The role of hydrophobic amino acid grafts in the enhancement of membrane-disruptive activity of pH-responsive pseudo-peptides

pH-responsive polymers have been synthesised by grafting l-valine (PV-75), l-leucine (PL-75) and l-phenylalanine (PP-75) onto the pendant carboxylic acid moieties of a pseudo-peptide, poly(l-lysine iso-phthalamide), at a stoichiometric degree of substitution of 75 mol%. The effect of such modification on the pH-, concentration- and time-dependent cell membrane-disruptive activity of the grafted polymers has been investigated using a haemolysis model. At 0.025 mg mL(−1), the grafted polymers were almost non-haemolytic at pH 7.4, but mediated considerable membrane lysis after 60 min in the pH range characteristic of early endosomes, which ranked in the order: PP-75 > PL-75 > PV-75 > poly(l-lysine iso-phthalamide). PP-75 was 35-fold more lytic on a molar basis than the membrane-lytic peptide melittin. With increasing concentration, the grafted polymers showed an increased ability to lyse cell membranes and caused noticeable membrane disruption at physiological pH. The mechanism of the polymer-mediated membrane destabilisation has been investigated. The in-vitro cytotoxicity of the grafted polymers has been assessed using a propidium iodide fluorescence assay. It has been demonstrated by confocal microscopy that the grafted polymers can induce a significant release of endocytosed materials into the cytoplasm of HeLa cells, which is a feature critical for drug delivery applications

Single-crystal growth and dependences on the hole concentration and magnetic field of the magnetic ground state in the edge-sharing CuO2_2 chain system Ca2+x_{2+x}Y2−x_{2-x}Cu5_5O10_{10}

We have succeeded in growing large-size single-crystals of Ca$_{2+x}$Y$_{2-x}$Cu$_5$O$_{10}$ with $0 \le x \le 1.67$ and measured the magnetic susceptibility, specific heat and magnetization curve, in order to study the magnetic ground state in the edge-sharing CuO$_2$ chain as a function of hole concentration and magnetic field. In $0 \le x \le 1.3$, it has been found that an antiferromagnetically ordered phase with the magnetic easy axis along the b-axis is stabilized and that a spin-flop transition occurs by the application of magnetic fields parallel to the b-axis. The antiferromagnetic transition temperature decreases with increasing $x$ and disappears around $x =$ 1.4. Alternatively, a spin-glass phase appears around $x = 1.5$. At $x = 1.67$ where the hole concentration is $\sim$ 1/3 per Cu, it appears that a spin-gap state is formed owing to the formation of spin-singlet pairs. No sign of the coexistence of an antiferromagnetically ordered state and a spin-gap one suggested in Ca$_{1-x}$CuO$_2$ has been found in Ca$_{2+x}$Y$_{2-x}$Cu$_5$O$_{10}$.Comment: 13 pages, 12 figures, 1 tabl

Dynamic Spin Response for Heisenberg Ladders

We employ the recently proposed plaquette basis to investigate static and dynamic properties of isotropic 2-leg Heisenberg spin ladders. Simple non-interacting multi-plaquette states provide a remarkably accurate picture of the energy/site and dynamic spin response of these systems. Insights afforded by this simple picture suggest a very efficient truncation scheme for more precise calculations. When the small truncation errors are accounted for using recently developed Contractor Renormalization techniques, very accurate results requiring a small fraction of the computational effort of exact calculations are obtained. These methods allow us to determine the energy/site, gap, and spin response of 2x16 ladders. The former two values are in good agreement with density matrix renormalization group results. The spin response calculations show that nearly all the strength is concentrated in the lowest triplet level and that coherent many-body effects enhance the response/site by nearly a factor of 1.6 over that found for 2x2 systems.Comment: 9 pages with two enclosed postscript figure

SOME RESULTS ON THE DESIGN OF EXPERIMENTS FOR COMPARING UNREPLICATED TREATMENTS

In early generation variety trials, large numbers of new varieties may be compared, and little seed is usually available for each variety. A so-called unreplicated trial has each new variety on just one plot at a site, but includes several (often around 5) replicated check or control (or standard) varieties. The total proportion of check plots is usually between 10% and 20%. The aim of the trial is to choose some (around 1/3) good performing varieties to go on for further testing, rather than precise estimation of their mean yield. Now that spatial analyses of data from field experiments are becoming more common, there is interest in an efficient layout of an experiment given a proposed spatial analysis. Some possible design criteria are discussed, and efficient layouts under spatial dependence are considered

Spin Dynamics in the Magnetic Chains Arrays of Sr14Cu24O41: a Neutron Inelastic scattering Investigation

Below about 150 K, the spin arrangement in the chain arrays of Sr14Cu24O41 is shown to develop in two dimensions (2D). Both the correlations and the dispersion of the observed elementary excitations agree well with a model of interacting dimers. Along the chains, the intra- and inter-dimer distances are equal to 2 and about 3 times the distance (c) between neighboring Cu ions. While the intra-dimer coupling is J about 10 meV, the inter-dimer couplings along and between the chains are of comparable strenght, J// about -1.1 meV and Jperp about 1.7 meV, respectively. This remarkable 2D arrangement satisfies the formal Cu valence of the undoped compound. Our data suggest also that it is associated with a relative sliding of one chain with respect to the next one, which, as T decreases, develops in the chain direction. A qualitative analysis shows that nearest inter-dimer spin correlations are ferromagnetic, which, in such a 2D structure, could well result from frustration effects.Comment: 4 pages, 5 figures, submitted to Phys.Rev.B, date of receipt 29 June 199

Pathologies in International Policy Transfer:The Case of the OECD Tax Transparency Initiative

ABSTRACT The importance of international organizations to the development and diffusion of international policy norms is widely recognized but is increasingly tempered by an appreciation of the pathologies of policy transfer. Using a case study of the OECD’s campaign to promote transparency in global tax affairs, this paper identifies a new and relatively distinctive form of dysfunctional policy transfer. Specifically it argues that international organizations face bureaucratic incentives to promote weak or lowest common denominator standards in order to maximize their prospects of brokering successful international agreements. However the paper also notes that while international organizations may have a short-term interest in promoting weak standards, their longer-term legitimacy is often tied to the effectiveness of the standards they promote. It is argued that this dynamic often leads to incremental policy change

Dynamical Spin Response Functions for Heisenberg Ladders

We present the results of a numerical study of the 2 by L spin 1/2 Heisenberg ladder. Ground state energies and the singlet-triplet energy gaps for L = (4-14) and equal rung and leg interaction strengths were obtained in a Lanczos calculation and checked against earlier calculations by Barnes et al. (even L up to 12). A related moments technique is then employed to evaluate the dynamical spin response for L=12 and a range of rung to leg interaction strength ratios (0 - 5). We comment on two issues, the need for reorthogonalization and the rate of convergence, that affect the numerical utility of the moments treatment of response functions.Comment: Revtex, 3 figure

Stability of the Haldane phase in anisotropic magnetic ladders

We have considered the properties of anisotropic two-leg ladder models with S=1/2 or S=1 spins on the rungs, using White's density matrix renormalization group method. We have generalized the method by taking into account the symmetries of the model in order to reduce the dimensions of the matrix to be diagonalized, thereby making possible to consider more states. The boundaries in the parameter space of the extended region, where the Haldane phase exists, are estimated.Comment: 19 pages, 5 figure