The term multivalency (polyvalency) in the biological science is defined as the simultaneous binding of multiple ligands to one receptor (or multiple receptors to one ligand). The possibility of gaining potency and selectivity was significantly increased through the use of multivalent ligand as a homo- or hetero-dimer, thus multivalent ligands provided a more attractive strategy to design novel anti-HIV agents with therapeutic applications. Moreover, similar to phenomenon of multivalency, an alternative strategy is called the “mixed sites inhibitor”, viz. a single molecule that possesses enough chemical space to maximize interactions with its complementary binding pocket, or to bind simultaneously in more than one regions in a target. Actually, the addition of a third heterocyclic nucleus to the parent compound resulted in “mixed sites” anti-HIV agents with broad spectrum of activities against the mutant HIV-1 strains. Based on current representative examples, the present article provided a brief review on the rationale for the design of different classes of multivalency anti-HIV agents and also discussed the advantages over their monomeric counterparts, providing a novel paradigm to facilitate the development of anti-HIV/AIDS therapeutic agents in treatment of HIV infected community. Keywords: HIV, AIDS, multivalency/polyvalency approach, drug design, chemical space, “mixed sites inhibitor”
Higher life expectancy is associated with an increased prevalence of chronic diseases, diseases of long duration and generally slow progression (WHO).This phenomenon has an increasing impact on healthcare delivery and costs.Since more than a decade the chronic care model has been proposed to transform daily care for patients with chronic illnesses from acute and reactive to a proactive, planned approach.In the literature there is evidence that the model can improve chronic care and in some cases reduce health care costs.Implementation of the model requires organization which is a challenge for primary care being mainly a 'cottage industry'.European countries differ in their implementation strategy.Some countries rely mainly on incentives for providers, while others introduce also incentives for patients and insurers.This workshop outlines the implementation and evaluation of the chronic care model in countries which differ in their implementation strategy.The added value of this workshop Downloaded from https://academic.oup.com/eurpub/
The present work shows that optimization of mechanical properties via heat treatment of parts produced by Selective Laser Melting (SLM) is profoundly different compared to conventionally processed Ti6Al4V. In order to obtain optimal mechanical properties, specific treatments are necessary due to the specific microstructure resulting from the SLM process. SLM is an additive manufacturing technique through which components are built by selectively melting powder layers with a focused laser beam. The process is characterized by short laser-powder interaction times and localized high heat input, which leads to steep thermal gradients, rapid solidification and fast cooling. In this research, the effect of several heat treatments on the microstructure and mechanical properties of Ti6Al4V processed by SLM is studied. A comparison is made with the effect of these treatments on hot forged and subsequently mill annealed Ti6Al4V with an original equiaxed microstructure. For SLM produced parts, the original martensite α′ phase is converted to a lamellar mixture of α and β for heat treating temperatures below the β-transus (995°C), but features of the original microstructure are maintained. Treated above the β-transus, extensive grain growth occurs and large β grains are formed which transform to lamellar α + β upon cooling. Post treating at 850°C for 2h, followed by furnace cooling increased the ductility of SLM parts to 12.84±1.36%, compared to 7.36±1.32% for as-built parts.
No abstract is provided for this article.
Currently the most frequently pursued drugs for the treatment of herpesvirus infections are acyclovir, ganciclovir, and foscarnet. However, clinical usefulness of these compounds is limited by toxicity (particularly in ganciclovir and foscarnet use) and by the emergence of drug-resistant viruses in immunosuppressed patients. Therefore, the development of new, effective antiherpesvirus drugs is one of the top priorities in current antiviral drug research.
