Towards personality-based user adaptation: psychologically informed stylistic language generation

Conversation is an essential component of social behavior, one of the primary means by which humans express intentions, beliefs, emotions, attitudes and personality. Thus the development of systems to support natural conversational interaction has been a long term research goal. In natural conversation, humans adapt to one another across many levels of utterance production via processes variously described as linguistic style matching, entrainment, alignment, audience design, and accommodation. A number of recent studies strongly suggest that dialogue systems that adapted to the user in a similar way would be more effective. However, a major research challenge in this area is the ability to dynamically generate user-adaptive utterance variations. As part of a personality-based user adaptation framework, this article describes personage, a highly parameterizable generator which provides a large number of parameters to support adaptation to a user’s linguistic style. We show how we can systematically apply results from psycholinguistic studies that document the linguistic reflexes of personality, in order to develop models to control personage’s parameters, and produce utterances matching particular personality profiles. When we evaluate these outputs with human judges, the results indicate that humans perceive the personality of system utterances in the way that the system intended.     

Crystal structure of the bacterial ribosomal decoding site complexed with a synthetic doubly functionalized paromomycin derivative: a new specific binding mode to an a-minor motif enhances in vitro antibacterial activity

The crystal structure of the complex between oligonucleotide containing the bacterial ribosomal decoding site (A site) and the synthetic paromomycin analogue 1, which contains the gamma-amino-alpha-hydroxybutyryl (L-haba) group at position N1 of ring II (2-DOS ring), and an ether chain with an O-phenethylaminoethyl group at position C2' of ring III, is reported. Interestingly, next to the paromomycin analogue 1 specifically bound to the A site, a second molecule of 1 with a different conformation is observed at the crystal packing interface which mimics the A-minor interaction between two bulged-out adenines from the A site and the codon-anticodon stem of the mRNA-tRNA complex. Improved antibacterial activity supports the conclusion that analogue 1 might affect protein synthesis on the ribosome in two different ways: 1) specific binding to the A site forces maintenance of the "on" state with two bulged out adenines, and 2) a new binding mode of 1 to an A-minor motif which stabilizes complex formation between the ribosome and the mRNA-tRNA complex regardless of whether the codon-anticodon stem is of the cognate or near-cognate type.     

Predicting and tuning physicochemical properties in lead optimization: amine basicities

This review describes simple and useful concepts for predicting and tuning the pK(a) values of basic amine centers, a crucial step in the optimization of physical and ADME properties of many lead structures in drug-discovery research. The article starts with a case study of tricyclic thrombin inhibitors featuring a tertiary amine center with pK(a) values that can be tuned over a wide range, from the usual value of around 10 to below 2 by (remote) neighboring functionalities commonly encountered in medicinal chemistry. Next, the changes in pK(a) of acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and sulfur functionalities, as well as carbonyl and carboxyl derivatives are systematically analyzed, leading to the derivation of simple rules for pK(a) prediction. Electronic and stereoelectronic effects in cyclic amines are discussed, and the emerging computational methods for pK(a) predictions are briefly surveyed. The rules for tuning amine basicities should not only be of interest in drug-discovery research, but also to the development of new crop-protection agents, new amine ligands for organometallic complexes, and in particular, to the growing field of amine-based organocatalysis.     

Highly selective synthesis of 2‐butoxy ethanol over Mg/Al/V mixed oxides catalysts derived from hydrotalcites

The catalytic activity of a series of mixed oxides obtained by the thermal decomposition of hydrotalcite‐like precursors was assessed for the alkoxylation of n-butanol with ethylene oxide. The calcination products of a decavanadate intercalated magnesium–aluminium layered double hydroxide were shown to possess extremely high activity for the alkoxylation reaction achieving up to 100% conversion in batch reaction. In all cases, the catalysts exhibit a much higher selectivity towards the monoglycol adduct than that obtained with the industrial catalyst. This revised version was published online in July 2006 with corrections to the Cover Date.     

Electrochemical treatment of bisphenol-A using response surface methodology

The decomposition of bisphenol-A (BPA) in synthetic solution and in municipal effluent was investigated using an electro-oxidation process. Electrolysis was conducted using a cylindrical electrolytic cell containing two circular anodes (expanded metal) and two circular cathodes (stainless steel) alternated in the electrode pack. Different anode materials (Ti/SnO₂, Ti/IrO₂ and Ti/PbO₂) were tested, and Ti/PbO₂ was found to be the most effective electrode for BPA degradation. An experimental design methodology (2³ Box–Behnken design) was applied to determine the optimal experimental conditions in terms of cost effectiveness. The BPA concentration (C ₀ = 1.0 mg l⁻¹) could be optimally diminished by up to 90% by applying a current intensity of 2.0 A for a 100-min reaction period in the presence of 250 mg Na₂SO₄ l⁻¹ (used as a supporting electrolyte). Then, the optimal conditions were applied on a municipal wastewater effluent (sampled after secondary treatment) artificially contaminated with 1 mg BPA l⁻¹ without the addition of a supporting electrolyte. The treatment was more effective with the municipal effluent due to the presence of a high concentration of chloride ions that could easily be transformed into active chlorine. BPA could be oxidized by both direct anodic electrochemical oxidation (by means of OH·) and indirect electrochemical oxidation via mediators, such as hypochlorous acid generated by chloride oxidation. Both actions (direct and indirect effects) lead to the formation of powerful oxidizing agents capable of rapidly oxidizing BPA.     

Preparation and characterization of scleroglucan drug delivery films: The effect of freeze‐thaw cycling

This study examined the effect of the freeze‐thaw process on the physical properties of films prepared from scleroglucan (Scl) hydrogels, suitable for drug delivery applications. Films made from Scl, using glycerol as plasticizer, were prepared from hydrogels by two procedures: a room temperature drying (RTD) method and a freeze‐thaw cyclic process, before the application of RTD, which results in a reinforced physically cross‐linked network. Films were characterized by studies of water vapor transmission (WVT), swelling, tensile tests, ESEM microscopy, FTIR, and drug release measurements. These determinations showed significant differences between films obtained by both treatments. The films prepared through freeze‐thaw cycles showed an important increase of the tensile strength with respect to those corresponding to films only air dried and a decreasing swelling degree in direct relationship to the number of freeze‐thaw cycles. A model drug, Theophylline, was included in these biocompatible films for in vitro drug release measurements, using a flat Franz cell. The physical differences observed between Scl films prepared with both methods can be explained proposing that the number of crosslinking points by hydrogen bonding increase when increasing the number of freezing and thawing cycles used for film preparation. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Aryl Bis‐Sulfonamide Inhibitors of IspF from Arabidopsis thaliana and Plasmodium falciparum

2‐Methylerythritol 2,4‐cyclodiphosphate synthase (IspF) is an essential enzyme for the biosynthesis of isoprenoid precursors in plants and many human pathogens. The protein is an attractive target for the development of anti‐infectives and herbicides. Using a photometric assay, a screen of 40 000 compounds on IspF from Arabidopsis thaliana afforded symmetrical aryl bis‐sulfonamides that inhibit IspF from A. thaliana (AtIspF) and Plasmodium falciparum (PfIspF) with IC₅₀ values in the micromolar range. The ortho‐bis‐sulfonamide structural motif is essential for inhibitory activity. The best derivatives obtained by parallel synthesis showed IC₅₀ values of 1.4 μm against PfIspF and 240 nm against AtIspF. Substantial herbicidal activity was observed at a dose of 2 kg ha^?1. Molecular modeling studies served as the basis for an in silico search targeted at the discovery of novel, non‐symmetrical sulfonamide IspF inhibitors. The designed compounds were found to exhibit inhibitory activities in the double‐digit micromolar IC₅₀ range.     

A Perinatal Palatable High-Fat Diet Increases Food Intake and Promotes Hypercholesterolemia in Adult Rats

The main goal of the present study was to evaluate the long-term effects of a perinatal palatable high-fat diet on the food intake and cholesterol profile of adult rats. Male Wistar rats (aged 22 days) were divided into two groups according to their mother’s diet during gestation and lactation (C _p, n = 10; pups from control mothers; and HL_p n = 10; pups from mothers fed a palatable high-fat diet). At the 76th day, pups were housed individually for 14 days, and daily food consumption was determined during a period of 6 days. Blood from 100-day-old rats was sampled by cardiac puncture. Fasting (12 h) serum glucose, total cholesterol, LDL-C, HDL-C, triglycerides (TG), and VLDL-C levels were determined. The measurement of food intake was higher in the animals submitted to a hyperlipidic diet during the perinatal period. Serum total cholesterol, LDL-C, HDL-C, TG, VLDL-C and glycemia were increased in the HL_p group compared to the control group. Our findings show that an early life environment with a high-fat diet can contribute to metabolic disease in later life.     

Long-Term Measures of Dyslipidemia,Inflammation, and Oxidative Stress in Rats Fed a High-Fat/High-Fructose Diet

Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL-6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid-reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies.