X-ray optics for the cavity-based X-ray free-electron laser.

A cavity-based X-ray free-electron laser (CBXFEL) is a possible future direction in the development of fully coherent X-ray sources. CBXFELs consist of a low-emittance electron source, a magnet system with several undulators and chicanes, and an X-ray cavity. The X-ray cavity stores and circulates X-ray pulses for repeated FEL interactions with electron pulses until the FEL reaches saturation. CBXFEL cavities require low-loss wavefront-preserving optical components: near-100%-reflectivity X-ray diamond Bragg-reflecting crystals, outcoupling devices such as thin diamond membranes or X-ray gratings, and aberration-free focusing elements. In the framework of the collaborative CBXFEL research and development project of Argonne National Laboratory, SLAC National Accelerator Laboratory and SPring-8, we report here the design, manufacturing and characterization of X-ray optical components for the CBXFEL cavity, which include high-reflectivity diamond crystal mirrors, a diamond drumhead crystal with thin membranes, beryllium refractive lenses and channel-cut Si monochromators. All the designed optical components have been fully characterized at the Advanced Photon Source to demonstrate their suitability for the CBXFEL cavity application.

At-wavelength characterization of X-ray wavefronts in Bragg diffraction from crystals.

The advent of next-generation synchrotron radiation sources and X-ray free-electron lasers calls for high-quality Bragg-diffraction crystal optics to preserve the X-ray beam coherence and wavefront. This requirement brings new challenges in characterizing crystals in Bragg diffraction in terms of Bragg-plane height errors and wavefront phase distortions. Here, a quantitative methodology to characterize crystal optics using a state-of-the-art at-wavelength wavefront sensing technique and statistical analysis is proposed. The method was tested at the 1-BM-B optics testing beamline at the Advanced Photon Source for measuring silicon and diamond crystals in a self-referencing single-crystal mode and an absolute double-crystal mode. The phase error sensitivity of the technique is demonstrated to be at the λ/100 level required by most applications, such as the characterization of diamond crystals for cavity-based X-ray free-electron lasers.

Resonant X-ray excitation of the nuclear clock isomer 45Sc.

Resonant oscillators with stable frequencies and large quality factors help us to keep track of time with high precision. Examples range from quartz crystal oscillators in wristwatches to atomic oscillators in atomic clocks, which are, at present, our most precise time measurement devices1. The search for more stable and convenient reference oscillators is continuing2-6. Nuclear oscillators are better than atomic oscillators because of their naturally higher quality factors and higher resilience against external perturbations7-9. One of the most promising cases is an ultra-narrow nuclear resonance transition in 45Sc between the ground state and the 12.4-keV isomeric state with a long lifetime of 0.47 s (ref. 10). The scientific potential of 45Sc was realized long ago, but applications require 45Sc resonant excitation, which in turn requires accelerator-driven, high-brightness X-ray sources11 that have become available only recently. Here we report on resonant X-ray excitation of the 45Sc isomeric state by irradiation of Sc-metal foil with 12.4-keV photon pulses from a state-of-the-art X-ray free-electron laser and subsequent detection of nuclear decay products. Simultaneously, the transition energy was determined as [Formula: see text] with an uncertainty that is two orders of magnitude smaller than the previously known values. These advancements enable the application of this isomer in extreme metrology, nuclear clock technology, ultra-high-precision spectroscopy and similar applications.

Facile and scalable fabrication of exosome-mimicking nanovesicles through PEGylated lipid detergent-aided cell extrusion.

We report a scalable fabrication method to generate exosome-mimicking nanovesicles (ENVs) by using a biocompatible, cell-binding lipid detergent during cell extrusion. A PEGylated mannosylerythritol lipid (MELPEG) detergent was rationally engineered to strongly associate with phospholipid membranes to increase cell membrane deformability and the corresponding friction force during extrusion and to enhance the dispersibility of ENVs. Compared to cell extrusion without detergent, cell extrusion in the presence of MELPEG increased the ENV production yield by approximately 20 times and cellular protein content per MELPEG-functionalized ENV by approximately 2-fold relative to that of unmodified ENVs. We verified that MELPEG strongly binds to ENV membranes and increases membrane deformability via expansion/swelling while preserving the integrity of the phospholipid bilayer structure. The results highlight that the MELPEG-aided cell extrusion process broadly applies to various cell lines; hence, it could be helpful in the production of ENVs for tissue regeneration, drug delivery, and cancer nanomedicine.

Outcomes of Empirical Treatment With Intravenous Immunoglobulin G Combined With Low-Dose Aspirin in Women With Unexplained Recurrent Pregnancy Loss.

BACKGROUND: To assess the clinical efficacy of intravenous immunoglobulin G (IVIG) administration combined with low-dose aspirin in women with unexplained recurrent pregnancy loss (RPL). METHODS: We retrospectively analyzed the medical records of patients who had been diagnosed with unexplained RPL and treated with IVIG and low-dose aspirin between January 2000 and March 2020 at Asan Medical Center. We analyzed pregnancy outcomes and their association with the percentage of natural killer (NK) cells. RESULTS: The study analyzed a total of 93 patients and 113 natural and assisted reproductive technology pregnancy cycles. The live birth rate per cycle was 73.5% (83/113), and the term delivery rate was 86.7% (72/83). The live birth rate was high regardless of the type of RPL, method of pregnancy, timing of IVIG treatment, and presence or absence of autoantibodies. In addition, the live birth rate was significantly higher in patients who received IVIG more than once, compared with patients who received IVIG only once (77.8% vs. 42.9%, P = 0.006). There was no significant association between the NK cell counts and live birth rate (65.5% in the group with NK cell < 12%, and 69.7% in that with NK cell ≥ 12%, P = 0.725). Among all patients, 87.6% had no complications, and there were no congenital malformation among newborn babies. CONCLUSION: IVIG combined with low-dose aspirin treatment showed favorable pregnancy outcomes regardless of the patient's NK cell counts (%).

Diamond channel-cut crystals for high-heat-load beam-multiplexing narrow-band X-ray monochromators.

Next-generation high-brilliance X-ray photon sources call for new X-ray optics. Here we demonstrate the possibility of using monolithic diamond channel-cut crystals as high-heat-load beam-multiplexing narrow-band mechanically stable X-ray monochromators with high-power X-ray beams at cutting-edge high-repetition-rate X-ray free-electron laser (XFEL) facilities. The diamond channel-cut crystals fabricated and characterized in these studies are designed as two-bounce Bragg reflection monochromators directing 14.4 or 12.4 keV X-rays within a 15 meV bandwidth to 57Fe or 45Sc nuclear resonant scattering experiments, respectively. The crystal design allows out-of-band X-rays transmitted with minimal losses to alternative simultaneous experiments. Only ≲2% of the incident ∼100 W X-ray beam is absorbed in the 50 µm-thick first diamond crystal reflector, ensuring that the monochromator crystal is highly stable. Other X-ray optics applications of diamond channel-cut crystals are anticipated.

Identification of Renoprotective Phytosterols from Mulberry (Morus alba) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells.

The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree (Morus alba L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. Morus alba fruit is a well-known edible fruit commonly used in traditional folk medicine. Chemical investigation of M. alba fruit resulted in the isolation and identification of six phytosterols (1-6). Their structures were determined as 7-ketositosterol (1), stigmast-4-en-3ß-ol-6-one (2), (3ß,6α)-stigmast-4-ene-3,6-diol (3), stigmast-4-ene-3ß,6ß-diol (4), 7ß-hydroxysitosterol 3-O-ß-d-glucoside (5), and 7α-hydroxysitosterol 3-O-ß-d-glucoside (6) by analyzing their physical and spectroscopic data as well as liquid chromatography/mass spectrometry data. All compounds displayed protective effects against cisplatin-induced LLC-PK1 cell damage, improving cisplatin-induced cytotoxicity to more than 80% of the control value. Compound 1 displayed the best effect at a relatively low concentration by inhibiting the percentage of apoptotic cells following cisplatin treatment. Its molecular mechanisms were identified using Western blot assays. Treatment of LLC-PK1 cells with compound 1 decreased the upregulated phosphorylation of p38 and c-Jun N-terminal kinase (JNK) following cisplatin treatment. In addition, compound 1 significantly suppressed cleaved caspase-3 in cisplatin-induced LLC-PK1 cells. Taken together, these findings indicated that cisplatin-induced apoptosis was significantly inhibited by compound 1 in LLC-PK1 cells, thereby supporting the potential of 7-ketositosterol (1) as an adjuvant candidate for treating cisplatin-induced nephrotoxicity.

Influence of pretreatment of insulin on the phosphorylation of extracellular receptor kinase by gonadotropin-releasing hormone and gonadotropins in cultured human granulosa cells.

OBJECTIVE: To investigate the influence of pretreatment of insulin on the phosphorylation of ERK1/2 by gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in cultured human granulosa cells. STUDY DESIGN: Human granulosa cells were collected from 20 women (age: 20-35 years) who underwent controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer at Asan Medical Center (Seoul, South Korea). The presence of the receptors for insulin, GnRH, FSH, and LH in human granulosa cells was identified by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The granulosa cells were treated with 10 nM insulin or 10 nM GnRH for 5 min or 30 min and with 10 nM FSH or 10 nM LH for 24 h or 48 h. The cells were also pretreated with insulin for 30 min prior to treatment with GnRH, FSH, or LH. Western blot analysis was used to analyze ERK1/2 phosphorylation. RESULTS: RT-PCR showed that the receptors for insulin, GnRH, FSH, and LH were expressed in human granulosa cells. Insulin, GnRH, FSH, and LH could activate ERK1/2 phosphorylation. Pretreatment with insulin inhibited ERK1/2 phosphorylation induced by GnRH and FSH while augmenting ERK1/2 phosphorylation induced by LH. CONCLUSIONS: Insulin might have a negative effect on GnRH and FSH regulation by attenuating the action of GnRH and FSH in the phosphorylation of ERK1/2 in human granulosa cells. In contrast, insulin might have a positive effect on LH regulation by potentiating the action of LH in the phosphorylation of ERK1/2. Our results showed that insulin is clearly an important regulator of human reproductive function at the ovarian level.

Development of ozone monitoring system in ozone-treated water.

An ozone concentration meter in ozonated water has been developed and manufactured. The measurement of ozone concentration is based on the use of a photometric method. The range of measured ozone concentration is varied from 0.1 to 10 mg/l. The principle of operation of the meter is based on recording the difference in the absorption coefficients of ultraviolet radiation by the analyzed ozonated water and the reference (ozone-free) water. The meter was calibrated on an automated measuring stand using a monochromator and a photomultiplier tube. Such a device could be very useful in water purification systems or wastewater treatment plants. The developed meter provided high accuracy and stability of readings, operation without maintenance, full automation of measurement, and automatic correction of zero drift.

Estrogenic Activity of Mycoestrogen (3ß,5α,22E)-Ergost-22-en-3-ol via Estrogen Receptor α-Dependent Signaling Pathways in MCF-7 Cells.

Armillariella tabescens (Scop.) Sing., a mushroom of the family Tricholomataceae, has been used in traditional oriental medicine to treat cholecystitis, improve bile secretion, and regulate bile-duct pressure. The present study evaluated the estrogen-like effects of A. tabescens using a cell-proliferation assay in an estrogen-receptor-positive breast cancer cell line (MCF-7). We found that the methanol extract of A. tabescens fruiting bodies promoted cell proliferation in MCF-7 cells. Using bioassay-guided fractionation of the methanol extract and chemical investigation, we isolated and identified four steroids and four fatty acids from the active fraction. All eight compounds were evaluated by E-screen assay for their estrogen-like effects in MCF-7 cells. Among the tested isolates, only (3ß,5α,22E)-ergost-22-en-3-ol promoted cell proliferation in MCF-7 cells; this effect was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of (3ß,5α,22E)-ergost-22-en-3-ol was evaluated using Western blot analysis to detect the expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), Akt, and estrogen receptor α (ERα). We found that (3ß,5α,22E)-ergost-22-en-3-ol induced an increase in phosphorylation of ERK, PI3K, Akt, and ERα. Together, these experimental results suggest that (3ß,5α,22E)-ergost-22-en-3-ol is responsible for the estrogen-like effects of A. tabescens and may potentially aid control of estrogenic activity in menopause.

Small Bragg-plane slope errors revealed in synthetic diamond crystals.

Wavefront-preserving X-ray diamond crystal optics are essential for numerous applications in X-ray science. Perfect crystals with flat Bragg planes are a prerequisite for wavefront preservation in Bragg diffraction. However, this condition is difficult to realize in practice because of inevitable crystal imperfections. Here, X-ray rocking curve imaging is used to study the smallest achievable Bragg-plane slope errors in the best presently available synthetic diamond crystals and how they compare with those of perfect silicon crystals. It is shown that the smallest specific slope errors in the best diamond crystals are about 0.08 (3) µrad mm-2. These errors are only 50% larger than the 0.05 (2) µrad mm-2 specific slope errors measured in perfect silicon crystals. High-temperature annealing at 1450°C of almost flawless diamond crystals reduces the slope errors very close to those of silicon. Further investigations are in progress to establish the wavefront-preservation properties of these crystals.

Diffraction gratings with two-orders-of-magnitude-enhanced dispersion rates for sub-meV resolution soft X-ray spectroscopy.

Diffraction gratings with large angular dispersion rates are central to obtaining high spectral resolution in grating spectrometers operating over a broad spectral range from infrared to soft X-ray domains. The greatest challenge is of course to achieve large dispersion rates in the short-wavelength X-ray domain. Here it is shown that crystals in non-coplanar asymmetric X-ray Bragg diffraction can function as high-reflectance broadband soft X-ray diffraction gratings with dispersion rates that are at least two orders of magnitude larger than those that are possible with state-of-the-art man-made gratings. This opens new opportunities to design and implement soft X-ray resonant inelastic scattering (RIXS) spectrometers with spectral resolutions that are up to two orders of magnitude higher than what is currently possible, to further advance a very dynamic field of RIXS spectroscopy, and to make it competitive with inelastic neutron scattering. Examples of large-dispersion-rate crystal diffraction gratings operating near the 930 eV L3 absorption edge in Cu and of the 2.838 keV L3-edge in Ru are presented.

Hard-X-Ray Spectroscopy with a Spectrographic Approach.

Hard-x-ray spectroscopy relies on a suite of modern techniques for studies of vibrational, electronic, and magnetic excitations in condensed matter. At present, the energy resolution of these techniques can be improved only by decreasing the spectral window of the involved optics-monochromators and analyzers-thereby sacrificing the intensity. Here, we demonstrate hard-x-ray spectroscopy with greatly improved energy resolution without narrowing the spectral window by adapting principles of spectrographic imaging to the hard-x-ray regime. Similar to Newton's classical prism, the hard-x-ray spectrograph disperses different "colors"-i.e., energies-of x-ray photons in space. Then, selecting each energy component with a slit ensures high energy resolution, whereas measuring x-ray spectra with all components of a broad spectral window keeps the intensity. We employ the principles of spectrographic imaging for phonon spectroscopy. Here the new approach revealed anomalous soft atomic dynamics in α-iron, a phenomenon which was not previously reported in the literature. We argue that hard-x-ray spectrographic imaging also could be a path to discovering new physics in studies of electronic and magnetic excitations.

Hard X-ray self-seeding commissioning at PAL-XFEL.

A wake monochromator based on a large-area diamond single crystal for hard X-ray self-seeding has been successfully installed and commissioned in the hard X-ray free-electron laser (FEL) at the Pohang Accelerator Laboratory with international collaboration. For this commissioning, the self-seeding was demonstrated with a low bunch charge (40 pC) and the nominal bunch charge (180 pC) of self-amplified spontaneous emission (SASE) operation. The FEL pulse lengths were estimated as 7 fs and 29.5 fs, respectively. In both cases, the average spectral brightness increased by more than three times compared with the SASE mode. The self-seeding experiment was demonstrated for the first time using a crystal with a thickness of 30 µm, and a narrow bandwidth of 0.22 eV (full width at half-maximum) was obtained at 8.3 keV, which confirmed the functionality of a crystal with such a small thickness. In the nominal bunch-charge self-seeding experiment, the histogram of the intensity integrated over a 1 eV bandwidth showed a well defined Gaussian profile, which is evidence of the saturated FEL and a minimal electron-energy jitter (∼1.2 × 10-4) effect. The corresponding low photon-energy jitter (∼2.4 × 10-4) of the SASE FEL pulse, which is two times lower than the Pierce parameter, enabled the seeding power to be maximized by maintaining the spectral overlap between SASE FEL gain and the monochromator.

Betulinic Acid Suppresses Ovarian Cancer Cell Proliferation through Induction of Apoptosis.

Ovarian cancer is one of the leading causes of cancer deaths worldwide in women, and the most malignant cancer among the different gynecological cancers. In this study, we explored potentially anticancer compounds from Cornus walteri (Cornaceae), the MeOH extract of which has been reported to show considerable cytotoxicity against several cancer cell lines. Phytochemical investigations of the MeOH extract of the stem and stem bark of C. walteri by extensive application of chromatographic techniques resulted in the isolation of 14 compounds (1-14). The isolated compounds were evaluated for inhibitory effects on the viability of A2780 human ovarian carcinoma cells and the underlying molecular mechanisms were investigated. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to assess the anticancer effects of compounds 1-14 on A2780 cells, which showed that compound 11 (betulinic acid) reduced the viability of these cells in a concentration-dependent manner and had an half maximal (50%) inhibitory concentration (IC50) of 44.47 µM at 24 h. Nuclear staining and image-based cytometric assay were carried out to detect the induction of apoptosis by betulinic acid. Betulinic acid significantly increased the condensation of nuclei and the percentage of apoptotic cells in a concentration-dependent manner in A2780 cells. Western blot analysis was performed to investigate the underlying mechanism of apoptosis. The results indicated that the expression levels of cleaved caspase-8, -3, -9, and Bax were increased in A2780 cells treated with betulinic acid, whereas those of Bcl-2 were decreased. Thus, we provide the experimental evidence that betulinic acid can induce apoptosis in A2780 cells through both mitochondria-dependent and -independent pathways and suggest the potential use of betulinic acid in the development of novel chemotherapeutics for ovarian cancer therapy.

Optical Properties, Synthesis, and Potential Applications of Cu-Based Ternary or Quaternary Anisotropic Quantum Dots, Polytypic Nanocrystals, and Core/Shell Heterostructures.

This review summaries the optical properties, recent progress in synthesis, and a range of applications of luminescent Cu-based ternary or quaternary quantum dots (QDs). We first present the unique optical properties of the Cu-based multicomponent QDs, regarding their emission mechanism, high photoluminescent quantum yields (PLQYs), size-dependent bandgap, composition-dependent bandgap, broad emission range, large Stokes' shift, and long photoluminescent (PL) lifetimes. Huge progress has taken place in this area over the past years, via detailed experimenting and modelling, giving a much more complete understanding of these nanomaterials and enabling the means to control and therefore take full advantage of their important properties. We then fully explore the techniques to prepare the various types of Cu-based ternary or quaternary QDs (including anisotropic nanocrystals (NCs), polytypic NCs, and spherical, nanorod and tetrapod core/shell heterostructures) are introduced in subsequent sections. To date, various strategies have been employed to understand and control the QDs distinct and new morphologies, with the recent development of Cu-based nanorod and tetrapod structure synthesis highlighted. Next, we summarize a series of applications of these luminescent Cu-based anisotropic and core/shell heterostructures, covering luminescent solar concentrators (LSCs), bioimaging and light emitting diodes (LEDs). Finally, we provide perspectives on the overall current status, challenges, and future directions in this field. The confluence of advances in the synthesis, properties, and applications of these Cu-based QDs presents an important opportunity to a wide-range of fields and this piece gives the reader the knowledge to grasp these exciting developments.

Thick "Swiss Cheese" Appearance of Uterine Endometrium in Postmenopausal Women with Different Gynecologic Conditions.

OBJECTIVES: To uncover gynecologic conditions with similar transvaginal sonographic findings of thick uterine endometrium with honeycomb appearance in pre-and postmenopausal women. METHODS: We retrospectively reviewed cases of patients with endometrial tissue biopsy from January 2010 to December 2016. We also collected office flexible hysteroscopic findings and surgical pathologic results. We analyzed data from 393 patients with confirmed endometrial pathology. Among these patients, 69 had transvaginal ultrasonographic images with thick uterine endometrium and honeycomb or "Swiss cheese" appearance. RESULTS: We found gynecologic conditions such as submucosal leiomyoma with degeneration, endometrial polyp, pseudocystic endometrial change associated with tamoxifen use, progesterone associated endometrial change, pyometra, retained placenta, and uterine synechiae manifested with similar thick endometrium with "Swiss cheese" appearance in transvaginal sonographic images. The most common diagnosis in postmenopausal women was atrophic endometritis, followed by endometrial cancer and endometrial polyps. The most common diagnosis in premenopausal women was abnormal uterine bleeding without pathologic conditions. CONCLUSIONS: Sonographic findings of thick uterine endometrium with "Swiss cheese" appearance need to be considered together with a thorough review of the patient's history and chief complaint before making a tentative diagnosis due to the various conditions sharing the feature.

High Bragg reflectivity of diamond crystals exposed to multi-kW†mm-2 X-ray beams.

X-ray free-electron lasers in the oscillator configuration (XFELO) are future fully coherent hard X-rays sources with ultrahigh spectral purity. X-ray beams circulate in an XFELO optical cavity comprising diamond single crystals. They function as high-reflectance (close to 100%), narrowband (∼10 meV) Bragg backscattering mirrors. The average power density of the X-ray beams in the XFELO cavity is predicted to be as high as ∼10 kW mm-2. Therefore, XFELO feasibility relies on the ability of diamond crystals to withstand such a high radiation load and preserve their high reflectivity. Here the endurance of diamond crystals to irradiation with multi-kW mm-2 power density X-ray beams is studied. It is shown that the high Bragg reflectivity of the diamond crystals is preserved after the irradiation, provided it is performed at ∼1 × 10-8 Torr high-vacuum conditions. Irradiation under 4 × 10-6 Torr results in a ∼1 meV shift of the Bragg peak, which corresponds to a relative lattice distortion of 4 × 10-8, while the high Bragg reflectivity stays intact.

Efficiency and coherence preservation studies of Be refractive lenses for XFELO application.

Performance tests of parabolic beryllium refractive lenses, considered as X-ray focusing elements in the future X-ray free-electron laser oscillator (XFELO), are reported. Single and double refractive lenses were subject to X-ray tests, which included: surface profile, transmissivity measurements, imaging capabilities and wavefront distortion with grating interferometry. Optical metrology revealed that surface profiles were close to the design specification in terms of the figure and roughness. The transmissivity of the lenses is >94% at 8 keV and >98% at 14.4 and 18 keV. These values are close to the theoretical values of ideal lenses. Images of the bending-magnet source obtained with the lenses were close to the expected ones and did not show any significant distortion. Grating interferometry revealed that the possible wavefront distortions produced by surface and bulk lens imperfections were on the level of ∼λ/60 for 8 keV photons. Thus the Be lenses can be succesfully used as focusing and beam collimating elements in the XFELO.