Abstract
Signal-induced noise is observed in Hamamatsu R11265
Multianode Photomultiplier Tubes, manifesting up to several
microseconds after the single photoelectron response signal and
localised in ...specific anodes. The mean number of noise pulses varies
between devices, and shows significant dependence on the applied
high-voltage. The characterisation of this noise and the mitigation
strategies to perform optimal single-photon counting at 40 MHz, as
required by the LHCb Ring-Imaging Cherenkov detectors, are
reported.
Abstract
The TORCH detector provides low-momentum particle identification, combining Time of Flight (TOF) and Cherenkov techniques to achieve charged particle pi/K/p separation between 2–20 GeV/c ...over a flight distance of 10 m. The measurement requires a timing resolution of 70 ps for single Cherenkov photons. For precision photon detection, customised Micro-Channel Plate Photomultiplier Tubes (MCP-PMTs) with high precision TOF measurement electronics have been developed. The electronics measures time-over-threshold from the MCP-PMT and features a 10-Gigabit Ethernet readout. This paper reports the design and performance of a 5120-channel system which currently instruments a pair of MCP-PMTs, but has the capacity to read out ten customised MCP-PMT devices in the future.
The TORCH time-of-flight detector is designed to provide a 15 ps timing resolution for charged particles, resulting in
π
/K particle identification up to 10 GeV/c momentum over a 10 m flight path. ...Cherenkov photons, produced in a quartz plate of 10 mm thickness, are focused onto an array of micro-channel plate photomultipliers (MCP-PMTs) which measure the photon arrival times and spatial positions. A half-scale (660 × 1250 × 10 mm
3
) TORCH demonstrator module has been tested in an 8 GeV/c mixed proton-pion beam at CERN. Customised square MCP-PMTs of active area 53 × 53 mm
2
and granularity 64 × 64 pixels have been employed, which have been developed in collaboration with an industrial partner. The single-photon timing performance and photon yields have been measured as a function of beam position in the radiator, giving measurements which are consistent with expectations. The expected performance of TORCH for high luminosity running of the LHCb Upgrade II has been simulated.
Victims of acute radiation exposure are susceptible to hematopoietic toxicity due to bone marrow damage and loss of mature blood elements. Here, we evaluated cord blood–derived endothelial progenitor ...cells (CB-EPCs) as a potential cellular therapy for mitigation of hematologic acute radiation syndrome. CB-EPCs express endothelial cell markers and maintain their growth characteristics beyond 10+ passages without diminishing their doubling capacity. Further, CB-EPCs can be cryopreserved in vapor-phase liquid nitrogen and easily recovered for propagation, making them an attractive nonimmunogenic cellular therapy for off-the-shelf use. Importantly, we show CB-EPCs have the capacity to potently expand adult human bone marrow hematopoietic progenitor cells both in vitro and in vivo.
To demonstrate the role of CB-EPCs in promoting in vivo human immune reconstitution after irradiation, we employed a novel humanized mouse model established by transplant of CD34+ bone marrow cells from 9 unique adult organ donors into immunocompromised NSG-SGM3 mice. The response of the humanized immune system to ionizing irradiation was then tested by exposure to 1 Gy followed by subcutaneous treatment of CB-EPCs, Food and Drug Administration–approved growth factor pegfilgrastim (0.3 mg/kg), or saline.
At day 7, total human bone marrow was decreased by 80% in irradiated controls. However, treatment with either growth factor pegfilgrastim or CB-EPCs increased recovery of total human bone marrow by 2.5-fold compared with saline. Notably, CB-EPCs also increased recovery of both human CD34+ progenitors by 5-fold and colony-forming capacity by 3-fold versus saline. Additionally, CB-EPCs promoted recovery of endogenous bone marrow endothelial cells as observed by both increased vessel area and length compared with saline.
These findings indicate the feasibility of using humanized mice engrafted with adult bone marrow for radiation research and the development of CB-EPCs as an off-the-shelf cellular therapy for mitigation of hematologic acute radiation syndrome.
Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family which has been extensively studied for its roles in neural development, long-term memory, brain injury, and ...neurodegenerative diseases. BDNF signaling through tropomyosin receptor kinase B (TrkB) stimulates neuronal cell survival. For this reason, small molecule TrkB agonists are under pre-clinical develoment for the treatment of a range of neurodegenerative diseases and injuries. Our laboratory recently reported BDNF is secreted by pro-regenerative endothelial progenitor cells (EPCs) which support hematopoietic reconstitution following total body irradiation (TBI). Here we report BDNF-TrkB signaling plays a novel regenerative role in bone marrow and thymic regeneration following radiation injury. Exogenous administration of BDNF or TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) following myelosuppressive radiation injury promoted faster recovery of mature blood cells and hematopoietic stem cells capable of multi-lineage reconstitution. BDNF promotes hematopoietic regeneration via activation of PDGFRα+ bone marrow mesenchymal stem cells (MSCs) which increase secretion of hematopoietic cytokines interleukin 6 (IL-6) and leukemia inhibitory factor (LIF) in response to TrkB activation. These data suggest pharmacologic activation of the BDNF pathway with either BDNF or 7,8-DHF may be beneficial for treatment of radiation or chemotherapy induced myelosuppression.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A hydraulic calcium phosphate cement having dicalcium phosphate dihydrate (DCPD) as end-product of the setting reaction was implanted in a cylindrical defect in the diaphysis of sheep for up to 6 ...months. The composition of the cement was investigated as a function of time. After setting, the cement composition consisted essentially of a mixture of DCPD and
β-tricalcium phosphate (
β-TCP). In the first few weeks of implantation, the edges of the cement samples became depleted in DCPD, suggesting a selective dissolution of DCPD, possibly due to low pH conditions. The cement resorption at this stage was high. After 8 weeks, the resorption rate slowed down. Simultaneously, a change of the color and density of the cement center was observed. These changes were due to the conversion of DCPD into a poorly crystalline apatite. Precipitation started after 6–8 weeks and progressed rapidly. At 9 weeks, the colored central zone reached its maximal size. The fraction of
β-TCP in the cement was constant at all time. Therefore, this study demonstrates that the resorption rate of DCPD cement is more pronounced as long as DCPD is not transformed in vivo.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Performance simulation of BaBar DIRC bar boxes in TORCH Föhl, K.; Brook, N.; Castillo García, L. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2017, Volume:
876
Journal Article
Peer reviewed
Open access
TORCH is a large-area precision time-of-flight detector based on the DIRC principle. The DIRC bar boxes of the BaBar experiment at SLAC could possibly be reused to form a part of the TORCH detector ...time-of-flight wall area, proposed to provide positive particle identification of low momentum kaons in the LHCb experiment at CERN. For a potential integration of BaBar bar boxes into TORCH, new imaging readout optics are required. From the several designs of readout optics that have been considered, two are used in this paper to study the effect of BaBar bar optical imperfections on the detector reconstruction performance. The kaon-pion separation powers obtained from analysing simulated photon hit patterns show the performance reduction for a BaBar bar of non-square geometry compared to a perfectly rectangular cross section.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
TORCH—a Cherenkov based time-of-flight detector van Dijk, M.W.U.; Brook, N.H.; Castillo García, L. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2014, Volume:
766
Journal Article
Peer reviewed
Open access
TORCH is an innovative high-precision time-of-flight system to provide particle identification in the difficult intermediate momentum region up to 10 GeV/c . It is also suitable for large-area ...applications. The detector provides a time-of-flight measurement from the imaging of Cherenkov photons emitted in a 1 cm thick quartz radiator. The photons propagate by total internal reflection to the edge of the quartz plate and are then focused onto an array of photon detectors at the periphery. A time-of-flight resolution of about 10-15 ps per incident charged particle needs to be achieved to allow a three sigma kaon-pion separation up to 10 GeV/c momentum for the TORCH located 9.5 m from the interaction point. Given ~30~30 detected photons per incident charged particle, this requires measuring the time-of-arrival of individual photons to about 70 ps. This paper will describe the design of a TORCH prototype involving a number of ground-breaking and challenging techniques.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Radiation-induced lung injury is a major dose-limiting toxicity for thoracic radiation therapy patients. In experimental models, treatment with angiotensin converting enzyme (ACE) inhibitors ...mitigates radiation pneumonitis; however, the mechanism of action is not well understood. Here, we evaluate the direct role of ACE inhibition on lung immune cells.
ACE expression and activity were determined in the lung immune cell compartment of irradiated adult rats after either high dose fractionated radiation therapy to the right lung (5 fractions × 9 Gy) or a single dose of 13.5 Gy partial body irradiation. Mitigation of radiation-induced pneumonitis with the ACE-inhibitor lisinopril was evaluated in the 13.5 Gy rat partial body irradiation model. During pneumonitis, we characterized inflammation and immune cell content in the lungs and bronchoalveolar lavage fluid. In vitro mechanistic studies were performed using primary human monocytes and the human monocytic THP-1 cell line.
In both the partial body irradiation and fractionated radiation therapy models, radiation increased ACE activity in lung immune cells. Treatment with lisinopril improved survival during radiation pneumonitis (P = .0004). Lisinopril abrogated radiation-induced increases in bronchoalveolar lavage fluid monocyte chemoattractant protein 1 (chemokine ligand 2) and MIP-1a cytokine levels (P < .0001). Treatment with lisinopril reduced both ACE expression (P = .006) and frequency of CD45+ CD11b+ lung myeloid cells (P = .004). In vitro, radiation injury acutely increased ACE activity (P = .045) and reactive oxygen species (ROS) generation (P = .004) in human monocytes, whereas treatment with lisinopril blocked radiation-induced increases in both ACE and ROS. Radiation-induced ROS generation was blocked by pharmacologic inhibition of either NADPH oxidase 2 (P = .012) or the type 1 angiotensin receptor (P = .013).
These data demonstrate radiation-induced ACE activation within the immune compartment promotes the pathogenesis of radiation pneumonitis, while ACE inhibition suppresses activation of proinflammatory immune cell subsets. Mechanistically, our in vitro data demonstrate radiation directly activates the ACE/type 1 angiotensin receptor pathway in immune cells and promotes generation of ROS via NADPH oxidase 2.
PDF
