Generation of a quasi-monoergetic proton beam from laser-irradiated sub-micron droplets

Proton bursts with a narrow spectrum at an energy of (2.8 +/- 0.3 MeV) are accelerated from sub-micron water spray droplets irradiated by high-intensity (similar to 5 x 10(19)W/cm(2)), high-contrast (similar to 10(10)), ultra-short (40 fs) laser pulses. The acceleration is preferentially in the laser propagation direction. The explosion dynamics is governed by a residual ps-scale laser pulse pedestal which "mildly" preheats the droplet and changes its density profile before the arrival of the high intensity laser pulse peak. As a result, the energetic electrons extracted from the modified target by the high-intensity part of the laser pulse establish an anisotropic electrostatic field which results in anisotropic Coulomb explosion and proton acceleration predominantly in the forward direction. Hydrodynamic simulations of the target pre-expansion and 3D particle-in-cell simulations of the measured energy and anisotropy of the proton emission have confirmed the proposed acceleration scenario. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4731712]

Proteomics and phylogenetic analysis of the cathepsin L protease family of the helminth pathogen Fasciola hepatica:Expansion of a repertoire of virulence-associated factors

Cathepsin L proteases secreted by the helminth pathogen Fasciola hepatica have functions in parasite virulence including tissue invasion and suppression of host immune responses. Using proteomics methods alongside phylogenetic studies we characterized the profile of cathepsin L proteases secreted by adult F. hepatica and hence identified those involved in host-pathogen interaction. Phylogenetic analyses showed that the Fasciola cathepsin L gene family expanded by a series of gene duplications followed by divergence that gave rise to three clades associated with mature adult worms (Clades 1, 2, and 5) and two clades specific to infective juvenile stages (Clades 3 and 4). Consistent with these observations our proteomics studies identified representatives from Clades 1, 2, and 5 but not from Clades 3 and 4 in adult F. hepatica secretory products. Clades 1 and 2 account for 67.39 and 27.63% of total secreted cathepsin Ls, respectively, suggesting that their expansion was positively driven and that these proteases are most critical for parasite survival and adaptation. Sequence comparison studies revealed that the expansion of cathepsin Ls by gene duplication was followed by residue changes in the S2 pocket of the active site. Our biochemical studies showed that these changes result in alterations in substrate binding and suggested that the divergence of the cathepsin L family produced a repertoire of enzymes with overlapping and complementary substrate specificities that could cleave host macromolecules more efficiently. Although the cathepsin Ls are produced as zymogens containing a prosegment and mature domain, all secreted enzymes identified by MS were processed to mature active enzymes. The prosegment region was highly conserved between the clades except at the boundary of prosegment and mature enzyme. Despite the lack of conservation at this section, sites for exogenous cleavage by asparaginyl endopeptidases and a Leu-Ser[downward arrow]His motif for autocatalytic cleavage by cathepsin Ls were preserved.

Identifying optimal sites for natural recovery and restoration of impacted biogenic habitats in a special area of conservation using hydrodynamic and habitat suitability modelling

Selection of sites for successful restoration of impacted shellfish populations depends on understanding the dispersion capability and habitat requirements of the species involved. In Strangford Lough, Northern Ireland, the horse mussel (Modiolus modiolus) biogenic reefs cover only a fraction of their historical range with the remaining reefs badly damaged and requiring restoration. Previous experimental trials suggest that translocation of horse mussels accelerates reef recovery and has therefore been proposed as a suitable restoration technique. We used a series of coupled hydrodynamic and particle dispersal models to assess larval dispersion from remnant and translocated populations to identify suitable areas for adult live M. modiolus translocation in Strangford Lough, Northern Ireland. A maximum entropy model (MAXENT) was used to identify if dispersing larvae could reach habitat suitable for adult M. modiolus. From these we predicted if translocated mussels will reseed themselves or be able to act as larval sources for nearby reefs. The dispersal models showed that the remnant M. modiolus populations are largely self-recruiting with little connectivity between them. The majority of larvae settled near the sources and movement was largely dependent on the tides and not influenced by wind or waves. Higher reef elevation resulted in larvae being able to disperse further away from the release point. However, larval numbers away from the source population are likely to be too low for successful recruitment. There was also little connectivity between the Irish Sea and Strangford Lough as any larvae entering the Lough remained predominantly in the Strangford Narrows. The areas covered by these self-seeding populations are suitable for M. modiolus translocation according to the MAXENT model. As a result of this work and in conjunction with other field work we propose a combination of total protection of all remaining larval sources and small scale translocations onto suitable substrata in each of the identified self-recruiting areas.

Magnetic instability in a dilute circular rarefaction wave

The growth of magnetic fields in the density gradient of a rarefaction wave has been observed in simulations and in laboratory experiments. The thermal anisotropy of the electrons, which gives rise to the magnetic instability, is maintained by the ambipolar electric field. This simple mechanism could be important for the magnetic field amplification in astrophysical jets or in the interstellar medium ahead of supernova remnant shocks. The acceleration of protons and the generation of a magnetic field by the rarefaction wave, which is fed by an expanding circular plasma cloud, is examined here in form of a 2D particle-in-cell simulation. The core of the plasma cloud is modeled by immobile charges, and the mobile protons form a small ring close to the cloud's surface. The number density of mobile protons is thus less than that of the electrons. The protons of the rarefaction wave are accelerated to 1/10 of the electron thermal speed, and the acceleration results in a thermal anisotropy of the electron distribution in the entire plasma cloud. The instability in the rarefaction wave is outrun by a TM wave, which grows in the dense core distribution, and its magnetic field expands into the rarefaction wave. This expansion drives a secondary TE wave. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4769128]

From hyperactive children to ADHD adults:Observations on the expansion of medical categories

Medicalization is by definition, about the extension of medical boundaries. Analogous to "domain expansion," extant medicalized categories can expand to become broader and more inclusive. This paper examines the emergence of Attention Deficit Hyperactivity Disorder (ADHD) in adults. ADHD, commonly known as Hyperactivity, became established in the 1970s as a diagnosis for children; it expanded first to include "adult hyperactives" and, in the 1990s, "ADHD Adults." This allowed for the inclusion of an entire population of people and their problems that were excluded by the original conception of hyperactive children. We show how lay, professional, and media claims help establish the expanded diagnostic category. We identify particular aspects of the social context that contributed to the rise of adult ADHD and outline some of the social implications of ADHD in adults, especially the medicalization of underperformance and the availability of new disability rights. Adult ADHD serves as an exemplar of several cases of diagnostic expansion, an important avenue of increasing medicalization.

Magnetic field suppression in collision-less shocks generated during the expansion of a dense plasma into a rarefied medium

A two-dimensional numerical study of the expansion of a dense plasma through a more rarefied one is reported. The electrostatic ion-acoustic shock, which is generated during the expansion, accelerates the electrons of the rarefied plasma inducing a superthermal population which reduces electron thermal anisotropy. The Weibel instability is therefore not triggered and no self-generated magnetic fields are observed, in contrast with published theoretical results dealing with plasma expansion into vacuum. © The Author(s) 2013.

JAK2V617F homozygosity arises commonly and recurrently in PV and ET, but PV is characterized by expansion of a dominant homozygous subclone

Subclones homozygous for JAK2V617F are more common in polycythemia vera (PV) than essential thrombocythemia (ET), but their prevalence and significance remain unclear. The JAK2 mutation status of 6495 BFU-E, grown in low erythropoietin conditions, was determined in 77 patients with PV or ET. Homozygous-mutant colonies were common in patients with JAK2V617F-positive PV and were surprisingly prevalent in JAK2V617F-positive ET and JAK2 exon 12-mutated PV. Using microsatellite PCR to map loss-of-heterozygosity breakpoints within individual colonies, we demonstrate that recurrent acquisition of JAK2V617F homozygosity occurs frequently in both PV and ET. PV was distinguished from ET by expansion of a dominant homozygous subclone, the selective advantage of which is likely to reflect additional genetic or epigenetic lesions. Our results suggest a model in which development of a dominant JAK2V617F-homzygous subclone drives erythrocytosis in many PV patients, with alternative mechanisms operating in those with small or undetectable homozygous-mutant clones.

Clonal expansion of hypermutated measles virus in a SSPE brain

Nucleotide sequence analysis was carried out to study genes encoding the matrix (M) protein of measles virus (MV) from several regions of the brain of a case of subacute sclerosing panencephalitis. This analysis revealed the presence of MV with 'wild-type' sequences as well as variants which had undergone at least five biased hypermutation events (U to C and A to G in the positive strand sequences). Despite the presence of MV variants with genes encoding the intact matrix protein open reading frame, M protein could not be detected in any of the brain regions. The distribution of virus variants was studied by cDNA cloning and sequence analysis and by in situ hybridization. The hypermutated viruses appeared to expand clonally throughout the brain of patient B.

Ex Vivo Expansion of Human Outgrowth Endothelial Cells Leads to IL-8-Mediated Replicative Senescence and Impaired Vasoreparative Function

Harnessing outgrowth endothelial cells (OECs) for vasoreparative therapy and tissue-engineering requires efficient ex-vivo expansion. How such expansion impacts on OEC function is largely unknown. In this study, we show that OECs become permanently cell-cycle arrested after ex-vivo expansion, which is associated with enlarged cell size, ß-galactosidase activity, DNA damage, tumour suppressor pathway activation and significant transcriptome changes. These senescence hallmarks were coupled with low telomerase activity and telomere shortening, indicating replicative senescence. OEC senescence limited their regenerative potential by impairing vasoreparative properties in-vitro and in-vivo. Integrated transcriptome-proteome analysis identified inflammatory signalling pathways as major mechanistic components of the OEC senescence programme. In particular, IL8 was an important facilitator of this senescence; depletion of IL8 in OECs significantly extended ex-vivo lifespan, delayed replicative senescence and enhanced function. While the ability to expand OEC numbers prior to autologous or allogeneic therapy remains a useful property, their replicative senescence and associated impairment of vasorepair needs to be considered. The current study also suggests that modulation of the senescence-associated secretory phenotype (SASP) could be used to optimise OEC therapy.

Comparison of lagrangian and eulerian simulations of slurry flows in a sudden expansion

From a review of technical literature, it was not apparent if the Lagrangian or the Eulerian dispersed phase modeling approach was more valid to simulate dilute erosive slurry flow. In this study, both modeling approaches were employed and a comparative analysis of performances and accuracy between the two models was carried out. Due to an impossibility to define, for the Eulerian model already implemented in FLUENT, a set of boundary conditions consistent with the Lagrangian impulsive equations, an Eulerian dispersed phase model was integrated in the FLUENT code using subroutines and user-defined scalar equations. Numerical predictions obtained from the two different approaches for two-phase flow in a sudden expansion were compared with the measured data. Excellent agreement was attained between the predicted and observed fluid and particle velocity in the axial direction and for the kinetic energy. Erosion profiles in a sudden expansion computed using the Lagrangian scheme yielded good qualitative agreement with measured data and predicted a maximum impact angle of 29 deg at the fluid reattachment point. The Eulerian model was adversely affected by the reattachment of the fluid phase to the wall and the simulated erosion profiles were not in agreement with the Lagrangian or measured data. Furthermore, the Eulerian model under-predicted the Lagrangian impact angle at all locations except the reattachment point. © 2010 American Society of Mechanical Engineers.

A Hydrodynamic Modelling Framework for Strangford Lough Part 1: Tidal Model

Hydrodynamic models are a powerful tool that can be used by a wide range of end users to assist in predicting the effects of both physical and biological processes on local environmental conditions. This paper describes the development of a tidal model for Strangford Lough, Northern Ireland, a body of water renowned for the location of the first grid-connected tidal turbine, SeaGen, as well as the UK’s third Marine Nature Reserve. Using MIKE 21 modelling software, the development, calibration and performance of the modelare described in detail. Strangford Lough has a complex flow pattern with high flows through the Narrows (~3.5 m/s) linking the main body of the Lough to the Irish Sea and intricate flow patterns around the numerous islands. With the aid of good quality tidal and current data obtained throughout the Lough during the model development, the surface elevation and current magnitude between the observed and numerical model were almost identical with model skill >0.98 and >0.84 respectively. The applicability of the model is such that it can be used as an important tool for the prediction of important ecological processes as well as engineering applications within Strangford Lough.

Understanding macroalgal dispersal in a complex hydrodynamic environment: a combined population genetic and physical modelling approach

Gene flow in macroalgal populations can be strongly influenced by spore or gamete dispersal. This, in turn, is influenced by a convolution of the effects of current flow and specific plant reproductive strategies. Although several studies have demonstrated genetic variability in macroalgal populations over a wide range of spatial scales, the associated current data have generally been poorly resolved spatially and temporally. In this study, we used a combination of population genetic analyses and high-resolution hydrodynamic modelling to investigate potential connectivity between populations of the kelp Laminaria digitata in the Strangford Narrows, a narrow channel characterized by strong currents linking the large semi-enclosed sea lough, Strangford Lough, to the Irish Sea. Levels of genetic structuring based on six microsatellite markers were very low, indicating high levels of gene flow and a pattern of isolation-by-distance, where populations are more likely to exchange migrants with geographically proximal populations, but with occasional long-distance dispersal. This was confirmed by the particle tracking model, which showed that, while the majority of spores settle near the release site, there is potential for dispersal over several kilometres. This combined population genetic and modelling approach suggests that the complex hydrodynamic environment at the entrance to Strangford Lough can facilitate dispersal on a scale exceeding that proposed for L. digitata in particular, and the majority of macroalgae in general. The study demonstrates the potential of integrated physical–biological approaches for the prediction of ecological changes resulting from factors such as anthropogenically induced coastal zone changes.

Air-Sea Exchange of Legacy POPs in the North Sea Based on Results of Fate and Transport, and Shelf-Sea Hydrodynamic Ocean Models

The air-sea exchange of two legacy persistent organic pollutants (POPs), γ-HCH and PCB 153, in the North Sea, is presented and discussed using results of regional fate and transport and shelf-sea hydrodynamic ocean models for the period 1996–2005. Air-sea exchange occurs through gas exchange (deposition and volatilization), wet deposition and dry deposition. Atmospheric concentrations are interpolated into the model domain from results of the EMEP MSC-East multi-compartmental model (Gusev et al, 2009). The North Sea is net depositional for γ-HCH, and is dominated by gas deposition with notable seasonal variability and a downward trend over the 10 year period. Volatilization rates of γ-HCH are generally a factor of 2–3 less than gas deposition in winter, spring and summer but greater in autumn when the North Sea is net volatilizational. A downward trend in fugacity ratios is found, since gas deposition is decreasing faster than volatilization. The North Sea is net volatilizational for PCB 153, with highest rates of volatilization to deposition found in the areas surrounding polluted British and continental river sources. Large quantities of PCB 153 entering through rivers lead to very high local rates of volatilization.