Synthesis and evaluation of an intercalator-polyamide hairpin designed to target the inverted CCAAT box 2 in the topoisomerase IIalpha promoter

The synthesis and DNA-binding properties of a novel naphthalimide-polyamide hairpin (3) designed to target the inverted CCAAT box 2 (ICB2) site on the topoisomerase IIalpha (topoIIalpha) promoter are described. The polyamide component of 3 was derived from the minor-groove binder, 2, and tailored to bind to the 5'-TTGGT sequence found in and flanking ICB2. The propensity of mitonafide 4 to intercalate between G-C base pairs was exploited by the incorporation of a naphthalimide moiety at the N terminus of 2. Hybrid 3 targeted 5'-CGATTGGT and covered eight contiguous base pairs, which included the underlined ICB2 site. DNase I footprinting analysis with the topoIIalpha promoter sequence demonstrated that 3 bound selectively to the ICB2 and ICB3 sites. Thermal-denaturation studies confirmed these results, and the highest degree of stabilization was found for ICB2 and -3 in preference to ICB1 (4.1, 4.6, and 0.6 degrees C, respectively). CD studies confirmed minor-groove binding and suggested a 1:1 binding stoichiometry. Emission-titration experiments established intercalative binding. Surface plasmon resonance results showed strong binding to ICB2 (2.5x10(7) M(-1)) with no observable binding to ICB1. Furthermore, the binding constant of 3 to ICB2 was larger than that of the parent polyamide 2. The increased binding affinity was primarily due to a reduction in the dissociation-rate constant of the polyamide-DNA complex, which can be attributed to the N-terminal naphthalimide moiety. In addition, the binding site of 3 was larger than that of 2, which innately improved sequence selectivity. We conclude that the polyamide-naphthalimide 3 selectively binds to the ICB2 site by simultaneous intercalation and minor-groove binding, and warrants further investigation as a model compound for the regulation of topoIIalpha gene expression.     

Paradoxical effects of testing: Retrieval enhances both accurate recall and suggestibility in eyewitnesses.

Although retrieval practice typically enhances memory retention, it can also impair subsequent eyewitness memory accuracy (Chan, Thomas, & Bulevich, 2009). Specifically, participants who had taken an initial test about a witnessed event were more likely than nontested participants to recall subsequently encountered misinformation—an effect we called retrieval-enhanced suggestibility (RES). Here, we sought to test the generality of RES and to further elucidate its underlying mechanisms. To that end, we tested a dual mechanism account, which suggests that RES occurs because initial testing (a) enhances learning of the later misinformation by reducing proactive interference and (b) causes the reactivated memory trace to be more susceptible to later interference (i.e., a reconsolidation account). Three major findings emerged. First, RES was found after a 1-week delay, where a robust testing benefit occurred for event details that were not contradicted by later misinformation. Second, blockage of reconsolidation was unnecessary for RES to occur. Third, initial testing enhanced learning of the misinformation even when proactive interference played a minimal role. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Small High-Density Lipoprotein (HDL) Subclasses are Increased with Decreased Activity of HDL-Associated Phospholipase A2 in Subjects with Prediabetes

Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A₂ (HDL-LpPLA₂) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA₂.     

Agent-based framework for intelligent natural language interface

In this contribution, we present a framework for an intelligent natural language interface (NLI) that suits the need of embedded platform, using agent-based approach. The proposed framework is motivated by an ongoing speech technology research project aimed at developing a generic synthesizer for information disseminating systems in local languages. The architecture is based on various forms of action representations with a sequence of transformations that converts users’ input (text or speech) into a suitable set of agent actions that produce response to the input. This approach incrementally minimizes the complexity and ambiguity of the natural language input by using predefined sets of interim actions at different levels, hence, increasing the robustness and reliability of the NLI.     

Spray‐Coated Silver Nanowires as Top Electrode Layer in Semitransparent P3HT:PCBM‐Based Organic Solar Cell Devices

Silver nanowire (Ag NW) thin films are investigated as top electrodes in semitransparent inverted organic solar cells. The performance of semitransparent poly(3‐hexylthiophene‐2,5‐diyl):[6,6]‐phenyl‐C61‐butyric acid methyl ester (P3HT:PCBM) organic solar cells with Ag NW top electrode layers is found to match very closely the performance of reference devices based on thermally evaporated, highly reflective metal silver top electrodes. The optical losses of the semitransparent electrodes are investigated in detail and analyzed in terms of transmission, scattering, and reflection losses. The impact on an external back reflector is shown to increase the light harvesting efficiency of optically thin devices. Further analysis of transparent devices under illumination from the indium tin oxide (ITO) backside and through the Ag NW front electrode open the possibility to gain deep insight into the vertical microstructure related devices performance. Overall, Ag NW top electrodes are established as a serious alternative to TCO based electrodes. Semitransparent devices with efficiencies of over η = 2.0% are realized.     

Performance evaluation of poly (methacrylic acid) as corrosion inhibitor in the presence of iodide ions for mild steel in H2SO4 solution

The inhibition performance of poly (methacrylic acid) (PMAA) and the effect of addition of iodide ions on the inhibition efficiency for mild steel corrosion in 0.5 M H₂SO₄ solution were investigated in the temperature range of 303–333 K using electrochemical, weight loss, scanning electron microscopy (SEM), and water contact angles measurements. The results show that PMAA is a moderate inhibitor for mild steel in 0.5 M H₂SO₄ solution. Addition of small amount of KI to PMAA significantly upgraded the inhibition efficiency up to 96.7%. The adsorption properties of PMAA and PMAA + KI are estimated by considering thermodynamic and kinetic parameters. The results reveal that PMAA alone was physically adsorbed onto the mild steel surface, while comprehensive adsorption mode characterized the adsorption of PMAA + KI. Adsorption of PMAA and PMAA + KI followed Temkin adsorption isotherm. The SEM and water contact angle images confirmed the enhanced PMAA film formation on mild steel surface by iodide ions.     

Hydrodynamics of a rectangular liquid JET in an immiscible liquid–liquid system

Volume of fluid and continuum surface force methodologies were applied to two‐ and three‐dimensionally model the motion of a liquid jet injected vertically downward from a rectangular nozzle into another immiscible liquid. Grid independent solutions were obtained for a 10 mm² nozzle with aspect ratios in the range 1–10. It was found that unlike the 3D simulation, the 2D CFD model was not able to predict the necking and breakup features observed in the experimental system. The 3D model showed that upon exiting the rectangular nozzle the liquid jet underwent a transition before becoming circular in cross‐section and eventually reaching an equilibrium diameter prior to breakup into droplets. For a given nozzle geometry it was found that equilibrium jet diameter increased with increasing liquid volumetric flowrate, with good agreement between CFD simulations and experimental observations. The 3D model was applied to rectangular nozzles with different aspect ratios and it was found that for a given liquid flowrate there was an optimum aspect ratio for generating minimum‐sized droplets, which was approximately 30% less than for a circular nozzle with the same cross‐sectional area. © 2011 Canadian Society for Chemical Engineering     

Young children's understanding of desire formation.

Two studies examined preschoolers' appreciation of how mental states arise. In Study 1, children aged 3 to 5 (24 at each age) better understood perception-generated beliefs (e.g., that looking in a certain location generates a belief about the location's content) and attitude-generated desires (e.g., that positive experiences with an activity generate a desire to partake of the activity again) than physiology-generated desires (e.g., that not eating for a long time generates a desire for food). In Study 2, 4- and 5-year-olds (48 at each age) better understood the effects of quantity of experience (e.g.. eating a lot vs. a little) than of time of experience (eating just now vs. a long time ago) on physiological states and desires. The findings suggest that whether children reason in more advanced fashion about desires or beliefs depends on which aspects of these mental states are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Optimized deposition and characterization of nanocrystalline magnesium indium oxide thin films for opto-electronic applications

Transparent conducting magnesium indium oxide films (MgIn₂O₄) were deposited on to quartz substrates without a buffer layer at an optimized deposition temperature of 450 °C to achieve high transmittance in the visible spectral range and electrical conductivity in the low temperature region. Magnesium ions are distributed over the tetrahedral and octahedral sites of the inverted spinel structure with preferential orientation along (3 1 1) Miller plane. The possible mechanism that promotes conductivity in this system is the charge transfer between the resident divalent (Mg²⁺) and trivalent (In³⁺) cations in addition to the available oxygen vacancies in the lattice. A room temperature electrical conductivity of 1.5 × 10⁻⁵ S cm⁻¹ and an average transmittance >75% have been achieved. Hall measurements showed n-type conductivity with electron mobility value 0.95 × 10⁻² cm² V⁻¹ s⁻¹ and carrier concentration 2.7 × 10¹⁹ cm⁻³. Smoothness of the film surface observed through atomic force microscope measurements favors this material for gas sensing and opto-electronic device development.