Folate binding protein—Outlook for drug delivery applications

Serum proteins represent an important class of drug and imaging agent delivery vectors. In this minireview, key advantages of using serum proteins are discussed, followed by the particular advantages and challenges associated with employing soluble folate binding protein. In particular, approaches employing drugs that target folate metabolism are reviewed. Additionally, the slow-onset, tightbinding interaction of folate with folate binding protein and the relationship to a natural oligomerization mechanism is discussed. These unique aspects of folate binding protein suggest interesting applications for the protein as a vector for further drug and imaging agent development.     

Development of a capillary gel electrophoresis method for monitoring disulfide isomer heterogeneity in IgG2 antibodies

A CGE method for monitoring the disulfide isomer distribution characteristic of IgG2 MAbs is presented. Disulfide heterogeneity of MAbs has been studied using various chromatographic and electrophoretic methods. Although CGE operates using a different selectivity mechanism from that of sorption chromatographic techniques, similar trends are present in the data, which allow the CGE method to be used as a complementary method for studying disulfide isomer distribution. This article focuses on the optimization of a capillary‐based gel electrophoresis method that can be used to support antibody development including bioprocess optimization, antibody characterization, release, and formulation stability assessment.     

On the dynamics of radially symmetric granulomas

A granuloma is a collection of macrophages that contains bacteria or other foreign substances that the body?s immune response is unable to eliminate. In this paper we present a simple mathematical model of radially symmetric granuloma dynamics. The model consists of a coupled system of two semi-linear parabolic equations for the macrophage density, and the bacterial density. The boundary of the granuloma is free. This simple framework makes it possible to conduct a mathematical analysis of the system dynamics. In particular, we show that the model system has a unique solution, and that, depending on the biological parameters; the bacterial load either disappears over time or persists. We use numerical methods to establish the existence of stationary solutions and examine how a stationary solution changes with the reproductive rate of the bacteria. These simulations show that the structure of the granuloma breaks down as the reproductive rate of the bacteria increases.     

Matrix Concentration for Products

Foundations of Computational Mathematics - This paper develops nonasymptotic growth and concentration bounds for a product of independent random matrices. These results sharpen and generalize...     

Synthesis and Crystal Structure of a Decamethyleuropocene Complex Supported by a “Clamshell” Ligand

Abstract  

The coordination of decamethyleuropocene to a “clamshell” 1,2-bis(imino)acenaphthene (BIAN) ligand is accompanied by a one-electron redox process. The crystal structure of the Eu³⁺ product has been determined. The complex crystallizes in the triclinic space group P-1, with a = 12.065(2), b = 15.391(3), c = 17.266(4) ?, α = 73.71, β = 73.93(3), γ = 81.40(3)°, V = 2948.3(10) ?³ and Z = 2. The pyridine moiety of the clamshell ligand is not coordinated to the Eu³⁺ center.     

Sulfonium Salts as Acceptors in Electron Donor-Acceptor Complexes

The photoactivation of electron donor-acceptor complexes has emerged as a sustainable, selective and versatile strategy for the generation of radical species. Electron donor-acceptor (EDA) complexation, however, imposes electronic constraints on the donor and acceptor components and this can limit the range of radicals that can be generated using the approach. New EDA complexation strategies exploiting sulfonium salts allow radicals to be generated from native functionality. For example, aryl sulfonium salts, formed by the activation of arenes, can serve as the acceptor components in EDA complexes due to their electron-deficient nature. This “sulfonium tag” approach relaxes the electronic constraints on the parent substrate and dramatically expands the range of radicals that can be generated using EDA complexation. In this review, these new applications of sulfonium salts will be introduced and the areas of chemical space rendered accessible through this innovation will be highlighted.     

Silica-based nanoprobes for biomedical imaging and theranostic applications

Nanoparticle-based contrast agents are attracting a great deal of attention for various biomedical imaging and theranostic applications. Compared to conventional contrast agents, nanoparticles possess several potential advantages to improve in vivo detection and to enhance targeting efficiency. Silica-based nanoprobes can be engineered to achieve longer blood circulation times, specific clearance pathways, and multivalent binding. In this tutorial review, we summarize the latest progress on designing silica-based nanoprobes for imaging and theranostic applications. The synthesis of both solid silica and mesoporous silica nanoparticles is described, along with different approaches used for surface functionalization. Special emphasis is placed on the application of silica-based nanoprobes in optical, magnetic resonance, and multimodal imaging. The latest breakthroughs in the applications of silica nanoparticles as theranostic agents are also highlighted.     

Rheological properties of binary associating polymers

Dynamics of associating polymer solutions above the reversible gelation point are studied. Each macromolecule consists of a soluble backbone (B) and a small fraction of specific strongly interacting groups (A or C stickers) attached to B. A mixture of B–A and B–C associating polymers with 1:1 stoichiometric ratio is considered. As a result of AC association, the polymers reversibly gelate above the overlap concentration. It is shown that (1) the network strands are linear complexes (double chains) of B–A and B–C; (2) “diffusion” of the network junction points is characterized by an apparent activation energy, which can be significantly higher than the energy of one AC bond; (3) most importantly, the randomness of sticker distribution along the chain can significantly slow down the network relaxation leading to a markedly non-Maxwellian viscoelastic behavior. The theory elucidates the most essential features of rheological behavior of polysaccharide associating systems (with A = adamantyl moiety, C = β-cyclodextrin, B = either chitosan or hyaluronan) including similar behavior of G ^′ and G ^″ in a wide frequency range, strong temperature dependence of the characteristic frequency ω _x , and an extremely strong effect of added free stickers (fC) on the dynamics. This paper was presented at Annual European Rheology Conference (AERC) held in Hersonisos, Crete, Greece, April 27–29, 2006.     

The extended QUALIFLEX method for multiple criteria decision analysis based on interval type-2 fuzzy sets and applications to medical decision making

QUALIFLEX, a generalization of Jacquet-Lagreze’s permutation method, is a useful outranking method in decision analysis because of its flexibility with respect to cardinal and ordinal information. This paper develops an extended QUALIFLEX method for handling multiple criteria decision-making problems in the context of interval type-2 fuzzy sets. Interval type-2 fuzzy sets contain membership values that are crisp intervals, which are the most widely used of the higher order fuzzy sets because of their relative simplicity. Using the linguistic rating system converted into interval type-2 trapezoidal fuzzy numbers, the extended QUALIFLEX method investigates all possible permutations of the alternatives with respect to the level of concordance of the complete preference order. Based on a signed distance-based approach, this paper proposes the concordance/discordance index, the weighted concordance/discordance index, and the comprehensive concordance/discordance index as evaluative criteria of the chosen hypothesis for ranking the alternatives. The feasibility and applicability of the proposed methods are illustrated by a medical decision-making problem concerning acute inflammatory demyelinating disease, and a comparative analysis with another outranking approach is conducted to validate the effectiveness of the proposed methodology.