Low energy polarization sensitivity of the Gas Pixel Detector Muleri, F.; Soffitta, P.; Baldini, L. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
2008, 2008-1-00, Volume:
584, Issue:
1
Journal Article
Peer reviewed
Open access
An X-ray photoelectric polarimeter based on the Gas Pixel Detector has been proposed to be included in many upcoming space missions to fill the gap of about 30 years from the first (and to date only) ...positive measurement of polarized X-ray emission from an astrophysical source. The estimated sensitivity of the current prototype peaks at an energy of about 3
keV, but the lack of readily available polarized sources in this energy range has prevented the measurement of detector polarimetric performances.
In this paper we present the measurement of the Gas Pixel Detector polarimetric sensitivity at energies of a few keV and the new, light, compact and transportable polarized source that was devised and built to this aim. Polarized photons are produced, from unpolarized radiation generated with an X-ray tube, by means of Bragg diffraction at nearly
45
∘
. The diffraction angle is constrained with two orthogonal capillary plates, which allow good collimation with limited size thanks to the
10
μ
m
diameter holes. Polarized photons at energy as low as a few keV can be produced with a proper choice of diffracting crystal, while the maximum energy is limited by the X-ray tube voltage, since all the orders defined by the crystal lattice spacing are diffracted. The best trade-off between reasonable fluxes and high degree of polarization can be achieved selecting the degree of collimation provided by capillary plates.
The employment of mosaic graphite and flat aluminum crystals allow the production of nearly completely polarized photons at 2.6, 3.7, and 5.2
keV from the diffraction of unpolarized continuum or line emission. The measured modulation factor of the Gas Pixel Detector at these energies is in good agreement with the estimates derived from a Monte Carlo software, which was up to now employed for driving the development of the instrument and for estimating its low energy sensitivity. In this paper we present the excellent polarimetric performance of the Gas Pixel Detector at energies where the peak sensitivity is expected. These measurements not only support our previous claims of high sensitivity but confirm the feasibility of astrophysical X-ray photoelectric polarimetry.
Background
Sacral nerve stimulation (SNS) is a validated treatment for fecal incontinence, although the mechanism of action remains unknown. Short‐term effects of SNS on the intestinal epithelial ...barrier (IEB) have been reported previously. The aim of our study was to assess the impact of a 1‐week SNS on the IEB in a preclinical model.
Methods
Fourteen pigs were implanted for bilateral SNS. Seven pigs received 7‐day stimulation, whereas the remaining animals received no stimulation. Rectal biopsies were performed before and after SNS. We assessed IEB permeability, mucosal tight junction and cytokine mRNA expression, IL‐6 production in an organotypic culture model, and neuromuscular transmission in muscle strips.
Key Results
IEB permeability was not modified after stimulation, as compared with baseline. The PAR‐induced increase in IEB permeability and the mucosal ZO‐1 mRNA decrease observed in the controls were not observed into the stimulated group. Cytokine overexpression was not observed in the mucosa in either group. SNS decreased IL‐6 production in the organotypic culture model. In the stimulated group, the area‐under‐the‐curve of the EFS‐induced contractile response was significantly increased.
Conclusions & Inferences
The main conclusions of our work are (i) the successful development of a preclinical model of bilateral SNS and (ii) in physiological conditions, 1‐week SNS did not lead to functional changes in the mucosa. While under stress‐induced conditions, SNS modified the properties of the IEB, leading to a decrease in its permeability. Neuromuscular transmission was modified by SNS, leading to neuronal hyperexcitability. These results add evidence to the reinforcement of the IEB by SNS.
Our work has successfully developed a preclinical model of bilateral SNS for which, in physiological conditions, 1‐week SNS did not lead to functional changes in the mucosa. While under stress‐induced conditions, SNS modified the properties of the IEB, leading to a decrease in its permeability. Our results add evidence to the reinforcement of the IEB by SNS.
Hypertension is one of the most frequent pathologies in the industrialized world. Although recognized to be dependent on a combination of genetic and environmental factors, its molecular basis ...remains elusive. Increased activity of the monomeric G protein RhoA in arteries is a common feature of hypertension. However, how RhoA is activated and whether it has a causative role in hypertension remains unclear. Here we provide evidence that Arhgef1 is the RhoA guanine exchange factor specifically responsible for angiotensin II-induced activation of RhoA signaling in arterial smooth muscle cells. We found that angiotensin II activates Arhgef1 through a previously undescribed mechanism in which Jak2 phosphorylates Tyr738 of Arhgef1. Arhgef1 inactivation in smooth muscle induced resistance to angiotensin II-dependent hypertension in mice, but did not affect normal blood pressure regulation. Our results show that control of RhoA signaling through Arhgef1 is central to the development of angiotensin II-dependent hypertension and identify Arhgef1 as a potential target for the treatment of hypertension.
Response of the GLAST LAT calorimeter to relativistic heavy ions Lott, B.; Piron, F.; Blank, B. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
05/2006, Volume:
560, Issue:
2
Journal Article
Peer reviewed
The CsI calorimeter of the Gamma-Ray Large-Area Space Telescope (GLAST) will be calibrated in flight with cosmic-ray heavy ions. In order to determine the response of the calorimeter to relativistic ...heavy ions lighter than Fe, an experiment was carried out at the GSI heavy ion facility using the Fragment Separator (FRS). The measured response exhibits an unexpected feature for light ions, opposite to that observed at low incident energy: for a given deposited energy, the observed signal is greater for these ions than for protons (or more generally
Z
=
1
minimum ionizing particles). Pulse shapes are found to be almost identical for carbon ions and
Z
=
1
particles, with a significant slow scintillation component, which constitutes another departure from the low-energy behavior. Data on the energy resolution for the individual CsI crystals and on the loss of ions due to nuclear reactions in the calorimeter are also presented.
Pulsars are among the prime targets for the Large Area Telescope (LAT) aboard the recently launched
Fermi observatory. The LAT will study the gamma-ray Universe between 20
MeV and 300
GeV with ...unprecedented detail. Increasing numbers of gamma-ray pulsars are being firmly identified, yet their emission mechanisms are far from being understood. To better investigate and exploit the LAT capabilities for pulsar science, a set of new detailed pulsar simulation tools have been developed within the LAT collaboration. The structure of the pulsar simulator package (
PulsarSpectrum) is presented here. Starting from photon distributions in energy and phase obtained from theoretical calculations or phenomenological considerations, gamma-rays are generated and their arrival times at the spacecraft are determined by taking into account effects such as barycentric effects and timing noise. Pulsars in binary systems also can be simulated given orbital parameters. We present how simulations can be used for generating a realistic set of gamma-rays as observed by the LAT, focusing on some case studies that show the performance of the LAT for pulsar observations.
Abstract
Background
There is no biomarker to guide first-line of biotherapy in ulcerative colitis (UC). The main objective of this multicenter pilot study was to demonstrate the feasibility of ...identifying a4b7 and/or TNF-a expressing cells by dual-band confocal endomicroscopy (CLE) into the mucosa to predict the response to vedolizumab as first-line biotherapy. NCT02878083.
Methods
Patients with moderate to severe UC, naïve of biotherapy were prospectively included and received vedolizumab. Patients were evaluated clinically, biologically, endoscopically and histologically at week 22. Nonresponding patients were subsequently treated by adalimumab and were evaluated at week 30. Prior to the initiation of vedolizumab, during endoscopy, 8 biopsies were taken for extemporaneous and ex vivo analysis by CLE, histology and confocal microscopy. Fresh biopsies were treated with vedolizumab coupled with FITC and adalimumab coupled with Alexa-Fluor to analyze their respective fluorescence (figure) in one step with the Dual-band CLE system (Mauna Kea Technologies, France). The number and the surface of positive stained areas visualized by CLE were counted and compared between responders and non-responders. Blood samples were collected before each infusion and were used to analyze the immune cells (LT, LB, NK, monocytes) by FACS and vedolizumab trough levels. Frozen biopsies were analyzed by confocal microscopy (Opal Akoya multiplexing; Tyramide signal amplification) after labeling by an anti-a4b7 antibody.
Results
19 patients out of the 20 initially planned were included. Clinical remission, endoscopic improvement (Mayo ≤ 1), endoscopic remission (Mayo 0) at W22 were respectively 58%, 58% and 45%. 18 out of 19 patients (95%) could be analyzed by CLE. The number and surface of vedolizumab-FITC stained areas were numerically superior in responder patients at week22; by contrast, no difference was found for the areas marked by adalimumab-Alexa-fluor. A threshold value of 6 areas marked in CLE by the vedolizumab-FITC at week 0 discriminated responders and non-responders at week 22 with a Se of 78% and a Sp of 85%. No difference of circulating cell population has been identified between responders and non-responders and the vedolizumab trough levels were not predictive of the response. In confocal microscopy, 15 patients have been analyzed; the percentage of a4b7-binding cells was not different between responders (n=9) and non-responders (n=6)
Conclusion
This study confirms the feasibility of extemporaneous identification by dual-band CLE of the mucosal cells expressing a4b7 and/or TNF-a. Results suggest that only the proportion of cells binding vedolizumab-FITC in the mucosa was indicative of the response to vedolizumab
Introduction:
Self-expanding metal stents (SEMS) are commonly used in the palliation of dysphagia in patients with inoperable esophageal carcinoma. However, they predispose to gastroesophageal reflux ...when deployed across the gastroesophageal junction. The aims of this study were to: 1) assess the influence of the antireflux valve on trans-prosthetic reflux (primary outcome); and 2) compare the results of SEMS with and without antireflux valve in terms of reflux symptoms, quality of life (QOL), improvement of dysphagia and adverse events (secondary outcomes).
Patients and methods:
Thirty-eight patients were enrolled in nine centers. Carcinomas were locally advanced (47 %) or metastatic. After randomization, patients received either a covered SEMS with antireflux valve (n = 20) or a similar type of SEMS with no antireflux device but assigned to standard proton pump inhibitor therapy and postural advice (n = 18). Trans-prosthetic reflux was assessed at day 2 using a radiological score based on barium esophagography performed after Trendelenburg maneuver and graded from 0 (no reflux) to 12 (maximum). Monthly telephone interviews were conducted for Organisation Mondiale de la Santé (OMS) scoring from 0 (excellent) to 5 (poor), QOL assessment (based on the Reflux-Qual Simplifié scoring system) from 0 (poor) to 100 (excellent), dysphagia scoring from 0 (no dysphagia) to 5 (complete dysphagia) and regurgitation scoring from 0 (no regurgitation) to 16 (maximum).
Results:
No difference was noted in terms of age, sex, size of lesion, prosthesis length or need for dilation prior to SEMS placement. No difficulty in placing SEMS nor complications were noted. Radiological scores of reflux were found to be significantly lower in patients with an antireflux stent compared to the conventional stent and associated measures. The regurgitation scores were significantly decreased in patients with antireflux stents during the first 2 months after stent placement and thereafter, they were similar in the two groups. QOL and dysphagia were improved in both groups. Survival rates were comparable in the two groups.
Conclusions:
No difference was observed between the two types of SEMS regarding the palliation of dysphagia and improvement of QOL. However, SEMS with an antireflux valve were more effective in preventing trans-prosthetic gastroesophageal reflux but at the cost of an increased likehood of minor adverse events (migrations and/or obstruction of the SEMS).
We present a catalog of sources detected above 10 GeV by the Fermi Large Area Telescope (LAT) in the first 7 years of data using the Pass 8 event-level analysis. This is the Third Catalog of Hard ...Fermi -LAT Sources (3FHL), containing 1556 objects characterized in the 10 GeV–2 TeV energy range. The sensitivity and angular resolution are improved by factors of 3 and 2 relative to the previous LAT catalog at the same energies (1FHL). The vast majority of detected sources (79%) are associated with extragalactic counterparts at other wavelengths, including 16 sources located at very high redshift ( z > 2). Of the sources, 8% have Galactic counterparts and 13% are unassociated (or associated with a source of unknown nature). The high-latitude sky and the Galactic plane are observed with a flux sensitivity of 4.4 to 9.5 × 10{sup −11} ph cm{sup −2} s{sup −1}, respectively (this is approximately 0.5% and 1% of the Crab Nebula flux above 10 GeV). The catalog includes 214 new γ -ray sources. The substantial increase in the number of photons (more than 4 times relative to 1FHL and 10 times to 2FHL) also allows us to measure significant spectral curvature for 32 sources and find flux variability for 163 of them. Furthermore, we estimate that for the same flux limit of 10{sup −12} erg cm{sup −2} s{sup −1}, the energy range above 10 GeV has twice as many sources as the range above 50 GeV, highlighting the importance, for future Cherenkov telescopes, of lowering the energy threshold as much as possible.
We present the second catalog of flaring gamma-ray sources (2FAV) detected with the Fermi All-sky Variability Analysis (FAVA), a tool that blindly searches for transients over the entire sky observed ...by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. With respect to the first FAVA catalog, this catalog benefits from a larger data set, the latest LAT data release (Pass 8), as well as from an improved analysis that includes likelihood techniques for a more precise localization of the transients. Applying this analysis to the first 7.4 years of Fermi observations, and in two separate energy bands 0.1–0.8 GeV and 0.8–300 GeV, a total of 4547 flares were detected with significance greater than 6σ (before trials), on the timescale of one week. Through spatial clustering of these flares, 518 variable gamma-ray sources were identified. Based on positional coincidence, likely counterparts have been found for 441 sources, mostly among the blazar class of active galactic nuclei. For 77 2FAV sources, no likely gamma-ray counterpart has been found. For each source in the catalog, we provide the time, location, and spectrum of each flaring episode. Studying the spectra of the flares, we observe a harder-when-brighter behavior for flares associated with blazars, with the exception of BL Lac flares detected in the low-energy band. The photon indexes of the flares are never significantly smaller than 1.5. For a leptonic model, and under the assumption of isotropy, this limit suggests that the spectrum of freshly accelerated electrons is never harder than p∼2.
The spatial extension of a γ -ray source is an essential ingredient to determine its spectral properties, as well as its potential multiwavelength counterpart. The capability to spatially resolve γ ...-ray sources is greatly improved by the newly delivered Fermi -Large Area Telescope (LAT) Pass 8 event-level analysis, which provides a greater acceptance and an improved point-spread function, two crucial factors for the detection of extended sources. Here, we present a complete search for extended sources located within 7° from the Galactic plane, using 6 yr of Fermi -LAT data above 10 GeV. We find 46 extended sources and provide their morphological and spectral characteristics. This constitutes the first catalog of hard Fermi -LAT extended sources, named the Fermi Galactic Extended Source Catalog, which allows a thorough study of the properties of the Galactic plane in the sub-TeV domain.
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