Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication

AbstractHepatitis C virus (HCV) is a positive-strand RNA virus that frequently causes persistent infection associated with severe liver disease. HCV nonstructural protein 5A (NS5A) is essential for viral replication. Here, the kinase Raf-1 was identified as a novel cellular binding partner of NS5A, binding to the C-terminal domain of NS5A. Raf-1 colocalizes with NS5A in the HCV replication complex. The interaction of NS5A with Raf-1 results in increased Raf-1 phosphorylation at serine 338. Integrity of Raf-1 is crucial for HCV replication: inhibition of Raf-1 by the small-molecule inhibitor BAY43-9006 or downregulation of Raf-1 by siRNA attenuates viral replication

Demonstration of Gd-GEM detector design for neutron macromolecular crystallography applications

The European Spallation Source (ESS) in Lund, Sweden will become the world's most powerful thermal neutron source. The Macromolecular Diffractometer (NMX) at the ESS requires three 51.2 x 51.2~cm$^{2}$ detectors with reasonable detection efficiency, sub-mm spatial resolution, a narrow point spread function (PSF) and good time resolution. This work presents measurements with the improved version of the NMX detector prototype consisting of a Triple-GEM detector with natural Gd converter and a low material budget readout. The detector was successfully tested at the neutron reactor of the Budapest Neutron Centre (BNC) and at the D16 instrument at the Institut Laue-Langevin (ILL) in Grenoble. The measurements with Cadmium and Gadolinium masks in Budapest demonstrate that the point spread function of the detector lacks long tails that could impede the measurement of diffraction spot intensities. On the D16 instrument at ILL, diffraction spots from Triose phosphate isomerase w/ 2-phosphoglycolate (PGA) inhibitor were measured both in the D16 Helium-3 detector and the Gd-GEM. The comparison between the two detectors show a similar point spread function in both detectors, and the expected efficiency ratio compared to the Helium-3 detector. Both measurements together thus give good indications that the Gd-GEM detector fits the requirements for the NMX instrument at ESS

X-ray imaging with gaseous detectors using the VMM3a and the SRS

The integration of the VMM3a Application-Specific Integrated Circuit (ASIC) into RD51's Scalable Readout System (SRS) provides a versatile tool for the readout of Micro-Pattern Gaseous Detectors (MPGDs). With its self-triggered high-rate readout, its analogue part that allows to get information on the deposited energy in the detector, and its so-called neighbouring-logic that allows to recover information on the charge distribution, this new system has features of particular interest for digital X-ray imaging. In the present article, we want to emphasise the capabilities of VMM3a/SRS by presenting results of X-ray imaging studies. We will highlight the advantages on the energy and the spatial resolution provided by the neighbouring-logic. In the first part, we focus on spatial resolution studies. We show how segmented readout structures introduce a repeating pattern in the distribution of the reconstructed positions (using the centre-of-gravity method) and how this behaviour can be mitigated with the neighbouring-logic. As part of these studies, we explore as well an alternative position reconstruction algorithm. In the second part of the article, we present the energy resolution studies.Peer reviewe

Rate-capability of the VMM3a front-end in the RD51 Scalable Readout System

The VMM3a is an Application Specific Integrated Circuit (ASIC), specifically developed for the readout of gaseous detectors. Originally developed within the ATLAS New Small Wheel (NSW) upgrade, it has been successfully integrated into the Scalable Readout System (SRS) of the RD51 collaboration. This allows, to use the VMM3a also in small laboratory set-ups and mid-scale experiments, which make use of Micro-Pattern Gaseous Detectors (MPGDs). As part of the integration of the VMM3a into the SRS, the readout and data transfer scheme was optimised to reach a high rate-capability of the entire readout system and profit from the VMM3a’s high single-channel rate-capability of 3.6 Mhits∕s. The optimisation focused mainly on the handling of the data output stream of the VMM3a, but also on the development of a trigger-logic between the front-end cards and the DAQ computer. In this article, two firmware implementations of the non-ATLAS continuous readout mode are presented, as well as the implementation of the trigger-logic. Afterwards, a short overview on X-ray imaging results is presented, to illustrate the high rate-capability from an application point-of-view.Peer reviewe

Infrastructure for Detector Research and Development towards the International Linear Collider

The EUDET-project was launched to create an infrastructure for developing and testing new and advanced detector technologies to be used at a future linear collider. The aim was to make possible experimentation and analysis of data for institutes, which otherwise could not be realized due to lack of resources. The infrastructure comprised an analysis and software network, and instrumentation infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture

Development of the scalable readout system for micro-pattern gas detectors and other applications

Developed within RD51 Collaboration for the Development of Micro-Pattern Gas Detectors Technologies, the Scalable Readout System (SRS) is intended as a general purpose multichannel readout solution for a wide range of detector types and detector complexities. The scalable architecture, achieved using multi-Gbps point-to-point links with no buses involved, allows the user to tailor the system size to his needs. The modular topology enables the integration of different front-end ASICs, giving the user the possibility to use the most appropriate front-end for his purpose or to build a heterogeneous experimental apparatus which integrates different front-ends into the same DAQ system. Current applications include LHC upgrade activities, geophysics or homeland security applications as well as detector R&D. The system architecture, development and running experience will be presented, together with future prospects, ATCA implementation options and application possibilities.Martoiu, S.; Muller, H.; Tarazona Martínez, A.; Toledo Alarcón, JF. (2013). Development of the scalable readout system for micro-pattern gas detectors and other applications. Journal of Instrumentation. 8(3):1-11. doi:10.1088/1748-0221/8/03/C03015S1118

Timing performance of a Micro-Channel-Plate Photomultiplier Tube

The spatial dependence of the timing performance of the R3809U-50 Micro-Channel-Plate PMT (MCP-PMT) by Hamamatsu was studied in high energy muon beams. Particle position information is provided by a GEM tracker telescope, while timing is measured relative to a second MCP-PMT, identical in construction. In the inner part of the circular active area (radius r5.5 mm) the time resolution of the two MCP-PMTs combined is better than 10 ps. The signal amplitude decreases in the outer region due to less light reaching the photocathode, resulting in a worse time resolution. The observed radial dependence is in quantitative agreement with a dedicated simulation. With this characterization, the suitability of MCP-PMTs as t0 reference detectors has been validated.Peer reviewe

Precise charged particle timing with the PICOSEC detector

The experimental requirements in near future accelerators (e.g. High Luminosity-LHC) has stimulated intense interestin development of detectors with high precision timing capabilities. With this as a goal, a new detection concept called PICOSEC,which is based to a “two-stage” MicroMegas detector coupled to a Cherenkov radiator equipped with a photocathode has beendeveloped. Results obtained with this new detector yield a time resolution of 24 ps for 150 GeV muons and 76 ps for single pho-toelectrons. In this paper we will report on the performance of the PICOSEC in test beams, as well as simulation studies andmodelling of its timing characteristicsPeer reviewe

Precise timing with the PICOSEC-Micromegas detector

This work presents the concept of the PICOSEC-Micromegas de-tector to achieve a time resolution below 30 ps. PICOSEC consists of a two-stageMicromegas detector coupled to a Cherenkov radiator and equipped with a photo-cathode. The results from single-channel prototypes as well as the understanding ofthe detector in terms of detailed simulations and preliminary results from a multi-channel prototype are presented.Peer reviewe

Charged particle timing at sub-25 picosecond precision : The PICOSEC detection concept

The PICOSEC detection concept consists in a “two-stage” Micromegas detector coupled to a Cherenkov radiator and equipped with a photocathode. A proof of concept has already been tested: a single-photoelectron response of 76 ps has been measured with a femtosecond UV laser at CEA/IRAMIS, while a time resolution of 24 ps with a mean yield of 10.4 photoelectrons has been measured for 150 GeV muons at the CERN SPS H4 secondary line. This work will present the main results of this prototype and the performance of the different detector configurations tested in 2016-18 beam campaigns: readouts (bulk, resistive, multipad) and photocathodes (metallic+CsI, pure metallic, diamond). Finally, the prospects for building a demonstrator based on PICOSEC detection concept for future experiments will be discussed. In particular, the scaling strategies for a large area coverage with a multichannel readout plane, the R&D on solid converters for building a robust photocathode and the different resistive configurations for a robust readout.Peer reviewe