Mechanisms of cytotoxicity in human ovarian carcinoma cells exposed to free Mce6 or HPMA copolymer-Mce6 conjugates

It is essential to understand cellular responses on photodynamic therapy (PDT) to design delivery systems that maximize cytotoxic effects coupled with minimal induction of side effects or protective mechanisms (or both). Here, we investigated mechanisms of toxicity in human ovarian carcinoma A2780 cells treated with structurally diverse N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer (P)-mesochlorin e6 monoethylenediamine (Mce6) conjugates that possessed differential subcellular accumulation or covalent attachments of photosensitizers (or both). Apoptosis and necrosis were observed after photoactivation, with increased apoptotic responses observed in cells exposed to conjugates possessing Mce6 linkage via a lysosomally degradable tetrapeptide spacer (HPMA copolymer-Mce6 conjugates containing Mce6 bound via glycylphenylalanylleucylglycine [GFLG] linker [P-GFLG-Mce6], HPMA copolymer-Mce6 conjugates containing Mce6 bound via a GFLG spacer and containing nuclear localization sequence, PKKKRKV132K(FITC)C [NLS(fluorescein-5-isothiocyanate [FITC])] bound via a thioether linkage [P-NLS(FITC)-GFLG-Mce6]). Furthermore, the induction of necrosis was more pronounced in cells exposed to conjugates containing both a nuclear localization sequence (NLS) and Mce6 bound by a degradable linker (P-NLS(FITC)-GFLG-Mce6). Caspase-independent mechanisms of cell death were identified in cells treated with nuclear-targeted conjugates possessing Mce6 attached using a nondegradable tether (HPMA copolymer-Mce6 conjugates containing Mce6 bound via a GG spacer and containing NLS(FITC) bound via a thioether linkage [P-NLS(FITC)-GG-Mce6]), whereas low levels of apoptosis and necrosis were detected in cells exposed to photoactivated nontargeted HPMA copolymer-Mce6 conjugates containing Mce6 coupled through a nondegradable spacer (HPMA copolymer-Mce6 conjugates containing Mce6 bound via GG linker [P-GG-Mce6]). Variations in gene expression were observed in cells on PDT. Specifically, HSP70 expression was solely detected in cells treated with P-GFLG-Mce6, whereas the loss of detection of several genes were observed in cells treated with P-NLS(FITC)-GFLG-Mce6. Variations in cellular responses on PDT using different HPMA copolymer-Mce6 conjugates will prove useful in the design of optimal HPMA copolymer PDT delivery systems.     

Non-Transitive Generalizations of Subdirect Products of Linearly Ordered Rings

Weakly associative lattice rings (wal-rings) are non-transitive generalizations of lattice ordered rings (l-rings). As is known, the class of l-rings which are subdirect products of linearly ordered rings (i.e. the class of f-rings) plays an important role in the theory of l-rings. In the paper, the classes of wal-rings representable as subdirect products of to-rings and ao-rings (both being non-transitive generalizations of the class of f-rings) are characterized and the class of wal-rings having lattice ordered positive cones is described. Moreover, lexicographic products of weakly associative lattice groups are also studied here.     

Morita Equivalence of Sketches

Equivalence of sketches S and T means the equivalence of their categories Mod_S and Mod_T of all Set-valued models. E. Vitale and the second author have characterized equivalence of limit-sketches by means of bimodels, where a bimodel for limit sketches S and T is a model of S in the category Mod_T. For general sketches, we show that an analogous result holds provided that Mod_T is substituted by a more complex category; e.g., in case of limit-coproduct sketches, that category is (Mod_T), the free product completion of Mod_T.     

Cr:Tm:Ho:YAG (2.1 μm) and Nd:YAG (1.444 μm) pulsed-laser lithotripsy of bile duct stones

The Nd:YAG (1.444 m) and Cr:Tm:Ho:YAG (2.1 m) free-running laser systems of the output energy of 300 mJ per pulse and repetition rate 1 Hz have been developed and used for bile duct stones fragmentation study in vitro. A total of 67 human bile duct stones of known sizes, collected from surgical sources were used in the experiments. Insensitivity of the stones fragmentation to the type of the laser used, and insensitivity of the fragmentation efficiency to the type of stone, was observed. No pathological changes of the tissue were observed for non-human soft tissue laser irradiation (in vitro) by 1, 2, and 5 pulses of the Cr:Th:Ho:YAG radiation of the fluency of 1.6 J/cm². The lasers are found to be good candidates for laser lithotripsy.     

On the efficiency of small-angle Čerenkov second harmonic generation in optical waveguides

It is well known that in the non-depleted pump approximation, the efficiency of a second harmonic generation (SHG) of a guided mode in a non-linear optical waveguide increases quadratically with the interaction length (P ₂ L ²), and linearly (P ₂ L) in the erenkov regime. The efficiency of the erenkov SHG in the waveguide with a non-linear substrate and linear guiding layer is known to be strongly peaked at a particular pump wavelength and a particular waveguide thickness, with the erenkov angle approaching zero. The known theory predicts an infinite efficiency value at the peak, however. In this contribution, a simple integral expression for the SHG efficiency in the erenkov regime is derived. For large erenkov angles and interaction lengths it yields the expected P ₂ L dependence, while in the limit of small erenkov angles the dependence is found to have the form of P L ^3/2, possessing also a finite value at the efficiency peak. The condition determining the accurate position of the efficiency peak in the waveguide thickness–pump wavelength plane is given, too.     

The possibility to use ‘energy plus transmutation’ set-up for neutron production and transport benchmark studies

The set-up ‘energy plus transmutation’, consisting of a thick lead target and a natural uranium blanket, was irradiated by relativistic proton beams with the energy from 0.7 GeV up to 2 GeV. Neutron field was measured in different places of this set-up using different activation detectors. The possibilities of using the obtained data for benchmark studies are analyzed in this paper. Uncertainties of experimental data are shown and discussed. The experimental data are compared with results of simulation with MCNPX code.      

A study of Ga layers on Si(1 0 0)-(2 × 1) by SR-PES: Influence of adsorbed water

Results for deposition and thermal annealing of gallium on the Si(1 0 0)-(2 × 1) surface achieved by synchrotron radiation photoelectron spectroscopy (SR-PES) and low energy electron diffraction (LEED) are presented. In addition to deposition of Ga on a clean surface, the influence of water adsorption on the arrangement of gallium atoms was also studied. The results on Ga deposition at a higher temperature (490 °C) are consistent with a Ga ad-dimer model showing equivalent bond arrangement of all Ga atoms for coverages up to 0.5 ML. The deposition onto a surface with adsorbed water at room temperature led to a disordered gallium growth. In this case gallium atoms bind to silicon dimers already binding fragments of adsorbed water. A subsequent annealing of these layers leads to a surface structure similar to the Ga-(2 × 2), however, it is less ordered, probably due to the presence of silicon oxides formed from water fragments.     

Controlled grafting of cellulose esters using SET‐LRP process

Here, we present the first example of application of single‐electron transfer living radical polymerization (SET‐LRP) process to a controlled grafting of cellulose esters, cellulose diacetate (CDA), and cellulose acetate butyrate (CAB). The cellulose ester macroinitiators with various functionality densities have been prepared by acylation of the backbones with 2‐bromoisobutyryl (BrIB) and dichloroacetyl (DCA) groups, respectively. Methacrylate monomers were polymerized using DCA‐functionalized macroinitiators in the presence of pentamethyldiethylene triamine as a ligand. At 30 °C, the reaction is rather slow, reaching about 10% conversion after 3 to 6 h of polymerization, whereas the higher temperature (60 °C) perceptibly speeds up the polymerization so that methyl methacrylate (MMA) conversion is ～30% after 5 h. Graft copolymers with random‐type and diblock‐type grafts having amphiphilic character were also synthesized. For acrylate grafting (BuA and t‐BuA), BrIB‐functionalized macroinitiators are more convenient in a combination with a low concentration of Cu(0) and Me₆TREN as a ligand and polymerization is detectably faster even at the lower temperature than that of MMA. Kinetic studies show “living” character of both the graftings. Important advantages of SET‐LRP, compared with classic ATRP, are (i) higher polymerization rate, (ii) lower extent of recombination of the growing grafts and (iii) negligible coloration of the products with catalytic residua, so that the prepared polymers do not require additional careful purification. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010