Folate binding protein—Outlook for drug delivery applications

Serum proteins represent an important class of drug and imaging agent delivery vectors. In this minireview, key advantages of using serum proteins are discussed, followed by the particular advantages and challenges associated with employing soluble folate binding protein. In particular, approaches employing drugs that target folate metabolism are reviewed. Additionally, the slow-onset, tightbinding interaction of folate with folate binding protein and the relationship to a natural oligomerization mechanism is discussed. These unique aspects of folate binding protein suggest interesting applications for the protein as a vector for further drug and imaging agent development.     

The Dial-a-Ride Problem (DARP): Variants,modeling issues and algorithms

The Dial-a-Ride Problem (DARP) consists of designing vehicle routes and schedules for n users who specify pick-up and drop-off requests between origins and destinations. The aim is to plan a set of m minimum cost vehicle routes capable of accommodating as many users as possible, under a set of constraints. The most common example arises in door-to-door transportation for elderly or disabled people. The purpose of this article is to review the scientific literature on the DARP. The main features of the problem are described and classified and some modeling issues are discussed. A summary of the most important algorithms is provided.AMS classification: 90B06, 90C27, 90C59     

An Efficient Routing Scheme Based on Node Attributes for Opportunistic Networks in Oceans

Along with the fast development of the marine economy and ever-increasing human activities, handy and reliable marine networking services are increasingly required in recent years. The ocean faces challenges to support cost-effective communication due to its special environments. Opportunistic networks with easy deployment and self-curing capability are expected to play an important role to adapt to such dynamic networking environments. In the literature, routing schemes for opportunistic networks mainly exploit node mobility and local relaying technologies. They did not take into account the impact of node behaviors on encountering opportunities and in case of no further relaying, network performance would be greatly degraded. To solve the problem, we propose an efficient routing scheme based on node attributes for opportunistic networks. We first construct delivery competency to predict the further relay nodes. Then a forwarding willingness mechanism is introduced to evaluate the relaying probability combining device capacity and movement behaviors of nodes. Finally, the utility metric is used to make decisions on message forwarding. The results show that the proposed scheme improves network performance in terms of delivery ratio, average latency, and overhead ratio as compared to other schemes.     

BMP-6 Loaded Polyelectrolyte Complex Nanoparticles Inducing Osteogenic Differentiation and Apoptosis of Malignant Plasma Cells for Local Treatment of Multiple Myeloma

In the malignant plasma cell disease multiple myeloma (MM), bone lesions and resulting fractures caused by MM cell (MMC) accumulation represent a major cause of morbidity and mortality. Despite recent advantages in systemic treatment, residual MMCs remain, especially in bone lesions. Therefore an interfacial delivery system for local treatment of MM and induced bone disease based on polyelectrolyte complex nanoparticles (PEC NP) loaded with bone morphogenetic protein 6 (BMP-6) inducing de-novo bone formation and MMC apoptosis is presented herein. BMP-6 loaded PEC NP are fabricated by defined mixing bio-related cationic and anionic polysaccharides and BMP-6 according to molar ratio of BMP-6/PEC-NP of 1/3. BMP-6/PEC NP bound to a model substrate releases 10% BMP-6 sustainably within two weeks as accessed by infrared spectroscopy. BMP-6 loaded PEC NP adheres to cell membranes of MMCs and MSCs and activated phosphorylation of Smad 1/5. Osteogenic differentiation (ALP-concentration) is enhanced in MSCs (p < 0.05). All patient samples (10/10) of MMCs show significant induction of apoptosis (median 84%, p < 0.05). Finally, BMP-6/PEC NP are successfully integrated in a commercial hyaluronic acid based hydrogel material revealing MMC death as principal proof for the local treatment of MM induced bone lesions.