MVP and Vaults: a role in the radiation response

[EN] Vaults are evolutionary highly conserved ribonucleoproteins particles with a hollow barrel-like structure. The main component of vaults represents the 110 kDa major vault protein (MVP), whereas two minor vaults proteins comprise the 193 kDa vault poly(ADP-ribose) polymerase (vPARP) and the 240 kDa telomerase-associated protein-1 (TEP-1). Additionally, at least one small and untranslated RNA is found as a constitutive component. MVP seems to play an important role in the development of multidrug resistance. This particle has also been implicated in the regulation of several cellular processes including transport mechanisms, signal transmission and immune responses. Vaults are considered a prognostic marker for different cancer types. The level of MVP expression predicts the clinical outcome after chemotherapy in different tumour types. Recently, new roles have been assigned to MVP and vaults including the association with the insulin-like growth factor-1, hypoxia-inducible factor-1alpha, and the two major DNA double-strand break repair machineries: non-homologous endjoining and homologous recombination. Furthermore, MVP has been proposed as a useful prognostic factor associated with radiotherapy resistance. Here, we review these novel actions of vaults and discuss a putative role of MVP and vaults in the response to radiotherapy.

Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy

[EN] Background: Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. Methods: Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results: Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. Conclusions: A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe subcutaneous late toxicity after clinical treatment at high radiation doses in our series. However, due to the small sample size, other prospective studies with higher number of patients are needed to validate these results.

Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

[EN] Background: DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed. Methods: Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results: Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p < 0.0001 in all cases). Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). A statistically significant inverse correlation was found between initial damage to DNA and radio-induced apoptosis at 1 Gy (p = 0.034). A trend toward 2 Gy (p = 0.057) and 8 Gy (p = 0.067) was observed after 24 hours of incubation. Conclusions: An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity.

Growth rates and the evolution of heavy metals concentrations in segments of different ages of the terrestrial moss Pseudoscleropodium purum

Ecología, Facultad de Biología, Universidad de Santiago de Compostela

Estimating the contribution of terrestrial organic matter in the South-Western margin of Baja California during the late Holocene

Universidad de Las Palmas de Gran Canaria. Facultad de Ciencias del Mar. Trabajo Fin de Título para la obtención del Graduado en Ciencias del Mar, 2013-2014

An experimental and theoretical approach to correct for the scattered radiation in an X-ray computer tomography system for industrial applications

The main problem connected to cone beam computed tomography (CT) systems for industrial applications employing 450 kV X-ray tubes is the high amount of scattered radiation which is added to the primary radiation (signal). This stray radiation leads to a significant degradation of the image quality. A better understanding of the scattering and methods to reduce its effects are therefore necessary to improve the image quality. Several studies have been carried out in the medical field at lower energies, whereas studies in industrial CT, especially for energies up to 450 kV, are lacking. Moreover, the studies reported in literature do not consider the scattered radiation generated by the CT system structure and the walls of the X-ray room (environmental scatter). In order to investigate the scattering on CT projections a GEANT4-based Monte Carlo (MC) model was developed. The model, which has been validated against experimental data, has enabled the calculation of the scattering including the environmental scatter, the optimization of an anti-scatter grid suitable for the CT system, and the optimization of the hardware components of the CT system. The investigation of multiple scattering in the CT projections showed that its contribution is 2.3 times the one of primary radiation for certain objects. The results of the environmental scatter showed that it is the major component of the scattering for aluminum box objects of front size 70 x 70 mm2 and that it strongly depends on the thickness of the object and therefore on the projection. For that reason, its correction is one of the key factors for achieving high quality images. The anti-scatter grid optimized by means of the developed MC model was found to reduce the scatter-toprimary ratio in the reconstructed images by 20 %. The object and environmental scatter calculated by means of the simulation were used to improve the scatter correction algorithm which could be patented by Empa. The results showed that the cupping effect in the corrected image is strongly reduced. The developed CT simulation is a powerful tool to optimize the design of the CT system and to evaluate the contribution of the scattered radiation to the image. Besides, it has offered a basis for a new scatter correction approach by which it has been possible to achieve images with the same spatial resolution as state-of-the-art well collimated fan-beam CT with a gain in the reconstruction time of a factor 10. This result has a high economic impact in non-destructive testing and evaluation, and reverse engineering.

An adaptive solar radiation numerical model

[EN]A numerical model for the evaluation of solar radiation in different locations is presented. The solar radiation model is implemented taking into account the terrain surface using two-dimensional adaptive meshes of triangles that are constructed using a refinement/derefinement procedure in accordance with the variations of terrain surface and albedo. The selected methodology defines the terrain characteristics with a minimum number of points so that the computational cost is reduced for a given accuracy. The model can be used in atmospheric sciences as well as in other fields such as electrical engineering, since it allows the user to find the optimal location for maximum power generation in photovoltaic or solar thermal power plants...

Solar radiation estimation using a numerical model

[EN]A solar radiation numerical model is presented. It is intented to be useful for different purposes like the evaluation of the suitability of possible locations for solar power stations. This model allows the user to evaluate the radiation values in any location easily, and estimate the solar power generation taking into account not only the radiation level, but also the terrain surface conditions considering the cast shadows. The solar radiation model is implemented taking into account the terrain surface using 2-D adaptive meshes of triangles, which are constructed using a refinement/derefinement procedure in accordance with the variations of terrain surface and albedo...

A new predictive solar radiation numerical model

[EN]A predictive solar radiation numerical model is presented. Starting from the works of, a solar radiation numerical model is developed considering the terrain surface through 2-D adaptive meshes of triangles which are constructed using a refinement/derefinement procedure in accordance with the variations of terrain surface and albedo. The effect of shadows is considered in each time step. Solar radiation is first computed for clear-sky (CS) conditions and then, real-sky values are computed daily in terms of the CS index computed using all the observational data which are available for each day at several points of the studied zone…

Effects of solar radiation on marine bacterial and phytoplankton heterotrophic activities

Programa de doctorado: Oceanografía (Bienio 2006-2008). Universidad de Las Palmas de Gran Canaria, Departamento de Biología y Institut de Ciéncies del Mar.

Time-of-flight two-photon photoemission spectromicroscopy with femtosecond laser radiation

Time-of-flight photoemission spectromicroscopy was used to measure and compare the two-photon photoemission (2PPE) spectra of Cu and Ag nanoparticles with linear dimensions ranging between 40 nm and several 100 nm, with those of the corresponding homogeneous surfaces. 2PPE was induced employing femtosecond laser radiation from a frequency-doubled Ti:sapphire laser in the spectral range between 375 nm and 425 nm with a pulse width of 200 fs and a repetition rate of 80 MHz. The use of a pulsed radiation source allowed us to use a high-resolution photoemission electron microscope as imaging time-of-flight spectrometer, and thus to obtain spectroscopic information about the laterally resolved electron signal. Ag nanoparticle films have been deposited on Si(111) by electron-beam evaporation, a technique leading to hemispherically-shaped Ag clusters. Isolated Cu nanoparticles have been generated by prolonged heating of a polycrystalline Cu sample. If compared to the spectra of the corresponding homogeneous surfaces, the Cu and Ag nanoparticle spectra are characterized by a strongly enhanced total 2PPE yield (enhancement factor up to 70), by a shift (about 0.1 eV) of the Fermi level onset towards lower final state energies, by a reduction of the work function (typically by 0.2 eV) and by a much steeper increase of the 2PPE yield towards lower final state energies. The shift of the Fermi level onset in the nanoparticle spectra has been explained by a positive unit charge (localized photohole) residing on the particle during the time-scale relevant for the 2PPE process (few femtoseconds). The total 2PPE yield enhancement and the different overall shape of the spectra have been explained by considering that the laser frequency was close to the localized surface plasmon resonance of the Cu and Ag nanoparticles. The synchronous oscillations induced by the laser in the metal electrons enhance the near-zone (NZ) field, defined as the linear superposition of the laser field and the field produced in the vicinity of the particles by the forced charge oscillations. From the present measurements it is clear that the NZ field behavior is responsible for the 2PPE enhancement and affects the 2PPE spatial and energy distribution and its dynamics. In particular, its strong spatial dependence allows indirect transitions through real intermediate states to take place in the metal clusters. Such transitions are forbidden by momentum conservation arguments and are thus experimentally much less probable on homogeneous surfaces. Further, we investigated specially tailored moon-shaped small metal nanostructures, whose NZ field was theoretically predicted, and compared the calculation with the laterally resolved 2PPE signal. We could show that the 2PPE signal gives a clear fingerprint of the theoretically predicted spatial dependence of the NZ field. This potential of our method is highly attractive in the novel field of plasmonics.

Extraterrestrial and terrestrial outdoor applications of Mössbauer spectroscopy

„Extraterrestrische und terrestrische Anwendungen eines miniaturisierten Mössbauer-Spektrometers“ Die vorliegende Arbeit befasst sich mit Anwendungen eines miniaturisierten Mössbauer- Spektrometers (MIMOS II), dessen Entwicklung in den frühen neunziger Jahren am Institut für Kernphysik der Technischen Universität Darmstadt unter Professor Egbert Kankeleit und seinen Mitarbeitern begann. Seit 1998 sind die Entwicklungsarbeiten im Arbeitskreis von Prof. Gütlich am Institut für Anorganische und Analytische Chemie der Johannes Gutenberg- Universität Mainz von Dr. Göstar Klingelhöfer und Mitarbeitern fortgesetzt worden. Vorrangiges Ziel war dabei der geplante Einsatz des Spektrometers zu mineralogischen Untersuchungen im Weltall. Entsprechend ist das Projekt mit erheblichen finanziellen Mitteln des Forschungsinstituts der Deutschen Luft- und Raumfahrt (DLR) in Bonn unterstützt worden. Bei den beiden Missionen, die im Jahre 2003 von der NASA zum Mars gesandt wurden und im Januar dieses Jahres die beiden „Mars Exploration Rover“ (MER) "Spirit" und "Opportunity" erfolgreich auf der Marsoberfläche abgesetzt haben, ist jeweils ein MIMOS II-Gerät zur Charakterisierung eisenhaltiger Minerale und Böden während der laufenden Mission im Einsatz. Einige Ergebnisse von MIMOS II an Gestein und Böden der Marsoberfläche werden in der vorliegenden Arbeit präsentiert und diskutiert. Diese Ergebnisse wurden vom MIMOS II-Consortium unter Führung von Dr. Göstar Klingelhöfer, mit Unterstützung des Ingenieurs- und Wissenschaftsteams von MER am Jet Propulsion Laboratory in Kalifornien, erlangt. Erste Spektren, die von Proben im Gusev-Krater (Landestelle von „Spirit“) aufgenommen wurden und in dieser Arbeit vorgestellt werden, weisen auf das Vorkommen von forsteritischem Olivin, Pyroxen, Magnetit hin; daneben zeigt sich ein von Eisen(III) herrührendes Quadrupoldublett, das (noch) nicht eindeutig zugeordnet werden konnte. Aus den gewonnenen Daten wurde geschlossen, dass physikalische Verwitterung der vorherrschende Veränderungsprozess in den Ebenen des Gusev-Kraters ist. Um die Fähigkeiten von MIMOS II in der Charakteriserung extraterrestrischen Materials vor dem Start zum Mars zu demonstrieren, wurde eine Auswahl von chondritischen, Eisenund Marsmeteoriten gemessen. Ein Datenanalysepaket, basierend auf künstlichen neuronalen Netzwerken, genetischen Algorithmen und "fuzzy" Logik, wurde erstellt, erfolgreich getestet und während der Echtzeit-Operation der MER benutzt. Eine Datenbasis von Mössbauer-Parametern und Referenzen von veröffentlichten Studien über den Temperaturbereich des Mars wurde zusammengestellt. Die Werkzeuge zur Datenanalyse eröffnen neue Einsatzmöglichkeiten des miniaturisierten Mössbauer-Spektrometers in vielen Bereichen ausserhalb des Physikllabors. Einige davon werden in dieser Arbeit vorgestellt, wie z.B.die Pigmentcharakterisierung, die Echtheit archäologischer Artefakte oder in-situ Luftverschmutzungsmessungen. Datum: 20.07.2004 1. Betreuer: Professor Dr. P. Gütlich Paulo A. de Souza Jr. GAFEP/GETEP Departamento de Pelotização - DIPE Companhia Vale do Rio Doce - CVRD Tel.: (27) 3333-4609 - Carrier (835)

Emissions of volatile organic compounds from tropical savanna vegetation and biomass burning

This dissertation focuses on characterizing the emissions of volatile organic compounds (VOCs) from grasses and young trees, and the burning of biomass mainly from Africa and Indonesia. The measurements were performed with a proton-transfer-reaction mass spectrometer (PTR-MS). The biogenic emissions of tropical savanna vegetation were studied in Calabozo (Venezuela). Two field campaigns were carried out, the first during the wet season (1999) and the second during the dry season (2000). Three grass species were studied: T. plumosus, H. rufa and A. canescens, and the tree species B. crassifolia, C. americana and C. vitifolium. The emission rates were determined with a dynamic plant enclosure system. In general, the emissions increased exponentially with increasing temperature and solar radiation. Therefore, the emission rates showed high variability. Consequently, the data were normalized to a standard temperature of 30°C, and standard emission rates thus determined allowed for interspecific and seasonal comparisons. The range of average daytime (10:00-16:00) emission rates of total VOCs measured from green (mature and young) grasses was between 510-960 ngC/g/h. Methanol was the primary emission (140-360 ngC/g/h), followed by acetaldehyde, butene and butanol and acetone with emission rates between 70-200 ngC/g/h. The emissions of propene and methyl ethyl ketone (MEK) were <80 ngC/g/h, and those of isoprene and C5-alcohols were between 10-130 ngC/g/h. The oxygenated species represented 70-75% of the total. The emission of VOCs was found to vary by up to a factor of three between plants of the same species, and by up to a factor of two between the different species. The annual source of methanol from savanna grasses worldwide estimated in this work was 3 to 4.4 TgC, which could represent up to 12% of the current estimated global emission from terrestrial vegetation. Two of the studied tree species, were isoprene emitters, and isoprene was also their primary emission (which accounted for 70-94% of the total carbon emitted) followed by methanol and butene + butanol. The daytime average emission rate of isoprene measured in the wet season was 27 mgC/g/h for B. crassifolia, and 123 mgC/g/h for C. vitifolium. The daytime emissions of methanol and butene + butanol were between 0.3 and 2 mgC/g/h. The total sum of VOCs emission measured during the day in the wet season was between 30 and 130 mgC/g/h. In the dry season, in contrast, the methanol emissions from C. vitifolium saplings –whose leaves were still developing– were an order of magnitude higher than in the wet season (15 mgC/g/h). The isoprene emission from B. crassifolia in the dry season was comparable to the emission in the wet season, whereas isoprene emission from C. vitifolium was about a factor of three lower (~43 mgC/g/h). Biogenic emission inventories show that isoprenoids are the most prominent and best-studied compounds. The standard emission rates of isoprene and monoterpenes of the measured savanna trees were in the lower end of the range found in the literature. The emission of other biogenic VOCs has been sparsely investigated, but in general, the standard emissions from trees studied here were within the range observed in previous investigations. The biomass burning study comprised the measurement of VOCs and other trace-gas emissions of 44 fires from 15 different fuel types, primarily from Africa and Indonesia, in a combustion laboratory. The average sum of emissions (excluding CO2, CO and NO) from African fuels was ~18 g(VOC)/kg. Six of the ten most important emissions were oxygenated VOCs. Acetic acid was the major emission, followed by methanol and formaldehyde. The emission of methane was of the same order as the methanol emission (~5 g/kg), and that of nitrogen-containing compounds was ~1 g/kg. An estimate of the VOC source from biomass burning of savannas and grasslands worldwide suggests that the sum of emissions is about 56 Tg/yr, of which 34 Tg correspond to oxygenated VOCs, 14 Tg to unsaturated and aromatic compounds, 5 Tg to methane and 3 Tg to N-compounds. The estimated emissions of CO, CO2 and NO are 216, 5117 and 9.4 Tg/yr, respectively. The emission factors reported here for Indonesian fuels are the first results of laboratory fires using Indonesian fuels. Acetic acid was the highest organic emission, followed by acetol, a compound not previously reported in smoke, methane, mass 97 (tentatively identified as furfural, dimethylfuran and ethylfuran), and methanol. The sum of total emissions of Indonesian fuels was 91 g/kg, which is 5 times higher than the emissions from African fuels. The results of this study reinforces the importance of oxygenated compounds. Due to the vast area covered by tropical savannas worldwide, the biogenic and biomass burning emission of methanol and other oxygenated compounds may be important for the regional and even global tropospheric chemistry.

Indoor and Outdoor Natural Radioactivity in the Vulsini Volcanic District (Central Italy): Estimation of Doses and Radiological Risks

Terrestrial radioactivity for most individual is the major contributor to the total dose and is mostly provided by 238U, 232Th and 40K radionuclides. In particular indoor radioactivity is principally due to 222Rn, a radioactive noble gas descendent of 238U, second cause of lung cancer after cigarettes smoking. Vulsini Volcanic District is a well known quaternary volcanic area located between the northern Latium and southern Tuscany (Central Italy). It is characterized by an high natural radiation background resulting from the high concentrations of 238U, 232Th and 40K in the volcanic products. In this context, subduction-related metasomatic enrichment of incompatible elements in the mantle source coupled with magma differentiation within the upper crust has given rise to U, Th and K enriched melts. Almost every ancient village and town located in this part of Italy has been built with volcanic rocks pertaining to the Vulsini Volcanic District. The radiological risk of living in this area has been estimated considering separately: a. the risk associated with buildings made of volcanic products and built on volcanic rock substrates b. the risk associated to soil characteristics. The former has been evaluated both using direct 222Rn indoor measurements and simulations of “standard rooms” built with the tuffs and lavas from the Vulsini Volcanic District investigated in this work. The latter has been carried out by using in situ measurements of 222Rn activity in the soil gases. A radon risk map for the Bolsena village has been developed using soil radon measurements integrating geological information. Data of airborne radioactivity in ambient aerosol at two elevated stations in Emilia Romagna (North Italy) under the influence of Fukushima plume have been collected, effective doses have been calculated and an extensive comparison between doses associated with artificial and natural sources in different area have been described and discussed.