Molecular Architecture of Non-Linear Polymers: Kinetic Modeling and Experimental Characterization of the System Methyl Methacrylate + Ethylene Glycol Dimethacrylate

A general kinetic approach allowing the prediction of the molecular architecture of non-linear polymers is applied to the study of the copolymerization of methyl methacrylate (MMA) with ethylene glycol dimethacrylate (EGDMA). Dynamic predictions of molecular weight distributions, sequence length distributions and mean square radius of gyration are possible before and after gelation. A set of experiments concerning the copolymerization of MMA and EGDMA was carried out in toluene solution at 60 °C for which classic radical kinetics is a good approximation. The time evolution of key polymer properties was followed using a SEC system with a refractive index detector coupled with MALLS allowing the determination of absolute weight average molecular weight and apparent molecular size distributions as well as z-average radius of gyration. Special focus was given to assess the influence of the initial amount of cross-linker on the dynamics of the non-linear structure build-up of these products. A kinetic scheme comprising 23 different chemical species and 76 chemical reactions was used in the modeling studies of this chemical system. Most of the kinetic parameters used in the simulations have been collected from previous studies. For experiments at low monomer conversion (up to about 0.5) a good agreement between predictions and experimental measurements is observed for molecular weights and z-average radius of gyration by fitting a small number of parameters describing gel effect (with a conversion dependent but chain length independent termination rate parameter) and the relative propagation on pendant double bonds. However, predicted values of weight-average molecular weights and z-average radius of gyration before gelation are too low at higher monomer conversions with non-linear systems. The likely cause is the presence of intramolecular reactions which should not be neglected in these circumstances.     

A self consistent normalized calibration protocol for three dimensional magnetic resonance gel dosimetry

In a clinical setting, mixed and inconsistent results have been reported using Magnetic Resonance Relaxation imaging of irradiated aqueous polymeric gels as a three-dimensional dosimeter, for dose verification of conformal radiation therapy. The problems are attributed to the difficulty of identifying an accurate dose calibration protocol for each delivered gel at the radiation site in a clinical setting. While careful calibration is done at the gel manufacturing site in a controlled laboratory setting, there is no guarantee that the dose sensitivity of the gels remains invariant upon delivery, irradiation, magnetic resonance imaging and storage at the clinical site. In this study, we have compared three different dose calibration protocols on aqueous polymeric gels for a variety of irradiation scenarios done in a clinical setting. After acquiring the three-dimensional proton relaxation maps of the irradiated gels, the dose distributions were generated using the off-site manufacturer provided calibration curve (Cal-1), the on-site external tube gel calibration (Cal-2) and the new on-site internal normalized gel calibration (Cal-3) protocols. These experimental dose distributions were compared with the theoretical dose distributions generated by treatment-planning systems. We observed that the experimental dose distributions generated from the Cal-1 and Cal-2 protocols were off by 10% to 40% and up to 200% above the predicted maximum dose, respectively. On the other hand, the experimental dose distributions generated from the Cal-3 protocol matched reasonably well with the theoretical dose distributions to within 10% difference. Our result suggests that an independent on-site normalized internal calibration must be performed for each batch of gel dosimeters at the time of MR relaxation imaging in order to account for the variations in dose sensitivity caused by various uncontrollable conditions in a clinical setting such as oxygen contamination, temperature changes and shelf life of the delivered gel between manufacturing and MR acquisitions.     

Fluorinated resveratrol and pterostilbene

A general method for the synthesis of polyhydroxylated stilbene monofluorinated on the central double bond based on the Suzuki reaction between a bromofluoroolefin and a phenylboronic acid is described. Synthesis of fluorinated analogues of resveratrol and pterostilbene was achieved using this strategy.     

A peptide-derived strategy for specifically targeting the mitochondria and ER of cancer cells: a new approach in fighting cancer

An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. Here, we present a new approach in cancer therapy that specifically targets the mitochondria and ER of cancer cells. We developed a peptide derived from the flexible and transmembrane domains of the human protein NAF-1/CISD2. This peptide (NAF-1^44-67) specifically permeates through the plasma membranes of human epithelial breast cancer cells, abolishes their mitochondria and ER, and triggers cell death with characteristics of apoptosis, ferroptosis and necroptosis. In vivo analysis revealed that the peptide significantly decreases tumor growth in mice carrying xenograft human tumors. Computational simulations of cancer vs. normal cell membranes reveal that the specificity of the peptide to cancer cells is due to its selective recognition of their membrane composition. NAF-1^44-67 represents a promising anti-cancer lead compound that acts via a unique mechanism.

An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance.     

Standing waves for the NLS on the double-bridge graph and a rational–irrational dichotomy

We study standing waves of NLS equation posed on the double-bridge graph: two semi-infinite half-lines attached at a circle. At the two vertices Kirchhoff boundary conditions are imposed. The configuration of the graph is characterized by two lengths, $L_1$ and $L_2$. We study the solutions with possibly nontrivial components on the half-lines and a cnoidal component on the circle. The problem is equivalent to a nonlinear boundary value problem in which the boundary condition depends on the spectral parameter ω. After classifying the solutions with rational $L_1/L_2$, we turn to $L_1/L_2$ irrational showing that there exist standing waves only in correspondence to a countable set of negative frequencies ${\omega }_n$. Moreover we show that the frequency sequence admits cluster points and any negative real number can be a limit point of frequencies choosing a suitable irrational geometry $L_1/L_2$. These results depend on basic properties of diophantine approximation of real numbers.     

Denumerable controlled Markov chains with strong average optimality criterion: Bounded & unbounded costs

This paper studies discrete-time nonlinear controlled stochastic systems, modeled by controlled Markov chains (CMC) with denumerable state space and compact action space, and with an infinite planning horizon. Recently, there has been a renewed interest in CMC with a long-run, expected average cost (AC) optimality criterion. A classical approach to study average optimality consists in formulating the AC case as a limit of the discounted cost (DC) case, as the discount factor increases to 1, i.e., as the discounting effectvanishes. This approach has been rekindled in recent years, with the introduction by Sennott and others of conditions under which AC optimal stationary policies are shown to exist. However, AC optimality is a rather underselective criterion, which completely neglects the finite-time evolution of the controlled process. Our main interest in this paper is to study the relation between the notions of AC optimality andstrong average cost (SAC) optimality. The latter criterion is introduced to asses the performance of a policy over long but finite horizons, as well as in the long-run average sense. We show that for bounded one-stage cost functions, Sennott's conditions are sufficient to guarantee thatevery AC optimal policy is also SAC optimal. On the other hand, a detailed counterexample is given that shows that the latter result does not extend to the case of unbounded cost functions. In this counterexample, Sennott's conditions are verified and a policy is exhibited that is both average and Blackwell optimal and satisfies the average cost inequality.     

Access to the spiro hydrindandione ring system of Fredericamycin A through a Friedel-Crafts reaction.

Condensation of 1,4-dimethoxybenzene with 1,1-cyclopentane dicarboxylic acid or 1,1-indan dicarboxylic acid derivatives led to the title compounds.