Natural Products Extracted from Fungal Species as New Potential Anti-Cancer Drugs: A Structure-Based Drug Repurposing Approach Targeting HDAC7

Mushrooms can be considered a valuable source of natural bioactive compounds with potential polypharmacological effects due to their proven antimicrobial, antiviral, antitumor, and antioxidant activities. In order to identify new potential anticancer compounds, an in-house chemical database of molecules extracted from both edible and non-edible fungal species was employed in a virtual screening against the isoform 7 of the Histone deacetylase (HDAC). This target is known to be implicated in different cancer processes, and in particular in both breast and ovarian tumors. In this work, we proposed the ibotenic acid as lead compound for the development of novel HDAC7 inhibitors, due to its antiproliferative activity in human breast cancer cells (MCF-7). These promising results represent the starting point for the discovery and the optimization of new HDAC7 inhibitors and highlight the interesting opportunity to apply the “drug repositioning” paradigm also to natural compounds deriving from mushrooms.     

Investment optimization on port’s development by fuzzy integer programming

In this research, the main purpose is to formulate a model to determine the optimum investment on port development from national investment prospective; on the other hand, costs and benefits are calculated from consumer and investor’s viewpoint. The formulated model is an integer-programming model. The emphasis is on how to formulate an investment optimization problem where cargo operation, investment costs, cargo-handling capacity, cargo transportation network, and the world maritime fleet constraints are included. Fuzzy numbers are used for cargo forecast study results. The output of the model is the type of design ships and design berths which are needed in each sub period, so that the port planner (the government) will find out the optimum development plan of port in each sub period when there is uncertainty in cargo handling forecast (fuzzy numbers).     

A survey of berth allocation and quay crane scheduling problems in container terminals

Due to the variety of technical equipments and terminal layouts, research has produced a multitude of optimization models for seaside operations planning in container terminals. To provide a support in modeling problem characteristics and in suggesting applicable algorithms this paper reviews the relevant literature. For this purpose new classification schemes for berth allocation problems and quay crane scheduling problems are developed. Particular focus is put on integrated solution approaches which receive increasing importance for the terminal management.     

Distribution-free vessel deployment for liner shipping

One important problem faced by the liner shipping industry is the fleet deployment problem. In this problem, the number and type of vessels to be assigned to the various shipping routes need to be determined, in such a way that profit is maximized, while at the same time ensuring that (most of the time) sufficient vessel capacity exists to meet shipping demand. Thus far, the standard assumption has been that complete probability distributions can be readily specified to model the uncertainty in shipping demand. In this paper, it is argued that such distributions are hard, if not impossible, to obtain in practice. To relax this oftentimes restrictive assumption, a new distribution-free optimization model is proposed that only requires the specification of the mean, standard deviation and an upper bound on the shipping demand. The proposed model possesses a number of attractive properties: (1) It can be seen as a generalization of an existing variation of the liner fleet deployment model. (2) It remains a mixed integer linear program and (3) The model has a very intuitive interpretation. A numerical case study is provided to illustrate the model.     

Group and individual heterogeneity in a stochastic frontier model: Container terminal operators

Container ports are a major component of international trade and the global supply chain. Hence, the improvement of port efficiency can have a significant impact on the wider maritime economy. This paper deconstructs a representation in the existing literature that neglects the heterogeneity of individual and group-specific terminal operators. In its place, we present a hierarchical model to make a connection between efficiency and terminal operator group characteristics. The paper develops a stochastic frontier model that controls not only individual heterogeneity but also group-specific variations. The model decomposes the total stochastic derivation from the frontier into inefficiency, individual heterogeneity, group-specific variations, and noise components, with the estimation being performed using Markov chain Monte Carlo simulations. The validity of the model is tested with a panel of container terminal operator data from 1997-2004. Our findings show that terminal operator groups are important in promoting terminal efficiency at the global level, and that the operators with stevedore backgrounds show a higher efficiency than carriers.     

A tree search method for the container loading problem with shipment priority

This paper addresses a special kind of container loading problem with shipment priority. We present a tree search method, which is based on a greedy heuristic. In the greedy heuristic, blocks made up of identical items with the same orientation are selected for packing into a container. Five evaluation functions are proposed for block selection, and the different blocks selected by each evaluation function constitute the branches of the search tree. A method of space splitting and merging is also embedded in the algorithm to facilitate efficient use of the container space. In addition, the proposed algorithm covers an important constraint called shipment priority to solve practical problems. The validity of the proposed algorithm is examined by comparing the present results with those of published algorithms using the same data.     

Permanent medialization of the paralyzed vocal fold utilizing botulinum toxin and Gelfoam

The clinical picture of a paralyzed vocal fold often has the same appearance as a subluxated arytenoid, with anterior and medial displacement of the arytenoid and a foreshortened and lax vocal fold. Previous work by the authors has shown that a subluxated arytenoid may be permanently repositioned by reduction and selective injection of the intrinsic laryngeal musculature with botulinum toxin. The injection changes the forces within the larynx, allowing the arytenoid to be brought back to proper position on the cricoid cartilage. This concept has been extended to the paralyzed vocal fold. It has been noted that even a clinically paralyzed vocal fold has voluntary motor units that may still act on the arytenoid through residual action from the interarytenoid and synkinesis. These forces are significant enough to manipulate the arytenoid and, thus, the vocal fold, into its correct, adducted position. In this paper, the arytenoid is mobilized to free any fibrosis. The thyroarytenoid and lateral cricoarytenoid muscles are then injected to prevent any forward synkinetic pull on the arytenoid. Next, a Gelfoam injection medializes the vocal fold to create glottic closure. This rebalancing sufficiently positions the arytenoid, so that valvular function is permanently restored. In the ten patients studied for over 1 year, there was a 90% success rate as measured by videostroboscopy, phonation time, and V-RQOL analysis. There were no untoward complications. All the materials used are nonpermanent. The procedure does not limit other techniques from being performed at a later time.     

Dynamic repositioning for vehicle sharing with setup costs

This study considers a multi-period two-region repositioning problem with setup repositioning costs involved for vehicle sharing systems. We find that incorporating such costs can influence the total cost significantly and complicate the structure of the optimal policy. Moreover, we manage to partially characterize the optimal policy, and then develop an easy-to-implement heuristic policy. The performance of the heuristic policy and the influence of setup repositioning costs on policies are assessed numerically.     

基于矩阵式遗传算法的进出口集装箱堆场箱位分配策略

为提高集装箱码头堆场系统的运作效率,本文针对集装箱码头进出口堆场的空间分配问题,建立了在“作业面”作业模式下以集卡水平运输距离最短为目标,考虑各箱位作业量均衡的集装箱箱位分配模型,对计划时段内的进出口箱箱位分配进行全局优化．采用矩阵式的实数编码方式的遗传算法对模型进行了求解,使用最优解保存策略保证了最终的优化结果．最后通过仿真算例,验证了本文所建立的箱位分配模型对优化堆场空间资源分配,提高进出口箱流转速度的适用性．     

Integrated scheduling of crane handling and truck transportation in a maritime container terminal

This paper studies the interactions between crane handling and truck transportation in a maritime container terminal by addressing them simultaneously. Yard trucks are shared among different ships, which helps to reduce empty truck trips in the terminal area. The problem is formulated as a constraint programming model and a three-stage algorithm is developed. At the first stage, crane schedules are generated by a heuristic method. At the second stage, the multiple-truck routing problem is solved based on the precedence relations of the transportation tasks derived from the first stage. At the last stage a complete solution is constructed by using a disjunctive graph. The three procedures are linked by an iterative structure, which facilitates the search for a good solution. The computational results indicate that the three-stage algorithm is effective for finding high-quality solutions and can efficiently solve large problems.