Status of the TORCH time-of-flight project Harnew, N.; Bhasin, S.; Blake, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2020, Volume:
952
Journal Article
Peer reviewed
Open access
TORCH is a time-of-flight detector, designed to provide charged π∕K particle identification up to a momentum of 10GeV/c for a 10m flight path. To achieve this level of performance, a time resolution ...of 15 ps per incident particle is required. TORCH uses a plane of quartz of 1 cm thickness as a source of Cherenkov photons, which are then focussed onto square Micro-Channel Plate Photomultipliers (MCP-PMTs) of active area 53 × 53mm2, segmented into 8 × 128 pixels equivalent. A small-scale TORCH demonstrator with a customised MCP-PMT and associated readout electronics has been successfully operated in a 5GeV/c mixed pion/proton beam at the CERN PS facility. Preliminary results indicate that a single-photon resolution better than 100ps can be achieved. The expected performance of a full-scale TORCH detector for the Upgrade II of the LHCb experiment is also discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ATP-binding cassette (ABC) transporter proteins carry diverse substrates across cell membranes. Whereas clinically relevant ABC exporters are implicated in various diseases or cause multidrug ...resistance of cancer cells, bacterial ABC importers are essential for the uptake of nutrients, including rare elements such as molybdenum. A detailed understanding of their mechanisms requires direct visualization at high resolution and in distinct conformations. Our recent structure of the multidrug ABC exporter Sav1866 has revealed an outward-facing conformation of the transmembrane domains coupled to a closed conformation of the nucleotide-binding domains, reflecting the ATP-bound state. Here we present the 3.1 Å crystal structure of a putative molybdate transporter (ModB2C2) from Archaeoglobus fulgidus in complex with its binding protein (ModA). Twelve transmembrane helices of the ModB subunits provide an inward-facing conformation, with a closed gate near the external membrane boundary. The ATP-hydrolysing ModC subunits reveal a nucleotide-free, open conformation, whereas the attached binding protein aligns the substrate-binding cleft with the entrance to the presumed translocation pathway. Structural comparison of ModB2C2A with Sav1866 suggests a common alternating access and release mechanism, with binding of ATP promoting an outward-facing conformation and dissociation of the hydrolysis products promoting an inward-facing conformation.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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Beam tests of a large-scale TORCH time-of-flight demonstrator Hancock, T.H.; Bhasin, S.; Blake, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2020, Volume:
958
Journal Article
Peer reviewed
Open access
The TORCH time-of-flight detector is designed to provide particle identification in the momentum range 2−10GeV∕c over large areas. The detector exploits prompt Cherenkov light produced by charged ...particles traversing a 10mm thick quartz plate. The photons propagate via total internal reflection and are focused onto a detector plane comprising position-sensitive Micro-Channel Plate Photo-Multiplier Tubes (MCP-PMT) detectors. The goal is to achieve a single-photon timing resolution of 70ps, giving a timing precision of 15ps per charged particle by combining the information from around 30 detected photons. The MCP-PMT detectors have been developed with a commercial partner (Photek Ltd, UK), leading to the delivery of a square tube of active area 53×53mm2 with a granularity of 8×128pixels equivalent. A large-scale demonstrator of TORCH, having a quartz plate of dimensions 660×1250×10mm3 and read out by a pair of MCP-PMTs with custom readout electronics, has been verified in a test beam campaign at the CERN PS. Preliminary results indicate that the required performance is close to being achieved. The anticipated performance of a full-scale TORCH detector at the LHCb experiment is presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
TORCH is a time-of-flight detector designed to perform particle identification over the momentum range 2–10 GeV/c for a 10 m flight path. The detector exploits prompt Cherenkov light produced by ...charged particles traversing a quartz plate of 10mm thickness. Photons are then trapped by total internal reflection and directed onto a detector plane instrumented with customised position-sensitive Micro-Channel Plate Photo-Multiplier Tube (MCP-PMT) detectors. A single-photon timing resolution of 70ps is targeted to achieve the desired separation of pions and kaons, with an expectation of around 30 detected photons per track. Studies of the performance of a small-scale TORCH demonstrator with a radiator of dimensions 120×350×10mm3 have been performed in two test-beam campaigns during November 2017 and June 2018. Single-photon time resolutions ranging from 104.3ps to 114.8ps and 83.8ps to 112.7ps have been achieved for MCP-PMTs with granularity 4 × 64 and 8 × 64 pixels, respectively. Photon yields are measured to be within ∼10% and ∼30% of simulation, respectively. Finally, the outlook for future work with planned improvements is presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Between 5 and 10% of adults infected with the hepatitis B virus (HBV) develop a chronic infection lasting longer than 6 months, which may lead to advanced liver disease. HBV can be classified into ...six genotypic families: A, B, C, D, E and F, but only genotypes A and D are significantly represented in western Europe, where they account for some 90% of cases of infection with HBV. In the present study, we investigated a possible association between HBV genotype A or D and clinical outcome of the infection. We compared the prevalence of these genotypes in a group of patients with chronic active hepatitis to that of a group with acute resolving hepatitis. In patients with chronic active hepatitis, genotype A was found in 28 of 35 patients and genotype D in only four. The remaining three patients were infected with genotype non‐A, non‐D. In contrast, genotype D was found in 24 of 30 patients with acute hepatitis, whilst genotype A was found in only three patients of this group. Three were infected with genotype non‐A, non‐D. Our results show a clear association between genotype A and chronic outcome (Ficher’s exact test: two‐sided P‐value, P < 0.0001). They suggest that HBV genotypes may play a role in the virus–host relationship. Possible mechanisms for such a role are discussed.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Phage display is an in vitro selection technique that allows for the rapid isolation of proteins with desired properties including increased affinity, specificity, stability, and new enzymatic ...activity. The power of phage display relies on the phenotype-to-genotype linkage of the protein of interest displayed on the phage surface with the encoding DNA packaged within the phage particle, which allows for selective enrichment of library pools and high-throughput screening of resulting clones. As an in vitro method, the conditions of the binding selection can be tightly controlled. Due to the high-throughput nature, rapidity, and ease of use, phage display is an excellent technological platform for engineering antibody or proteins with enhanced properties. Here, we describe methods for synthesis, selection, and screening of phage libraries with particular emphasis on designing humanizing antibody libraries and combinatorial scanning mutagenesis libraries. We conclude with a brief section on troubleshooting for all stages of the phage display process.
We describe and evaluate a model chain for studying streamflow responses to climate variations and anthropogenic climate change. The model chain was developed for the Rhine basin upstream of Cologne, ...a 145,000 km2 river basin in Central Europe north of the Alps. It encompasses a regional climate model (RCM) at grid spacings of 56 and 14 km, and a distributed hydrological model with a grid spacing of 1 km. The hydrological model is one‐way nested into the RCM through a downscaling interface, which introduces fine‐scale structures in the forcing data (i.e. temperature, precipitation, total net surface radiation, 10‐m wind speed, and relative humidity). Biases in precipitation and temperature are accounted for by catchment‐dependent but seasonally constant correction factors. Apart from these bias corrections, the hydrological model is forced by hourly RCM data. In the evaluation we compare a 5‐year integration driven by observed lateral boundary conditions (ECMWF reanalysis) against daily analysis of high‐density rain‐gauge data and streamflow data. The regional climate model is found to qualitatively reproduce the main mesoscale precipitation patterns and their seasonal evolution. Systematic biases are, however, found in the distribution of precipitation with topographic height in the Alpine region and at adjacent hill ranges. The RCM also reproduces intercatchment variations in the frequency distribution of daily precipitation. Simulated runoff resembles closely the mean annual cycle, and daily runoff agrees well with observations in timing and amplitude of runoff events for lowland gauges. Larger model errors are found for high‐altitude Alpine catchments. The 14‐km RCM provides much finer and more realistic precipitation fields compared to the 56‐km RCM, but these improvements did not have a significant impact on the skill of the hydrological model to simulate streamflow. The model chain was found to reproduce observed month‐to‐month variations of basin‐mean winter precipitation and streamflow with correlations between 0.85 and 0.95. This result provides confidence that the model chain is able to represent key processes related to streamflow variations in response to climate variations and climate change.
Abstract
The performance of the ring-imaging Cherenkov detectors at
the LHCb experiment is determined during the LHC Run 2 period
between 2015 and 2018. The stability of the Cherenkov angle
...resolution and number of detected photons with time and running
conditions is measured. The particle identification performance is
evaluated with data and found to satisfy the requirements of the
physics programme.
Mammalian target of rapamycin complex 2 (mTORC2) is a protein kinase complex that plays an important role in energy homeostasis. Loss of adipose mTORC2 reduces lipogenic enzyme expression and de novo ...lipogenesis in adipose tissue. Adipose-specific mTORC2 knockout mice also display triglyceride accumulation in the liver. However, the mechanism and physiological role of hepatic triglyceride accumulation upon loss of adipose mTORC2 are unknown. Here, we show that loss of adipose mTORC2 increases the expression of de novo lipogenic enzymes in the liver, thereby causing accumulation of hepatic triglyceride and hypertriglyceridemia. Simultaneous inhibition of lipogenic enzymes in adipose tissue and liver by ablating mTORC2 in both tissues prevented accumulation of hepatic triglycerides and hypertriglyceridemia. However, loss of adipose and hepatic mTORC2 caused severe insulin resistance and glucose intolerance. Thus our findings suggest that increased hepatic lipogenesis is a compensatory mechanism to cope with loss of lipogenesis in adipose tissue, and further suggest that mTORC2 in adipose tissue and liver plays a crucial role in maintaining whole body energy homeostasis.
Loss of adipose and hepatic mTORC2 causes diabetes.
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