Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery

The design of a non-viral gene delivery vehicle capable of delivering and releasing a functional nucleic acid cargo intracellularly remains a formidable challenge. For systemic gene therapy to be successful a delivery vehicle is required that protects the nucleic acid cargo from enzymatic degradation, extravasates from the vasculature, traverses the cell membrane, disrupts the endosomal vesicles and unloads the cargo at its destination site, namely the nucleus for the purposes of gene delivery. This manuscript reports the extensive investigation of a novel amphipathic peptide composed of repeating RALA units capable of overcoming the biological barriers to gene delivery both in vitro and in vivo. Our data demonstrates the spontaneous self-assembly of cationic DNA-loaded nanoparticles when the peptide is complexed with pDNA. Nanoparticles were < 100 nm, were stable in the presence of serum and were fusogenic in nature, with increased peptide α-helicity at a lower pH. Nanoparticles proved to be non-cytotoxic, readily traversed the plasma membrane of both cancer and fibroblast cell lines and elicited reporter-gene expression following intravenous delivery in vivo. The results of this study indicate that RALA presents an exciting delivery platform for the systemic delivery of nucleic acid therapeutics.

Dynamics and structure of self-generated magnetics fields on solids following high contrast, high intensity laser irradiation

The dynamics of self-generated magnetic B-fields produced following the interaction of a high contrast, high intensity (I > 10¹⁹W cm^-2) laser beam with thin (3 μm thick) solid (Al or Au) targets is investigated experimentally and numerically. Two main sources drive the growth of B-fields on the target surfaces. B-fields are first driven by laser-generated hot electron currents that relax over ∼10-20 ps. Over longer timescales, the hydrodynamic expansion of the bulk of the target into vacuum also generates B-field induced by non-collinear gradients of density and temperature. The laser irradiation of the target front side strongly localizes the energy deposition at the target front, in contrast to the target rear side, which is heated by fast electrons over a much larger area. This induces an asymmetry in the hydrodynamic expansion between the front and rear target surfaces, and consequently the associated B-fields are found strongly asymmetric. The sole long-lasting (>30 ps) B-fields are the ones growing on the target front surface, where they remain of extremely high strength (∼8-10 MG). These B-fields have been recently put by us in practical use for focusing laser-accelerated protons [B. Albertazzi et al., Rev. Sci. Instrum. 86, 043502 (2015)]; here we analyze in detail their dynamics and structure.

Self-focusing and envelope pulse generation in nonlinear magnetic metamaterials

The self-modulation of waves propagating in nonlinear magnetic metamaterials is investigated. Considering the propagation of a modulated amplitude magnetic field in such a medium, we show that the self-modulation of the carrier wave leads to a spontaneous energy localization via the generation of localized envelope structures (envelope solitons), whose form and properties are discussed. These results are also supported by numerical calculations.

Self-perception in overweight and obese children: a cross-sectional study

Aim The aim of this study was to examine the relationship between obesity and self-esteem in children in relation to specific domains of their self-perception, and further to explore the extent to which this may vary by gender and economic circumstances. Method A total of 211 children aged 8–9 years drawn from both advantaged and disadvantaged areas of Belfast completed the Harter Self-Perception Profile for Children and measures of body mass index were obtained. Results Overweight, impoverished children had significantly reduced social acceptance and physical competence scores. Boys had significantly lower scores than girls in the behavioural conduct domain. Girls had significantly lower scores than boys for the athletic competence. Conclusion These results suggest that risk factors of increased weight and impoverished backgrounds have a combined negative effect, placing some children at increased risk of having lower self-perceptions in some, but not all domains. Health interventions for childhood obesity should consider the likelihood of specific relationships between physical and psychosocial factors.

Authorizing a tradition: Theory, criticism and (self-) canonization in French Caribbean writing

As critics have noted, Antillean literature has developed in tandem with a strong (self-) critical and theoretical body of work. The various attempts to theorize Antillean identity (négritude, antillanité, créolité) have been controversial and divisive, and the literary scene has been characterized as explosive, incestuous and self-referential. Yet writers aligned with, or opposed to, a given theory often have superior visibility. Meanwhile writers who claim to operate outside the boundaries of theory, such as Maryse Condé, are often canny theoretical operators who, from prestigious academic or cultural positions, manipulate readers’ responses and their own self-image through criticism. While recent polemics have helped to raise the critical stock of the islands generally, they have particularly enhanced the cultural capital of Chamoiseau and Condé, whose literary antagonism is in fact mutually sustaining. Both writers, through a strong awareness of (and contribution to) the critical field in which their work is read, position themselves as canonical authors.

Anger, aggression, and self-harm in PTSD and complex PTSD

This study examined the contribution of complex posttraumatic stress disorder (PTSD) diagnosis and symptomatology to the difficulties of anger, aggression, and self-harm in a Northern Ireland clinical community sample. A "current complex PTSD" (CCPTSD) group (n = 11) was compared with a "current PTSD" group (n = 31) on self-report measures of these variables. The CCPTSD group demonstrated significantly higher levels of physical aggression and selfharm than the PTSD group. The complex PTSD symptom of 'alterations in self-perception' was a significant predictor of aggression and history of self-harm, suggesting the potential role of posttraumatic shame and self-loathing in PTSD theoretical models of these destructive behaviors. Social desirability was a notable confounding influence in the assessment of anger, aggression, and self-harm in traumatised individuals.

Trauma typology as a risk factor for aggression and self-harm in a complex PTSD population: The mediating role of alterations in self-perception

This study examined the role of prolonged, repeated traumatic experiences such as childhood and sectarian trauma in the development of posttraumatic aggression and self-harm. Forty-four adult participants attending therapy for complex trauma in Northern Ireland were obtained via convenience sampling. When social desirability was controlled, childhood emotional and physical neglect were significant correlates of posttraumatic hostility and history of self-harm. These relationships were mediated by alterations in self-perception (e.g., shame, guilt). Severity of sectarian-related experiences was not related to self-destructive behaviors. Moreover, none of the trauma factors were related to overt aggressive behavior. The findings have implications for understanding risk factors for posttraumatic aggression and self-harm, as well as their treatment. © 2013 Copyright Taylor & Francis Group, LLC.