Implications of the serpentine phase transition on the behaviour of beryllium and lithium-boron of subducted ultramafic rocks

The Totalp-Platta-Malenco ophiolites in the Eastern Central Alps offer a unique opportunity to study the behaviour of Li, Be and B in ultramafic rocks in response to serpentinization and to progressive Alpine metamorphism. These units represent the remnants of a former ocean-continent transition that was intensely serpentinized during exposure on the Jurassic seafloor of the Ligurian Tethys. From north to the south, three isograd reactions (lizardite double right arrow antigorite + brucite; lizardite + talc double right arrow antigorite; lizardite + tremolite double right arrow antigorite + diopside) have been used to quantify the evolution of the light element content of metamorphic minerals. We determined the Li, Be and B concentrations in major silicate minerals from the ultramafic bodies of Totalp, Platta and Malenco by secondary ion mass spectrometry. Mantle minerals have Be concentrations (e.g. <0.001-0.009 mu g/g in olivine) similar to the metamorphic minerals that replace them (e.g. <0.001-0.016 mu g/g in serpentine). The mantle signature of Be is thus neither erased during seafloor alteration nor by progressive metamorphism from prehnite-pumpellyite to epidote-amphibolite facies. In contrast, the Li and B inventories of metamorphic minerals are related to the lizardite-to-antigorite transition. Both elements display higher concentrations in the low-temperature serpentine polymorph lizardite (max. 156 mu/g Li, max. 318 mu g/g B) than in antigorite (max. 0.11 mu g/g Li, max. 12 mu g/g B). Calculated average B/Li ratios for lizardite (similar to 1395) and antigorite (similar to 115) indicate that Li fractionates from B during the lizardite-to-antigorite transition during prograde metamorphism in ultramafic rocks. In subduction zones, this signature is likely to be recorded in the B-rich nature of forearc fluids. Relative to oceanic mantle the Be content of mantle clinopyroxene is much higher, but similar to Be values from mantle xenoliths and subduction-related peridotite massifs. These data support previous hypothesis that the mantle rocks from the Eastern Central Alps have a subcontinental origin. We conclude that Be behaves conservatively during subduction metamorphism of ultramafic rocks, at least at low-temperature, and thus retains the fingerprint of ancient subduction-related igneous events in mantle peridotites. (C) 2010 Elsevier Ltd. All rights reserved.

The early Miocene rotation of the Corso-Sardinian block. New paleomagnetic constraints for the end of the motion

The paleomagnetic investigations carried out in the 70's on Oligo-Miocene volcanics of Sardinia have demonstrated that the island was turned by 35-30 degrees clockwise from 33 Ma up to 3-1-20.5 Ma and rotated counterclockwise in a few million years [De Jong et al., 1969, 1973; Bobier et Coulon, 1970; Coulon et al., 1974; Manzoni, 1974, 1975; Bellon rr nl.. 1977: Edel et Lortscher, 1977; Edel, 1979, 1980]. Since then, the end of the rotation fixed at 19 Ma by Montigny er al. [1981] was the subject of discussions and several studies associating paleomagnetism and radiometric dating were undertaken [Assorgia er al., 1994: Vigliotti et Langenheim, 1995: Deino et al., 1997; Gattacceca rt Deino, 1999]. This is a contribution to this debate that is hampered by thr important secular variation recorded in the volcanics. The only way to get our of this problem is to sample series of successive flows as completely as possible, and to reduce the effect of secular variation by the calculation of means. Sampling was performed north of Bonorva in 5 pyroclastic flows that belong to the upper ignimbritic series SI2 according to Coulon rr nl. [1974] or LBLS according to Assorgia et al. [1997] (fig. I). Ar-40/Ar-39 dating of biotites from the debris flow (MDF) has yielded an age or 18.35 +/- 0.03 Ma [Dubois, 2000]. Five of the investigated sites are located beneath the debris flow ITV, TVB, TVD, SPM85, SPM86), one site was cured in the matrix of the debris flow (MDF) and one in 4 metric blocks included in the flow (DFC). Another site was sampled in the upper ash flow (PDM) that marks the end of the pyroclastic activity, just before the marine transgression. According to micropaleontological and radiometric dating this transgression has occurred between 18.35 and 17.6 Ma [Dubois, 2000]. After removal of a soft viscous component, the thermal demagnetization generally shows a univectorial behaviour of the remanent magnetization (fig. 2a). The maximum unblocking temperatures of 580-620 degrees (tab. I) and a rapid saturation below 100 mT (fig. 3) indicate that the carrier of the characteristic magnetization is magnetite. The exception comes: from the upper site PDM in which were found two characteristic components, one with a normal polarity and low unblocking temperatures up to 350 degreesC and one with a reversed polarity and maximum unblocking temperatures at 580-600 degreesC of magnetite. After calculation of a mean direction for each flow, the mean << Al >> direction 4 degrees /57 degrees (alpha (95) = 13 degrees) computed with the mean directions for the 5 flows may be considered as weakly affected by secular variation. But the results require a more careful examination. The declinations are N to NNW beneath the debris flow. NNW in the debris flow. and NNE (or SSW) above the debris flow, The elongated distribution of the directions obtained at sites TVB and TVD. scattered from the mean direction of TV to the mean direction of MDF is interpreted as due to partial overprinting during the debris How volcanic episode, The low temperature component PDMa is likely related to the alteration seen on thin sections and is also viewed as an overprint. As NNE/SSW directions occur as well below (mean direction << B >> : 5 degrees /58 degrees) as above the debris flow (PDMb : 200 degrees/-58 degrees). the NNW directions (<< C >> : 337 degrees /64 degrees) associated with the debris flow volcanism may be interpreted as resulting from a magnetic field excursion. According to the polarity scale of Cande and Kent [1992, 1995] and the radiometric age of MDF, the directions with normal polarity (TV, TVB, TVD, SPM85. SPM86a. MDF. DFC) may represent the period 5En. while the directions with reversed polarity PDMb and SPM86b were likely acquired during the period 5Dr. Using the mean << Al >> direction, the mean << B >>, or the PDM direction (tab. I). the deviation in declination with the direction of stable Europe 6.4 degrees /58.7 degrees (alpha (95) = 8 degrees) for a selection of 4 middle Tertiary poles by Besse et Courtillot [1991] or 7 degrees /56 degrees (alpha (95) = 3 degrees) for 19 poles listed by Edel [1980] can be considered as negligible. Using the results from the uppermost ignimbritic layer of Anglona also emplaced around 18.3 Ma [Odin rt al.. 1994]. the mean direction << E >> (3 degrees /51.5 degrees) leads to the same conclusion. On the contrary, when taking into account all dated results available for the period 5En (mean direction << D >> 353 degrees /56 degrees for 45 sites) (tab. II). the deviation 13 degrees is much more significant. As the rotation of Sardinia started around 21-20.5 Ma. the assumption of a constant velocity of rotation and the deviations of the Sardinia directions with respect to the stable Europe direction locate the end of the motion between 18.3 and 17.2 or 16.7 Ma (fig. 4). During the interval 18.35-17.5 Ma, the marine transgression took place. At the same period a NE-SW shortening interpreted as resulting from the collision of Sardinia with Apulia affected different parts of the island [Letouzey et al., 1982]. Consequently, the new paleomagnetic results and the tectono-sedimentary evolution are in favour of an end of the rotation at 17.5-18 Ma.

Evolutionary and biomedical consequences of internal melanins.

The adaptive function of melanin located in the integument is well known. Although pigments are also deposited in various internal organs, their function is unclear. A review of the literature revealed that 'internal melanin' protects against parasites, pollutants, low temperature, oxidative stress, hypoxemia and UV light, and is involved in the development and function of organs. Importantly, several studies have shown that the amount of melanin deposited on the external body surface is correlated with the amount located inside the body. This finding raises the possibility that internal melanin plays more important physiological roles in dark than light-colored individuals. Internal melanin and coloration may therefore not evolve independently. This further emphasizes the major role played by indirect selection in evolutionary processes.

Constraints on palaeodrainage evolution induced by uplift and exhumation on the southern flank of the Zagros-Iranian Plateau

Foreland sedimentary rocks from the northern Fars region of Iran contain a record of deformation associated with the Cenozoic collision between Arabia and Eurasia that resulted in formation of the Zagros orogen. The timing of the deformation associated with this event is poorly known. To address this we conducted a study of Miocene foreland sedimentary rocks (19.7-14.8 Ma) of the Chahar-Makan syncline using clast composition, clay mineralogy and low-temperature fission-track dating. The results showed that most of the sedimentary rocks were sourced from ophiolitic rocks. Detrital apatite fission-track (AFT) age signatures of Miocene sedimentary rocks record exhumation in the hanging wall of the Main Zagros Thrust and confirm that the change from underthrusting of the stretched Arabian margin to widespread crustal thickening and deformation in the Zagros region is no younger than 19.7 Ma. A transition from Late Oligocene to Mesozoic-Eocene AFT detrital age signatures between 19.7-16.6 Ma and 16.6-13.8 Ma is interpreted to reflect a possible rearrangement of palaeodrainage distribution that resulted from folding and expansion-uplift of the Zagros-Iranian Plateau region.

Thermal energetics of the New-Guinean moss-forest rat (Rattus niobe) in comparison with other tropical murid rodents.

The thermal energetics of rodents from cool, wet tropical highlands are poorly known. Metabolic rate, body temperature and thermal conductance were measured in the moss-forest rat, Rattus niobe (Rodentia), a small murid endemic to the highlands of New Guinea. These data were evaluated in the context of the variation observed in the genus Rattus and among tropical murids. In 7 adult R. niobe, basal metabolic rate (BMR) averaged 53.6±6.6mLO2h(-1), or 103% of the value predicted for a body mass of 42.3±5.8g. Compared to other species of Rattus, R. niobe combines a low body temperature (35.5±0.6°C) and a moderately low minimal wet thermal conductance cmin (5.88±0.7mLO2h(-1)°C(-1), 95% of predicted) with a small size, all of which lead to reduced energy expenditure in a constantly cool environment. The correlations of mean annual rainfall and temperature, altitude and body mass with BMR, body temperature and cmin were analyzed comparatively among tropical Muridae. Neither BMR, nor cmin or body temperature correlated with ambient temperature or altitude. Some of the factors which promote high BMR in higher latitude habitats, such as seasonal exposure to very low temperature and short reproductive season, are lacking in wet montane tropical forests. BMR increased with rainfall, confirming a pattern observed among other assemblages of mammals. This correlation was due to the low BMR of several desert adapted murids, while R. niobe and other species from wet habitats had a moderate BMR.

Structure et évolution thermique de la croûte supérieure des chaînes de subduction : approches thermologique et modélisation numérique, dans les North Cascades (U.S.A) et de la zone de faille Motagua (Guatemala)

Cette thèse cible l'étude de la structure thermique de la croûte supérieure (<10km) dans les arcs magmatiques continentaux, et son influence sur l'enregistrement thermochronologique de leur exhumation et de leur évolution topographique. Nous portons notre regard sur deux chaînes de montagne appartenant aux Cordillères Américaines : Les Cascades Nord (USA) et la zone de faille Motagua (Guatemala). L'approche utilisée est axée sur la thermochronologie (U-Th-Sm)/He sur apatite et zircon, couplée avec la modélisation numérique de la structure thermique de la croûte. Nous mettons en évidence la variabilité à la fois spatiale et temporelle du gradient géothermique, et attirons l'attention du lecteur sur l'importance de prendre en compte la multitude des processus géologiques perturbant la structure thermique dans les chaînes de type cordillère, c'est à dire formées lors de la subduction océanique sous un continent.Une nouvelle approche est ainsi développée pour étudier et contraindre la perturbation thermique autour des chambres magmatiques. Deux profiles âge-elevation (U-Th-Sm)/He sur apatite et zircon, ont été collectées 7 km au sud du batholithe de Chilliwack, Cascades Nord. Les résultats montrent une variabilité spatiale et temporelle du gradient géothermique lors de l'emplacement magmatique qui peut être contrainte et séparé de l'exhumation. Durant l'emplacement de l'intrusion, la perturbation thermique y atteint un état d'équilibre (-80-100 °C/km) qui est fonction du flux de magma et de ia distance à la source du magma, puis rejoint 40 °C/km à la fin du processus d'emplacement magmatique.Quelques nouvelles données (U-Th)/He, replacées dans une compilation des données existantes dans les Cascades Nord, indiquent une vitesse d'exhumation constante (-100 m/Ma) dans le temps et l'espace entre 35 Ma et 2 Ma, associée à un soulèvement uniforme de la chaîne contrôlé par l'emplacement de magma dans la croûte durant toute l'activité de l'arc. Par contre, après ~2 Ma, le versant humide de la chaîne est affecté par une accélération des taux d'exhumation, jusqu'à 3 km de croûte y sont érodés. Les glaciations ont un triple effet sur l'érosion de cette chaîne: (1) augmentation des vitesses d'érosion, d'exhumation et de soulèvement la où les précipitations sont suffisantes, (2) limitation de l'altitude contrôlé par la position de Γ Ε LA, (3) élargissement du versant humide et contraction du versant aride de la chaîne.Les modifications des réseaux de drainage sont des processus de surface souvent sous-estimés au profil d'événements climatiques ou tectoniques. Nous proposons une nouvelle approche couplant une analyse géomorphologique, des données thermochronologiques de basse température ((U-Th-Sm)/He sur apatite et zircon), et l'utilisation de modélisation numérique thermo-cinématique pour les mettre en évidence et les dater; nous testons cette approche sur la gorge de la Skagit river dans les North Cascades.De nouvelles données (U-Th)/He sur zircons, complétant les données existantes, montrent que le déplacement horizontal le long de la faille transformante continentale Motagua, la limite des plaques Caraïbe/Amérique du Nord, a juxtaposé un bloc froid, le bloc Maya (s.s.), contre un bloque chaud, le bloc Chortis (s.s.) originellement en position d'arc. En plus de donner des gammes d'âges thermochronologiques très différents des deux côtés de la faille, le déplacement horizontal rapide (~2 cm/a) a produit un fort échange thermique latéral, résultant en un réchauffement du côté froid et un refroidissement du côté chaud de la zone de faille de Motagua.Enfin des données (U-Th-Sm)/He sur apatite témoignent d'un refroidissement Oligocène enregistré uniquement dans la croûte supérieure de la bordure nord de la zone de faille Motagua. Nous tenterons ultérieurement de reproduire ce découplage vertical de la structure thermique par la modélisation de la formation d'un bassin transtensif et de circulation de fluides le long de la faille de Motagua. - This thesis focuses on the influence of the dynamic thermal structure of the upper crust (<10km) on the thermochronologic record of the exhumational and topographic history of magmatic continental arcs. Two mountain belts from the American Cordillera are studied: the North Cascades (USA) and the Motagua fault zone (Guatemala). I use a combined approach coupling apatite and zircon (U-Th-Sm}/He thermochronology and thermo- kinematic numerical modelling. This study highlights the temporal and spatial variability of the geothermal gradient and the importance to take into account the different geological processes that perturb the thermal structure of Cordilleran-type mountain belts (i.e. mountain belts related to oceanic subduction underneath a continent}.We integrate apatite and zircon (U-Th)/He data with numerical thermo-kinematic models to study the relative effects of magmatic and surface processes on the thermal evolution of the crust and cooling patterns in the Cenozoic North Cascades arc (Washington State, USA). Two age-elevation profiles that are located 7 km south of the well-studied Chiliiwack intrusions shows that spatial and temporal variability in geothermal gradients linked to magma emplacement can be contrained and separated from exhumation processes. During Chiliiwack batholith emplacement at -35-20 Ma, the geothermal gradient of the country rocks increased to a very high steady-state value (80-100°C/km), which is likely a function of magma flux and the distance from the magma source area. Including temporally varying geothermal gradients in the analysis allows quantifying the thermal perturbation around magmatic intrusions and retrieving a relatively simple denudation history from the data.The synthesis of new and previously published (U-Th)/He data reveals that denudation of the Northern Cascades is spatially and temporally constant at -100 m/Ma between ~32 and ~2 Ma, which likely reflects uplift due to magmatic crustal thickening since the initiation of the Cenozoic stage of the continental magmatic arc. In contrast, the humid flank of the North Cascades is affected by a ten-fold acceleration in exhumation rate at ~2 Ma, which we interpret as forced by the initiation of glaciations; around 3 km of crust have been eroded since that time. Glaciations have three distinct effects on the dynamics of this mountain range: (1) they increase erosion, exhumation and uplift rates where precipitation rates are sufficient to drive efficient glacial erosion; (2) they efficiently limit the elevation of the range; (3) they lead to widening of the humid flank and contraction of the arid flank of the belt.Drainage reorganizations constitute an important agent of landscape evolution that is often underestimated to the benefit of tectonic or climatic events. We propose a new method that integrates geomorphology, low-temperature thermochronometry (apatite and zircon {U-Th-Sm)/He), and 3D numerical thermal-kinematic modelling to detect and date drainage instability producing recent gorge incision, and apply this approach to the Skagit River Gorge, North Cascades.Two zircon (U-Th)/He age-elevation profiles sampled on both sides of the Motagua Fault Zone (MFZ), the boundary between the North American and the Caribbean plates, combined with published thermochronological data show that strike-slip displacement has juxtaposed the cold Maya block (s.s.) against the hot, arc derived, Chortis block (s.s ), producing different age patterns on both sides of the fault and short-wavelength lateral thermal exchange, resulting in recent heating of the cool side and cooling of the hot side of the MFZ.Finally, an apatite (U-Th-Sm)/He age-elevation profile records rapid cooling at -35 Ma localized only in the upper crust along the northern side of the Motagua fault zone. We will try to reproduce these data by modeling the thermal perturbation resulting from the formation of a transtensional basin and of fluid flow activity along a crustal- scale strike-slip fault.

Micro-patterning of biomolecules on polymer substrates.

UV−excimer laser photoablation was used, in combination with surface blocking techniques, to pattern proteins on the surfaces of polyimide and poly(ethylene terephthalate). This technique involves physical adsorption of avidin through laser-defined openings in low-temperature laminates or adsorbed protein blocking layers. Visualization of biomolecular patterns were monitored using avidin and fluorescein-labeled biotin as a model receptor−ligand couple. Adsorbed proteins could be shown to bind to UV-laser-treated polymer surfaces up to three times higher than on commercially available polymers. UV-laser photoablation was also used for the generation of three-dimensional structure, which leads to the possibility of biomolecule patterning within polymer-based microanalytical systems. The simplicity and easy handling of the described technique facilitate its application in microdiagnostic devices.

Comparison of different methods for thin section EM analysis of Mycobacterium smegmatis.

Bacteria are generally difficult specimens to prepare for conventional resin section electron microscopy and mycobacteria, with their thick and complex cell envelope layers being especially prone to artefacts. Here we made a systematic comparison of different methods for preparing Mycobacterium smegmatis for thin section electron microscopy analysis. These methods were: (1) conventional preparation by fixatives and epoxy resins at ambient temperature. (2) Tokuyasu cryo-section of chemically fixed bacteria. (3) rapid freezing followed by freeze substitution and embedding in epoxy resin at room temperature or (4) combined with Lowicryl HM20 embedding and ultraviolet (UV) polymerization at low temperature and (5) CEMOVIS, or cryo electron microscopy of vitreous sections. The best preservation of bacteria was obtained with the cryo electron microscopy of vitreous sections method, as expected, especially with respect to the preservation of the cell envelope and lipid bodies. By comparison with cryo electron microscopy of vitreous sections both the conventional and Tokuyasu methods produced different, undesirable artefacts. The two different types of freeze-substitution protocols showed variable preservation of the cell envelope but gave acceptable preservation of the cytoplasm, but not lipid bodies, and bacterial DNA. In conclusion although cryo electron microscopy of vitreous sections must be considered the 'gold standard' among sectioning methods for electron microscopy, because it avoids solvents and stains, the use of optimally prepared freeze substitution also offers some advantages for ultrastructural analysis of bacteria.

Two-stage prograde and retrograde Variscan metamorphism of glaucophane-eclogites, blueschists and greenschists from Ile de Groix (Brittany, France)

On Ile de Groix, Variscan metamorphic former tholeiitic and alkaline basalts occur as glaucophane-eclogites, blueschists and greenschists in isolated lenses and layers within metapelites. Whole-rock delta O-18(SMOW) values of the metabasites show limited variations (10.4-12.0 parts per thousand) and no systematic differences among rock types and metamorphic grades. This provides no argument for large-scale blueschist-to-greenschist transformation driven by infiltration of externally derived fluids. Metamorphic mineralogical changes should have been triggered by internal fluids. Element variations in interlayered blue- and greenschists can be attributed to magmatic fractionation. Assemblages with garnet, clinopyroxene and glaucophane of a high-pressure/low-temperature (HP-LT) metamorphism M1, and NaCa-amphiboles (barroisite, magnesiohornblende, actinolite) of a medium-pressure/medium-temperature metamorphism M2 crystallized during deformation Dl. Detailed core-rim zonation profiles display increasing and then decreasing Al-IV in glaucophane of M1. NaCa-amphiboles of M2, mantling glaucophane and crystallized in porphyroblasts, show first increasing, then decreasing, Al-IV and Al-IV. Empirically calibrated thermobarometers allowed P-T path reconstructions. In glaucophane-eclogites of a metamorphic zone I, a prograde evolution to M1 peak conditions at 400-500 degreesC/10-12 kbar was followed by a retrograde P-T path within the glaucophane stability field. The subsequent M2 evolution was again prograde up to > 600 degreesC at 8 kbar and then retrograde. Similarly, in metamorphic zones II and III, prograde and retrograde paths of MI and M2 at lower maximal temperatures and pressures exist. The almost complete metamorphic cycle during M2 signalizes that the HP-LT rocks escaped from an early erosion by a moderate second burial event and explains the longlasting slow uplift with low average cooling rates.

Magmatic-dominated fluid evolution in the Jurassic Nambija gold skarn deposits (southeastern Ecuador)

The Jurassic (approximately 145 Ma) Nambija oxidized gold skarns are hosted by the Triassic volcanosedimentary Piuntza unit in the sub-Andean zone of southeastern Ecuador. The skarns consist dominantly of granditic garnet (Ad(20-98)) with subordinate pyroxene (Di(46-92)Hd(17-42)Jo(0-19)) and epidote and are spatially associated with porphyritic quartz-diorite to granodiorite intrusions. Endoskarn is developed at the intrusion margins and grades inwards into a potassic alteration zone. Exoskarn has an outer K- and Na-enriched zone in the volcanosedimentary unit. Gold mineralization is associated with the weakly developed retrograde alteration of the exoskarn and occurs mainly in sulfide-poor vugs and milky quartz veins and veinlets in association with hematite. Fluid inclusion data for the main part of the prograde stage indicate the coexistence of high-temperature (500A degrees C to > 600A degrees C), high-salinity (up to 65 wt.% eq. NaCl), and moderate- to low-salinity aqueous-carbonic fluids interpreted to have been trapped at pressures around 100-120 MPa, corresponding to about 4-km depth. Lower-temperature (510-300A degrees C) and moderate- to low-salinity (23-2 wt.% eq. NaCl) aqueous fluids are recorded in garnet and epidote of the end of the prograde stage. The microthermometric data (Th from 513A degrees C to 318A degrees C and salinity from 1.0 to 23 wt.% eq. NaCl) and delta(18)O values between 6.2aEuro degrees and 11.5aEuro degrees for gold-bearing milky quartz from the retrograde stage suggest that the ore-forming fluid was dominantly magmatic. Pressures during the early retrograde stage were in the range of 50-100 MPa, in line with the evidence for CO(2) effervescence and probable local boiling. The dominance of magmatic low-saline to moderately saline oxidizing fluids during the retrograde stage is consistent with the depth of the skarn system, which could have delayed the ingression of external fluids until relatively low temperatures were reached. The resulting low water-to-rock ratios explain the weak retrograde alteration and the compositional variability of chlorite, essentially controlled by host rock compositions. Gold was precipitated at this stage as a result of cooling and pH increase related to CO(2) effervescence, which both result in destabilization of gold-bearing chloride complexes. Significant ingression of external fluids took place after gold deposition only, as recorded by delta(18)O values of 0.4aEuro degrees to 6.2aEuro degrees for fluids depositing quartz (below 350A degrees C) in sulfide-rich barren veins. Low-temperature (< 300A degrees C) meteoric fluids (delta(18)O(water) between -10.0aEuro degrees and -2.0aEuro degrees) are responsible for the precipitation of late comb quartz and calcite in cavities and veins and indicate mixing with cooler fluids of higher salinities (about 100A degrees C and 25 wt.% eq. NaCl). The latter are similar to low-temperature fluids (202-74.5A degrees C) with delta(18)O values of -0.5aEuro degrees to 3.1aEuro degrees and salinities in the range of 21.1 to 17.3 wt.% eq. CaCl(2), trapped in calcite of late veins and interpreted as basinal brines. Nambija represents a deep equivalent of the oxidized gold skarn class, the presence of CO(2) in the fluids being partly a consequence of the relatively deep setting at about 4-km depth. As in other Au-bearing skarn deposits, not only the prograde stage but also the gold-precipitating retrograde stage is dominated by fluids of magmatic origin.

Origin of siderite mineralisation in Petrova and Trgovska Gora Mts., NW Dinarides

The Petrova and Trgovska Gora Mts. (Gora=Mountain) are Variscan basement units incorporated into the northwestern Dinarides during the Alpine orogeny. They host numerous siderite-quartz-polysulphide, siderite-chalcopyrite, siderite-galena and barite veins, as well as stratabound hydrothermal-replacement ankerite bodies within carbonates in non-metamorphosed, flysch-like Permo-Carboniferous sequences. The deposits have been mined for Cu, Pb, Ag and Fe ores since Medieval times. Fluid inclusion studies of quartz from siderite-polysulphide-quartz and barite veins of both regions have shown the presence of primary aqueous NaCl-CaCl(2)+/- MgCl(2)-H(2)O +/- CO(2) inclusions. The quartz-sulphide stage of both regions show variable salinities; 2.7-26.2 wt% NaCl eq. for the Trgovska Gora region and 3.4-23.4 wt% NaCl eq. for the Petrova gora region, and similar homogenisation temperatures (100-230A degrees C). Finally, barite is precipitated from low salinity-low temperature solutions (3.7-15.8 wt % NaCl equ. and 115-145A degrees C). P-t conditions estimated via isochore construction yield formation temperatures between 180-250A degrees C for the quartz-sulphide stage and 160-180A degrees C for the barite stage, using a maximum lithostatic pressure of 1 kbar (cc. 3 km of overburden). The sulphur isotope composition of barite from both deposits indicates the involvement of Permian seawater in ore fluids. This is supported by the elevated bromium content of the fluid inclusion leachates (120-660 ppm in quartz, 420-960 ppm in barite) with respect to the seawater, indicating evaporated seawater as the major portion of the ore-forming fluids. Variable sulphur isotope compositions of galena, pyrite and chalcopyrite, between -3.2 and +2.7aEuro degrees, are interpreted as a product of incomplete thermal reduction of the Permian marine sulphate mixed with organically- and pyrite-bound sulphur from the host sedimentary rocks. Ore-forming fluids are interpreted as deep-circulating fluids derived primarily from evaporated Permian seawater and later modified by interaction with the Variscan basement rocks. (40)Ar/(39)Ar data of the detrital mica from the host rocks yielded the Variscan age overprinted by an Early Permian tectonothermal event dated at 266-274 Ma. These ages are interpreted as those reflecting hydrothermal activity correlated with an incipient intracontinental rifting in the Tethyan domain. Nevertheless, 75 Ma recorded at a fine-grained sericite sample from the alteration zone is interpreted as a result of later resetting of white mica during Campanian opening/closure of the Sava back arc in the neighbouring Sava suture zone (Ustaszewski et al. 2008).

Post-Plutonic Magmatism: from the Source to the Emplacement of an Upper Crustal Dyke Swarm, Adamello Massif, Italy

Magmas of the arc-tholeiitic and calc-alkaline differentiation suites contribute substantially to the formation of continental crust in subduction zones. Different geochemical-petrological models have been put forward to achieve evolved magmas forming large volumes of tonalitic to granitic plutons, building an important part of the continental crust. Primary magmas produced in the mantle wedge overlying the subducted slab migrate through the mantle and the crust. During the transfer, magma can accumulate in intermediate reservoirs at different levels where crystallization leads to differentiation and the heat transfer from the magma, together with gained heat from solidification, lead to partial melting of the crust. Partial melts can be assimilated and mix with more primitive magma. Moreover, already formed crystal cumulates or crystal mushes can be recycled and reactivated to transfer to higher crustal levels. Magma transport in the crust involves fow through fractures within a brittle elastic rock. The solidified magma filled crack, a dyke, can crosscut previously formed geological structures and thus serves as a relative or absolute time marker. The study area is situated in the Adamello massif. The Adamello massif is a composite of plutons that were emplaced between 42 and 29 million years. A later dyke swarm intruded into the southern part of the Adamello Batholith. A fractionation model covering dyke compositions from picrobasalts to dacites results in the cummulative crystallization of 17% olivine, 2% Cr-rich spinel, 18% clinopyroxene, 41% amphibole, 4% plagioclase and 0.1% magnetite to achieve an andesitic composition out of a hydrous primitive picrobasalt. These rocks show a similar geochemical evolution as experimental data simulating fractional crystallization and associated magma differentiation at lower crustal depth (7-10 kbar). The peraluminous, corundum normative composition is one characteristic of more evolved dacitic magmas, which has been explained in a long lasting debate with two di_erent models. Melting of mafic crust or politic material provides one model, whereas an alternative is fractionation from primary mantle derived melts. Amphibole occurring in basaltic-andesitic and andesitic dyke rocks as fractionating cumulate phase extracted from lower crustal depth (6-7.5 kbar) is driving the magmas to peraluminous, corundum normative compositions, which are represented by tonalites forming most of the Adamello Batholith. Most primitive picrobasaltic dykes have a slightly steepened chondrite normalized rare earth elements (REE) pattern and the increased enrichment of light-REE (LREE) for andesites and dacites can be explained by the fractional crystallization model originating from a picrobasalt, taking the changing fractionating phase assemblage and temperature into account. The injection of hot basaltic magma (~1050°C) in a closely spaced dyke swarm increases the surface of the contact to the mainly tonalitic wallrock. Such a setting induces partial melting of the wall rock and selective assimilation. Partial melting of the tonalite host is further expressed through intrusion breccias from basaltic dykes. Heat conduction models with instantaneous magma injection for such a dyke swarm geometry can explain features of partial melting observed in the field. Geochemical data of minerals and bulk rock further underline the selective or bulk assimilation of the tonalite host rock at upper crustal levels (~2-3 kbar), in particular with regard to light ion lithophile elements (LILE) such as Sr, Ba and Rb. Primitive picrobasalts carry an immiscible felsic assimilant as enclaves that bring along refractory rutile and zircon with textures typically found in oceanic plagiogranites or high pressure/low-temperature metamorphic rocks in general. U-Pb data implies a lower Cretaceous age for zircon not yet described as assimilant in Eocene to Oligocene magmatic rocks of the Central Southern Alps. The distribution of post-plutonic dykes in large batholiths such as the Adamello is one of the key features for understanding the regional stress field during the post-batholith emplacement cooling history. The emplacement of the regional dyke swarm covering the southern part of the Adamello massif was associated with consistent left lateral strike-slip movement along magma dilatation planes, leading to en echelon segmentation of dykes. Through the dilation by magma of pre-existing weaknesses and cracks in an otherwise uniform host rock, the dyke propagation and according orientation in the horizontal plane adjusted continuously perpendicular to least compressive remote stress σ3, resulting in an inferred rotation of the remote principal stress field. Les magmas issus des zones de subduction contribuent substantiellement à la formation de la croûte continentale. Les plutons tonalitiques et granitiques représentent, en effet, une partie importante de la croûte continentale. Des magmas primaires produits dans le 'mantle wedge ', partie du manteau se trouvant au-dessus de la plaque plongeante dans des zones de subduction, migrent à travers le manteau puis la croûte. Pendant ce transfert, le magma peut s'accumuler dans des réservoirs intermédiaires à différentes profondeurs. Le stockage de magma dans ces réservoirs engendre, d'une part, la différentiation des magmas par cristallisation fractionnée et, d'autre part, une fusion partielle la croûte continentale préexistante associée au transfert de la chaleur des magmas vers l'encaissant. Ces liquides magmatiques issus de la croûte peuvent, ensuite, se mélanger avec des magmas primaires. Le transport du magma dans la croûte implique notamment un flux de magma à travers différentes fractures recoupant les roches encaissantes élastiques. Au cours de ce processus de migration, des cumulats de cristaux ou des agrégats de cristaux encore non-solidifiés, peuvent être recyclés et réactivés pour être transportés à des niveaux supérieures de la croûte. Le terrain d'étude est situé dans le massif d'Adamello. Celui-ci est composé de plusieurs plutons mis en place entre 42 et 29 millions d'années. Dans une phase tardive de l'activité magmatique liée à ce batholite, une série de filons de composition variable allant de picrobasalte à des compositions dacitiques s'est mise en place la partie sud du massif. Deux modèles sont proposés dans la littérature, pour expliquer la formation des magmas dacitiques caractérisés par des compositions peralumineux (i.e. à corindon normatif). Le premier modèle propose que ces magmas soient issus de la fusion de matériel mafique et pélitique présent dans la partie inférieur de la croûte, alors que le deuxième modèle suggère une évolution par cristallisation fractionnée à partir de liquides primaires issus du manteau. Un modèle de cristallisation fractionnée a pu être développé pour expliquer l'évolution des filons de l'Adamello. Ce modèle explique la formation des filons dacitiques par la cristallisation fractionnée de 17% olivine, 2% spinelle riche en Cr, 18% clinopyroxène, 41% amphibole, 4% plagioclase et 0.1% magnetite à partir de liquide de compositions picrobasaltiques. Ce modèle prend en considération les contraintes pétrologiques déduites de l'observation des différents filons ainsi que du champ de stabilité des différentes phases en fonction de la température. Ces roches montrent une évolution géochimique similaire aux données expérimentales simulant la cristallisation fractionnée de magmas évoluant à des niveaux inférieurs de la croûte (7-10 kbar). Le modèle montre, en particulier, le rôle prépondérant de l'amphibole, une phase qui contrôle en particulier le caractère peralumineux des magmas différentiés ainsi que leurs compositions en éléments en traces. Des phénomènes de fusion partielle de l'encaissant tonalitique lors de la mise en place de _lons mafiques sont observée sur le terrain. L'injection du magma basaltique chaud (~1050°C) sous forme de filons rapprochés augmente la surface du contact avec l'encaissante tonalitique. Une telle situation produit la fusion partielle des roches encaissantes nécessaire à l'incorporation d'enclaves mafiques observés au sein des tonalites. Pour comprendre les conditions nécessaires pour la fusion partielle des roches encaissantes, des modèles de conduction thermique pour une injection simultanée d'une série de filons ont été développées. Des données géochimiques sur les minéraux et sur les roches totales soulignent qu'au niveau supérieur de la croûte, l'assimilation sélective ou totale de l'encaissante tonalitique modifie la composition du liquide primaire pour les éléments lithophiles tel que le Sr, Ba et Rb. Un autre aspect important concernant la pétrologie des filons de l'Adamello est la présence d'enclaves felsiques dans les filons les plus primitifs. Ces enclaves montrent, en particulier, des textures proches de celles rencontrées dans des plagiogranites océaniques ou dans des roches métamorphiques de haute pression/basse température. Ces enclaves contiennent du zircon et du rutile. La datations de ces zircons à l'aide du géochronomètre U-Pb indique un âge Crétacé inférieur. Cet âge est important, car aucune roche de cet âge n'a été considérée comme un assimilant potentiel pour des roches magmatiques d'âge Eocène à Oligocène dans les Alpes Sud Centrales. La réparation spatiale des filons post-plutoniques dans des grands batholites tel que l'Adamello, est une caractéristique clé pour la compréhension des champs de contraintes lors du refroidissement du batholite. L'orientation des filons va, en particulier, indiqué la contrainte minimal au sein des roches encaissante. La mise en place de la série de filon recoupant la partie Sud du massif de l'Adamello est associée à un décrochement senestre, un décrochement que l'on peut lié aux contraintes tectoniques régionales auxquelles s'ajoutent l'effet de la dilatation produite par la mise en place du batholite lui-même. Ce décrochement senestre produit une segmentation en échelon des filons.

Glucose release from GLUT2-null hepatocytes: characterization of a major and a minor pathway.

We previously reported that glucose can be released from GLUT2-null hepatocytes through a membrane traffic-based pathway issued from the endoplasmic reticulum. Here, we further characterized this glucose release mechanism using biosynthetic labeling protocols. In continuous pulse-labeling experiments, we determined that glucose secretion proceeded linearly and with the same kinetics in control and GLUT2-null hepatocytes. In GLUT2-deficient hepatocytes, however, a fraction of newly synthesized glucose accumulated intracellularly. The linear accumulation of glucose in the medium was inhibited in mutant, but not in control, hepatocytes by progesterone and low temperature, as previously reported, but, importantly, also by microtubule disruption. The intracellular pool of glucose was shown to be present in the cytosol, and, in pulse-chase experiments, it was shown to be released at a relatively slow rate. Release was not inhibited by S-4048 (an inhibitor of glucose-6-phosphate translocase), cytochalasin B, or progesterone. It was inhibited by phloretin, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, and low temperature. We conclude that the major release pathway segregates glucose away from the cytosol by use of a membrane traffic-based, microtubule-dependent mechanism and that the release of the cytosolic pool of newly synthesized glucose, through an as yet unidentified plasma membrane transport system, cannot account for the bulk of glucose release.

Elemental and isotopic zoning in natural alpine quartz

THESIS ABSTRACT : Stable isotope geochemistry is used to help resolve a large number of geological questions. In order to do this, it is essential to understand the different mechanisms that govern isotopic fractionation processes between different phases and to identify the conditions required to reach equilibrium fractionation. However, at low temperatures, these processes are poorly constrained and many factors can induce differential partitioning of the isotopes between sectors of a mineral species and the fluid during mineral growth. This can result in so-called 'sector zoning' of a mineral species. The aim of this thesis is to evaluate the occurrence of sector zoning of the oxygen isotopes and trace elements in natural α-quartz crystals and to identify the reasons for such zoning. The implications for the fluid-mineral interactions are studied in the context of the Alpine metamorphism. The approach chosen has focused on examining the crystal structure, cathodoluminescence appearance (CL), and on relating elemental (e.g. Li, Na, Al, P, K, Ca, Ge, Ti, Fe) to stable oxygen isotope compositions between and along different growth sectors. Low temperature quartz samples were selected from Alpine veins in different localities, where growth conditions have already been well constrained. The mineralogy as well as the isotopic compositions of the host rocks were also investigated, in order to interpret the variations obtained between the different growth stages in the framework of fluid-rock interaction during Alpine metamorphism. Depending on the growth conditions, most of the studied quartz is strongly zoned in CL, and it reveals corresponding zonations in the trace element content (e.g. growth zoning). Aluminium, substituting for Si in the lattice, was found in concentrations up to 1000's ppma, and its distribution is strongly related to Li and H and to a lesser extent, to Ge. Elemental sector zoning is evident from the distribution of these three elements since they exhibit differences in their respective concentrations between faces for distinct growth zones, with prismatic faces having the lowest Al contents. Quartz from veins in magmatic rocks, for example, tend to have lower Al concentrations and similar concentrations of Li and Ti suggesting also a contribution of these elements from the host rock. The relationship between Al and Li is still correlated. Only Alpine crystals grown at higher temperatures (~400°C) without any CL zoning feature are free of these impurities and do not show such zoning characteristics. Differences in the δ18O values were measured between different faces principally in the AIenriched growth zones or stages. These results were confirmed by the means of two different methods (in situ/non in situ). However, it was determined that the Al concentrations do not affect significantly oxygen isotope fractionations at 300°C. The results altogether suggest that the presence of sector zoning in quartz crystals is real, but not universal, and henceforth should be taken into consideration for any use of these systems. The occurrence of disequilibrium partitioning has been enhanced and is possibly related to kinetic processes as well as structural effects that do not affect similarly trace element incorporation and isotopic fractionation. In situ measurements also revealed fine scale δ18O zonations along growth paths that are useful to constrain fluid-rock interactions during Alpine metamorphism. Variations in the δ18O values present along growth vectors indicate changes in the fluid composition and origin. Association with oxygen isotope composition of the host rock allows for the deduction of interactions between rocks, veins and consequently fluids, as well as fluid regimes. RESUME DE LA THESE : A basses températures, (i.e. <400°C) les différents mécanismes qui régissent le fractionnement isotopique ainsi que les conditions nécessaires pour établir un état d'équilibre sont peu connus et nombre de paramètres peuvent entraîner un partitionnement chimique différentiel entre différents secteurs d'un minéral et le fluide en contact. Ainsi, ce travail de thèse a pour but d'évaluer la possible présence de zonages sectoriels en isotopes de l'oxygène mais aussi en éléments traces dans des cristaux naturels de quartz-α de basses températures, ainsi que les raisons d'un tel phénomène et enfin ses implications sur les interactions fluide-roche, principalement dans le cadre du métamorphisme Alpin. La structure et l'apparence en cathodoluminescence (CL) des échantillons ont été caractérisées avant de retracer en détail les compositions en élément traces (Li, Na, Al, P, K, Ca, Ge, Ti, Fe) et en isotopes de l'oxygène, le long et entre différents secteurs. Les échantillons de quartz sélectionnés proviennent majoritairement de veines Alpine de différentes localités, où les conditions de croissance ont été déjà bien caractérisées. Les compositions minéralogiques et isotopiques de la roche encaissante ont aussi été examinées, pour contraindre les variations obtenues dans un contexte Alpin. Selon leurs conditions de croissance, la plupart des cristaux étudiés sont fortement zonés, ce qui est souligné par un zonage des concentrations en éléments traces (e.g. zonage de croissance). L'Aluminium, qui peut se substituer à la Silice dans le réseau cristallin, a été retrouvé jusqu'en très grandes concentrations dans certaines zones (plusieurs milliers de ppma). De plus, la distribution en Al est fortement liée à celles de Li et H, ainsi que dans une moindre mesure à Ge. La présence de zonage sectoriel est évidente au niveau de ces éléments qui montrent de larges différences de concentrations entre différentes faces pour une même zone de croissance, avec les concentrations les plus basses retrouvées dans les faces prismatiques. Les quartz de veines situées dans des roches magmatiques par exemple possèdent des concentrations en Li et Ti de même ordre de grandeur, confirmant le rôle de la composition de la roche encaissante. La relation Li/Al est toujours fortement présente, mais ce rapport est fonction de la face mesurée. Seuls les cristaux Alpins de plus hautes températures (400°C) ne possédant pas de zones en CL ne présentent aucune de ces caractéristiques. Des différences dans les valeurs de δ18O de zones identiques enrichies en Al ont clairement été mesurées entre les différentes faces r, z, et m, mais aussi au sein d'une même seule zone, indiquant que le fractionnement a probablement eu lieu en déséquilibre. Il a été déterminé que la présence d'Al dans ces teneurs n'avait qu'un faible effet sur le fractionnement isotopique de l'oxygène. L'utilisation de deux méthodes différentes a permis d'obtenir des résultats in situ et non in situ concordants. La comparaison des résultats obtenus permet de démontrer que le zonage sectoriel est bien présent dans certains cristaux de quartz, et dépend des conditions de formation. La présence d'un partitionnement différentiel des éléments traces peut être due à des effets cinétiques aussi bien que structuraux, alors que le zonage sectoriel des isotopes de l'oxygène aurait d'autres origines. Il est alors évident que la possibilité de zonage sectoriel doit être désormais pris en considération avant toute interprétations de données isotopiques de cristaux zonés. Les mesures in situ ont de plus permis de distinguer de fines variations des valeurs δ18O au cours de la croissance, qui peuvent aider à retracer la circulations des fluides dans les Alpes durant cette période. En association avec les compositions des roches encaissantes, ii est possible de déduire les interactions entre roches, veines, et par conséquent fluides, au cours de différentes étapes. RESUME GRAND PUBLIC : La géochimie des isotopes stables a pris beaucoup d'importance depuis ces dernières années pour aider à résoudre nombre de questions géologiques, en se basant sur les caractéristiques du fractionnement isotopiques pour différents systèmes. Il est donc nécessaire d'avoir une connaissance approfondie des mécanismes qui s'appliquent au fractionnement isotopique entre les minéraux et les fluides à partir desquels ils se forment. Ces mécanismes ont été bien approchés par différents types de calibrations pour des systèmes à hautes températures, cependant cela n'est pas aussi évident pour les systèmes à des températures inférieures à 400-500°C. Ce travail de thèse a pour but d'aider à la description et la compréhension des phénomènes qui peuvent affecter le fractionnement isotopique à basses températures, ainsi que leurs implications, à partir de l'étude de cristaux de quartz. Le choix des échantillons s'est porté sur des cristaux naturels formés à des températures inférieures ou égales à 400°C, provenant majoritairement de fissures hydrothermales Alpines dont les conditions de formation ont déjà été déterminées. L'étude des cristaux Alpin permet de plus de replacer les résultats obtenus dans le contexte du métamorphisme Alpin au cours du Miocène (21-13 Ma). Après examen de la structure et de la morphologie des cristaux, et leur caractérisation par cathodoluminescence (CL), des analyses chimiques détaillées sur les éléments en traces pouvant entrer dans le réseau cristallin du quartz comme impuretés (i.e. Li, Na, Al, P, K, Ca, Ge, Ti), et des isotopes stables de l'oxygène, ont été menées. En fonction des conditions de croissance, la plupart des cristaux présentent des zonations, qui peuvent être facilement reliées à la distribution des éléments traces analysés par microsonde électronique, sonde ionique (SIMS) et LA-ICPMS. De fortes concentrations d'Aluminium (plusieurs milliers de parties par million atomique) ont pu être observées dans les zones les plus externes des cristaux. De plus, les concentrations en Al et en Li sont toujours corrélées; la présence d'Hydrogène déduite à partir d'analyses par FTIR suit cette même tendance. Les différentes faces des cristaux présentent des concentrations distinctes d'Al, Li et H pour des mêmes zones de croissance, avec par exemple les concentrations les plus faibles dans les zones des faces prismatiques. Cela implique la présence d'un zonage sectoriel, qui a déjà été observé principalement dans des carbonates mais jamais décrit auparavant pour des quartz. Seuls les cristaux alpins homogènes en CL dont la croissance s'est faite à plus haute température (400°C) ne présentent aucune de ces caractéristiques. Par analogie avec le zonage sectoriel en Al, élément qui se substitue au Si dans le réseau cristallin du quartz, il est possible de penser qu'un zonage sectoriel pourrait aussi s'appliquer aux isotopes de l'oxygène. Des précédentes études avaient en effet émis cette hypothèse. Nos résultats ont été obtenus à partir d'analyses à la fois in- situ par SIMS, et par extraction assistée par laser-CO2 sur des parties de quartz soigneusement séparées, et sont en accord entre les deux méthodes. Un zonage sectoriel est en effet bien présent pour les cristaux alpins, mais principalement au niveau des zones très riches en Aluminium. Cependant, il a été déterminé que la présence d'Al dans ces teneurs avait un effet plus que minimal sur le fractionnement isotopique de l'oxygène. Des différences importantes ont été observées entre les faces r & z mais aussi au sein d'une même et seule zone, indiquant que le fractionnement a pu avoir lieu en déséquilibre, ce qui est aussi visible au niveau des valeurs totalement opposées entre faces pour la dernière phase de croissance de certains cristaux. Ainsi l'association de ces résultats laisse suggérer que la présence d'un zonage sectoriel peut être liée à différents paramètres tels que le taux de croissance ou la structure de surface du cristal, mais qui n'affectent pas de la même façon l'incorporation des éléments traces et le fractionnement isotopique. La possibilité d'un zonage sectoriel est importante à prendre en compte lors de toute interprétation de données isotopiques. Les analyses des isotopes de l'oxygène effectuées par SIMS ont aussi permis de distinguer des variations importantes à petite échelle au cours de la croissance. Des mesures faites par laser CO2 sur certaines roches encaissantes, ont permis distinguer plusieurs étapes dans la croissance des minéraux et de déduire le rôle de l'encaissant et le type de fluide. En association avec de précédentes études, il a été ainsi possible de mieux contraindre la formation de ces cristaux dans le contexte alpin et la circulation de fluide au cours du métamorphisme alpin durant le Miocène.

Design and establishment of a biobank in a multicenter prospective cohort study of elderly patients with venous thromboembolism (SWITCO65+).

In the field of thrombosis and haemostasis, many preanalytical variables influence the results of coagulation assays and measures to limit potential results variations should be taken. To our knowledge, no paper describing the development and maintenance of a haemostasis biobank has been previously published. Our description of the biobank of the Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+) is intended to facilitate the set-up of other biobanks in the field of thrombosis and haemostasis. SWITCO65+ is a multicentre cohort that prospectively enrolled consecutive patients aged ≥65 years with venous thromboembolism at nine Swiss hospitals from 09/2009 to 03/2012. Patients will be followed up until December 2013. The cohort includes a biobank with biological material from each participant taken at baseline and after 12 months of follow-up. Whole blood from all participants is assayed with a standard haematology panel, for which fresh samples are required. Two buffy coat vials, one PAXgene Blood RNA System tube and one EDTA-whole blood sample are also collected at baseline for RNA/DNA extraction. Blood samples are processed and vialed within 1 h of collection and transported in batches to a central laboratory where they are stored in ultra-low temperature archives. All analyses of the same type are performed in the same laboratory in batches. Using multiple core laboratories increased the speed of sample analyses and reduced storage time. After recruiting, processing and analyzing the blood of more than 1,000 patients, we determined that the adopted methods and technologies were fit-for-purpose and robust.