Studies on the uptake of glucose derivatives by red blood cells

Erythrocytes express the same glucose transporter (GLUT-1) as is present in the blood-brain barrier. With the aim of testing the viability of using this transport system to deliver glucosyl drug derivatives to the brain, the uptake of several dopamine-glucose conjugates and a few structurally related analogues by erythrocytes was studied with HPLC and (1)H MAS NMR spectroscopy. The results showed that slight structural changes determine the uptake of glycoconjugates by red blood cells. However, experiments in the presence of glucose transport inhibitors showed that none of the conjugates that efficiently crossed the cell membrane were transported by GLUT-1.     

Neutral lipids of chickpea flour and protein isolates

The neutral lipids composition of defatted chickpea flour and two types of protein isolates has been studied. The main compounds in neutral lipids are triacylglycerols, free fatty acids, and diacylglycerols. Other compounds present are wax esters, free fatty alcohols, and free sterols. The main fatty acids in neutral lipids are C_18:2 and C_18:1 among the unsaturated, and C_16:0 and C_18:0 among the saturated acids. Free and esterified alcohols range from C_16:0 to C_28:0, the majority being those with an even number of carbon atoms. Sterols observed are β-sito-sterol, campesterol, stigmasterol, and δ-5-avenasterol. Triacyl-glycerols are partially hydrolyzed, and the amounts of unsaturated sterols and unsaturated fatty acids are reduced as a result of the chemical treatment during production of the protein isolates.     

Probing the S1′ Site for the Identification of Non‐Zinc‐Binding MMP‐2 Inhibitors

Matrix metalloproteinases (MMPs) are zinc‐dependent enzymes involved in several pathological states. Among them, MMP‐2 is a relevant therapeutic target because of its role in cancer development and progression. Many MMP inhibitors (MMPIs) have been discovered over the last 30 years, and the majority of them contain a functional group that binds the zinc ion (zinc‐binding group; ZBG). Unfortunately, no MMPIs have reached the market yet, owing to toxic effects due to unselective interactions of the ZBG. The new generation of MMPIs that do not bind the zinc ion could overcome problems of selectivity and toxicity, but have so far been developed only for MMP‐8, ‐12, and ‐13. In this work, a virtual screening protocol was established by combining ligand‐ and structure‐based methods to identify non‐zinc‐binding MMP‐2 inhibitors using a new‐generation MMP‐8 inhibitor as a probe to find unexplored interactions in the MMP‐2 S1′ site. The screening allowed the identification of micromolar MMP‐2 inhibitors that putatively avoid binding the zinc ion, as demonstrated by docking calculations. The LIA model, built to correlate predicted and experimental binding energies of the identified non‐zinc‐binding MMP‐2 hits, underpins the reliability of the predicted docking poses.     

Maximum likelihood estimation for the three-parameter Weibull cdf of strength in presence of concurrent flaw populations

For a correct strength characterization of brittle materials, not only the maximum stress at fracture, but also the geometry of the specimens has to be considered thus taking into account the variable stress state and the size effect. Additionally, fracture may occur due to different fracture modes, as for example surface or edge defects. The authors propose a maximum likelihood estimator to obtain the cumulative distribution functions of strength for surface and edge flaw populations separately, both being three-parameter Weibull cdfs referred to an elemental surface area or elemental edge length, respectively. The method has been applied to simulated 3-point bending test data. The estimated Weibull parameters have been used to compute the cdfs of strength for specimens with different size, providing also the confidence bounds calculated by means of the bootstrap method. Finally, fracture data of 4-point bending tests on silicon carbide have been evaluated with the proposed method.     

Adsorption and decomposition of H2S on Pd(1 1 1) surface: a first-principles study

Gradient-corrected density functional theory was used to investigate the adsorption of H₂S on Pd(1 1 1) surface. Molecular adsorption was found to be stable with H₂S binding preferentially at top sites. In addition, the adsorption of other S moieties (SH and S) was investigated. SH and S were found to be preferentially bind at the bridge and fcc sites, respectively. The reaction pathways and energy profiles for H₂S decomposition giving rise to adsorbed S and H were determined. Both H₂S_(ad) → SH_(ad) + H_(ad) and SH_(ad) → S_(ad) + H_(ad) reactions were found to have low barriers and high exothermicities. This reveals that the decomposition of H₂S on Pd(1 1 1) surface is a facile process.     

Developing pyrrole-derived antimycobacterial agents: a rational lead optimization approach

Tuberculosis (TB) represents a never-ending challenge toward which research efforts are needed. Drug resistance is the key problem that scientists in the field need to fight. The development of new drugs endowed with novel modes of action against different biological targets is of extreme importance; these new agents should also exhibit lower toxicity compared with the anti-TB drugs currently available. Furthermore, new drugs should be inexpensive since most of the TB-infected population lives in developing nations. In the last few years, numerous researchers have focused their attention on TB, leading to the discovery of some interesting compounds. Among these, the pyrrole-derived compounds we developed can be considered very promising antimycobacterial agents. Aided by molecular modeling studies, we synthesized numerous compounds characterized by the same 1,5-diarylpyrrole scaffold and elucidated very interesting antitubercular/antimycobacterial properties. Some compounds identified are extremely promising and represent a step towards the design of novel lead structures in the fight against TB. Our efforts to this end are reviewed here.     

Incorporation of polyfluorenes into poly(lactic acid) films for sensor and optoelectronics applications

Films of neat and plasticized biodegradable poly(lactic acid) (PLA) matrices containing anionic conjugated polyelectrolytes, poly[9,9‐bis(4‐phenoxybutylsulfonate)]fluorene‐2,7‐diyl‐alt‐arylenes, with 1,4‐phenylene and 4,4″‐p‐terphenylene, respectively, as arylene groups or a neutral poly(9,9‐dialkylfluorene) for comparison were prepared by solution casting. These films were characterized using differential scanning calorimetry, thermogravimetry, scanning electron microscopy and fluorescence spectroscopy. In addition, the effects of plasticizer on the thermal properties and the oxygen permeability of the PLA films were measured through the oxygen transmission rate. Results show that it is possible to obtain thin, optically transparent and luminescent films with potential in oxygen sensing, exhibiting good thermal and photochemical stability. At high polyelectrolyte content, evidence is found for phase separation and aggregate formation and it is no longer possible to obtain completely homogeneous films. The possibility of incorporating the cationic metal complex tris(2,2′‐bipyridyl)ruthenium(II) into plasticized PLA films containing conjugated polyelectrolytes for dual‐wavelength ratiometric luminescence sensing is also discussed. Copyright © 2012 Society of Chemical Industry     

Prediction of contact maps with neural networks and correlated mutations

Contact maps of proteins are predicted with neural network-basedmethods, using as input codings of increasing complexity includingevolutionary information, sequence conservation, correlatedmutations and predicted secondary structures. Neural networksare trained on a data set comprising the contact maps of 173non-homologous proteins as computed from their well resolvedthree-dimensional structures. Proteins are selected from theProtein Data Bank database provided that they align with atleast 15 similar sequences in the corresponding families. Thepredictors are trained to learn the association rules betweenthe covalent structure of each protein and its contact map witha standard back propagation algorithm and tested on the sameprotein set with a cross-validation procedure. Our results indicatethat the method can assign protein contacts with an averageaccuracy of 0.21 and with an improvement over a random predictorof a factor >6, which is higher than that previously obtainedwith methods only based either on neural networks or on correlatedmutations. Furthermore, filtering the network outputs with aprocedure based on the residue coordination numbers, the accuracyof predictions increases up to 0.25 for all the proteins, withan 8-fold deviation from a random predictor. These scores arethe highest reported so far for predicting protein contact maps.     

The production of carbon nanotube reinforced poly(vinyl) butyral nanofibers by the Forcespinning® method

Poly(vinyl) butyral (PVB) nanofibers (NFs) and carbon nanotube (CNT) reinforced PVB NF composites were developed by using the Forcespinning® technology. PVB was dissolved in a mixture of ethanol and methanol (7:3 wt/wt) at various concentrations, and the solutions were spun at rotational speeds varying between 3,000 and 9,000 rpm. The CNT/PVB solutions were prepared using the same solvent ratio with varying the concentration of CNTs. The results show that the diameter of the PVB fibers increased with increasing rotational speed; however the standard deviation of the fiber diameter distribution decreased. The morphology and thermal properties of the developed fiber systems were studied by DSC, TGA, Raman, and FTIR. The effect of CNT on the mechanical properties of the developed fibers was investigated by carrying out tensile tests at different strain rates. Raman and FTIR analyses indicate a noncovalent π–π stacking interactions and hydrogen bonding between CNT and the PVB NFs. Adding CNT to the PVB NF matrix resulted in improved tensile strength by 150%. POLYM. ENG. SCI., 55:81–87, 2015. © 2014 Society of Plastics Engineers