Correction in trans for Fabry disease: expression, secretion and uptake of alpha-galactosidase A in patient-derived cells driven by a high-titer recombinant retroviral vector.

Fabry disease is an X-linked metabolic disorder due to a deficiency of alpha-galactosidase A (alpha-gal A; EC 3.2.1.22). Patients accumulate glycosphingolipids with terminal alpha-galactosyl residues that come from intracellular synthesis, circulating metabolites, or from the biodegradation Of senescent cells. Patients eventually succumb to renal, cardio-, or cerebrovascular disease. No specific therapy exists. One possible approach to ameliorating this disorder is to target corrective gene transfer therapy to circulating hematopoietic cells. Toward this end, an amphotropic virus-producer cell line has been developed that produces a high titer (>10(6) i.p. per ml) recombinant retrovirus constructed to transduce and correct target cells. Virus-producer cells also demonstrate expression of large amounts of both intracellular and secreted alpha-gal A. To examine the utility of this therapeutic vector, skin fibroblasts from Fabry patients were corrected for the metabolic defect by infection with this recombinant virus and secreted enzyme was observed. Furthermore, the secreted enzyme was found to be taken up by uncorrected cells in a mannose-6-phosphate receptor-dependent manner. In related experiments, immortalized B cell lines from Fabry patients, created as a hematologic delivery test system, were transduced. As with the fibroblasts, transduced patient B cell lines demonstrated both endogenous enzyme correction and a small amount of secretion together with uptake by uncorrected cells. These studies demonstrate that endogenous metabolic correction in transduced cells, combined with secretion, may provide a continuous source of corrective material in trans to unmodified patient bystander cells (metabolic cooperativity).

Panégyrique de Sainte Geneviève, patrone de Paris, prononcé dans son temple le jour de la fête du miracle des ardens.

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Refractometer based on fiber Bragg grating Fabry-Pérot cavity embedded with a narrow microchannel

We report on inscription of microchannels of different widths in optical fiber using femtosecond (fs) laser inscription assisted chemical etching and the narrowest channel has been created with a width down to only 1.2µm. Microchannels with 5µm and 35µm widths were fabricated together with Fabry-Pérot (FP) cavities formed by UV laser written fiber Bragg gratings (FBGs), creating high function and linear response refractometers. The device with a 5µm microchannel has exhibited a refractive index (RI) detection range up to 1.7, significantly higher than all fiber grating RI sensors. In addition, the microchannel FBG FP structures have been theoretically simulated showing excellent agreement with experimental measured characteristics.

A multiwavelength low-power wavelength-locked slotted Fabry-Perot laser source for WDM applications

Wavelength-locking of a multiwavelength stabilized slotted Fabry-Perot (SFP) laser to a single-mode laser source is experimentally demonstrated. The SFP resonates at channels spaced by similar to 8 nm between 1510 and 1565 nm over a wide range of temperatures and drive currents. Under low-power (<- 20 dBm) external optical injection, wavelength-locking with a sidemode suppression ratio (SMSR) > 25 dB is achieved. A locking width of > 25 GHz and SMSR > 30 dB can be achieved for each locked wavelength channel at injection power > - 16 dBm.

Fiber Bragg grating Fabry-Perot structures under loading and their applications in switchable multi-wavelength lasers

Characteristics of fiber Bragg grating based Fabry-Perot (FBG-FP) structures under transversal loading are investigated. A novel switchable multi-wavelength fiber laser employing loaded FBG-FP is also demonstrated. © 2012 OSA.

High speed and high resolution demodulation system for hybrid WDM/FDM based fiber microstructure sensor network by using Fabry-Perot filter

Hybrid WDM/TDM enabled microstructure based optical fiber sensor network with large capacity is proposed. Assisted by Fabry-Perot filter, the demodulation system with high speed of 500Hz and high wavelength resolution less than 4.91pm is realized. © OSA 2015.

Fabry-Perot micro-structured polymer optical fibre sensors for opto-acoustic endoscopy

Opto-Acoustic Endoscopy (OAE) requires sensors with a high sensitivity and small physical dimensions in order to facilitate integration into an endoscope of less than 1mm in diameter. We present fibre Bragg grating (FBG) and Fabry- Perot intrinsic fibre sensors for ultrasound detection. We present a structure profile characterisation setup to analyse tune the fibre sensors in preparation for ultrasonic detection. We evaluate the suitability of the different structures and grating parameters for ultrasonic sensing. By analysing the prepared gratings, we enable the optimisation of the profile and a simplification of the detection regime for an optimal interferometric OAE configuration.

Microfiber Fabry-Perot interferometer for dual-parameter sensing

We propose and demonstrate a microfiber Fabry-Perot interferometer (MFPI) fabricated by taper-drawing microfiber at the center of a uniform fiber Bragg grating (FBG). The MFPI employing the two separated sections of FBG as reflectors and a length of microfiber as its cavity is derived. Theoretic study shows that the reflection spectrum of such MFPI is consisted of two parts-interference fringes induced by multi-beam interference and reflection spectrum envelope induced by FBGs. Temperature affects both interference fringes and reflection wavelength of FBGs while ambient refractive index (RI) only influences the interference fringes, i.e., MFPI has different response to temperature and RI. Therefore, MFPI for simultaneous sensing of RI and temperature is experimentally demonstrated by tracking a reflection peak of interference fringes and the Bragg wavelength of the FBGs, which are respectively assisted by frequency domain processing and Gaussian fitting of the optical spectrum. Consequently, wavelength measurement resolution of 0.5 pm is realized. © 1983-2012 IEEE.

Optical RI sensor based on an in-fiber bragg grating fabry-perot cavity embedded with a micro-channel

We report a linear response optical refractive index (RI) sensor, which is fabricated based on a micro-channel created within a Fabry Perot (F-P) cavity by chemical etching assisted by femtosecond laser inscription. The experimental results show the F-P resonance peak has a linear response with the RI of medium and the measuring sensitivity is proportion to the length of micro-channel. The sensor with 5 μm -long micro-channel exhibited an RI sensitivity of 1.15nm/RIU and this sensitivity increased to 9.08nm/RIU when widening the micro-channel to 35μm. Furthermore, such micro-channel FP sensors show a much broader RI sensing dynamic range (from 1.3 to 1.7) than other reported optical fiber sensors. © 2012 SPIE.

Performance analysis of polymer optical fibre based Fabry-Perot sensor formed by two uniform Bragg gratings

The stress sensitivity of polymer optical fibre (POF) based Fabry-Perot sensors formed by two uniform Bragg gratings with finite dimensions is investigated. POF has received high interest in recent years due to its different material properties compared to its silica counterpart. Biocompatibility, a higher failure strain and the highly elastic nature of POF are some of the main advantages. The much lower Young’s modulus of polymer materials compared to silica offers enhanced stress sensitivity to POF based sensors which renders them great candidates for acoustic wave receivers and any kind of force detection. The main drawback in POF technology is perhaps the high fibre loss. In a lossless fibre the sensitivity of an interferometer is proportional to its cavity length. However, the presence of the attenuation along the optical path can significantly reduce the finesse of the Fabry-Perot interferometer and it can negatively affect its sensitivity at some point. The reflectivity of the two gratings used to form the interferometer can be also reduced as the fibre loss increases. In this work, a numerical model is developed to study the performance of POF based Fabry-Perot sensors formed by two uniform Bragg gratings with finite dimensions. Various optical and physical properties are considered such as grating physical length, grating effective length which indicates the point where the light is effectively reflected, refractive index modulation of the grating, cavity length of the interferometer, attenuation and operating wavelength. Using this model, we are able to identify the regimes in which the PMMA based sensor offer enhanced stress sensitivity compared to silica based one.

Low-linewidth and tunable single frequency 1x2 multimode-interferometer-Fabry-Perot laser diode

In this paper, we present a novel 1x2 multi-mode-interferometer-Fabry-Perot (MMI-FP) laser diode, which demonstrated tunable single frequency operation with more than 30dB side mode suppression ratio (SMSR) and a tuning range of 25nm in the C and L bands, as well as a 750 kHz linewidth. These lasers do not require material regrowth and high resolution gratings; resulting in a simpler process that can significantly increase the yield and reduce the cost.