Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications

Many nanosized particulate systems are being developed as intravascular carriers to increase the levels of therapeutic agents delivered to targets, with the fewest side effects. The surface of these carriers is often functionalized with biological recognition molecules for specific, targeted delivery. However, there are a series of biological barriers in the body that prevent these carriers from localizing at their targets at sufficiently high therapeutic concentrations. Here we show a multistage delivery system that can carry, release over time and deliver two types of nanoparticles into primary endothelial cells. The multistage delivery system is based on biodegradable and biocompatible mesoporous silicon particles that have well-controlled shapes, sizes and pores. The use of this system is envisioned to open new avenues for avoiding biological barriers and delivering more than one therapeutic agent to the target at a time, in a time-controlled fashion.     

A neural model of visually guided steering, obstacle avoidance, and route selection.

A neural model is developed to explain how humans can approach a goal object on foot while steering around obstacles to avoid collisions in a cluttered environment. The model uses optic flow from a 3-dimensional virtual reality environment to determine the position of objects on the basis of motion discontinuities and computes heading direction, or the direction of self-motion, from global optic flow. The cortical representation of heading interacts with the representations of a goal and obstacles so that the goal acts as an attractor of heading and obstacles act as repellers. In addition, the model maintains fixation on the goal object by generating smooth pursuit eye movements. Eye rotations can distort the optic flow field, complicating heading perception, and the model uses extraretinal signals to correct for this distortion and accurately represent heading. The model explains how motion processing mechanisms in cortical areas middle temporal, medial superior temporal, and posterior parietal cortex can be used to guide steering. The model quantitatively simulates human psychophysical data about visually guided steering, obstacle avoidance, and route selection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthetic strategies and structural aspects of metal-mediated multiporphyrin assemblies

Porphyrins play a major role as active chromophores in artificial systems mimicking the natural photoinduced processes. The formation of coordination bonds between peripheral donor sites on the porphyrins and external metal fragments has proven to be an efficient alternative to covalent synthesis for the construction of multiporphyrin assemblies, whose complexity and beauty gradually approach those of the multichromophore systems found in nature. In a modular approach, relatively simple metal-mediated porphyrin adducts, owing to their thermodynamic and kinetic stability, can be exploited as building blocks in the construction of higher order architectures. Thus, multichromophore systems become accessible on demand, with a limited synthetic effort. The collection of solid-state structures reported here demonstrates that the flexibility of the porphyrins and the metal junctions, combined with the conformational freedom of the coordination bonds, may lead to assemblies with hardly predictable architectures. Examples in which X-ray structural determination was essential for establishing the real composition and geometry of the multiporphyrin assemblies are highlighted.     

Consolidation of soft clay foundation improved by geosynthetic-reinforced granular columns: Numerical evaluation

Soft clays are problematic soils as they present high compressibility and low shear strength. There are several methods for improving in situ conditions of soft clays. Based on the geotechnical problem's geometry and characteristics, the in situ conditions may require reinforcement to restrain instability and construction settlements. Granular columns reinforced by geosynthetic material are widely used to reduce settlements of embankments on soft clays. They also accelerate the consolidation rate by reducing the drainage path's length and increasing the foundation soil's bearing capacity. In this study, the performance of encased and layered granular columns in soft clay is investigated and discussed. The numerical results show the significance of geosynthetic stiffness and the column length on the embankment settlements. Furthermore, the results show that granular columns may play an important role in dissipating the excess pore water pressures and accelerating the consolidation settlements of embankments on soft clays.     

LRG1 Expression Is Elevated in the Eyes of Patients with Neovascular Age-Related Macular Degeneration

Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium–choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.     

Changes in durum wheat kernel and pasta proteins induced by toasting and drying processes

Durum wheat kernels were subjected to a toasting process and the proteins characterised by size exclusion-high performance liquid chromatography (SE-HPLC) and sodium dodecyl sulphate–polyacrylamide gel electrophoresis. With this physical process, albumins and globulins, as well as glutenins and gliadins, polymerised as seen by a shift of the SE-HPLC profile to lower elution times. The polymerisation seemed to happen mainly through disulphide bonds, even though the participation of ω-gliadins to the aggregation suggested the involvement of other kinds of interactions. It led to the revelation of a new peak originated by thermal aggregation of small polymeric proteins. The changes in the chromatographic profile were accompanied by increasing amounts of total unextractable polymeric proteins. The replacement of semolina with toasted durum wheat flour (5%, 10%, 15%, 20% and 30%) for the production of pasta in the shape of spaghetti significantly (p < 0.001) affected the molecular size distribution of the polymeric proteins, even though the replacement of semolina with 5% and 10% of toasted durum wheat flour (TDWF) did not significantly (p > 0.05) change the unextractable polymeric proteins (UPP) when compared with spaghetti made with 100% durum semolina. On the other hand, the replacements of semolina with 15–30% TDWF showed significant (p < 0.001) increase in UPP when compared with 100% durum semolina spaghetti.     

Evolution of phenolic compounds in virgin olive oil during storage

Phenolic compounds are of fundamental importance to the shelf life of virgin olive oils because of their antioxidative properties. In this paper, the evolution of simple and complex olive oil phenols during 18 mon of storage is studied by high-performance liquid chromatography (HPLC) analysis. The olive oils under examination were from various olive cultivars, harvested in two sectors in the same region at different stages of ripeness. The findings indicate that it is not the variety but rather the ripeness of the olives and the soil and climate that influence the phenol composition of virgin olive oil. In addition, a positive correlation was found between the age of the oils and the tyrosol to total phenols ratio. Lastly, gas chromatography-mass spectrometry analysis confirmed that the unidentified peaks detected by HPLC were of a phenolic nature.