An empirical evaluation of active learning strategies for profile elicitation in a conversational recommender system

Journal of Intelligent Information Systems - Conversational Recommender Systems have received widespread attention in both research and practice. They assist people in finding relevant and...     

Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation

HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents.     

Mixed Lubrication with C18 Fatty Acids: Effect of Unsaturation

In this paper, the lubrication mechanism of fatty acids is revisited with a new approach combining experimental and computational chemistry studies. The lubricating properties of single and mixtures of stearic, oleic and linoleic acids in a synthetic Poly-Alpha-Olefin base oil (PAO4) on iron oxide surface are investigated under mixed boundary regime with temperatures from 50 °C up to 150 °C. Low friction coefficient (about 0.055) with no visible wear is reported in the presence of single stearic acid at high temperature. This lubricating behavior is inhibited in the presence of unsaturated fatty acids highlighting an anti-synergic effect of a saturated/unsaturated mixture, especially at 150 °C. To understand the anti-synergic effect and the adsorption mechanism of these molecules, molecular dynamic (MD) and quantum chemistry simulations are performed to evaluate their diffusion coefficient in PAO4 and their adsorption mechanism on iron oxide at different temperatures. MD simulation results show a faster diffusion toward the surface for unsaturated fatty acids than for saturated fatty acid at all the studied temperatures. This means that unsaturated molecules arrive and mainly adsorb before stearic acid on the surface leading to a tribological behavior of the mixture characteristic of the unsaturated molecule. Computational chemistry suggests that all fatty acids (saturated and unsaturated) adsorption mechanism is due to the chemisorption of the carboxylic group on iron oxide surface with no desorption up to 150 °C.     

In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against A. mellifera and H. sapiens Receptors

Background. Poisoning from pesticides can be extremely hazardous for non-invasive species, such as bees, and humans causing nearly 300,000 deaths worldwide every year. Several pesticides are recognized as endocrine disruptors compounds that alter the production of the normal hormones mainly by acting through their interaction with nuclear receptors (NRs). Among the insecticides, one of the most used is pyriproxyfen. As analogous to the juvenile hormone, the pyriproxyfen acts in the bee’s larval growth and creates malformations at the adult organism level. Methods. This work aims to investigate the possible negative effects of pyriproxyfen and its metabolite, the 4′-OH-pyriproxyfen, on human and bee health. We particularly investigated the mechanism of binding of pyriproxyfen and its metabolite with ultraspiracle protein/ecdysone receptor (USP-EcR) dimer of A. mellifera and the relative heterodimer farnesoid X receptor/retinoid X receptor alpha (FXR-RXRα) of H. sapiens using molecular dynamic simulations. Results. The results revealed that pyriproxyfen and its metabolite, the 4′-OH- pyriproxyfen, stabilize each dimer and resulted in stronger binders than the natural ligands. Conclusion. We demonstrated the endocrine interference of two pesticides and explained their possible mechanism of action. Furthermore, in vitro studies should be carried out to evaluate the biological effects of pyriproxyfen and its metabolite.     

A Comparative Analysis of the Photo-Protective Effects of Soy Isoflavones in Their Aglycone and Glucoside Forms

Isoflavones exist in nature predominantly as glucosides such as daidzin or genistin and are rarely found in their corresponding aglycone forms daidzein and genistein. The metabolism and absorption of isoflavones ingested with food is well documented, but little is known about their use as topical photo-protective agents. The aim of this study was to investigate in a comparative analysis the photo-protective effects of isoflavones in both their aglycone and glucoside forms. In human skin fibroblasts irradiated with 60 mJ/cm² ultraviolet B (UVB), we measured the expression levels of COX-2 and Gadd45, which are involved in inflammation and DNA repair, respectively. We also determined the cellular response to UVB-induced DNA damage using the comet assay. Our findings suggest that both the isoflavone glucosides at a specific concentration and combination with an aglycone mixture exerted an anti-inflammatory and photo-protective effect that prevented 41% and 71% of UVB-induced DNA damage, respectively. The advantages of using either isoflavone glucosides or an aglycone mixture in applications in the field of dermatology will depend on their properties and their different potential uses.     

Chemical modification of organosolv lignin using boronic acid-containing reagents

Organosolv lignin was chemically modified with boron-containing reagents using a novel “graft-to” approach. The newly synthesized graft copolymers were prepared by covalently linking boron end-functionalized polycaprolactone (PCL) macromolecular reagents with organosolv lignin via reversible covalent bonds. Using a combination of ¹H, ¹³C, ¹⁹F, and ¹¹B NMR, it has been shown that arylboronate ester bonds are involved in the key linkages between the polyester grafts and the lignin core. Using a straightforward synthetic procedure and altering both the PCL graft density and the PCL molecular weight, a selection of compositions were studied. The newly prepared lignin-g-PCL copolymers were analyzed by differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). The Lignin-PCL₅₂₀₀ series shows an increase in PCL crystallinity with an increase PCL graft density. However, the crystallinity of the PCL in the lignin-g-PCL₉₁₀₀ set of materials remained constant throughout the series. TGA analysis for all lignin-g-PCL copolymers prepared herein show thermal decomposition near 300 °C.     

Effect of Temperature on Lubricated Steel/Steel Systems With or Without Fatty Acids Additives Using an Oscillating Dynamic Tribometer

The friction behavior of steel/steel contacts lubricated with glycerol, 150NS and PAO4 is investigated using a new technique. Then, three additives are used in PAO4 lubricant: oleic, linoleic and stearic acids. The experiments are performed at different temperatures. Moreover, nearly all the systems operate in either the mixed or boundary lubrication regime. The experimental methodology is able, with a high accuracy and without any force transducer, two contributions of friction: μ ₀, velocity-independent contribution and μ ₁, velocity-dependent one. This study shows that glycerol is the most effective in reducing friction among the three pure lubricants. In addition, only glycerol affects the viscous damping of the system at some operating conditions. Using the additives in PAO4, the friction is reduced. More precisely, the unsaturated fatty acids are more significant in reducing the friction than saturated acids. Moreover, the viscous damping of the apparatus is slightly affected as additives are used in PAO4.     

A nuclear export signal in Kap95p is required for both recycling the import factor and interaction with the nucleoporin GLFG repeat regions of Nup116p and Nup100p

During nuclear import, cytosolic transport factors move through the nuclear pore complex (NPC) to the nuclear compartment. Kap95p is required during import for docking the nuclear localization signal-receptor and ligand to the NPC. Recycling of this factor back to the cytoplasm is necessary for continued rounds of import; however, the mechanism for Kap95p recycling is unknown. We have determined that recycling of Kap95p requires a nuclear export signal (NES). A region containing the NES in Kap95p was sufficient to mediate active nuclear export in a microinjection assay. Moreover, the NES was necessary for function. Mutation of the NES in Kap95p resulted in a temperaturesensitive import mutant, and immunofluorescence microscopy experiments showed that the mutated Kap95p was not recycled but instead localized in the nucleus and at the nuclear envelope. Srp1p, the yeast nuclear localization signal-receptor, also accumulated in the nuclei of the arrested kap95 mutant cells. Wild-type and NES-mutated Kap95p both bound Gsp1p (the yeast Ran/TC4 homologue), Srp1p, and the FXFG repeat region of the nucleoporin Nup1p. In contrast, the NES mutation abolished Kap95p interaction with the GLFG repeat regions from the nucleoporins Nup116p and Nup100p. In vivo interaction was demonstrated by isolation of Kap95p from yeast nuclear lysates in either protein A-tagged Nup116p or protein A-tagged Nup100p complexes. The protein A-tagged Nup116p complex also specifically contained Gle2p. These results support a model in which a step in the recycling of Kap95p is mediated by interaction of an NES with GLFG regions. Analysis of genetic interactions suggests Nup116p has a primary role in Kap95p recycling, with Nup100p compensating in the absence of Nup116p. This finding highlights an important role for a subfamily of GLFG nucleoporins in nuclear export processes.     

The “Piano dell’Acqua” sinkholes (San Basile,Northern Calabria,Italy)

The occurrence of sinkholes not directly related to karst has been determined in several areas worldwide in recent years. These phenomena may be particularly dangerous to humans and infrastructure due to their subtle origin and need to be carefully examined. In this work, we describe five sinkholes recently identified in a hilly setting of Southern Italy characterized by Pliocene conglomerate and sand, and variously dislocated by tectonic structures. The sinkholes were examined by different methods (interpretation of multi-temporal aerial photos, geological, geomorphological and geophysical surveys). An historical analysis was performed to collect and critically evaluate information regarding the age of the phenomena. Based on this information, it can be conjectured that two of the five sinkholes developed during the 2000–2001 winter; two of the remaining probably originated during the 70s; the last one opened sometime between February 2001 and November 2007. Based on such chronology, attempts have been performed to identify the likely triggers, through hydrological and seismic analyses. In both cases, no immediate correlation could be found. The origin of the studied phenomena remains uncertain, and may be related to sub-cutaneous erosion, in an area that is renowned to be rich in groundwater. Local changes in the water table, related to climate and/or man-induced activities, may have triggered the development of the cover suffusion-type sinkholes. The present work highlights the potential for this type of phenomena to occur in geological settings without the direct presence of soluble rocks at the surface, a condition quite common in Southern Italy, and the need to carry out further studies in order to better comprehend their mechanisms of origin and successive evolution, and to properly evaluate the related hazard.