Toxoplasma gondii major surface antigen (SAG1): in vitro analysis of host cell binding

Previous studies have indicated that SAG1, the major surface molecule of the protozoan parasite Toxoplasma gondii, is an important attachment ligand for the host cell. However, the research data that supports this claim comes largely from studies investigating tachyzoite binding, and not SAG1 binding per se. In this study we successfully developed an in vitro attachment assay to directly evaluate the mechanism of SAG1-host cell binding. Competition experiments were then performed using SAG1 that had been pre-treated with the neoglycoprotein BSA-glucosamide or with antibody. Soluble BSA-glucosamide blocked SAG1 attachment to MDBK cells in a dose-dependent manner, implying that SAG1 binding is mediated, in part, via attachment to host cell surface glucosamine. Interestingly, pre-incubation of SAG1 in polyclonal sera from chronically infected mice failed to block binding. This challenges the assumption that anti-SAG1 antibodies block parasite attachment through the masking of SAG1 host cell binding domains. Taken together, this evidence presents new strategies for understanding SAG1-mediated attachment

Powerful proteins from polyp possessing predators

Cnidarians are soft bodied animals possessing complex venom systems which have evolved to allow for the capture of arthropod and vertebrate prey, as well as to defend themselves against such predators. The effects of these venoms on humans, as a result of envenomation, has been studied for many decades, whereas the possibility of using these proteins to fight human disease is in its infancy. Drug discovery utilisation of Cnidarian venoms has been hampered by availability of animals and suitable extraction techniques that allow for study of such protein toxins. Studies of toxins that have been suitably purified for drug discovery have, by in large, only investigated target engagement and negated to investigate other drug like properties such as absorption, dispersion, metabolism, and excretion (ADME). This chapter will review the sourcing of Cnidaria for drug discovery, extraction of venom components, actions of venoms on drug relevant targets and their suitability as drug like molecules

Temporal and spectral characteristics of a marine piling operation in shallow water

Analysis of the underwater radiate acoustic characteristics for marine piling operations for two pile diameters, 2m and 4.74m, in a relatively shallow water site are presented. Measurements of the entire piling sequence for several piles were conducted at ranges from 10m to 22km for piles in 10-20 m water depth. Variations in the temporal and spectral characteristics of radiated energy are analysed in context of pile size, range from source, hammer energy used and pile penetration depth. Analysis of hammer energy used shows a strong interdependence between mechanical strike ‘hammer’ energy and underwater radiated acoustic energy. This process appears ‘coarsely’ linear for individual piling operations although considerable variation in overall gradient were observed between operations. For individual hammer energy step increases often the largest increases in radiated energy were observed at the initial hammer energy increase, with subsequent strikes at the same hammer energy resulting in a gradual reduction in radiated energy to a level 1-2 dB lower. These effects are potentially due to sediment compacting / relaxation effects relating to the time and number of strikes and penetration. Temporal and spectral variations in radiated energy due to pile penetration are also examined for fixed hammer energy and range. Simultaneous recordings of radiated energy made at increasing distances from the pile showed evidence of temporal and spectral dispersion effects consistent with relatively shallow water propagation. Correlation of received levels at various ranges in differing seabed topographies were made suggesting complex shallow water modal propagation dependant on both the source and environment characteristics including seabed topography, sediment type and water column acoustic properties

Abundance and evolution of galaxy clusters in cosmological models with massive neutrino

The time evolution of the number density of galaxy clusters and their mass and temperature functions are used to constrain cosmological parameters in the spatially flat dark matter models containing a fraction of hot particles (massive neutrino) additional to cold and baryonic matter. We test the modified MDM models with cosmic gravitational waves and show that they neither pass the cluster evolution test nor reproduce the observed height of the first acoustic peak in $\Delta T/T$ spectrum, and therefore should be ruled out. The models with a non-zero cosmological constant are in better agreement with observations. We estimate the free cosmological parameters in $\Lambda$MDM with a negligible abundance of gravitational waves, and find that within the parameter ranges $h\in (0.6, 0.7)$, $n\in (0.9, 1.1)$, (i) the value of $\Omega_\Lambda$ is strongly affected by a small fraction of hot dark matter, $f_\nu\equiv\Omega_\nu /\Omega_m\in (0, 0.2)$: $0.45 <\Omega_\Lambda <0.7$ ($1\sigma$ CL), and (ii) the redshift evolution of galaxy clusters alone reveals the following explicit correlation between $\Omega_\Lambda$ and $f_\nu$: $\Omega_\Lambda +0.5f_\nu =0.65\pm 0.1$. The present accuracy of observational data allows only to bound the fraction of hot matter, $f_\nu\in (0, 0.2)$ (the number of massive neutrino species remains undelimited, $N_\nu =1, 2, 3$).Comment: 9 pages, 7 figures, submitted in A&

Uniform random generation of large acyclic digraphs

Directed acyclic graphs are the basic representation of the structure underlying Bayesian networks, which represent multivariate probability distributions. In many practical applications, such as the reverse engineering of gene regulatory networks, not only the estimation of model parameters but the reconstruction of the structure itself is of great interest. As well as for the assessment of different structure learning algorithms in simulation studies, a uniform sample from the space of directed acyclic graphs is required to evaluate the prevalence of certain structural features. Here we analyse how to sample acyclic digraphs uniformly at random through recursive enumeration, an approach previously thought too computationally involved. Based on complexity considerations, we discuss in particular how the enumeration directly provides an exact method, which avoids the convergence issues of the alternative Markov chain methods and is actually computationally much faster. The limiting behaviour of the distribution of acyclic digraphs then allows us to sample arbitrarily large graphs. Building on the ideas of recursive enumeration based sampling we also introduce a novel hybrid Markov chain with much faster convergence than current alternatives while still being easy to adapt to various restrictions. Finally we discuss how to include such restrictions in the combinatorial enumeration and the new hybrid Markov chain method for efficient uniform sampling of the corresponding graphs.Comment: 15 pages, 2 figures. To appear in Statistics and Computin

Weak localization of Dirac fermions in graphene beyond the diffusion regime

We develop a microscopic theory of the weak localization of two-dimensional massless Dirac fermions which is valid in the whole range of classically weak magnetic fields. The theory is applied to calculate magnetoresistance caused by the weak localization in graphene and conducting surfaces of bulk topological insulators.Comment: 5 pages, 2 figure

Vlasov-Maxwell, self-consistent electromagnetic wave emission simulations in the solar corona

1.5D Vlasov-Maxwell simulations are employed to model electromagnetic emission generation in a fully self-consistent plasma kinetic model for the first time in the solar physics context. The simulations mimic the plasma emission mechanism and Larmor drift instability in a plasma thread that connects the Sun to Earth with the spatial scales compressed appropriately. The effects of spatial density gradients on the generation of electromagnetic radiation are investigated. It is shown that 1.5D inhomogeneous plasma with a uniform background magnetic field directed transverse to the density gradient is aperiodically unstable to Larmor-drift instability. The latter results in a novel effect of generation of electromagnetic emission at plasma frequency. When density gradient is removed (i.e. when plasma becomes stable to Larmor-drift instability) and a $low$ density, super-thermal, hot beam is injected along the domain, in the direction perpendicular to the magnetic field, plasma emission mechanism generates non-escaping Langmuir type oscillations which in turn generate escaping electromagnetic radiation. It is found that in the spatial location where the beam is injected, the standing waves, oscillating at the plasma frequency, are excited. These can be used to interpret the horizontal strips observed in some dynamical spectra. Quasilinear theory predictions: (i) the electron free streaming and (ii) the beam long relaxation time, in accord with the analytic expressions, are corroborated via direct, fully-kinetic simulation. Finally, the interplay of Larmor-drift instability and plasma emission mechanism is studied by considering $dense$ electron beam in the Larmor-drift unstable (inhomogeneous) plasma. http://www.maths.qmul.ac.uk/~tsiklauri/movie1.mpg * http://www.maths.qmul.ac.uk/~tsiklauri/movie2.mpg * http://www.maths.qmul.ac.uk/~tsiklauri/movie3.mpgComment: Solar Physics (in press, the final, accepted version

A methodology for the measurement of radiated noise from marine piling

This paper describes a methodology that has been developed for measuring marine piling noise, which is designed to record the temporal, spatial and spectral characteristics of the radiated sound field. Results are presented for measurements of two pile diameters, 2m and 4.74m, in a shallow water site off the east coast of the UK. Measurements of the entire piling sequence for several piles were conducted at ranges from 10 m to 22 km for piles in 10-20 m water depth. To assess variations in the temporal, spatial and spectral characteristics, a number of recording systems were simultaneously deployed at various ranges and depths, allowing the full piling sequence to be measured. This allowed assessment of source level variation at fixed locations, and the effect of propagation within the water column

Microwave pyrolysis of Laminaria digitata to produce unique seaweed-derived bio-oils

Microwave pyrolysis has become an attractive form of processing technology to generate bio-oil, bio-char and syngas from different biomass feedstocks. In this study, microwave pyrolysis was performed on the UK native seaweed Laminaria digitata and its extract residue from a bio-refinery process. Pyrolysis of these two feedstocks was successfully achieved without the requirement of microwave susceptors, as pelletizing the biomass was sufficient to allow microwave pyrolysis to occur. It was found that average energy requirements as low as 1.84–2.83 kJ g−1 were required to pyrolyse 55–70% of both feedstocks and bio-oil yields of 5–8% and 10–14% for native and extraction residue L. digitata were produced, respectively. Maximum microwave pyrolysis processing times were in the order of 200 s. The bio-oil generated from both feedstocks contained no phenolic based compounds, but a greater number of nitrogen-containing compounds and compounds derived from macroalgal polysaccharides. Yields of certain compounds differed in bio-oils generated from the two L. digitata feedstocks, however it was observed that specific energy did not have a direct influence on bio-oil compound yield. Furthermore, the identification of a particular nitrogen-containing compound L-Proline, 1-methyl-5-oxo-, methylester is thought to be a unique product of microwave pyrolysis when carbon-based additives are avoided

Nuttier Bubbles

We construct new explicit solutions of general relativity from double analytic continuations of Taub-NUT spacetimes. This generalizes previous studies of 4-dimensional nutty bubbles. One 5-dimensional locally asymptotically AdS solution in particular has a special conformal boundary structure of $AdS_3\times S^1$. We compute its boundary stress tensor and relate it to the properties of the dual field theory. Interestingly enough, we also find consistent 6-dimensional bubble solutions that have only one timelike direction. The existence of such spacetimes with non-trivial topology is closely related to the existence of the Taub-NUT(-AdS) solutions with more than one NUT charge. Finally, we begin an investigation of generating new solutions from Taub-NUT spacetimes and nuttier bubbles. Using the so-called Hopf duality, we provide new explicit time-dependent backgrounds in six dimensions.Comment: 32 pages, 1 figure; v.3. typos corrected. Matches the published versio