Synthesis,Characterization, and Biological Evaluation of a Dual-Action Ligand Targeting αvβ3 Integrin and VEGF Receptors

A dual-action ligand targeting both integrin α_Vβ₃ and vascular endothelial growth factor receptors (VEGFRs), was synthesized via conjugation of a cyclic peptidomimetic α_Vβ₃ Arg-Gly-Asp (RGD) ligand with a decapentapeptide. The latter was obtained from a known VEGFR antagonist by acetylation at the Lys13 side chain. Functionalization of the precursor ligands was carried out in solution and in the solid phase, affording two fragments: an alkyne VEGFR ligand and the azide integrin α_Vβ₃ ligand, which were conjugated by click chemistry. Circular dichroism studies confirmed that both the RGD and VEGFR ligand portions of the dual-action compound substantially adopt the biologically active conformation. In vitro binding assays on isolated integrin α_Vβ₃ and VEGFR-1 showed that the dual-action conjugate retains a good level of affinity for both its target receptors, although with one order of magnitude (10/20 times) decrease in potency. The dual-action ligand strongly inhibited the VEGF-induced morphogenesis in Human Umbilical Vein Endothelial Cells (HUVECs). Remarkably, its efficiency in preventing the formation of new blood vessels was similar to that of the original individual ligands, despite the worse affinity towards integrin α_Vβ₃ and VEGFR-1.     

Thermodynamic study of (heptane + amine) mixtures. III: Excess and partial molar volumes in mixtures with secondary,tertiary, and cyclic amines at 298.15 K

Excess molar volumes V^E at 298.15 K were determined by means of a vibrating tube densimeter for binary mixtures of {heptane + open chain secondary (diethyl to dibutyl) and tertiary (triethyl to tripentyl) amines} as well as for cyclic imines (C₂, C₃, C₄, C₆, and C₇) and primary cycloalkylamines (C₅, C₆, C₇, and C₁₂). The V^E values were found positive for mixtures involving small size amines, with V^E decreasing as the size increases. Negative V^E’s were found for tributyl- and tripentylamine, heptamethylenimine, and cyclododecylamine. Mixtures of heptane with cycloheptylamine showed an s-shaped curve.Partial molar volumes $V^{°}$ of amines at infinite dilution in heptane were obtained from V^E and compared with $V^{°}$ of hydrocarbons and other classes of organic compounds taken from literature. An additivity scheme, based on the intrinsic volume approach, was applied to estimate group (CH₃, CH₂, CH, C, NH₂, NH, N, OH, O, CO, and COO) contributions to $V^{°}$. These contributions, the effect of cyclization on $V^{°}$, and the limiting slope of the apparent excess molar volumes were discussed in terms of solute–solvent and solute–solute interactions.     

New antidepressant drug candidate: Hypericum montbretti extract

This study was designed to investigate possible antidepressant-like effects of the extract prepared from the flowers of Hypericum montbretti Spach. (Guttiferae, Clusiaceae). Phytochemical constituents of the methanolic extract were analysed by HPLC method. The main flavonoid component was detected as rutin, and another highly concentrated phenolic compound was quercitrin. Antidepressant activity of the extract was examined by tail suspension and modified forced swimming tests, whereas the motor coordination of the animals was tested by the Rota-Rod apparatus. Reboxetine at a dose of 20 mg?kg?1 was used as a reference drug. Dose-dependent antidepressant activity was observed in both tests following the administration of extract at 100 and 250 mg?kg?1 doses. To the best of our knowledge, this is the first study reporting the antidepressant activity of H. montbretti extract. Additionally, the results of this work support previous papers reporting the antidepressant activity of rutin.     

Bergamot (<Emphasis Type="Italic">Citrus bergamia</Emphasis> Risso) fruit extracts and identified components alter expression of interleukin 8 gene in cystic fibrosis bronchial epithelial cell lines

Background  

Cystic fibrosis (CF) airway pathology is a fatal, autosomal, recessive genetic disease characterized by extensive lung inflammation. After induction by TNF-α, elevated concentrations of several pro-inflammatory cytokines (i.e. IL-6, IL-1β) and chemokines (i.e. IL-8) are released from airway epithelial cells. In order to reduce the excessive inflammatory response in the airways of CF patients, new therapies have been developed and in this respect, medicinal plant extracts have been studied. In this article we have investigated the possible use of bergamot extracts (Citrus bergamia Risso) and their identified components to alter the expression of IL-8 associated with the cystic fibrosis airway pathology.     

Thermodynamics of the glass transition

A thermodynamic analysis of the glass transition in polymers is presented, which predicts, with a minimum of assumptions, three of the four inequalities which have consistently been observed experimentally: i.e., that specific heat and isothermal compressibility of the glass are lower than those of the rubber, and that the Prigogine-Defay ratio is larger than unity. The analysis cannot predict the fact that the thermal expansion coefficient of the glass is also lower than that of the rubber, and indeed the converse situation is not a thermodynamic impossibility.     

Entire solutions for a semilinear fourth order elliptic problem with exponential nonlinearity

We investigate entire radial solutions of the semilinear biharmonic equation Δ²u=λexp(u) in Rn, n?5, λ>0 being a parameter. We show that singular radial solutions of the corresponding Dirichlet problem in the unit ball cannot be extended as solutions of the equation to the whole of Rn. In particular, they cannot be expanded as power series in the natural variable s=log|x|. Next, we prove the existence of infinitely many entire regular radial solutions. They all diverge to −∞ as |x|→∞ and we specify their asymptotic behaviour. As in the case with power-type nonlinearities [F. Gazzola, H.-Ch. Grunau, Radial entire solutions for supercritical biharmonic equations, Math. Ann. 334 (2006) 905-936], the entire singular solution x?−4log|x| plays the role of a separatrix in the bifurcation picture. Finally, a technique for the computer assisted study of a broad class of equations is developed. It is applied to obtain a computer assisted proof of the underlying dynamical behaviour for the bifurcation diagram of a corresponding autonomous system of ODEs, in the case n=5.     

Moiré interferometric fringe patterns about crack tips: Experimental observations and numerical simulation

The local deformation about fatigue cracks has been investigated by the coherent optics method of moiré interferometry. The complexity of the interference fringe patterns motivated the parallel development of companion numerical models for simulating moiré interferometric response for known boundary conditions. Experimental patterns are here examined in the light of computer-generated fringe systems for a stationary crack in elastic as well as elastic-plastic solids. Various effects due to material plasticity, specimen-dependent non-singular stress, and mixed mode loading are identified in the fringe patterns.     

On a Possible Continuous Analogue of the Szpilrajn Theorem and its Strengthening by Dushnik and Miller

The Szpilrajn theorem and its strengthening by Dushnik and Miller belong to the most quoted theorems in many fields of pure and applied mathematics as, for instance, order theory, mathematical logic, computer sciences, mathematical social sciences, mathematical economics, computability theory and fuzzy mathematics. The Szpilrajn theorem states that every partial order can be refined or extended to a total (linear) order. The theorem by Dushnik and Miller states, moreover, that every partial order is the intersection of its total (linear) refinements or extensions. Since in mathematical social sciences or, more general, in any theory that combines the concepts of topology and order one is mainly interested in continuous total orders or preorders in this paper some aspects of a possible continuous analogue of the Szpilrajn theorem and its strengthening by Dushnik and Miller will be discussed. In particular, necessary and sufficient conditions for a topological space to satisfy a possible continuous analogue of the Dushnik-Miller theorem will be presented. In addition, it will be proved that a continuous analogue of the Szpilrajn theorem does not hold in general. Further, necessary and in some cases necessary and sufficient conditions for a topological space to satisfy a possible continuous analogue of the Szpilrajn theorem will be presented.      

The role of the Fox–Wright functions in fractional sub-diffusion of distributed order

The fundamental solution of the fractional diffusion equation of distributed order in time (usually adopted for modelling sub-diffusion processes) is obtained based on its Mellin–Barnes integral representation. Such solution is proved to be related via a Laplace-type integral to the Fox–Wright functions. A series expansion is also provided in order to point out the distribution of time-scales related to the distribution of the fractional orders. The results of the time fractional diffusion equation of a single order are also recalled and then re-obtained from the general theory.     

Fluorescence Enhancement of Aflatoxins Using Native and Substituted Cyclodextrins

Cyclodextrins have been used as fluorescence enhancers in HPLC to improve thedetection limits of aflatoxins, cancerogens which can be found in severalfoodstuffs. In this work, a screening of several cyclodextrins has been performedin order to find the factors affecting the fluorescence enhancement. Evidence for formationof a 1 : 1 AF-CD inclusion complex has been achieved by titration and competitiveexperiments with adamantanecarboxylic acid and by fluorescence quenching by KI.Stability constants of the AF-CD complexes were evaluated.