A Log-linear model of grain size influence on the geochemistry of sediments

Sediment composition is mainly controlled by the nature of the source rock(s), and chemical (weathering) and physical processes (mechanical crushing, abrasion, hydrodynamic sorting) during alteration and transport. Although the factors controlling these processes are conceptually well understood, detailed quantification of compositional changes induced by a single process are rare, as are examples where the effects of several processes can be distinguished. The present study was designed to characterize the role of mechanical crushing and sorting in the absence of chemical weathering. Twenty sediment samples were taken from Alpine glaciers that erode almost pure granitoid lithologies. For each sample, 11 grain-size fractions from granules to clay (ø grades <-1 to >9) were separated, and each fraction was analysed for its chemical composition. The presence of clear steps in the box-plots of all parts (in adequate ilr and clr scales) against ø is assumed to be explained by typical crystal size ranges for the relevant mineral phases. These scatter plots and the biplot suggest a splitting of the full grain size range into three groups: coarser than ø=4 (comparatively rich in SiO2, Na2O, K2O, Al2O3, and dominated by “felsic” minerals like quartz and feldspar), finer than ø=8 (comparatively rich in TiO2, MnO, MgO, Fe2O3, mostly related to “mafic” sheet silicates like biotite and chlorite), and intermediate grains sizes (4≤ø <8; comparatively rich in P2O5 and CaO, related to apatite, some feldspar). To further test the absence of chemical weathering, the observed compositions were regressed against three explanatory variables: a trend on grain size in ø scale, a step function for ø≥4, and another for ø≥8. The original hypothesis was that the trend could be identified with weathering effects, whereas each step function would highlight those minerals with biggest characteristic size at its lower end. Results suggest that this assumption is reasonable for the step function, but that besides weathering some other factors (different mechanical behavior of minerals) have also an important contribution to the trend. Key words: sediment, geochemistry, grain size, regression, step function

An update of the mechanisms of resistance to EGFR-tyrosine kinase inhibitors in breast cancer: gefitinib (Iressatrade mark)-induced changes in the expression and nucleo-cytoplasmic trafficking of HER-ligands (Review)

Intrinsic resistance to the epidermal growth factor receptor (EGFR; HER1) tyrosine kinase inhibitor (TKI) gefitinib, and more generally to EGFR TKIs, is a common phenomenon in breast cancer. The availability of molecular criteria for predicting sensitivity to EGFR-TKIs is, therefore, the most relevant issue for their correct use and for planning future research. Though it appears that in non-small-cell lung cancer (NSCLC) response to gefitinib is directly related to the occurrence of specific mutations in the EGFR TK domain, breast cancer patients cannot be selected for treatment with gefitinib on the same basis as such EGFR mutations have been reported neither in primary breast carcinomas nor in several breast cancer cell lines. Alternatively, there is a general agreement on the hypothesis that the occurrence of molecular alterations that activate transduction pathways downstream of EGFR (i.e., MEK1/MEK2 - ERK1/2 MAPK and PI-3'K - AKT growth/survival signaling cascades) significantly affect the response to EGFR TKIs in breast carcinomas. However, there are no studies so far addressing a role of EGF-related ligands as intrinsic breast cancer cell modulators of EGFR TKI efficacy. We recently monitored gene expression profiles and sub-cellular localization of HER-1/-2/-3/-4 related ligands (i.e., EGF, amphiregulin, transforming growth factor-α, ß-cellulin, epiregulin and neuregulins) prior to and after gefitinib treatment in a panel of human breast cancer cell lines. First, gefitinibinduced changes in the endogenous levels of EGF-related ligands correlated with the natural degree of breast cancer cell sensitivity to gefitinib. While breast cancer cells intrinsically resistant to gefitinib (IC50 ≥15 μM) markedly up-regulated (up to 600 times) the expression of genes codifying for HERspecific ligands, a significant down-regulation (up to 106 times) of HER ligand gene transcription was found in breast cancer cells intrinsically sensitive to gefitinib (IC50 ≤1 μM). Second, loss of HER1 function differentially regulated the nuclear trafficking of HER-related ligands. While gefitinib treatment induced an active import and nuclear accumulation of the HER ligand NRG in intrinsically gefitinib-resistant breast cancer cells, an active export and nuclear loss of NRG was observed in intrinsically gefitinib-sensitive breast cancer cells. In summary, through in vitro and pharmacodynamic studies we have learned that, besides mutations in the HER1 gene, oncogenic changes downstream of HER1 are the key players regulating gefitinib efficacy in breast cancer cells. It now appears that pharmacological inhibition of HER1 function also leads to striking changes in both the gene expression and the nucleo-cytoplasmic trafficking of HER-specific ligands, and that this response correlates with the intrinsic degree of breast cancer sensitivity to the EGFR TKI gefitinib. The relevance of this previously unrecognized intracrine feedback to gefitinib warrants further studies as cancer cells could bypass the antiproliferative effects of HER1-targeted therapeutics without a need for the overexpression and/or activation of other HER family members and/or the activation of HER-driven downstream signaling cascades

Robustness against large-scale failures in communications networks

This thesis studies robustness against large-scale failures in communications networks. If failures are isolated, they usually go unnoticed by users thanks to recovery mechanisms. However, such mechanisms are not effective against large-scale multiple failures. Large-scale failures may cause huge economic loss. A key requirement towards devising mechanisms to lessen their impact is the ability to evaluate network robustness. This thesis focuses on multilayer networks featuring separated control and data planes. The majority of the existing measures of robustness are unable to capture the true service degradation in such a setting, because they rely on purely topological features. One of the major contributions of this thesis is a new measure of functional robustness. The failure dynamics is modeled from the perspective of epidemic spreading, for which a new epidemic model is proposed. Another contribution is a taxonomy of multiple, large-scale failures, adapted to the needs and usage of the field of networking.

Developing a desertification indicator system for a small Mediterranean catchment: a case study from the Serra de Rodes, Alt Empordà, Catalunya, NE Spain

La desertificació és un problema de degradació de sòls de gran importància en regions àrides, semi-àrides i sub-humides, amb serioses conseqüències ambientals, socials i econòmiques com a resultat de l'impacte d'activitats humanes en combinació amb condicions físiques i medi ambientals desfavorables (UNEP, 1994). L'objectiu principal d'aquesta tesi va ser el desenvolupament d'una metodologia simple per tal de poder avaluar de forma precisa l'estat i l'evolució de la desertificació a escala local, a través de la creació d'un model anomenat sistema d'indicators de desertificació (DIS). En aquest mateix context, un dels dos objectius específics d'aquesta recerca es va centrar en l'estudi dels factors més importants de degradació de sòls a escala de parcel.la, comportant un extens treball de camp, analisi de laboratori i la corresponent interpretació i discussió dels resultats obtinguts. El segon objectiu específic es va basar en el desenvolupament i aplicació del DIS. L'àrea d'estudi seleccionada va ser la conca de la Serra de Rodes, un ambient típic Mediterràni inclòs en el Parc Natural del Cap de Creus, NE Espanya, el qual ha estat progressivament abandonat pels agricultors durant el segle passat. Actualment, els incendis forestals així com el canvi d'ús del sòl i especialment l'abandonament de terres són considerats els problemes ambientals més importants a l'àrea d'estudi (Dunjó et al., 2003). En primer lloc, es va realitzar l'estudi dels processos i causes de la degradació dels sòls a l'àrea d'interés. En base a aquest coneixement, es va dur a terme la identificació i selecció dels indicadors de desertificació més rellevants. Finalment, els indicadors de desertificació seleccionats a escala de conca, incloent l'erosió del sòl i l'escolament superficial, es van integrar en un model espaial de procés. Ja que el sòl és considerat el principal indicador dels processos d'erosió, segons la FAO/UNEP/UNESCO (1979), tant el paisatge original així com els dos escenaris d'ús del sòl desenvolupats, un centrat en el cas hipotétic del pas d'un incendi forestal, i l'altre un paisatge completament cultivat, poden ser ambients classificats sota baixa o moderada degradació. En comparació amb l'escenari original, els dos escenaris creats van revelar uns valors més elevats d'erosió i escolament superficial, i en particular l'escenari cultivat. Per tant, aquests dos hipotètic escenaris no semblen ser una alternativa sostenible vàlida als processos de degradació que es donen a l'àrea d'estudi. No obstant, un ampli ventall d'escenaris alternatius poden ser desenvolupats amb el DIS, tinguent en compte les polítiques d'especial interés per la regió de manera que puguin contribuir a determinar les conseqüències potencials de desertificació derivades d'aquestes polítiques aplicades en aquest escenari tan complexe espaialment. En conclusió, el model desenvolupat sembla ser un sistema força acurat per la identificació de riscs presents i futurs, així com per programar efectivament mesures per combatre la desertificació a escala de conca. No obstant, aquesta primera versió del model presenta varies limitacions i la necessitat de realitzar més recerca en cas de voler desenvolupar una versió futura i millor del DIS.