Near-infrared absorbing Ru(ii) complexes act as immunoprotective photodynamic therapy (PDT) agents against aggressive melanoma

Mounting evidence over the past 20 years suggests that photodynamic therapy (PDT), an anticancer modality known mostly as a local treatment, has the capacity to invoke a systemic antitumor immune response, leading to protection against tumor recurrence. For aggressive cancers such as melanoma, where chemotherapy and radiotherapy are ineffective, immunomodulating PDT as an adjuvant to surgery is of interest. Towards the development of specialized photosensitizers (PSs) for treating pigmented melanomas, nine new near-infrared (NIR) absorbing PSs based on a Ru(ii) tris-heteroleptic scaffold [Ru(NNN)(NN)(L)]Cl_n, were explored. Compounds 2, 6, and 9 exhibited high potency toward melanoma cells, with visible EC₅₀ values as low as 0.292–0.602 μM and PIs as high as 156–360. Single-micromolar phototoxicity was obtained with NIR-light (733 nm) with PIs up to 71. The common feature of these lead NIR PSs was an accessible low-energy triplet intraligand (³IL) excited state for high singlet oxygen (¹O₂) quantum yields (69–93%), which was only possible when the photosensitizing ³IL states were lower in energy than the lowest triplet metal-to-ligand charge transfer (³MLCT) excited states that typically govern Ru(ii) polypyridyl photophysics. PDT treatment with 2 elicited a pro-inflammatory response alongside immunogenic cell death in mouse B16F10 melanoma cells and proved safe for in vivo administration (maximum tolerated dose = 50 mg kg⁻¹). Female and male mice vaccinated with B16F10 cells that were PDT-treated with 2 and challenged with live B16F10 cells exhibited 80 and 55% protection from tumor growth, respectively, leading to significantly improved survival and excellent hazard ratios of ≤0.2.

Ru(ii) photosensitizers (PSs) destroy aggressive melanoma cells, triggering an immune response that leads to protection against tumor challenge and mouse survival.     

Über Chalkogenolate. 131. Untersuchungen über Rhodanine 2. Kristall- und Molekülstruktur von 5-Methylrhodanin

On Chalcogenolates. 131. Studies on Rhodanines 2. Crystal and Molecular Structure of 5-Methyl Rhodanine The title compound crystallizes with Z = 4 in the monoclinic space group P2₁/c with cell dimensions a = 6.087(1), b = 6.846(4), c = 15.336(2) Å, β = 99.85(1)°. The crystal and molecular structure has been determined from single crystal X-ray data at ?25°C and refined to a conventional R of 0.044. The structure consists of discrete 5-methyl-2-thio-4-oxo-thiazolidine molecules, which are linked together by N? H…?O hydrogen bridges. The thiazolidine ring is plane. The compound contains no located double-bonds.     

Multilevel ILU decomposition

Summary. In this paper, the multilevel ILU (MLILU) decomposition is introduced. During an incomplete Gaussian elimination process new matrix entries are generated such that a special ordering strategy yields distinct levels. On these levels, some smoothing steps are computed. The MLILU decomposition exists and the corresponding iterative scheme converges for all symmetric and positive definite matrices. Convergence rates independent of the number of unknowns are shown numerically for several examples. Many numerical experiments including unsymmetric and anisotropic problems, problems with jumping coefficients as well as realistic problems are presented. They indicate a very robust convergence behavior of the MLILU method. Received June 13, 1997 / Revised version received March 17, 1998     

Local bounded commutative residuated ℓ-monoids

Bounded commutative residuated lattice ordered monoids (Rℓ-monoids) are a common generalization of, e.g., BL-algebras and Heyting algebras. In the paper, the properties of local and perfect bounded commutative Rℓ-monoids are investigated.     

On the analytic solution of the lane-emden equation

The Lane-Emden equation describing temperature in a star in hydrostatic equilibrium was recently solved analytically by N.T. Shawagfeh [1] with highly accurate results using decomposition [1–9]. Further consideration suggests some computational advantage, avoidance of the initial transformations, possible generalizations in astrophysics, and a measurement to determine masses of the cepheids.     

Quantum Monte Carlo study of the optical and diffusive properties of the vacancy defect in diamond

Fixed-node diffusion quantum Monte Carlo (DMC) calculations of the ground and excited state energetics of the neutral vacancy defect in diamond are reported. The multiplet structure of the defect is modeled using guiding wave functions of the Slater-Jastrow type with symmetrized multideterminant Slater parts. For the ground state we obtain the 1E state in agreement with experiment. The calculated energy of the lowest dipole allowed transition is consistent with the experimentally observed GR1 band, which has long been identified with the neutral vacancy in diamond, although no previous first-principles ab initio calculation of this transition exists. The calculated multiplet splitting of over 2 eV indicates the importance of a proper treatment of electron exchange and correlation in this system. DMC calculations of the formation and migration energy of the vacancy defect are presented.     

An anomaly in the isotopomer shift of the hyperfine spectrum of LiI

A high-precision examination of the hyperfine spectrum of 6LiI in comparison with 7LiI shows a shift in the iodine nuclear electric quadrupole moment that cannot be accounted for by a model in which the electric field gradient at the iodine site is assumed to depend only upon the internuclear distance between Li and I. The other hyperfine interactions are consistent between the two isotopomers, including the previously reported electric hexadecapole interaction of the iodine nucleus.     

Inversion of nonlinear stochastic operators

The operator-theoretic method (Adomian and Malakian, J. Math. Anal. Appl.76(1), (1980), 183–201) recently extended Adomian's solutions of nonlinear stochastic differential equations (G. Adomian, Stochastic Systems Analysis, in “Applied Stochastic Processes,” Nonlinear Stochastic Differential Equations, J. Math. Anal. Appl.55(1) (1976), 441–452; On the modeling and analysis of nonlinear stochastic systems, in “Proceeding, International Conf. on Mathematical Modeling.” Vol. 1, pp. 29–40) to provide an efficient computational procedure for differential equations containing polynomial, exponential, and trigonometric nonlinear terms N(y). The procedure depends on the calculation of certain quantities A_n and B_n. This paper generalizes the calculation of the A_n and B_n to much wider classes of nonlinearities of the form N(y, y′,…). Essentially, the method provides a systematic computational procedure for differential equations containing any nonlinear terms of physical significance. This procedure depends on a recurrence rule from which explicit general formulae are obtained for the quantities A_n and B_n for any order n in a convenient form. This paper also demonstrates the significance of the iterative series decomposition proposed by Adomian for linear stochastic operators in 1964 and developed since 1976 for nonlinear stochastic operators. Since both the nonlinear and stochastic behavior is quite general, the results are extremely significant for applications. Processes need not, for example, be limited to either Gaussian processes, white noise, or small fluctuations.     

Nonlinear stochastic differential delay equations

The methods used by Adomian and his co-workers to solve linear and nonlinear stochastic differential equations will be demonstrated to be applicable to differential equations, deterministic or stochastic, involving delays (constant, time dependent, or random).