Mechanism of Formation of Cadmium Oxalate Liesegang Rings

Qualitative and semiquantitative study of the Liesegang rings formed by the reaction of oxalic acid and cadmium chloride in the acidic range of pH in silica hydrogel is made. The behaviour of Jablczynski's space constant and Morce-Pierce's time constant at various temperatures, pH and concentration of outer electrolyte is studied. The possible mechanisms for the above observed behaviour are suggested. The deviations from Isemura's general obserations are interprerted by considering two particular aspects, viz., comparatively larger crystals constituting the rings and the irreversibility of inner and outer electrolytes.     

The Varietal Influence of Flavour Precursors from Grape Marc on Monoterpene and C13-Norisoprenoid Profiles in Wine as Determined by Membrane-Assisted Solvent Extraction (MASE) GC-MS

The winemaking by-product grape marc (syn. pomace) contains significant quantities of latent flavour in the form of flavour precursors which can be extracted and used to modulate the volatile composition of wine via chemical hydrolysis. Varietal differences in grapes are widely known with respect to their monoterpene content, and this work aimed to extend this knowledge into differences due to cultivar in volatiles derived from marc precursors following wine-like storage conditions. Marc extracts were produced from floral and non-floral grape lots on a laboratory-scale and from Muscat Gordo Blanco marc on a winery -scale, added to a base white wine for storage over five to six months, before being assessed using a newly developed membrane-assisted solvent extraction gas chromatography-mass spectrometry (GC-MS) method. The geraniol glucoside content of the marc extracts was higher than that of juices produced from each grape lot. In all wines with added marc extract from a floral variety, geraniol glucoside concentration increased by around 150–200%, with increases also observed for non-floral varieties. The relative volatile profile from extracts of the floral varieties was similar but had varied absolute concentrations. In summary, while varietally pure extracts would provide the greatest control over flavour outcomes when used in winemaking, aggregated marc parcels from floral cultivars may provide a mechanism to simplify the production logistics of latent flavour extracts for use in the wine sector.     

Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid

Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent K_D of 50 nm  and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies.     

Negative ion electrospray mass spectrometry of nucleotides: ionization from water solution with SF6 discharge suppression

The total current and selected ion currents from the electrospray ionization (ES1) of 10^?5 M solutions of cocaine hydrochloride and deoxycytidine monophosphate (dCMP) monosodium salt in methanol and water solvents were compared in positive and negative ion modes, respectively, without and with SF₆, gas as a discharge suppressant. The ESI onset voltages (V_on), were the same for the positive and negative ion modes. The V_on, for methanol was much lower than that for water and in agreement with the equation of D. P. H. Smith, who attributes the difference to the higher surface tension of water. The onset of electric discharge (V_dis) without SF₆, occurred at lower capillary voltages for the negative relative to the positive ion mode for methanol; but V_dis is much higher than V_on for methanol, and discharges do not interfere with ESI operation. For water, V_on ≈ V_dis in the absence of SF₆, in the negative ion mode, and ESI operation is impossible without SF₆, discharge suppression. The discharge problem in the positive ion mode is less severe, but SF₆, is still very useful. A dynamic range of 10 ^?7–10^?5 M was obtained by selected ion monitoring of [dCMP - H]^? at 4.5 and 20 μL/min. flows. Subpicomole detection limits for the nucleotide salt were obtained under these conditions.     

Astringency Sensitivity to Tannic Acid: Effect of Ageing and Saliva

Astringency is an important sensory characteristic of food and beverages containing polyphenols. However, astringency perception in elderly people has not been previously documented. The aim of the present work was to evaluate sensitivity to astringency as a function of age, salivary flow and protein amount. Fifty-four panellists, including 30 elderly people (age = 75 ± 4.2 years) and 24 young people (age = 29.4 ± 3.8 years), participated in this study. Astringency sensitivity was evaluated by the 2-alternative forced choice (2-AFC) procedure using tannic acid solutions. Whole saliva was collected for 5 min before and after the sensory tests. The results showed that the astringency threshold was significantly higher in the elderly group than the young group. No correlation was observed between the salivary protein amount and threshold value. However, a negative correlation between salivary flow and threshold was observed in the young group only. These results showed a difference in oral astringency perception as a function of age. This difference can be linked to salivary properties that differ as a function of age.     

N.M.R. Spectra of the Fuchs0Nes: Structure of Naphthofuchsone

Following the initial synthesis of the fuchsones¹I, (α, η -diphenyl-1,4-benzoquinone methides), numerous substituted members of this series have been described by workers interested in triphenylmethane dyes. The fuchsones have been synthesized by the sulfuric acid condensation of benzilic acid and appropriate phenol¹, by dehydration of 4-hydroxytriphenylcarbinol², by oxidation 4-hydroxytri-phenylmethane and by photochemically induced reactions benzophenones with 2,6-dialkylphenols⁴.     

XNBR/LDH nanocomposites: Effect of vulcanization and organic modifier on nanofiller dispersion and strain‐induced crystallization

In elastomer/organo clay nanocomposites, the morphological characteristics, and hence the mechanical properties, of the vulcanizates are strongly influenced by the organic modifier and the vulcanization process. When the elastomer itself undergoes strain‐induced crystallization, both the organic modifier and the dispersed filler particles could significantly influence the crystallization process. These phenomena are very common in case of natural rubber‐based vulcanizates. In this study, the similar effects have been demonstrated with carboxylated nitrile rubber (XNBR) and organically modified layered double hydroxide (O‐LDH)‐based nanocomposites. The effect of size of the organic modifier was obviously visible on the interlayer distance of O‐LDH and also on the morphological reorganization of the dispersed O‐LDH particles during vulcanization process. The strain‐induced crystallization of the XNBR was found to be strongly dependent on the morphological change that occurs during vulcanization process. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2010     

Theoretical optimization of Irinotecan-based anticancer strategies in the case of drug-induced efflux

The anticancer drug Irinotecan (CPT11) is known to trigger the induction of ATP-Binding Cassette (ABC) transporters, responsible for the efflux of the drug and its metabolites outside of the cells. The drug-modulated overexpression of those transporters prevents its accumulation in the intracellular medium, therefore decreasing its efficacy. A critical clinical concern lies in the design of CPT11-based therapeutic strategies which eradicate a maximum number of cancer cells despite their ability to become resistant. In order to address this issue, we supplemented an existing mathematical model of CPT11 molecular pharmacokinetics–pharmacodynamics (PK–PD) with a new model of CPT11-induced overexpression of ABC transporters. We then theoretically optimized exposure to CPT11 given as a single agent or combined either with ABC transporter inhibitors, or with inhibitors of nuclear factors whose activation is responsible for transporter overexpression. We firstly considered a cancer cell population endowed with the ability of inducing their transporters. For any drug combination, we concluded that the highest concentration of CPT11 should be administered in order to kill a maximum number of cancer cells, despite the triggering of resistance. We then considered a population of healthy cells which were assumed to be identical to cancer cells except that they were not able to become resistant. Optimal schemes were defined as the ones which maximized DNA damage in cancer cells under the constraint of DNA damage in healthy cells not exceeding a tolerability threshold. The optimal therapeutic strategy consisted in combining CPT11 with ABC transporter inhibitors as it achieved a complete reversal of resistance by means of the lowest concentrations of CPT11.