Development of orally active oxytocin antagonists: studies on 1-(1-[4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2- methoxybenzoyl]piperidin-4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines

The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N-oxide groups. This modification has led to the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for iv administration, and excellent selectivity against the human arginine vasopressin receptors. Incorporation of a 5-fluoro substituent on the central benzoyl ring of this class of oxytocin antagonists enhanced in vitro and in vivo potency but was detrimental to the pharmacokinetic profiles of these compounds. Although lipophilic substitution around the pyridine ring of compound 30 gave higher affinity in vitro, such substituents were a metabolic liability and caused shortfalls in vivo. Two approaches to prevent this metabolism, addition of a cyclic constraint and incorporation of trifluoromethyl groups, were examined. The former approach was ineffective because of metabolic hydroxylation on the constrained ring system, whereas the latter showed improvement in plasma pharmacokinetics in some cases.     

Tocopherols and tocotrienols as free radical-scavengers in refined vegetable oils and their stability during deep-fat frying

The aim of this study was to assess the effect of total tocopherols and tocotrienols of refined vegetable oils on oil radical-scavenging activity and to investigate the stability of the various homologues during the deep-fat frying of French fries. Eight different refined vegetable oils were investigated, having variable levels of natural tocopherols and tocotrienols. A direct correlation between the radical-scavenging capacity of the oils, measured by the DPPH test, and the total content of natural tocopherols and tocotrienols was found. Frying experiments showed that the stability of the different tocopherols and tocotrienols present in the refined vegetable oils basically depend on two factors: the fatty acid composition of the oil, in particular polyunsaturated fatty acid content, and the kind of tocopherol and tocotrienol homologues present. The more oxidizable the oil, on the basis of fatty acid composition, the more stable were the tocopherolic antioxidants. Among the different homologues, γ-tocotrienol in palm super olein proved to be the least stable during the deep-fat frying, thus preserving the other homologues.     

Comparison of dynamic headspace and simultaneous distillation extraction techniques used for the analysis of the volatile components in three European PDO ewes’ milk cheeses

This preliminary study aims to compare two different extraction and concentration methods often used for the gas chromatographic analysis of volatile components in food to determine the advantages and drawbacks of both for future routine investigation of PDO (protected designation origin) ewes’ milk cheeses. Roncal, Pecorino Sardo and Fiore Sardo were investigated at different ripening stages. The dynamic headspace technique using a Purge & Trap device (DHS) makes it possible to extract more highly volatile compounds than the simultaneous distillation extraction (SDE) method. Consequently, the latter is more efficient for extracting low-volatile components such as phenols, free fatty acids, lactones and longer-chain aldehydes, ketones, alcohols and esters. These two extraction methods are therefore complementary.     

Optimisation of cake fat quantity and composition using response surface methodology

The influence of fat quantity and composition on the characteristics of a chemically leavened baked product was investigated, applying a central composite design combined with response surface methodology. Fats were blends of palm oil and palm olein with different slip melting points (from 36.3 to 11.3 °C, in dependence of increasing olein content). Fat content (from 5.3% to 30.7% on batter) and percentage of olein in the fat blend (from 42.7% to 92.2%) were varied. The increase of fat quantity enhanced cake softness, while lowering the volume; higher olein contents also decreased cake firmness. An optimised formulation containing 19.7% fat with 92% olein in the fat blend and showing good structural properties, comparable to those of a 18% butter reference cake, was identified. The optimised and the butter cake showed specific volume of 2.25 and 2.23 cm³ g^?1, respectively, and load at 25% strain of 7.68 and 5.63 N. These results demonstrated the possibility to replace butter with a liquid vegetable fat blend, thus increasing unsaturated fat content and reducing total cholesterol in the product.     

Electro-tactile device for material texture simulation

This paper deals with the simulation of material texture by means of electro-tactile stimuli, which directly derive from real material properties. The research presents a novel tactile display by its hardware and software system architecture and the elaboration procedure to generate the stimulating signals, and validates the adopted simulation strategy by experimental testing. The tactile system elaborates data from scans of real material samples and generates electrical stimuli to reproduce roughness and texture coarseness sensations. It also adds a coherent sound feedback to improve the realism of the simulation. The research defines also an experimental protocol based on the theory of Psychophysics to carry out system calibration and tests with users. The scope is to validate the proposed tactile system as a new tool for material simulation, which can be adopted for material virtual prototyping in several fields (product design, textile and clothing, gaming and entertainment, virtual museum, rehabilitation, etc.). Experimentations have been carried out to measure the users’ response to our different material classes (wood, paper, rubber and textile fabric). Experimental results concern how good the adopted simulation approach is and the analysis of the human tactile perception simulated by the system. Main findings relate to the system performance and the users’ response in terms of signal recognition and material class discrimination.     

Elemental and mineral characterisation of Coastal Antarctic Aerosols in snow using PIXE and SEM-EDAX

The chemical constituents of snow from a 3 m pit sampled at a coastal Antarctic site were characterised by means of PIXE and SEM-EDAX. Oxygen isotope dating revealed that the pit spanned an 8-year period, from 1986 to 1994. Concentrations measured by PIXE ranged from less than 1 ng g⁻¹ of H₂O for Cu, and Zn to several tens of ng g⁻¹ for Si, S and Cl. The major elements found were Si, S, Al, and Na, which contributed more than 75% of the element loading. Snow layers with elevated Cl concentration were regularly found along the pit. The mineralogy of the insoluble particles determined by SEM-EDAX analyses showed that quartz, plagioclase and clays were the prevalent minerals. The proportion of each element in the insoluble phase was comparable with that previously found in similar studies.     

Minimal free resolutions of some configurations of fat lines

In this paper we compute the minimal free resolution and then the Hilbert function of a \(m\) -homogeneous fat complete grid in \(\mathbb {P}^3_\mathbf {K}\) . This proves a conjecture about the minimal free resolution of these configurations of lines.     

Palladium nanoparticle deposition via precipitation: a new method to functionalize macroporous silicon

We present an original two-step method for the deposition via precipitation of Pd nanoparticles into macroporous silicon. The method consists in immersing a macroporous silicon sample in a PdCl₂/DMSO solution and then in annealing the sample at a high temperature. The impact of composition and concentration of the solution and annealing time on the nanoparticle characteristics is investigated. This method is compared to electroless plating, which is a standard method for the deposition of Pd nanoparticles. Scanning electron microscopy and computerized image processing are used to evaluate size, shape, surface density and deposition homogeneity of the Pd nanoparticles on the pore walls. Energy-dispersive x-ray spectroscopy (EDX) and x-ray photoelectron spectroscopy (XPS) analyses are used to evaluate the composition of the deposited nanoparticles. In contrast to electroless plating, the proposed method leads to homogeneously distributed Pd nanoparticles along the macropores depth with a surface density that increases proportionally with the PdCl₂ concentration. Moreover EDX and XPS analysis showed that the nanoparticles are composed of Pd in its metallic state, while nanoparticles deposited by electroless plating are composed of both metallic Pd and PdO_x.