Two-Pulse Ionization Injection into Quasi-Linear Laser Wakefields

We describe a scheme for controlling electron injection into the quasi-linear wakefield driven by a guided drive pulse via ionization of a dopant species by a collinear injection laser pulse with a short Rayleigh range. The scheme is analyzed by particle in cell simulations which show controlled injection and acceleration of electrons to an energy of 370 MeV, a relative energy spread of 2%, and a normalized transverse emittance of 3.0 {\mu}m. This is an arXiv version of the original APS paper. It should be cited as N. Bourgeois, J. Cowley, and S. M. Hooker, Phys. Rev. Lett. 111, 155004 (2013). APS link here: http://link.aps.org/doi/10.1103/PhysRevLett.111.155004Comment: 5 pages, 4 figure

Theoretical modelling of the collapse of a shelled ultrasound contrast agent used in the treatment of cancer

Strathclyde theses - ask staff. Thesis no. : T14627Premanufactured shelled microbubbles composed of a protein shell are currently licensed in the UK as ultrasound imaging contrast agents. Current research is focussing on using the shelled microbubbles as transportation mechanisms for localised drug delivery particularly in the treatment of various types of cancer. The aim of this PhD study is to identify how the shell's material parameters influence the collapse and relaxation times of the shelled microbubbles. A theoretical model is proposed which utilises an analytical approach to predict the dynamics of a stressed, compressible shelled microbubble. This model can be used to identify the optimal material parameters for the shells. A neo-Hookean, compressible strain energy density function is used to model the potential energy per unit volume of the shell. A stress is applied to the inner surface of the spherical shell whilst setting the outer surface's stress to zero. The collapse phase of the stressed shelled microbubble is then considered. Applying the momentum balance law,a dynamical model is used to predict the dynamics of the collapsing shelled microbubble. An analytical approach is adopted using an asymptotic expansion. A second model is then constructed to model the deformation of an open, shelled microbubble. This is achieved by considering a reference configuration (stress free)consisting of a shelled microbubble with a spherical cap removed. This is then deformed angularly and radially by applying a stress load to the free edge of the shell. This forms a deformed open sphere possessing a stress. This is used to represent the change in geometry of a shelled microbubble. The third and final model focusses on developing a Rayleigh-Plesset equation for an incompressible,thin shelled, gas loaded shelled microbubble with a shell that is composed of a liquid-crystalline material. The technique of linearisation is used to predict the shelled microbubble's natural frequency and relaxation time. The influence of the material properties of the shell on the natural frequency and relaxation time are discussed.Premanufactured shelled microbubbles composed of a protein shell are currently licensed in the UK as ultrasound imaging contrast agents. Current research is focussing on using the shelled microbubbles as transportation mechanisms for localised drug delivery particularly in the treatment of various types of cancer. The aim of this PhD study is to identify how the shell's material parameters influence the collapse and relaxation times of the shelled microbubbles. A theoretical model is proposed which utilises an analytical approach to predict the dynamics of a stressed, compressible shelled microbubble. This model can be used to identify the optimal material parameters for the shells. A neo-Hookean, compressible strain energy density function is used to model the potential energy per unit volume of the shell. A stress is applied to the inner surface of the spherical shell whilst setting the outer surface's stress to zero. The collapse phase of the stressed shelled microbubble is then considered. Applying the momentum balance law,a dynamical model is used to predict the dynamics of the collapsing shelled microbubble. An analytical approach is adopted using an asymptotic expansion. A second model is then constructed to model the deformation of an open, shelled microbubble. This is achieved by considering a reference configuration (stress free)consisting of a shelled microbubble with a spherical cap removed. This is then deformed angularly and radially by applying a stress load to the free edge of the shell. This forms a deformed open sphere possessing a stress. This is used to represent the change in geometry of a shelled microbubble. The third and final model focusses on developing a Rayleigh-Plesset equation for an incompressible,thin shelled, gas loaded shelled microbubble with a shell that is composed of a liquid-crystalline material. The technique of linearisation is used to predict the shelled microbubble's natural frequency and relaxation time. The influence of the material properties of the shell on the natural frequency and relaxation time are discussed

A mathematical model of sonoporation using a liquid-crystalline shelled microbubble

In recent years there has been a great deal of interest in using thin shelled microbubbles as a transportation mechanism for localised drug delivery, particularly for the treatment of various types of cancer. The technique used for such site-specific drug delivery is sonoporation. Despite there being numerous experimental studies on sonoporation, the mathematical modelling of this technique has still not been extensively researched. Presently there exists a very small body of work that models both hemispherical and spherical shelled microbubbles sonoporating due to acoustic microstreaming. Acoustic microstreaming is believed to be the dominant mechanism for sonoporation via shelled microbubbles. Rather than considering the shell of the microbubble to be composed of a thin protein, which is typical in the literature, in this paper we consider the shell to be a liquid-crystalline material. Up until now there have been no studies reported in the literature pertaining to sonoporation of a liquid-crystalline shelled microbubble. A mathematical expression is derived for the maximum wall shear stress, illustrating its dependency on the shell’s various material parameters. A sensitivity analysis is performed for the wall shear stress considering the shell’s thickness; its local density; the elastic constant of the liquid-crystalline material; the interfacial surface tension and; the shell’s viscoelastic properties. In some cases, our results indicate that a liquid-crystalline shelled microbubble may yield a maximum wall shear stress that is two orders of magnitude greater than the stress generated by commercial shelled microbubbles that are currently in use within the scientific community. In conclusion, our preliminary analysis suggests that using liquid-crystalline shelled microbubbles may significantly enhance the efficiency of site-specific drug delivery

Geomorphological control on boulder transport and coastal erosion before, during and after an extreme extra-tropical cyclone

Extreme wave events in coastal zones are principal drivers of geomorphic change. Evidence of boulder entrainment and erosional impact during storms is increasing. However, there is currently poor time coupling between pre- and post-storm measurements of coastal boulder deposits. Importantly there are no data reporting shore platform erosion, boulder entrainment and/or boulder transport during storm events – rock coast dynamics during storm events are currently unexplored. Here, we use high-resolution (daily) field data to measure and characterise coastal boulder transport before, during and after the extreme Northeast Atlantic extra-tropical cyclone Johanna in March 2008. Forty-eight limestone fine-medium boulders (n = 46) and coarse cobbles (n = 2) were tracked daily over a 0.1 km2 intertidal area during this multi-day storm. Boulders were repeatedly entrained, transported and deposited, and in some cases broken down (n = 1) or quarried (n = 3), during the most intense days of the storm. Eighty-one percent (n = 39) of boulders were located at both the start and end of the storm. Of these, 92% were entrained where entrainment patterns were closely aligned to wave parameters. These data firmly demonstrate rock coasts are dynamic and vulnerable under storm conditions. No statistically significant relationship was found between boulder size (mass) and net transport distance. Graphical analyses suggest that boulder size limits the maximum longshore transport distance but that for the majority of boulders lying under this threshold, other factors influence transport distance. Paired analysis of 20 similar sized and shaped boulders in different morphogenic zones demonstrates that geomorphological control affects entrainment and transport distance – where net transport distances were up to 39 times less where geomorphological control was greatest. These results have important implications for understanding and for accurately measuring and modelling boulde

Mathematical modelling of the collapse time of an unfolding shelled microbubble

There is considerable interest at the moment on using shelled microbubbles as a transportation mechanism for localised drug delivery, specifically in the treatment of various cancers. In this report a theoretical model is proposed which predicts the collapse time of an unfolding shelled microbubble. A neo-Hookean, compressible strain energy density function is used to model the potential energy per unit volume of the shell. This is achieved by considering a reference configuration (stress free) consisting of a shelled microsphere with a hemispherical cap removed. This is then displaced angularly and radially by applying a stress load to the free edge of the shell. This forms a deformed open sphere possessing a stress. This is then used as an initial condition to model the unfolding of the shell back to its original stress free configuration. Asymptotic expansion along with the conservation of mass and energy are then used to determine the collapse times for the unfolding shell and how the material parameters influence this. The theoretical model is compared to published experimental results

Dynamical model of an oscillating shelled microbubble

There is considerable interest at the moment on using shelled microbubbles as a transportation mechanism for localised drug delivery, specifically in the treatment of various cancers. In this report a theoretical model is proposed which predicts the dynamics of an oscillating shelled microbubble. A neo-Hookean, compressible strain energy density function is used to model the potential energy per unit volume of the shell. The shell is then stressed by applying a series of small radially directed stress steps to the inner surface of the shell whilst setting the outer surface’s stress to zero. The spatial profiles of the Cauchy radial and angular (hoop) stresses that are created within the shell during this quasistatic inflationary process are then stored as the shelled microbubble is inflated. The shelled microbubble is then allowed to collapse by setting the stress at the inner surface to zero. The model which results is then used to predict the dynamics of the shelled microbubble as it oscillates about its equilibrium state. A linear approximation is then used to allow analytical insight into both the quasistatic inflationary and oscillating phases of the shelled microbubble. Numerical results from the full nonlinear model are produced which show the influence of the shell’s thickness, Poisson ratio and shear modulus on the rate of oscillation of the shelled microbubble and these are compared to the approximate analytical solution. The theoretical model’s collapse time is compared to published experimental results

Transportin 3 Promotes a Nuclear Maturation Step Required for Efficient HIV-1 Integration

The HIV/AIDS pandemic is a major global health threat and understanding the detailed molecular mechanisms of HIV replication is critical for the development of novel therapeutics. To replicate, HIV-1 must access the nucleus of infected cells and integrate into host chromosomes, however little is known about the events occurring post-nuclear entry but before integration. Here we show that the karyopherin Transportin 3 (Tnp3) promotes HIV-1 integration in different cell types. Furthermore Tnp3 binds the viral capsid proteins and tRNAs incorporated into viral particles. Interaction between Tnp3, capsid and tRNAs is stronger in the presence of RanGTP, consistent with the possibility that Tnp3 is an export factor for these substrates. In agreement with this interpretation, we found that Tnp3 exports from the nuclei viral tRNAs in a RanGTP-dependent way. Tnp3 also binds and exports from the nuclei some species of cellular tRNAs with a defective 3'CCA end. Depletion of Tnp3 results in a re-distribution of HIV-1 capsid proteins between nucleus and cytoplasm however HIV-1 bearing the N74D mutation in capsid, which is insensitive to Tnp3 depletion, does not show nucleocytoplasmic redistribution of capsid proteins. We propose that Tnp3 promotes HIV-1 infection by displacing any capsid and tRNA that remain bound to the pre-integration complex after nuclear entry to facilitate integration. The results also provide evidence for a novel tRNA nucleocytoplasmic trafficking pathway in human cells