Evaluation of the optical switching characteristics of erbium-doped fibres for the development of a fibre Bragg grating sensor interrogator

A polling topology that employs optical switching based on the properties of erbium-doped fibres (EDFs) is used to interrogate an array of FBGs. The properties of the EDF are investigated in its pumped and un-pumped states and the EDFs’ switching properties are evaluated by comparing them with a high performance electronically controlled MEM optical switch. Potential advantages of the proposed technique are discussed. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

Photodegradable by Yellow-Orange Light degFusionRed Optogenetic Module with Autocatalytically Formed Chromophore

Optogenetic systems driven by yellow-orange light are required for the simultaneous regulation of several cellular processes. We have engineered the red fluorescent protein FusionRed into a 26 kDa monomeric optogenetic module, called degFusionRed. Unlike other fluorescent protein-based optogenetic domains, which exhibit light-induced self-inactivation by generating reactive oxygen species, degFusionRed undergoes proteasomal degradation upon illumination with 567 nm light. Similarly to the parent protein, degFusionRed has minimal absorbance at 450 nm and above 650 nm, making it spectrally compatible with blue and near-infrared-light-controlled optogenetic tools. The autocatalytically formed chromophore provides degFusionRed with an additional advantage over most optogenetic tools that require the binding of the exogenous chromophores, the amount of which varies in different cells. The degFusionRed efficiently performed in the engineered light-controlled transcription factor and in the targeted photodegradation of the protein of interest, demonstrating its versatility as the optogenetic module of choice for spectral multiplexed interrogation of various cellular processes

Efficient large-scale multiplexing of fiber Bragg grating and fiber Fabry-Perot sensors for structural health monitoring applications

Fiber Bragg gratings have been demonstrated as a versatile sensor for structural health monitoring. We present an efficient and cost effective multiplexing method for fiber Bragg grating and fiber Fabry-Perot sensors based on a broadband mode-locked fiber laser source and interferometric interrogation. The broadband, pulsed laser source permits time and wavelength division multiplexing to be employed to achieve very high sensor counts. Interferometric interrogation also permits high strain resolutions over large frequency ranges to be achieved. The proposed system has the capability to interrogate several hundred fiber Bragg gratings or fiber Fabry-Perot sensors on a single fiber, whilst achieving sub-microstrain resolution over bandwidths greater than 100 kHz. Strain resolutions of 30n epsilon/Hz(1/2) and 2 n epsilon/Hz(1/2) are demonstrated with the fiber Bragg grating and fiber Fabry-Perot sensor respectively. The fiber Fabry-Perot sensor provides an increase in the strain resolution over the fiber Bragg grating sensor of greater than a factor of 10. The fiber Bragg gratings are low reflectivity and could be fabricated during the fiber draw process providing a cost effective method for array fabrication. This system would find applications in several health monitoring applications where large sensor counts are necessary, in particular acoustic emission

Impact detection techniques using fibre-optic sensors for aerospace & defence

Impact detection techniques are developed for application in the aerospace and defence industries. Optical fibre sensors hold great promise for structural health monitoring systems and methods of interrogating fibre Bragg gratings (FBG) are investigated given the need for dynamic strain capture and multiplexed sensors. An arrayed waveguide grating based interrogator is developed. The relationships between key performance indicators, such as strain range and linearity of response, and parameters such as the FBG length and spectral width are determined. It was found that the inclusion of a semiconductor optical amplifier could increase the signal-to-noise ratio by ~300% as the system moves to its least sensitive. An alternative interrogator is investigated utilising two wave mixing in erbium-doped fibre in order to create an adaptive system insensitive to quasistatic strain and temperature drifts. Dynamic strain sensing was demonstrated at 200 Hz which remained functional while undergoing a temperature shift of 8.5 °C. In addition, software techniques are investigated for locating impact events on a curved composite structure using both time-of-flight triangulation and neural networks. A feature characteristic of composite damage creation is identified in dynamic signals captured during impact. An algorithm is developed which successfully distinguishes between signals characteristic of a non-damaging impact with those from a damaging impact with a classification accuracy of 93 – 96%. Finally, a demonstrator system is produced to exhibit some of the techniques developed in this thesis

Multiplexed cellular profiling identifies an organoselenium compound as an inhibitor of CRM1-mediated nuclear export

Chromosomal region maintenance 1 (CRM1 also known as Xpo1 and exportin-1) is the receptor for the nuclear export controlling the intracellular localization and function of many cellular and viral proteins that play a crucial role in viral infections and cancer. The inhibition of CRM1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses, for the treatment of cancer, and to overcome therapy resistance. Recently, selinexor has been approved as the first CRM1 inhibitor for the treatment of multiple myeloma, providing proof of concept for this therapeutic option with a new mode of action. However, selinexor is associated with dose-limiting toxicity and hence, the discovery of alternative small molecule leads that could be developed as less toxic anticancer and antiviral therapeutics will have a significant impact in the clinic. Here, we report a CRM1 inhibitor discovery platform. The development of this platform includes reporter cell lines that monitor CRM1 activity by using red fluorescent protein or green fluorescent protein-labeled HIV-1 Rev protein with a strong heterologous nuclear export signal. Simultaneously, the intracellular localization of other proteins, to be interrogated for their capacity to undergo CRM1-mediated export, can be followed by co-culturing stable cell lines expressing fluorescent fusion proteins. We used this platform to interrogate the mode of nuclear export of several proteins, including PDK1, p110α, STAT5A, FOXO1, 3, 4 and TRIB2, and to screen a compound collection. We show that while p110α partially relies on CRM1-dependent nuclear export, TRIB2 is exported from the nucleus in a CRM1-independent manner. Compound screening revealed the striking activity of an organoselenium compound on the CRM1 nuclear export receptorThis article is based upon work from COST Action STRATAGEM, CA17104, supported by COST (European Cooperation in Science and Technology) (www.cost.eu, accessed in March 2022). Romano Silvestri is indebted to AIRC, IG 2020, code no. 24703. This work was supported by the Spanish Ministry of Science, Innovation and Universities through Grant RTI2018-094629-B-I00 to Wolfgang Link. Miguel Machuqueiro thanks Fundaçao para a Ciência e Tecnologia ˜ (Portugal) for CEECIND/02300/2017 (grant), UIDB/04046/2020 and UIDP/04046/2020 (projects

Targeted Proteomics in Translational and Clinical Studies

This chapter provides a concise overview on the methods and applications of targeted proteomics in the context of translational and clinical studies. Mass spectrometry-based targeted proteomics has emerged as a promising technique for protein and peptide quantification, presenting a great potential for clinical applications. While significant amount of discovery works have been carried out in both genomics and proteomics for an assortment of diseases, it has been challenging in further characterizing individual protein targets for their biological significance and clinical value due to the lack of effective and “universal” techniques. The development of targeted proteomics approach opened a unique avenue to bridge the discovery-based genomics and proteomics with candidate-based protein analysis, which is clinically highly relevant. Targeted proteomics analysis has been implemented on a variety of instrument platforms, and applied for a wide range of studies, from blood biomarker detection to pathway-driven mechanistic investigations, with the triple quadrupole-based selected reaction monitoring (SRM) technique being the most widely used method. With a right combination of calibration approach, internal standards, and sample preparation strategies, mass spectrometry-based targeted analysis has proven to be of inter-laboratory reproducibility and sensitivity in analyzing many clinical specimens. More recently, the advent of mass spectrometry with high frequencies and resolutions yielded the data independent acquisition (DIA) techniques, such as sequential window acquisition of all theoretical fragment ion spectra (SWATH). The unbiased nature of DIA methods would enable a wider analytical scope and a greater robustness in targeted analysis, representing a paradigm shift in targeted proteomics

EGFL6 regulates the asymmetric division, maintenance and metastasis of ALDH+ ovarian cancer cells

Little is known about the factors that regulate the asymmetric division of cancer stem-like cells. Here we demonstrate that EGFL6, a stem cell regulatory factor expressed in ovarian tumor cells and vasculature, regulates ALDH+ ovarian cancer stem-like cells (CSC). EGFL6 signaled at least in part via the oncoprotein SHP2 with concomitant activation of ERK. EGFL6 signaling promoted the migration and asymmetric division of ALDH+ ovarian CSC. As such, EGFL6 increased not only tumor growth but also metastasis. Silencing of EGFL6 or SHP2 limited numbers of ALDH+ cells and reduced tumor growth, supporting a critical role for EGFL6/SHP2 in ALDH+ cell maintenance. Notably, systemic administration of an EGFL6-neutralizing antibody we generated restricted tumor growth and metastasis, specifically blocking ovarian cancer cell recruitment to the ovary. Together, our results offer a preclinical proof of concept for EGFL6 as a novel therapeutic target for the treatment of ovarian cancer

Fiber Optic Sensors for Harsh and High Radiation Environments in Aerospace Applications

In the upcoming space revolutions aiming at the implementation of automated, smart, and self-aware crewless vehicles and reusable spacecraft, sensors play a significant role in the control systems. In particular, fiber optic sensors, with their small footprint and electromagnetic immunity, represent a great opportunity in aerospace. The radiation environment and the harsh conditions in which these sensors will operate represent a challenge for the potential user in the aerospace vehicle design and the fiber optic sensor specialist. We present a review that aims to be a primer in the field of fiber optic sensors in radiation environments for aerospace. We review the main aerospace requirements and their relationship with fiber optics. We also present a brief overview of fiber optics and sensors based on them. Finally, we present different examples of applications in radiation environments for aerospace applications