YOYO as a Dye to Track Penetration of LK15 DNA Complexes in Spheroids: Use and Limits

To elucidate the reasons underlying the poor penetration of non-viral vectors in tissues, relating transport properties to physico-chemical parameters of vectors may be crucial. These properties can be influenced by the presence of multiples labels that are used. Therefore utilizing a vector with minimum of labels preferably not more than one is important to studying penetration in tissues. The cell impermeant bisintercalating dye YOYO-1 was found suitable to both monitor the formation of complexes between DNA and an amphipathic peptide LK15 and, to track their penetration in HCT116 spheroids by confocal microscopy. The results revealed a limited decrease of fluorescence ascribed to the high affinity of YOYO-1 to bind DNA. The residual fluorescence of complexes can be exploited to monitor penetration into spheroids, after correction for YOYO-1 attenuation, and to revealing hyaluronidase-induced reduced binding. Hence high affinity dyes such as YOYO-1 with inefficiently quenched fluorescence may be important to establish a relation between novel medicines characteristics and penetration in tissues.     

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

Background  

Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.     

Market neutral portfolios

In this paper we consider the problem of constructing a market neutral portfolio. This is a portfolio of financial assets that (ideally) exhibits performance independent from that of an underlying market as represented by a benchmark index. We formulate this problem as a mixed-integer nonlinear program, minimising the absolute value of the correlation between portfolio return and index return. Our model is a flexible one that incorporates decisions as to both long and short positions in assets. Computational results, obtained using the software package Minotaur, are given for constructing market neutral portfolios for eleven different problem instances derived from universes defined by S&P international equity indices. We also compare our approach against an alternative approach based on minimising the absolute value of regression slope (the zero-beta approach).     

Index Funds—Construction and Performance Measurement

An index fund is an investment vehicle which mimics a stock-market index and thus exhibits market risk only. Fund managers can passively invest in index funds and concentrate on actively managing the remainder of their funds. This paper looks in detail at the use of statistical selection methods in the construction of these funds. The measurement of the ability of these funds to track the underlying index is examined. Emphasis is placed on the relevance of the horizon of the investor to the choice of measure of tracking error. Four different methods of index-fund construction are described and applied to Japanese stock-market data. The tracking abilities of the constructed funds, both in and out of sample, are compared and contrasted.