Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake

Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization results. On the contrary, cholesterol oligomers that were the best-internalized oligomers had poor antiproliferative activity, even worse than the unmodified floxuridine oligomer. Especially relevant is the effect induced by palmitic and folic acid derivatives generating the most active drugs. These results are of special interest for delivering other therapeutic oligonucleotides.     

Direct-Ink-Writing of Electroactive Polymers for Sensing and Energy Storage Applications

Considering the high levels of materials used in the fields of electronics and energy storage systems, it is increasingly necessary to take into consideration environmental impact. Thus, it is important to develop devices based on environmentally friendlier materials and/or processes, such as additive manufacturing techniques. In this work, poly(vinylidene fluoride) (PVDF) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) are prepared by direct-ink-writing (DIW) by varying solvent evaporation temperature and fill density percentage. Different morphologies for both polymers are obtained, including dense films and porous membranes, as well as different electroactive β-phase content, thermal and mechanical properties. The dielectric constant and piezoelectric d₃₃ coefficient for dense films reaches up to 16 at 1 kHz and 4 pC N⁻¹, respectively for PVDF-HFP with a fill density of 80 and a solvent evaporation temperature of 50 °C. Porous structures are developed for battery separator membranes in lithium-ion batteries, with a highest ionic conductivity value of 3.8 mS cm⁻¹ for the PVDF-HFP sample prepared with a fill density of 100 and a solvent evaporation temperature of 25 °C, the sample showing an excellent cycling performance. It is demonstrated that electroactive films and membranes can be prepared by direct-ink writing suitable for sensors/actuators and energy storage systems.     

Low-Thermal-Conductivity Rare-Earth Zirconates for Potential Thermal-Barrier-Coating Applications

Rare-earth zirconates have been identified as a class of low-thermal-conductivity ceramics for possible use in thermal barrier coatings (TBCs) for gas-turbine engine applications. To document and compare the thermal conductivities of important rare-earth zirconates, we have measured the thermal conductivities of the following hot-pressed ceramics: (i) Gd₂Zr₂O₇ (pyrochlore phase), (ii) Gd₂Zr₂O₇ (fluorite phase), (iii) Gd_2.58Zr_1.57O₇ (fluorite phase), (iv) Nd₂Zr₂O₇ (pyrochlore phase), and (v) Sm₂Zr₂O₇ (pyrochlore phase). We have also measured the thermal conductivity of pressureless-sintered 7 wt% yttria-stabilized zirconia (7YSZ)—the commonly used composition in current TBCs. All rare-earth zirconates investigated here showed nearly identical thermal conductivities, all of which were ∼30% lower than the thermal conductivity of 7YSZ in the temperature range 25°–700°C. This finding is discussed qualitatively with reference to thermal-conductivity theory.     

The Effects Of Humic Substances On Pinus Callus Are Reversed By 2,4-Dichlorophenoxyacetic Acid

The reversal of humic matter-induced inhibition of callus growth and metabolism by 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in Pinus laricio. Two forest humic fractions (relative molecular mass (M_r) > 3500), derived from soil under Fagus sylvatica (Fs) and Abies alba (Aa) plantation, were used. Pinus laricio callus was grown for a subculture period (4 weeks) on Basal Murashige and Skoog (MS) medium plus forest humic matters (Fs or Aa), at a concentration of 1 mg C/l, and then was transferred, for an additional four weeks, to a MS medium culture without humic matter, but with different hormones: indole-3-acetic acid (IAA, 2 mg/1) or 2,4-dichlorophenoxyacetic acid (2,4-D, 0.5 mg/1) and/or 6-benzylaminopurine (BAP, 0.25 mg/1). Growth of calluse, glucose, fructose, and sucrose contents, and activities of soluble and bound invertases, glucokinase, phosphoglucose isomerase, aldolase, and pyruvate kinase were monitored. The results show a negative effect of humic fractions on callus growth, due to decreased utilization of glucose and fructose, and decreased activities of glycolytic enzymes. The effects are reversible. Substitution of humic fractions with 2,4-D+BAP or 2,4-D is followed by an increase of glycolytic enzyme activities and, consequently, by the utilization of glucose and fructose that induces a restart of growth. In contrast, the inhibitory effects of humic fractions persist when they are substituted with BAP alone, indicating that only the auxin 2,4-D is capable of reversing the negative effects. A possible competitive action on the auxin-binding site between 2,4-D and the chemical structures in the forest humic fractions is suggested.     

Learning control in spatial coordinates for the path-following of autonomous vehicles

We prove the existence of a P-type (proportional-type) space-learning control, which, on the basis of a kinematic third order nonlinear model of an autonomous nonholonomic vehicle and by a proper choice of the proportional control gain, guarantees asymptotic tracking of planar curves whose uncertain curvature is L$L$-periodic in the curvilinear abscissa. The behavior of a human driver, who repetitively learns the correct action from the past experience in the space, is mathematically reproduced. A stability analysis is presented while simulation results demonstrate the effectiveness of the presented approach.     

Molecular dynamics for long-range interacting systems on graphic processing units

We present implementations of the numerical integration of systems with long-range interactions on graphic processing units for three N$N$-body models with long-range interactions of general interest: the Hamiltonian Mean Field, Ring and two-dimensional self-gravitating models. We discuss the algorithms, speedups and errors using one and two GPU units. Speedups can be as high as 140 compared to a serial code, and the overall relative error in the total energy is of the same order of magnitude as for the CPU code. The number of particles used in the tests range from 10,000 to 50,000,000 depending on the model.     

Effect of catalysts in the quality of syngas and by-products obtained by co-gasification of coal and wastes. 1. Tars and nitrogen compounds abatement

The aim of this work is to analyse the possibility of using co-gasification technology to process coal mixed with wastes to take profit of its energy content and at the same time to minimize the environmental impact associated with the use of wastes and to diminish the costs of flue gas treatment. The addition to coal of different types of materials, like: pine based waste, petcoke and polyethylene (PE), was not found to give rise to any operational problems, regarding both the feeding system and gasification process and led to higher energy conversions, however, the gas presented higher tars and hydrocarbons content. Several catalysts were tested, such as, dolomite, olivine, nickel and magnesium oxides, zinc oxides and cobalt and molybdenum oxides. Catalyst action was analysed in tars release and also in ammonia compounds reduction. The presence of catalysts allowed increasing hydrogen release, whilst there was a decrease in hydrocarbons and tars contents. A nickel-magnesium oxide was the catalyst that led to the highest reduction in hydrocarbons and tars. This catalyst also led to the lowest NH₃ content in the fuel gas produced, due to the catalyst efficiency in NH₃ destruction.     

Ion‐exchange resins. II. Acrylamide crosslinked copolymers as precursors for some ion exchangers

Crosslinked copolymers of acrylamide (AA) and ethylacrylate and some ion exchangers derived from them containing either primary amine groups, obtained by the Hofmann degradation of the amide groups, or carboxylic groups, obtained by the alkaline hydrolysis of the ester groups, were studied. Divinylbenzene and N,N′‐methylenebisacrylamide were used as crosslinkers. The starting copolymers and the corresponding ion exchangers were characterized by IR spectroscopy, swelling behavior, and thermogravimetric analysis. The ion‐exchanger properties were correlated with the crosslinker nature and the chemical reactions performed on the AA copolymers. The average molecular weight between two crosslinks, determined from the swelling data in water, was compared with that calculated on the basis of the copolymerization stoichiometry only for the carboxylic cation exchangers. In this way, the preservation of the crosslink density after the hydrolysis was revealed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2701–2707, 2003     

Occurrence patterns of alien freshwater turtles in a large urban pond ‘Archipelago’ (Rome,Italy): Suggesting hypotheses on root causes

The patterns of the occurrence and distribution of alien freshwater turtle species in an urban pond archipelago (Rome, Italy) were analysed, with the aim of exploring the role of a set of factors (type of ponds, landscape context, size area, distance from the nearest road) with a generalized linear model approach. A total of 311 ponds subdivided in three types (fountains, small basins, lakes) embedded in different landscape contexts (public parks, private parks, urban areas) at differing distances from the nearest road were sampled. Six non‐native freshwater turtle species in 31 sites were recorded (9.97%). Lakes exhibited the highest occurrence rates of alien freshwater turtles, compared to small basins and fountains. Freshwater turtle species in urbanized areas were only observed in parks (both public and private). In both the public and private parks, the lakes exhibited the highest percentage of occupied sites, with fountains being the lowest. A direct and significant relationship was observed between pond size and species richness. The distance from the nearest road did not appear to affect species richness. A first interpretation of the data from this study facilitated the postulation of two a posteriori hypotheses that should be tested, as follows: (i) the causal process of turtle release is random, and the rate of extinction (and recapture) is higher in smaller ponds, thus producing the observed pattern; and (ii) the turtle release is not random, and people actively select the ponds they consider more suitable for their pet animals. In this study, it appears the lakes were perceived by those who abandon their pets as the most ecologically suitable habitats among other pond types to accommodate the different species of turtles. Knowledge of people's attitudes in regard to releasing pet animals also might assist managers of public green spaces to develop strategies aimed to preserve local biodiversity, and to educate the public about the conservation issue represented by the alien species.