The GeV-TeV Connection in Galactic gamma-ray sources

Recent observations with atmospheric Cherenkov telescope systems such as H.E.S.S. and MAGIC have revealed a large number of new sources of very-high-energy (VHE) gamma-rays from 100 GeV - 100 TeV, mostly concentrated along the Galactic plane. At lower energies (100 MeV - 10 GeV) the satellite-based instrument EGRET revealed a population of sources clustering along the Galactic Plane. Given their adjacent energy bands a systematic correlation study between the two source catalogues seems appropriate. Here, the populations of Galactic sources in both energy domains are characterised on observational as well as on phenomenological grounds. Surprisingly few common sources are found in terms of positional coincidence and spectral consistency. These common sources and their potential counterparts and emission mechanisms will be discussed in detail. In cases of detection only in one energy band, for the first time consistent upper limits in the other energy band have been derived. The EGRET upper limits are rather unconstraining due to the sensitivity mismatch to current VHE instruments. The VHE upper limits put strong constraints on simple power-law extrapolation of several of the EGRET spectra and thus strongly suggest cutoffs in the unexplored energy range from 10 GeV - 100 GeV. Physical reasons for the existence of cutoffs and for differences in the source population at GeV and TeV energies will be discussed. Finally, predictions will be derived for common GeV - TeV sources for the upcoming GLAST mission bridging for the first time the energy gap between current GeV and TeV instruments.Comment: (1) Kavli Institute for Particle Astrophysics and Cosmology (KIPAC), Stanford, USA (2) Stanford University, W.W. Hansen Experimental Physics Lab (HEPL) and KIPAC, Stanford, USA (3) ICREA & Institut de Ciencies de l'Espai (IEEC-CSIC) Campus UAB, Fac. de Ciencies, Barcelona, Spain. (4) School of Physics and Astronomy, University of Leeds, UK. Paper Submitted to Ap

Fermi Detection of the Pulsar Wind Nebula HESS J1640-465

We present observations of HESS J1640-465 with the Fermi-LAT. The source is detected with high confidence as an emitter of high-energy gamma-rays. The spectrum lacks any evidence for the characteristic cutoff associated with emission from pulsars, indicating that the emission arises primarily from the pulsar wind nebula. Broadband modeling implies an evolved nebula with a low magnetic field resulting in a high gamma-ray to X-ray flux ratio. The Fermi emission exceeds predictions of the broadband model, and has a steeper spectrum, possibly resulting from a distinct excess of low energy electrons similar to what is inferred for both the Vela X and Crab pulsar wind nebulae.Comment: 6 pages, 5 figures, accepted for publication in Ap

Liver-specific knockout of arginase-1 leads to a profound phenotype similar to inducible whole body arginase-1 deficiency

Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype. Liver-selective Arg1 deletion was induced by using an adeno-associated viral (AAV)-thyroxine binding globulin (TBG) promoter-Cre recombinase vector administered to Arg1 "floxed" mice; Arg1(fl/fl) ). An AAV vector expressing an Arg1-enhanced green fluorescent protein (Arg1-eGFP) transgene was used for gene delivery, while intrasplenic injection of wild-type (WT) C57BL/6 hepatocytes after partial hepatectomy was used for cell delivery to "rescue" tamoxifen-treated Arg1-Cre mice. The results indicate that liver-selective loss of Arg1 (> 90% deficient) leads to a phenotype resembling the whole body knockout of Arg1 with lethality ≈ 3 weeks after Cre-induced gene disruption. Delivery of Arg1-eGFP AAV rescues more than half of Arg1 global knockout male mice (survival > 4 months) but a significant proportion still succumb to the enzyme deficiency even though liver expression and enzyme activity of the fusion protein reach levels observed in WT animals. Significant Arg1 enzyme activity from engrafted WT hepatocytes into knockout livers can be achieved but not sufficient for rescuing the lethal phenotype. This raises a conundrum relating to liver-specific expression of Arg1. On the one hand, loss of expression in this organ appears to be both necessary and sufficient to explain the lethal phenotype of the genetic disorder in mice. On the other hand, gene and cell-directed therapies suggest that rescue of extra-hepatic Arg1 expression may also be necessary for disease correction. Further studies are needed in order to illuminate the detailed mechanisms for pathogenesis of Arg1-deficiency

DETERMINATION OF THE PARTIAL PRESSURE OF HALOTHANE (OR ISOFLURANE) IN BLOOD

A gas chromatographic method is described for the direct quantitative determination of the partial pressure of halothane {or isoflurane) in blood as well as the blood-gas partition coefficient. A head space technique and a flame ionization detector were used. Standard blood was obtained by equilibrating patients' blood with known gas concentrations in a tonometer. Using an infra-red analyser to measure the halothane gas concentration in the tonometer and within the anaesthetic system allowed for the direct comparison of the partial pressure in blood to the partial pressure in the inspired gas. Technical problems associated with this procedure, and with comparable methods, are discusse

TARGET: A Digitizing And Trigger ASIC For The Cherenkov Telescope Array

The future ground-based gamma-ray observatory Cherenkov Telescope Array (CTA) will feature multiple types of imaging atmospheric Cherenkov telescopes, each with thousands of pixels. To be affordable, camera concepts for these telescopes have to feature low cost per channel and at the same time meet the requirements for CTA in order to achieve the desired scientific goals. We present the concept of the TeV Array Readout Electronics with GSa/s sampling and Event Trigger (TARGET) Application Specific Circuit (ASIC), envisaged to be used in the cameras of various CTA telescopes, e.g. the Gamma-ray Cherenkov Telescope (GCT), a proposed 2-Mirror Small-Sized Telescope, and the Schwarzschild-Couder Telescope (SCT), a proposed Medium-Sized Telescope. In the latest version of this readout concept the sampling and trigger parts are split into dedicated ASICs, TARGET C and T5TEA, both providing 16 parallel input channels. TARGET C features a tunable sampling rate (usually 1 GSa/s), a 16k sample deep buffer for each channel and on-demand digitization and transmission of waveforms with typical spans of ~100 ns. The trigger ASIC, T5TEA, provides 4 low voltage differential signal (LVDS) trigger outputs and can generate a pedestal voltage independently for each channel. Trigger signals are generated by T5TEA based on the analog sum of the input in four independent groups of four adjacent channels and compared to a threshold set by the user. Thus, T5TEA generates four LVDS trigger outputs, as well as 16 pedestal voltages fed to TARGET C independently for each channel. We show preliminary results of the characterization and testing of TARGET C and T5TEA.Comment: 6 pages, 8 figures, Proceedings of the 6th International Symposium on High-Energy Gamma-Ray Astronomy (Gamma2016

Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein

p21 inhibits cyclin-dependent kinase (CDK) activity and proliferating cell nuclear antigen (PCNA)-dependent DNA replication by binding to CDK/cyclin complexes and to PCNA through distinct domains. The human papillomavirus (HPV)-16 E7 oncoprotein (16E7) abrogated a DNA damage-induced cell cycle arrest in vivo, despite high levels of p21. Using cell lysates and purified proteins we show that 16E7 prevented p21 both from inhibiting CDK2/cyclin E activity and PCNA-dependent DNA replication, whereas the nononcogenic HPV-6 E7 had reduced effects. Inactivation of both inhibitory functions of p21 was attained through binding between 16E7 and sequences in the carboxy-terminal end of p21 that overlap with the PCNA-binding site and the second p21 cyclin-binding motif. These data imply that the carboxyl terminus of p21 simultaneously modulates both CDK activity and PCNA-dependent DNA replication and that a single protein, 16E7, can override this modulation to disrupt normal cell cycle control