Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling

In this report, inhibitors of the gamma-secretase enzyme have been exploited to characterize the antiproliferative relationship between target inhibition and cellular responses in Notch-dependent human T cell acute lymphoblastic leukemia (T-ALL) cell lines. Inhibition of gamma-secretase led to decreased Notch signaling, measured by endogenous NOTCH intracellular domain (NICD) formation, and was associated with decreased cell viability. Flow cytometry revealed that decreased cell viability resulted from a G(0)/G(1) cell cycle block, which correlated strongly to the induction of apoptosis. These effects associated with inhibitor treatment were rescued by exogenous expression of NICD and were not mirrored when a markedly less active enantiomer was used, demonstrating the gamma-secretase dependency and specificity of these responses. Together, these data strengthen the rationale for using gamma-secretase inhibitors therapeutically and suggest that programmed cell death may contribute to reduction of tumor burden in the clinic.     

"Magic rod" rotaxanes: the hydrogen bond-directed synthesis of molecular shuttles under thermodynamic control

[reaction: see text] Peptide [2]- and [3]rotaxanes are assembled in high yields under thermodynamic control using hydrogen bonding interactions and reversible cross olefin metathesis.     

Global isochrons of a planar system near a phaseless set with saddle equilibria

Given an attracting periodic orbit of a system of ordinary differential equations, one can assign an asymptotic phase to any initial condition that approaches such a periodic orbit. All initial conditions with the same asymptotic phase lie on what is known as an isochron. Isochrons foliate the basin of attraction, and may have intriguing geometric properties. We present here two cases of a planar vector field for which the basin boundary — also referred to as the phaseless set — contains saddle equilibria and their stable manifolds. A continuation-based approach, in combination with Poincaré compactification when the basin is unbounded, allows us to compute isochrons accurately and visualise them as smooth curves to clarify their overall geometry.     

IRAS investigation of a catenane adsorption on Au(1 1 1)

The adsorption of a benzylic amide [2]catenane on a Au(1 1 1) single crystal has been studied using infrared reflection absorption spectroscopy. The evolution of the infrared spectra during catenane deposition at different temperatures of the gold substrate (300 and 90 K) has been compared. Evidence of the catenane deformation upon chemisorption have been found at 300 K only. At 90 K the catenane is weakly adsorbed without any deformation.