Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers

Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the α_vβ₃‐integrin ligand cyclo[DKP–RGD]‐CH₂NH₂ ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified α_Vβ₃‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (α_Vβ₃?) and its subclone CCRF‐CEM α_Vβ₃ (α_Vβ₃+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM α_Vβ₃ versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload.     

Solutions of the Time-Harmonic Wave Equation in Periodic Waveguides: Asymptotic Behaviour and Radiation Condition

In this paper, we give the expression and the asymptotic behaviour of the physical solution of a time harmonic wave equation set in a periodic waveguide. This enables us to define a radiation condition and show well-posedness of the Helmholtz equation set in a periodic waveguide.     

A new space–time discretization for the Swift–Hohenberg equation that strictly respects the Lyapunov functional

The Swift–Hohenberg equation is a central nonlinear model in modern physics. Originally derived to describe the onset and evolution of roll patterns in Rayleigh–Bénard convection, it has also been applied to study a variety of complex fluids and biological materials, including neural tissues. The Swift–Hohenberg equation may be derived from a Lyapunov functional using a variational argument. Here, we introduce a new fully-discrete algorithm for the Swift–Hohenberg equation which inherits the nonlinear stability property of the continuum equation irrespectively of the time step. We present several numerical examples that support our theoretical results and illustrate the efficiency, accuracy and stability of our new algorithm. We also compare our method to other existing schemes, showing that is feasible alternative to the available methods.     

Organic‐acid mediated bulk polymerization of ε‐caprolactam and its copolymerization with ε‐caprolactone

Polyamides (PA) constitute one of the most important classes of polymeric materials and have gained strong position in different areas, such as textiles, fibers, and construction materials. Whereas most PA are synthesized by step‐growth polycondensation, PA 6 is synthesized by ring opening polymerization (ROP) of ε‐caprolactam (ε‐CLa). The most popular ROP methods involve the use of alkaline metal catalyst difficult to handle at large scale. In this article, we propose the use of organic acids for the ROP of ε‐CLa in bulk at 180 °C (below the polymer's melting point). Among evaluated organic acids, sulfonic acids were found to be the most effective for the polymerization of ε‐CLa , being the Brønsted acid ionic liquid: 1‐(4‐sulfobutyl)?3‐methylimidazolium hydrogen sulfate the most suitable due to its higher thermal stability. End‐group analysis by ¹H nuclear magnetic resonance and model reactions provided mechanistic insights and suggested that the catalytic activity of sulfonic acids was a function of not only the acid strength, but of the nucleophilic character of conjugate base as well. Finally, the ability of sulfonic acid to promote the copolymerization of ε‐CLa and ε‐caprolactone is demonstrated. As a result, poly(ε‐caprolactam‐co‐ε‐caprolactone) copolymers with considerably randomness are obtained. This benign route allows the synthesis of poly(ester amide)s with different thermal and mechanical properties. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2394–2402     

SDR receiver computational model for application in power control

Software-defined radio (SDR) permits dynamic switches of the employed radio access technology (RAT), over-the-air (OTA) software updates, software and hardware reuse. This extended flexibility comes at the price of a higher computing complexity and, in particular, the energy consumption at the receiver. The analysis of the computational profile of signal processing algorithms is of great importance in SDR for understanding the implication on the energy consumption. Several signal processing algorithms show a different profile as a function of the signal quality perceived at the receiver antenna. Therefore, power control policies have an implication on the computational performance of SDR receivers. Understanding the behaviour of these algorithms allows trading transmitted power against receiver energy consumption. This paper presents a model for characterizing the computational profile of Turbo and LDPC decoders and demonstrates is applicability in existing power control strategies.