On the first order operators in bimodules

We analyse the structure of the first order operators in bimodules introduced by A. Connes. We apply this analysis to the theory of connections on bimodules generalizing thereby several proposals.Comment: 13 pages, AMSLaTe

On a graded q-differential algebra

Given a unital associatve graded algebra we construct the graded q-differential algebra by means of a graded q-commutator, where q is a primitive N-th root of unity. The N-th power (N>1) of the differential of this graded q-differential algebra is equal to zero. We use our approach to construct the graded q-differential algebra in the case of a reduced quantum plane which can be endowed with a structure of a graded algebra. We consider the differential d satisfying d to power N equals zero as an analog of an exterior differential and study the first order differential calculus induced by this differential.Comment: 6 pages, submitted to the Proceedings of the "International Conference on High Energy and Mathematical Physics", Morocco, Marrakech, April 200

Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2

AbstractProstaglandin endoperoxide synthase 2, also referred to as cyclooxygenase 2 (COX-2), is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Rat intestinal epithelial (RIE) cells were permanently transfected with a COX-2 expression vector oriented in the sense (RIE-S) or antisense (RIE-AS) direction. The RIE-S cells expressed elevated COX-2 protein levels and demonstrated increased adhesion to extracellular matrix (ECM) proteins. E-cadherin was undetectable in RIE-S cells, but was elevated in parental RIE (RIE-P) and RIE-AS cells. RIE-S cells were resistant to butyrate-induced apoptosis, had elevated BCL2 protein expression, and reduced transforming growth factor β2 receptor levels. The phenotypic changes involving both increased adhesion to ECM and inhibition of apoptosis were reversed by sulindac sulfide (a COX inhibitor). These studies demonstrate that overexpression of COX-2 leads to phenotypic changes in intestinal epithelial cells that could enhance their tumorigenic potential

UPLC-MS/MS Analysis of Dextromethorphan-O-demethylation Kinetics in Rat Brain Microsomes

Formation of dextrorphan (DXT) from dextromethorphan (DXM) has been widely used to assess cytochrome P450 2D (CYP2D) activity. Additionally, the kinetics of CYP2D activity have been well characterized in the liver microsomes. However, studies in brain microsomes are limited due to the lower microsomal content and abundance of CYP2D in the brain relative to the liver. In the present study, we developed a micro-scale enzymatic incubation method, coupled with a sensitive UPLC-MS/MS assay for the quantitation of the rate of DXT formation from DXM in brain microsomes. Rat brain microsomes were incubated with different concentrations of DXM for various times. The reaction was stopped, and the proteins were precipitated by the addition of acetonitrile, containing internal standard (d3-DXT). After centrifugation, supernatant (2 μL) was injected onto a UPLC, C18 column with gradient elution. Analytes were quantitated using triple-quadrupole MS/MS with electrospray ionization in positive ion mode. The assay, which was validated for accuracy and precision in the linear range of 0.25 nM to 100 nM DXT, has a lower limit of quantitation of 0.125 fmol on the column. Using our optimized incubation and quantitation methods, we were able to reduce the incubation volume (25 μL), microsomal protein amount (5 μg), and incubation time (20 min), compared with reported methods. The method was successfully applied to estimation of the Michaelis-Menten (MM) kinetic parameters of dextromethorphan-O-demethylase activity in the rat brain microsomes (mean ± SD, n = 4), which showed a maximum velocity of 2.24 ± 0.42 pmol/min/mg and a MM constant of 282 ± 62 μM. It is concluded that by requiring far less biological material and time, our method represents a significant improvement over the existing techniques for investigation of CYP2D activity in rat brain microsomes

Peroxisome Proliferator-Activated Receptors and Progression of Colorectal Cancer

The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. These receptors are also ligand-dependent transcription factors responsible for the regulation of cellular events that range from glucose and lipid homeostases to cell differentiation and apoptosis. The importance of these receptors in lipid homeostasis and energy balance is well established. In addition to these metabolic and anti-inflammatory properties, emerging evidence indicates that PPARs can function as either tumor suppressors or accelerators, suggesting that these receptors are potential candidates as drug targets for cancer prevention and treatment. However, conflicting results have emerged regarding the role of PPARs on colon carcinogenesis. Therefore, further investigation is warranted prior to considering modulation of PPARs as an efficacious therapy for colorectal cancer chemoprevention and treatment

Hydrodynamic lift of vesicles under shear flow in microgravity

The dynamics of a vesicle suspension in a shear flow between parallel plates has been investigated under microgravity conditions, where vesicles are only submitted to hydrodynamic effects such as lift forces due to the presence of walls and drag forces. The temporal evolution of the spatial distribution of the vesicles has been recorded thanks to digital holographic microscopy, during parabolic flights and under normal gravity conditions. The collected data demonstrates that vesicles are pushed away from the walls with a lift velocity proportional to $\dot{\gamma} R^3/z^2$ where $\dot{\gamma}$ is the shear rate, $R$ the vesicle radius and $z$ its distance from the wall. This scaling as well as the dependence of the lift velocity upon vesicle aspect ratio are consistent with theoretical predictions by Olla [J. Phys. II France {\bf 7}, 1533--1540 (1997)].Comment: 6 pages, 8 figure