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The inâ situ confinement of nickel (Ni)-iron (Fe) nanoparticles (NPs) in a polymer-derived microporous silicon carboxynitride (Si-C-O-N)-based support is investigated to stimulate superior oxygen evolution reaction (OER) activity in an alkaline media. Firstly, we consider a commercial polysilazane (PSZ) and Ni and Fe chlorides to be mixed in N,N-dimethylformamide (DMF) and deliver after overnight solvent reflux a series of Ni-Fe : organosilicon coordination polymers. The latter are then heat-treated at 500 °C in flowing argon to form the title compounds. By considering a Ni : Fe ratio of 1.5, face centred cubic (fcc) NixFey alloy NPs with a size of 15-30â nm are inâ situ generated in a porous Si-C-O-N-based matrix displaying a specific surface area (SSA) as high as 237â m2 â g-1. Hence, encapsulated NPs are rendered accessible to promote electrocatalytic water oxidation. An OER overpotential as low as 315â mV at 10â mA â cm-2 is measured. This high catalytic performance (considering that the metal mass loading is as low as 0.24â mg cm-2) is rather stable as observed after an activation step; thus, validating our synthesis approach. This is clearly attributed to both the strong NP-matrix interaction and the confinement effect of the matrix as highlighted through post mortem microscopy observations.
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Caffeic acid (CA) exhibits a myriad of biological activities including cardioprotective action, antioxidant, antitumor, anti-inflammatory, and antimicrobial properties. On the other hand, CA presents low water solubility and poor bioavailability, which have limited its use for therapeutic applications. The objective of this study was to develop a nanohybrid of zinc basic salts (ZBS) and chitosan (Ch) containing CA (ZBS-CA/Ch) and evaluate its anti-edematogenic and antioxidant activity in dextran and carrageenan-induced paw edema model. The samples were obtained by coprecipitation method and characterized by X-ray diffraction, Fourier transform infrared (FT-IR), scanning electron microscope (SEM) and UV-visible spectroscopy. The release of caffeate anions from ZBS-CA and ZBS-CA/Ch is pH-dependent and is explained by a pseudo-second order kinetics model, with a linear correlation coefficient of R2 ≥ 0.99 at pH 4.8 and 7.4. The in vivo pharmacological assays showed excellent anti-edematogenic and antioxidant action of the ZBS-CA/Ch nanoparticle with slowly releases of caffeate anions in the tissue, leading to a prolongation of CA-induced anti-edematogenic and anti-inflammatory activities, as well as improving its inhibition or sequestration antioxidant action toward reactive species. Overall, this study highlighted the importance of ZBS-CA/Ch as an optimal drug carrier.
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Quitosano , Humanos , Quitosano/química , Preparaciones de Acción Retardada/química , Espectroscopía Infrarroja por Transformada de Fourier , Antioxidantes/farmacología , Antiinflamatorios/farmacología , Edema/patología , Zinc/químicaRESUMEN
We synthesized nickel (Ni) nanoparticles (NPs) in a high specific surface area (SSA) p-block element-containing inorganic compound prepared via the polymer-derived ceramics (PDC) route to dispatch the obtained nanocomposite towards oxygen evolution reaction (OER). The in situ formation of Ni NPs in an amorphous silicon carboxynitride (Si-C-O-N(H)) matrix is allowed by the reactive blending of a polysilazane, NiCl2 and DMF followed by the subsequent thermolysis of the Ni : organosilicon polymer coordination complex at a temperature as low as 500 °C in flowing argon. The final nanocomposite displays a BET SSA as high as 311 m2 g-1 while the structure of the NPs corresponds to face-centred cubic (fcc) Ni along with interstitial-atom free (IAF) hexagonal close-packed (hcp) Ni as revealed by XRD. A closer look into the compound through FEG-SEM microscopy confirms the formation of pure metallic Ni, while HR-TEM imaging reveals the occurrence of Ni particles featuring a fcc phase and surrounded by carbon layers; thus, forming core-shell structures, along with Ni NPs in an IAF hcp phase. By considering that this newly synthesized material contains only Ni without doping (e.g., Fe) with a low mass loading (0.15 mg cm-2), it shows promising OER performances with an overpotential as low as 360 mV at 10 mA cm-2 according to the high SSA matrix, the presence of the IAF hcp Ni NPs and the development of core-shell structures. Given the simplicity, the flexibility, and the low cost of the proposed synthesis approach, this work opens the doors towards a new family of very active and stable high SSA nanocomposites made by the PDC route containing well dispersed and accessible non-noble transition metals for electrocatalysis applications.
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From early April 2020, wildfires raged in the highly contaminated areas around the Chernobyl nuclear power plant (CNPP), Ukraine. For about 4 weeks, the fires spread around and into the Chernobyl exclusion zone (CEZ) and came within a few kilometers of both the CNPP and radioactive waste storage facilities. Wildfires occurred on several occasions throughout the month of April. They were extinguished, but weather conditions and the spread of fires by airborne embers and smoldering fires led to new fires starting at different locations of the CEZ. The forest fires were only completely under control at the beginning of May, thanks to the tireless and incessant work of the firefighters and a period of sustained precipitation. In total, 0.7-1.2 TBq 137Cs were released into the atmosphere. Smoke plumes partly spread south and west and contributed to the detection of airborne 137Cs over the Ukrainian territory and as far away as Western Europe. The increase in airborne 137Cs ranged from several hundred µBq·m-3 in northern Ukraine to trace levels of a few µBq·m-3 or even within the usual background level in other European countries. Dispersion modeling determined the plume arrival time and was helpful in the assessment of the possible increase in airborne 137Cs concentrations in Europe. Detections of airborne 90Sr (emission estimate 345-612 GBq) and Pu (up to 75 GBq, mostly 241Pu) were reported from the CEZ. Americium-241 represented only 1.4% of the total source term corresponding to the studied anthropogenic radionuclides but would have contributed up to 80% of the inhalation dose.
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Contaminantes Radiactivos del Aire , Accidente Nuclear de Chernóbil , Incendios , Incendios Forestales , Contaminantes Radiactivos del Aire/análisis , Radioisótopos de Cesio/análisis , Europa (Continente) , UcraniaRESUMEN
The ALLIANCE Strategic Research Agenda (SRA) for radioecology is a living document that defines a long-term vision (20 years) of the needs for, and implementation of, research in radioecology in Europe. The initial SRA, published in 2012, included consultation with a wide range of stakeholders (Hinton et al., 2013). This revised version is an update of the research strategy for identified research challenges, and includes a strategy to maintain and develop the associated required capacities for workforce (education and training) and research infrastructures and capabilities. Beyond radioecology, this SRA update constitutes a contribution to the implementation of a Joint Roadmap for radiation protection research in Europe (CONCERT, 2019a). This roadmap, established under the H2020 European Joint Programme CONCERT, provides a common and shared vision for radiation protection research, priority areas and strategic objectives for collaboration within a European radiation protection research programme to 2030 and beyond. Considering the advances made since the first SRA, this updated version presents research challenges and priorities including identified scientific issues that, when successfully resolved, have the potential to impact substantially and strengthen the system and/or practice of the overall radiation protection (game changers) in radioecology with regard to their integration into the global vision of European research in radiation protection. An additional aim of this paper is to encourage contribution from research communities, end users, decision makers and other stakeholders in the evaluation, further advancement and accomplishment of the identified priorities.
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Monitoreo de Radiación , Protección Radiológica , Europa (Continente)RESUMEN
The atomic scale structure of amorphous AsTe3 is investigated through X-ray diffraction, first-principles molecular dynamics (FPMD), and machine learning interatomic potentials (ML-GAP) obtained by exploiting the ab initio data. We obtain good agreement between the measured and modelled diffraction patterns. Our FPMD results show that As and Te obey the 8-N rule with average coordination numbers of 3 and 2, respectively. We find that small fractions of under and over coordinated As and Te atoms are present in the amorphous phase with about 6% (FPMD), and 13% (ML-GAP) of 3-fold Te. As is found at the center of pyramidal structures predominantly linked through Ten chains rather than rings. Despite the low As concentration in AsTe3, its local environment features a very high chemical disorder that manifests through the occurrence of homopolar bonds including at least 57% of As atoms.
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210Po and 210Pb represent the most abundant part of atmospheric aerosol long-lived natural radioactivity. Moreover, 210Pb-210Po monitoring in the atmosphere can be of interest for tracking extreme natural events that can enhance the level of alpha/beta radioactivity in air. In this paper, we question the possibility to use routine gross alpha/beta measurements in order to monitor 210Po, 210Pb and 210Po/210Pb ratio in the atmosphere. Based on joint gross alpha/beta measurement and 210Pb-210Po specific determination on 16 atmosphere samples, we show that (i) gross beta activity systematically overestimates 210Pb activity due to the presence of interfering beta emitters and (ii) gross alpha activity mostly reflects 210Po activity even if an underestimation is always observed due to alpha particle attenuation in the sample. In order to determine 210Po/210Pb ratio, we discuss the advantages of using gross alpha activity time variation compared to specific 210Po measurements. Finally, the gross alpha/beta ratio appear to be a good proxy of the 210Po/210Pb ratio when large-scale variations are to be monitored. We report a first reference level for the activity level of airborne 210Po in France of 13 ± 6 µBq/m3.
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Contaminantes Radiactivos del Aire/análisis , Radioisótopos de Plomo/análisis , Polonio/análisis , Monitoreo de Radiación , Partículas alfa , Atmósfera/química , Partículas beta , Francia , PlomoRESUMEN
In this work, the phase purity and size of zirconia nanocrystals samples were studied in terms of zirconium concentration, added water content, and subsequent use of a post solvothermal treatment. The progressive tetragonal-to-monoclinic transformation of zirconia sample was observed to be strongly related to the water content of the alcoholic medium. But more surprisingly, it has been shown that even under initially anhydrous conditions and for particle size below 5 nm, the phase purity of the samples was deteriorated by a side-reaction of alcohol dehydration catalyzed by the surface of the nanoparticles (NPs). Since the phase transformation is essentially driven by the water content of the reaction mixture, we have shown that it was possible to recover an excellent phase purity without the help of any usual dopants by adding a strong alkaline desiccating agent. Provided that a sufficient sodium to zirconium ratio was ensured, the formation of the monoclinic phase was not observed whatever the zirconium precursor concentration. The effectiveness of this cure was related to the ability of sodium metal to generate reactive alkoxide able to neutralize water and to catalyze an alternative sol-gel mechanism leading to the formation of the t-ZrO2 NPs.
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BACKGROUND: The ability of solid tumor cells to resist anoikis, apoptosis triggered by cell detachment from the extracellular matrix (ECM), is thought to be critical for 3D tumor growth. ErbB2/Her2 oncoprotein is often overproduced by breast tumor cells and blocks their anoikis by partially understood mechanisms. In our effort to understand them better, we observed that detachment of nonmalignant human breast epithelial cells from the ECM upregulates the transcription factor Irf6. Irf6 is thought to play an important role in mammary gland homeostasis and causes apoptosis by unknown mechanisms. We noticed that ErbB2, when overproduced by detached breast epithelial cells, downregulates Irf6. METHODS: To test whether ErbB2 downregulates Irf6 in human ErbB2-positive breast cancer cells, we examined the effect of ErbB2 inhibitors, such as the anti-ErbB2 antibody trastuzumab or the ErbB2/epidermal growth factor receptor small-molecule inhibitor lapatinib, on Irf6 in these cells. Moreover, we performed Irf6 IHC analysis of tumor samples derived from the locally advanced ErbB2-positive breast cancers before and after neoadjuvant trastuzumab-based therapies. To examine the role of Irf6 in anoikis of nonmalignant and ErbB2-overproducing breast epithelial cells, we studied anoikis after knocking down Irf6 in the former cells by RNA interference and after overproducing Irf6 in the latter cells. To examine the mechanisms by which cell detachment and ErbB2 control Irf6 expression in breast epithelial cells, we tested the effects of genetic and pharmacological inhibitors of the known ErbB2-dependent signaling pathways on Irf6 in these cells. RESULTS: We observed that trastuzumab and lapatinib upregulate Irf6 in ErbB2-positive human breast tumor cells and that neoadjuvant trastuzumab-based therapies tend to upregulate Irf6 in human breast tumors. We found that detachment-induced Irf6 upregulation in nonmalignant breast epithelial cells requires the presence of the transcription factor ∆Np63α and that Irf6 mediates their anoikis. We showed that ErbB2 blocks Irf6 upregulation in ErbB2-overproducing cells by activating the mitogen-activated protein kinases that inhibit ∆Np63α-dependent signals required for Irf6 upregulation. Finally, we demonstrated that ErbB2-driven Irf6 downregulation in ErbB2-overproducing breast epithelial cells blocks their anoikis and promotes their anchorage-independent growth. CONCLUSIONS: We have demonstrated that ErbB2 blocks anoikis of breast epithelial cells by downregulating Irf6.
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Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Transformación Celular Neoplásica/patología , Factores Reguladores del Interferón/metabolismo , Receptor ErbB-2/metabolismo , Anoicis/efectos de los fármacos , Antineoplásicos/uso terapéutico , Biopsia , Mama/citología , Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Técnicas de Cultivo de Célula , Línea Celular , Estudios de Cohortes , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Femenino , Humanos , Factores Reguladores del Interferón/genética , Terapia Neoadyuvante/métodos , Proyectos Piloto , ARN Interferente Pequeño/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The local structure of apatite-type lanthanum silicates of general formula La9.33+x(SiO4)6O2+3x/2 has been investigated by combining the atomic pair distribution function (PDF) method, conventional X-ray and neutron powder diffraction (NPD) data and density functional theory (DFT) calculations. DFT was used to build structure models with stable positions of excess oxide ions within the conduction channel. Two stable interstitial positions were obtained in accordance with literature, the first one located at the very periphery of the conduction channel, neighbouring the SiO4 tetrahedral units, and the second one closer to the channel axis. The corresponding PDFs and average structures were then calculated and tested against experimental PDFs obtained by X-ray total scattering and NPD Rietveld refinements results gathered from literature. It was shown that of the two stable interstitial positions obtained with DFT only the second one located within the channel is consistent with experimental data. This result consolidates one of the two main conduction mechanisms along the c-axis reported in the literature, namely the one involving cooperative movement of O4 and Oi ions.
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In the present paper the activity of uranium isotopes measured in plants and aerosols taken downwind of the releases of three nuclear fuel settlements was compared between them and with the activity measured at remote sites. An enhancement of 238U activity as well as 235U/238U anomalies and 236U are noticeable in wheat, grass, tree leaves and aerosols taken at the edge of nuclear fuel settlements, which show the influence of uranium chronic releases. Further plants taken at the edge of the studied sites and a few published data acquired in the same experimental conditions show that the 238U activity in plants is influenced by the intensity of the U atmospheric releases. Assuming that 238U in plant is proportional to the intensity of the releases, we proposed empirical relationships which allow to characterize the chronic releases on the ground. Other sources of U contamination in plants such as accidental releases and "delayed source" of uranium in soil are also discussed in the light of uranium isotopes signatures.
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Modelos Químicos , Monitoreo de Radiación/métodos , Contaminantes Radiactivos del Suelo/análisis , Uranio/análisis , CalibraciónRESUMEN
The Fukushima-labeled air mass arrival, and later the cesium-134 (134Cs), cesium-137 (137Cs) and particulate iodine-131 (hereafter noted 131Ip) maximum levels were registered in Europe at different dates depending on the location. Most of those data were obtained at low-altitude sampling areas. Here, we compare the airborne levels registered at different high-altitude European locations (from 850 m to about 3500 m). The integrated 137Cs activity concentration was not uniform with regard to the altitude even after a long travel time/distance from Japan. Moreover, the relation of integrated 137Cs vs. altitude showed a linear decrease up to an altitude of about 3000 m. A similar trend was noticed for 131Ip (particulate fraction) while it increased above 3000 m. Comparison with 7Be activity concentration showed that, as far as the high altitude location is concerned, the 137Cs and 134Cs maximum concentrations corresponded to the 7Be maximum, suggesting downdraft movements from high tropospheric or stratospheric layers to be responsible for 137,134Cs increase and peak values. This was also confirmed by high potential vorticity and low relative humidity registered during the peak values.
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Contaminantes Radiactivos del Aire/análisis , Radioisótopos de Cesio/análisis , Accidente Nuclear de Fukushima , Monitoreo de Radiación , Altitud , Atmósfera/química , Berilio/análisis , Europa (Continente) , JapónRESUMEN
Airborne activity levels of uranium and thorium series were measured in the vicinity (1.1 km) of a uranium (UF4) processing plant, located in Malvési, south of France. Regarding its impact on the environment, this facility is characterized by its routine atmospheric releases of uranium and by the emission of radionuclide-labelled particles from a storage pond filled with waste water or that contain dried sludge characterized by traces of plutonium and thorium ((230)Th). This study was performed during a whole year (November 2009-November 2010) and based on weekly aerosol sampling. Thanks to ICP-MS results, it was possible to perform investigations of uranium and thorium decay product concentration in the air. The number of aerosol filters sampled (50) was sufficient to establish a relationship between airborne radionuclide variations and the wind conditions. As expected, the more the time spent in the plume, the higher the ambient levels. The respective contributions of atmospheric releases and resuspension from local soil and waste ponds on ambient dust load and uranium-bearing aerosols were estimated. Two shutdown periods dedicated to facility servicing made it possible to estimate the resuspension contribution and to specify its origin (local or regional) according to the wind direction and remote background concentration. Airborne uranium mainly comes from the emission stack and, to a minor extent (â¼20%), from wind resuspension of soil particles from the surrounding fields and areas devoted to waste storage. Moreover, weighed activity levels were clearly higher during operational periods than for shutdown periods.
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Contaminantes Radiactivos del Aire/análisis , Contaminantes Radiactivos del Suelo/análisis , Torio/análisis , Uranio/análisis , Contaminantes Radiactivos del Agua/análisis , Francia , Espectrometría de Masas , Estaciones del Año , VientoRESUMEN
In this work we present for the first time empirical interatomic potentials that are able to reproduce TeO2-based systems. Using these potentials in classical molecular dynamics simulations, we obtained first results for the pure TeO2 glass structure model. The calculated pair distribution function is in good agreement with the experimental one, which indicates a realistic glass structure model. We investigated the short- and medium-range TeO2 glass structures. The local environment of the Te atom strongly varies, so that the glass structure model has a broad Q polyhedral distribution. The glass network is described as weakly connected with a large number of terminal oxygen atoms.
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Metal oxides are widely used in devices such as sensors, fuel cells, and oxygen permeation membranes. Understanding the oxide ion migration mechanism would provide fundamental insights into the relationships between the structure and properties such as ionic conductivity. The Ruddlesden-Popper perovskite (Sr,La)n+1(Fe,Co)nO3n+1 (n = 2) has characteristic oxygen permeation and ion conduction properties, resulting from the layered perovskite structure. To elucidate the ion migration mechanism in Sr2.46La0.54Fe2O7-δ (SLF) we used a combination of experimental techniques [X-ray powder diffraction (XRPD) and enthalpy investigations of the oxygen vacancy formation reaction] and computational techniques [the bond valence sum (BVS) approach and ab initio density functional theory (DFT)]. The structural analyses of SLF by XRPD and DFT agreed well. They showed that the oxygen vacancies in SLF are located at the O1 oxygen site, which is on the vertex shared by two FeO6 octahedra in the perovskite layer. Enthalpy of the oxygen vacancy formation changed at 830 °C. This is similar to the ionic conduction behavior reported for Sr3Fe2O7. The XRPD study indicates that the host structural framework did not change with temperature, while the oxygen/vacancy arrangement in SLF did change at 830 °C. The BVS and DFT studies suggested a change in the ion migration pathway, in which the ion migration through O1 sites becomes more important at temperatures higher than 830 °C.
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This study focused on parents' satisfaction with the special education and care services proposed to their child with autism spectrum disorders (ASD). Data were collected in three regions of France, using a questionnaire designed for the purpose of this study. Among the 530 families contacted, 212 filled in the questionnaire (response rate = 40.8%). Results showed that parents were globally satisfied with providers' involvement and motivation, but they felt they were not involved enough in their child's individualized program, that communication with providers was insufficient and that the services lacked ASD's specific tools and interventions. Among all families interviewed, parents of adolescents were the most unsatisfied and we hypothesized that this could be due to the specific issues regarding developmental changes and concern about the future at this period of life. Congruently with the literature, variables related to parental overall satisfaction were a regular communication with professionals, a specific, regularly updated individual program in which parents are associated, and specialized tools and interventions. The implications of these findings are discussed as well as future directions for clinicians to improve service delivery and allow the persons with ASD and their families to be more involved in the services.
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Trastornos Generalizados del Desarrollo Infantil/terapia , Comportamiento del Consumidor , Educación Especial , Servicios de Salud Mental , Padres , Adolescente , Niño , Preescolar , Femenino , Francia , Servicios de Salud , Humanos , Masculino , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Segregation and radioactive analysis of aerosols according to their aerodynamic size were performed in France, Austria, the Czech Republic, Poland, Germany, and Greece after the arrival of contaminated air masses following the nuclear accident at the Fukushima Dai-ichi nuclear power plant in March 2011. On the whole and regardless of the location, the highest activity levels correspond either to the finest particle fraction or to the upper size class. Regarding anthropogenic radionuclides, the activity median aerodynamic diameter (AMAD) ranged between 0.25 and 0.71 µm for (137)Cs, from 0.17 to 0.69 µm for (134)Cs, and from 0.30 to 0.53 µm for (131)I, thus in the "accumulation mode" of the ambient aerosol (0.1-1 µm). AMAD obtained for the naturally occurring radionuclides (7)Be and (210)Pb ranged from 0.20 to 0.53 µm and 0.29 to 0.52 µm, respectively. Regarding spatial variations, AMADs did not show large differences from place to place compared with what was observed concerning bulk airborne levels registered on the European scale. When air masses arrived in Europe, AMADs for (131)I were about half those for cesium isotopes. Higher AMAD for cesium probably results from higher AMAD observed at the early stage of the accident in Japan. Lower AMAD for (131)I can be explained by the adsorption of gaseous iodine on particles of all sizes met during transport, especially for small particles. Additionally, weathering conditions (rain) encountered during transport and in Europe in March and April contributed to the equilibrium of the gaseous to total (131)I ratio. AMAD slightly increased with time for (131)I whereas a clear decreasing trend was observed with the AMADs for (137)Cs and (134)Cs. On average, the associated geometric standard deviation (GSD) appeared to be higher for iodine than for cesium isotopes. These statements also bear out a gaseous (131)I transfer on ambient particles of a broad size range during transport. Highest weighted activity levels were found on the 0.49-0.95 µm and on the 0.18-0.36 µm size ranges in France and in Poland, respectively. The contribution from resuspension of old deposited (137)Cs was assessed for the coarse particle fractions only for the first sampling week.
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Contaminantes Radiactivos del Aire/análisis , Radioisótopos de Cesio/análisis , Accidente Nuclear de Fukushima , Radioisótopos de Yodo/análisis , Contaminantes Radiactivos del Aire/química , Radioisótopos de Cesio/química , Europa (Continente) , Radioisótopos de Yodo/química , Tamaño de la Partícula , Monitoreo de RadiaciónRESUMEN
The effects of intermolecular interactions of TeO(2) molecules in the (TeO(2))(n) oligomers on the polarizability (α) and second hyperpolarizability (γ) are investigated by the use of a density functional method. A significant intermolecular distance dependence of both quantities is observed. The huge dissociation-induced polarizability enhancement is analyzed in terms of the molecular orbital evolution. It is shown that the obtained results can provide a new look at the microscopic origin of the extraordinary dielectric properties of TeO(2) glass.
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The aspartic protease cathepsin D, a poor prognostic indicator of breast cancer, is abundantly secreted as procathepsin D by human breast cancer cells and self-activates at low pH in vitro, giving rise to catalytically active cathepsin D. Due to a lower extracellular pH in tumor microenvironments compared to normal tissues, cathepsin D may cleave pathophysiological substrates contributing to cancer progression. Here, we show by yeast 2-hybrid and degradomics analyses that cystatin C, the most potent natural secreted inhibitor of cysteine cathepsins, both binds to and is a substrate of extracellular procathepsin D. The amount of cystatin C in the extracellular environment is reduced in the secretome of mouse embryonic fibroblasts stably transfected with human cathepsin D. Cathepsin D extensively cleaved cystatin C in vitro at low pH. Cathepsin D secreted by breast cancer cells also processed cystatin C at the pericellular pH of tumors and so enhancing extracellular proteolytic activity of cysteine cathepsins. Thus, tumor derived cathepsin D assists breast cancer progression by reducing cystatin C activity, which, in turn, enhances cysteine cathepsin proteolytic activity, revealing a new link between protease classes in the protease web.