OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.     

An analytical framework for the design of intelligent algorithms for adaptive-rate MPEG video encoding in next-generation time-varying wireless networks

Adaptive rate video encoding is required to maximize efficiency when wireless links are involved in the communication. In fact, wireless channels are characterized by high, time-varying bit error rates. To cope efficiently with this problem adaptive forward error correction schemes have been proposed. These schemes introduce an amount of redundancy dependent on the channel conditions. Accordingly, the bandwidth available at the application layer changes: it increases when channel conditions improve, and decreases when channel conditions worsen. Obviously, the encoding parameters must be tuned to adapt the video source transmission rate to the available bandwidth. This adaptation is achieved by means of appropriate feedback laws, which are relationships between the encoding parameters to be used and other variables representing the state of the system. An analytical framework is introduced which can be used for the design of the feedback laws. To this purpose both the channel and the video source are modeled by means of Markov models. The resulting model of the whole system is denoted as SBBP/SBBP/1/K. Analysis is derived which allows to evaluate the most significant performance measures and, therefore, to design optimal feedback laws.     

Bacterial Over-Expression and Purification of the 3′phosphoadenosine 5′phosphosulfate (PAPS) Reductase Domain of Human FAD Synthase: Functional Characterization and Homology Modeling

FAD synthase (FADS, EC 2.7.7.2) is a key enzyme in the metabolic pathway that converts riboflavin into the redox cofactor, FAD. Human FADS is organized in two domains: -the 3′phosphoadenosine 5′phosphosulfate (PAPS) reductase domain, similar to yeast Fad1p, at the C-terminus, and -the resembling molybdopterin-binding domain at the N-terminus. To understand whether the PAPS reductase domain of hFADS is sufficient to catalyze FAD synthesis, per se, and to investigate the role of the molybdopterin-binding domain, a soluble “truncated” form of hFADS lacking the N-terminal domain (Δ_1-328-hFADS) has been over-produced and purified to homogeneity as a recombinant His-tagged protein. The recombinant Δ_1-328-hFADS binds one mole of FAD product very tightly as the wild-type enzyme. Under turnover conditions, it catalyzes FAD assembly from ATP and FMN and, at a much lower rate, FAD pyrophosphorolytic hydrolysis. The Δ_1-328-hFADS enzyme shows a slight, but not significant, change of K_m values (0.24 and 6.23 μM for FMN and ATP, respectively) and of k_cat (4.2 × 10⁻² s⁻¹) compared to wild-type protein in the forward direction. These results demonstrate that the molybdopterin-binding domain is not strictly required for catalysis. Its regulatory role is discussed in light of changes in divalent cations sensitivity of the Δ_1-328-hFADS versus wild-type protein.     

Transmission of adaptive MPEG video over time-varying wireless channels: modeling and performance evaluation

Wireless channels are characterized by high time-varying bit-error rates (BERs). To cope with this problem, several adaptive forward-error-correction (AFEC) schemes have been proposed in the literature. They work locally at the wireless link, adding a variable amount of redundancy to the transmitted data in order to maintain the packet error rate below an acceptable level. However, when such schemes are utilized, the bandwidth offered to the applications changes when channel conditions change. In this paper, the effects of these bandwidth variations are investigated in the case of real-time Motion Picture Experts Group (MPEG) video transmission. The MPEG encoder is controlled in order to adapt its emission rate to the current bandwidth offered by the wireless link. To this end, the encoding quality is diminished by the source rate controller when the transmission rate has to be decreased due to an increase in the channel BER, whereas it is improved when the transmission rate can be increased due to a decrease in the channel BER. A Markov-based model, denoted as SBBP/SBBP/1/K, has been introduced to model the scenario being considered. The analytical framework allows evaluation of the performance of the system and can be used to optimize the design of a video transmission system for wireless channels, providing the instruments to derive the tradeoff between information corruption in the wireless channel and MPEG video encoding quality.     

Strategies for Successful Over-Expression of Human Membrane Transport Systems Using Bacterial Hosts: Future Perspectives

Ten percent of human genes encode for membrane transport systems, which are key components in maintaining cell homeostasis. They are involved in the transport of nutrients, catabolites, vitamins, and ions, allowing the absorption and distribution of these compounds to the various body regions. In addition, roughly 60% of FDA-approved drugs interact with membrane proteins, among which are transporters, often responsible for pharmacokinetics and side effects. Defects of membrane transport systems can cause diseases; however, knowledge of the structure/function relationships of transporters is still limited. Among the expression of hosts that produce human membrane transport systems, E. coli is one of the most favorable for its low cultivation costs, fast growth, handiness, and extensive knowledge of its genetics and molecular mechanisms. However, the expression in E. coli of human membrane proteins is often toxic due to the hydrophobicity of these proteins and the diversity in structure with respect to their bacterial counterparts. Moreover, differences in codon usage between humans and bacteria hamper translation. This review summarizes the many strategies exploited to achieve the expression of human transport systems in bacteria, providing a guide to help people who want to deal with this topic.     

Polynomial Time Algorithms for 2-Edge-Connectivity Augmentation Problems

Given a 2-edge-connected, real weighted graph G with n vertices and m edges, the 2-edge-connectivity augmentation problem is that of finding a minimum weight set of edges of G to be added to a spanning subgraph H of G to make it 2-edge-connected. While the general problem is NP-hard and 2 -approximable, in this paper we prove that it becomes polynomial time solvable if H is a depth-first search tree of G . More precisely, we provide an efficient algorithm for solving this special case which runs in O(M · α(M,n)) time, where α is the classic inverse of Ackermann's function and M=m · α(m,n) . This algorithm has two main consequences: first, it provides a faster 2 -approximation algorithm for the general 2 -edge-connectivity augmentation problem; second, it solves in O(m · α(m,n)) time the problem of restoring, by means of a minimum weight set of replacement edges, the 2 -edge-connectivity of a 2-edge-connected communication network undergoing a link failure.     

Analytical evaluation of a tradeoff between energy efficiency and responsiveness of neighbor discovery in self-organizing ad hoc networks

Ad hoc networking enables novel communication paradigms which require the definition of new quality-of-service (QoS) parameters and frameworks for QoS support. The relevant QoS requirements are frequently antagonist and, consequently, an appropriate tradeoff has to be determined and achieved to fit all of them. As an example, the spontaneous networking featured by self-organizing ad hoc networks is possible only if neighboring communication nodes discover each other within a short period of time; however, velocity of discovery is paid in terms of energy consumption. In this paper, an analytical framework is derived which allows an evaluation of the tradeoff between energy efficiency and responsiveness in the discovery process. More specifically, the analytical framework allows either to achieve the highest velocity in the discovery process, given that the energy consumption is lower than a certain threshold, or to minimize the energy consumption given that specific requirements in terms of the discovery velocity are satisfied. The analytical framework is applied to significant case studies to derive design implications on neighbor discovery algorithms.     

Polynomial Time Algorithms for 2-Edge-Connectivity Augmentation Problems

Abstract. Given a 2-edge-connected, real weighted graph G with n vertices and m edges, the 2-edge-connectivity augmentation problem is that of finding a minimum weight set of edges of G to be added to a spanning subgraph H of G to make it 2-edge-connected. While the general problem is NP-hard and 2 -approximable, in this paper we prove that it becomes polynomial time solvable if H is a depth-first search tree of G . More precisely, we provide an efficient algorithm for solving this special case which runs in O (M · α(M,n)) time, where α is the classic inverse of Ackermann's function and M=m · α(m,n) . This algorithm has two main consequences: first, it provides a faster 2 -approximation algorithm for the general 2 -edge-connectivity augmentation problem; second, it solves in O (m · α(m,n)) time the problem of restoring, by means of a minimum weight set of replacement edges, the 2 -edge-connectivity of a 2-edge-connected communication network undergoing a link failure.