Changes in serum thyrotropin (TSH) in man during halofenate administration

Halofenate, a serum lipid-lowering agent which inhibits binding of thyroid hormone to thyroxine-binding globulin (TBG), was administered daily for 14 days to 8 hypothyroid subjects with elevated TSH concentrations as a result of incomplete thyroxine (T4) therapy. Drug administration resulted in mean increases in serum dialyzable fraction T4 (DFT4) of 52% over pretreatment levels (P less than 0.01) and in dialyzable fraction triiodothyronine (DFT3) of 26% in 7 subjects, (P less than 0.01). During halofenate treatment in these 7 subjects, serum TSH concentrations decreased significantly (mean = 39%, P less than 0.01) when DFT4 and DFT3 were increased by halofenate. In only two subjects was there a convincing temporal relationship between increased serum absolute free T4 (AFT4) and decreased serum TSH concentrations. Contrary to what would be predicted from the "free hormone hypothesis", changes in serum TSH concentration in these hypothyroid patients appeared to relate primarily to changes in the free fraction of circulating T4 and T3 (DFT4, DFT3), rather than to alterations in AFT4 or AFT3. Halofenate did not alter serum TBG binding capacity. An eighth subject did not show increased DFT4 and DFT3 during halofenate treatment despite achievement of therapeutic serum levels of the agent; in this patient, serum TSH levels rose progressively throughout the period of inadequate T4 replacement and halofenate administration. In hypothyroid patients, short-term halofenate use suggests that the pituitary-thyroid hormone feedback circuit can respond to increases in serum DFT4 and DFT3 in the absence of detactable increases in absolute free hormone concentrations.     

A general architecture in support of interactive, multimedia, location-based mobile applications

The widespread use of cellular telephones and the availability of user-location information are facilitating the development of new personalized, location-based applications. However, as of today, most of these applications are unidirectional and text-based where the user subscribes and the system sends a text message when appropriate. This article describes a modular and general architecture that supports the development of interactive, multimedia, location-based applications, providing an extra level of service to the users. The flexibility of the architecture is demonstrated by presenting the wireless safety security system (Wi-Via) and other potential applications     

Functionalized Cluster‐Assembled Magnetic Nanostructures for Applications to high Integration‐Density Devices

This paper presents recent results on the preparation and characterization of original magnetic nanostructures from nanoclusters preformed in the gas phase. Magnetic binary‐clusters (i.e. Co‐Sm, Co‐Pt, Co‐Ag) with rather well controlled sizes, structures and compositions, are prepared in the gas phase using a combined laser vaporization‐rare gas condensation source and subsequently deposited at low energy (LECBD : Low Energy Cluster Beam Deposition) on various functionalized substrates to grow cluster‐assembled magnetic nanostructures exhibiting specific magnetic properties. Especially a high magnetic anisotropy and consequently a high magnetic blocking temperature compatible with future applications to high density memory devices and spin electronics are expected. In this context of applications, 2D‐organized arrays of functionalized binary‐cluster assembled dots are prepared by LECBD on FIB‐functionalized substrates (FIB: Focussed Ion Beam) with the ultimate objective to reach areal densities in the range of the Tbits/in².     

Identification of Toxin Inhibitors Using a Magnetic Nanosensor‐Based Assay

A magnetic nanosensor‐based method is described to screen a library of drugs for potential binding to toxins. Screening is performed by measuring changes in the magnetic relaxation signal of the nanosensors (bMR nanosensors) in aqueous suspension upon addition of the toxin. The Anthrax lethal factor (ALF) is selected as a model toxin to test the ability of our bMR nanosensor‐based screening method to identify potential inhibitors of the toxin. Out of 30 molecules screened, sulindac, naproxen and fusaric acid are found to bind LF, with dissociation constants in the low micromolar range. Further biological analysis of the free molecules in solution indicate that sulindac and its metabolic products inhibited LF cytotoxicity to macrophages with IC₅₀ values in the micromolar range. Meanwhile, fusaric acid is found to be less effective at inhibiting LF cytotoxicity, while naproxen does not inhibit LF toxicity. Most importantly, when the sulindac and fusaric acid‐bMR nanosensors themselves are tested as LF inhibitors, as opposed to the corresponding free molecules, they are stronger inhibitors of LF with IC₅₀ values in the nanomolar range. Taken together, these studies show that a bMR nanosensors‐based assay can be used to screen known drugs and other small molecules for inhibitor of toxins. The method can be easily modified to screen for inhibitors of other molecular interactions and not only the selected free molecule can be study as potential inhibitors but also the bMR nanosensors themselves achieving greater inhibitory potential.     

Ozonation of Pyrolytic Aqueous Phase: Changes in the Content of Phenolic Compounds and Color

Ozonation on the phenols present in pyrolytic aqueous phases attained from biomass thermochemical conversion was evaluated. During ozonation, the dark color of original samples was found to decrease as a function of ozonation time. The oxidation kinetics of phenols was quantified by a method based on the color changes of samples. The oxidation profiles showed different behaviors and in some cases the phenols presented a positive correlation with the relative R color parameter, except eugenol, syringol, and vanillin which were markedly different. Finally, the color changes observed seem to be associated with the changes in the overall content of phenols and with the change in the molecular weight of the heavy fractions that include lignin oligomers.     

The structure solution of the F-type i-ZnMgHf from the X-ray diffraction

ABSTRACT

We report a successful growth of the ZnMgHf F-type icosahedral quasicrystal in the form of faceted single grains. By varying the heat treatment parameters we were able to obtain single crystals with a quality suitable for a single crystal X-ray diffraction which was conducted in a synchrotron facility. Ab initio structure solution by a charge flipping algorithm manifests the existence of two types of Bergman clusters. Clusters are differentiated by the preferential occupation of the high-symmetry positions by hafnium in a rhombic triacontahedron, being the outer shell of the atomic cluster.

This paper is part of a Thematic Issue on The Crystallographic Aspects of Metallic Alloys.     

Online-Based Kinetic Analysis of Higher Alcohol and Ester Synthesis During Winemaking Fermentations

The production of the major volatile carbon compounds corresponding to the predominant higher alcohols and esters synthesized during wine alcoholic fermentation was monitored using an online GC system. The accuracy and frequency of measurements made it possible to calculate kinetic parameters, in particular rates and specific rates of production. Using this original GC system and a model describing the evolution of the gas–liquid ratio during the fermentation process, kinetic gas–liquid balances of the synthesis of volatile compounds could be followed. This showed that, for esters—substantial proportions of which are lost in the off-gas (up to 40 % of the total production at 20 °C)—measurements of the liquid concentration, rather than of the total production (liquid content?+?losses), can lead to misinterpretations of yeast metabolism. The specific production rate of individual higher alcohols reached their maximum values before the exhaustion of the corresponding precursor amino acids. Isobutanol and isoamyl alcohol were formed from carbon metabolites and nitrogen metabolites and consequently were produced continuously throughout the fermentation process. In contrast, propanol synthesis was strongly correlated with the presence of assimilable nitrogen, during both the growth and stationary phases. Therefore, propanol appears to be a highly pertinent marker of nitrogen metabolism. Acetate ester concentrations correlated linearly with the concentrations of the corresponding higher alcohols, indicating that the availability of the precursors is the main limiting factor for the production of these esters. These results open possibilities for innovative approaches based on metabolic flux analysis and taking their dynamics into account.