Probing the interaction of hydrogen chloride with low-temperature water ice surfaces using thermal and electron-stimulated desorption

The interaction and autoionization of HCl on low-temperature (80-140 K) water ice surfaces has been studied using low-energy (5-250 eV) electron-stimulated desorption (ESD) and temperature programmed desorption (TPD). There is a reduction of H(+) and H(2)(+) and a concomitant increase in H(+)(H(2)O)(n=1-7) ESD yields due to the presence of submonolayer quantities of HCl. These changes are consistent with HCl induced reduction of dangling bonds required for H(+) and H(2)(+) ESD and increased hole localization necessary for H(+)(H(2)O)(n=1-7) ESD. For low coverages, this can involve nonactivated autoionization of HCl, even at temperatures as low as 80 K; well below those typical of polar stratospheric cloud particles. The uptake and autoionization of HCl is supported by TPD studies which show that for HCl doses ≤0.5 ± 0.2 ML (ML = monolayer) at 110 K, desorption of HCl begins at 115 K and peaks at 180 K. The former is associated with adsorption of a small amount of molecular HCl and is strongly dependent on the annealing history of the ice. The latter peak at 180 K is commensurate with desorption of HCl via recombinative desorption of solvated separated ion pairs. The activation energy for second-order desorption of HCl initially in the ionized state is 43 ± 2 kJ/mol. This is close to the zero-order activation energy for ice desorption.     

Breast Cancer Stem Cell Potent Copper(II)–Non‐Steroidal Anti‐Inflammatory Drug Complexes

The breast cancer stem cell (CSC) potency of a series of copper(II)–phenanthroline complexes containing the nonsteroidal anti‐inflammatory drug (NSAID), indomethacin, is reported. The most effective copper(II) complex in this series, 4 , selectivity kills breast CSC‐enriched HMLER‐shEcad cells over breast CSC‐depleted HMLER cells. Furthermore, 4 reduces the formation, size, and viability of mammospheres, to a greater extent than salinomycin, a potassium ionophore known to selectively inhibit CSCs. Mechanistic studies revealed that the CSC‐specificity observed for 4 arises from its ability to generate intracellular reactive oxygen species (ROS) and inhibit cyclooxygenase‐2 (COX‐2), an enzyme that is overexpressed in breast CSCs. The former induces DNA damage, activates JNK and p38 pathways, and leads to apoptosis.     

Development of a receptor-based microplate assay for the detection of beta-lactam antibiotics in different food matrices

The penicillin-binding protein PBP 2x* from Streptococcus pneumoniae has been utilised to develop a novel microplate assay for the detection and determination of penicillins and cephalosporins with intact beta-lactam structure in milk, bovine and porcine muscle juice, honey and egg. In the assay, the receptor protein is immobilised to a microplate in the first step. To each sample a bifunctional reagent is added, with ampicillin and digoxigenin as functional groups (DIG-AMPI). The amount of bifunctional reagent, which is bound via its ampicillin part to the receptor protein, decreases with increasing beta-lactam concentration in the sample. The detection step uses anti-digoxigenin F(ab) fragments marked with horseradish peroxidase. The more bifunctional reagent is bound to the receptor protein, the more antibody fragments are bound via the digoxigenin part of the reagent. A maximum colour development with tetramethylbenzidine as chromogen for the peroxidase reaction is achieved, when no beta-lactam residues are present. A fractional factorial design was applied to detect chemometrically effects and interactions of the assay parameters. For optimisation of the significant parameters a Box-Behnken design was used. The assay has been developed for various food matrices as screening test with the option for a quantitative assay, when the identity of the residual beta-lactam is known (e.g. elimination studies). Cefoperazon, cefquinome, cefazolin, cloxacillin, ampicillin and benzylpenicillin could be detected at levels corresponding to 1/2 EU maximum residue limit (MRL) in milk, meat juice from muscle tissue of different species, egg and honey (where applicable) without needing lengthy and elaborate sample pre-treatment. Matrix calibration curves are presented, which show that quantitative analyses are possible.     

SUBCELLULAR LOCALIZATION OF HEMATOPORPHYRIN DERIVATIVE IN BLADDER TUMOR CELLS IN CULTURE

Mitochondria have been implicated as a primary subcellular site of porphyrin localization and photodestruction. However, other organelles including the cell membrane, lysosomes and nucleus have been shown to be damaged by hematoporphyrin derivative (HpD) photosensitized destruction as well. In this study we attempted to follow the translocation of the fluorescent components of HpD in human bladder tumor cells (MGH-U1) in culture to determine whether specific subcellular localization occurs over time. Following a 30 min exposure to HpD the cellular fluorescence was examined immediately and 1, 2, 4, and 24 h after HpD removal using fluorescence microscopy and an interactive laser cytometer. The in vitro translocation of dye appeared to be fairly rapid with fluorescence present at the cell membrane and later (1-2 h) within a perinuclear area of the cytoplasm. To determine whether HpD had become concentrated into a specific subcellular organelle, these fluorescence distribution patterns were compared with fluorescent marker dyes specific for mitochondria, endoplasmic reticulum and other membranous organelles. The HpD fluorescence did not appear to be as discrete as the dyes specific for mitochondria or endoplasmic reticulum but appeared similar to the diffuse cytomembrane stain. Finally, the interaction between the fluorescent components of HpD and the cellular constituents was evaluated using a "fluorescence redistribution after photobleaching" technique. The results indicated that the mean lateral diffusion for HpD in MGH-U1 cells was 1.05 x 10(-8) cm2/s, a rate closer to that of lipid diffusion (10(-8)) than that of protein diffusion (10(-10)).(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective methodologies for the synthesis of biologically active piperidinic compounds

The synthesis of optically active substituted piperidines has been achieved by using four different methodologies. The first one is an intramolecular nucleophilic displacement of activated alcohol moieties that was used to build up the piperidine ring of (-)-prosophylline and (-)-slaframine, and the second one is a ring-closing metathesis of unsaturated amines which was employed in the synthesis of (+)-sedamine and 4a,5-dihydrostreptazoline. The third methodology is the alpha-functionalization of N-Boc piperidines which was particularly useful in the synthesis of argatroban, and the fourth one is a ring expansion of prolinols to 3-chloropiperidines or 3-hydroxypiperidines which was utilized to synthesize (-)-paroxetine, (-)-pseudoconhydrine, the piperidine ring of (-)-velbanamine and (+)-zamifenacin.     

Molecular damage in bi-isonicotinic acid adsorbed on rutile TiO2(1 1 0)

Here we present the characteristic signatures in X-ray absorption and photoemission spectroscopy for molecular damage in adsorbed monolayers of bi-isonicotinic acid on a rutile TiO₂(1 1 0) surface. Bi-isonicotinic acid is the anchor ligand through which many important inorganic complexes are bound to the surface of TiO₂ in dye-sensitized solar cells. The nature of the damage caused by excessive heating of the adsorbed monolayer is consistent with splitting the molecule into two adsorbed isonicotinic acid molecular fragments. The effect on the lowest unoccupied molecular orbitals (involved in electron transfer in the molecule) can be understood in terms of the adsorption geometry of the reaction products and their nearest neighbor interactions.     

A convergent approach toward phoslactomycins and leustroducsins

Synthetic studies devoted to the development of a convergent approach toward phoslactomycins and leustroducsins, a family of natural products inhibitors of serine/threonine phosphatase 2A, are reported. A formal synthesis of phoslactomycin B was achieved in which the key steps are a [2,3]-Wittig rearrangement to control the C4 and C5 stereocenters, a diastereoselective addition of an acetylenic Grignard reagent to an α-alkoxy ketone to create the C8 tertiary alcohol, and a relay ring-closing metathesis to construct the α,β-unsaturated δ-lactone. In this approach, all the stereocenters originate, either directly or indirectly, from catalytic enantioselective reductions of acetylenic ketones.     

Conceptualizing the curriculum enactment process in mathematics education

This article explores the following question: What does it mean to enact curriculum? In order to do so, it offers a conceptualization of the enacted curriculum and situates it within a curriculum policy, design, and enactment system. The system depicts the formal and operational domains in which curricular aims and objectives are developed and curriculum plans formulated and enacted. The authors situate the enacted mathematics curriculum in the operational part of the system and define it as the interactions between teachers and students around mathematical tasks of a lesson and collection of lessons, but argue that understanding what it means to enact curriculum involves examining the many places within the system that curricular elements are translated and transformed. The authors describe each of the articles in this special issue with respect to the framework.