TAS-116, a Well-Tolerated Hsp90 Inhibitor,Prevents the Activation of the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells

Chronic inflammation has been associated with several chronic diseases, such as age-related macular degeneration (AMD). The NLRP3 inflammasome is a central proinflammatory signaling complex that triggers caspase-1 activation leading to the maturation of IL-1β. We have previously shown that the inhibition of the chaperone protein, Hsp90, prevents NLRP3 activation in human retinal pigment epithelial (RPE) cells; these are cells which play a central role in the pathogenesis of AMD. In that study, we used a well-known Hsp90 inhibitor geldanamycin, but it cannot be used as a therapy due to its adverse effects, including ocular toxicity. Here, we have tested the effects of a novel Hsp90 inhibitor, TAS-116, on NLRP3 activation using geldanamycin as a reference compound. Using our existing protocol, inflammasome activation was induced in IL-1α-primed ARPE-19 cells with the proteasome and autophagy inhibitors MG-132 and bafilomycin A1, respectively. Intracellular caspase-1 activity was determined using a commercial caspase-1 activity kit and the FLICA assay. The levels of IL-1β were measured from cell culture medium samples by ELISA. Cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) measurements. Our findings show that TAS-116 could prevent the activation of caspase-1, subsequently reducing the release of mature IL-1β. TAS-116 has a better in vitro therapeutic index than geldanamycin. In summary, TAS-116 appears to be a well-tolerated Hsp90 inhibitor, with the capability to prevent the activation of the NLRP3 inflammasome in human RPE cells.     

Direct and Base Excision Repair-Mediated Regulation of a GC-Rich cis-Element in Response to 5-Formylcytosine and 5-Carboxycytosine

Stepwise oxidation of the epigenetic mark 5-methylcytosine and base excision repair (BER) of the resulting 5-formylcytosine (5-fC) and 5-carboxycytosine (5-caC) may provide a mechanism for reactivation of epigenetically silenced genes; however, the functions of 5-fC and 5-caC at defined gene elements are scarcely explored. We analyzed the expression of reporter constructs containing either 2′-deoxy-(5-fC/5-caC) or their BER-resistant 2′-fluorinated analogs, asymmetrically incorporated into CG-dinucleotide of the GC box cis-element (5′-TGGGCGGAGC) upstream from the RNA polymerase II core promoter. In the absence of BER, 5-caC caused a strong inhibition of the promoter activity, whereas 5-fC had almost no effect, similar to 5-methylcytosine or 5-hydroxymethylcytosine. BER of 5-caC caused a transient but significant promoter reactivation, succeeded by silencing during the following hours. Both responses strictly required thymine DNA glycosylase (TDG); however, the silencing phase additionally demanded a 5′-endonuclease (likely APE1) activity and was also induced by 5-fC or an apurinic/apyrimidinic site. We propose that 5-caC may act as a repressory mark to prevent premature activation of promoters undergoing the final stages of DNA demethylation, when the symmetric CpG methylation has already been lost. Remarkably, the downstream promoter activation or repression responses are regulated by two separate BER steps, where TDG and APE1 act as potential switches.     

Hydrophobic patterning of functional porous pigment coatings by inkjet printing

Paper-based analytical devices provide novel platforms for functional sensing applications, such as medical diagnostics and environmental monitoring. They are based on porous hydrophilic material, which transports the sample liquid by capillary action. The directional flow of aqueous liquids can be controlled by selective hydrophobising of pores. Earlier research in this field has concentrated on highly porous cellulose papers as base substrates, with no significant interest shown for pigment coatings. Such coatings can produce significantly thinner porous layers, thus requiring smaller sample volumes. This study investigates the hydrophobic patterning of custom-designed porous pigment coatings by functional inkjet printing. Tested coatings consisted of reference ground calcium carbonate and porous functionalised calcium carbonate (FCC) pigments combined with various binders, including microfibrillated cellulose. The hydrophobising custom-made inks contain polystyrene or alkyl ketene dimer (AKD) in p-xylene. The patterning is demonstrated by reaction arrays and simple channels. With polystyrene ink, successful hydrophobic barriers could be generated on all tested pigment/binder coatings, although generally requiring printing of multiple layers of barrier material. With AKD ink, hydrophobic patterns could be created successfully on coatings containing an organic binder, but not on coatings with inorganic sodium silicate as binder. The AKD ink generated hydrophobic barriers using fewer ink layers compared with polystyrene ink. Interestingly, AKD ink could hydrophobise the FCC pigment alone without binder, presumably due to hydroxyl groups on the pigment surface. Hydrophobic patterning of the pigment coatings is seen to require large amounts of hydrophobising agent, likely related to the high specific surface area.     

Removal of 4‐chlorophenol from contaminated water using coconut shell waste pretreated with chemical agents

BACKGROUND: At concentrations higher than 1 mg L^?1, 4‐chlorophenol (4‐CP) is very toxic to living organisms, and if ingested beyond the permitted concentration it causes health disorders such as cancer and mutation. This laboratory study investigates treatment of contaminated water laden with 4‐CP using coconut shell charcoal (CSC) waste. Batch studies were conducted to study the effects of dose, pH, and equilibrium time on 4‐CP removal. To improve 4‐CP removal, surface modification of the adsorbent with TiO₂, HNO₃, and/or NaOH was undertaken. RESULTS: At an initial 4‐CP concentration of 25 mg L^?1 under optimized conditions (dose 13.5 g L^?1, pH 2.0; agitation speed 150 rpm and 50 min equilibrium time), the NaOH‐treated CSC demonstrated a greater removal of 4‐CP (71%) than those oxidized with HNO₃ (40%) and/or coated with TiO₂ (52%). The adsorption capacity of the NaOH‐treated CSC (54.65 mg g^?1) was higher than those treated with HNO₃ (23.13 mg g^?1) or coated with TiO₂ (48.42 mg g^?1). CONCLUSION: Although treatment results using the NaOH‐treated CSC alone were promising, the treated effluents were still unable to meet the required limit of less than 1 mg L^?1. Therefore, subsequent treatments are still required to complement the removal of 4‐CP from the wastewater. Copyright © 2010 Society of Chemical Industry     

Mobile Fair Diary: hybrid interface for taking,browsing and sharing context-aware notes

This paper describes the Mobile Fair Diary (MFD), which is designed to allow a housing fair customer to make a personalized digital recording of his/her visit to a hectic fairground for later use. The MFD is a hybrid interface service comprising of an application for a camera equipped smart phone and a website accessed by a PC. The smart phone application is used for taking context-aware notes such as visual codes, photos, dictations and text. The notes are uploaded onto a website, where they can be viewed with a PC in a contextually ordered view for browsing, organizing and sharing. The MFD was empirically evaluated in a real-life environment of use with genuine end users by a large-scale field trial at a national housing fair. The results testify to the very successful design of the MFD with high usefulness.     

Inkjet-printed passive UHF RFID tags: review and performance evaluation

In this paper, the performance and the feasibility of inkjet-printed dipole RFID tag antennas are experimentally studied in the implementation of identifying objects with different electromagnetic properties. To estimate the performance quality, we compare our results to those obtained using traditional etched copper dipole tag antennas. We first examine the performance characteristics, i.e. the read range and the radiation patterns, of tags in free space. Then we attach the tags directly to target objects and compare the optimum performance on target objects to that of the tag in free space. The obtained results provide information about the behaviour of inkjet-printed tag antennas on different objects. This information can be used to optimize the inkjet-printed tag antenna performance for use on objects with different characteristics.     

Electrochemistry of surface grafted copper(II) benzoate complexes

Glassy carbon electrodes were grafted with carboxyphenyl groups by reduction of 4-carboxyphenyldiazonium tetrafluoroborate and these modified electrodes were characterised by cyclic voltammetry and ac impedance measurements. Cu(II) was reacted with the carboxyphenyl groups in the film to give a surface voltammetric response for the immobilised Cu(II)/Cu(I) couple. The results indicated an ECEC mechanism, in which the chemical steps correspond to the change of coordination environment following the electron transfer steps. The relaxation half-life time for the Cu(I) species formed after electron transfer was estimated at (140 ± 11) s. The large value of the peak width of 200 mV was analysed by modelling the voltammograms and the large value of the full width at half maximum (FWHM) could be explained by dispersion in the formal potentials of Cu centres present in a variety of environments in the films studied. An ECEC mechanism (scheme of square) is proposed for the electron transfer reaction considering that the chemical step after reduction of the Cu(II) complex corresponds to conformational changes within the attached layer. Experimental data clearly show that the oxidation of the reduced film can take place from different Cu(I) complexes formed along the reduction to the fully relaxed Cu(I) species.     

Predicting the spatial pattern of trees by airborne laser scanning

The spatial pattern of trees can be defined as a property of their location in relation to each other. In this study, the spatial pattern was summarized into three categories, regular, random, and clustered, using Ripley's L-function. The study was carried out at 79 sample plots located in a managed forest in Finland. The goal was to study how well the spatial pattern of trees can be predicted by airborne laser scanning (ALS) data. ALS-derived predictions were based upon individual tree detection (ITD), semi-individual tree detection (semi-ITD), and plot-level metrics calculated from the canopy height model, AREA. The kappa value for ITD was almost zero, which indicates no agreement. The semi-ITD and AREA methods performed better, although kappa values were only 0.34 and 0.24, respectively. It appears difficult to detect a particularly clustered spatial pattern.     

Aminopolycarboxylic acid functionalized adsorbents for heavy metals removal from water

Due to the excellent chelating properties of aminopolycarboxylic acid (APCAs), they can be used for the removal of metals from contaminated waters. This paper reviews the research results obtained for both commercial and self-prepared adsorbents functionalized with four most common APCAs: iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), and diethylenetriaminepentaacetic acid (DTPA). The structural characteristics and unique metal binding properties of these chelating adsorbents are presented. The theory of the adsorption phenomena is discussed based on the kinetics of adsorption, equilibrium adsorption isotherm models, and thermodynamic models. The most important applications of APCA-functionalized adsorbents are also described. APCA-functionalized adsorbents are found to be highly promising materials for metal removal from contaminated waters.