Modifications at the C-Terminus To Improve Pyrrole−Imidazole Polyamide Activity in Cell Culture

Pyrrole−imidazole (Py-Im) hairpin polyamides are a class of small molecule DNA minor groove binding compounds that have been shown to modulate endogenous gene expression in cell culture. Gene regulation by polyamides requires efficient cellular uptake and nuclear localization properties for candidate compounds. To further optimize Py-Im polyamides for enhanced potency in cell culture, a focused library of polyamides possessing various modifications at the C-terminus was synthesized and tested. Comparison of polyamide biological activity in two cell lines revealed tolerance for structural modifications and agreement in activity trends between cell lines. The use of an oxime linkage between the polyamide and an aromatic functionality on the C-terminus resulted in a ~20-fold increase in the potency of polyamides targeted to the androgen response element (ARE) in LNCaP cells by measuring AR-activated PSA expression

A sectoral analysis of Italy's development : 1861 -2010

Italy‘s economic growth over its 150 years of unified history did not occur at a steady pace nor was it balanced across sectors. Relying on an entirely new input (labour and capital) database by us built and presented in the Appendix, together with new Banca d‘Italia estimates of GDP by sector, this paper evaluates the different labour productivity growth trends within the Italian economy‘s sectors, as well as the contribution of structural change to productivity growth. Italy‘s performance is then set in an international context: a comparison of sectoral labour productivity growth rates and levels within a selected sample of countries (UK, US, Germany, Japan, India) allows us to better time, quantify and gauge the causes of Italy‘s catching-up process and subsequent more recent slowdown. Finally, the paper analyses the proximate sources of Italy‘s growth, relative to the other countries, in a standard growth accounting framework, in an attempt also to disentangle the contribution of both total factor productivity growth and capital deepening to the country‘s labour productivity dynamics

Solving variational inequalities with Stochastic Mirror-Prox algorithm

In this paper we consider iterative methods for stochastic variational inequalities (s.v.i.) with monotone operators. Our basic assumption is that the operator possesses both smooth and nonsmooth components. Further, only noisy observations of the problem data are available. We develop a novel Stochastic Mirror-Prox (SMP) algorithm for solving s.v.i. and show that with the convenient stepsize strategy it attains the optimal rates of convergence with respect to the problem parameters. We apply the SMP algorithm to Stochastic composite minimization and describe particular applications to Stochastic Semidefinite Feasability problem and Eigenvalue minimization