on all these studies, and analyze why the results are so contradictory.

This article discusses the use of heart rate monitors and the affect they had on training for Division I soccer program. The article explores heart rate monitors as a tool for coaches and atheletes alike. [ABSTRACT FROM AUTHOR]

Context. Since 2001, the radio quasar 3C 454.3 has undergone a period of high optical activity, culminating in the brightest optical state ever observed, during the 2004-2005 outburst. The Whole Earth Blazar Telescope (WEBT) consortium has carried out several multifrequency campaigns to follow the source behaviour.Aims. The GLAST-AGILE Support Program (GASP) was born from the WEBT to provide long-term continuous optical-to-radio monitoring of a sample of ?-loud blazars, during the operation of the AGILE and GLAST (now known as Fermi GST) ?-ray satellites. The main aim is to shed light on the mechanisms producing the high-energy radiation, through correlation analysis with the low-energy emission. Thus, since 2008 the monitoring task on 3C?454.3 passed from the WEBT to the GASP, while both AGILE and Fermi detected strong ?-ray emission from the source.Methods. We present the main results obtained by the GASP at optical, mm, and radio frequencies in the 2008-2009 season, and compare them with the WEBT?results from previous years.Results. An optical outburst was observed to peak in mid July?2008, when Fermi detected the brightest ?-ray levels. A?contemporaneous mm outburst maintained its brightness for a longer time, until the cm emission also reached the maximum levels. The behaviour compared in the three bands suggests that the variable relative brightness of the different-frequency outbursts may be due to the changing orientation of a curved inhomogeneous jet. The optical light curve is very well sampled during the entire season, which is also well covered by the various AGILE and Fermi observing periods. The relevant cross-correlation studies will be very important in constraining high-energy emission models.

Context. Since 1997, BL Lacertae has undergone a phase of high optical activity, with the occurrence of several prominent outbursts. Starting from 1999, the Whole Earth Blazar Telescope (WEBT) consortium has organized various multifrequency campaigns on this blazar, collecting tens of thousands of data points. One of the main issues in the study of this huge dataset has been the search for correlations between the optical and radio flux variations, and for possible periodicities in the light curves. The analysis of the data assembled during the first four campaigns (comprising also archival data to cover the period 1968?2003) revealed a fair optical-radio correlation in 1994?2003, with a delay of the hard radio events of ~100?days. Moreover, various statistical methods suggested the existence of a radio periodicity of ~8?years.Aims. In 2004 the WEBT started a new campaign to extend the dataset to the most recent observing seasons, in order to possibly confirm and better understand the previous results.Methods. In this campaign we have collected and assembled about 11?000 new optical observations from twenty telescopes, plus near-IR and radio data at various frequencies. Here, we perform a correlation analysis on the long-term R-band and radio light curves.Results. In general, we confirm the ~100-day delay of the hard radio events with respect to the optical ones, even if longer (~200?300?days) time lags are also found in particular periods. The radio quasi-periodicity is confirmed too, but the ?period? seems to progressively lengthen from?7.4 to 9.3?years in the last three cycles. The optical and radio behaviour in the last forty years suggests a scenario where geometric effects play a major role. In particular, the alternation of enhanced and suppressed optical activity (accompanied by hard and soft radio events, respectively) can be explained in terms of an emitting plasma flowing along a rotating helical path in a curved jet.

Aims. We report the detection by the AGILE satellite of a rapid ?-ray flare from the source 1AGL J1511-0908, associated with the powerful ?-ray quasar PKS 1510-089, during a pointing centered on the Galactic center region from 1 March to 30 March 2008. This source has been continuosly monitored in the radio-to-optical bands by the GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT). Moreover, the ?-ray flaring episode triggered three ToO observations by the Swift satellite in three consecutive days, starting from 20 March 2008. The quasi-simultaneous radio-to-optical, UV, X-ray and ?-ray coverage allows us to make a detailed study of the multifrequency time evolution, the spectral energy distribution of this source, and its theoretical interpretation based on the synchrotron and inverse Compton?(IC) emission mechanisms.Methods. During the radio-to-optical monitoring provided by the GASP-WEBT, AGILE observed the source with its two co-aligned imagers, the gamma-ray imaging detector (GRID) and the hard X-ray imager (SuperAGILE), which are sensitive in the 30?MeV?30?GeV and 18?60?keV energy bands, respectively.Results. In the period 1?16?March 2008, AGILE detected ?-ray emission from PKS 1510-089 at a significance level of 6.2-? with an average flux over the entire period of (84 ?17) ?10-8?photons?cm-2s-1for photon energies above 100?MeV. After a predefined satellite re-pointing, between 17 and 21 March 2008, AGILE detected the source at a significance level of 7.3-?, with an average flux (E > 100?MeV) of (134 ?29) ?10-8?photons?cm-2?s-1and a peak level of (281 ?68) ?10-8?photons?cm-2?s-1with daily integration. During the observing period January-April 2008, the source also showed an intense and variable optical activity, with several flaring episodes and a significant increase in the flux was observed at millimetric frequencies. Moreover, in the X-ray band, the Swift/XRT observations seem to show a harder-when-brighter behavior of the source spectrum.Conclusions. The flat spectrum radio quasar PKS?1510-089 showed strong activity between January and April 2008, with episodes of rapid variability from radio to ?-ray energy bands, in particular with a rapid ?-ray flaring episode. The spectral energy distribution of mid-March 2008 is modeled with a homogeneous one-zone synchrotron self Compton (SSC) emission plus contributions from inverse Compton scattering of external photons from both the accretion disk and the broad line region. Indeed, some features in the optical-UV spectrum seem to indicate Seyfert-like components such as the little and the big blue bumps.

Context. We report the detection by the AGILE (Astro-rivelatore Gamma a Immagini LEggero) satellite of an intense gamma-ray flare from the source AGL?J1511-0909, associated with the powerful quasar PKS?1510-089, during ten days of observations from 23?August to 1?September?2007.Aims. During the observation period, the source was in optical decrease following a flaring event monitored by the GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT). The simultaneous gamma-ray, optical, and radio coverage allows us to study the spectral energy distribution and the theoretical models based on the synchrotron and inverse Compton (IC) emission mechanisms.Methods. AGILE observed the source with its two co-aligned imagers, the Gamma-Ray Imaging Detector and the hard X-ray imager Super-AGILE sensitive in the 30?MeV?[Formula: see text][Formula: see text] 50?GeV and 18?[Formula: see text][Formula: see text] 60?keV bands, respectively.Results. Between 23 and 27 August 2007, AGILE detected gamma-ray emission from PKS?1510-089 when this source was located ~50?off-axis, with an average flux of (270 ?65)?? 10-8?photons?cm-2?s-1for photon energy above 100?MeV. In the following period, 28?August-1?September, after a satellite re-pointing, AGILE detected the source at ~35?off-axis, with an average flux (E?> 100?MeV) of (195 ?30)?? 10-8?photons?cm-2?s-1. No emission was detected by Super-AGILE, with a 3-? upper limit of 45?mCrab in 200?ks.Conclusions. The spectral energy distribution is modelled with a homogeneous one-zone synchrotron self Compton (SSC) emission plus contributions by external photons: the SSC?emission contributes primarily to the X-ray band, whereas the contribution of the IC from the external disc and the broad line region match the hard gamma-ray spectrum observed.

TASK two-pore-domain leak K+channels occur throughout the brain. However, TASK-1 and TASK-3 knockout (KO) mice have few neurological impairments and only mildly reduced sensitivities to inhalational anesthetics, contrasting with the anticipated functions and importance of these channels. TASK-1/-3 channel expression can compensate for the absence of GABAAreceptors in GABAAα6 KO mice. To investigate the converse, we analyzed the behavior of TASK-1 and -3 KO mice after administering drugs with preferential efficacies at GABAAreceptor subtypes: benzodiazepines (diazepam and flurazepam, active at α1βγ2, α2βγ2, α3βγ2, and α5βγ2 subtypes), zolpidem (α1βγ2 subtype), propofol (β2–3-containing receptors), gaboxadol (α4βδ and α6βδ subtypes), pregnanolone, and pentobarbital (many subtypes). TASK-1 KO mice showed increased motor impairment in rotarod and beam-walking tests after diazepam and flurazepam administration but not after zolpidem. They also showed prolonged loss of righting reflex induced by propofol and pentobarbital. Autoradiography indicated no change in GABAAreceptor ligand binding levels. These altered behavioral responses to GABAergic drugs suggest functional up-regulation of α2β2/3γ2 and α3β2/3γ2 receptor subtypes in TASK-1 KO mice. In addition, female, but not male, TASK-1 KO mice were more sensitive to gaboxadol, suggesting an increased influence of α4βδ or α6βδ subtypes. The benzodiazepine sensitivity of TASK-3 KO mice was marginally increased. Our results underline that TASK-1 channels perform such key functions in the brain that compensation is needed for their absence. Furthermore, because inhalation anesthetics act partially through GABAAreceptors, the up-regulation of GABAAreceptor function in TASK-1 KO mice might mask TASK-1 channel’s significance as a target for inhalation anesthetics.

TASK two-pore-domain leak K(+) channels occur throughout the brain. However, TASK-1 and TASK-3 knockout (KO) mice have few neurological impairments and only mildly reduced sensitivities to inhalational anesthetics, contrasting with the anticipated functions and importance of these channels. TASK-1/-3 channel expression can compensate for the absence of GABA(A) receptors in GABA(A) alpha6 KO mice. To investigate the converse, we analyzed the behavior of TASK-1 and -3 KO mice after administering drugs with preferential efficacies at GABA(A) receptor subtypes: benzodiazepines (diazepam and flurazepam, active at alpha1betagamma2, alpha2betagamma2, alpha3betagamma2, and alpha5betagamma2 subtypes), zolpidem (alpha1betagamma2 subtype), propofol (beta2-3-containing receptors), gaboxadol (alpha4betadelta and alpha6betadelta subtypes), pregnanolone, and pentobarbital (many subtypes). TASK-1 KO mice showed increased motor impairment in rotarod and beam-walking tests after diazepam and flurazepam administration but not after zolpidem. They also showed prolonged loss of righting reflex induced by propofol and pentobarbital. Autoradiography indicated no change in GABA(A) receptor ligand binding levels. These altered behavioral responses to GABAergic drugs suggest functional up-regulation of alpha2beta2/3gamma2 and alpha3beta2/3gamma2 receptor subtypes in TASK-1 KO mice. In addition, female, but not male, TASK-1 KO mice were more sensitive to gaboxadol, suggesting an increased influence of alpha4betadelta or alpha6betadelta subtypes. The benzodiazepine sensitivity of TASK-3 KO mice was marginally increased. Our results underline that TASK-1 channels perform such key functions in the brain that compensation is needed for their absence. Furthermore, because inhalation anesthetics act partially through GABA(A) receptors, the up-regulation of GABA(A) receptor function in TASK-1 KO mice might mask TASK-1 channel's significance as a target for inhalation anesthetics.

Aims. We present an update of the 3C?273's database hosted by the ISDC, completed with data from radio to gamma-ray observations over the last 10?years. We use this large data set to study the multiwavelength properties of this quasar, especially focussing on its variability behaviour.Methods. We study the amplitude of the variations and the maximum variability time scales across the broad-band spectrum and correlate the light curves in different bands, specifically with the X-rays, to search for possible connections between the emission at different energies.Results. 3C?273?shows variability at all frequencies, with amplitudes and time scales strongly depending on the energy and being the signatures of the different emission mechanisms. The variability properties of the X-ray band imply the presence of either two separate components (possibly a Seyfert-like and a blazar-like) or at least two parameters with distinct timing properties to account for the X-ray emission below and above ~20?keV. The dominant hard X-ray emission is most probably not due to electrons accelerated by the shock waves in the jet as their variability does not correlate with the flaring millimeter emission, but seems to be associated to long-timescale variations in the optical. This optical component is consistent with being optically thin synchrotron radiation from the base of the jet and the hard X-rays would be produced through inverse Compton processes (SSC and/or?EC) by the same electron population. We show evidence that this synchrotron component extends from the optical to the near-infrared domain, where it is blended by emission of heated dust that we find to be located within about 1 light-year from the ultraviolet source.

Aims. We have studied the flare characteristics of 55?AGN at 8?different frequency bands between 4.8 and 230?GHz. Our extensive database enables us to study the various observational properties of flares in these sources and compare our results with theoretical models.Methods. We visually extracted 159 individual flares from the flux density curves and calculated different parameters, such as the peak flux density and duration, in all the frequency bands. The selection of flares is based on the 22 and 37?GHz data from Mets?hovi Radio Observatory and 90 and 230?GHz data from the SEST?telescope. Additional lower frequency?4.8, 8, and 14.5?GHz data are from the University of Michigan Radio Observatory. We also calculated variability indices and compared them with earlier studies.Results. The observations seem to adhere well to the shock model, but there is still large scatter in the data. Especially the time delays between different frequency bands are difficult to study due to the incomplete sampling of the higher frequencies. The average duration of the flares is 2.5?years at 22 and 37?GHz, which shows that long-term monitoring is essential for understanding the typical behaviour in these sources. It also seems that the energy release in a flare is independent of the duration of the flare.

Context. The quasar-type blazar 3C 454.3 underwent a phase of high activity in summer and autumn?2007 that was intensively monitored in the radio-to-optical bands by the Whole Earth Blazar Telescope (WEBT). The ?-ray satellite Astro-rivelatore Gamma a Immagini LEggero (AGILE) detected this source first in late July, and then in November?December 2007.Aims. We present the multifrequency data collected by the WEBT and collaborators during the second AGILE observing period, complemented by contemporaneous data from the UltraViolet and Optical Telescope (UVOT) onboard the Swift satellite. The aim is to trace in detail the behaviour of the synchrotron emission from the blazar jet, and to investigate the contribution from the thermal emission component.Methods. Optical data from about twenty telescopes have been homogeneously calibrated and carefully assembled to construct an R-band light curve containing about 1340?data points over 42?days. This extremely well-sampled optical light curve allows us to follow the dramatic flux variability of the source in detail. In addition, we show radio-to-UV spectral energy distributions (SEDs) at different epochs, which represent different brightness levels.Results. In the considered period, the source varied by 2.6?mag over two weeks in the R?band. Many episodes of fast (i.e.?intranight) variability were observed, most notably on December?12, when a flux increase of about 1.1?mag in 1.5?h was detected, followed by a steep decrease of about 1.2?mag in 1?h. The contribution by the thermal component is difficult to assess, due to the uncertainties in the Galactic, and possibly also intrinsic, extinction in the UV?band. However, polynomial fitting of radio-to-UV?SEDs reveals an increasing spectral bending towards fainter states, suggesting a UV?excess likely due to the thermal emission from the accretion disc.Conclusions. Once the AGILE data are completely analysed, the low-frequency observations presented in this letter will offer a powerful tool to investigate optical-? flux correlations, i.e.?the relationship between the synchrotron and inverse-Compton emission components.

Context. Gigahertz-peaked spectrum (GPS) sources and high frequency peakers (HFPs) are among the smallest of active galactic nuclei currently believed to represent the earliest phases in the evolution of extragalactic radio sources. Recently there has been evidence of contamination by other types of radio sources among the GPS and HFP samples, but the confirmed GPS sources or HFPs also seem to form a very heterogeneous population.Aims. We study the statistical clustering of the GPS sources and the HFPs by taking as many source parameters as possible to find homogeneous groups among the sources. We expect the clustering to give us insight into the physical parameters that play a role in different source populations.Methods. We have collected a sample of 206 GPS sources and HFPs from the literature and gathered a massive database of various source properties, such as the redshift, the size, the polarization, the magnitudes, and the properties of the radio continuum. To visualize and to cluster these multidimensional data we used self-organising maps (SOM), which are neural networks trained by an unsupervised algorithm. We have classified the sources with an auxiliary classification to trace the locations of different types of radio continuum spectra on the map. Results. The sources form distinctive clusters on the map, which is supported by the accordant organisation of the non-numerical parameters not used in the analysis, such as the radio morphology and the optical identification. Our results confirm that the blazars contaminating the GPS and the HFP samples are physically different from the genuine GPS sources and HFPs, and they should be excluded from the samples. The genuine GPS sources form various clusters, which indicates the existence of different subpopulations, besides the expected galaxy-quasar dualism.

Aims. Since the CGRO operation in 1991?2000, one of the primary unresolved questions about the blazar ?-ray emission has been its possible correlation with the low-energy (in particular optical) emission. To help answer this problem, the Whole Earth Blazar Telescope (WEBT) consortium has organized the GLAST-AGILE Support Program (GASP) to provide the optical-to-radio monitoring data to be compared with the ?-ray detections by the AGILE and GLAST satellites. This new WEBT project started in early September 2007, just before a strong ?-ray detection of 0716+714 by AGILE.Methods. We present the GASP-WEBT optical and radio light curves of this blazar obtained in July?November 2007, about various AGILE pointings at the source. We construct NIR-to-UV spectral energy distributions (SEDs), by assembling GASP-WEBT data together with UV data from the Swift ToO observations of late October.Results. We observe a contemporaneous optical-radio outburst, which is a rare and interesting phenomenon in blazars. The shape of the SEDs during the outburst appears peculiarly wavy because of an optical excess and a UV drop-and-rise. The optical light curve is well sampled during the AGILE pointings, showing prominent and sharp flares. A future cross-correlation analysis of the optical and AGILE data will shed light on the expected relationship between these flares and the ?-ray events.

The TASK-3 channel is an acid-sensitive two-pore-domain K+channel, widely expressed in the brain and probably involved in regulating numerous neuronal populations. Here, we characterized the behavioral and pharmacological phenotypes of TASK-3 knockout (KO) mice. Circadian locomotor activity measurements revealed that the nocturnal activity of the TASK-3 KO mice was increased by 38% (P< 0.01) compared with wild-type littermate controls, light phase activity being similar. Although TASK-3 channels are abundant in cerebellar granule cells, the KO mice performed as well as the wild-type mice in walking on a rotating rod or along a 1.2-cm-diameter beam. However, they fell more frequently from a narrower 0.8-cm beam. The KO mice showed impaired working memory in the spontaneous alternation task, with the alternation percentage being 62 ± 3% for the wild-type mice and 48 ± 4% (P< 0.05) for the KO mice. Likewise, during training for the Morris water-maze spatial memory task, the KO mice were slower to find the hidden platform, and in the probe trial, the female KO mice visited fewer times the platform quadrant than the male KO and wild-type mice. In pharmacological tests, the TASK-3 KO mice showed reduced sensitivity to the inhalation anesthetic halothane and the cannabinoid receptor agonist WIN55212-2 mesylate [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] but unaltered responses to the α2 adrenoceptor agonist dexmedetomidine, the i.v. anesthetic propofol, the opioid receptor agonist morphine, and the local anesthetic lidocaine. Overall, our results suggest important contributions of TASK-3 channels in the neuronal circuits regulating circadian rhythms, cognitive functions, and mediating specific pharmacological effects.

The TASK-3 channel is an acid-sensitive two-pore-domain K(+) channel, widely expressed in the brain and probably involved in regulating numerous neuronal populations. Here, we characterized the behavioral and pharmacological phenotypes of TASK-3 knockout (KO) mice. Circadian locomotor activity measurements revealed that the nocturnal activity of the TASK-3 KO mice was increased by 38% (P < 0.01) compared with wild-type littermate controls, light phase activity being similar. Although TASK-3 channels are abundant in cerebellar granule cells, the KO mice performed as well as the wild-type mice in walking on a rotating rod or along a 1.2-cm-diameter beam. However, they fell more frequently from a narrower 0.8-cm beam. The KO mice showed impaired working memory in the spontaneous alternation task, with the alternation percentage being 62 +/- 3% for the wild-type mice and 48 +/- 4% (P < 0.05) for the KO mice. Likewise, during training for the Morris water-maze spatial memory task, the KO mice were slower to find the hidden platform, and in the probe trial, the female KO mice visited fewer times the platform quadrant than the male KO and wild-type mice. In pharmacological tests, the TASK-3 KO mice showed reduced sensitivity to the inhalation anesthetic halothane and the cannabinoid receptor agonist WIN55212-2 mesylate [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] but unaltered responses to the alpha2 adrenoceptor agonist dexmedetomidine, the i.v. anesthetic propofol, the opioid receptor agonist morphine, and the local anesthetic lidocaine. Overall, our results suggest important contributions of TASK-3 channels in the neuronal circuits regulating circadian rhythms, cognitive functions, and mediating specific pharmacological effects.

Inhalation anesthetics activate and cannabinoid agonists inhibit TWIK-related acid-sensitive K+channels (TASK)-1 two-pore domain leak K+channels in vitro. Many neuromodulators, such as noradrenaline, might also manifest some of their actions by modifying TASK channel activity. Here, we have characterized the basal behavioral phenotype of TASK-1 knockout mice and tested their sensitivity to the inhalation anesthetics halothane and isoflurane, the α2adrenoreceptor agonist dexmedetomidine, and the cannabinoid agonist WIN55212-2 mesylate [R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3,-de]-1,4-benzoxazinyl]-(1-naphtalenyl)methanone mesylate)]. TASK-1 knockout mice had a largely normal behavioral phenotype. Male, but not female, knockout mice displayed an enhanced acoustic startle response. The knockout mice showed increased sensitivity to thermal nociception in a hot-plate test but not in a tail-flick test. The analgesic, sedative, and hypothermic effects of WIN55212-2 (2–6 mg/kg s.c.) were reduced in TASK-1 knockout mice. These results implicate TASK-1-containing channels in supraspinal pain pathways, in particular those modulated by endogenous cannabinoids. TASK-1 knockout mice were less sensitive to the anesthetic effects of halothane and isoflurane than wild-type littermates, requiring higher anesthetic concentrations to induce immobility as reflected by loss of the tail-withdrawal reflex. Our results support the idea that the activation of multiple background K+channels is crucial for the high potency of inhalation anesthetics. Furthermore, TASK-1 knockout mice were less sensitive to the sedative effects of dexmedetomidine (0.03 mg/kg s.c.), suggesting a role for the TASK-1 channels in the modulation of function of the adrenergic locus coeruleus nuclei and/or other neuronal systems.

Inhalation anesthetics activate and cannabinoid agonists inhibit TWIK-related acid-sensitive K(+) channels (TASK)-1 two-pore domain leak K(+) channels in vitro. Many neuromodulators, such as noradrenaline, might also manifest some of their actions by modifying TASK channel activity. Here, we have characterized the basal behavioral phenotype of TASK-1 knockout mice and tested their sensitivity to the inhalation anesthetics halothane and isoflurane, the alpha(2) adrenoreceptor agonist dexmedetomidine, and the cannabinoid agonist WIN55212-2 mesylate [R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3,-de]-1,4-benzoxazinyl]-(1-naphtalenyl)methanone mesylate)]. TASK-1 knockout mice had a largely normal behavioral phenotype. Male, but not female, knockout mice displayed an enhanced acoustic startle response. The knockout mice showed increased sensitivity to thermal nociception in a hot-plate test but not in a tail-flick test. The analgesic, sedative, and hypothermic effects of WIN55212-2 (2-6 mg/kg s.c.) were reduced in TASK-1 knockout mice. These results implicate TASK-1-containing channels in supraspinal pain pathways, in particular those modulated by endogenous cannabinoids. TASK-1 knockout mice were less sensitive to the anesthetic effects of halothane and isoflurane than wild-type littermates, requiring higher anesthetic concentrations to induce immobility as reflected by loss of the tail-withdrawal reflex. Our results support the idea that the activation of multiple background K(+) channels is crucial for the high potency of inhalation anesthetics. Furthermore, TASK-1 knockout mice were less sensitive to the sedative effects of dexmedetomidine (0.03 mg/kg s.c.), suggesting a role for the TASK-1 channels in the modulation of function of the adrenergic locus coeruleus nuclei and/or other neuronal systems.