Carbonic anhydrase inhibitors: design of membrane-impermeant copper(II) complexes of DTPA-, DOTA-, and TETA-tailed sulfonamides targeting the tumor-associated transmembrane isoform IX

The synthesis and carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of two series of aromatic sulfonamides and their Cu(II) derivatives, incorporating metal-complexing moieties of the DTPA, DOTA, and TETA type are reported. The new compounds were designed in such a way as to possess high affinity for Cu(II) ions, exploiting four pendant carboxylate moieties in the DTPA derivatives, as well as the cyclen/cyclam macrocyles, and three pendant acetate moieties in the DOTA and TETA derivatives. The new derivatives showed modest inhibition of the cytosolic isoform CA I (K(I) values in the range of 66-2130 nM), were better CA II inhibitors (K(I) values in the range of 21-360 nM), and excellent inhibitors of the tumor-associated isoform CA IX (K(I) values in the range of 4.1-110 nM), with selectivity ratios for the inhibition of the tumor (CA IX) over the cytosolic (CA II) isozyme in the range of 10.74-20.88 for the best derivatives. Copper complexes were more inhibitory than the corresponding ligand sulfonamides, and showed membrane impermeability, thus, having the possibility to specifically target the transmembrane CA IX that has an extracellular active site. Incorporation of radioactive copper isotopes in this type of CA inhibitor may lead to interesting diagnostic/therapeutic applications for such compounds.     

Nanomaterials for Antiangiogenic Therapies for Cancer: A Promising Tool for Personalized Medicine

Angiogenesis is one of the hallmarks of cancer. Several studies have shown that vascular endothelium growth factor (VEGF) plays a leading role in angiogenesis progression. Antiangiogenic medication has gained substantial recognition and is commonly administered in many forms of human cancer, leading to a rising interest in cancer therapy. However, this treatment method can lead to a deteriorating outcome of resistance, invasion, distant metastasis, and overall survival relative to its cytotoxicity. Furthermore, there are significant obstacles in tracking the efficacy of antiangiogenic treatments by incorporating positive biomarkers into clinical settings. These shortcomings underline the essential need to identify additional angiogenic inhibitors that target numerous angiogenic factors or to develop a new method for drug delivery of current inhibitors. The great benefits of nanoparticles are their potential, based on their specific properties, to be effective mechanisms that concentrate on the biological system and control various important functions. Among various therapeutic approaches, nanotechnology has emerged as a new strategy for treating different cancer types. This article attempts to demonstrate the huge potential for targeted nanoparticles and their molecular imaging applications. Notably, several nanoparticles have been developed and engineered to demonstrate antiangiogenic features. This nanomedicine could effectively treat a number of cancers using antiangiogenic therapies as an alternative approach. We also discuss the latest antiangiogenic and nanotherapeutic strategies and highlight tumor vessels and their microenvironments.     

UV-shielding by a polyurethane/f-Oil fly ash-CeO2 protective coating

A waste material called oil fly ash (OFA) was acid-functionalized, yielding f-OFA-COOH, which was then reacted with cerium oxide (CeO₂) to make CeO₂-functionalized OFA, or f-OFA-CeO₂. Pristine OFA and f-OFA-CeO₂ were used to make waterborne polyurethane (WBPU) dispersions, referred to as WBPU/OFA and WBPU/f-OFA-CeO₂, respectively, with defined OFA and f-OFA-CeO₂ content. All the dispersions were applied to mild steel as organic coatings to evaluate their protective properties, such as their hydrophobicity, adhesive strength and UV-shielding resistance. These protective properties varied based on the OFA and f-OFA-CeO₂ content. The highest water contact angle, minimum water swelling and maximum adhesive strength were found using WBPU/f-OFA-CeO₂-20 coating (using 2.00 wt% f-OFA-CeO₂), which also showed the maximum ultraviolet (UV) absorption via UV–vis spectroscopy analysis. This UV shielding result also matched field test results, as that coating was found to exhibit the lowest UV degradation near a marine atmosphere, as shown by X-ray photoelectron spectroscopy (XPS) analysis. The least affected hydrophobicity was also recorded for the sample with the WBPU/f-OFA-CeO₂-20 coating.     

Experimental study about the effects of disc chipper settings on the distribution of wood chip size

Nowadays wood should be of principal sources of biomass. This wood is transformed into chips in order to increase automatic operations and to decrease the technical effort needed at the energy conversion plant. Typical high quality chips, which are used to feed small woodchip boilers, vary in size from 10 × 10 × 5 mm to 15 × 15 × 8 mm. Chips that are relatively square and flat are easily conveyed, augured, and fed into the system smoothly. We are mainly interested in the raw material of inferior quality. A disc chipper test bench was constructed in our laboratory to study the chipping process in cutting conditions which are similar to those used in the industry. The test bench design allows many factors to be varied include cutting speed, feed per tooth, cutting angles, anvil height and cutting direction. In this paper, we attempt to understand the effect of several factors on chip size distribution. Four feeds per tooth, four cutting angles, two sharpness angles and three cutting speeds were chosen to cut wet logs of oak and fir wood, while the other factors remained constant. The results are similar for both oak and fir. The proportion of small chips decreases when we increase the feed per tooth, the cutting angle and the sharpness angle, whereas it increases when the cutting speed is increased. The feed per tooth and the cutting speed have a linear effect on the variations in the size distribution, while the cutting angle has a non-linear effect on these variations.     

Volatile compounds of Baltic herring analysed by dynamic headspace sampling–gas chromatography–mass spectrometry

European Food Research and Technology - The effect of storage time at 6&;nbsp;°C on the volatile compounds of Baltic herring was studied using the dynamic headspace–gas...     

Perception of chemosensory stimuli and related responses to flavored yogurts in the young and elderly

This study examined the effects of chemosensory performance of two age groups on ratings of the just-right intensity of odor, flavor and coolness. Two experiments were conducted: (1) creation of a sensory profile by a trained panel and (2) hedonic testing of the yogurt samples by young (n=47, 20–35 years) and elderly (n=45, 65–82 years) subjects, who also participated in tests measuring their chemosensory performance. Eight yogurt samples (2×2×2 factorial design) were flavored with 6 or 10% sucrose, 0.2 or 0.8% lemon aroma and 0.004 or 0.012% menthol. Young subjects outperformed elderly in the olfactory, gustatory and trigeminal perception tests. Their performance in the chemosensory tests affected hedonic ratings of yogurts, especially in the case of the elderly. Among the elderly, just-right flavor was affected by the performance in olfactory, gustatory (sweet, sour) and trigeminal (menthol) tests. Just-right coolness was affected by olfactory perception and by identification of sweet taste. Pleasantness was affected by olfactory and menthol perception. Thus, stimulus-specific losses in chemosensory acuity of the elderly may lead to distorted perception of foods.     

Angiotensin I-converting enzyme inhibitory properties of whey protein digests: concentration and characterization of active peptides

The aim of this study was to identify whey-derived peptides with angiotensin I-converting enzyme (ACE) inhibitory activity. The bovine whey proteins alpha-lactalbumin and beta-lactoglobulin were hydrolysed with pepsin, trypsin, chymotrypsin, pancreatin, elastase or carboxypeptidase alone and in combination. The total hydrolysates were fractionated in a two step ultrafiltration process, first with a 30 kDa membrane and then with a 1 kDa membrane. Inhibition of ACE was analysed spectrophotometrically. The peptides were isolated by chromatography and identified by mass and sequencing analysis. The most potent inhibitory peptides were synthesized by the 9-fluorenylmethoxycarbonyl solid phase method. Inhibition of ACE was observed after hydrolysis with trypsin alone, and with an enzyme combination containing pepsin, trypsin and chymotrypsin. Whey protein digests gave a 50% inhibition (IC50) of ACE activity at concentration ranges within 345-1733 micrograms/ml. The IC50 values for the 1-30 kDa fractions ranged from 485 to 1134 micrograms/ml and for the < 1 kDa fraction from 109 to 837 mg/ml. Several ACE-inhibitory peptides were isolated from the hydrolysates by reversed-phase chromatography, and the potencies of the purified peptide fractions had IC50 values of 77-1062 microM. The ACE-inhibitory peptides identified were alpha-lactalbumin fractions (50-52), (99-108) and (104-108) and beta-lactoglobulin fractions (22-25), (32-40), (81-83), (94-100), (106-111) and (142-146).     

Silver versus white sheet as a back reflector for microcrystalline silicon solar cells deposited on LPCVD‐ZnO electrodes of various textures

We compare the performance of two back reflector designs on the optoelectrical properties of microcrystalline silicon solar cells. The first one consists of a 5‐µm‐thick low‐pressure chemical vapor deposition (LPCVD)‐ZnO electrode combined with a white sheet; the second one incorporates an Ag reflector deposited on a thin LPCVD‐ZnO layer (with thickness below 200 nm). For this latter design, the optical loss in the nano‐rough Ag reflector can be strongly reduced by smoothing the surface of the thin underlying ZnO layer, by means of an Ar‐plasma treatment. Because of its superior lateral conductivity, the thin‐ZnO/Ag back reflector design provides a higher fill factor than the dielectric back reflector design. When decreasing the roughness of the front electrode with respect to our standard front LPCVD‐ZnO layer, the electrical cell performance is improved; in addition, the implementation of the thin‐ZnO/Ag back reflector leads to a significant relative gain in light trapping. Applying this newly optimized combination of front and back electrodes, the conversion efficiency is improved from 8.9% up to 9.4%, for cells with an active‐layer thickness of only 1.1 µm. We thereby highlight the necessity to optimize simultaneously the front and back electrodes. Copyright © 2014 John Wiley & Sons, Ltd.     

Polymer electrolyte membrane fuel cell contamination: Testing and diagnosis of toluene-induced cathode degradation

The effects of toluene contamination on the performance of polymer electrolyte membrane (PEM) fuel cells were investigated, using various levels of toluene concentration in the air streams, under different operational conditions and with different catalyst loadings. Constant-current polarization and electrochemical impedance spectroscopy (EIS) were conducted to analyze the poisoning behaviour of toluene. The severity of the contamination effect increased with an increase in both the current density and the toluene concentration, but decreased with an increase in both the relative humidity (RH) and the cathode-side Pt loading. The toluene-poisoned fuel cell could not be fully recovered by replacing toluene-contaminated air with pure air. EIS measurements revealed that both kinetic resistance and mass transfer resistance increased as a result of toluene contamination, while membrane resistance remained unchanged. However, the increase in kinetic resistance was a major contributor to cell performance degradation.     

Forecasting the unresponsiveness to verbal command on the basis of EEG frequency progression during anesthetic induction with propofol

The objective of this study is to model the association between the electroencephalogram (EEG) spectral features and the novel r scale representing the sedative effects of the propofol anesthetic drug. On the basis of the r scale, the unresponsiveness to the verbal command (LVC) is forecasted. EEG recordings are taken from a 16-patient study population undergoing propofol anesthetic induction. EEG was filtered into consecutive 4-Hz passbands up to 28 Hz. Of these time-series, the amplitude envelopes were extracted and used as input features to the first and the second-order polynomial multiple linear regression models. The values r epsilon [0.4, 1] were predicted with the R2 value of 0.775 with a cross validation. The LVC times were forecasted with the median error of 5%-7% or equivalently 10-13 s. In contrast, using the median of the measured LVC times of the training population as a forecast, the corresponding error was 12% or 26 s. The results suggest an acceptable correlation between the r scale and the EEG spectrum in the studied range. Moreover, the r values of an individual can be predicted using a population model. The suggested framework enables forecasting the LVC, which may open new possibilities for steering the drug administration.