Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA is enriched of ...Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated with aggressiveness and drug resistance. Treatment with the anti-diabetic drug Metformin, has been recently associated with reduced incidence of iCCA. We aimed to evaluate the anti-cancerogenic effects of Metformin in vitro and in vivo on primary cultures of human iCCA. Our results showed that Metformin inhibited cell proliferation and induced dose- and time-dependent apoptosis of iCCA. The migration and invasion of iCCA cells in an extracellular bio-matrix was also significantly reduced upon treatments. Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells. After 12 days of treatment, a marked decrease of mesenchymal and EMT genes and an increase of epithelial genes were observed. After 2 months of treatment, in order to simulate chronic administration, Cytokeratin-19 positive cells constituted the majority of cell cultures paralleled by decreased Vimentin protein expression. Subcutaneous injection of iCCA cells previously treated with Metformin, in Balb/c-nude mice failed to induce tumour development. In conclusion, Metformin reverts the mesenchymal and EMT traits in iCCA by activating AMPK-FOXO3 related pathways suggesting it might have therapeutic implications.
Abstract
An in-vacuum Hall probe measurement system was designed, built, and used to measure four Cryogenic Permanent Magnet Undulators (CPMUs) at Diamond Light Source. The devices were tuned to ...correct the phase error at cold temperatures based on the measurements from the in-vacuum system. The in-vacuum system consists of a stretched wire system supplied by Danfysik and an in-house built Hall probe system. The Hall probe system has gone through two iterations: the first beam was prone to deforming with temperature changes; the second was made thicker following design changes to the magnet holders and girders of the CPMUs which allowed more space for the beam inside the vacuum vessel. The design and commissioning of the measurement system will be presented, along with some measurements of the CPMUs at room temperature and at 77 K. Details such as triggering of the Hall probe measurements, height compensation, and temperature compensation will be covered.
CPMU Development at Diamond Light Source Sharma, G; George, A; Hale, S ...
Journal of physics. Conference series,
01/2024, Volume:
2687, Issue:
3
Journal Article
Peer reviewed
Open access
Abstract
Over the last three years (2020-2022) Diamond Light Source has installed four in-house designed, built, and measured Cryogenic Permanent Magnet Undulators (CPMUs). All four are 2 m long with ...a 17.6 mm period and have a minimum operating gap of 4 mm. These have replaced existing 2 m long in-vacuum Pure Permanent Magnet (PPM) devices to improve the flux to several of Diamond’s MX (Macromolecular Crystallography) beamlines by a factor of 2-4. In this paper we present the mechanical and cryogenic design considerations, and the shimming procedures and tools developed to produce these devices. The performance of the CPMUs compared to their PPM counterparts will also be reviewed.
A compton spectrometer to monitor the ELI-NP gamma beam energy Borgheresi, R.; Adriani, O.; Albergo, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2019, Volume:
936
Journal Article
Peer reviewed
The ELI-NP facility (Extreme Light Infrastructure-Nuclear Physics) will deliver an intense and almost monochromatic gamma beam for frontier research in nuclear physics. Peculiar devices and ...techniques have been developed to measure and monitor the beam parameters during the commissioning and the operational phase. In this work we will present the Compton Spectrometer, designed to reconstruct the γ beam energy spectrum, by measuring the energy and the position of Compton scattered electrons. The energy and the angle of the scattered electron are measured by a High Purity Germanium detector and a double sided silicon strip detector. The associated photon is detected in coincidence with the electron by barium fluoride (BaF2) crystals for trigger purpose. In this work we report the status of the characterization carried out on the detectors composing the spectrometer.
•Compton spectrometer, designed to reconstruct the ELI-NP γ beam energy spectrum.•Energy of the scattered e− measured with a High Purity Germanium detector.•Scattered angle determined by a double sided silicon strip detector.•Scattered photon detected in coincidence by BaF2 crystals for trigger purpose.•Tests carried out on the components of the spectrometer are presented.
ELI–nuclear physics (NP) Gamma Beam System (GBS) is an intense and monochromatic gamma beam source based on inverse Compton interaction, currently being built in Bucharest, Romania. The gamma beam ...produced, with energy ranging from 0.2 to 20MeV, energy bandwidth 0.5% and flux of about 108photons/s, will be devoted to investigate a broad range of applications such as nuclear physics, astrophysics, material science and life sciences. The radiation produced by an inverse Compton interaction is not intrinsically monochromatic. In fact, the energy of the photons produced is related to the emission angle, therefore the energy bandwidth can be modified adjusting the collimation of the gamma beam. In order to define the optimal layout and evaluate the performance of a collimation system for the ELI–NP–GBS low-energy beamline (0.2–3.5MeV), a detailed Monte Carlo simulation activity has been carried out. The simulation, using Geant4 and MCNPX codes, included the transport of the gamma beam from the interaction point to the experimental area passing through vacuum pipes, vacuum chambers, collimation system and relative shielding. The effectiveness of the collimation system, in obtaining the required energy distribution and avoiding the contamination due to secondary radiation production, was evaluated. Also, the background radiation generated by collimation and the shielding layout have been studied.
ATLAS “Baby-DEMO” Zwalinski, L.; Bojdol, K.; Bortolin, C. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2019, Volume:
936
Journal Article
Peer reviewed
Open access
Evaporative CO2 has been selected as the main detector cooling technology for the Phase II upgrade of the LHC silicon detectors at CERN. In order to provide input to the ATLAS Pixel TDR about the ...minimum attainable cooling temperature by the end of 2017, ATLAS, with a contribution of CMS, has launched a dedicated detector cooling R&D study nick-named Baby-DEMO. The Baby-DEMO is the demonstration of a typical 2PACL CO2 cooling plant operating at the lowest temperature ever achieved. A real size ATLAS mock-up is used to hold realistic manifolding as its critical path might have strong impact on the cooling performance. Additionally, the “Baby-DEMO” program addresses the study of high power flexible vacuum insulated coaxial transfer lines and warm nose boiling enhancement as possible solutions for the Phase II upgrade. This paper describes the system design including CO2 plant, primary chiller and typical distribution. Challenges and solutions used to achieve the lowest possible evaporation temperatures are reported. The result of this study, even if at the preliminary stage, are of great interest for the design of the cooling systems that ATLAS and CMS will use in the Phase II era.
•Target minimum cooling evaporator temperature achieved, 5kW @ <−40°C at dummy load•Larger than expected temperature gradients observed in flex lines.•Stable long term operation at −47°C accumulator cooling.•Record low temperature of −50°C achieved with manual tricks.
A prototype x-ray system based on a liquid-metal-jet anode was evaluated within the framework of the LABSYNC project. The generated spectrum was measured using a CZT-based spectrometer and was ...compared with spectra simulated by three Monte Carlo codes: MCNPX, PENELOPE and EGS5. Notable differences in the simulated spectra were found. These are mainly attributable to differences in the models adopted for the electron-impact ionization cross section. The simulation that more closely reproduces the experimentally measured spectrum was provided by PENELOPE.
•The x-ray spectrum of a liquid-jet x-ray anode was measured with a CZT spectrometer.•Results were compared with Monte Carlo simulations using MCNPX, PENELOPE, EGS5.•Notable differences were found among the Monte Carlo simulated spectra.•The key role was played by the electron-impact ionization cross-section model used.•The experimentally measured spectrum was closely reproduced by the PENELOPE code.
Purpose:
A 3-year project called LABSYNC has been recently funded by the European Commission, with the aim of designing a radiation facility based on a compact light source, i.e., a laboratory-sized ...commercial synchrotron, capable of accelerating electrons up to 6 or 20 MeV. An accurate spectral description of hard x rays emitted from thin targets, irradiated by electron beams circulating in the storage ring, is of primary interest for the design and the characterization of a beamline. This article, Part I, aims at optimizing some of the parameters which are critical for the design of medical applications based on the above compact light source. The goal was to evaluate the dependence of photon fluence and beam monochromaticity on electron-beam energy, target material, and thickness.
Methods:
The transport of 6 and 20 MeV electrons in a thin molybdenum, rhodium, and tungsten target is studied by means of Monte Carlo simulations usingMCNPX. Configurations of the x-ray output port, different from the default forward-directed emission of the beam, are also investigated. A comparison with reference spectra for general diagnostic radiology and mammography is carried out.
Results:
It is shown that the emitted x-ray beams can be far more intense than those generated by conventional x-ray tubes for radiography applications. The profiles of the calculated polychromatic spectra resemble those generated by conventional x-ray tubes, with x-ray energies up to the energy of the incident-electron beam. An appreciable improvement in the monochromaticity of the beams can be obtained by viewing the x-ray emission from an output port antiparallel to the direction of the incident-electron beam.
Conclusions:
The optimum target thickness for tungsten target spectra is practically constrained by a trade-off between bremsstrahlung efficiency and focal-spot size requirements. A larger margin for optimization of target thickness is probably available for mammographic spectra. The constraint of a backward-directed (or, to a lesser extent, orthogonal) output port is to be considered mandatory for minimizing the high-energy tail of the spectral distribution and keeping the radiation dose to a reasonable level. It is also fundamental to evaluate the impact of the high-energy tail of the emitted spectra in x-ray imaging applications, since the energy range involved is significantly beyond the diagnostic range. This topic will be dealt with in Part II of the article.
The characterization of novel x-ray sources includes the measurement of the photon flux and the energy distribution of the beam produced. The aim of the BEATS2 experiment at INFN-LNF is the study of ...medical applications of an x-ray source based on Thomson relativistic backscattering. This source is expected to produce pulsed quasi-monochromatic x-ray beam with an instantaneous flux of 1020ph/s in pulses 10ps long and with an average energy of 20keV. A direct measurement of energy distribution of this beam with traditional detectors, such as HPGe, CZT or CdTe, is very difficult because of the extremely high photon flux. For this reason we have planned to use a technique based on beam filtration using k-edge absorbing foils in the energy range of interest (16–22keV). By measuring the photon flux of the photon beam filtered with appropriate thicknesses of k-edge absorbers, it is possible to retrieve the energy distribution of the incident x-ray beam. The energy resolution obtainable depends on the number and energy separation of k-edges of filter used.
A preliminary test of the technique was made using an x-ray tube with a tungsten anode at 22kVp, filtered with 3.1mm of Al providing an x-ray spectrum with an energy distribution similar to that expected from a Thomson source. The comparison between the results obtained directly measuring this spectrum with an HPGe detector and using the k-edge subtraction technique showed good agreement.
Characterization of a novel x-ray source: The MIRRORCLE-6X system Gambaccini, M.; Marziani, M.; Taibi, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2012, Volume:
664, Issue:
1
Journal Article
Peer reviewed
MIRRORCLE is a tabletop synchrotron light source being investigated within an EC funded project named LABSYNC. To evaluate the potential of this novel x-ray source for medical imaging applications, a ...set of measurements was performed at the MIRRORCLE factory in Japan. In particular, the aim of this work was to characterize the proposed compact x-ray source by determining different parameters, such as the intensity of the broad spectra produced with thin wire targets, the size of the focal spot and its distribution.
The average electron-beam impact current on wire targets was calculated by several methods and it was demonstrated to be in the range
0.5
–
1.0
μ
A
. By comparing these values with data available for conventional x-ray tubes, the current needed to achieve the same fluence as in a standard diagnostic examination was estimated to be about 0.1–0.5
mA. Finally, results from the measurements of the electron-beam impact cross-section on the target suggested that the diameter of the electron beam circulating in the storage ring is about 6
mm.
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