High temperature stability of natural maghemite: a magnetic and spectroscopic study

A combined magneto-mineralogical approach is used to diagnose maghemitization in magnetic grains of basaltic rock fragments from sand dunes in the Namibian desert in SW Africa. Data were obtained from static magnetic analysis, ferromagnetic resonance (FMR) spectroscopy, micro-Raman spectroscopy and electron microscopy. Micro-Raman spectroscopy showed that the magnetic grains in the lithic fragments form oxidative solid solution series with magnetite and maghemite as end-members. The five active Raman modes at 712, 665, 507, 380 and 344 cm−1 indicate that maghemite in the magnetic grains has well-defined structural properties. The FMR spectral analysis provides evidence for long-range dipolar coupling, which suggests intergrowth of the magnetic phases of the oxidative solid solution series. Thermomagnetic experiments and hysteresis measurements reveal a Curie temperature of about 890 K for this maghemite. Upon heating to 970 K part of the maghemite is altered to thermodynamically more stable hematite. After selective thermal decomposition of the maghemite in a protected atmosphere, the remaining magnetic phase has a Curie temperature of 850 K, characteristic for magnetite. The unique thermal stability of this natural maghemite above its Curie temperature is explained by the well-defined mineral structure, which formed during slow oxidative alteration of magnetite under arid climate condition

A covalent antagonist for the human adenosine A(2A) receptor

The structure of the human A(2A) adenosine receptor has been elucidated by X-ray crystallography with a high affinity non-xanthine antagonist, ZM241385, bound to it. This template molecule served as a starting point for the incorporation of reactive moieties that cause the ligand to covalently bind to the receptor. In particular, we incorporated a fluorosulfonyl moiety onto ZM241385, which yielded LUF7445 (4-((3-((7-amino-2-(furan-2-yl)-[1, 2, 4]triazolo[1,5-a][1, 3, 5]triazin-5-yl)amino)propyl)carbamoyl)benzene sulfonyl fluoride). In a radioligand binding assay, LUF7445 acted as a potent antagonist, with an apparent affinity for the hA(2A) receptor in the nanomolar range. Its apparent affinity increased with longer incubation time, suggesting an increasing level of covalent binding over time. An in silico A(2A)-structure-based docking model was used to study the binding mode of LUF7445. This led us to perform site-directed mutagenesis of the A(2A) receptor to probe and validate the target lysine amino acid K153 for covalent binding. Meanwhile, a functional assay combined with wash-out experiments was set up to investigate the efficacy of covalent binding of LUF7445. All these experiments led us to conclude LUF7445 is a valuable molecular tool for further investigating covalent interactions at this receptor. It may also serve as a prototype for a therapeutic approach in which a covalent antagonist may be needed to counteract prolonged and persistent presence of the endogenous ligand adenosine

A covalent antagonist for the human adenosine A2A receptor

The structure of the human A2A adenosine receptor has been elucidated by X-ray crystallography with a high affinity non-xanthine antagonist, ZM241385, bound to it. This template molecule served as a starting point for the incorporation of reactive moieties that cause the ligand to covalently bind to the receptor. In particular, we incorporated a fluorosulfonyl moiety onto ZM241385, which yielded LUF7445 (4-((3-((7-amino-2-(furan-2-yl)-[1, 2, 4]triazolo[1,5-a][1, 3, 5]triazin-5-yl)amino)propyl)carbamoyl)benzene sulfonyl fluoride). In a radioligand binding assay, LUF7445 acted as a potent antagonist, with an apparent affinity for the hA2A receptor in the nanomolar range. Its apparent affinity increased with longer incubation time, suggesting an increasing level of covalent binding over time. An in silico A2A-structure-based docking model was used to study the binding mode of LUF7445. This led us to perform site-directed mutagenesis of the A2A receptor to probe and validate the target lysine amino acid K153 for covalent binding. Meanwhile, a functional assay combined with wash-out experiments was set up to investigate the efficacy of covalent binding of LUF7445. All these experiments led us to conclude LUF7445 is a valuable molecular tool for further investigating covalent interactions at this receptor. It may also serve as a prototype for a therapeutic approach in which a covalent antagonist may be needed to counteract prolonged and persistent presence of the endogenous ligand adenosine.KEYWORDS: A2A adenosine receptor; Adenosine; Covalent antagonist; G protein-coupled receptors; Radioligand bindin

ANALYSE DES NUCLÉONS ÉJECTÉS DANS UNE RÉACTION QUASI ÉLASTIQUE (p, p?) A 400 MeV

Une expérience de coïncidences (p,pγ) a été réalisée avec des protons incidents de 400 MeV sur différentes cibles 24Mg, 27Al, 28Si, 60Ni auprès de 1'accélérateur Saturne

Complexation of Zr and Hf in fluoride-rich hydrothermal aqueous fluids and its significance for high field strength element fractionation

Zirconium and hafnium behave nearly identically in most geological processes due to their identical nominal ionic charge and similar radius. Some of the most pronounced exceptions from this rule are observed in fluoride-rich aqueous systems, suggesting that aqueous fluoride complexation may be involved in Zr/Hf fractionation. To understand the mechanisms causing this phenomenon, we investigated complexation of Zr4+ and Hf4+ in fluoride-rich (1.0 mol/kg HF) aqueous solutions at 40 MPa and 100–400 °C, using synchrotron X-ray absorption spectroscopy (X-ray absorption near edge structure and extended X-ray absorption fine structure) combined with classical and ab initio molecular dynamics simulations. The dominant experimentally observed complexes are [Zr(F,OH)4·2H2O]0 and [Hf(F,OH)4·2H2O]0, respectively. The first coordination shell comprises a distorted octahedron, with fluoride and hydroxide ligands at a similar mean radial distance (1.9–2.0 Å) from the central cation, and H2O ligands at a slightly greater distance (>2.1 Å). With increasing temperature, the H2O ligands move further out, causing first an increasing distortion of the octahedron and subsequently a partial transition to less hydrated complexes as a certain fraction of the H2O molecules move to the second shell at > 3 Å. As a consequence, the radial distance of the F- and OH– anions from the central cation, as well as the overall average radial distance of the first shell decreases due to decreased steric repulsion from the H2O ligands. Both experiments and simulations agree in that Hf forms slightly shorter bonds to its nearest neighbors than Zr. The results suggest two hypotheses for the mechanism of Zr/Hf fractionation during precipitation of minerals from fluoride-rich hydrothermal solutions: 1) The heavy twin (Hf) prefers the lower coordination (shorter bonds) and is thus less likely to enter into the higher coordination found in the solids. This mechanism would be analogous to equilibrium isotope fractionation. 2) The change of Hf into a higher coordination environment (e.g., from solution to solid) is slower because it forms stronger ligand-bonds than Zr. This would be analogous to reactive kinetic isotope fractionation. In either case mass dependent fractionation qualitatively matches the observations but mass independent effects on bond strength may also be significant. Quantitative investigations of these effects are needed and may also shed light on the currently still somewhat enigmatic fractionation behavior of Zr isotopes

A covalent antagonist for the human adenosine A_2A receptor

The structure of the human A(2A) adenosine receptor has been elucidated by X-ray crystallography with a high affinity non-xanthine antagonist, ZM241385, bound to it. This template molecule served as a starting point for the incorporation of reactive moieties that cause the ligand to covalently bind to the receptor. In particular, we incorporated a fluorosulfonyl moiety onto ZM241385, which yielded LUF7445 (4-((3-((7-amino-2-(furan-2-yl)-[1, 2, 4]triazolo[1,5-a][1, 3, 5]triazin-5-yl)amino)propyl)carbamoyl)benzene sulfonyl fluoride). In a radioligand binding assay, LUF7445 acted as a potent antagonist, with an apparent affinity for the hA(2A) receptor in the nanomolar range. Its apparent affinity increased with longer incubation time, suggesting an increasing level of covalent binding over time. An in silico A(2A)-structure-based docking model was used to study the binding mode of LUF7445. This led us to perform site-directed mutagenesis of the A(2A) receptor to probe and validate the target lysine amino acid K153 for covalent binding. Meanwhile, a functional assay combined with wash-out experiments was set up to investigate the efficacy of covalent binding of LUF7445. All these experiments led us to conclude LUF7445 is a valuable molecular tool for further investigating covalent interactions at this receptor. It may also serve as a prototype for a therapeutic approach in which a covalent antagonist may be needed to counteract prolonged and persistent presence of the endogenous ligand adenosine.Medicinal Chemistr

Nucleon-induced reactions at intermediate energies: New data at 96 MeV and theoretical status

Double-differential cross sections for light charged particle production (up to A=4) were measured in 96 MeV neutron-induced reactions, at TSL laboratory cyclotron in Uppsala (Sweden). Measurements for three targets, Fe, Pb, and U, were performed using two independent devices, SCANDAL and MEDLEY. The data were recorded with low energy thresholds and for a wide angular range (20-160 degrees). The normalization procedure used to extract the cross sections is based on the np elastic scattering reaction that we measured and for which we present experimental results. A good control of the systematic uncertainties affecting the results is achieved. Calculations using the exciton model are reported. Two different theoretical approches proposed to improve its predictive power regarding the complex particle emission are tested. The capabilities of each approach is illustrated by comparison with the 96 MeV data that we measured, and with other experimental results available in the literature.Comment: 21 pages, 28 figure

Evidence for Spinodal Decomposition in Nuclear Multifragmentation

Multifragmentation of a ``fused system'' was observed for central collisions between 32 MeV/nucleon 129Xe and natSn. Most of the resulting charged products were well identified thanks to the high performances of the INDRA 4pi array. Experimental higher-order charge correlations for fragments show a weak but non ambiguous enhancement of events with nearly equal-sized fragments. Supported by dynamical calculations in which spinodal decomposition is simulated, this observed enhancement is interpreted as a ``fossil'' signal of spinodal instabilities in finite nuclear systems.Comment: 4 pages, 4 figures, to be published in Phys. Rev. Letter

Signals for a Transition from Surface to Bulk Emission in Thermal Multifragmentation

Excitation-energy-gated two-fragment correlation functions have been studied between 2 to 9A MeV of excitation energy for equilibrium-like sources formed in $\pi^-$ and p + $^{197}$Au reactions at beam momenta of 8,9.2 and 10.2 GeV/c. Comparison of the data to an N-body Coulomb-trajectory code shows a decrease of one order of magnitude in the fragment emission time in the excitation energy interval 2-5A MeV, followed by a nearly constant breakup time at higher excitation energy. The observed decrease in emission time is shown to be strongly correlated with the increase of the fragment emission probability, and the onset of thermally-induced radial expansion. This result is interpreted as evidence consistent with a transition from surface-dominated to bulk emission expected for spinodal decomposition.Comment: 11 pages including 3 postscript figures (1 color