Fast Ejection Chain Algorithms for Vehicle Routing with Time Windows

This paper introduces new ejection chain strategies to effectively target vehicle routing problems with time window constraints (VRPTW). Ejection chain procedures are based on the idea of compound moves that allow a variable number of solution components to be modified within any single iteration of a local search algorithm. The yardstick behind such procedures is the underlying reference structure, which is the structure that is used to coordinate the moves that are available for the local search algorithm. The main contribution of the paper is a new reference structure that is particularly suited in order to handle the asymmetric aspects in a VRPTW. The new reference structure is a generalization of the doubly rooted reference structure introduced by Glover, resulting in a new, powerful neighborhood for the VRPTW. We use tabu search for the generation of the ejection chains. On a higher algorithmic level, we study the effect of different meta heuristics to steer the tabu chain ejection process. Computational results confirm that our approach leads to very fast algorithms that can compete with the current state of the art algorithms for the VRPTW.operations research and management science;

Complex carbohydrate recognition by proteins: Fundamental insights from bacteriophage cell adhesion systems

SummaryProtein–glycan interactions are ubiquitous in nature. Molecular description of complex formation and the underlying thermodynamics, however, are not well understood due to the lack of model systems. Bacteriophage tailspike proteins (TSP) possess binding sites for bacterial cell surfaces oligosaccharides. In this article we describe the analysis of TSP-oligosaccharide complexes. TSP provide large glycan interaction sites where affinity and specificity are guided by the protein surface solvation and the conformational space sampled by the respective glycan. Furthermore, we describe a computational approach to analyse the conformational space sampled by flexible glycans of bacterial origin, a prerequisite for a thorough understanding of TSP-oligosaccharide interactions

Design of Heuristic Algorithms for Hard Optimization

This open access book demonstrates all the steps required to design heuristic algorithms for difficult optimization. The classic problem of the travelling salesman is used as a common thread to illustrate all the techniques discussed. This problem is ideal for introducing readers to the subject because it is very intuitive and its solutions can be graphically represented. The book features a wealth of illustrations that allow the concepts to be understood at a glance. The book approaches the main metaheuristics from a new angle, deconstructing them into a few key concepts presented in separate chapters: construction, improvement, decomposition, randomization and learning methods. Each metaheuristic can then be presented in simplified form as a combination of these concepts. This approach avoids giving the impression that metaheuristics is a non-formal discipline, a kind of cloud sculpture. Moreover, it provides concrete applications of the travelling salesman problem, which illustrate in just a few lines of code how to design a new heuristic and remove all ambiguities left by a general framework. Two chapters reviewing the basics of combinatorial optimization and complexity theory make the book self-contained. As such, even readers with a very limited background in the field will be able to follow all the content

RGD_PLGA Nanoparticles with Docetaxel: A Route for Improving Drug Efficiency and Reducing Toxicity in Breast Cancer Treatment

Breast cancer is the leading cause of cancer-related death in women. Although many therapeutic approaches are available, systemic chemotherapy remains the primary choice, especially for triple-negative and advanced breast cancers. Unfortunately, systemic chemotherapy causes serious side effects and requires high doses to achieve an effective concentration in the tumor. Thus, the use of nanosystems for drug delivery may overcome these limitations. Herein, we formulated Poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing Docetaxel, a fluorescent probe, and a magnetic resonance imaging (MRI) probe. The cyclic RGD tripeptide was linked to the PLGA surface to actively target αvβ3 integrins, which are overexpressed in breast cancer. PLGA-NPs were characterized using dynamic light scattering, fast field-cycling 1H-relaxometry, and 1H-nuclear magnetic resonance. Their therapeutic effects were assessed both in vitro in triple-negative and HER2+ breast cancer cells, and in vivo in murine models. In vivo MRI and inductively coupled plasma mass spectrometry of excised tumors revealed a stronger accumulation of PLGA-NPs in the RGD_PLGA group. Targeted PLGAs have improved therapeutic efficacy and strongly reduced cardiac side effects compared to free Docetaxel. In conclusion, RGD-PLGA is a promising system for breast cancer treatment, with positive outcome in terms of therapeutic efficiency and reduction in side effects

Increased mean aliphatic lipid chain length in left ventricular hypertrophy secondary to arterial hypertension: A cross-sectional study

About 77.9 million (1 in 4) American adults have high blood pressure. High blood pressure is the primary cause of left ventricular hypertrophy (LVH), which represents a strong predictor of future heart failure and cardiovascular mortality. Previous studies have shown an altered metabolic profile in hypertensive patients with LVH. The goal of this study was to identify blood metabolomic LVH biomarkers by H NMR to provide novel diagnostic tools for rapid LVH detection in populations of hypertensive individuals. This cross-sectional study included 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the H NMR spectral data. From the H NMR-based metabolomic profiling, signals coming from methylene (-CH2-) and methyl (-CH3) moieties of aliphatic chains from plasma lipids were identified as discriminant variables. The -CH2-/-CH3 ratio, an indicator of the mean length of the aliphatic lipid chains, was significantly higher (P < 0.001) in the LVH group than in the hypertensive group without LVH and controls. Receiver operating characteristic curve showed that a cutoff of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC = 0.703, P-value < 0.001). We propose the -CH2-/-CH3 ratio from plasma aliphatic lipid chains as a biomarker for the diagnosis of left ventricular remodeling in hypertension