Analysis of Renal Cell Carcinoma Cell Response to the Enhancement of 5-aminolevulinic Acid-mediated Protoporphyrin IX Fluorescence by Iron Chelator Deferoxamine†

As a tumor photodiagnostic agent, 5-aminolevulinic acid (ALA) is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX) with fluorescence. ALA-PpIX fluorescence was evaluated in human renal cell carcinoma (RCC) cell lines and non-tumor HK-2 cell lines. We found that extracellular PpIX level was correlated with ABCG2 activity, illustrating its importance as a PpIX efflux transporter. Extracellular PpIX was also related to the K_m of ferrochelatase (FECH) that chelates PpIX with ferrous iron to form heme. The V_max of FECH was higher in all RCC cell lines tested than in the HK-2 cell line. TCGA dataset analysis indicates a positive correlation between FECH expression and RCC patient survival. These findings suggest FECH as an important biomarker in RCC. Effects of iron chelator deferoxamine (DFO) on the enhancement of PpIX fluorescence were assessed. DFO increased intracellular PpIX in both tumor and non-tumor cells, resulting in no gain in tumor/non-tumor fluorescence ratios. DFO appeared to increase ALA-PpIX more at 1-h than at 4-h treatment. There was an inverse correlation between ALA-PpIX fluorescence and the enhancement effect of DFO. These results suggest that enhancement of ALA-PpIX by DFO may be limited by the availability of ferrous iron in mitochondria following ALA administration.     

Approximate solutions and scalarization in set-valued optimization

Abstract

Certain notions of approximate weak efficient solutions are considered for a set-valued optimization problem based on vector and set criteria approaches. For approximate solutions based on the vector approach, a characterization is provided in terms of an extended Gerstewitz’s function. For the set approach case, two notions of approximate weak efficient solutions are introduced using a lower and an upper quasi order relations for sets and further compactness and stability aspects are discussed for these approximate solutions. Existence and scalarization using a generalized Gerstewitz’s function are also established for approximate solutions, based on the lower set order relation.     

Well-setness and scalarization in set optimization

In this paper, we consider a notion of global well-setness for a set optimization problem using the excess function. We give sufficient conditions for well-setness and establish Dontchev–Zolezzi type measure for well-setness. Moreover, we relate this notion with well-setness notion for a scalar problem obtained by using generalized Gerstewitz’s function.     

Optimization reformulations of the generalized Nash equilibrium problem using regularized indicator Nikaidô–Isoda function

In this paper, we extend the literature by adapting the Nikaidô–Isoda function as an indicator function termed as regularized indicator Nikaidô–Isoda function, and this is demonstrated to guarantee existence of a solution. Using this function, we present two constrained optimization reformulations of the generalized Nash equilibrium problem (GNEP for short). The first reformulation characterizes all the solutions of GNEP as global minima of the optimization problem. Later this approach is modified to obtain the second optimization reformulation whose global minima characterize the normalized Nash equilibria. Some numerical results are also included to illustrate the behaviour of the optimization reformulations.     

Convexity violations for noninteger parameters in certain lattice models

The convexity of the free energy is studied for several lattice models in situations in which a parameter which is normally a positive integer takes on noninteger real values. Examples include the numbern of components in then-vector model, the number of states in the Potts model, and the dimensionality of the lattice. In a typical case there is a critical value of the parameter such that convexity is preserved when the parameter exceeds the critical value, but can be violated for appropriate Hamiltonians whenever the parameter is less than the critical value, but not a positive integer. In several cases the critical value of the parameter increases with the size of the system, thus raising questions about the significance of a continuous variation of the parameter in the thermodynamic limit.     

A single amino acid Gly-tag enables metal-free protein purification

Analytically pure proteins are indispensable for diverse applications, including therapeutics. Here, we report a methodology where a single amino acid, glycine, enables metal-free protein purification. This robust platform is enabled by a Gly-tag resin for site-specific capture, enrichment, and release through chemically triggered C–C bond dissociation by resonance-assisted electron density polarization.

Gly-tag resin precisely captures and releases a protein with one glycine at the N-terminus. The user-friendly protocol delivers analytically pure protein free of metal contaminants.     

One-level reformulation of the bilevel Knapsack problem using dynamic programming

In this paper, we consider the Bilevel Knapsack Problem (BKP), which is a hierarchical optimization problem in which the feasible set is determined by the set of optimal solutions for a parametric Knapsack Problem. We introduce a new reformulation of the BKP into a one-level integer programming problem using dynamic programming. We propose an algorithm that allows the BKP to be solved exactly in two steps. In the first step, a dynamic programming algorithm is used to compute the set of follower reactions to leader decisions. In the second step, an integer problem that is equivalent to the BKP is solved using a branch-and-bound algorithm. Numerical results are presented to show the performance of our method.     

Luminescent charge-transfer complexes: tuning emission in binary fluorophore mixtures

Charge-transfer (CT) complexes composed of a π-electron-poor naphthalene diimide (NDI) derivative combined with a series of π-electron-rich donors were investigated. Solutions of the CT complexes are nonemissive; however, solid-state complexes and aqueous suspensions display emission that is dependent on the energy of the HOMO of the electron donor. Crystallographic analysis of a pyrene-NDI complex reveals columnar packing and a high degree of frontier molecular orbital (FMO) overlap that likely contributes to the observed optical properties. The fluorescent CT particles are utilized as imaging agents; additional luminescent CT complexes may be realized by considering FMO energies and topologies.