2,840 research outputs found
A Prototype Fast Multiplicity Discriminator for ALICE L0 Trigger
The design details and test results of a prototype Multiplicity Discriminator (MD) for the ALICE L0 Trigger electronics are presented. The MD design is aimed at the earliest trigger decision founded on a fast multiplicity signal cut, in both options for the ALICE centrality detector: Micro Channel Plates or Cherenkov counters. The MD accepts detector signals with an amplitude range of plus-minus 2.5 V, base duration of 1.8 ns and rise time of 300-400 ps. The digitally controlled threshold settings give an accuracy better than 0.4% at the maximum amplitude of the accepted pulses. The MD internal latency of 15 ns allows for a decision every LHC bunch crossing period, even for the 40 MHz of p-p collisions
Vitamin C inhibits platelet expression of CD40 ligand
Upon stimulation with agonists, platelets express CD40 ligand (CD40L), a transmembrane protein implicated in the initiation and progression of atherosclerotic disease. We have recently discovered that oxidative stress plays a major role in platelet CD40L expression. In this study, we sought to determine whether vitamin C, a known antioxidant, is able to influence platelet CD40L expression. In vitro experiments were done by stimulating platelets with collagen in the presence or absence of vitamin C (50-100 mu M) or vehicle as control. An in vivo study was done in 10 healthy subjects who were randomized to intravenous infusion of placebo or 1 g vitamin C for 45 min in a crossover design. At the end of infusion platelet CD40L and O2- were measured. The in vitro study demonstrated that vitamin C dose dependently inhibited platelet CD40L expression without affecting agonist-induced platelet aggregation. In subjects treated with placebo no changes of platelet CD40L and O2- were observed; conversely, vitamin C infusion caused a significant and parallel decrease of platelet O2- (-70%, P < 0.001) and CD40L (-68%, P < 0.001). Platelet aggregation was not modified by either treatment. This study suggests that water-soluble antioxidants, which scavenge superoxide radicals, may reduce platelet CD40L expression. (c) 2005 Elsevier Inc. All rights reserved
gp91phox-dependent expression of platelet CD40 ligand
Background-CD40 ligand (CD40L) expression on platelets is mediated by agonists, but the underlying mechanism is still unclear. Methods and Results-CD40L expression was measured in platelets from healthy subjects both with and without the addition of antioxidants or a phospholipase A2 (PLA2) inhibitor and in platelets from 2 patients with an inherited deficiency of gp91phox. Immunoprecipitation analysis was also performed to determine whether normal platelets showed gp91phox expression. Unlike catalase and mannitol, superoxide dismutase inhibited agonist-induced platelet CD40L expression in healthy subjects. Immunoprecipitation analysis also showed that platelets from healthy subjects expressed gp91phox. In 2 male patients with inherited gp91phox deficiency, collagen-, thrombin-, and arachidonic acid-stimulated platelets showed an almost complete absence of superoxide anion (O2-) and CD40L expression. Incubation of platelets from healthy subjects with a PLA2 inhibitor almost completely prevented agonist-induced O2- and CD40L expression. Conclusions-These data provide the first evidence that platelet CD40L expression occurs via arachidonic acid-mediated gp91phox activation
Oxidative stress-mediated platelet CD40 ligand upregulation in patients with hypercholesterolemia: effect of atorvastatin
Objectives: We speculated that in patients with hypercholesterolemia CD40L overexpression could depend on low-density lipoprotein (LDL)-induced enhanced intraplatelet formation of O-2(.-) and statin could reduce platelet CD40L via interference with platelet O-2(.-) production. Background: CD40L is a protein with inflammatory and thrombotic properties. CD40L is upregulated in platelets from hypercholesterolemic (HC) patients but the underlying mechanism is unclear. Methods: Collagen-induced platelet CD40L and platelet O-2(.-) expression were investigated in 40 HC patients and 40 healthy subjects. HC patients were then randomized to either a diet (n = 20) (group A) or atorvastatin 10 mg day (n = 20) (group B); the above variables were measured at baseline and after 3 and 30 days of treatment. O-2(.-) and CD40L were also measured in vitro in LDL-treated platelets with or without nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor or atorvastatin added. Results: Compared with controls, HC patients showed higher values of platelet CD40L (P < 0.001) and O-2(.-) (P < 0.001). Platelet CD40L was significantly correlated with O-2(.-) (P < 0.001). The interventional trial showed no changes in group A and a significant and parallel decrease in platelet CD40L (P < 0.001) and O-2(.-) (P < 0.001) in group B. In vitro studies demonstrated that LDL-induced platelet CD40L and GP IIb/IIIa (PAC1 binding) activation via the NADPH oxidase pathway. CD40L upregulation was counteracted by atorvastatin in a dose-dependent fashion. Conclusions: This study suggests that in patients with hypercholesterolemia platelet CD40L is upregulated via NADPH oxidase-dependent O-2(.-) generation. Atorvastatin downregulated CD40L with an oxidative stress-mediated mechanism likely involving platelet NADPH oxidase, an effect that seemed to be independent of its cholesterol-lowering action
Cerebral Microcirculatory Responses of Insulin-Resistant Rats are Preserved to Physiological and Pharmacological Stimuli
AbstractWe study a programming language with a built-in ground type for real numbers. In order for the language to be sufficiently expressive but still sequential, we consider a construction proposed by Boehm and Cartwright. The non-deterministic nature of the construction suggests the use of powerdomains in order to obtain a denotational semantics for the language. We show that the construction cannot be modelled by the Plotkin or Smyth powerdomains, but that the Hoare powerdomain gives a computationally adequate semantics. As is well known, Hoare semantics can be used in order to establish partial correctness only. Since computations on the reals are infinite, one cannot decompose total correctness into the conjunction of partial correctness and termination as is traditionally done. We instead introduce a suitable operational notion of strong convergence and show that total correctness can be proved by establishing partial correctness (using denotational methods) and strong convergence (using operational methods). We illustrate the technique with a representative example
Effet de la pression interstitielle sur la réponse sismique des sols : modélisation numérique 1D-3 Composantes
International audienceDuring strong quakes, the propagation of seismic waves in soil layers involves nonlinearities changing with the excitation level. A nonlinear hysteretic law is necessary to describe the variations of the stiffness and the energy dissipation during the seismic shaking. Furthermore, the influence of the pore pressure (cyclic mobility and liquefaction) cannot be neglected for saturated soils under strong quakes. Starting from a FEM formulation describing 1D propagation and three-dimensional loading ("1D-3 components approach"), the influence of the water is accounted for through a relation between the pore pressure and the work of the shear stress initially proposed by Iai. This model describes the variations of the pore pressure from the three-dimensional stress state of the soil. It has been validated through comparisons to laboratory tests (cyclic triaxial tests on saturated sands) and an analysis under three-dimensional excitations (seismic loading polarized along the 3 directions of space). The results involving 3 simultaneous excitation components and a single component in 3 separated analyses show the influence of the loading path on the seismic response and the pore pressure build-up
Study of a New Trigger on Multiplicity and Primary Interaction Vertex using the ALICE Silicon Pixel Detector
New trigger inputs for the ALICE Central Trigger Processor (CTP) are proposed. They are based on the use of Fast Multiplicity (FM) output signals generated by the ALICE Silicon Pixel Detector (SPD). These can be used for a multiplicity based centrality trigger and for a fast on-line computation of the primary vertex. A simple algorithm for primary vertex location at the trigger level is proposed. The precision that can be achieved with this method on centrality selection and primary vertex location, is discussed for interactions with different pseudo-rapidity density level. The feasibility of background rejection is also considered
Management of lymphoma survivor patients in Italy: an evaluation by Fondazione Italiana Linfomi
Several outpatient models for the follow-up of cancer survivors have been developed worldwide. A multidisciplinary approach is often necessary to guarantee the best monitoring of long-term toxicities. Guidelines also indicate a close education on healthy lifestyles. In this context, we have analyzed the Italian follow-up modalities of lymphoma survivors, with the aim to have a starting line to hypothesize and plan the best model for Italian hematology centers
Proteomics signature of autoimmune atrophic gastritis: towards a link with gastric cancer
Background: Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC.
Methods: Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC-MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients.
Results: 2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC-MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was "tricarboxylic acid cycle". Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC).
Conclusion: This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC
Fast front-end L0 trigger electronics for ALICE FMD-MCP tests and performance
We present design details and new measurements of the performance of fast electronics for the Forward Multiplicity Detector for ALICE. These detectors based on sector type Microchannel Plates (MCP) forming several disks gave the very first trigger decision in the experiment (L0). Fast passive summators integrated with the detectors are used for linear summation of up to eight isochronous signal channels from MCP pads belonging to one sector. Two types of microelectronics design thin film summators were produced. We present test results for these summators, working in the frequency range up to 1 Ghz. New low noise preamplifiers have been built to work with these summators. The new design shows a good performance with the usable frequency range extended up to 1 Ghz. An upgrade of the functional scheme for the L0 ALICE pre-trigger design is also presented.Abstract:List of figures Figure 1: ALICE L0 Trigger Front-End Electronics Functional Scheme. Figure 2: UHF design for a fast passive summator based on directional couplers. Figure 3: Photo of an industrially produced passive summator based on circular bridges. Figure 4: Oscillogram of the fast 4 signals separated by different delays shown at the fast output of the passive summator. Figure 5: The same as in Figure 4, but with the delays removed. Figure 6: Fast preamplifier layout. Figure 7: Gain versus Frequency Response for fast preamplifier. Figure 8: Transition response of the preamplifier for a 100 psec rise time step function. Figure 9: The shape of the MCP signal measured after the summator and fast preamplifier. </A
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