Ferrous Iron Under Oxygen-Rich Conditions in the Deep Mantle.

Recent experiments have demonstrated the existence of previously unknown iron oxides at high pressure and temperature including newly discovered pyrite-type FeO2 and FeO2Hx phases stable at deep terrestrial lower mantle pressures and temperatures. In the present study, we probed the iron oxidation state in high-pressure transformation products of Fe3+OOH goethite by in situ X-ray absorption spectroscopy in laser-heated diamond-anvil cell. At pressures and temperatures of ~91 GPa and 1,500-2,350 K, respectively, that is, in the previously reported stability field of FeO2Hx, a measured shift of -3.3 ± 0.1 eV of the Fe K-edge demonstrates that iron has turned from Fe3+ to Fe2+. We interpret this reductive valence change of iron by a concomitant oxidation of oxygen atoms from O2- to O-, in agreement with previous suggestions based on the structures of pyrite-type FeO2 and FeO2Hx phases. Such peculiar chemistry could drastically change our view of crystal chemistry in deep planetary interiors.

Resolving ultrafast heating of dense cryogenic hydrogen.

We report on the dynamics of ultrafast heating in cryogenic hydrogen initiated by a ≲300 fs, 92 eV free electron laser x-ray burst. The rise of the x-ray scattering amplitude from a second x-ray pulse probes the transition from dense cryogenic molecular hydrogen to a nearly uncorrelated plasmalike structure, indicating an electron-ion equilibration time of ∼0.9 ps. The rise time agrees with radiation hydrodynamics simulations based on a conductivity model for partially ionized plasma that is validated by two-temperature density-functional theory.

Unraveling the solid-liquid-vapor phase transition dynamics at the atomic level with ultrafast x-ray absorption near-edge spectroscopy.

X-ray absorption near-edge spectroscopy (XANES) is a powerful probe of electronic and atomic structures in various media, ranging from molecules to condensed matter. We show how ultrafast time resolution opens new possibilities to investigate highly nonequilibrium states of matter including phase transitions. Based on a tabletop laser-plasma ultrafast x-ray source, we have performed a time-resolved (∼3 ps) XANES experiment that reveals the evolution of an aluminum foil at the atomic level, when undergoing ultrafast laser heating and ablation. X-ray absorption spectra highlight an ultrafast transition from the crystalline solid to the disordered liquid followed by a progressive transition of the delocalized valence electronic structure (metal) down to localized atomic orbitals (nonmetal-vapor), as the average distance between atoms increases.

Picosecond short-range disordering in isochorically heated aluminum at solid density.

Using ultrafast x-ray probing, we experimentally observed a progressive loss of ordering within solid-density aluminum as the temperature raises from 300 K to >10{4} K. The Al sample was isochorically heated by a short ( approximately ps), laser-accelerated proton beam and probed by a short broadband x-ray source around the Al K edge. The loss of short-range ordering is detected through the progressive smoothing of the time-resolved x-ray absorption near-edge spectroscopy (XANES) structure. The results are compared with two different theoretical models of warm dense matter and allow us to put an upper bound on the onset of ion lattice disorder within the heated solid-density medium of approximately 10 ps.

Identification of Senior At Risk scale predicts 30-day mortality among older patients with acute heart failure. / La escala Identification of Senior at Risk predice la mortalidad a los 30 días en los pacientes mayores con insuficiencia cardiaca aguda.

OBJECTIVE: To assess the value of frailty screening tool (Identification of Senior at Risk [ISAR]) in predicting 30-day mortality risk in older patients attended in emergency department (ED) for acute heart failure (AHF). DESIGN: Observational multicenter cohort study. SETTING: OAK-3 register. SUBJECTS: Patients aged ≥65 years attended with ADHF in 16 Spanish EDs from January to February 2016. INTERVENTION: No. VARIABLES: Variable of study was ISAR scale. The outcome was all-cause 30-day mortality. RESULTS: We included 1059 patients (mean age 85±5,9 years old). One hundred and sixty (15.1%) cases had 0-1 points, 278 (26.3%) 2 points, 260 (24.6%) 3 points, 209 (19.7%) 4 points, and 152 (14.3%) 5-6 points of ISAR scale. Ninety five (9.0%) patients died within 30 days. The percentage of mortality increased in relation to ISAR category (lineal trend P value <.001). The area under curve of ISAR scale was 0.703 (95%CI 0.655-0.751; P<.001). After adjusting for EFFECT risk categories, we observed a progressive increase in odds ratios of ISAR scale groups compared to reference (0-1 points). CONCLUSIONS: scale is a brief and easy tool that should be considered for frailty screening during initial assessment of older patients attended with AHF for predicting 30-day mortality.

High repetition rate laser produced soft x-ray source for ultrafast x-ray absorption near edge structure measurements.

Recent progress in high intensity ultrafast laser systems provides the opportunity to produce laser plasma x-ray sources exhibiting broad spectrum and high average x-ray flux that are well adapted to x-ray absorption measurements. In this paper, the development of a laser based x-ray absorption near edge structure (XANES) beamline exhibiting high repetition rate by using the Advanced Laser Light Source (ALLS) facility 100 Hz laser system (100 mJ, 35 fs at 800 nm) is presented. This system is based on a broadband tantalum solid target soft x-ray source and a grazing incidence grating spectrometer in the 1-5 nm wavelength range. To demonstrate the high potential of this laser based XANES technique in condensed matter physics, material science, or biology, measurements realized with several samples are presented: VO2 vanadium L edge, Si3N4 nitrogen K edge, and BPDA/PPD polyimide carbon K edge. The characteristics of this laser based beamline are discussed in terms of brightness, signal to noise ratio, and compared to conventional synchrotron broadband x-ray sources which allow achieving similar measurements. Apart from the very compact size and the relative low cost, the main advantages of such a laser based soft x-ray source are the picosecond pulse duration and the perfect synchronization between this x-ray probe and a laser pulse excitation which open the way to the realization of time resolved x-ray absorption measurements with picosecond range time resolution to study the dynamics of ultrafast processes and phase transition.

High dynamic range streak camera for subpicosecond time-resolved x-ray spectroscopy.

The full characterization of a time resolved x-ray spectrometer is presented. It is based on the coupling of a conical crystal with a subpicosecond x-ray streak camera. The detector is designed to operate in accumulation mode at high repetition rate (up to 1 kHz) allowing signal to noise ratio as high as 10(4):1. Optical switches have been used to limit the jitter induced in the subpicosecond range, demonstrating the very long term stability (a few hours) of the entire device. The data analysis have been developed to get the spectral and temporal resolution of an ultrashort laser-plasma-based x-ray source.

Proteoglycan synthesis in chondrocyte cultures from osteoarthrotic and normal human articular cartilage.

Chondrocytes derived by outgrowth from normal and osteoarthrotic human femoral head cartilage were grown in high density cultures for five passages. Cultures were analysed for their sulfated macromolecular components in medium, layer-matrix and intracellular compartments. Two fractions were obtained: typical proteoglycans and glycosaminoglycan-peptides (Mr approx. 60 000) which might result from an enzymatic degradation of proteoglycans. Proteoglycans from normal and osteoarthrotic cultures exhibited similar biochemical properties (size, protein:uronic acid ratio, glycosaminoglycan composition). Slightly less proteoglycans were aggregated with hyaluronic acid in osteoarthrotic than in normal cultures. Three populations of proteoglycan subunit were obtained under dissociative conditions (Sepharose CL-2B) in both normal and osteoarthrotic cultures: proteoglycan 1 (Kav=0.04), proteoglycan 2 (Kav=0.26) which were aggregated with hyaluronic acid in associative conditions, and proteoglycan 4 (Kav=0.48). A fourth population, proteoglycan 3 (Kav=0.33, Sepharose 2B and CL-2B) was intracellular in osteoarthrotic cultures. After a 4 day incubation period, about 60% more proteoglycans were found in osteoarthrotic than in normal cultures (medium+52%, layer-matrix + 44% and 17 times the normal value inside the cells). Proteoglycan distribution kinetics in the three compartments showed a higher net accumulation of proteoglycans in osteoarthrotic-derived cultures.

Effects of S-adenosylmethionine on human articular chondrocyte differentiation. An in vitro study.

The effect of S-adenosyl-L-methionine (SAMe) on human articular osteoarthritic chondrocytes was studied using a thick-layer culture model. Three SAMe concentrations were tested (1, 10, and 100 micrograms/ml). For 10 micrograms/ml, the most efficient dose, a significant rise in the incorporation levels of 35S-sulfate and 3H-serine was observed, as was as an increase in the hexuronic acid content. All the parameters seem to express a more active protein synthesis, particularly for proteoglycans. Under the same conditions, the proliferation rate of chondrocytes does not undergo important variations. These results point to a direct action on the cell metabolism but little is known concerning the mechanism involved.

15-(p[75Br]bromophenyl)pentadecanoic acid: pharmacokinetics and potential as heart agent.

Preparation, quality control, and pharmacokinetics of 15-(p-[75Br]bromophenyl)pentadecanoic acid (BPPA) were studied, with particular emphasis on the fate of the label and the usefulness of BPPA as a heart agent. BPPA labeled with the positron emitter Br-75 (T 1/2 = 98 min) was prepared in 55% radiochemical yield with a specific activity of greater than or equal to 1000 Ci/mmol. While the uptake of BPPA in the heart muscle is as fast and efficient as that of aliphatic omega-halofatty acids, its elimination is delayed, owing mainly to an inhibited beta oxidation and the formation of lipophilic catabolites. The blood activity and its time course are identical to those of omega-halofatty acids, but no free bromide appears in any body fluid or organ. The complex pharmacokinetic behavior of stable lipophilic catabolites prevents a quantitative background correction. In contrast to aliphatic omega-halofatty acids, a quantitative evaluation of myocardial metabolism is not possible. Br-75 BPPA, however, is well suited for positron emission tomography of the heart.

Molecular interface characterization in human bone matrix. I. Biochemical and IR spectroscopic studies.

The aim of this work is the characterization of interfaces in calcified tissues. In order to separate the non-collagenous bone proteins, according to their interaction with collagen or hydroxyapatite crystals, 10 sequential bone demineralizations using EDTA alone were carried out, followed by four sequential extractions using both EDTA and GuHCl. The extracts were characterized by SDS-PAGE, IR spectrum analysis, and kinetics of demineralization and proteins released. A great proportion of non-collagenous proteins are bound to the collagen matrix, many of which have a high affinity to it. This work demonstrates that collagen is not directly linked to the mineralized phase.

In vitro comparative evaluation under static conditions of the hemocompatibility of four types of tubing for cardiopulmonary bypass.

A comparative in vitro assessment of 4 types of tubing representative of the materials currently used in cardiopulmonary bypass (CPB) procedures was conducted under static conditions using liquid extracts of the materials or direct contact with fresh human blood or serum. The parameters monitored were biomarkers of coagulation and fibrinolytic cascades, the complement system and cell activation. Silicone and PVC tubing were shown to be non-cytotoxic and non-hemolytic. Heparin-coated PVC tubing did present a certain degree of cytotoxicity especially when in direct contact. Thrombosis was found to be significantly lower with the same heparin-coated material. To a lesser extent, platinum-cured silicone also showed a reduced thrombotic tendency. None of the materials activated platelets or the complement system. With platinum-cured silicone tubing, constant and lower leukocyte adhesion was evidenced at the different experimental time points. This could reflect reduced cell activation.

Cytocompatibility of two coating materials, amorphous alumina and silicon carbide, using human differentiated cell cultures.

The cytocompatibility of two coating materials, amorphous alumina and silicon carbide deposited by radio-frequency sputtering, was studied using alveolar bone osteoblasts and gingival fibroblasts from human healthy tissues. Cytocompatibility was assessed at the level of both the basic (attachment, proliferation and cell protein content) and the specific features (intracellular alkaline phosphatase activity and the cytoskeleton) of the cells in direct contact with the coating. Titanium was used as the reference material. The results showed that both silicon carbide and amorphous alumina are cytocompatible for human fibroblasts and osteoblasts, whereas titanium appears the least cytocompatible of all the three substrates. Moreover, the amorphous alumina coating seems slightly bioactive. It seems that these coatings, particularly amorphous alumina, could be used to protect alloys against corrosion, and consequently combine the good mechanical properties of the alloys with the good biocompatibility of the coatings. These coatings seem to perform more suitably than titanium if the strength of the bond between the coating and the underlying alloys is strong enough to give a stable composite material.

Characterization of interfaces in human calcified tissue.

Thermostimulated current spectroscopy has been applied to the investigation of molecular mobility in human calcified tissue. A comparative study of extracts at various stages of demineralization is presented. The response of an organic-mineral complex interphase has been identified.

Fibrin seal in wound healing: effect of thrombin and [Ca2+] on human skin fibroblast growth and collagen production.

To assess the interaction of a fibrin sealant with wound healing, an in vitro study using human skin fibroblasts was carried out. The effect of thrombin and calcium concentrations in the sealant on the growth parameters and collagen synthesis by normal human skin fibroblasts was examined. The fibroblast proliferation was increased 3 times for 50 and 25 IU of thrombin/ml. However for 20 mM [Ca2+], this stimulating effect of thrombin was observed after an 8 day incubation period, whereas it was observed as soon as the 2nd day in the presence of 2 mM [Ca2+]. The high rate of [Ca2+] (20 mM) partly inhibited DNA synthesis: for 2 mM [Ca2+], the incorporation of [3H]-Thymidine was 4 times greater than for 20 mM [Ca2+]. Further experiments demonstrated that human skin fibroblasts in the presence of 50 IU of thrombin/ml and 2 mM [Ca2+] in fibrin seal could increase the type I and III collagen synthesis while increasing the ratio of type III to type I. Thus, our results suggest that in vivo wound healing which required fibroblast growth and collagen synthesis can be stimulated in the presence of fibrin glue which is in good accordance with previous clinical observations.

Production of epidermal sheets in a serum free culture system: a further appraisal of the role of extracellular calcium.

Rhenwald and Green's technique is currently the standard method for growing stratifying epidermal cell cultures. The serum free system developed in Ham's laboratory (MCDB 153) was designed to grow keratinocyte monolayers in clonogenic conditions. Our aim was to optimize conditions in serum-free MCDB 153 for culturing epidermal sheets from adult normal skin, and to assess the effect of extracellular calcium and temperature on proliferation and differentiation of cultured keratinocytes. Sixteen strains derived from plastic surgery specimens (mean age of donors 37 years; range 5-89) were used. Primary cultures were seeded at an optimal density of 8 x 10(4) cells/cm2 in primary cultures and 10(4) cells/cm2 in secondary cultures in complete medium including EGF, insulin, hydrocortisone and bovine pituitary extract, supplemented with isoleucine, tyrosine, methionine, phenylalanine, tryptophane and histidine. Amino acid (AA) supplementation allows a 5.8-fold increase in cell counts at confluency and monolayers with densely packed cells are obtained. In AA supplemented cultures, confluency is obtained in 16 +/- 3 days in primary cultures and in 13 +/- 0.5 days at first passages. Switches to 1.1 mM calcium at first or second passages resulted in a significant increase in cell counts (P less than 0.001), when compared with AA supplemented low calcium cultures. Low temperature/low calcium cultures resulted in a 50% decrease in cell counts. Low temperature/high calcium cultures gave similar cell counts as the 37 degrees C controls. AA and calcium supplemented cultures were evaluated for differentiation markers: involucrin expression was increased, keratins 5, 6, 14, 17 were expressed, and the sheets were 6-10 layers thick by electron microscopy, with keratohyalin granules and cornified envelopes appearing at layers 3-6 (from basal layer). Dispase treatment allowed an easy detachment of these sheets. These results show that the culture medium MCDB 153 can be adapted without serum supplementation to batch culture of human adult keratinocytes to produce epidermal sheets suitable for grafting. They also indicate that extracellular calcium in physiological range of concentration is not a sufficient signal for growth arrest when other growth conditions are optimized.

Radioimmunodetection of rat and rabbit cartilage using a monoclonal antibody specific to link proteins.

Biodistribution analysis using [125I]Fab-6F3 specific to link proteins from human articular cartilage performed in rats by autoradiography showed a high concentration of radioactivity in all cartilaginous tissues. Preliminary immunoscintigraphic assays were performed in rabbits. Front and side view images of whole animals exhibited high uptake in cartilage tissue of the knee articulation, in the invertebral disk and the humeral head. This fixation was still detected 24 h post-injection, although high washout of radioactivity was observed.

The effect of recombinant human basic fibroblast growth factor rhFGF-2 on human osteoblast in growth and phenotype expression.

This paper describes the studies of human recombinant basic fibroblast growth factor (rhFGF-2) for its effects on human osteoblast growth and phenotype expression. During a 24-h period of treatment, rhFGF-2 highly stimulated DNA synthesis in a dose-related fashion with a maximum stimulation of 150% for 1 ng/ml. On the other hand, rhFGF-2 decreases alkaline phosphatase activity, synthesis of type I collagen, and cumulative amount of osteocalcin. Moreover, rhFGF-2 provoked a threefold increase in the amount of intracellular cAMP. Scatchard plots show the presence of two classes of [125I] rhFGF-2 receptors. This data suggests that rhFGF-2 which stimulate cell replication may act indirectly as an anabolic agent and stimulate some of the phenotypic expression markers.

Human bone marrow stromal cells express an osteoblastic phenotype in culture.

This study reports the selection and characterization of osteogenic precursors from human bone marrow which were isolated by two "clonings" and successive subculturing. These cell lines express alkaline phosphatase activity. Gel electrophoresis of [3H]-proline labeled cultures showed that the cloned cells produce only type I collagen. They synthetize osteocalcin and osteonectin. They respond to 1,25 dihydroxy vitamin D3 by increasing osteocalcin synthesis and secretion, and to parathyroid hormone by increasing cyclic AMP synthesis. After the third subculture in the absence of beta-glycerophosphate, these cell lines formed lots of clusters which exhibit high alkaline phosphatase activity and positive von Kossa staining. X-ray energy spectrum shows that these cells are surrounded by "budding" structures containing calcium and phosphorus with a ratio Ca:P identical to those of pure hydroxyapatite. This process was associated with 45Ca uptake into the cells. All these data support the selection of osteogenic cells which may be of considerable clinical importance.

Pharmacokinetics and metabolism of [35S]-Thiazolidine carboxylic acid in the rat. I. Elimination and distribution.

The localization and elimination of 35S-Thiazolidine carboxylic acid has been studied in rats following a single oral dose (100 mg/kg) and multiple oral doses (100 mg/kg/day) over 15 days. The compound was rapidly and completely absorbed as evaluated by the time of the maximum plasma 35S-concentration (140 micrograms eq/ml at 30 min) and the amount of radioactivity in the feces (less than 1% of the dose over 48 h). Urinary excretion seems to be the unique route of elimination. There was specific tissue accumulation of drug or metabolite, particularly in liver (29% of the dose at 3 h), pancreas (7% of the dose at 3 h), adrenals (320 micrograms eq/g at 3 h), pituitary and thyroid (230 micrograms eq/g at 3h). Fixation of radioactivity appears significantly higher after chronic treatment than after acute treatment.