Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended.

Passive nonlinear pulse shaping in normally dispersive fiber

We propose a simple method for passive nonlinear optical pulse shaping that utilizes pulse prechirping and nonlinear propagation in a normally dispersive nonlinear fiber to generate various temporal waveforms of practical interest from conventional laser pulses.

Passive nonlinear pulse shaping in normally dispersive fiber systems

We propose a novel approach to characterize the parabolically-shaped pulses that can be generated from more conventional pulses via nonlinear propagation in cascaded sections of commercially available normally dispersive (ND) fibers. The impact of the initial pulse chirp on the passive pulse reshaping is examined. We furthermore demonstrate that the combination of pulse pre-chirping and propagation in a single ND fiber yields a simple, passive method for generating various temporal waveforms of practical interest.

Role of the transgenic human thyrotropin receptor A-subunit in thyroiditis induced by A-subunit immunization and regulatory T cell depletion

Transgenic BALB/c mice that express intrathyroidal human thyroid stimulating hormone receptor (TSHR) A-subunit, unlike wild-type (WT) littermates, develop thyroid lymphocytic infiltration and spreading to other thyroid autoantigens after T regulatory cell (Treg) depletion and immunization with human thyrotropin receptor (hTSHR) adenovirus. To determine if this process involves intramolecular epitope spreading, we studied antibody and T cell recognition of TSHR ectodomain peptides (A–Z). In transgenic and WT mice, regardless of Treg depletion, TSHR antibodies bound predominantly to N-terminal peptide A and much less to a few downstream peptides. After Treg depletion, splenocytes from WT mice responded to peptides C, D and J (all in the A-subunit), but transgenic splenocytes recognized only peptide D. Because CD4+ T cells are critical for thyroid lymphocytic infiltration, amino acid sequences of these peptides were examined for in silico binding to BALB/c major histocompatibility complex class II (IA–d). High affinity subsequences (inhibitory concentration of 50% < 50 nm) are present in peptides C and D (not J) of the hTSHR and mouse TSHR equivalents. These data probably explain why transgenic splenocytes do not recognize peptide J. Mouse TSHR mRNA levels are comparable in transgenic and WT thyroids, but only transgenics have human A-subunit mRNA. Transgenic mice can present mouse TSHR and human A-subunit-derived peptides. However, WT mice can present only mouse TSHR, and two to four amino acid species differences may preclude recognition by CD4+ T cells activated by hTSHR-adenovirus. Overall, thyroid lymphocytic infiltration in the transgenic mice is unrelated to epitopic spreading but involves human A-subunit peptides for recognition by T cells activated using the hTSHR.

Do ‘passive’ medical titanium surfaces deteriorate in service in the absence of wear?

Globally, more than 1000 tonnes of titanium (Ti) is implanted into patients in the form of biomedical devices on an annual basis. Ti is perceived to be ‘biocompatible’ owing to the presence of a robust passive oxide film (approx. 4 nm thick) at the metal surface. However, surface deterioration can lead to the release of Ti ions, and particles can arise as the result of wear and/or corrosion processes. This surface deterioration can result in peri-implant inflammation, leading to the premature loss of the implanted device or the requirement for surgical revision. Soft tissues surrounding commercially pure cranial anchorage devices (bone-anchored hearing aid) were investigated using synchrotron X-ray micro-fluorescence spectroscopy and X-ray absorption near edge structure. Here, we present the first experimental evidence that minimal load-bearing Ti implants, which are not subjected to macroscopic wear processes, can release Ti debris into the surrounding soft tissue. As such debris has been shown to be pro-inflammatory, we propose that such distributions of Ti are likely to effect to the service life of the device.

Passive mode-locked lasing by injecting a carbon nanotube-solution in the core of an optical fiber

In this paper, we propose a saturable absorber (SA) device consisting on an in-fiber micro-slot inscribed by femtosecond laser micro fabrication, filled by a dispersion of Carbon Nanotubes (CNT). Due to the flexibility of the fabrication method, efficient and simple integration of the mode-locking device directly into the optical fiber is achieved. Furthermore, the fabrication process offers a high level of control over the dimensions and location of the micro-slots. We apply this fabrication flexibility to extend the interaction length between the CNT and the propagating optical field along the optical fiber, hence enhancing the nonlinearity of the device. Furthermore, the method allows the fabrication of devices that operate by either a direct field interaction (when the central peak of the propagating optical mode passes through the nonlinear media) or an evanescent field interaction (only a fraction of the optical mode interacts with the CNT). In this paper, several devices with different interaction lengths and interaction regimes are investigated. Self-starting passively modelocked laser operation with an enhanced nonlinear interaction is observed using CNT-based SAs in both interaction regimes. This method constitutes a simple and suitable approach to integrate the CNT into the optical system as well as enhancing the optical nonlinearity of CNT-based photonic devices.

In-fiber microchannel device filled with a carbon nanotube dispersion for passive mode-lock lasing

Fueled by their high third-order nonlinearity and nonlinear saturable absorption, carbon nanotubes (CNT) are expected to become an integral part of next-generation photonic devices such as all-optical switches and passive mode-locked lasers. However, in order to fulfill this expectation it is necessary to identify a suitable platform that allows the efficient use of the optical properties of CNT. In this paper, we propose and implement a novel device consisting of an optofluidic device filled with a dispersion of CNT. By fabricating a microchannel through the core of a conventional fiber and filling it with a homogeneous solution of CNTs on Dimethylformamide (DMF), a compact, all-fiber saturable absorber is realized. The fabrication of the micro-fluidic channel is a two-step process that involves femtosecond laser micro-fabrication and chemical etching of the laser-modified regions. All-fiber high-energy, passive mode-locked lasing is demonstrated with an output power of 13.5 dBm. The key characteristics of the device are compactness and robustness against optical, mechanical and thermal damage.

All-optical passive 2R regeneration of dispersion-managed RZ data at 40 and 80 Gbit/s using in-line NOLMs

We demonstrate that the use of in-line nonlinear optical loop mirrors (NOLMs) in dispersion-managed (DM) transmission systems dominated by amplitude noise can achieve passive 2R regeneration of a 40 and 80 Gbit/s RZ data stream. This is an indication that the use of this approach could obviate the need for full-regeneration in high data rate, strong DM systems, when intra-channel four-wave mixing poses serious problems.

Study of the operating regime for all-optical passive 2R regeneration of dispersion-managed RZ data at 40 Gb/s using in-line NOLMs

In this letter, we numerically demonstrate that the use of inline nonlinear optical loop mirrors in strongly dispersion-managed transmission systems dominated by pulse distortion and amplitude noise can achieve all-optical passive 2R regeneration of a 40-Gb/s return-to-zero data stream. We define the tolerance limits of this result to the parameters of the input pulses.

All-optical passive 2R regeneration for N×40 Gbit/s WDM transmission using NOLM and novel filtering technique

We propose an all-optical passive 2R regeneration method for WDM (N×40 Gbit/s) dispersion-managed RZ transmission based on specially designed WDM guiding filters and in-line nonlinear optical loop mirrors. By system optimisation, the feasibility of 150 GHz-spaced × l6 channel transmission over 25,000 km of standard fibre is numerically demonstrated.

All-optical passive quasi-regeneration in transoceanic 40 Gbit/s return-to-zero transmission systems with strong dispersion management

A method of all-optical passive quasi-regeneration in transoceanic 40 Gbit/s return-to-zero transmission systems with strong dispersion management was described. The use of in-line nonlinear optical loop mirrors (NOLM) by the method was demonstrated. The quasi-regeneration of signals performed by NOLMs was found to improve the systems's performance.

All-optical passive regeneration of 40 Gbit/s soliton data stream using dispersion management and in-line NOLMs

It is numerically demonstrated, for the first time, that dispersion management and in-line nonlinear optical loop mirrors can achieve all-optical passive regeneration and distance-unlimited transmission of a soliton data stream at 40 Gbit/s over standard fibre.

Passive regeneration in 40 Gbit/s-based WDM dispersion-managed RZ transmission systems by in-line NOLMs

All-optical passive regeneration in 40 Gbit/s-based wavelength-division-multiplexed (WDM) dispersion-managed return-to-zero (RZ) transmission system was discussed. In-line nonlinear optical loop mirrors (NOLM) were used. A feasibility of 300 GHz-spaced two channel unlimited transmission and 150 GHz-spaced two channel 25000 km transmission over the standard fiber were found.

All-optical passive regeneration of 40 Gbit/s soliton data stream using dispersion-management and in-line nonlinear optical loop mirrors

We numerically demonstrate for the first time that dispersion management and in-line nonlinear optical loop mirrors can achieve all-optical passive regeneration and distance-unlimited transmission of a soliton data stream at 40 Gbit/s over standard fibre.