Variation of strand break yield for plasmid DNA irradiated with high-Z metal nanoparticles.

PURPOSE: Poly(ADP-ribose) polymerase (PARP) plays an important role in DNA repair, and PARP inhibitors can enhance the activity of DNA-damaging agents in vitro and in vivo. AG014699 is a potent PARP inhibitor in phase II clinical development. However, the range of therapeutics with which AG014699 could interact via a DNA-repair based mechanism is limited. We aimed to investigate a novel, vascular-based activity of AG014699, underlying in vivo chemosensitization, which could widen its clinical application. EXPERIMENTAL DESIGN: Temozolomide response was analyzed in vitro and in vivo. Vessel dynamics were monitored using "mismatch" following the administration of perfusion markers and real-time analysis of fluorescently labeled albumin uptake in to tumors established in dorsal window chambers. Further mechanistic investigations used ex vivo assays of vascular smooth muscle relaxation, gut motility, and myosin light chain kinase (MLCK) inhibition. RESULTS: AG014699 failed to sensitize SW620 cells to temozolomide in vitro but induced pronounced enhancement in vivo. AG014699 (1 mg/kg) improved tumor perfusion comparably with the control agents nicotinamide (1 g/kg) and AG14361 (forerunner to AG014699; 10 mg/kg). AG014699 and AG14361 relaxed preconstricted vascular smooth muscle more potently than the standard agent, hydralazine, with no impact on gut motility. AG014699 inhibited MLCK at concentrations that relaxed isolated arteries, whereas AG14361 had no effect. CONCLUSION: Increased vessel perfusion elicited by AG014699 could increase tumor drug accumulation and therapeutic response. Vasoactive concentrations of AG014699 do not cause detrimental side effects to gut motility and may increase the range of therapeutics with which AG014699 could be combined with for clinical benefi

Listening to lanthanide complexes: Determination of the intrinsic luminescence quantum yield by nonradiative relaxation

The photophysical properties of lanthanide complexes have been studied extensively; however, fundamental parameters such as the intrinsic quantum yield as well as radiative and nonradiative decay rates are difficult or even impossible to measure experimentally. Herein, a photoacoustic (PA) method is proposed to determine the intrinsic quantum yield of lanthanide complexes with lifetimes in the order of milliseconds. This method is used to determine the intrinsic quantum yields for europium (III)-containing metallomesogens as well as terbium(III) complexes. The results show that the PA signal is sensitive to both the lifetime and the ratio of the fast-to-slow heat component of the samples. It is found that there is an efficient ligand sensitization and a moderate intrinsic quantum yield for the complexes. The intrinsic quantum yield of Eu3+ in the metallomesogens exhibits an obvious increase upon the isotropic liquid to smectic A transition. The proposed PA method is quite simple, and con contribute to a clearer understanding of the photophysical processes in luminescent lanthanide complexes.

Do minimum wages raise employment? Evidence from the US retail-trade sector

This paper examines the impact of minimum wages on earnings and employment in selected branches of the retail-trade sector, 1990-2005, using county-level data on employment and a panel regression framework that allows for county-specific trends in sectoral outcomes. We focus on specific subsectors within retail trade that are identified as particularly low-wage. We find little evidence of disemployment effects once we allow for geographic-specific trends. Indeed, in many sectors the evidence points to modest (but robust) positive employment effects. (C) 2009 Elsevier B.V. All rights reserved.

Ownership structure, organisational flexibility and store performance in retail chains.

Drawing on agency and flexible capability perspectives, the authors develop a theoretical framework explaining the impact of ownership structure on organisational flexibility and store performance in retail chains. The researchers argue that franchised stores attract more entrepreneurial managers with more flexible capabilities and they have a stronger incentive to align their flexible capabilities with the demands of the business environment. A sample of 105 franchised and company-owned stores of an optical retail chain is used to test the hypotheses. Furthermore, the study found strong support for the hypotheses that 'Franchised stores have a higher structural flexibility than company-owned stores', but only weak support for operational and strategic flexible capabilities. Furthermore, in line with the study's theoretical framework, it has been found that in a highly turbulent business environment, franchised stores perform better than company-owned stores. The paper concludes with a discussion of the implications for theory development and management of ownership structures in retail chains.

Dioxygenase-catalysed cis-dihydroxylation of meta-substituted phenols to yield cyclohexenone cis-diol and derived enantiopure cis-triol metabolites

cis-Dihydroxylation of meta-substituted phenol (m-phenol) substrates, to yield the corresponding cyclohexenone cis-diol metabolites, was catalysed by arene dioxygenases present in mutant and recombinant bacterial strains. The presence of cyclohexenone cis-diol metabolites and several of their cyclohexene and cyclohexane cis-triol derivatives was detected by LC-TOFMS analysis and confirmed by NMR spectroscopy. Structural and stereochemical analyses of chiral ketodiol bioproducts, was carried out using NMR and CD spectroscopy and stereochemical correlation methods. The formation of enantiopure cyclohexenone cis-diol metabolites is discussed in the context of postulated binding interactions of the m-phenol substrates at the active site of toluene dioxygenase (TDO).

Multiple site dioxygenase-catalysed cis-dihydroxylation of polycyclic azaarenes to yield a new class of bis-cis-diol metabolites

The enhanced stability of new mono-cis-dihydrodiol bacterial metabolites of tricyclic azaarenes has facilitated the dioxygenase-catalysed formation and isolation of the corresponding bis-cis-dihydrodiols (cis-tetraols) and a three step chemoenzymatic route to the derived arene oxide mammalian metabolites.

Reaction of elemental chalcogens with imidazolium acetates to yield imidazole-2-chalcogenones: direct evidence for ionic liquids as proto-carbenes

Mechanistic analysis of the reaction between elemental sulfur or selenium and 1,3-dialkylimidazolium acetate ionic liquids, in the absence of an external base or solvent, affords evidence for the equilibrium presence of carbene species in these ionic liquids. It demonstrates the potential to control, through anion selection, the concentration of carbene in stable ionic liquids.

The role of higher-order chromatin structure in the yield and distribution of DNA double-strand breaks in cells irradiated with X-rays or alpha-particles

Purpose: To determine whether the non-random distributions of DNA double-strand breaks in cells observed after alpha-particle irradiation are related to the higher-order structure of the chromatin within the nucleus.