The first GCT camera for the Cherenkov Telescope Array

The Gamma Cherenkov Telescope (GCT) is proposed to be part of the Small Size Telescope (SST) array of the Cherenkov Telescope Array (CTA). The GCT dual-mirror optical design allows the use of a compact camera of diameter roughly 0.4 m. The curved focal plane is equipped with 2048 pixels of ~0.2{\deg} angular size, resulting in a field of view of ~9{\deg}. The GCT camera is designed to record the flashes of Cherenkov light from electromagnetic cascades, which last only a few tens of nanoseconds. Modules based on custom ASICs provide the required fast electronics, facilitating sampling and digitisation as well as first level of triggering. The first GCT camera prototype is currently being commissioned in the UK. On-telescope tests are planned later this year. Here we give a detailed description of the camera prototype and present recent progress with testing and commissioning.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

Socio-sexuality and episodic memory function in women: further evidence of an adaptive “mating mode”

The functionalist memory perspective predicts that information of adaptive value may trigger specific processing modes. It was recently demonstrated that women's memory is sensitive to cues of male sexual dimorphism (i.e., masculinity) that convey information of adaptive value for mate choice because they signal health and genetic quality, as well as personality traits important in relationship contexts. Here, we show that individual differences in women's mating strategies predict the effect of facial masculinity cues upon memory, strengthening the case for functional design within memory. Using the revised socio-sexual orientation inventory, Experiment 1 demonstrates that women pursuing a short-term, uncommitted mating strategy have enhanced source memory for men with exaggerated versus reduced masculine facial features, an effect that reverses in women who favor long-term committed relationships. The reversal in the direction of the effect indicates that it does not reflect the sex typicality of male faces per se. The same pattern occurred within women's source memory for women's faces, implying that the memory bias does not reflect the perceived attractiveness of faces per se. In Experiment 2, we reran the experiment using men's faces to establish the reliability of the core finding and replicated Experiment 1's results. Masculinity cues may therefore trigger a specific mode within women's episodic memory. We discuss why this mode may be triggered by female faces and its possible role in mate choice. In so doing, we draw upon the encoding specificity principle and the idea that episodic memory limits the scope of stereotypical inferences about male behavior

Unos L-alanil-L-glutamina tijekom kratkotrajne visokointenzivne vježbe u uvjetima blagoga hidracijskoga stresa

The effect of acute L-alanyl-L-glutamine (AG) ingestion on selected hormonal and electrolyte measures was examined during repetitive, short duration, high intensity exercise with mild hypohydration. Subjects (20.3±1.1 yrs; 180.3±10.4 cm; 83.1±14.0 kg; 11.6±3.6% body fat) reported to the Human Performance Laboratory on four occasions. During each trial subjects were hypohydrated to -2.5% of their baseline body mass. During one trial (DHY) subjects rested in a recumbent position for 45 minutes before commencing the exercise session. During the other three trials subjects were rehydrated to 1.5% of their baseline body mass, before exercise, by drinking water only (W), or with two different doses of AG – a low dose (LDAG: 0.05 g�kg-1) and a high dose (HDAG: 0.2 g�kg-1). The exercise protocol consisted of ten 10-second sprints on a cycle ergometer with a 1-min rest between each sprint. Blood draws were collected once the subject achieved the desired level of hypohydration, immediately pre-exercise, immediately post-exercise, and 24 hrs postexercise. Blood samples were analyzed for glutamine, potassium, sodium, aldosterone, arginine vasopressin, C-reactive protein, interleukin-6, malondialdehyde, testosterone, cortisol, ACTH, and growth hormone. The area under the curve (AUC) analysis demonstrated significantly greater sodium concentrations for DHY compared to all other trials. The AUC analysis for aldosterone showed significantly lower concentrations at LDAG compared to DHY. No other differences between trials were observed in any other hormonal or biochemical responses. AG ingestion during a short duration, anaerobic exercise and mild hypohydration stress had a limited effect on selected hormonal and biochemical measures.Učinci akutnoga, trenutačnoga uzimanja L-alanil-L-glutamina (AG) na odabrane hormonske i elektrolitne pokazatelje ispitani su tijekom ponavljajuće kratkotrajne visokointenzivne aktivnosti u uvjetima blage hipohidracije ispitanika. Ispitanici (20,3±1,1 godina; 180,3±10,4 cm; 83,1±14,0 kg; 11,6±3,6% tjelesne masti) bili su testirani u Human Performance Laboratory u četiri navrata. Tijekom svakoga pojedinačnoga mjerenja ispitanici su bili hipohidrirani do -2,5% svoje početne, osnovne tjelesne mase. Tijekom prvoga testiranja (DHY) ispitanici su se odmarali ležeći 45 minuta prije no što su počeli provoditi protokol vježbanja. Tijekom sljedeća tri mjerenja ispitanici su rehidrirani do 1,5% njihove početne tjelesne mase prije vježbanja, i to: pijenjem samo vode (W) te unosom dviju različitih doza AG - male doze (LDAG: 0,05 g∙kg-1) i velike doze (HDAG: 0,2 g∙kg-1). Protokol vježbanja sastojao se od po deset sprintova na bicikl-ergometru u trajanju od 10 sekunda s jednominutnim odmorom između svakoga sprinta. Uzorci krvi vađeni su odmah nakon što je ispitanik dosegao željenu razinu hipohidracije, neposredno prije početka vježbanja, neposredno nakon završetka vježbanja i 24 sata nakon vježbanja. U uzorcima krvi analizirana je koncentracija glutamina, kalija, natrija, aldosterona, arginin vazopresina, C-reaktivnoga proteina, interleukina-6, malondialdehida, testosterona, kortizola, ACTH-a i hormona rasta. Analiza površine ispod krivulje pokazala je statistički značajno veću razinu koncentracije natrija u ispitanika u prvom testu (DHY) u odnosu na sva ostala mjerenja. Analiza površine ispod krivulje za aldosteron je pokazala značajno nižu koncentraciju u testu LDAG u odnosu na test DHY. Nisu zapažene značajne razlike između pojedinih mjerenja ni u jednoj drugoj hormonskoj i biokemijskoj reakciji na protokol vježbanja. Uzimanje AG tijekom kratkotrajne anaerobne aktivnosti i u stanju blagoga hipohidracijskoga stresa pokazalo je ograničene učinke na odabrane hormonske i biokemijske pokazatelje

Operating performance of the gamma-ray Cherenkov telescope: An end-to-end Schwarzschild-Couder telescope prototype for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CIA) consortium aims to build the next-generation ground-based very high-energy gamma-ray observatory. The array will feature different sizes of telescopes allowing it to cover a wide gamma-ray energy band from about 20 GeV to above 100 TeV. The highest energies, above 5 TeV, will be covered by a large number of Small-Sized Telescopes (SSTs) with a field-of-view of around 9. The Gamma-ray Cherenkov Telescope (GCT), based on Schwarzschild-Couder dual-mirror optics, is one of the three proposed SST designs. The GCT is described in this contribution and the first images of Cherenkov showers obtained using the telescope and its camera are presented. These were obtained in November 2015 in Meudon, France. (C) 2016 Published by Elsevier B.V

Operating performance of the gamma-ray Cherenkov telescope: An end-to-end Schwarzschild–Couder telescope prototype for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) consortium aims to build the next-generation ground-based very-high-energy gamma-ray observatory. The array will feature different sizes of telescopes allowing it to cover a wide gamma-ray energy band from about 20 GeV to above 100 TeV. The highest energies, above 5 TeV, will be covered by a large number of Small-Sized Telescopes (SSTs) with a field-of-view of around 9°. The Gamma-ray Cherenkov Telescope (GCT), based on Schwarzschild–Couder dual-mirror optics, is one of the three proposed SST designs. The GCT is described in this contribution and the first images of Cherenkov showers obtained using the telescope and its camera are presented. These were obtained in November 2015 in Meudon, France

Operating performance of the gamma-ray Cherenkov telescope: An end-to-end Schwarzschild–Couder telescope prototype for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) consortium aims to build the next-generation ground-based very-high-energy gamma-ray observatory. The array will feature different sizes of telescopes allowing it to cover a wide gamma-ray energy band from about 20 GeV to above 100 TeV. The highest energies, above 5 TeV, will be covered by a large number of Small-Sized Telescopes (SSTs) with a field-of-view of around 9°. The Gamma-ray Cherenkov Telescope (GCT), based on Schwarzschild–Couder dual-mirror optics, is one of the three proposed SST designs. The GCT is described in this contribution and the first images of Cherenkov showers obtained using the telescope and its camera are presented. These were obtained in November 2015 in Meudon, rance