Ageing in the LHCb outer tracker: Aromatic hydrocarbons and wire cleaning Tuning, N.; Bachmann, S.; Bagaturia, Y. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2011, Letnik:
656, Številka:
1
Journal Article
Recenzirano
The LHCb Outer Tracker straw tubes have shown to suffer from gain loss after irradiation in the laboratory at moderate intensities. Under irradiation an insulating layer is formed on the anode wire. ...The ageing is caused by contamination of the counting gas due to outgassing of the plastifier di-isopropyl-naphthalene in araldite AY103-1 used at construction. This paper presents irradiation results with and without the plastifier, together with the mass spectra of the glue samples. In addition, the effects of wire heating and large currents are presented.
The LHCb Outer Tracker (OT) detector has shown to suffer from gain loss after irradiation in the laboratory at moderate intensities. Under irradiation an insulating layer is formed on the anode wire. ...The ageing is caused by contamination of the counting gas due to outgassing of the glue used in construction namely araldite AY103-1. The gain loss is concentrated upstream the gas flow, and at moderate irradiation intensity only. The ageing rate is reduced by longterm flushing and by the addition of a few percent of
O
2
to the gas mixture. Furthermore, applying a large positive high voltage (beyond the amplification regime) removes the insulating deposits without damaging the wire surface. This paper presents both the characteristics of the ageing phenomenon and the beneficial treatments.
The LHCb Outer Tracker is a gaseous detector covering an area of 5x6 m2 with 12 double layers of straw tubes. The detector with its services are described together with the commissioning and ...calibration procedures. Based on data of the first LHC running period from 2010 to 2012, the performance of the readout electronics and the single hit resolution and efficiency are presented. The efficiency to detect a hit in the central half of the straw is estimated to be 99.2%, and the position resolution is determined to be approximately 200 um. The Outer Tracker received a dose in the hottest region corresponding to 0.12 C/cm, and no signs of gain deterioration or other ageing effects are observed.
One quarter of the Forward Ring Imaging Cherenkov (Forward RICH) detector has been installed and operated in the DELPHI experiment. The detector covers the forward-backward regions (15 degrees < ...theta <35 degrees ). Two radiator systems are used for particle identification in the momentum range up to 40 GeV/c, i.e., a liquid perfluorohexane and perfluorobutane gas. UV-photons with wavelengths from approximately 170 nm to approximately 200 nm (7.3-6.2 eV) are detected with high efficiency. The total active area of the photon detector is approximately 8 m/sup 2/.< >
To determine the association between increasing volumes of crystalloids and colloids administered before transfusion of packed red blood cells in women with persistent postpartum haemorrhage and ...adverse maternal outcomes.
Retrospective cohort study in the Netherlands. Women with persistent postpartum haemorrhage and known clear fluids volume for resuscitation were included. Women who received ≤2 L of clear fluids were the reference group. We determined the effect of every additional litre of clear fluids on total blood loss, severe maternal morbidity and mortality. Results were adjusted for patient and bleeding characteristics.
Of the 883 included women, 199 received ≤2 L of clear fluids. Median blood loss for the reference group was 2.9 L (interquartile range 2.2–3.4). Adjusted mean difference in blood loss compared with the reference group was 0.2 L (95% confidence interval −0.1 to 0.5) for women in the >2 to ≤3 L, 0.4 L (0.1–0.7) for the >3 to ≤4 L category, 0.6 L (0.5–0.7) for the >4 to ≤5 L category, and 1.9 L (1.5–2.3) for the >5 to ≤7 L category. Adjusted odds ratios for adverse maternal outcomes were 1.0 (0.7–1.6), 1.2 (0.8–1.9), 1.8 (1.1–3.1) and 4.4 (2.6–7.5) for women in the 2 to ≤3 L category, >3 to ≤4 L, >4 to ≤5 L, and >5 to ≤7 L volume categories respectively. Results were similar in strata of different severities of bleeding.
Clear fluids volume >4 L was independently associated with adverse maternal outcome in women with persistent postpartum haemorrhage.
The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum ...haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions.
In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission.
One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment.
The definition persistent postpartum haemorrhage identified women with severe postpartum haemorrhage at an early stage of haemorrhage, unlike definitions based on blood transfusion. It also captured a large majority of adverse maternal outcomes, almost as large as the definition of ≥1 L blood loss, which is commonly applied as a definition of postpartum haemorrhage rather than severe haemorrhage.
Background: The prothrombin G20210A mutation is associated with increased plasma prothrombin levels and risk of thrombosis. The mechanism by which this mutation leads to increased prothrombin ...expression is as yet unclear and still the subject of debate. Objectives: The aim of this study was to investigate the effect of the G20210A mutation on mRNA and protein expression. Methods: We made a set of constructs containing the prothrombin 5′‐regulatory region, the firefly luciferase reporter gene and the prothrombin 3′‐UTR+ downstream region. The latter element contained either the 20210G or A allele and was inserted either as a single unit (constructs G1 and A1) or in tandem (A1A2, G1G2, A1G2, G1A2). Constructs were transiently expressed in HepG2 cells. Expression was evaluated by luciferase assays and reverse transcriptase‐polymerase chain reaction (RT‐PCR), followed by quantification of the products and determination of the ratio of poly(A)site usage. RT‐PCR sequencing was used for determination of the actual site of polyadenylation in mRNAs from constructs G1 and A1 and from endogenous prothrombin mRNAs from HepG2 cells and human liver tissue. Results: The A1 constructs expressed 1.2‐fold more protein than the G1 constructs. The double constructs expressed 1.4‐fold more protein (A1A2 vs. G1G2). Similar results were found in a set of constructs in which an SV40 promoter replaced the prothrombin 5′‐regulatory region. Ratios of poly(A) site usage (expressed as ratio poly(A) site 1 and 2) for the tandem constructs were similar for constructs with two Gs or As at both poly(A)sites; 2.92 (95% confidence interval 2.39–3.45) and 2.75 (2.55–2.95). pA1/pA2 ratios were 1.46 (1.11–1.81) for G1A2 and 6.29 (5.48–7.10) for A1G2 constructs with different poly(A) sites, indicating that the poly(A)site with the 20210A variant is favored over the normal site. In 20210G mRNAs, the G at 20210 was the last non‐A nucleotide in the majority of mRNAs, whereas in most 20210A mRNAs, the last non‐A nucleotide was the C at 20209. Over 70% of the prothrombin 20210G mRNAs from HepG2 cells and human liver tissue is polyadenylated at position 20210. Conclusions: The 20210A variant has a more effective poly(A) site, leading to increased mRNA and protein expression, irrespective of the promoter and gene. It does not affect the position of poly(A) attachment.
To find genetic causes of high plasma prothrombin levels, an established prothrombotic risk factor. we searched for sequence variations in the prothrombin gene. We selected subjects with the 20210-GG ...genotype (since the 20210-A allele is already known to be associated with high levels) and elevated prothrombin levels (> or = 130 U/dl) from the Leiden Thrombophilia Study (LETS). No mutations were found in the 1 kb promoter region of the prothrombin gene in seven individuals with an isolated high prothrombin level. Comparison of the allelic frequencies of four different polymorphisms in the prothrombin gene in healthy volunteers and in the control subjects among the selected LETS individuals indicated a higher frequency of the 19911-G allele in the latter group (allele frequency 52 vs. 78%, respectively). Homozygous carriers of the 19911-G allele had 8 U/dl higher plasma prothrombin levels than 19911-AA carriers. This difference in prothrombin levels did not affect the thrombotic risk in 20210-GG carriers. In heterozygous 20210-A carriers the odds ratio increased from 1.6 (95% CI: 0.6-4.3) in subjects with 19911-A to 4.7 (1.6-14.0) in subjects with 19911-G on the other prothrombin allele.
Background: Prothrombin is a key component in blood coagulation. Overexpression of prothrombin leads to an increased risk of venous thrombosis. Therefore, the study of the transcriptional regulation ...of the prothrombin gene may help to identify mechanisms of overexpression. Objectives: The aim of our study was to localize the regions within the prothrombin enhancer responsible for its activity, to identify the proteins binding to these regions, and to establish their functional importance. Methods: We constructed a set of prothrombin promoter 5′ deletion constructs containing the firefly luciferase reporter gene, which were transiently transfected in HepG2, HuH7 and HeLa cells. Putative transcription factor (TF) binding sites were evaluated by electrophoretic mobility shift assays. The functional importance of each TF binding site was evaluated by site directed mutagenesis and transient transfection of the mutant constructs. Results: We confirmed the major contribution of the enhancer region to the transcriptional activity of the prothrombin promoter. Analysis of this region revealed putative binding sites for hepatocyte nuclear factor HNF4, HNF3‐beta and specificity protein(Sp)1. We identified six different TFs binding to three evolutionary conserved sites in the enhancer: HNF4‐alpha (site 1), HNF1‐alpha, HNF3‐beta and an as yet unidentified TF (site 2) and the ubiquitously expressed TFs Sp1 and Sp3 (site 3). Mutagenesis studies showed that loss of binding of HNF3‐beta resulted in a considerable decrease of enhancer activity, whereas loss of HNF4‐alpha or Sp1/Sp3 resulted in milder reductions. Conclusions: The prothrombin enhancer plays a major role in regulation of prothrombin expression. Six different TFs are able to bind to this region. At least three of these TFs, HNF4‐alpha, HNF3‐beta and Sp1/Sp3, are important in regulation of prothrombin expression.
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