Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2'deoxyuridine (5F,2'dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other transporter mediated uptake of adenosine, uridine, 5F,2'dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1). To verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the corresponding L. major and L. mexicana genes, expressing each in T. brucei. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [3H]-uridine but not of [3H]-inosine. Conversely, the NT2-like genes mediated uptake of [3H]-inosine but not [3H]-uridine. Among pyrimidine antimetabolites tested, 5-FU and 5F,2'dUrd were the most effective antileishmanials; resistance to both analogs was induced in L. major and L. mexicana. In each case it was found that the resistant cells had lost the transport capacity for the inducing drug. Metabolomics analysis found that the mechanism of action of 5-FU and 5F-2'dUrd was similar in both Leishmania species, with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine salvage system is highly conserved in Leishmania species - essential information for the development of pyrimidine-based chemotherapy.

Te output feedback eigenvalue assignment problem for discrete-time systems is considered. Te problem is formulated frst as

an unconstrained minimization problem, where a three-term nonlinear conjugate gradient method is proposed to fnd a local

solution. In addition, a cut to the objective function is included, yielding an inequality constrained minimization problem, where a

logarithmic barrier method is proposed for fnding the local solution. Te conjugate gradient method is further extended to tackle

the eigenvalue assignment problem for the two cases of decentralized control systems and control systems with time delay. Te

performance of the methods is illustrated through various test examples.

Optimistic concurrency control is widely studied in the literature due to the properties of non-blocking and deadlock free execution especially in the domain of real-time systems. In this paper we review the substantial research of optimistic concurrency control protocols. We characterize them into four categories and explore their properties. Then we investigate the general concepts and properties related to Optimistic concurrency control Finally, we demonstrate a comparison table between the varieties of these

protocols.

Malignant melanoma is one of the most rapidly increasing cancers globally and it is the most dangerous form of human skin cancer. Dermoscopy is one of the major imaging modalities used in the diagnosis of melanoma. Early detection of melanoma can be helpful and usually curable. Due to the difficulty for dermatologists in the interpretation of dermoscopy images, Computer Aided Diagnosis systems can be very helpful to facilitate the early detection. The automated detection of the lesion borders is one of the most important steps in dermoscopic image analysis. In this paper, we present a fully automated method for melanoma border detection using image processing techniques. The hair and several noises aredetected and removed by applying a bank of directional filters and Image Inpainting method respectively. A hybrid method is developed by combining Particle Swarm Optimization and Markov Random Field methods, in order to delineate the border of the lesion area in the images. The method was tested on a dataset of 200 dermoscopic images, and the experimental results show that our method is superior in terms of the accuracy of drawing the lesion borders compared to alternative methods.