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The innovative mechanism of steady-state microbunching (SSMB) promises a potent light source, featuring high repetition rate and coherent radiation. The laser modulator, comprising an undulator and an optical enhancement cavity, is pivotal in SSMB. A high-finesse prototype optical enhancement cavity for SSMB with an average power of 55 kW is described in this paper. Preliminary design of the laser modulator, experimental setup, and methods to address frequency degeneracy and power coupling issues are discussed. D-shaped mirrors are utilized to successfully suppress the modal instability. This study is the first to illustrate the finesse reduction caused by high-order mode damping during experiments. The experimental and simulation results match closely. A cavity power coupling model is established, and the experimental results verify the correctness of the coupling model. A method for estimating the absorption coefficient through thermal-induced evolution of cavity mode has been implemented. Experimental results demonstrate a high-average-power enhancement cavity with a finesse of 16 518 ± 103 and an estimated average absorption coefficient of 12 ppm for the cavity mirrors. The findings contribute to the advancement of SSMB by providing insights into the design and operation of high-power optical enhancement cavities.
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Ultrafast electron diffraction (UED) stands as a powerful technique for real-time observation of structural dynamics at the atomic level. In recent years, the use of MeV electrons from radio frequency guns has been widely adopted to take advantage of the relativistic suppression of the space charge effects that otherwise limit the temporal resolution of the technique. Nevertheless, there is not a clear choice for the optimal energy for a UED instrument. Scaling to beam energies higher than a few MeV does pose significant technical challenges, mainly related to the inherent increase in diffraction camera length associated with the smaller Bragg angles. In this study, we report a solution by using a compact post-sample magnetic optical system to magnify the diffraction pattern from a crystal Au sample illuminated by an 8.2 MeV electron beam. Our method employs, as one of the lenses of the optical system, a triplet of compact, high field gradients (>500 T/m), small-gap (3.5 mm) Halbach permanent magnet quadrupoles. Shifting the relative position of the quadrupoles, we demonstrate tuning the magnification by more than a factor of two, a 6× improvement in camera length, and reciprocal space resolution better than 0.1 Å-1 in agreement with beam transport simulations.
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A promising accelerator light source mechanism called steady-state microbunching (SSMB) is being actively studied. With the combination of strong coherent radiation from microbunching and high repetition rate of a storage ring, high-average-power narrow-band radiation can be anticipated from an SSMB storage ring, with wavelengths ranging from THz to soft X-ray. Such a novel light source could provide new opportunities for accelerator photon science like high-resolution angle-resolved photoemission spectroscopy and industrial applications like extreme ultraviolet (EUV) lithography. In this paper, a theoretical and numerical study of the average and statistical properties of coherent radiation from SSMB are presented. The results show that 1â kW average-power quasi-continuous-wave EUV radiation can be obtained from an SSMB ring provided that an average current of 1â A and a microbunch train with bunch length of 3â nm can be formed at the radiator which is assumed to be an undulator. Together with the narrow-band feature, the EUV photon flux can reach 6â ×â 1015â photonsâ s-1 within a 0.1â meV energy bandwidth, which is three orders of magnitude higher than that in a conventional synchrotron source and is appealing for fundamental condensed matter physics and other research. In this theoretical investigation, we have generalized the definition and derivation of the transverse form factor of an electron beam which can quantify the impact of its transverse size on coherent radiation. In particular, it has been shown that the narrow-band feature of SSMB radiation is strongly correlated with the finite transverse electron beam size. Considering the pointlike nature of electrons and quantum nature of radiation, the coherent radiation fluctuates from microbunch to microbunch, or for a single microbunch from turn to turn. Some important results concerning the statistical properties of SSMB radiation are presented, with a brief discussion on its potential applications, for example the beam diagnostics. The presented work is of value for the development of SSMB to better serve potential synchrotron radiation users. In addition, this also sheds light on understanding the radiation characteristics of free-electron lasers, coherent harmonic generation, etc.
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Standardized hepatocellular carcinoma (HCC) screening is very important for early diagnosis. Chinese and international HCC clinical guidelines recommend regular ultrasound screening for high-risk patients. Noninvasive dynamic enhanced imaging technology should be selected for the positive screenin population to get the further diagnosis, including contrast-enhanced ultrasound (CEUS), dynamic contrast-enhanced CT, dynamic contrast-enhanced MRI and Gd-EOB-DTPA enhanced MRI (EOB MRI). In clinical practice, early diagnose of HCC relies on accurate identification and stratification of high-risk patients, and systematic approach based on dynamic contrast-enhanced imaging.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Diagnóstico Precoce , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Sensibilidade e EspecificidadeRESUMO
Electron diffraction through a thin patterned silicon membrane can be used to create complex spatial modulations in electron distributions. By precisely varying parameters such as crystallographic orientation and wafer thickness, the intensity of reflections in the diffraction plane can be controlled and by placing an aperture to block all but one spot, we can form an image with different parts of the patterned membrane, as is done for bright-field imaging in microscopy. The patterned electron beams can then be used to control phase and amplitude of subsequent x-ray emission, enabling novel coherent x-ray methods. The electrons themselves can also be used for femtosecond time resolved diffraction and microscopy. As a first step toward patterned beams, we demonstrate experimentally and through simulation the ability to accurately predict and control diffraction spot intensities. We simulate MeV transmission electron diffraction patterns using the multislice method for various crystallographic orientations of a single crystal Si(001) membrane near beam normal. The resulting intensity maps of the Bragg reflections are compared to experimental results obtained at the Accelerator Structure Test Area Ultrafast Electron Diffraction (ASTA UED) facility at SLAC. Furthermore, the fraction of inelastic and elastic scattering of the initial charge is estimated along with the absorption of the membrane to determine the contrast that would be seen in a patterned version of the Si(001) membrane.
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We present the first demonstration of THz driven bunch compression and timing stabilization of a relativistic electron beam. Quasi-single-cycle strong field THz radiation is used in a shorted parallel-plate structure to compress a few-fC beam with 2.5 MeV kinetic energy by a factor of 2.7, producing a 39 fs rms bunch length and a reduction in timing jitter by more than a factor of 2 to 31 fs rms. This THz driven technique offers a significant improvement to beam performance for applications like ultrafast electron diffraction, providing a critical step towards unprecedented timing resolution in ultrafast sciences, and other accelerator applications using femtosecond-scale electron beams.
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The development of ultrafast gas electron diffraction with nonrelativistic electrons has enabled the determination of molecular structures with atomic spatial resolution. It has, however, been challenging to break the picosecond temporal resolution barrier and achieve the goal that has long been envisioned-making space- and-time resolved molecular movies of chemical reaction in the gas-phase. Recently, an ultrafast electron diffraction (UED) apparatus using mega-electron-volt (MeV) electrons was developed at the SLAC National Accelerator Laboratory for imaging ultrafast structural dynamics of molecules in the gas phase. The SLAC gas-phase MeV UED has achieved 65 fs root mean square temporal resolution, 0.63 Å spatial resolution, and 0.22 Å-1 reciprocal-space resolution. Such high spatial-temporal resolution has enabled the capturing of real-time molecular movies of fundamental photochemical mechanisms, such as chemical bond breaking, ring opening, and a nuclear wave packet crossing a conical intersection. In this paper, the design that enables the high spatial-temporal resolution of the SLAC gas phase MeV UED is presented. The compact design of the differential pump section of the SLAC gas phase MeV UED realized five orders-of-magnitude vacuum isolation between the electron source and gas sample chamber. The spatial resolution, temporal resolution, and long-term stability of the apparatus are systematically characterized.
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We demonstrate the electromagnetic performance of waveguides for femtosecond electron beam bunch manipulation and compression with strong-field terahertz (THz) pulses. The compressor structure is a dispersion-free exponentially-tapered parallel-plate waveguide (PPWG) that can focus single-cycle THz pulses along one dimension. We show test results of the tapered PPWG structure using electro-optic sampling (EOS) at the interaction region with peak fields of at least 300 kV/cm, given 0.9 µJ of incoming THz energy. We also present a modified shorted design of the tapered PPWG for better beam manipulation and reduced magnetic field as an alternative to a dual-feed approach. As an example, we demonstrate that with 5 µJ of THz energy, the PPWG compresses a 2.5 MeV electron bunch by a compression factor of more than 4, achieving a bunch length of about 18 fs.
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PURPOSE: Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures. METHODS: Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for ≤ 1 year. RESULTS: In total, 271 and 278 patients received CT-P6 and trastuzumab, respectively. pCR and breast pCR rates were comparable between treatment groups regardless of age, region, or clinical stage. Overall, 47.6% (CT-P6) and 52.2% (trastuzumab) of patients experienced study drug-related treatment-emergent adverse events (TEAEs), including 17 patients reporting heart failure (CT-P6: 10; trastuzumab: 7). Two CT-P6 and three trastuzumab patients discontinued adjuvant treatment due to TEAEs. CONCLUSION: Adjuvant CT-P6 demonstrated comparable efficacy and safety to trastuzumab at 1 year in patients with HER2-positive EBC, supporting CT-P6 and trastuzumab comparability.
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Medicamentos Biossimilares , Neoplasias da Mama/tratamento farmacológico , Insuficiência Cardíaca , Trastuzumab , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/farmacocinética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Monitoramento de Medicamentos/métodos , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/farmacocinética , Resultado do TratamentoRESUMO
The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subångström length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.
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The very-high-frequency gun (VHF-Gun) is a new concept photo-injector developed and built at the Lawrence Berkeley National Laboratory (LBNL) for generating high-brightness electron beams capable of driving X-ray free electron lasers (FELs) at MHz-class repetition rates. The gun that purposely uses established and mature radiofrequency and mechanical technologies has demonstrated over the last many years the capability of reliably operating in continuous wave mode at the design accelerating fields and required vacuum and mechanical performance. The results of VHF-Gun technology demonstration were reported elsewhere [Sannibale et al., Phys. Rev. Spec. Top.-Accel. Beams 15, 103501 (2012)]; here in this paper, we provide and analyze examples of the experimental results of the first high-brightness beam tests performed at the Advanced Photo-injector EXperiment test facility at LBNL that demonstrated the gun capability of delivering the beam quality required for driving high repetition rate X-ray FELs.
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Electron-lattice coupling strength governs the energy transfer between electrons and the lattice and is important for understanding the material behavior under highly non-equilibrium conditions. Here we report the results of employing time-resolved electron diffraction at MeV energies to directly study the electron-lattice coupling strength in 40-nm-thick polycrystalline copper excited by femtosecond optical lasers. The temporal evolution of lattice temperature at various pump fluence conditions were obtained from the measurements of the Debye-Waller decay of multiple diffraction peaks. We observed the temperature dependence of the electron-lattice relaxation time which is a result of the temperature dependence of electron heat capacity. Comparison with two-temperature model simulations reveals an electron-lattice coupling strength of (0.9 ± 0.1) × 1017 W/m3/K for copper.
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The ultrafast laser excitation of matters leads to nonequilibrium states with complex solid-liquid phase-transition dynamics. We used electron diffraction at mega-electron volt energies to visualize the ultrafast melting of gold on the atomic scale length. For energy densities approaching the irreversible melting regime, we first observed heterogeneous melting on time scales of 100 to 1000 picoseconds, transitioning to homogeneous melting that occurs catastrophically within 10 to 20 picoseconds at higher energy densities. We showed evidence for the heterogeneous coexistence of solid and liquid. We determined the ion and electron temperature evolution and found superheated conditions. Our results constrain the electron-ion coupling rate, determine the Debye temperature, and reveal the melting sensitivity to nucleation seeds.
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"The technical support from SLAC Accelerator Directorate, Technology Innovation Directorate, LCLS laser division and Test Facility Division is gratefully acknowledged. We thank S.P. Weathersby, R.K. Jobe, D. McCormick, A. Mitra, S. Carron and J. Corbett for their invaluable help and technical assistance. Research at SLAC was supported through the SIMES Institute which like the LCLS and SSRL user facilities is funded by the Office of Basic Energy Sciences of the U.S. Department of Energy under Contract No. DE-AC02-76SF00515. The UED work was performed at SLAC MeV-UED, which is supported in part by the DOE BES SUF Division Accelerator & Detector R&D program, the LCLS Facility, and SLAC under contract Nos. DE-AC02-05-CH11231 and DE-AC02-76SF00515. Use of the Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515."and"Work at BNL was supported by DOE BES Materials Science and Engineering Division under Contract No: DE-AC02-98CH10886. J.C. would like to acknowledge the support from National Science Foundation Grant No. 1207252. E.E.F. would like to acknowledge support from the U.S. Department of Energy (DOE), Office of Basic Energy Sciences (BES) under Award No. DE-SC0003678."This has been corrected in both the PDF and HTML versions of the Article.
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Magnetostriction, the strain induced by a change in magnetization, is a universal effect in magnetic materials. Owing to the difficulty in unraveling its microscopic origin, it has been largely treated phenomenologically. Here, we show how the source of magnetostriction-the underlying magnetoelastic stress-can be separated in the time domain, opening the door for an atomistic understanding. X-ray and electron diffraction are used to separate the sub-picosecond spin and lattice responses of FePt nanoparticles. Following excitation with a 50-fs laser pulse, time-resolved X-ray diffraction demonstrates that magnetic order is lost within the nanoparticles with a time constant of 146 fs. Ultrafast electron diffraction reveals that this demagnetization is followed by an anisotropic, three-dimensional lattice motion. Analysis of the size, speed, and symmetry of the lattice motion, together with ab initio calculations accounting for the stresses due to electrons and phonons, allow us to reveal the magnetoelastic stress generated by demagnetization.
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To understand and control the basic functions of physical, chemical and biological processes from micron to nano-meter scale, an instrument capable of visualizing transient structural changes of inhomogeneous materials with atomic spatial and temporal resolutions, is required. One such technique is femtosecond electron microdiffraction, in which a short electron pulse with femtosecond-scale duration is focused into a micron-scale spot and used to obtain diffraction images to resolve ultrafast structural dynamics over a localized crystalline domain. In this letter, we report the experimental demonstration of time-resolved mega-electron-volt electron microdiffraction which achieves a 5⯵m root-mean-square (rms) beam size on the sample and a 110 fs rms temporal resolution. Using pulses of 10k electrons at 4.2 MeV energy with a normalized emittance 3â¯nm-rad, we obtained high quality diffraction from a single 10⯵m paraffin (C44H90) crystal. The phonon softening mode in optical-pumped polycrystalline Bi was also time-resolved, demonstrating the temporal resolution limits of the instrument. This new characterization capability will open many research opportunities in material and biological sciences.
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We apply time-resolved MeV electron diffraction to study the electron-lattice energy relaxation in thin film Au-insulator heterostructures. Through precise measurements of the transient Debye-Waller-factor, the mean-square atomic displacement is directly determined, which allows to quantitatively follow the temporal evolution of the lattice temperature after short pulse laser excitation. Data obtained over an extended range of laser fluences reveal an increased relaxation rate when the film thickness is reduced or the Au-film is capped with an additional insulator top-layer. This behavior is attributed to a cross-interfacial coupling of excited electrons in the Au film to phonons in the adjacent insulator layer(s). Analysis of the data using the two-temperature-model taking explicitly into account the additional energy loss at the interface(s) allows to deduce the relative strength of the two relaxation channels.
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This study aimed to investigate role of long noncoding RNA PTENP1 regulating PTEN expression via miR-19b to affect breast cancer (BC) progression. We measured expressions of PTENP1, miR-19b and PTEN in 65 matched BC cancerous and noncancerous tissues by quantitative real-time fluorescence PCR (qRT-PCR) and investigated the biological effects of PTENP1 in BC MDA-MB-231 cells by several in vitro experiments including CCK8, wound healing, transwell and Annexin V-FITC/PI analysis. Besides, the competing endogenous RNA (ceRNA) activity of PTENP1 on miR-19b was detected by luciferase reporter assay, and the expressions of related genes and proteins were determined by western blot assay and qRT-PCR. Increased PTENP1 and PTEN and decreased miR-19b were observed in BC tissues and cell lines. Further, PTENP1 and PTEN are direct targets of miR-19b, and overexpressed PTENP1 in MDA-MB-231 cells could supress cell proliferation, migration and invasion and promote cell apoptosis. Moreover, PTENP1 could upregulate PTEN via its ceRNA interaction on miR-19b, as well as induced the upregulation of p53 and downregulation of p-AKT. Enhanced PTENP1 could inhibit BC cell growth, metastasis and tumourigenicity by inhibiting miR-19b and facilitating PTEN in BC, thereby may represent a novel target for diagnosis and treatment of BC.
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Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Interferência de RNA , RNA Longo não Codificante/genética , Regiões 3' não Traduzidas , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Genes Reporter , HumanosRESUMO
Single crystals of LiCdY5(BO3)6 were successfully grown from a Li2O-B2O3 flux, and its lanthanide homotypic compounds, LiCdRE5(BO3)6 (RE = Sm-Lu), have been prepared by solid-state reaction. They crystallize in the noncentrosymmetric space group P6522 with cell parameters in the ranges of a = 7.0989(2)-6.9337(1) Å and c = 25.9375(1)-24.8960(6) Å. As a representative example, LiCdY5(BO3)6 features a triangular lattice in the ab plane composed of three distinct crystallographic Y sites. The triangular lattices spaced with the same distance of [Formula: see text]c are further stacked to build three-dimensional frameworks by reinforcement of the isolated planar BO3 groups and distorted LiO4 tetrahedra. Magnetic measurements show that Eu and Sm compounds exhibit typical Van Vleck-type paramagnetism and other rare-earth borates show weak antiferromagnetic behavior. In addition, UV-vis-near-IR diffuse-reflectance and photoluminescence spectra were performed to understand the transition energy levels of active rare-earth ions and their relationships to magnetism.