Mirror Position Determination for the Alignment of Cherenkov Telescopes

Imaging Atmospheric Cherenkov Telescopes (IACTs) need imaging optics with large apertures to map the faint Cherenkov light emitted in extensive air showers onto their image sensors. Segmented reflectors fulfill these needs using mass produced and light weight mirror facets. However, as the overall image is the sum of the individual mirror facet images, alignment is important. Here we present a method to determine the mirror facet positions on a segmented reflector in a very direct way. Our method reconstructs the mirror facet positions from photographs and a laser distance meter measurement which goes from the center of the image sensor plane to the center of each mirror facet. We use our method to both align the mirror facet positions and to feed the measured positions into our IACT simulation. We demonstrate our implementation on the 4 m First Geiger-mode Avalanche Cherenkov Telescope (FACT).Comment: 11 figures, small ray tracing performance simulation, and implementation demonstratio

Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis

Despite the potential of the inhibitor of apoptosis proteins (IAPs) to block cytochrome c–dependent caspase activation, the critical function of IAPs in regulating mammalian apoptosis remains unclear. We report that the ability of endogenous IAPs to effectively regulate caspase activation depends on the differentiation state of the cell. Despite being expressed at equivalent levels, endogenous IAPs afforded no protection against cytochrome c–induced apoptosis in naïve pheochromocytoma (PC12) cells, but were remarkably effective in doing so in neuronally differentiated cells. Neuronal differentiation was also accompanied with a marked reduction in Apaf-1, resulting in a significant decrease in apoptosome activity. Importantly, this decrease in Apaf-1 protein was directly linked to the increased ability of IAPs to stringently regulate apoptosis in neuronally differentiated PC12 and primary cells. These data illustrate specifically how the apoptotic pathway acquires increased regulation with cellular differentiation, and are the first to show that IAP function and apoptosome activity are coupled in cells

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652

Performance update of an event-type based analysis for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) will be the next-generation observatory in the field of very-high-energy (20 GeV to 300 TeV) gamma-ray astroparticle physics. The traditional approach to data analysis in this field is to apply quality cuts, optimized using Monte Carlo simulations, on the data acquired to maximize sensitivity. Subsequent steps of the analysis typically use the surviving events to calculate one set of instrument response functions (IRFs) to physically interpret the results. However, an alternative approach is the use of event types, as implemented in experiments such as the Fermi-LAT. This approach divides events into sub-samples based on their reconstruction quality, and a set of IRFs is calculated for each sub-sample. The sub-samples are then combined in a joint analysis, treating them as independent observations. In previous works we demonstrated that event types, classified using Machine Learning methods according to their expected angular reconstruction quality, have the potential to significantly improve the CTA angular and energy resolution of a point-like source analysis. Now, we validated the production of event-type wise full-enclosure IRFs, ready to be used with science tools (such as Gammapy and ctools). We will report on the impact of using such an event-type classification on CTA high-level performance, compared to the traditional procedure and present preliminary results of the improvement

The extreme HBL behaviour of Markarian 501 during 2012

A multiwavelength campaign was organized to take place between March and July of 2012. Excellent temporal coverage was obtained with more than 25 instruments, including the MAGIC, FACT and VERITAS Cherenkov telescopes, the instruments on board the Swift and Fermi spacecraft, and the telescopes operated by the GASP-WEBT collaboration. Mrk 501 showed a very high energy (VHE) gamma-ray flux above 0.2 TeV of $\sim$0.5 times the Crab Nebula flux (CU) for most of the campaign. The highest activity occurred on 2012 June 9, when the VHE flux was $\sim$3 CU, and the peak of the high-energy spectral component was found to be at $\sim$2 TeV. This study reports very hard X-ray spectra, and the hardest VHE spectra measured to date for Mrk 501. The fractional variability was found to increase with energy, with the highest variability occurring at VHE, and a significant correlation between the X-ray and VHE bands. The unprecedentedly hard X-ray and VHE spectra measured imply that their low- and high-energy components peaked above 5 keV and 0.5 TeV, respectively, during a large fraction of the observing campaign, and hence that Mrk 501 behaved like an extreme high-frequency- peaked blazar (EHBL) throughout the 2012 observing season. This suggests that being an EHBL may not be a permanent characteristic of a blazar, but rather a state which may change over time. The one-zone synchrotron self-Compton (SSC) scenario can successfully describe the segments of the SED where most energy is emitted, with a significant correlation between the electron energy density and the VHE gamma-ray activity, suggesting that most of the variability may be explained by the injection of high-energy electrons. The one-zone SSC scenario used reproduces the behaviour seen between the measured X-ray and VHE gamma-ray fluxes, and predicts that the correlation becomes stronger with increasing energy of the X-rays

Rapid development and persistence of efficient subglacial drainage under 900 m-thick ice in Greenland

Intensive study of the Greenland Ice Sheet's (GrIS) subglacial drainage has been motivated by its importance for ice dynamics and for nutrient/sediment export to coastal ecosystems. This has revealed consistent seasonal development of efficient subglacial drainage in the lower ablation area. While some hydrological models show qualitative agreement with field data, conflicting evidence (both field- and model-based) maintains uncertainty in the extent and rate of efficient drainage development under thick (∼1 km) ice. Here, we present the first simultaneous time series of directly-observed subglacial drainage evolution, supraglacial hydrology and ice dynamics over 11 weeks in a large GrIS catchment. We demonstrate development of a fast/efficient subglacial drainage system extending from the margin to beneath ice >900 m thick, which then persisted with little response to highly variable moulin inputs including extreme melt events and extended periods (2 weeks) of low melt input. This efficient system evolved within ∼3 weeks at a moulin initiated when a fracture intersected a supraglacial river (rather than hydrofracture and lake drainage). Ice flow response to surface melt inputs at this site follows a pattern commonly observed in the lower GrIS ablation area, and by assuming a strong relationship between ice dynamics and subglacial hydrology, we infer that efficient subglacial drainage evolution is widespread under 900 m-thick ice in west Greenland. This time series of tracer transit characteristics through a developing and then persistent efficient drainage system provides a unique data set with which to validate and constrain existing numerical drainage system models, extending their capability for simulating drainage system evolution under current and future conditionspublishedVersio

Two Distinct Domains within CIITA Mediate Self-Association: Involvement of the GTP-Binding and Leucine-Rich Repeat Domains

CIITA is the master regulator of class II major histocompatibility complex gene expression. We present evidence that CIITA can self-associate via two domains: the C terminus (amino acids 700 to 1130) and the GTP-binding domain (amino acids 336 to 702). Heterotypic and homotypic interactions are observed between these two regions. Deletions within the GTP-binding domain that reduce GTP-binding and transactivation function also reduce self-association. In addition, two leucine residues in the C-terminal leucine-rich repeat region are critical for self-association as well as function. This study reveals for the first time a complex pattern of CIITA self-association. These interactions are discussed with regard to the apoptosis signaling proteins, Apaf-1 and Nod1, which share domain arrangements similar to those of CIITA

CIITA stimulation of transcription factor binding to major histocompatibility complex class II and associated promoters in vivo

CIITA is a master transactivator of the major histocompatibility complex class II genes, which are involved in antigen presentation. Defects in CIITA result in fatal immunodeficiencies. CIITA activation is also the control point for the induction of major histocompatibility complex class II and associated genes by interferon-γ, but CIITA does not bind directly to DNA. Expression of CIITA in G3A cells, which lack endogenous CIITA, followed by in vivo genomic footprinting, now reveals that CIITA is required for the assembly of transcription factor complexes on the promoters of this gene family, including DRA, Ii, and DMB. CIITA-dependent promoter assembly occurs in interferon-γ-inducible cell types, but not in B lymphocytes. Dissection of the CIITA protein indicates that transactivation and promoter loading are inseparable and reveal a requirement for a GTP binding motif. These findings suggest that CIITA may be a new class of transactivator

Ketogenic diet uncovers differential metabolic plasticity of brain cells

To maintain homeostasis, the body, including the brain, reprograms its metabolism in response to altered nutrition or disease. However, the consequences of these challenges for the energy metabolism of the different brain cell types remain unknown. Here, we generated a proteome atlas of the major central nervous system (CNS) cell types from young and adult mice, after feeding the therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) and during neuroinflammation. Under steady-state conditions, CNS cell types prefer distinct modes of energy metabolism. Unexpectedly, the comparison with KD revealed distinct cell type–specific strategies to manage the altered availability of energy metabolites. Astrocytes and neurons but not oligodendrocytes demonstrated metabolic plasticity. Moreover, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic cross-talk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease