The epithelial-mesenchymal transition (EMT) is a crucial morphological event that occurs during the progression of epithelial tumors. EMT can be induced by transforming growth factor β (TGF-β) in ...certain kinds of cancer cells through the induction of Snail, a key regulator of EMT. We have previously found that TGF-β remarkably induces Snail expression in cooperation with Ras signals; however, the underlying mechanism of this synergism has not yet been determined. Here, we demonstrate that signal transducer and activator of transcription 3 (STAT3) acts as a mediator that synergizes TGF-β and Ras signals. The overexpression of STAT3 enhanced Snail induction, whereas siRNA-mediated knockdown of STAT3 inhibited it. The STAT3-YF mutant, which has Tyr 705 substituted with Phe, did not enhance Snail induction. Several STAT3 mutants lacking transcriptional activity also failed to enhance it; however, the putative STAT3-binding elements in the Snail promoter regions were not required for STAT3-mediated Snail induction. Protein inhibitor of activated STAT3 (PIAS3) inhibited the enhanced Snail promoter activity induced by TGF-β and Ras. The interaction between PIAS3 and STAT3 was reduced by TGF-β in cells harboring oncogenic Ras, whereas TGF-β promoted the binding of PIAS3 to Smad3, a crucial mediator of TGF-β signaling. Therefore, these findings suggest that STAT3 enhances Snail induction when it is dissociated from PIAS3 by TGF-β in cooperation with Ras signals.
In the field of beam physics, two frontier topics have taken center stage due to their potential to enable new approaches to discovery in a wide swath of science. These areas are: advanced, high ...gradient acceleration techniques, and x-ray free electron lasers (XFELs). Further, there is intense interest in the marriage of these two fields, with the goal of producing a very compact XFEL. In this context, recent advances in high gradient radio-frequency cryogenic copper structure research have opened the door to the use of surface electric fields between 250 and 500 MV m−1. Such an approach is foreseen to enable a new generation of photoinjectors with six-dimensional beam brightness beyond the current state-of-the-art by well over an order of magnitude. This advance is an essential ingredient enabling an ultra-compact XFEL (UC-XFEL). In addition, one may accelerate these bright beams to GeV scale in less than 10 m. Such an injector, when combined with inverse free electron laser-based bunching techniques can produce multi-kA beams with unprecedented beam quality, quantified by 50 nm-rad normalized emittances. The emittance, we note, is the effective area in transverse phase space (x, p x /m e c) or (y, p y /m e c) occupied by the beam distribution, and it is relevant to achievable beam sizes as well as setting a limit on FEL wavelength. These beams, when injected into innovative, short-period (1-10 mm) undulators uniquely enable UC-XFELs having footprints consistent with university-scale laboratories. We describe the architecture and predicted performance of this novel light source, which promises photon production per pulse of a few percent of existing XFEL sources. We review implementation issues including collective beam effects, compact x-ray optics systems, and other relevant technical challenges. To illustrate the potential of such a light source to fundamentally change the current paradigm of XFELs with their limited access, we examine possible applications in biology, chemistry, materials, atomic physics, industry, and medicine-including the imaging of virus particles-which may profit from this new model of performing XFEL science.
Recent studies of the performance of radio-frequency (rf) copper cavities operated at cryogenic temperatures have shown a dramatic increase in the maximum achievable surface electric field. We ...propose to exploit this development to enable a new generation of photoinjectors operated at cryogenic temperatures that may attain, through enhancement of the launch field at the photocathode, a significant increase in five-dimensional electron beam brightness. We present detailed studies of the beam dynamics associated with such a system, by examining an S-band photoinjector operated at250MV/mpeak electric field that reaches normalized emittances in the 40 nm-rad range at charges (100–200 pC) suitable for use in a hard x-ray free-electron laser (XFEL) scenario based on the LCLS. In this case, we show by start-to-end simulations that the properties of this source may give rise to high efficiency operation of an XFEL, and permit extension of the photon energy reach by an order of magnitude, to over 80 keV. The brightness needed for such XFELs is achieved through low source emittances in tandem with high current after compression. In the XFEL examples analyzed, the emittances during final compression are preserved using microbunching techniques. Extreme low emittance scenarios obtained at pC charge, appropriate for significantly extending temporal resolution limits of ultrafast electron diffraction and microscopy experiments, are also reviewed. While the increase in brightness in a cryogenic photoinjector is mainly due to the augmentation of the emission current density via field enhancement, further possible increases in performance arising from lowering the intrinsic cathode emittance in cryogenic operation are also analyzed. Issues in experimental implementation, including cavity optimization for lowering cryogenic thermal dissipation, external coupling, and cryocooler system, are discussed. We identify future directions in ultrahigh field cryogenic photoinjectors, including scaling to higher frequency, use of novel rf structures, and enabling of an extremely compact hard x-ray FEL.
Abstract
The luminosity requirements of TeV-class linear colliders demand use of intense charged beams at high repetition rates. Such features imply multi-bunch operation with long current trains ...accelerated over the km length scale. Consequently, particle beams are exposed to the mutual parasitic interaction due to the long-range wakefields excited by the leading bunches in the accelerating structures. Such perturbations to the motion induce transverse oscillations of the bunches, potentially leading to instabilities such as transverse beam break-up. Here we present a dedicated tracking code that studies the effects of long-range transverse wakefield interaction among different bunches in linear accelerators. Being described by means of an efficient matrix formalism, such effects can be included while preserving short computational times. As a reference case, we use our code to investigate the performance of a state-of-the-art linear collider currently under design and, in addition, we discuss possible mitigation techniques based on frequency detuning and damping.
Achieving maximum electron beam brightness in photoinjectors requires detailed control of the 3D bunch shape and precise tuning of the beam focusing. Even in state-of-the-art designs, slice emittance ...growth due to nonlinear space charge forces and partial nonlaminarity often remains non-negligible. In this work, we introduce a new means to linearize the transverse slice phase space: a sacrificial portion of the bunch’s own charge distribution, formed into a wavebroken shock front by highly nonlinear space charge forces within the gun, whose downstream purpose is to dynamically linearize the desired bunch core. We show that linearization of an appropriately prepared bunch can be achieved via strongly nonlaminar focusing of the sacrificial shock front, while the inner core focuses laminarly. This leads to a natural spatial separation of the two distributions: a dense core surrounded by a diffuse halo of sacrificial charge that can be collimated. Multiobjective genetic algorithm optimizations of the ultracompact x-ray free electron laser injector employ this concept, and we interpret it with an analytic model that agrees well with the simulations. In simulation, we demonstrate a final bunch charge of 100 pC, peak current ∼ 30 A, and a sacrificial charge of 150 pC (250 pC total emitted from cathode) with normalized emittance growth of < 20 nm rad due to space charge. This implies a maximum achievable brightness approximately an order of magnitude greater than existing free electron laser injector designs. Published by the American Physical Society 2024
The production of high spectral brilliance radiation from electron beam sources depends critically on the electron beam qualities. One must obtain very high electron beam brightness, implying ...simultaneous high peak current and low emittance. These attributes are enabled through the use of very high field acceleration in a radio-frequency (rf) photoinjector source. Despite the high fields currently utilized, there is a limit on the achievable peak current in high brightness operation, in the range of tens of Ampere. This limitation can be overcome by the use of a hybrid standing wave/traveling wave structure; the standing wave portion provides acceleration at a high field from the photocathode, while the traveling wave part yields strong velocity bunching. This approach is explored here in a C-band scenario, at field strengths (>100MV/m) at the current state-of-the-art. It is found that one may arrive at an electron beam with many hundreds of Amperes with well-sub-micron normalized emittance. This extremely compact injector system also possesses attractive simplification of the rf distribution system by eliminating the need for an rf circulator. We explore the use of this device in a compact 400 MeV-class source, driving both inverse Compton scattering and free-electron laser radiation sources with unique, attractive properties.
Development of a new 2-inch hybrid photo-detector using MPPC Fukasawa, A.; Hotta, Y.; Ishizu, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2018, Letnik:
912
Journal Article
Recenzirano
We have newly developed a Hybrid Photo-Detector (HPD) with 2-inch diameter. It consists of a bialkali photocathode and a 3 mm x 3 mm Multi-Pixel-Photon Counter (MPPC) sealed in a glass tube. The ...electric field inside the tube is designed so that photoelectrons emitted from the photocathode are collected in the MPPC, where photoelectrons are amplified. For conventional HPDs with an avalanche diode, extremely high voltage such as -8kV has to be provided to achieve gain sufficient for single photon detection. However, our HPD with MPPC has single photon sensitivity only with lower voltage like PMTs due to high gain of MPPC. In addition, this device can cover larger area with only one MPPC. These features enable us to easily handle high performance HPD in various applications, such as high energy physics, biomedical field etc. This test sample was produced in 2016, and we have checked its basic characteristics. The peak photocathode quantum efficiency was found to be very high of 37% at the wavelength of 340 nm. We have confirmed that HPD with MPPC has capability of single photon detection in low operation voltage less than -2 kV. This report will present detailed performance studies of this sample.
•A HPD with 2-inch diameter has been developed.•The peak photocathode quantum efficiency was found to be very high.•Capability of single photon detection in -1.5kV operation was confirmed.
Dark matter and double beta decay experiments require extremely low radioactivity within the detector materials. For this purpose, the University of California, Los Angeles and Hamamatsu Photonics ...have developed the QUartz Photon Intensifying Detector (Q
upid), an ultra-low background photodetector based on the Hybrid Avalanche Photo Diode (HAPD) and entirely made of ultraclean synthetic fused silica. In this work we present the basic concept of the Q
upid and the testing measurements on Q
upids from the first production line.
Screening of radioactivity at the Gator facility in the Laboratori Nazionali del Gran Sasso has shown that the Q
upids safely fulfill the low radioactive contamination requirements for the next generation zero background experiments set by Monte Carlo simulations.
The quantum efficiency of the Q
upid at room temperature is
>
30
% at the xenon scintillation wavelength. At −100
°C, the Q
upid shows a leakage current smaller than 1
nA and a global gain of 10
5. In these conditions, the photocathode and the anode show
>
95
%
linearity up to
1
μ
A
for the cathode and 3
mA for the anode. The photocathode and collection efficiency are uniform to 80% over the entire surface. In parallel with single photon counting capabilities, the Q
upids have a good timing response: 1.8 ±0.1
ns rise time, 2.5 ±0.2
ns fall time, 4.20 ±0.05
ns (FWHM) pulse width, and 160 ±30
ps (FWHM) transit time spread.
The Q
upids have also been tested in a liquid xenon environment, and scintillation light from
57Co and
210Po radioactive sources was observed.
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