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.     

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     

Pulse height defect in pCVD and scCVD diamond based detectors

Polycrystalline (pCVD) and single crystal (scCVD) diamond films grown from Chemical Vapour Deposition (CVD), if sufficiently pure at Raman analysis, are very good materials for beam or flux monitors inside accelerators or nuclear reactors. This is because they are very hard to damage in high radiation fields and very resistant to high temperatures. Films of pCVD diamond are, however, not so good as spectroscopy detectors due to inhomogeneities induced by their growth in grains with the consequent presence of grain boundaries which worsen their energy resolution. The latter can be significantly improved by growing scCVD diamond films onto HPHT synthetic diamond substrates. We have shown that it is possible to measure the density of defects inside diamond specimens using as probes suitable penetrating nuclear radiations. With the preliminary results reported here we'll show that, bombarding CVD diamond films grown at Roma “Tor Vergata” with energetic protons and ⁴He, ⁶Li and ¹²C ions produced in the accelerators of Catania laboratories, the pulse height defects are higher than those in silicon detectors and likewise well described by a power law in the deposited energy. Furthermore, we'll show that pulse heights for the same particles seem to depend on the duration of the measurement, thus exhibiting a sort of depolarization of the insulator when exposed to the electric voltage which makes it a particle detector.     

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.     

Evaluation of the thermal and mechanical properties of poly(ε‐caprolactone), low‐density polyethylene,and their blends

The thermal and mechanical properties of low‐density polyethylene (LDPE), poly(ε‐caprolactone) (PCL), and their blends were evaluated. Differential scanning calorimetry showed that increasing the PCL content of the blend did not change the LDPE melting temperature, but reduced the crystallinity by up to 16.8%. This behavior was related to interactions between the PCL chains and the crystalline phase of LDPE. Tensile strength and elongation at break values for the blends were lower than those for the pure polymers, which suggested an incompatibility between the polymers. The values for Young's modulus under tensile increased when PCL was added to LDPE. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91:3909–3914, 2004     

Total content and dialyzable iron and zinc in foods from northern and Southern Mexico

Developing countries diets are based on a variety of plant foods that often are the main suppliers of important amounts of iron (Fe) and zinc (Zn). The objectives of this study were 1) to measure the total and dialyzable amounts of Fe and Zn in foods from Northern Mexico (Sonora) and from Southern Mexico (Oaxaca) and 2) to evaluate the effect of meat content of diets on the dialyzable amount of Fe and Zn. Methods to calculate the total dialyzable amount of Fe and Zn, were those of the AOAC and of Shen et al. Total Fe in e northern Mexican foods went from 0.78 +/- 0.0 to 11.59 +/- to 0.03 mg/ 100g (dry weight, DW); in southern Mexican foods the same micronutrient amounts were 0.86 +/- 0.18 to 8.8 +/- 0.57 mg/100 g (BS). Total Zn values were 0.91 +/- 0.00 to 13.58 +/- 0.05 mg/100 g (DW) in Sonora, and 0.64 +/- 0.18 to 20.80 +/- 0.33 mg/100 g (DW) in Oaxaca. In northern Mexico, foods dialyzable Fe had values from 0.1 +/- 0.04% to 10.6 +/- 0.36% and for Zn from 4.0 +/- 0.21% to 55.32 +/- 0.14%. Meanwhile, the range of values of dialyzable Fe for foods from Oaxaca were from 0.22 +/- 0.06% to 9.40 +/- 0.14% for and from 2.41 +/- 0.26% to 54.27 +/- 1.49% for dialyzable Zn. The average value for dialyzable Fe was higher in the foods that contained meat or meat products (p= 0.001).