Tissue localization of tumor antigen-loaded mouse dendritic cells applied as an anti-tumor vaccine and their influence on immune response.

The recognition, internalization and intracellular processing of antigen are the main functions of dendritic cells (DCs). In the course of these processes, DCs differentiate and acquire the ability to produce cytokines responsible for polarization of the immunological response. Therefore, vaccination with tumor antigen-loaded DCs is one of the most promising approaches to induce tumor-specific immune response. The purpose of this study was to analyze the migratory abilities, from an injection site to tumor-draining lymph nodes (tLN), of DCs applied as an anti-tumor vaccine and their capacity for immune response activation. Mouse DCs of the established JAWS II cell line transduced with EGFP gene or ex vivo bone marrow-isolated DCs (BM-DCs) stained with intravital CFDA dye were loaded with MC38 colon carcinoma tumor lysate (TAg) and then administered peritumorally to MC38 tumor-bearing C57BL/6 mice. On the first, third, fifth and seventh days after injection the tumors, tLNs and spleens were examined. The TAg-loaded DCs migrated more effectively to the tLNs than did the unloaded control DCs; however, the majority of them remained in the tumor vicinity. Immunohistological analysis of the tumor tissues demonstrated that only TAg-loaded DCs activated an immune response. Seven days after DCs vaccine administration, numerous necrotic areas and some apoptotic bodies were observed in the tumor tissue. However, the anti-MC38 tumor cytotoxic activity of spleen and tLN cells from mice treated with both TAg-loaded and unloaded DCs reached a maximum on the fifth day after DC injection. Concluding, TAg-loaded DCs migrated more efficiently to tLNs and were more effective activators of local (but not systemic) cellular immune response than were unloaded DCs. We hypothesize that only the application of TAg-loaded DCs to tumor-bearing mice as an adjuvant supporting chemotherapy may activate a more effective anti-tumor response

A revised description of Gyrodactylus cichlidarum Paperna, 1968 (Gyrodactylidae) from the Nile tilapia, Oreochromis niloticus niloticus (Cichlidae), and its synonymy with G. niloticus Cone, Arthur et Bondad-Reantaso, 1995

A recent infestation of Gyrodactylus cichlidarum Paperna, 1968 on yolk sac fry of Nile tilapia, Oreochromis niloticus niloticus (L.), in an isolated aquarium system in the UK resulted in high mortalities and provided an opportunity to study this species in greater detail. A tentative identification was made using the measurements and drawings of the ventral bar and hamuli provided in the original description; however, details on the morphology of the marginal hooks were lacking. A comparison of the gyrodactylid material collected from O. n. niloticus with the holotype of G. cichlidarum, the only known available specimen, from Mango tilapia, Sarotherodon galilaeus galilaeus (L.), confirmed its identity. Proteolytic digestion and image analysis of he opisthaptoral hard parts were used to obtain tissue-free, accurate measurements as part of a complete revised. description of G. cichlidarum. Further, a comparison of G. cichlidarum from both hosts with the holotype and several paratypes of Gyrodactylus niloticus Cone, Arthur et Bondad-Reantaso, 1995 cited as parasitizing captive stocks of Nile tilapia in the Philippines revealed the two species to be synonymous. An 803 bp fragment of the ribosomal internal transcribed spacers I and 2 and the 5.8S was obtained and is provided with the revised description. This is the first DNA sequence from a Gyrodactylus species originating from the African continent. The sequence is very divergent from other species in the genus and only the 5.8S sequence places it unambiguously in the genus Gyrodactylus. In addition to G. cichlidarum, two specimens of another morphological similar species of Gyrodactylus were also found on the UK held stock of O. n. niloticus. These latter specimens, Gyrodactylus sp., differed from G. cichlidarum in having a longer hamulus point with a smaller hamulus aperture and possessing marginal hook sickles that had a shorter shaft with a longer point giving the sickles a more rounded, closed appearanc

FlashCam: A fully digital camera for CTA telescopes

The future Cherenkov Telescope Array (CTA) will consist of several tens of telescopes of different mirror sizes. CTA will provide next generation sensitivity to very high energy photons from few tens of GeV to >100 TeV. Several focal plane instrumentation options are currently being evaluated inside the CTA consortium. In this paper, the current status of the FlashCam prototyping project is described. FlashCam is based on a fully digital camera readout concept and features a clean separation between photon detector plane and signal digitization/triggering electronics.Comment: In Proceedings of the 2012 Heidelberg Symposium on High Energy Gamma-Ray Astronomy. All CTA contributions at arXiv:1211.184

FlashCam: a fully-digital camera for the medium-sized telescopes of the Cherenkov Telescope Array

The FlashCam group is currently preparing photomultiplier-tube based cameras proposed for the medium-sized telescopes (MST) of the Cherenkov Telescope Array (CTA). The cameras are designed around the FlashCam readout concept which is the first fully-digital readout system for Cherenkov cameras, based on commercial FADCs and FPGAs as key components for the front-end electronics modules and a high performance camera server as back-end. This contribution describes the progress of the full-scale FlashCam camera prototype currently under construction, as well as performance results also obtained with earlier demonstrator setups. Plans towards the production and implementation of FlashCams on site are also briefly presented.Comment: 8 pages, 6 figures. In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Performance Verification of the FlashCam Prototype Camera for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is a future gamma-ray observatory that is planned to significantly improve upon the sensitivity and precision of the current generation of Cherenkov telescopes. The observatory will consist of several dozens of telescopes with different sizes and equipped with different types of cameras. Of these, the FlashCam camera system is the first to implement a fully digital signal processing chain which allows for a traceable, configurable trigger scheme and flexible signal reconstruction. As of autumn 2016, a prototype FlashCam camera for the medium-sized telescopes of CTA nears completion. First results of the ongoing system tests demonstrate that the signal chain and the readout system surpass CTA requirements. The stability of the system is shown using long-term temperature cycling.Comment: 5 pages, 13 figures, Proceedings of the 9th International Workshop on Ring Imaging Cherenkov Detectors (RICH 2016), Lake Bled, Sloveni

The SST-1M camera for the Cherenkov Telescope Array

The prototype camera of the single-mirror Small Size Telescopes (SST-1M) proposed for the Cherenkov Telescope Array (CTA) project has been designed to be very compact and to deliver high performance over thirty years of operation. The camera is composed of an hexagonal photo-detection plane made of custom designed large area hexagonal silicon photomultipliers and a high throughput, highly configurable, fully digital readout and trigger system (DigiCam). The camera will be installed on the telescope structure at the H. Niewodnicza{\'n}ski institute of Nuclear Physics in Krakow in fall 2015. In this contribution, we review the steps that led to the development of the innovative photo-detection plane and readout electronics, and we describe the test and calibration strategy adopted.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.05894; Full consortium author list at http://cta-observatory.or

Human Genotyping and An Experimental Model Reveal NPR-C as A Possible Contributor to Morbidity In Coarctation Of The Aorta

Coarctation of the aorta (CoA) is a common congenital cardiovascular (CV) defect characterized by a stenosis of the descending thoracic aorta. Treatment exists, but many patients develop hypertension (HTN). Identifying the cause of HTN is challenging because of patient variability (e.g., age, follow-up duration, severity) and concurrent CV abnormalities. Our objective was to conduct RNA sequencing of aortic tissue from humans with CoA to identify a candidate gene for mechanistic studies of arterial dysfunction in a rabbit model of CoA devoid of the variability seen with humans. We present the first known evidence of natriuretic peptide receptor C (NPR-C; aka NPR3) downregulation in human aortic sections subjected to high blood pressure (BP) from CoA versus normal BP regions (validated to PCR). These changes in NPR-C, a gene associated with BP and proliferation, were replicated in the rabbit model of CoA. Artery segments from this model were used with human aortic endothelial cells to reveal the functional relevance of altered NPR-C activity. Results showed decreased intracellular calcium ([Ca2+]i) activity to C-type natriuretic peptide (CNP). Normal relaxation induced by CNP and atrial natriuretic peptide was impaired for aortic segments exposed to elevated BP from CoA. Inhibition of NPR-C (M372049) also impaired aortic relaxation and [Ca2+]i activity. Genotyping of NPR-Cvariants predicted to be damaging revealed that rs146301345 was enriched in our CoA patients, but sample size limited association with HTN. These results may ultimately be used to tailor treatment for CoA based on mechanical stimuli, genotyping, and/or changes in arterial function

Large scale characterization and calibration strategy of a SiPM-based camera for gamma-ray astronomy

The SST-1M is a 4-m diameter mirror Davies-Cotton gamma-ray telescope. It has been designed to cover the energy range above 500 GeV and to be part of an array of telescopes separated by 150-200 m. Its innovative camera is featuring large area hexagonal silicon photo-multipliers as photon detectors and a fully digital trigger and readout system. Here, the strategy and the methods for its calibration are presented, together with the obtained results. In particular, the off and on-site calibration strategies are demonstrated on the first camera prototype. The performances of the camera in terms of charge and time resolution are described