Generating bounded solutions for multi-demand multidimensional knapsack problems: a guide for operations research practitioners

A generalization of the 0-1 knapsack problem that is hard-to-solve both theoretically (NP-hard) and in practice is the multi-demand multidimensional knapsack problem (MDMKP). Solving an MDMKP can be difficult because of its conflicting knapsack and demand constraints. Approximate solution approaches provide no guarantees on solution quality. Recently, with the use of classification trees, MDMKPs were partitioned into three general categories based on their expected performance using the integer programming option of the CPLEX® software package on a standard PC: Category A—relatively easy to solve, Category B—somewhat difficult to solve, and Category C—difficult to solve. However, no solution methods were associated with these categories. The primary contribution of this article is that it demonstrates, customized to each category, how general-purpose integer programming software (CPLEX in this case) can be iteratively used to efficiently generate bounded solutions for MDMKPs. Specifically, the simple sequential increasing tolerance (SSIT) methodology will iteratively use CPLEX with loosening tolerances to efficiently generate these bounded solutions. The real strength of this approach is that the SSIT methodology is customized based on the particular category (A, B, or C) of the MDMKP instance being solved. This methodology is easy for practitioners to use because it requires no time-consuming effort of coding problem specific-algorithms. Statistical analyses will compare the SSIT results to a single-pass execution of CPLEX in terms of execution time and solution quality

Fullerenes and their potential in nanomedicine

Carboxyfullerenes are closed carbon spheres which are being actively pursued globally for a wide range of applications. Their inherent properties and ability to be functionalized with side-chains results in nearly limitless new chemical structures making them ideal platform molecules for new solutions to basic biological problems. In general, two classes of fullerenes exist for nanomedicine applications; empty cage and metallo-fullerenes. The carbon cage (usually C60 and C70) of empty cage fullerenes are anti-oxidants, thus potential therapeutics for inflammatory diseases. Our discovery that certain fullerene derivatives can stabilize and prevent pro-inflammatory mediator release from human tissue mast cells make them ideal candidates for diseases controlled by MC mediators (e.g. arthritis, asthma, etc.). New research findings using metallo-fullerenes with gadolinium inside the carbon cage as diagnostics using Magnetic Resonance Imaging for inflammatory diseases suggest metallo-fullerenes are more sensitive than current contrast agents, have the ability to be targeted to disease specific biomarkers, and are safe

Liposomal formulation of amphiphilic fullerene antioxidants

Novel amphiphilic fullerene[70] derivatives that are rationally designed to intercalate in lipid bilayers are reported, as well as its vesicular formulation with surprisingly high loading capacity up to 65% by weight. The amphiphilic C70 bisadduct forms uniform and dimensionally stable liposomes with auxiliary natural phospholipids as demonstrated by buoyant density test, particle size distribution, and 31P NMR. The antioxidant property of fullerenes is retained in the bipolarly functionalized C70 derivative, amphiphilic liposomal malonylfullerene[70] (ALM), as well as in its liposomal formulations, as shown by both electron paramagnetic resonance (EPR) studies and in vitro reactive oxygen species (ROS) inhibition experiments. The liposomally formulated ALM efficiently quenched hydroxyl radicals and superoxide radicals. In addition, the fullerene liposome inhibited radical-induced lipid peroxidation and maintained the integrity of the lipid bilayer structure. This new class of liposomally formulated, amphipathic fullerene compounds represents a novel drug delivery system for fullerenes and provides a promising pathway to treat oxidative stress-related diseases

The Role of Horseshoe Crabs in the Biomedical Industry and Recent Trends Impacting Species Sustainability

Every year the Atlantic horseshoe crab (Limulus polyphemus) arrives on shore to spawn, a sight once taken for granted. However, in addition to the gradual climate changes impacting all ecosystems, commercial demand from the widespread application of Atlantic horseshoe crab blood in industrial endotoxin testing and steady use as eel and whelk bait has brought the future of this enduring species into question. In response, regulations have been adopted to enhance the traceability and record keeping of horseshoe crab harvest, which has historically been difficult to track. However, these regulations do not restrict or limit LAL harvest in any significant manner. Still, sometimes-lethal biomedical bleeding process and associated behavioral changes pose a risk to horseshoe crab viability after bleeding and once returned to the waters. As a result, regulators and environmentalists are concerned that current trends and overfishing of this marine arthropod will significantly impact the surrounding ecosystem. This review examines their role and recent trends in the biomedical industry that are impacting these ancient creatures and the derivative effect on shorebirds, while considering emerging alternatives where feasible, as well as ways to ensure sustainable and pragmatic harvesting strategies. Ultimately, healthy populations of horseshoe crabs are vital to restoring and maintaining ecosystems while balancing the need for medical and research applications entirely dependent on these unique creatures

Uptake and distribution of fullerenes in human mast cells

Fullerenes are carbon cages of variable size that can be derivatized with various side chain moieties resulting in compounds that are being developed into nanomedicines. Although fullerene use in several preclinical in vitro and in vivo models of disease has demonstrated their potential as diagnostic and therapeutic agents, little is known about how they enter cells, what organelles they target, and the time course for their cellular deposition. Fullerenes (C70) that have already been shown to be potent inhibitors of mast cell (MC)–mediated allergic inflammation were conjugated with Texas red (TR) and used in conjunction with confocal microscopy to determine mechanisms of uptake, the organelle localization, and the duration they can be detected in situ. We show that C70-TR are nonspecifically endocytosed into MCs, where they are shuttled throughout the cytoplasm, lysosomes, mitochondria, and into endoplasmic reticulum at different times. No nuclear or secretory granule localization was observed. The C70-TR remained detectable within cells at 1 week. These studies show that MCs endocytose fullerenes, where they are shuttled to organelles involved with calcium and reactive oxygen species production, which may explain their efficacy as cellular inhibitors

A synthetic crustacean bait to stem forage fish depletion

Crustaceans, such as crab and lobster, comprise an important global food commodity. They are captured in traps using primarily forage fish (e.g. anchovies, herring, and menhaden), as bait. Approximately 18 million tons of these fish are used annually to bait traps, worldwide (U. Nations, 2014). In addition to natural predators dependent on forage fish (Pikitch et al., 2012), myriad other factors are further intensifying demand and collectively threatening stocks (e.g. Omega-3 supplements, pet food, livestock feed,–in addition to direct human consumption). Forage fish capture methods pose collateral environmental risks from by-catch (e.g. seals, dolphins, turtles) indiscriminately killed in nets. Sustainable alternatives to stem further depletion are desperately needed, and toward this end, a synthetic crustacean bait has been developed. The technology mimics molecules released from forage fish by employing a formulation that is dispersed at a controlled rate from a soluble matrix. The synthetic bait reliably caught stone crab, blue crab, and American lobster in field trials. This technology addresses major ecological threats, while providing economic and operational benefits to the crustacean fishing industry

Fullerene nanomaterials potentiate hair growth

Hair loss is a common symptom resulting from a wide range of disease processes and can lead to stress in affected individuals. The purpose of this study was to examine the effect of fullerene nanomaterials on hair growth. We used shaved mice as well as SKH-1 “bald” mice to determine if fullerene-based compounds could affect hair growth and hair follicle numbers. In shaved mice, fullerenes increase the rate of hair growth as compared with mice receiving vehicle only. In SKH-1 hairless mice fullerene derivatives given topically or subdermally markedly increased hair growth. This was paralleled by a significant increase in the number of hair follicles in fullerene-treated mice as compared with those mice treated with vehicle only. The fullerenes also increased hair growth in human skin sections maintained in culture. These studies have wide-ranging implications for those conditions leading to hair loss, including alopecia, chemotherapy, and reactions to various chemicals

Study Examining Fullerene Toxicity Raises Questions as to the Purity of the Nanomaterials and Erroneous Experimental Conclusions

To the Editor, We are compelled to comment on a recent article in your journal “C60 Exposure Augments Cardiac Ischemia/Reperfusion Injury and Coronary Artery Contraction in Sprague Dawley Rats; 138(2), 365–378” by Thompson1 in which various conclusions were made concerning the toxicity of C60. In this study, insoluble C60 was mixed with polyvinylpyrrolidone (PVP) and used to challenge rats which were then surgically induced to examine various cardiovascular toxicity parameters. Both intravenously (IV) and intratracheally (IT) exposure to the C60-PVP mixture resulted in expansion of myocardial infarction in male and female rats following I/R injury, elevated inflammatory cytokines, and augmented vasocontraction of coronary arteries