PKM and the maintenance of memory.

How can memories outlast the molecules from which they are made? Answers to this fundamental question have been slow coming but are now emerging. A novel kinase, an isoform of protein kinase C (PKC), PKMzeta, has been shown to be critical to the maintenance of some types of memory. Inhibiting the catalytic properties of this kinase can erase well-established memories without altering the ability of the erased synapse to be retrained. This article provides an overview of the literature linking PKMzeta to memory maintenance and identifies some of the controversial issues that surround the bold implications of the existing data. It concludes with a discussion of the future directions of this domain

Extending the Fermi-LAT Data Processing Pipeline to the Grid

The Data Handling Pipeline ("Pipeline") has been developed for the Fermi Gamma-Ray Space Telescope (Fermi) Large Area Telescope (LAT) which launched in June 2008. Since then it has been in use to completely automate the production of data quality monitoring quantities, reconstruction and routine analysis of all data received from the satellite and to deliver science products to the collaboration and the Fermi Science Support Center. Aside from the reconstruction of raw data from the satellite (Level 1), data reprocessing and various event-level analyses are also reasonably heavy loads on the pipeline and computing resources. These other loads, unlike Level 1, can run continuously for weeks or months at a time. In addition it receives heavy use in performing production Monte Carlo tasks. The software comprises web-services that allow online monitoring and provides charts summarizing work flow aspects and performance information. The server supports communication with several batch systems such as LSF and BQS and recently also Sun Grid Engine and Condor. This is accomplished through dedicated job control services that for Fermi are running at SLAC and the other computing site involved in this large scale framework, the Lyon computing center of IN2P3. While being different in the logic of a task, we evaluate a separate interface to the Dirac system in order to communicate with EGI sites to utilize Grid resources, using dedicated Grid optimized systems rather than developing our own. (abstract abridged)Comment: This is an author-created, un-copyedited version of an article accepted for publication in Journal of Physics: Conference Series. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/1742-6596/396/3/03212

Habituation of the C-start response in larval zebrafish exhibits several distinct phases and sensitivity to NMDA receptor blockade.

The zebrafish larva has been a valuable model system for genetic and molecular studies of development. More recently, biologists have begun to exploit the surprisingly rich behavioral repertoire of zebrafish larvae to investigate behavior. One prominent behavior exhibited by zebrafish early in development is a rapid escape reflex (the C-start). This reflex is mediated by a relatively simple neural circuit, and is therefore an attractive model behavior for neurobiological investigations of simple forms of learning and memory. Here, we describe two forms of short-lived habituation of the C-start in response to brief pulses of auditory stimuli. A rapid form, persisting for ≥1 min but <15 min, was induced by 120 pulses delivered at 0.5-2.0 Hz. A more extended form (termed "short-term habituation" here), which persisted for ≥25 min but <1 h, was induced by spaced training. The spaced training consisted of 10 blocks of auditory pulses delivered at 1 Hz (5 min interblock interval, 900 pulses per block). We found that these two temporally distinguishable forms of habituation are mediated by different cellular mechanisms. The short-term form depends on activation of N-methyl-d-aspartate receptors (NMDARs), whereas the rapid form does not

Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia.

Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories

The missing GeV {\gamma}-ray binary: Searching for HESS J0632+057 with Fermi-LAT

The very high energy (VHE; >100 GeV) source HESS J0632+057 has been recently confirmed as a \gamma-ray binary, a subclass of the high mass X-ray binary (HMXB) population, through the detection of an orbital period of 321 days. We performed a deep search for the emission of HESS J0632+057 in the GeV energy range using data from the Fermi Large Area Telescope (LAT). The analysis was challenging due to the source being located in close proximity to the bright \gamma-ray pulsar PSR J0633+0632 and lying in a crowded region of the Galactic plane where there is prominent diffuse emission. We formulated a Bayesian block algorithm adapted to work with weighted photon counts, in order to define the off-pulse phases of PSR J0633+0632. A detailed spectral-spatial model of a 5 deg circular region centred on the known location of HESS J0632+057 was generated to accurately model the LAT data. No significant emission from the location of HESS J0632+057 was detected in the 0.1-100 GeV energy range integrating over ~3.5 years of data; with a 95% flux upper limit of F_{0.1-100 GeV} < 3 x 10-8 ph cm-2 s-1. A search for emission over different phases of the orbit also yielded no significant detection. A search for source emission on shorter timescales (days--months) did not yield any significant detections. We also report the results of a search for radio pulsations using the 100-m Green Bank Telescope (GBT). No periodic signals or individual dispersed bursts of a likely astronomical origin were detected. We estimated the flux density limit of < 90/40 \mu Jy at 2/9 GHz. The LAT flux upper limits combined with the detection of HESS J0632+057 in the 136-400 TeV energy band by the MAGIC collaboration imply that the VHE spectrum must turn over at energies <136 GeV placing constraints on any theoretical models invoked to explain the \gamma-ray emission.Comment: 11 pages, 4 figures, accepted for publication in Monthly Notices of the Royal Astronomical Society (MNRAS) Main Journa

The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study.

IntroductionDuchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense mutations were followed for 48 weeks in a multicenter, randomized, double-blind, placebo-controlled trial of ataluren. Placebo arm data (N = 57) provided insight into the natural history of the 6-minute walk test (6MWT) and other endpoints.MethodsEvaluations performed every 6 weeks included the 6-minute walk distance (6MWD), timed function tests (TFTs), and quantitative strength using hand-held myometry.ResultsBaseline age (≥7 years), 6MWD, and selected TFT performance are strong predictors of decline in ambulation (Δ6MWD) and time to 10% worsening in 6MWD. A baseline 6MWD of &lt;350 meters was associated with greater functional decline, and loss of ambulation was only seen in those with baseline 6MWD &lt;325 meters. Only 1 of 42 (2.3%) subjects able to stand from supine lost ambulation.ConclusionFindings confirm the clinical meaningfulness of the 6MWD as the most accepted primary clinical endpoint in ambulatory DMD trials

R-044. Limiting the number of embryos transferred does not significantly influence the outcome of conventional IVF treatment

SEB 1104 TECHNICAL DRG.- 14 D SEP (2

The LSST DESC data challenge 1: Generation and analysis of synthetic images for next-generation surveys

Data Challenge 1 (DC1) is the first synthetic data set produced by the Rubin Observatory Legacy Survey of Space and Time (LSST) Dark Energy Science Collaboration (DESC). DC1 is designed to develop and validate data reduction and analysis and to study the impact of systematic effects that will affect the LSST data set. DC1 is comprised of r-band observations of 40 deg2 to 10 yr LSST depth. We present each stage of the simulation and analysis process: (a) generation, by synthesizing sources from cosmological N-body simulations in individual sensor-visit images with different observing conditions; (b) reduction using a development version of the LSST Science Pipelines; and (c) matching to the input cosmological catalogue for validation and testing. We verify that testable LSST requirements pass within the fidelity of DC1. We establish a selection procedure that produces a sufficiently clean extragalactic sample for clustering analyses and we discuss residual sample contamination, including contributions from inefficiency in star-galaxy separation and imperfect deblending. We compute the galaxy power spectrum on the simulated field and conclude that: (i) survey properties have an impact of 50 per cent of the statistical uncertainty for the scales and models used in DC1; (ii) a selection to eliminate artefacts in the catalogues is necessary to avoid biases in the measured clustering; and (iii) the presence of bright objects has a significant impact (2-6) in the estimated power spectra at small scales (&gt; 1200), highlighting the impact of blending in studies at small angular scales in LSST