Itaconic acid is a mammalian metabolite induced during macrophage activation

Itaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and (13)C-labeling, we have detected ITA in both macrophage-like VM-M3 and RAW 264.7 tumor cell lines as well as stimulated and unstimulated primary murine macrophages. Macrophage activation by addition of lipopolysaccharide and IFN-γ markedly increased ITA production and secretion. Crude cell extracts synthesize ITA via decarboxylation of cis-aconitate, indicative of a novel mammalian cis-aconitic decarboxylase activity. Our results highlight a previously unidentified biosynthetic pathway related to TCA cycle metabolism in mammalian cells and a novel metabolite that likely plays a role in macrophage-based immune response.     

Structural optimization of cyclic sulfonamide based novel HIV-1 protease inhibitors to picomolar affinities guided by X-ray crystallographic analysis

Synthesis and HIV-1 protease inhibitory activity of compound 5 based on the structure of a novel cyclic sulfonamide pharmacophore has been recently disclosed from our group. X-ray crystallographic structure of 5 when bound to the HIV-1 protease defined its binding mode. The importance of the geometry of the substitution at C4–Me (S configuration) was emphasized. In the present paper we wish to disclose the design of novel inhibitors 47 and 48 based on the X-ray structure of compound 5 bound to the HIV-1 protease, their synthesis and activity against HIV-1 protease. By making changes at the C4 position and the carbamate linkage the above compounds 47 and 48 were found to be approximately one hundred fold more active compared to 5 and their K_i values are in the picomolar range. An unusual observation regarding the activity and geometry was made with compounds 51 and 52. X-ray results demonstrate that 48 and 52 bind to the same binding pocket with simultaneous change in the conformation of the cyclic sulfonamide ring.     

The Status of the Wave Function in Dynamical Collapse Models

No Heading The idea that in dynamical wave function collapse models the wave function is superfluous is investigated. Evidence is presented for the conjecture that, in a model of a field theory on a 1+1 lightcone lattice, knowing the field configuration on the lattice back to some time in the past, allows the wave function or quantum state at the present moment to be calculated, to arbitrary accuracy so long as enough of the past field configuration is known.     

New high-energy luminescence bands from Co2+ in ZnSe

Three sharp absorption features in the energy range 2.36–2.55 eV have been detected in the transmission spectrum of Co-diffused ZnSe, and a number of luminescence transitions originating from the lowest of these states at 2.361 eV have been observed. Photoluminescence excitation spectra prove that these are high energy excited states of the Co²⁺_Zn impurity, a conclusion confirmed by comparison of measured and predicted luminescence energies. This represents the first identification of luminescence branching from a higher excited state of a transition metal ion in any semiconductor. The sharp, weakly phonon-coupled transitions involve either intra-impurity excitation or transitions from the impurity to localised states split off from a minimum in the conduction band. The implications of these observations for the mechanism of host-impurity energy transfer and for the nature of the excited state wavefunctions are discussed.     

Trilocal structures. V. Wave equations

In addition to the usual centroid-time wave equation, a trilocal structure will need to satisfy two relative-time wave equations. When the trilocal wave function is expanded in tree functions, each of the three wave equations becomes an infinite matrix equation, but when the four auxiliary conditions (defined in earlier articles in this series) are introduced, each wave equation reduces to a set of 16 linear homogeneous equations in 16 unknown expansion coefficients (the first 16 coefficients in the tree expansion). The 48 linear equations, in the 16 unknownC _j , are given explicitly. Every 16-by-16 determinant, formed from any 16 of these 48 linear homogeneous equations, must vanish if the trilocal structure is to be an acceptable solution; this requirement will be used in later calculations.     

The strengths of bonding and degree of distortion from octahedral symmetry by Mössbauer spectroscopy

The use and the limitations of Mössbauer quadrupole splittings in the differential analysis of iron(II) and iron(III) in strong field complexes is investigated. By way of example, some literature Mössbauer data on dithiolene complexes of iron are interpreted in terms of the environment of the iron atom. In the six-coordinated complexes, there is considerable distortion from octahedral symmetry (corresponding to 31200 cm^–1). In the five-coordinated complexes, the distortion is also large (corresponding to 32200 cm^–1), and the values of the ratio, /ga, of the molecular orbital coefficients are found to follow the trend that would be expected from the usual bond strengths of the various ligands.

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Zusammenfassung Die Grenzen in der Anwendung der Mössbauer-Quadrupol-Aufspaltung in der Differential-analyse von Fe(II) und Fe(III) in Komplexen mit starken Feldern werden untersucht. Der Einfluß der Umgebung des Eisenatoms wird zur Deutung von Mössbauer-Daten von Dithiolenkomplexen des Eisens herangezogen. In den sechsfach koordinierten Komplexen liegt eine beträchtliche Störung der Oktaedersymmetrie vor (31200 cm^–1). Ebenso ist die Störung in fünffach koordinierten Komplexen erheblich (32200 cm^–1). Die Werte für das Verhältnis der MO-Koeffizienten / liegen in einem Bereich, den man für die üblichen Bindungsstärken der verschiedenen Liganden erwartet.

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Résumé Etude de l'utilisation des couplages quadrupolaires Mössbauer dans l'analyse différentielle des fers II et III dans des complexes à champ fort. A titre d'exemple on interprète en terme d'environnement de l'atome de fer certaines données de la littérature sur l'effet Mössbauer dans les complexes dithiolene Fer. Dans les complexes hexacoordinnés on s'écarte considérablement de la symétrie octaedrique (distortion correspondant à 3-1200 cm^–1). Dans les complexes pentacoordinnés, la distortion est aussi importante (correspondant à 3-2200 cm^–1) et les valeurs des rapports /. des coefficients des orbitales moléculaires suivent la loi à laquelle on peut s'attendre d'après les forces de liaisons usuelles des différents ligands.

     

TL dating and XRF clay provenance analysis of ancient brick at Cuicul Roman city,Algeria

In this work, a terra-cotta brick collected from the famous archaeological Roman city Cuicul, Algeria, was successfully dated by thermoluminescence. The provenance of the fabrication material was also identified by X-ray fluorescence analysis (XRF). The results obtained show that the brick was probably made in 198 A.D. This date is in good agreement with the history of the dated site and the neighborhood Caracalla arch edified in honour to Caracalla emperor (211–217 A.D.). The XRF study demonstrates that the raw clay used for the fabrication of the brick is local and well selected by the Roman builders.