Consideration of the dielectric response for radiation chemistry simulations.

The spur reaction, a spatially nonhomogeneous chemical reaction following ionization, is crucial in radiolysis or photolysis in liquids, but the spur expansion process has yet to be elucidated. One reason is the need to understand the role of the dielectric response of the solvating molecules surrounding the charged species generated by ionization. The dielectric response corresponds to the time evolution of the permittivity and might affect the chemical reaction-diffusion of the species in a spur expansion process. This study examined the competitive relationship between reaction-diffusion kinetics and the dielectric response by solving the Debye-Smoluchowski equation while considering the dielectric response. The Coulomb force between the charged species gradually decreases with the dielectric response. Our calculation results found a condition where fast recombination occurs before the dielectric response is complete. Although it has been reported that the primary G-values of free electrons depend on the static dielectric constant under low-linear-energy transfer radiation-induced ionization, we propose that considering the dielectric response can provide a deeper insight into fast recombination reactions under high-linear-energy transfer radiation- or photo-induced ionization. Our simulation method enables the understanding of fast radiation-induced phenomena in liquids.

Application of High-Energy-Resolution X-ray Absorption Spectroscopy at the U L3-Edge to Assess the U(V) Electronic Structure in FeUO4.

FeUO4 was studied to clarify the electronic structure of U(V) in a metal monouranate compound. We obtained the peak splitting of spectra utilizing high-energy-resolution fluorescence detection-X-ray absorption near-edge structure (HERFD-XANES) spectroscopy at the U L3-edge, which is a novel technique in uranium(V) monouranate compounds. Theoretical calculations revealed that the peak splitting was caused by splitting of the 6d orbital of U(V) in FeUO4, which would be used to detect minor U(V) species. Such distinctive electronic states are of major interest to researchers and engineers working in various fields, from fundamental physics to the nuclear industry and environmental sciences for actinide elements.

Radiation Chemistry Provides Nanoscopic Insights into the Role of Intermediate Phases in CeO2 Mesocrystal Formation.

The role of intermediate phases in CeO2 mesocrystal formation from aqueous CeIII solutions subjected to γ-radiation was studied. Radiolytically formed hydroxyl radicals convert soluble CeIII into less soluble CeIV . Transmission electron microscopy (TEM) and X-ray diffraction studies of samples from different stages of the process allowed the identification of several stages in CeO2 mesocrystal evolution following the oxidation to CeIV : (1) formation of hydrated CeIV hydroxides, serving as intermediates in the liquid-to-solid phase transformation; (2) CeO2 primary particle growth inside the intermediate phase; (3) alignment of the primary particles into "pre-mesocrystals" and subsequently to mesocrystals, guided by confinement of the amorphous intermediate phase and accompanied by the formation of "mineral bridges". Further alignment of the obtained mesocrystals into supracrystals occurs upon slow drying, making it possible to form complex hierarchical architectures.

Radiation-induced effects on the extraction properties of hexa-n-octylnitrilo-triacetamide (HONTA) complexes of americium and europium.

The candidate An(iii)/Ln(iii) separation ligand hexa-n-octylnitrilo-triacetamide (HONTA) was irradiated under envisioned SELECT (Solvent Extraction from Liquid waste using Extractants of CHON-type for Transmutation) process conditions (n-dodecane/0.1 M HNO3) using a solvent test loop in conjunction with cobalt-60 gamma irradiation. The extent of HONTA radiolysis and complementary degradation product formation was quantified by HPLC-ESI-MS/MS. Further, the impact of HONTA radiolysis on process performance was evaluated by measuring the change in 243Am and 154Eu distribution ratios as a function of absorbed gamma dose. HONTA was found to decay exponentially with increasing dose, affording a dose coefficient of d = (4.48 ± 0.19) × 10-3 kGy-1. Multiple degradation products were detected by HPLC-ESI-MS/MS with dioctylamine being the dominant quantifiable species. Both 243Am and 154Eu distribution ratios exhibited an induction period of ∼70 kGy for extraction (0.1 M HNO3) and back-extraction (4.0 M HNO3) conditions, after which both values decreased with absorbed dose. The decrease in distribution ratios was attributed to a combination of the destruction of HONTA and ingrowth of dioctylamine, which is capable of interfering in metal ion complexation. The loss of HONTA with absorbed gamma dose was predominantly attributed to its reaction with the n-dodecane radical cation (R˙+). These R˙+ reaction kinetics were measured for HONTA and its 241Am and 154Eu complexes using picosecond pulsed electron radiolysis techniques. All three second-order rate coefficients (k) were essentially diffusion limited in n-dodecane indicating a significant reaction pathway: k(HONTA + R˙+) = (7.6 ± 0.8) × 109 M-1 s-1, k(Am(HONTA)2 + R˙+) = (7.1 ± 0.7) × 1010 M-1 s-1, and k(Eu(HONTA)2 + R˙+) = (9.5 ± 0.5) × 1010 M-1 s-1. HONTA-metal ion complexation afforded an order-of-magnitude increase in rate coefficient. Nanosecond time-resolved measurements showed that both direct and indirect HONTA radiolysis yielded the short-lived (<100 ns) HONTA radical cation and a second long-lived (µs) species identified as the HONTA triplet excited state. The latter was confirmed by a series of oxygen quenching picosecond pulsed electron measurements, affording a quenching rate coefficient of k(3[HONTA]* + O2) = 2.2 × 108 M-1 s-1. Overall, both the HONTA radical cation and triplet excited state are important precursors to the suite of measured HONTA degradation products.

Abemaciclib-induced epithelial-mesenchymal transition mediated by cyclin-dependent kinase 4/6 independent of cell cycle arrest pathway.

Abemaciclib (ABM), a cyclin-dependent kinase 4/6 inhibitor, shows pharmacological effects in cell cycle arrest. Epithelial-mesenchymal transition is an important cellular event associated with pathophysiological states such as organ fibrosis and cancer progression. In the present study, we evaluated the contribution of factors associated with cell cycle arrest to ABM-induced epithelial-mesenchymal transition. Treatment with 0.6 µM ABM induced both cell cycle arrest and epithelial-mesenchymal transition-related phenotypic changes. Interestingly, the knockdown of cyclin-dependent kinase 4/6, pharmacological targets of ABM or cyclin D1, which forms complexes with cyclin-dependent kinase 4/6, resulted in cell cycle arrest at the G1-phase and induction of epithelial-mesenchymal transition, indicating that downregulation of cyclin-dependent kinase 4/6-cyclin D1 complexes would mimic ABM. In contrast, knockdown of the Rb protein, which is phosphorylated by cyclin-dependent kinase 4/6, had no effect on the expression level of α-smooth muscle actin, an epithelial-mesenchymal transition marker. Furthermore, ABM-induced epithelial-mesenchymal transition was not affected by Rb knockdown, suggesting that Rb is not involved in the transition process. Our study is the first to suggest that cyclin-dependent kinase 4/6-cyclin D1 complexes, as pharmacological targets of ABM, may contribute to ABM-induced epithelial-mesenchymal transition, followed by clinical disorders such as organ fibrosis and cancer progression. This study suggests that blocking epithelial-mesenchymal transition might be a promising way to prevent negative side effects caused by a medication (ABM) without affecting its ability to treat the disease.

UO2 dissolution in bicarbonate solution with H2O2: the effect of temperature.

Upon nuclear waste canister failure and contact of spent nuclear fuel with groundwater, the UO2 matrix of spent fuel will interact with oxidants in the groundwater generated by water radiolysis. Bicarbonate (HCO3-) is often found in groundwater, and the H2O2 induced oxidative dissolution of UO2 in bicarbonate solution has previously been studied under various conditions. Temperatures in the repository at the time of canister failure will differ depending on the location, yet the effect of temperature on oxidative dissolution is unknown. To investigate, the decomposition rate of H2O2 at the UO2 surface and dissolution of UVI in bicarbonate solution (0.1, 1, 10 and 50 mM) was analysed at various temperatures (10, 25, 45 and 60 °C). At [HCO3-] ≥ 1 mM, the concentration of dissolved UVI decreased with increasing temperature. This was attributed to the formation of UVI-bicarbonate species at the surface and a change in the mechanism of H2O2 decomposition from oxidative to catalytic. At 0.1 mM, no obvious correlation between temperature and U dissolution was observed, and thermodynamic calculations indicated this was due to a change in the surface species. A pathway to explain the observed dissolution behaviour of UO2 in bicarbonate solution as a function of temperature was proposed.

Temperature dependent absorption spectra of Br(-), Br2(•-), and Br3(-) in aqueous solutions.

The absorption spectra of Br(2)(•-) and Br(3)(-) in aqueous solutions are investigated by pulse radiolysis techniques from room temperature to 380 and 350 °C, respectively. Br(2)(•-) can be observed even in supercritical conditions, showing that this species could be used as a probe in pulse radiolysis at high temperature and even under supercritical conditions. The weak temperature effect on the absorption spectra of Br(2)(•-) and Br(3)(-) is because, in these two systems, the transition occurs between two valence states; for example, for Br(2)(-) we have (2)Σ(u) → (2)Σ(g) transition. These valence transitions involve no diffuse final state. However, the absorption band of Br(-) undergoes an important red shift to longer wavelengths. We performed classical dynamics of hydrated Br(-) system at 20 and 300 °C under pressure of 25 MPa. The radial distribution functions (rdf's) show that the strong temperature increase (from 20 to 300 °C) does not change the radius of the solvent first shell. On the other hand, it shifts dramatically (by 1 Å) the second maximum of the Br-O rdf and introduces much disorder. This shows that the first water shell is strongly bound to the anion whatever the temperature. The first two water shells form a cavity of a roughly spherical shape around the anion. By TDDFT method, we calculated the absorption spectra of hydrated Br(-) at two temperatures and we compared the results with the experimental data.

The kinetics and mechanism of H2O2 decomposition at the U3O8 surface in bicarbonate solution.

In the event of nuclear waste canister failure in a deep geological repository, groundwater interaction with spent fuel will lead to dissolution of uranium (U) into the environment. The rate of U dissolution is affected by bicarbonate (HCO3 -) concentrations in the groundwater, as well as H2O2 produced by water radiolysis. To understand the dissolution of U3O8 by H2O2 in bicarbonate solution (0.1-50 mM), dissolved U concentrations were measured upon H2O2 addition (300 µM) to U3O8/bicarbonate mixtures. As the H2O2 decomposition mechanism is integral to the dissolution of U3O8, the kinetics and mechanism of H2O2 decomposition at the U3O8 surface was investigated. The dissolution of U3O8 increased with bicarbonate concentration which was attributed to a change in the H2O2 decomposition mechanism from catalytic at low bicarbonate (≤5 mM HCO3 -) to oxidative at high bicarbonate (≥10 mM HCO3 -). Catalytic decomposition of H2O2 at low bicarbonate was attributed to the formation of an oxidised surface layer. Second-order rate constants for the catalytic and oxidative decomposition of H2O2 at the U3O8 surface were 4.24 × 10-8 m s-1 and 7.66 × 10-9 m s-1 respectively. A pathway to explain both the observed U3O8 dissolution behaviour and H2O2 decomposition as a function of bicarbonate concentration was proposed.

Transfection with pax6 gene of mouse embryonic stem cells and subsequent cell cloning induced retinal neuron progenitors, including retinal ganglion cell-like cells, in vitro.

OBJECTIVE: It is theoretically possible to induce various cell types, including retinal neurons, from embryonic stem cells (ESCs). pax6 regulates early events in eye development, including the generation of retinal ganglion cells (RGCs). We previously reported the successful induction of corneal epithelial cells from ESCs transfected with the pax6 gene. Here, we attempted to establish cloned RGC-like cells from ESCs transfected with the pax6 gene. METHODS: Undifferentiated mouse ESCs were transfected with pax6 cDNA by electroporation, followed by selection with G418. We conducted limiting-dilution culture of pax6-transfected cells. We expanded the cloned pax6-transfected cells, which expressed nestin and musashi-1, for further characterization in culture media containing fibronectin. The cells were characterized using RT-PCR, immunostaining, electron microscopy, renal subcapsular transplantation assay and Ca imaging. RESULTS: We obtained clonally expanding pax6-transfected cells, all of which were positive for six3, sonic hedgehog (shh), math5, brn3, thy1 and melanopsin, by using several ESCs. When transplanted into a mouse renal capsule, they differentiated into neurons with elongated axons, expressing betaIII tubulin and neurofilament middle chain, and were free from teratoma development. Electron-microscopic examination showed neurotubules and neurofilaments in the axon-like processes of the cloned pax6-transfected cells. High KCl stimulation increased free Ca influx on Ca2+ imaging. CONCLUSIONS: ESCs were applicable for the induction of retinal progenitor cells, including RGC-like cells, by transfection with the pax6 gene and subsequent limiting-dilution culture. Cloned cell lines may be useful to analyze the requirements for retinal progenitor cell differentiation, and our study suggests the clinical application of this cell type.

γ-Radiation and H2O2 induced oxidative dissolution of uranium(iv) oxide in aqueous solution containing phthalic acid.

This study aims to reveal possible involvements of organic acids in the oxidative dissolution of UO2. Using phthalic acid as a model compound, we have measured adsorption on UO2 and investigated effects on the reaction between H2O2 and UO2 and on oxidative dissolution induced by γ-irradiation. Significant adsorption of phthalic acid was observed even at neutral pH. However, the reaction between H2O2 and UO2 in phthalic acid solution induced oxidative dissolution of U(vi) similar to in aqueous bicarbonate solution. Moreover, degradation products of phthalic acid were not detected after the reaction of H2O2. These results indicate that even though phthalic acid adsorbs on the UO2 surface, it is not involved in the interfacial reaction of H2O2. In contrast, the dissolution of U by irradiation was inhibited in aqueous phthalic acid solution, whereas H2O2 generated by radiolysis was consumed by UO2. Based on these contrasting results, possible roles of radical species generated by water radiolysis were discussed.

Spectroscopic Studies of Mössbauer, Infrared, and Laser-Induced Luminescence for Classifying Rare-Earth Minerals Enriched in Iron-Rich Deposits.

Rare-earth (RE) phosphates often appear as an accessory phase in igneous or metamorphic rocks; however, these rocks are composed of myriad chemical elements and nuclides that interfere with the qualitative or quantitative analyses of the RE phosphates over a range of concentrations in the absence of a pretreatment. In addition, the limit of each analytical methodology constrains the approach as well as the usefulness of the results in geoscience applications. Here, we report the specific mineral characterization of RE-containing ores from Yen Phu mine, Vietnam, using a range of state-of-the-art spectroscopic techniques in conjunction with microscopy: Mössbauer spectroscopy, infrared microspectroscopy, time-resolved laser-induced fluorescence spectroscopy (TRLFS), and scanning electron microscopy with energy-dispersive X-ray spectroscopy. Because the distribution of each element in the deposit differs, such combinatorial works are necessary and could lead to more plausible answers to questions surrounding the point of origin of RE elements. The results of our Mössbauer spectroscopic analysis indicate that the three ores sampled at different locations all contain magnetite-like, hematite-like, and iron(III) salts other than hematite. In addition, we confirmed the presence of phosphate around the grain boundary in the magnetite-like mineral phase by infrared microspectroscopic analysis. The present analytical findings of trace amounts of europium(III) using TRLFS suggest that the europium ions generate identical luminescence spectra despite being embedded in three different matrices of iron minerals. This demonstration highlights the benefits of combinatorial spectroscopic analyses to gain insights into the effects of the environment of REs on their solid-state chemistry and shows the potential utility of TRLFS as a resource mining tool. Further applications of this approach in the analytical screening of rocks and minerals are feasible.

Experimental transplantation of corneal epithelium-like cells induced by Pax6 gene transfection of mouse embryonic stem cells.

PURPOSE: Corneal epithelial stem cells are deficient in cases of limbal disorders, leading to conjunctival epithelial ingrowth, vascularization, and eventually visual disturbance. We introduced the eye development-associated transcription factor pax6 to embryonic stem (ES) cells and tested whether pax6-transfected cells resembling purified corneal epithelial cells were applicable as a cell source for corneal transplantation. METHODS: pax6 cDNA with green fluorescence protein was electrotransfected to ES cells and the cells were cultured with G418 for 14 days. They were characterized by reverse transcription-polymerase chain reaction and immunohistochemistry. The cells were transplanted onto experimentally damaged mouse corneas. Histologic reconstitution of the corneal epithelium was assessed. RESULTS: pax6-transfected cells formed a monolayer of epithelium-like cells in vitro. They expressed cytokeratin12, a specific keratin of corneal epithelial cells, E-cadherin, and CD44, which are important adhesion molecules of corneal epithelial cells on the cell membrane. They accumulated to make a colony that gave a staining pattern of reticular configuration for cytokeratin 12, E-cadherin, and CD44. When the cells were transplanted onto damaged cornea, they have been kept alive on the cornea. CONCLUSIONS: The purified corneal epithelium-like cells derived from ES cells transfected with pax6 gene adapted to the injured cornea and were kept alive on it. These results suggested application of ES cell-derived corneal epithelial cells for treating corneal injuries.

Alterations in the corneal nerve and stem/progenitor cells in diabetes: preventive effects of insulin-like growth factor-1 treatment.

This study aimed to investigate whether corneal nerve and corneal stem/progenitor cells are altered in insulin-like growth factor-I (IGF-I-) treated individuals with diabetes. A group consisting of db/db mice with type 2 diabetes mellitus (DM) and a wild-type group were assessed by neural and corneal stem/progenitor cell markers immunostaining and real-time PCR. Moreover, the expression of corneal nerve and stem/progenitor cell markers was examined in IGF-1-treated diabetic mice. Compared with a normal cornea, swelling and stratification of the corneal epithelium were noted in db/db mice. Beta-III tubulin immunostaining revealed that the corneal subbasal plexuses in diabetic mice were thinner with fewer branches. mRNA expression levels of Hes1, Keratin15, and p75 (corneal stem/progenitor cell markers) and the intensity and number of positive cells of Hes1 and Keratin19 immunostaining diminished in the diabetic corneas. Compared with the subbasal nerve density in the normal group, a decrease in the diabetic group was observed, whereas the corneal subbasal nerve density increased in IGF-1-treated diabetic group. The decreased expression of Hes1 and Keratin19 was prevented in IGF-1-treated diabetic group. Our data suggest that corneal nerve and stem/progenitor cells are altered in type 2 DM, and IGF-I treatment is capable of protecting against corneal damage in diabetes.

Imaging of a severe case of acute hydrops in a patient with keratoconus using anterior segment optical coherence tomography.

AIM: To investigate the clinical and diagnostic findings of a patient with acute hydrops using anterior segment optical coherence tomography (AS-OCT). METHODS: The AS-OCT findings of a 43-year-old patient with acute hydrops associated with keratoconus were examined. At the initial examination and during follow-up, evaluation of the anterior segment was performed. RESULTS: The patient presented with decreased visual acuity, pain, and redness in the right eye. The symptoms, clinical presentation, and topographical findings of the right eye confirmed the diagnosis of acute corneal hydrops. Changes in the stroma and Descemet's membrane during the healing process of acute hydrops could be demonstrated by high-resolution AS-OCT. The use of contact lenses was improved at the last follow-up visit after 8 months and increased visual acuity to 20/20 with correction. CONCLUSIONS: AS-OCT is a useful tool for studying the morphologic features of acute hydrops.

Induction of corneal epithelium-like cells from cynomolgus monkey embryonic stem cells and their experimental transplantation to damaged cornea.

PURPOSE: We previously reported the successful transplantation of corneal epithelium-like cells derived from mouse embryonic stem (ES) cells onto injured mouse cornea. Here, we tested whether nonhuman primate ES cells have ability to differentiate into corneal epithelial cells and whether monkey ES cell-derived corneal epithelium-like cells were applicable for the experimental transplantation to damaged cornea. METHODS: Monkey ES cells were cultivated on type IV collagen-coated dishes for various days to induce differentiation into corneal epithelium-like cells. The differentiation was evaluated by reverse transcription-polymerase chain reaction and immunostaining. The corneal epithelium-like cells were transplanted to the injured mouse cornea. Reconstitution of the corneal epithelium was evaluated by immunostaining. RESULTS: The cells cultured on type IV collagen showed cobblestone-like appearance resembling epithelial cells. They expressed messenger RNA of pax6, p63, E-cadherin, CD44, proliferating cell nuclear antigen, keratin 3, and keratin 12. Protein expressions of pax6, keratin 3/12, p63, proliferating cell nuclear antigen, E-cadherin, and CD44 were confirmed by immunostaining. When the corneal epithelium-like cells were transplanted, they adhered to the corneal stroma, leading to formation of multiple cell layers. The grafted cells were stained with anti-human nuclear protein antibody, which cross-reacted with nuclei of monkey cells but not with those of mouse cells. They retained the expressions of keratin 3/12, E-cadherin, and CD44. CONCLUSIONS: We induced corneal epithelium-like cells from monkey ES cells with moderate efficiency. The cells were successfully transplanted onto the injured mouse cornea. This is the first demonstration that nonhuman primate ES cells were induced to differentiate into corneal epithelium-like cells, which were applicable for transplantation to an animal model of corneal injury.

Temperature effect on the absorption spectrum of the hydrated electron paired with a lithium cation in deuterated water.

The absorption spectra of the hydrated electron in 1.0 to 4.0 M LiCl or LiClO4 deuterated water solutions were measured by pulse radiolysis techniques from room temperature to 300 degrees C at a constant pressure of 25 MPa. The results show that when the temperature is increased and the density is decreased, the absorption spectrum of the electron in the presence of a lithium cation is shifted to lower energies. Quantum classical molecular dynamics (QCMD) simulations of an excess electron in bulk water and in the presence of a lithium cation have been performed to compare with the experimental results. According to the QCMD simulations, the change in the shape of the spectrum is due to one of the three p-like excited states of the solvated electron destabilized by core repulsion. The study of s --> p transition energies for the three p-excited states reveals that for temperatures higher than room temperature, there is a broadening of each individual s --> p absorption band due to a less structured water solvation shell.