Increased flow of fatty acids toward beta-oxidation in developing seeds of Arabidopsis deficient in diacylglycerol acyltransferase activity or synthesizing medium-chain-length fatty acids.

Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fatty acid beta-oxidation was used as a tool to study fatty acid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0. 06 mg g(-1) dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward beta-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fatty acids into triacylglycerides by recycling the fatty acids via beta-oxidation and that a considerable flow toward beta-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids.

Dose-dependent effect of atrial natriuretic peptide on blood pressure, heart rate, and skin blood flow of normal volunteers.

Synthetic atrial natriuretic peptide, containing 26 amino acids in the rat sequence, L-364, 343 (Ileu-ANP), was infused intravenously at increasing rates (1-40 micrograms/min) into four normal volunteers. Mean intraarterial blood pressure decreased and heart rate increased in cumulative-dose-dependent fashion. Skin blood flow as measured with a laser Doppler device rose already with a cumulative dose of 55 micrograms Ileu-ANP and further rises were directly related to dose. The only side effects observed were those accompanying symptomatic hypotension at higher doses. These findings provide strong evidence that Ileu-ANP acts as a vasodilator in normal volunteers.

A stable and 40Ar/39Ar isotope study of a major thrust in the Helvetic nappes (Swiss Alps) - Evidence for fluid-flow and constraints on nappe kinematics

Stable isotope and Ar-40/Ar-39 measurements,were made on samples associated with a major tectonic discontinuity in the Helvetic Alps, the basal thrust of the Diablerets nappe (external zone of the Alpine Belt) in order to determine both the importance of fluids in this thrust zone and the timing of thrusting. A systematic decrease in the delta(18)O values (up to 6 parts per thousand) of calcite, quartz, and white mica exists within a 10- to 70-m-wide zone over a distance of 37 km along the thrust, and they become more pronounced toward the root of the nappe. A similar decrease in the delta(13)C values of calcite is observed only in the deepest sections (up to 3 parts per thousand). The delta D-SMOW (SMOW = standard mean ocean water) values of white mica are -54 parts per thousand +/- 8 parts per thousand (n = 22) and are independent of the distance from the thrust. These variations are interpreted to reflect syntectonic solution reprecipitation during fluid passage along the thrust. The calculated delta(18)O and delta D values (versus SMOW) for the fluid in equilibrium with the analyzed minerals is 12 parts per thousand to 16 parts per thousand and -30 parts per thousand to +5 parts per thousand, respectively, for assumed temperatures of 250 to 450 degrees C. The isotopic and structural data are consistent with fluids derived from the deep-seated roots of the Helvetic nappes where large volumes of Mesozoic sediments were metamorphosed to the amphibolite facies, It is suggested that connate and metamorphic waters, overpressured by rapid tectonic burial in a subductive system escaped by upward infiltration along moderately dipping pathways until they reached the main shear zone at the base of the moving pile, where they were channeled toward the surface, This model also explains the mechanism by which large amounts of fluid were removed from the Mesozoic sediments during Alpine metamorphism. White mica Ar-49/Ar-39 ages vary from 27 Ma far from the Diablerets thrust to 15 Ma along the thrust. An older component is observed in micas far from the thrust, interpreted as a detrital signature, and indicates that regional metamorphic temperatures were less than about 350 degrees C. The;plateau and near plateau ages nearest the thrust are consistent with either neocrystallization of white mica or argon loss by recrystallization during thrusting, which may have been enhanced in the zones of highest fluid flow. The 15 Ma Ar-40/Ar-39 age plateau measured on white mica sampled exactly on the thrust surface dates the end of both fluid flow and tectonic transport.

Shallow-level migmatization of gabbros in a metamorphic contact aureole, Fuerteventura Basal Complex, Canary Islands

Migmatization of gabbroic rocks at 2-3 kbar has occurred in the metamorphic contact aureole of a mafic pluton in the Fuerteventura Basal Complex (Canary Island;). Migmatites are characterized by a dense network: of closely spaced millimetre-wide leucocratic veins with perfectly preserved igneous textures. They are all relatively enriched in Al, Na I: Sr Ba, Nb, Y and the rare earth elements compared with the unaffected country rock beyond the aureole. Migmatization under such low-pressure conditions war possible because of the unusual tectonic and magmatic contact in which ii occurred. Multiple basic intrusions associated with extrusive volcanic activity created high heat flow in a small area. Alkaline and metasomatized rocks present in the country rock of the intruding pluton were leached by high-temperature fluids during contact metamorphism. These enriched fluids then favoured partial melting of the host gabbroic rocks, and contaminated both the leucosomes and melanosomes. A transpressive tectonic setting at the time of intrusion created shearing along the contact between the intrusion and its host rock. This shearing enhanced circulation of the fluids and allowed segregation of the nea-formed melts from their restite by opening tension veins into which the melts migrated. Depending on the relative timing of melt segregation and recrystallization leucosomes range in composition from a 40-60% mixture of clinopyroxene (+/- amphibole) and plagioclase to almost pure feldspathic veins. Comparable occurrences of gabbros migmatized at low pressure are expected only at a snail scale in localized areas of high heat flow in the presence of fluids, such as in. mid-ocean ridges or ocean-islands.

Formation of chlorite during thrust fault reactivation. Record of fluid origin and P-T conditions in the Monte Perdido thrust fault (southern Pyrenees)

The chemical and isotopic compositions of clay minerals such as illite and chlorite are commonly used to quantify diagenetic and low-grade metamorphic conditions, an approach that is also used in the present study of the Monte Perdido thrust fault from the South Pyrenean fold-and-thrust belt. The Monte Perdido thrust fault is a shallow thrust juxtaposing upper Cretaceous-Paleocene platform carbonates and Lower Eocene marls and turbidites from the Jaca basin. The core zone of the fault, about 6 m thick, consists of intensely deformed clay-bearing rocks bounded by major shear surfaces. Illite and chlorite are the main hydrous minerals in the fault zone. Illite is oriented along cleavage planes while chlorite formed along shear veins (< 50 mu m in thickness). Authigenic chlorite provides essential information about the origin of fluids and their temperature. delta O-18 and delta D values of newly formed chlorite support equilibration with sedimentary interstitial water, directly derived from the local hanging wall and footwall during deformation. Given the absence of large-scale fluid flow, the mineralization observed in the thrust faults records the P-T conditions of thrust activity. Temperatures of chlorite formation of about 240A degrees C are obtained via two independent methods: chlorite compositional thermometers and oxygen isotope fractionation between cogenetic chlorite and quartz. Burial depth conditions of 7 km are determined for the Monte Perdido thrust reactivation, coupling calculated temperature and fluid inclusion isochores. The present study demonstrates that both isotopic and thermodynamic methods applied to clay minerals formed in thrust fault are useful to help constrain diagenetic and low-grade metamorphic conditions.

Preservation of an extreme transient geotherm in the Raft River detachment shear zone

Extensional detachment systems separate hot footwalls from cool hanging walls, but the degree to which this thermal gradient is the product of ductile or brittle deformation or a preserved original transient geotherm is unclear. Oxygen isotope thermometry using recrystallized quartz-muscovite pairs indicates a smooth thermal gradient (140 degrees C/100 m) across the gently dipping, quartzite-dominated detachment zone that bounds the Raft River core complex in northwest Utah (United States). Hydrogen isotope values of muscovite (delta D-Ms similar to-100 parts per thousand) and fluid inclusions in quartz (delta D-Fluid similar to-85 parts per thousand) indicate the presence of meteoric fluids during detachment dynamics. Recrystallized grain-shape fabrics and quartz c-axis fabric patterns reveal a large component of coaxial strain (pure shear), consistent with thinning of the detachment section. Therefore, the high thermal gradient preserved in the Raft River detachment reflects the transient geotherm that developed owing to shearing, thinning, and the potentially prominent role of convective flow of surface fluids.

A new approach in the treatment of high flow native AV fistula: the open-pore external scaffolding prosthesis

Objective: The vascular access steal syndrome is a complication occurring in 1-6% after native arterio-venous (AV) fistulas, often due to huge diameter of the vein. This results in very high flow, which could also be responsible for cardiac overload. The aim of this study is to evaluate the efficiency of a new approach in the treatment of this pathology using open-pore external scaffolding prosthesis.Methods: This a retrospective review of all patients presenting symptomatic high flow after native AV fistula between January 2007 and December 2009 in 3 vascular centers. Pre-operative duplex exam confirmed the diagnosis of high flow. The operation consisted in preparation of the whole fistula, measurement of the flow and section on the venous side. The vein was wrapped with this 6 to 8 mm open-pore external scaffolding prosthesis (ProVena, BBraun, Germany) according to its diameter and to the flow and then sutured. Measurement of the flow was repeated. Patients were followed by duplex exam at 1 week and at 1, 3, 6 and 12 months. Procedural success was defined as complete implantation of the prosthesis and reduction of the flow. Primary outcomes were reduction of the flow and recovery of the symptoms and secondary endpoint was patency of the fistula.Results: During the study period, 14 patients, with a mean age of 65・8 years old, have been operated with this technique.There were 2 native forearmfistulas and 12 on the armwith a mean pre-operative flow of 2600 ml/min (1800-3800). The mode of presentation was pain in 6 patients, neurological disorders in 10 and necrosis in 4. Moreover, 3 patients had cardiac insufficiency due to high flow in the fistula. The procedure was technically successful in 100% of cases. Re-intervention was necessary in 2 patients due to hematoma. Recovery of the initial symptoms occurred in 13 patients (93%). The mean flow reduction was 1200 ml/min (600-2000). In 1 patient, a persistent steal syndrome despite flow reduction to 1400 ml/min resulted in fistula closure 2 months later. At a mean follow-up of 22 months (4-35), all remaining patients (13/14) presented a patent fistula without recurrence.Conclusion: This new approach seems to be safe and effective in the treatment of symptomatic high flow native AV fistulas by significantly reducing the flow and avoiding closure of the vascular access. Longer follow-up with more patients are necessary to evaluate the risk of recurrence.

Continuous arterial spin labeling of mouse cerebral blood flow using an actively-detuned two-coil system at 9.4T.

Among numerous magnetic resonance imaging (MRI) techniques, perfusion MRI provides insight into the passage of blood through the brain's vascular network non-invasively. Studying disease models and transgenic mice would intrinsically help understanding the underlying brain functions, cerebrovascular disease and brain disorders. This study evaluates the feasibility of performing continuous arterial spin labeling (CASL) on all cranial arteries for mapping murine cerebral blood flow at 9.4 T. We showed that with an active-detuned two-coil system, a labeling efficiency of 0.82 ± 0.03 was achieved with minimal magnetization transfer residuals in brain. The resulting cerebral blood flow of healthy mouse was 99 ± 26 mL/100g/min, in excellent agreement with other techniques. In conclusion, high magnetic fields deliver high sensitivity and allowing not only CASL but also other MR techniques, i.e. (1)H MRS and diffusion MRI etc, in studying murine brains.

Fluid evolution at the Variscan front in the vicinity of the Aachen thrust

Quartz-carbonate-chlorite veins were studied in borehole samples of the RWTH-1 well in Aachen. Veins formed in Devonian rocks in the footwall of the Aachen thrust during Variscan deformation and associated fluid flow. Primary fluid inclusions indicate subsolvus unmixing of a homogenous H(2)O-CO(2)-CH(4)-(N(2))-Na-(K)-Cl fluid into a H(2)O-Na-(K)-Cl solution and a vapour-rich CO(2)-(H(2)O, CH(4), N(2)) fluid. The aqueous end-member composition resembles that of metamorphic fluids of the Variscan front zone with salinities ranging from 4 to 7% NaCl equiv. and maximum homogenisation temperatures of close to 400A degrees C. Pressure estimates indicate a burial depth between 4,500 and 8,000 m at geothermal gradients between 50 and 75A degrees C/26 MPa, but pressure decrease to sublithostatic conditions is also indicated, probably as a consequence of fracture opening during episodic seismic activity. A second fluid system, mainly preserved in pseudo-secondary and secondary fluid inclusions, is characterised by fluid temperatures between 200 and 250A degrees C and salinities of < 5% NaCl equiv. Bulk stable isotope analyses of fluids released from vein quartz, calcite, and dolomite by decrepitation yielded delta D(H2O) values from -89 to -113 aEuro degrees, delta(13)C(CH4) from -26.9 to -28.9aEuro degrees (VPDB) and delta(13)C(CO2) from -12.8 to -23.3aEuro degrees (VPDB). The low delta D and delta(13)C range of the fluids is considered to be due to interaction with cracked hydrocarbons. The second fluid influx caused partial isotope exchange and disequilibrium. It is envisaged that an initial short lived flux of hot metamorphic fluids expelled from the epizonal metamorphic domains of the Stavelot-Venn massif. The metamorphic fluid was focused along major thrust faults of the Variscan front zone such as the Aachen thrust. A second fluid influx was introduced from formation waters in the footwall of the Aachen thrust as a consequence of progressive deformation. Mixing of the cooler and lower salinity formation water with the hot metamorphic fluid during episodic fluid trapping resulted in an evolving range of physicochemical fluid inclusion characteristics.

Direct numerical simulations of interface dynamics to link capillary pressure and total surface energy

The flow of two immiscible fluids through a porous medium depends on the complex interplay between gravity, capillarity, and viscous forces. The interaction between these forces and the geometry of the medium gives rise to a variety of complex flow regimes that are difficult to describe using continuum models. Although a number of pore-scale models have been employed, a careful investigation of the macroscopic effects of pore-scale processes requires methods based on conservation principles in order to reduce the number of modeling assumptions. In this work we perform direct numerical simulations of drainage by solving Navier-Stokes equations in the pore space and employing the Volume Of Fluid (VOF) method to track the evolution of the fluid-fluid interface. After demonstrating that the method is able to deal with large viscosity contrasts and model the transition from stable flow to viscous fingering, we focus on the macroscopic capillary pressure and we compare different definitions of this quantity under quasi-static and dynamic conditions. We show that the difference between the intrinsic phase-average pressures, which is commonly used as definition of Darcy-scale capillary pressure, is subject to several limitations and it is not accurate in presence of viscous effects or trapping. In contrast, a definition based on the variation of the total surface energy provides an accurate estimate of the macroscopic capillary pressure. This definition, which links the capillary pressure to its physical origin, allows a better separation of viscous effects and does not depend on the presence of trapped fluid clusters.

Optimized venous return with a self-expanding cannula: from computational fluid dynamics to clinical application.

The Smart canula concept allows for collapsed cannula insertion, and self-expansion within a vein of the body. (A) Computational fluid dynamics, and (B) bovine experiments (76+/-3.8 kg) were performed for comparative analyses, prior to (C) the first clinical application. For an 18F access, a given flow of 4 l/min (A) resulted in a pressure drop of 49 mmHg for smart cannula versus 140 mmHg for control. The corresponding Reynolds numbers are 680 versus 1170, respectively. (B) For an access of 28F, the maximal flow for smart cannula was 5.8+/-0.5 l/min versus 4.0+/-0.1 l/min for standard (P<0.0001), for 24F 5.5+/-0.6 l/min versus 3.2+/-0.4 l/min (P<0.0001), and for 20F 4.1+/-0.3 l/min versus 1.6+/-0.3 l/min (P<0.0001). The flow obtained with the smart cannula was 270+/-45% (20F), 172+/-26% (24F), and 134+/-13% (28F) of standard (one-way ANOVA, P=0.014). (C) First clinical application (1.42 m2) with a smart cannula showed 3.55 l/min (100% predicted) without additional fluids. All three assessment steps confirm the superior performance of the smart cannula design.

Stable hydrogen and oxygen isotope composition of waters from mine tailings in different climatic environments

The stable isotope composition of waters (delta H-2, delta O-18) can be used as a natural tracer of hydrologic processes in systems affected by acid mine drainage. We investigated the delta H-2 and delta O-18 values of pore waters from four oxidizing sulfidic mine tailings impoundments in different climatic regions of Chile (Piuquenes at La Andina with Alpine climate, Cauquenes and Caren at El Teniente with Mediterranean climate, and Talabre at the Chuquicamata deposit with hyperarid climate). No clear relationship was found between altitude and isotopic composition. The observed displacement of the tailings pore waters from the local meteoric water line toward higher delta O-18 values (by similar to +2% delta O-18 relative to delta H-2) is partly due to water-rock interaction processes, including hydration and O-isotope exchange with sulfates and Fe(III) oxyhydroxides produced by pyrite oxidation. In most tailings, from the saturated zone toward the surface, isotopically different zones can be distinguished. Zone I is characterized by an upward depletion of H-2 and O-18 in the pore waters from the saturated zone and the lowermost vadose zone, due to ascending diffused isotopically light water triggered by the constant loss of water vapor by evaporation at the surface. In zone II, the capillary flow of a mix of vapor and liquid water causes an evaporative isotopic enrichment in H-2 and O-18. At the top of the tailings in dry climate a zone III between the capillary zone and the surface contains isotopically light diffused and atmospheric water vapor. In temperate climates, the upper part of the profile is affected by recent rainfall and zone III may not differ isotopically from zone II.

Origin of amphibole megacrysts in the Pliocene-Pleistocene basalts of the Carpathian-Pannonian region

Major and trace element compositions, stable H and 0 isotope compositions and Fe 31 contents of amphibole megacrysts of Pliocene-Pleistocene alkaline basalts have been investigated to obtain information on the origin of mantle fluids beneath the Carpathian-Pannonian region. The megacrysts have been regarded as igneous cumulates formed in the mantle and brought to the surface by the basaltic magma. The studied amphiboles have oxygen isotope compositions (5.4 +/- 0.2 %., 1 sigma), supporting their primary mantle origin. Even within the small 6180 variation observed, correlations with major and trace elements are detected. The negative delta(18)O-MgO and the positive delta(18)O-La/Sm(N) correlations are interpreted to have resulted from varying degrees of partial melting. The halogen (F, Cl) contents are very low (< 0.1 wt. %), however, a firm negative (F+Cl)-MgO correlation (R(2) = 0.84) can be related to the Mg-Cl avoidance in the amphibole structure. The relationships between water contents, H isotope compositions and Fe 31 contents of the amphibole megacrysts revealed degassing. Selected undegassed amphibole megacrysts show a wide 813 range from -80 to -20 parts per thousand. The low delta D value is characteristic of the normal mantle, whereas the high delta D values may indicate the influence of fluids released from subducted oceanic crust. The chemical and isotopic evidence collectively suggest that formation of the amphibole megacrysts is related to fluid metasomatism, whereas direct melt addition is insignificant.

Quantification of nicotine, cotinine, trans-3'-hydroxycotinine and varenicline in human plasma by a sensitive and specific UPLC-tandem mass-spectrometry procedure for a clinical study on smoking cessation.

A sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of nicotine, its metabolites cotinine and trans-3'-hydroxycotinine and varenicline in human plasma was developed and validated. Sample preparation was realized by solid phase extraction of the target compounds and of the internal standards (nicotine-d4, cotinine-d3, trans-3'-hydroxycotinine-d3 and CP-533,633, a structural analog of varenicline) from 0.5mL of plasma, using a mixed-mode cation exchange support. Chromatographic separations were performed on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1×100mm, 1.7μm). A gradient program was used, with a 10mM ammonium formate buffer pH 3/acetonitrile mobile phase at a flow of 0.4mL/min. The compounds were detected on a triple quadrupole mass spectrometer, operated with an electrospray interface in positive ionization mode and quantification was performed using multiple reaction monitoring. Matrix effects were quantitatively evaluated with success, with coefficients of variation inferior to 8%. The procedure was fully validated according to Food and Drug Administration guidelines and to Société Française des Sciences et Techniques Pharmaceutiques. The concentration range was 2-500ng/mL for nicotine, 1-1000ng/mL for cotinine, 2-1000ng/mL for trans-3'-hydroxycotinine and 1-500ng/mL for varenicline, according to levels usually measured in plasma. Trueness (86.2-113.6%), repeatability (1.9-12.3%) and intermediate precision (4.4-15.9%) were found to be satisfactory, as well as stability in plasma. The procedure was successfully used to quantify nicotine, its metabolites and varenicline in more than 400 plasma samples from participants in a clinical study on smoking cessation.