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

Magnetization of undoped 2-leg S = 1/2 spin ladders in La4Sr10Cu24O41

Magnetization data of single crystalline La4Sr10Cu24O41 are presented. In this compound, doped spin chains and undoped spin ladders are realized. The magnetization, at low temperatures, is governed by the chain subsystem with a finite interchain coupling which leads to short range antiferromagnetic spin correlations. At higher temperatures, the response of the chains can be estimated in terms of a Curie-Weiss law. For the ladders, we apply the low-temperature approximation for a S=1/2 2-leg spin ladder by Troyer et al.Comment: 2 pages, 2 figure

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

The Occurrence of Bioactive Micromonosporae in Aquatic Habitats of the Sunshine Coast in Australia

Screening strategies based on the ecological knowledge of antibiotic producing microorganisms and their roles in the natural environment are being increasingly employed in the search for novel antibiotic agents. Micromonosporae are common inhabitants of aquatic habitats and have proved to be a continuing source of novel bioactive compounds including antibacterial and antitumor agents. The ecological distribution and frequency of bioactive micromonosporae in Sunshine Coast region aquatic habitats were studied through a range of selective isolation procedures designed to negatively select against the isolation of unwanted microbial taxa commonly associated with marine environments. It was revealed that bioactive compound producing species of micromonosporae were present in the aquatic habitats of the Sunshine Coast region in Australia

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

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

An inherently parallel Monte Carlo linear systems solver applied to neutron diffusion equations

Linear solvers are often used to solve neutron diffusion problems. These tools have two significant shortcomings. First, parallel implementations provide only a modest speedup. The operations cannot be divided cleanly between processors. Second, for large matrices they can be very slow. Our primary goal is to find a new method for solving linear systems which reduces the impact of these two problems. In this study, we consider a different kind of approach. We employ a Monte Carlo algorithm in two dimensions to solve our linear systems probabilistic ally. We develop our probabilistic model and describe the formulation of our linear system. We also discuss our random sampling technique in some detail. We tally our solutions for both the forward and adjoint problems using path length and last event estimators. Computational results are compared to analytic and numerical benchmark solutions for three metrics: accuracy, convergence, and efficiency. The results detailed herein indicate that the method we have developed can be competitive with common linear solvers. We develop an on-the-fly algorithm as well, which is intended to make more efficient use of our computing resources. While this algorithm exhibits longer run-times, it is far less taxing on the system memory