Design of Enzymatically Cleavable Prodrugs of a Potent Platinum‐Containing Anticancer Agent

Using a versatile synthetic approach, a new class of potential ester prodrugs of highly potent, but systemically too toxic, platinum–acridine anticancer agents was generated. The new hybrids contain a hydroxyl group, which has been masked with a cleavable lipophilic acyl moiety. Both butanoic (butyric) and bulkier 2‐propanepentanoic (valproic) esters were introduced. The goals of this design were to improve the drug‐like properties (e.g., logD) and to reduce the systemic toxicity of the pharmacophore. Two distinct pathways by which the target compounds undergo effective ester hydrolysis, the proposed activating step, have been confirmed: platinum‐assisted, self‐immolative ester cleavage in a low‐chloride environment (LC‐ESMS, NMR spectroscopy) and enzymatic cleavage by human carboxylesterase‐2 (hCES‐2) (LC‐ESMS). The valproic acid ester derivatives are the first example of a metal‐containing agent cleavable by the prodrug‐converting enzyme. They show excellent chemical stability and reduced systemic toxicity. Preliminary results from screening in lung adenocarcinoma cell lines (A549, NCI‐H1435) suggest that the mechanism of the valproic esters may involve intracellular deesterification.     

The role of different linear and non-linear channels of relaxation in scintillator non-proportionality

The non-proportional dependence of a scintillator's light yield on primary particle energy is believed to be influenced crucially by the interplay of non-linear kinetic terms in the radiative and non-radiative decay of excitations versus locally deposited excitation density. A calculation of energy deposition, −dE/dx, along the electron track for NaI is presented for an energy range from several electron-volt to 1 MeV. Such results can be used to specify an initial excitation distribution, if diffusion is neglected. An exactly solvable two-channel (exciton and hole(electron)) model containing 1st and 2nd order kinetic terms is constructed and used to illustrate important features seen in non-proportional light-yield curves, including a dependence on pulse shaping (detection gate width).     

Octadecyltrimethylammonium surfactant-immobilized cation exchange membranes for solid-phase extraction of phenolic compounds

In this study, octadecyltrimethylammonium surfactant was immobilized onto a cation exchange membrane for the application in solid-phase extraction of phenolic compounds. The results indicate that an HCl prewashing step and the use of hydroxide (or methoxide) counter ion could greatly improve the immobilized surfactant capacity. Through elemental and thermogravimetric analyses, the resulted immobilization percentage on the membrane (compared to membrane ion exchange capacity) was about 50, 100, and 150%, respectively, for the feed surfactant amount of 150, 2000, and 5000 μmol (volume = 20 mL). Phenol, 4-nitrophenol, 2,4-dimethylphenol, 2,4-dichlorophenol, 4-chloro-3-methylphenol, and bisphenol A were the tested compounds in a breakthrough volume experiment. The order of the obtained breakthrough volume values is similar to that of K_ow values of the phenolic compounds. In the solid-phase extraction process from a feed mixture of 0.1 ppm for 4-nitrophenol, 2,4-dichlorophenol, and 4-chloro-3-methylphenol, high concentration factors and almost complete recoveries were achieved. Moreover, by increasing the membrane volume, a larger sample volume could be processed without any deterioration in performance.     

Semilinear fractional integro-differential equations with compact semigroup

In this paper, we study the local and global existence of mild solutions to a class of fractional integro-differential equations in an arbitrary Banach space associated with operators generating compact semigroup on the Banach space.     

A direct preparation of fluorinated imides

N-Fluorosulfuryltrifluoroacetimide and N-chlorosulfuryltrifluoroacetimide have been prepared in high yield by a one-step reaction of trifluorothiolacetic acid with the corresponding fluoro- and chlorosulfuryl isocyanates. The trifluoroacetimides are easily purified by vacuum sublimation from the crude product mixture.     

Functional Interdependence in Coupled Dissipative Structures: Physical Foundations of Biological Coordination

Coordination within and between organisms is one of the most complex abilities of living systems, requiring the concerted regulation of many physiological constituents, and this complexity can be particularly difficult to explain by appealing to physics. A valuable framework for understanding biological coordination is the coordinative structure, a self-organized assembly of physiological elements that collectively performs a specific function. Coordinative structures are characterized by three properties: (1) multiple coupled components, (2) soft-assembly, and (3) functional organization. Coordinative structures have been hypothesized to be specific instantiations of dissipative structures, non-equilibrium, self-organized, physical systems exhibiting complex pattern formation in structure and behaviors. We pursued this hypothesis by testing for these three properties of coordinative structures in an electrically-driven dissipative structure. Our system demonstrates dynamic reorganization in response to functional perturbation, a behavior of coordinative structures called reciprocal compensation. Reciprocal compensation is corroborated by a dynamical systems model of the underlying physics. This coordinated activity of the system appears to derive from the system’s intrinsic end-directed behavior to maximize the rate of entropy production. The paper includes three primary components: (1) empirical data on emergent coordinated phenomena in a physical system, (2) computational simulations of this physical system, and (3) theoretical evaluation of the empirical and simulated results in the context of physics and the life sciences. This study reveals similarities between an electrically-driven dissipative structure that exhibits end-directed behavior and the goal-oriented behaviors of more complex living systems.     

Descent Monomials, P-Partitions and Dense Garsia-Haiman Modules

A two-variable analogue of the descents monomials is defined and is shown to form a basis for the dense Garsia-Haiman modules. A two-variable generalization of a decomposition of a P-partition is shown to give the algorithm for the expansion into this descent basis. Some examples of dense Garsia-Haiman modules include the coinvariant rings associated with certain complex reflection groups.     

An iterative substructuring algorithm for equilibrium equations

Summary The topic of iterative substructuring methods, and more generally domain decomposition methods, has been extensively studied over the past few years, and the topic is well advanced with respect to first and second order elliptic problems. However, relatively little work has been done on more general constrained least squares problems (or equivalent formulations) involving equilibrium equations such as those arising, for example, in realistic structural analysis applications. The potential is good for effective use of iterative algorithms on these problems, but such methods are still far from being competitive with direct methods in industrial codes. The purpose of this paper is to investigate an order reducing, preconditioned conjugate gradient method proposed by Barlow, Nichols and Plemmons for solving problems of this type. The relationships between this method and nullspace methods, such as the force method for structures and the dual variable method for fluids, are examined. Convergence properties are discussed in relation to recent optimality results for Varga's theory ofp-cyclic SOR. We suggest a mixed approach for solving equilibrium equations, consisting of both direct reduction in the substructures and the conjugate gradient iterative algorithm to complete the computations.Dedicated to R. S. Varga on the occasion of his 60th birthdayResearch completed while pursuing graduate studies sponsored by the Department of Mathematical Sciences, US Air Force Academy, CO, and funded by the Air Force Institute of Technology, WPAFB, OHResearch supported by the Air Force under grant no. AFOSR-88-0285 and by the National Science Foundation under grant no. DMS-89-02121     

Assessment of nanoparticle loading and dispersion in polymeric materials using optical wavefront correlation

Small concentrations (≤5 wt. %) of nanoparticles in polymeric materials can potentially result in improvements in material properties and functionality. However, poor or non-uniform particle dispersion resulting in clustering (agglomeration) in polymer nanocomposites (PNCs) limits the potential for property enhancement. Achieving good dispersion is considered essential for large-scale production and commercialization of PNCs. New and effective measurement techniques capable of quantitatively characterizing particle loading and dispersion would significantly contribute towards understanding and optimizing the material performance of PNCs and, consequently, play a pivotal role in product development. This paper presents the results of a study using a static light scattering technique, optical wavefront correlation (OWC), for discriminating between different particle loadings and levels of dispersion. The technique has been applied to a range of PNCs, including epoxy resins reinforced with nanoclay platelets or silica microspheres, and zinc oxide and lithium aluminate reinforced polypropylene.