The Rare Anaphylaxis-Associated FcγRIIa3 Exhibits Distinct Characteristics From the Canonical FcγRIIa1.

FcγRIIa is an activating FcγR, unique to humans and non-human primates. It induces antibody-dependent proinflammatory responses and exists predominantly as FcγRIIa1. A unique splice variant, we designated FcγRIIa3, has been reported to be associated with anaphylactic reactions to intravenous immunoglobulins (IVIg) therapy. We aim to define the functional consequences of this FcγRIIa variant associated with adverse responses to IVIg therapy and evaluate the frequency of associated SNPs. FcγRIIa forms from macaque and human PBMCs were investigated for IgG-subclass specificity, biochemistry, membrane localization, and functional activity. Disease-associated SNPs were analyzed by sequencing genomic DNA from 224 individuals with immunodeficiency or autoimmune disease. FcγRIIa3 was identified in macaque and human PBMC. The FcγRIIa3 is distinguished from the canonical FcγRIIa1 by a unique 19-amino acid cytoplasmic insertion and these two FcγRIIa forms responded distinctly to antibody ligation. Whereas FcγRIIa1 was rapidly internalized, FcγRIIa3 was retained longer at the membrane, inducing greater calcium mobilization and cell degranulation. Four FCGR2A SNPs were identified including the previously reported intronic SNP associated with anaphylaxis, but in only 1 of 224 individuals. The unique cytoplasmic element of FcγRIIa3 delays internalization and is associated with enhanced cellular activation. The frequency of the immunodeficiency-associated SNP varies between disease populations but interestingly occurred at a lower frequency than previously reported. None-the-less enhanced FcγRIIa3 function may promote a proinflammatory environment and predispose to pathological inflammatory responses.

Modified Organosilica Core-Shell Nanoparticles for Stable pH Sensing in Biological Solutions.

Continuous monitoring using nanoparticle-based sensors has been successfully employed in complex biological systems, yet the sensors still suffer from poor long-term stability partially because of the scaffold materials chosen to date. Organosilica core-shell nanoparticles containing a mixture of covalently incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is presented as a continuous pH sensor for application in biological media. In contrast to previous studies focusing on similar materials, we sought to investigate the sensor characteristics (dynamic range, sensitivity, response time, stability) as a function of material properties. The ratio of the fluorescence intensities at specific wavelengths was found to be highly sensitive to pH over a physiologically relevant range (4.5-8) with a response time of <100 ms, significantly faster than that of previously reported response times using silica-based particles. Particles produced stable, pH-specific signals when stored at room temperature for more than 80 days. Finally, we demonstrated that the nanosensors successfully monitored the pH of a bacterial culture over 15 h and that pH changes in the skin of mouse cadavers could also be observed via in vivo fluorescence imaging following subcutaneous injection. The understanding gained from linking sensor characteristics and material properties will inform the next generation of optical nanosensors for continuous-monitoring applications.

Numerical investigation on the effects of fabrication conditions on fiber Bragg grating spectra using the phase mask technique.

A numerical investigation on how fiber Bragg grating fabrication conditions using the phase mask technique affect the harmonic components of the Bragg wavelength is presented. Both the properties of the phase mask and saturation effects are investigated to determine the underlying cause of the rise of various harmonic reflections other than the Bragg wavelength. Results are compared with published data by various authors.

Variations of the growth of harmonic reflections in fiber Bragg gratings fabricated using phase masks.

The growth of reflectance peaks from optical fiber Bragg gratings has been studied to determine the relative importance of grating features when writing with the phase-mask technique. Measurements of spectra for two different fiber types using two distinct phase masks allowed the contribution from grating features of half the phase-mask periodicity and of the phase-mask periodicity at the Bragg wavelength to be determined. The dominance of the latter periodicity was ascribed to either the small fiber core diameter that limited the extent of the Talbot diffraction pattern, or the enhanced ±2 diffraction orders of a custom-made phase mask used.

Super-resolution imaging and statistical analysis of CdSe/CdS Core/Shell semiconductor nanocrystals.

Here we present a multifunctional algorithm. Firstly a super-resolution method is presented for optically imaging the spatial distribution of semiconductor nanocrystals with nanometre localisation. Secondly highly resolved multiple photoluminescence trajectories of hundreds of single semiconductor nanocrystals are obtained simultaneously.

Fabrication of a pi-phase-shifted fiber Bragg grating at twice the Bragg wavelength with the standard phase mask technique.

A pair of reflection peaks/transmission dips, at twice the Bragg wavelength, were observed in spectra of a Type I fiber Bragg grating written with the standard phase mask technique. The occurrence of two peaks/dips, rather than one, is attributed to the interleaved refractive index modulations along the fiber core, with the periodicity of the phase mask that has been observed previously in images of gratings that cause destructive interference in a reflected wave at the Bragg condition owing to the pi phase difference between the grating phases. Thus the standard phase mask technique produced an alternative type of pi-phase-shifted grating at twice the design Bragg wavelength.

Quantitative investigation of the refractive-index modulation within the core of a fiber Bragg grating.

A comparison is made between the modeled and experimentally determined microscopic images of a type I Bragg grating produced in the core of an optical fiber using the ultraviolet irradiation of a phase mask. The simulated image of the refractive-index distribution, which assumes a linear relationship between the irradiation intensity and the refractive-index change, is in good agreement with the measured image.