Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis,Characterization, DNA/Protein Binding and Cytotoxicity Studies

“Drug repositioning” is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y³⁺, La³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm³⁺ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (K_b) towards double stranded DNA in the range of 9.33 × 10⁴ − 10.72 × 10⁵. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.     

A study of the aerodynamics of a generic container freight wagon using Large-Eddy Simulation

In this work simulations using the Large Eddy Simulation technique have been made of the flow around a generic container freight wagon model. The model consists of one 11.8 m standard length container placed on a wagon. Details of the undercarriage such as wheels are included, but the container is generic and smoothed in comparison to a real freight wagon. The Reynolds number of the flow is 10⁵ based on the container width of 2.354 m. Two cases have been considered in the study, one case where the wagon is standing alone and one case where it is submerged into a train set with wagons ahead and behind the wagon. The latter case is simulated using periodic boundary condition. Both the time-averaged and the instantaneous flow around the wagon for the two cases are described. For the single wagon case, it is found that the separation bubble formed on the roof of the container oscillates back and forth in the streamwise direction and that this oscillation is in phase with oscillations found in the upper shear layer of the ring vortex in the wake. The mechanism that is causing the synchronization of the oscillations of the separation bubble at the front and the upper shear layers in the wake is found to be waves of vorticity being shed from the separation bubble. The time-averaged ring vortex in the near wake of the single wagon is found to be inclined due to the disturbance of the undercarriage details on flow in the lower shear layer. The lower center of the ring vortex is located closer to the base face than the upper center. The drag coefficient of the wagon in the periodic case was found to be only 10% of that of the single wagon case. This is due to two symmetrical counter-rotating vortices found in the gaps which make the train set appear as a single body to the oncoming flow and shielding the wagon from any direct impingement of the flow. The counter-rotating vortices in the gap are found to inhibit periodic oscillations in the lateral direction. These oscillations cause vortical structures to form by the air that is pushed out from the gap and these flow structures cause a dominating oscillation of non-dimensional frequency St=0.12 in the side force signal.     

Beyond the LAN: Ethernet’s Evolution into the Public Network

This article details the evolution of Ethernet into Gigabit Ethernet and how this LAN-based technology has undergone major transformations over time. From its data rates and distances to supported media and functionality, Ethernet has greatly improved, enabling it to surmount many of its former limitations and in so doing to expand beyond the LAN into the MAN and now even the WAN. In this article, Pioneer Consulting explores the evolution further by focusing on some of the major technological directions in the Ethernet equipment industry.     

Estimating the cycle time of three-stage material handling systems

Because of high investment costs, the productivity of material handling systems must be accurately estimated before various logistical, industrial, or transportation systems can be implemented. This paper proposes analytical models for three-stage material handling systems. Two possible approaches to the estimation of the productivity of three-stage material handling systems are considered: one, the continuous Markov chain model, and two, approximated mathematical models. The approximated models are based on the probability theory and permit very accurate calculations of the compound cycle time in cases when the probability distribution of the “technical” cycle times of each stage is known. Finally, some numerical results obtained by the proposed models are compared with those results obtained by a simulation study.     

Berth allocation at indented berths for mega-containerships

This paper addresses the berth allocation problem at a multi-user container terminal with indented berths for fast handling of mega-containerships. In a previous research conducted by the authors, the berth allocation problem at a conventional form of the multi-user terminal was formulated as a nonlinear mathematical programming, where more than one ship are allowed to be moored at a specific berth if the berth and ship lengths restriction is satisfied. In this paper, we first construct a new integer linear programming formulation for easier calculation and then the formulation is extended to model the berth allocation problem at a terminal with indented berths, where both mega-containerships and feeder ships are to be served for higher berth productivity. The berth allocation problem at the indented berths is solved by genetic algorithms. A wide variety of numerical experiments were conducted and interesting findings were explored.     

质子照相中容器引起的模糊

 为了弄清质子照相中容器引起模糊的大小,以质子与吸收体的多次库仑相互作用为基础,结合负幺阵成像磁透镜系统的特性,推导出了容器模糊的半高全宽表达式。研究表明:容器的模糊半高全宽与容器至客体的距离成正比,与容器厚度的均方根成正比,与质子的动量成反比;容器的前后壁都对模糊有贡献;相同条件下,计算得到Al制容器的模糊小于Fe制容器的模糊;半径200 cm、厚5 cm的Al制容器的模糊为1.30 mm,大于客体的模糊,同时蒙特卡罗程序的模拟也得到了相同的结果。     

Storage space allocation models for inbound containers in an automatic container terminal

This paper studies the problem of improving the operations efficiency for retrieving inbound containers in a modern automatic container terminal. In the terminal, when an external truck arrives to collect a container stored in a specific container block, it waits at one end of the block where an automatic stack crane will retrieve the container and deliver it to the truck. With the aim of reducing the expected external truck waiting time which is determined by how the containers are stored in a block, we propose two correlated approaches for the operations efficiency improvement, (1) by designing an optimized block space allocation to store the inbound containers after they are discharged from vessels, and (2) by conducting overnight re-marshaling processes to re-organize the block space allocation after some containers are retrieved. For the block space allocation problem, we consider three optimization models under different strategies of storing containers, namely, a non-segregation model, a single-period segregation model, and a multiple-period segregation model. Optimal solution methods are proposed for all three models. For the re-marshaling problem with a given time limit, we find that the problem is NP-hard and develop a heuristic algorithm to solve the problem. We then use simulation to validate our models and solution approaches. Simulation results reveal important managerial insights such as the advantage of the multiple-period segregation over the myopic single-period segregation, the possibility of overflow of the segregation model, and the benefit of re-marshaling.     

Benefits of a truck appointment system on the service quality of inland transport modes at a multimodal container terminal

Container terminals pay more and more attention to the service quality of inland transport modes such as tucks, trains and barges. Truck appointment systems are a common approach to reduce truck turnaround times. This paper provides a tool to use the truck appointment system to increase not only the service quality of trucks, but also of trains, barges and vessels. We propose a mixed integer linear programming model to determine the number of appointments to offer with regard to the overall workload and the available handling capacity. The model is based on a network flow representation of the terminal and aims to minimize overall delays at the terminal. It simultaneously determines the number of truck appointments to offer and allocates straddle carriers to different transport modes. Numerical experiments, conducted on actual data, quantify the benefits of this combined solution approach. Discrete-event simulation validates the results obtained by the optimization model in a stochastic environment.     

Optimal berth allocation and time-invariant quay crane assignment in container terminals

Due to the dramatic increase in the world’s container traffic, the efficient management of operations in seaport container terminals has become a crucial issue. In this work, we focus on the integrated planning of the following problems faced at container terminals: berth allocation, quay crane assignment (number), and quay crane assignment (specific). First, we formulate a new binary integer linear program for the integrated solution of the berth allocation and quay crane assignment (number) problems called BACAP. Then we extend it by incorporating the quay crane assignment (specific) problem as well, which is named BACASP. Computational experiments performed on problem instances of various sizes indicate that the model for BACAP is very efficient and even large instances up to 60 vessels can be solved to optimality. Unfortunately, this is not the case for BACASP. Therefore, to be able to solve large instances, we present a necessary and sufficient condition for generating an optimal solution of BACASP from an optimal solution of BACAP using a post-processing algorithm. In case this condition is not satisfied, we make use of a cutting plane algorithm which solves BACAP repeatedly by adding cuts generated from the optimal solutions until the aforementioned condition holds. This method proves to be viable and enables us to solve large BACASP instances as well. To the best of our knowledge, these are the largest instances that can be solved to optimality for this difficult problem, which makes our work applicable to realistic problems.     

Reversibly controllable guest binding in precisely defined cavities: selectivity, induced fit, and switching in novel resorcin[4]arene-based container molecules

Two molecular baskets are presented, which were constructed based on a resorcin[4]arene platform. The molecules completely surround suitable guests, such as cyclo- or oxacycloalkanes, and bind them with high strength. The thermodynamic parameters for inclusion complexation were determined as well as the influence of encapsulation on the ring inversion barrier of bound cyclohexane. Two-dimensional NMR spectroscopy clearly shows the existence of a directed attractive interaction between oxacyclohexane and one of the hosts, which constrains the rotation of the bound molecule. Both containers exhibit remarkable binding selectivity as a consequence of their precisely defined structures. They both differentiate between homologous cycloalkanes, and whereas cyclohexane binds best within the larger of the two interior cavities, cyclopentane fits best in the smaller one. The selectivity is governed by ideal filling of space. We have conducted molecular dynamics experiments to understand the thermal fluctuations in the cavity sizes when a guest is bound. The simulations show that within a very narrow range the hosts adapt their binding site to different guests in order to optimize the fraction of occupied space. Once a binding geometry is established, it is characterized by a very low degree of flexibility. The guest-hosting properties of both molecules can be suspended by an external stimulus: addition of acid induces an opening of portals in the structures and immediately releases all bound cargo. Neutralization of the solution completely restores the initial state.