Thermochronological approach to the late Neogene exhumation of the European Alps

Sediment flux from the Alps shows a sharp increase around the Mio-Pliocene boundary (~5 Ma). This observation, linked to the exhumation of the Swiss Molasse basin since ca. 5-4 Ma has led to the suggestion that the Alps experienced accelerated exhumation and isostatic uplift at the orogen scale since this time. The core objectives of this thesis are to assess whether we can document post 5 Ma exhumation of the Alps and its spatial and temporal development, and to review the different potential (tectonic or climatic) factors controlling this denudation. I have developed a novel technique that uses isoage contours associated with age-elevation relationships to exploit the unique density of fission-track ages in the western European Alps, reconstruct cooling isoage surfaces and estimate exhumation rates on the orogen scale between 13.5 and 2.5 Ma. The exhumation histories reconstructed for eight areas of the Western Alps display strong similarities in timing and rate with orogen-wide average denudation rates inferred from sediment volumes. Exhumation rates increased more than twofold since Late Miocene times, and may have been locally modulated by the distinct response of different tectonic units. I then searched for correlation between the spatial pattern of long-term exhumation rates, from the apatite fission-track record, and potential controlling parameters. In the Western Alps, long-term exhumation rates correlate strongly with presentday rates of rock uplift, implying that the rock uplift pattern observed today is ancient. I also observed that the spatial pattern of released seismic energy does not correlate with rock uplift or exhumation, which suggests that exhumation is controlled by isostatic rebound rather than by active tectonic uplift. The lack of correlation between exhumation rates and the presentday distribution of precipitation suggests that the present-day pattern is either non representative of the long-term trend or that factors other than precipitation rate dominate the intensity of exhumation. In order to study the exhumation history in more detail, I sampled two elevation profiles in the central Aar massif (Switzerland) and the western Lepontine Alps (Italy) for AFT and AHe dating which are characterised by steep age-elevation relationships around 8 and 4 Ma. I used the Pecube model to predict AFT and AHe ages according to several tens of exhumation scenarios and compared modeled and measured ages. The results of numerical modeling do not reject the hypothesis of two exhumation pulses at 9-7 and 5-3 Ma in the Aar massif. However, this signal is not detected in the Lepontine Alps, and contingent upon further flexural modeling, the exhumation recorded in the Aar massif since 5 Ma does not match the amount required to explain the denudation in the Swiss Molasse basin by flexural isostatic rebound. Rather, the data hint at an additional mechanism of rock uplift, such as the delamination of lithospheric mantle.Le flux de sédiments en provenance des Alpes montre une importante augmentation à la limite Mio-Pliocène (~5 Ma). Cette observation, liée à l'exhumation du bassin molassique suisse depuis 5-4 Ma, a conduit à suggérer que les Alpes ont connu une exhumation et un uplift isostatique accélérés à l'échelle de l'orogène depuis cette période. Les objectifs principaux de cette thèse sont de déterminer s'il existe une hausse de l'exhumation alpine après 5 Ma, de préciser son extension spatiale et temporelle, et de passer en revue les différents facteurs potentiels (tectoniques ou climatiques) contrôlant cette dénudation. J'ai développé durant la thèse une nouvelle technique utilisant les contours isoâge associés aux relations âge-élévation pour, à partir de la mise à jour d'une base de données d'âges par traces de fission dans les Alpes Européennes occidentales, reconstruire des surfaces de refroidissement isoâge et estimer les taux d'exhumation de l'orogène entre 13,5 et 2,5 Ma. Les taux et les périodes d'exhumation obtenus pour huit zones des Alpes Occidentales présentent de fortes similarités avec la dénudation moyenne de l'orogène estimée à partir du volume de sédiments péri-alpins. Les taux d'exhumation ont plus que doublé depuis la fin du Miocène, et peuvent avoir été modulés localement par les caractéristiques des différentes unités tectoniques. J'ai ensuite recherché des corrélations entre les valeurs de taux d'exhumation à long terme, dérivées des données d'âge par traces de fission, et les paramètres de contrôle potentiels. Dans les Alpes Occidentales, les taux d'exhumation à long terme sont fortement corrélés avec les taux d'uplift rocheux présents, suggérant que les valeurs d'uplift actuelles ont peu changé récemment. J'ai aussi observé que la distribution de l'énergie sismique libérée n'est pas corrélée avec l'uplift rocheux ou l'exhumation, ce qui suggère que l'exhumation est contrôlée par rebond isostatique plutôt que par un uplift tectonique actif. L'absence de corrélation entre les taux d'exhumation et la distribution des précipitations actuelles suggère qu'elles ne sont pas représentatives d'une tendance à long terme, ou bien que des facteurs autres que le taux de précipitations contrôlent l'intensité de l'exhumation. Dans le but d'étudier davantage en détail l'histoire de l'exhumation, j'ai réalisé un échantillonnage le long de deux profils altitudinaux dans le centre du massif de l'Aar (Suisse) et à l'ouest des Alpes Lepontines (Italie). Les âges AFT et AHe obtenus se caractérisent par des pentes très élevées de la relation âge-élévation aux alentours de 8 et 4 Ma. J'ai utilisé le modèle Pecube pour prédire des âges AFT et AHe selon plusieurs dizaines de scénarios d'exhumation, et j'ai comparé les âges mesurés et prédits. Les résultats des modèles numériques ne permettent pas de rejetter l'hypothèse de deux phases de forte exhumation à 9-7 et 5-3 Ma dans le massif de l'Aar. Cependant, ce signal n'est pas détecté dans les Alpes Lepontines, et sous-réserve de l'apport d'une modélisation flexurale additionnelle, la quantité d'exhumation dans le massif de l'Aar depuis 5 Ma ne permet pas d'expliquer l'exhumation du bassin molassique suisse par rebond flexural isostatique. Au contraire, ces résultats sont de nature à conforter l'existence d'un mécanisme d'uplift rocheux additionnel tel que le détachement de manteau lithosphérique épaissi

Increase in late Neogene denudation of the European Alps confirmed by analysis of a fission-track thermochronology database

International audienceA sharp increase in deposited sediment volume since Pliocene times has been observed worldwide and in particular around the European Alps. This phenomenon has been linked to a rise in denudation rates controlled by an increase of either climatic or tectonic forcing. Observation of in-situ cooling histories for orogens is critical to assess the reality of the inferred increase in denudation rates, and to determine whether this phenomenon is widespread or localized at active tectonic structures. We exploit the unique density of fission-track ages in the Western European Alps to reconstruct cooling isoage surfaces and to estimate exhumation rates on the orogen scale between 13.5 and 2.5 Ma. Our novel technique is based on the association of isoage contours with age–elevation relationships. It uses map-view interpolation, enabling a spatio-temporal analysis of exhumation rates over the entire Western Alps. The resulting exhumation histories reconstructed for eight areas of the Western Alps display strong similarities in timing and rates with orogen-wide average denudation rates inferred from sediment volumes. This consistency validates the use of both techniques for the study of an orogen characterized by strong relief and high recent exhumation rates. We conclude that exhumation rates in the Western Alps have increased more than twofold since Late Miocene times. This increase may have been locally modulated by the distinct response of different tectonic units

The effect of displacement distribution asymmetry on the accuracy of phase-shift velocimetry in porous media

Phase-shift velocimetry provided by pulsed magnetic field gradient experiments is the fastest magnetic resonance technique for measuring velocity. However, critical issues have been reported when studying flow through porous media. These lead to inaccurate velocimetry results, with no clear explanation emerging. In this work we investigate the effect of asymmetries in the distribution of intra-voxel displacements on the accuracy of phase-shift velocimetry. This is particularly relevant to flow through porous media, where the presence of stagnant pores or differential flow is known to result in asymmetric displacement distributions. Here, tailored intra-voxel distributions are achieved using a simple phantom combined with a single large voxel. Combining experimental results with simulations, we demonstrate that the presence of asymmetries in the intra-voxel displacement distributions, common in studies of porous materials, can lead to important velocimetry errors

Accurate phase-shift velocimetry in rock

AbstractSpatially resolved Pulsed Field Gradient (PFG) velocimetry techniques can provide precious information concerning flow through opaque systems, including rocks. This velocimetry data is used to enhance flow models in a wide range of systems, from oil behaviour in reservoir rocks to contaminant transport in aquifers. Phase-shift velocimetry is the fastest way to produce velocity maps but critical issues have been reported when studying flow through rocks and porous media, leading to inaccurate results. Combining PFG measurements for flow through Bentheimer sandstone with simulations, we demonstrate that asymmetries in the molecular displacement distributions within each voxel are the main source of phase-shift velocimetry errors. We show that when flow-related average molecular displacements are negligible compared to self-diffusion ones, symmetric displacement distributions can be obtained while phase measurement noise is minimised. We elaborate a complete method for the production of accurate phase-shift velocimetry maps in rocks and low porosity media and demonstrate its validity for a range of flow rates. This development of accurate phase-shift velocimetry now enables more rapid and accurate velocity analysis, potentially helping to inform both industrial applications and theoretical models

Assessment of the Public Administration Tools for the improvement of the Eco-efficiency of Small and Medium Sized Enterprises

Small and Medium Sized Enterprises (SME) face barriers to the implementation and development of eco-efficiency that could be overcome taking advantage of the adequate stimuli and incentives. A previous research and a thorough literature analysis show Public Administration (PA) is a key stakeholder. PA could use better its tools to stimulate SME to improve their ecoefficiency. Among these tools it can be named well known command and control tools like legislation or taxes, but also price policies, green procurement, ecological education, eco-innovation support and others. This paper reviews these tools and how they contribute to overcome barriers to ecoefficiency by offering external and internal incentives for SME. The analysis is focused on the case of Venezuelan public administration and SME but it can be generalized to other case studies. In addition, a panel of experts validates the results and assesses the public administration tools by means of the policy Delphi method. The assessment is based on criteria like: market influence, capability of the public administration for controlling results, tool costs, impact on public administration image, timespan to get results, etc. The assessment, therefore, allows ranking and understanding the tools according to their effectiveness and efficiency to support SME to improve their ecoefficiency. Due to the specific characteristics of the case study: SME of Venezuela, the method shows the best mix of public administration tools includes mainly command and control tools. Also the mix includes certain new-approach tools like advertising about responsible consumption and eco-efficient products, or education/training in environmental responsibility. The method also allows understanding better how the tools will help accomplishing the objectives for ecoefficiency of the public administration. Therefore, this research provides a method for raising information to be used when planning the actions to improve eco-efficiency of the SME.Fernández-Viñé, MB.; Gómez-Navarro, T.; Capuz-Rizo, SF. (2013). Assessment of the Public Administration Tools for the improvement of the Eco-efficiency of Small and Medium Sized Enterprises. Journal of Cleaner Production. 47:265-273. doi:10.1016/j.jclepro.2012.08.026S2652734

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

The known breast cancer (BC) susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1,LSP1 and 2q35 confer increased risks of BC for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of three additional SNPs, rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11 and rs10941679 at 5p12 and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased BC risk for BRCA2 carriers (per-allele Hazard Ratio (HR)=1.10, 95%CI:1.03-1.18, p=0.006 and HR=1.09, 95%CI:1.01-1.19, p=0.03, respectively). Neither SNP was associated with BC risk for BRCA1 carriers and rs6504950 was not associated with BC for either BRCA1 or BRCA2 carriers. Of the nine polymorphisms investigated, seven were associated with BC for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, p-values:7×10−11-0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (p=0.0049, 0.03 respectively). All risk associated polymorphisms appear to interact multiplicatively on BC risk for mutation carriers. Based on the joint genotype distribution of the seven risk associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e. between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Abstract Introduction Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects