Synthesis and antibacterial profiles of targeted triclosan derivatives

There is an ongoing urgent need for new targeted antibacterial com pounds with novel mechanisms of action for the treatment of infections caused by bacteria that are resistant to currently available materials. Since the expression of glycosidase enzymes within bacteria is unequally distributed, glycoside derivatives of antibacterial agents offer potential as targeted prodrugs for bacterial infections. Herein we report the synthesis and characterisation of four α-D-glycopyranosides and three β-D-glycopyranosides of the broad antibacterial agent triclosan, in generally good synthetic yields, and with excellent purities. Each glycoside was analysed to determine its ability to inhibit the growth of a wide range of Gram-negative and Gram-positive organisms, including many of clinical significance. All of the triclosan glycosides that were synthesized demonstrated antibacterial activity against many of the organisms that were examined. For example, β-galactoside (3a) and α-arabinoside (3c) had MIC values of 0.5 μg/ ml for several strains of S. aureus and S. haemolyticus. The triclosan glycosides were also generally found to be more water soluble and much more selective than the underivatized triclosan, making them ideal both for the targeted inhibition of bacterial growth and as agents for the selective recovery of bacteria from mixed cultures. In the latter case, two Bacillus strains could be identified from various strains of Bacillus and Staphylococcus after inoculation onto Nutri ent Agar No. 2 with 0.25 μg/ ml tri closan-α-D-glucopyranoside (3e). This glucoside may, therefore, be of use for the isolation and identification of the foodpoisoing organism Bacillus cereus

Generic theory of colloidal transport

We discuss the motion of colloidal particles relative to a two component fluid consisting of solvent and solute. Particle motion can result from (i) net body forces on the particle due to external fields such as gravity; (ii) slip velocities on the particle surface due to surface dissipative phenomena. The perturbations of the hydrodynamic flow field exhibits characteristic differences in cases (i) and (ii) which reflect different patterns of momentum flux corresponding to the existence of net forces, force dipoles or force quadrupoles. In the absence of external fields, gradients of concentration or pressure do not generate net forces on a colloidal particle. Such gradients can nevertheless induce relative motion between particle and fluid. We present a generic description of surface dissipative phenomena based on the linear response of surface fluxes driven by conjugate surface forces. In this framework we discuss different transport scenarios including self-propulsion via surface slip that is induced by active processes on the particle surface. We clarify the nature of force balances in such situations.Comment: 22 pages, 1 figur

Phoretic Motion of Spheroidal Particles Due To Self-Generated Solute Gradients

We study theoretically the phoretic motion of a spheroidal particle, which generates solute gradients in the surrounding unbounded solvent via chemical reactions active on its surface in a cap-like region centered at one of the poles of the particle. We derive, within the constraints of the mapping to classical diffusio-phoresis, an analytical expression for the phoretic velocity of such an object. This allows us to analyze in detail the dependence of the velocity on the aspect ratio of the polar and the equatorial diameters of the particle and on the fraction of the particle surface contributing to the chemical reaction. The particular cases of a sphere and of an approximation for a needle-like particle, which are the most common shapes employed in experimental realizations of such self-propelled objects, are obtained from the general solution in the limits that the aspect ratio approaches one or becomes very large, respectively.Comment: 18 pages, 5 figures, to appear in European Physical Journal

Periodic and Quasiperiodic Motion of an Elongated Microswimmer in Poiseuille Flow

We study the dynamics of a prolate spheroidal microswimmer in Poiseuille flow for different flow geometries. When moving between two parallel plates or in a cylindrical microchannel, the swimmer performs either periodic swinging or periodic tumbling motion. Although the trajectories of spherical and elongated swimmers are qualitatively similar, the swinging and tumbling frequency strongly depends on the aspect ratio of the swimmer. In channels with reduced symmetry the swimmers perform quasiperiodic motion which we demonstrate explicitely for swimming in a channel with elliptical cross section

Litigating Terror in The Sinai After The Egyptian Spring Revolution: Should States Be Liable to Foreign Investors for Failure to Prevent Terrorist Attacks?

The ambiguity of the due diligence standard of the Full Protection and Security obligation in investment treaties persists to this day. A recent ICSID tribunal found a developing state liable for breaching the Full Protection and Security obligation due to its inability to protect a foreign investment against terrorist attacks in a remote deserted area. In this article, we analytically criticize the Ampal v. Egypt arbitral award against the comprehensive factual matrix behind the case. Based on our criticism of Ampal, we argue that developing states should not be liable for failing to prevent or stop terrorist attacks under the Full Protection and Security obligation when they exert efforts relevant to their limited capacity to offer such protection. Further, we argue that investors should also optimize political risk insurance offered by the Multilateral Investment Guarantee Agency when they choose to invest in a host state that might be vulnerable to terrorist attacks, might face potential insurgencies, or suffer from political turmoil. Finally, we highlight the importance of integrating other subfields of international law – such as international human rights law – to the international investment arbitration system, especially in defining what acts or omissions are required of a host state to fulfill the due diligence standard of the Full Protection and Security Obligation

Hydration and Ordering of Lamellar Block Copolymer Films under Controlled Water Vapor

Amphiphilic block copolymers within a range of volume fraction spontaneously form vesicles in aqueous solution, where a water core is enclosed by a polymer bilayer. Thin-film rehydration is a method used to produce vesicles routinely; a thin film is immersed in water, the film swells, and vesicles are formed which bleb off from the film surface. We have studied the early stages of hydration for PEO–PBO block copolymer thin films under controlled water vapor conditions to understand this formation mechanism and so enable more efficient ways to encapsulate molecules using this method. Neutron and X-ray measurements show that the initial film exhibits weakly ordered structure with isotropic parallel and vertical orientation; the films initially swell and maintain the same orientation. At a critical point the layer swells rapidly and makes highly ordered lamellae structure at the same time. The lamellae are almost exclusively oriented parallel to the substrate and swell with increasing water absorption

Deconstructing the outsider puzzle: The legitimation journey of novelty

The proposition that outsiders often are crucial carriers of novelty into an established institutional field has received wide empirical support. But an equally compelling proposition points to the following puzzle: the very same conditions that enhance outsiders' ability to make novel contributions also hinder their ability to carry them out. We seek to address this puzzle by examining the contextual circumstances that affect the legitimation of novelty originating from a noncertified outsider that challenged the status quo in an established institutional field. Our research case material is John Harrison's introduction of a new mechanical method for measuring longitude at sea-the marine chronometer- which challenged the dominant astronomical approach.We find that whether an outsider's new offer gains or is denied legitimacy is influenced by (1) the outsider's agency to further a new offer, (2) the existence of multiple audiences with different dispositions toward this offer, and (3) the occurrence of an exogenous jolt that helps create a more receptive social space. We organize these insights into a multilevel conceptual framework that builds on previouswork but attributes a more decisive role to the interplay between endogenous and exogenous variables in shaping a field's shifting receptiveness to novelty. The framework exposes the interdependencies between the micro-, meso-, and macro-level processes that jointly affect an outsider's efforts to introduce novelty into an existing field

Active Brownian Particles. From Individual to Collective Stochastic Dynamics

We review theoretical models of individual motility as well as collective dynamics and pattern formation of active particles. We focus on simple models of active dynamics with a particular emphasis on nonlinear and stochastic dynamics of such self-propelled entities in the framework of statistical mechanics. Examples of such active units in complex physico-chemical and biological systems are chemically powered nano-rods, localized patterns in reaction-diffusion system, motile cells or macroscopic animals. Based on the description of individual motion of point-like active particles by stochastic differential equations, we discuss different velocity-dependent friction functions, the impact of various types of fluctuations and calculate characteristic observables such as stationary velocity distributions or diffusion coefficients. Finally, we consider not only the free and confined individual active dynamics but also different types of interaction between active particles. The resulting collective dynamical behavior of large assemblies and aggregates of active units is discussed and an overview over some recent results on spatiotemporal pattern formation in such systems is given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte