Thermal stability of copper nitride thin films: The role of nitrogen migration

The atomic composition, structural, morphological, and optical properties of N-rich copper nitride thin films have been investigated prior to and after annealing them in vacuum at temperatures up to 300 °C. Films were characterized by means of ion-beam analysis (IBMA), X-ray diffraction (XRD), atomic force microscopy (AFM), and spectroscopic ellipsometry techniques (SE). The data reveal that even when the total (integrated over the whole thickness) atomic composition of the films remains constant, nitrogen starts to migrate from the bulk to the film surface, without out-diffusing, at temperatures as low as 100 °C. This migration leads to two chemical phases with different atomic concentration of nitrogen, lattice parameters, and crystallographic orientation but with the same crystal structure. XRD experimental and Rietveld refined data seem to confirm that nitrogen excess accommodates in interstitial locations within the anti-ReO3 crystal lattice forming a solid solution. The influence of nitrogen migration on the optical (electronic) properties of the films will be discusse

Characterization of human immunodeficiency virus type 1 mutantswith decreased sensitivity to proteinase inhibitor Ro 31-8959

AbstractA human immunodeficiency virus type 1 (HIV-1) variant with highly reduced susceptibility to Ro 31-8959, an inhibitor of the viral proteinase, has been selected by repeated passage of wild-type virus in CEM cells in the presence of increasing concentrations of the inhibitor. Peptide sequences of the proteinase of selected virus were obtained from proviral DNA. Sequence comparison to wild-type (wt) proteinase demonstrated two amino acid substitutions in the resistant virus, a Gly to Val exchange at position 48 and a Leu to Met exchange at position 90. Furthermore, sequences of intermediate passage virus suggest contributions from positions 12, 36, 57, and 63 in early steps of resistance development. The selected virus showed a ca. 40-fold increase in 50% inhibitory concentration of Ro 31-8959. Growth kinetics of resistant virus were comparable to wild-type virus and the resistant genotype proved to be stable in the absence of inhibitor. Directed mutagenesis of the HIV-1 HXB2 proteinase at positions 48 and 90 suggested that each mutation alone led to a moderate decrease in sensitivity of the recombinant virus to proteinase inhibitor. However, a recombinant virus carrying both mutations in the proteinase gene showed a significant reduction in its sensitivity to Ro 31-8959 thus proving the importance of these exchanges for the resistance phenotype

Conjugation of a peptide autoantigen to gold nanoparticles for intradermally administered antigen specific immunotherapy

Antigen specific immunotherapy aims to tolerise patients to specific autoantigens that are responsible for the pathology of an autoimmune disease. Immune tolerance is generated in conditions where the immune response is suppressed and thus gold nanoparticles (AuNPs) are an attractive drug delivery platform due to their anti-inflammatory effects and their potential to facilitate temporal and spatial delivery of a peptide autoantigen in conjunction with pro-tolerogenic elements. In this study we have covalently attached an autoantigen, currently under clinical evaluation for the treatment of type 1 diabetes (PIC19-A3 peptide), to AuNPs to create nanoscale (<5 nm), negatively charged (−40 to −60 mV) AuNP-peptide complexes for immunotherapy. We also employ a clinically approved microneedle delivery system, MicronJet600, to facilitate minimally-invasive intradermal delivery of the nanoparticle constructs to target skin-resident antigen presenting cells, which are known to be apposite target cells for immunotherapy. The AuNP-peptide complexes remain physically stable upon extrusion through microneedles and when delivered into ex vivo human skin they are able to diffuse rapidly and widely throughout the dermis (their site of deposition) and, perhaps more surprisingly, the overlying epidermal layer. Intracellular uptake was extensive, with Langerhans cells proving to be the most efficient cells at internalising the AuNP-peptide complex (94% of the local population within the treated region of skin). In vitro studies showed that uptake of the AuNP-peptide complexes by dendritic cells reduced the capacity of these cells to activate naïve T cells. This indicator of biological functionality encourages further development of the AuNP-peptide formulation, which is now being evaluated in clinical trials

Cognitive functioning in children with internalising, externalising and dysregulation problems: a population-based study

Psychiatric symptoms in childhood are closely related to neurocognitive deficits. However, it is unclear whether