Structural Determinants of the Selectivity of 3‐Benzyluracil‐1‐acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10

The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3 ) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4 ), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells.     

Changes in Lipid Class and Fatty Acid Composition of Cultures of <Emphasis Type=Italic>Pavlova lutheri</Emphasis>, in Response to Light Intensity

Aquaculture is a growing commercial activity worldwide, which resorts more and more often to microalgae as feed; the lipid composition of such microalgae is a critical factor with regard to the fish growth rate upon ingestion. The aim of this work was thus to study the influence of light intensity on the lipid profile of a known microalga, Pavlova lutheri. Several semi-continuous cultures were carried out, and biochemical parameters such as lipid, protein, carbohydrate, and chlorophyll contents were quantified. Lipids were specifically fractionated into classes by TLC, and those in each class were subjected to GC afterwards in an attempt to ascertain their fatty acid profile. Evidence was consequently provided which showed that cultures grown under low light intensity (9 W m⁻²) possess a higher fraction of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids esterified in polar classes—which are those with a more favorable role in aquaculture. It was also demonstrated that intermediate levels of light intensity (19 W m⁻²) may be misleading in terms of favorable effects upon EPA and DHA contents—because there is an increase in their total yields and productivities, but they appear mostly esterified into triacylglycerols; this may be a favorable deed for production and purification, but is metabolically not so effective in aquaculture. The highest EPA and DHA productivities attained were 1.29 and 0.69 mg L⁻¹ day⁻¹, respectively, at intermediate levels of light intensity (19 W m⁻²).     

Infiltration and Top Seed Growth-Textured YBCO Bulks With Multiple Holes

The recently reported hole-patterned YBa₂Cu₃O _y (Y123) bulks with improved superconducting properties are highly interesting from material quality and application variety points of view. It is well known that the core of plain bulk superconductors needs to be fully oxygenated and some defects like cracks, pores, and voids must be suppressed in order that the material can trap a high magnetic field or carry a high current density. To minimize the above defects, we have used a combination of standard superconducting ceramic processing and an infiltration technique to prepare regularly perforated YBa₂Cu₃O _y (Y123) bulk superconductors. This process leads to negligible shrinkage upon annealing and a uniform distribution of Y211 inclusions. Texture was evidenced by neutron pole figure measurements. Flux mapping was used to verify the superconducting homogeneity of the samples and to investigate the field-trapping ability. In addition, the textured drilled samples were reinforced using resin or metal impregnation and the influence of the different processing steps on the hardness of the materials has been investigated.     

Modeling of complex interfaces: Gadolinium‐doped ceria in contact with yttria‐stabilized zirconia

Gadolinium‐doped ceria (GDC) and yttria‐stabilized zirconia (YSZ) are well‐known electrolyte materials in solid oxide fuel cells (SOFCs). Although they can be used independently, it is common to find them in combination in SOFCs, where they are used as protective layers against the formation of secondary phases or electron conduction blockers. Despite their different optimum operating temperatures, it appears that oxygen conduction is not affected by their interface. However, the intrinsic mechanisms of oxygen diffusion at these interfaces still remain unclear. One of the main difficulties when modeling the contact between different materials, or indeed different particles of the same material, is caused by the structural complexity of these systems. If we wish to evaluate the properties of the materials, we first need to obtain a model that includes the main features of the GDC/YSZ interface, such as large‐scale defects or cation interdiffusion in the contiguous phase. Since the generation of such a mixed system is complicated, we show here how the “amorphization and recrystallization” strategy can help us to obtain realistic systems. In this, the first of our papers on the structure and properties of layered GDC/YSZ materials, we discuss the structural features of the grain boundary between GDC and YSZ obtained by molecular dynamics simulations.     

Synthesis and characterization of hindered‐phenol‐containing amine moieties as antioxidants for polypropylene copolymers

(4‐Ethylphenyl)‐3,5‐ditertiarybutyl‐4‐hydroxybenzylamine, 1‐phenyl‐4‐(3,5‐ditertiarybutyl‐4‐hydroxybenzyl)piperazine, and 1‐(3,5‐ditertiarybutyl‐4‐hydroxybenzyl)piperidine were synthesized and characterized, and their performance in polypropylene copolymer (PPCP) was tested by multiple extrusions in a Brabender plasticorder. The thermooxidative stability of PPCP was assessed by the measurement of oxidative induction time at 200 ± 1°C, and the thermal stability was assessed by observation of the change in the melt flow rate. A comparative study of the synthesized antioxidants with the commercially available antioxidant 2,6‐ditertiarybutyl‐4‐methylphenol was made. The presence of phenolic and amino groups influenced the performance of the antioxidants. The performance of the antioxidants influenced the thermal stability of the PPCP. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1097–1103, 2004     

Water retention and gas relative permeability of two industrial concretes

This experimental study aims at identifying the water retention properties of two industrial concretes to be used for long term underground nuclear waste storage structures. Together with water retention, gas transfer properties are identified at varying water saturation level, i.e. relative gas permeability is assessed directly as a function of water saturation level S_w. The influence of the initial de-sorption path and of the subsequent re-saturation are analysed both in terms of water retention and gas transfer properties. Also, the influence of concrete microstructure upon water retention and relative gas permeability is assessed, using porosity measurements, analysis of the BET theory from water retention properties, and MIP. Finally, a single relative gas permeability curve is proposed for each concrete, based on Van Genuchten–Mualem's statistical model, to be used for continuous modelling approaches of concrete structures, both during drying and imbibition.     

Segmentation of multiple sclerosis lesions in brain MRI: A review of automated approaches

Automatic segmentation of multiple sclerosis (MS) lesions in brain MRI has been widely investigated in recent years with the goal of helping MS diagnosis and patient follow-up. However, the performance of most of the algorithms still falls far below expert expectations. In this paper, we review the main approaches to automated MS lesion segmentation. The main features of the segmentation algorithms are analysed and the most recent important techniques are classified into different strategies according to their main principle, pointing out their strengths and weaknesses and suggesting new research directions. A qualitative and quantitative comparison of the results of the approaches analysed is also presented. Finally, possible future approaches to MS lesion segmentation are discussed.     

Reorientation patterns in central-place foraging: internal clocks and klinokinesis

We study central-place foraging patterns of Aphaenogaster senilis ants at a population level by video framing individual ant trajectories in a circular arena with a nest connected to its centre. The ants naturally leave and enter the nest and forage generating non-trivial movement patterns around the nest. Our data analysis indicated that the trajectories observed can be classified into two strategies: the risk-averse strategy, which involves wandering around the nest without departing far from it and the risk-prone strategy, which involves long exploration paths with periodic returns to the central region, nearby the nest. We found that both risk-prone and risk-averse strategies exhibit qualitatively the same reorientation patterns, with the time between consecutive reorientations covering a wide range of scales, and fitting a stretched exponential function. Nevertheless, differences in the temporal scales and the time variability of such reorientation events differ, together with other aspects of motion, such as average speed and turns. Our results give experimental evidence that the internal mechanisms driving reorientations in ants tend to favour frequently long relocations, as theory predicts for efficient exploration in patchy landscapes, but ants engaged in central-place foraging can modulate such behaviour to control distances from the nest. Previous works on the species support the idea that risk-prone and risk-averse strategies may reflect actual differences between individuals age and experience; these factors (age and experience) should be then relevant in modulating the internal reorientation clocks. To support the validity of our findings, we develop a random-walk model combining stretched exponential reorientation clocks with klinokinesis that fits the time length and the travelled distance distributions of the observed trajectories.