Relieving the first bottleneck in the drug discovery pipeline:using array technologies to rationalize membrane protein production

The slow down in the drug discovery pipeline is, in part, owing to a lack of structural and functional information available for new drug targets. Membrane proteins, the targets of well over 50% of marketed pharmaceuticals, present a particular challenge. As they are not naturally abundant, they must be produced recombinantly for the structural biology that is a prerequisite to structure-based drug design. Unfortunately, however, obtaining high yields of functional, recombinant membrane proteins remains a major bottleneck in contemporary bioscience. While repeated rounds of trial-and-error optimization have not (and cannot) reveal mechanistic details of the biology of recombinant protein production, examination of the host response has provided new insights. To this end, we published an early transcriptome analysis that identified genes implicated in high-yielding yeast cell factories, which has enabled the engineering of improved production strains. These advances offer hope that the bottleneck of membrane protein production can be relieved rationally.

The effect of zinc and titanium on the structure of calcium-sodium phosphate based glass

An array of different structural probes has been used to define the effect of adding Zn and Ti to a sodium-calcium phosphate glass. X-ray absorption spectroscopy at the Zn K-edge suggests that the Zn atoms occupy mixed (4- and 6-fold) sites within the glass matrix. X-ray diffraction reveals a feature at 2.03 angstrom that develops with the addition of Zn and Ti and is consistent with Zn-O and Ti-O near-neighbour distances. Neutron diffraction is used to resolve two distinct P-O distances and highlights the decrease in P center dot center dot center dot P coordination number from 2.0 to 1.7 as the Ti metal concentration rises, which is attributed to the O/P fraction moving away from the metaphosphate value of 3.0 to 3.1 with the addition of Ti. Other correlations, such as those associated with CaO(x) and NaO(x) polyhedra, remain largely unaffected. These results suggest that the network forming P center dot center dot center dot P correlation is most disrupted, with the disorder parameter rising from 0.07 to 0.10 angstrom with the additional modifiers. Zn appears to be introduced into the network as a direct replacement for Ca and causes no structural variation over the composition range studied.

Tilted fibre Bragg grating based 800nm WDM interrogation system for strain, temperature and refractive index sensing

We report the implementation of a low-cost high-resolution WDM interrogation system operating around 800nm region with bandwidth up to 60 nm and resolution of 13 pm by utilising a tilted fibre Bragg grating as an out-coupling device and a CCD-array detector. The system has been evaluated for interrogating fibre Bragg grating based strain, temperature sensors, giving sensitivities of 0.6 pm/µe and 5.6 pm/°C which are in good agreement with previously reported values. Furthermore, the system has been utilised to detect refractive index change of sample liquids, demonstrating a capability of measuring index change as small as 10-5.

Respiratory function monitoring using a real-time three-dimensional fiber-optic shaping sensing scheme based upon fiber Bragg gratings

An array of in-line curvature sensors on a garment is used to monitor the thoracic and abdominal movements of a human during respiration. The results are used to obtain volumetric changes of the human torso in agreement with a spirometer used simultaneously at the mouth. The array of 40 in-line fiber Bragg gratings is used to produce 20 curvature sensors at different locations, each sensor consisting of two fiber Bragg gratings. The 20 curvature sensors and adjoining fiber are encapsulated into a low-temperature-cured synthetic silicone. The sensors are wavelength interrogated by a commercially available system from Moog Insensys, and the wavelength changes are calibrated to recover curvature. A three-dimensional algorithm is used to generate shape changes during respiration that allow the measurement of absolute volume changes at various sections of the torso. It is shown that the sensing scheme yields a volumetric error of 6%. Comparing the volume data obtained from the spirometer with the volume estimated with the synchronous data from the shape-sensing array yielded a correlation value 0.86 with a Pearson's correlation coefficient p <0.01.

Polarization-independent high-resolution spectral interrogation of FBGs using a BFBG-CCD array for optical sensing applications

Optical fibre strain sensors using Fibre Bragg Gratings (FBGs) are poised to play a major role in structural health monitoring in a variety of application from aerospace to civil engineering. At the heart of technology is the optoelectronic instrumentation required to convert optical signals into measurands. Users are demanding compact, lightweight, rugged and low cost solutions. This paper describes development of a new device based on a blazed FBG and CCD array that can potentially meet the above demands. We have shown that this very low cost technique may be used to interrogate a WDM array of sensor gratings with highly accurate and highly repeatable results unaffected by the polarisation state of the radiation. In this paper, we present results showing that sensors may be interrogated with an RMS error of 1.7pm, drift below 0.12pm and dynamic range of up to 65nm.

Tilted fibre Bragg grating based 800nm WDM interrogation system for strain, temperature and refractive index sensing

We report the implementation of a low-cost high-resolution WDM interrogation system operating around 800nm region with bandwidth up to 60 nm and resolution of 13 pm by utilising a tilted fibre Bragg grating as an out-coupling device and a CCD-array detector. The system has been evaluated for interrogating fibre Bragg grating based strain, temperature sensors, giving sensitivities of 0.6 pm/µe and 5.6 pm/°C which are in good agreement with previously reported values. Furthermore, the system has been utilised to detect refractive index change of sample liquids, demonstrating a capability of measuring index change as small as 10-5.

Real-time 3D shape sensing and reconstruction scheme based upon fibre optic bragg gratings

An array of FBG curvature sensors are wavelength-interrogated and the recovered data combined with a three-dimensional algorithm to reconstruct in real time the enveloped object with a 1% to 9% volumetric error. © 2012 OSA.

Respiratory function monitoring using a real-time three-dimensional fiber-optic shaping sensing scheme based upon fiber Bragg gratings

An array of in-line curvature sensors on a garment is used to monitor the thoracic and abdominal movements of a human during respiration. The results are used to obtain volumetric changes of the human torso in agreement with a spirometer used simultaneously at the mouth. The array of 40 in-line fiber Bragg gratings is used to produce 20 curvature sensors at different locations, each sensor consisting of two fiber Bragg gratings. The 20 curvature sensors and adjoining fiber are encapsulated into a low-temperature-cured synthetic silicone. The sensors are wavelength interrogated by a commercially available system from Moog Insensys, and the wavelength changes are calibrated to recover curvature. A three-dimensional algorithm is used to generate shape changes during respiration that allow the measurement of absolute volume changes at various sections of the torso. It is shown that the sensing scheme yields a volumetric error of 6%. Comparing the volume data obtained from the spirometer with the volume estimated with the synchronous data from the shape-sensing array yielded a correlation value 0.86 with a Pearson's correlation coefficient p <0.01.

The application of a long period grating sensor array scheme to human respiratory plethysmography

Preliminary results are given for a long period grating sensing array scheme based upon a derivative spectroscopy interrogation technique for Human Respiratory Plethysmography with simultaneous measurements of a spirometer, reasonable agreement with recorded volumetric changes was found.

Low-Power Tracking Image Sensor Based on Biological Models of Attention

This paper presents implementation of a low-power tracking CMOS image sensor based on biological models of attention. The presented imager allows tracking of up to N salient targets in the field of view. Employing "smart" image sensor architecture, where all image processing is implemented on the sensor focal plane, the proposed imager allows reduction of the amount of data transmitted from the sensor array to external processing units and thus provides real time operation. The imager operation and architecture are based on the models taken from biological systems, where data sensed by many millions of receptors should be transmitted and processed in real time. The imager architecture is optimized to achieve low-power dissipation both in acquisition and tracking modes of operation. The tracking concept is presented, the system architecture is shown and the circuits description is discussed.

All-fiber loading sensor based on 45° and 81° tilted fiber gratings

Cardiovascular health of the human population is a major concern for medical clinicians, with cardiovascular diseases responsible for 48% of all deaths worldwide, according to the World Health Organisation. Therefore the development of new practicable and economical diagnostic tools to scrutinise the cardiovascular health of humans is a major driver for clinicians. We offer a new technique to obtain seismocardiographic signals covering both ballistocardiography (below 20Hz) and audible heart sounds (20Hz upwards). The detection scheme is based upon an array of curvature/displacement sensors using fibre optic long period gratings interrogated using a variation of the derivative spectroscopy interrogation technique. © 2014 SPIE.

Polarization-independent high-resolution spectral interrogation of FBGs using a BFBG-CCD array for optical sensing applications

Optical fibre strain sensors using Fibre Bragg Gratings (FBGs) are poised to play a major role in structural health monitoring in a variety of application from aerospace to civil engineering. At the heart of technology is the optoelectronic instrumentation required to convert optical signals into measurands. Users are demanding compact, lightweight, rugged and low cost solutions. This paper describes development of a new device based on a blazed FBG and CCD array that can potentially meet the above demands. We have shown that this very low cost technique may be used to interrogate a WDM array of sensor gratings with highly accurate and highly repeatable results unaffected by the polarisation state of the radiation. In this paper, we present results showing that sensors may be interrogated with an RMS error of 1.7pm, drift below 0.12pm and dynamic range of up to 65nm.

Cost-effective optical coherence tomography spectrometer based on a tilted fiber Bragg grating

A compact, fiber-based spectrometer for biomedical application utilizing a tilted fiber Bragg grating (TFBG) as integrated dispersive element is demonstrated. Based on a 45° UV-written PS750 TFBG a refractive spectrometer with 2.06 radiant/μm dispersion and a numerical aperture of 0.1 was set up and tested as integrated detector for an optical coherence tomography (OCT) system. Featuring a 23 mm long active region at the fiber the spectrum is projected via a cylindrical lens for vertical beam collimation and focused by an achromatic doublet onto the detector array. Covering 740 nm to 860 nm the spectrometer was optically connected to a broadband white light interferometer and a wide field scan head and electronically to an acquisition and control computer. Tomograms of ophthalmic and dermal samples obtained by the frequency domain OCT-system were obtained achieving 2.84 μm axial and 7.6 μm lateral resolution. © 2014 SPIE.

Direction Finding Estimators of Cyclostationary Signals in Array Processing for Microwave Power Transmission

A solar power satellite is paid attention to as a clean, inexhaustible large- scale base-load power supply. The following technology related to beam control is used: A pilot signal is sent from the power receiving site and after direction of arrival estimation the beam is directed back to the earth by same direction. A novel direction-finding algorithm based on linear prediction technique for exploiting cyclostationary statistical information (spatial and temporal) is explored. Many modulated communication signals exhibit a cyclostationarity (or periodic correlation) property, corresponding to the underlying periodicity arising from carrier frequencies or baud rates. The problem was solved by using both cyclic second-order statistics and cyclic higher-order statistics. By evaluating the corresponding cyclic statistics of the received data at certain cycle frequencies, we can extract the cyclic correlations of only signals with the same cycle frequency and null out the cyclic correlations of stationary additive noise and all other co-channel interferences with different cycle frequencies. Thus, the signal detection capability can be significantly improved. The proposed algorithms employ cyclic higher-order statistics of the array output and suppress additive Gaussian noise of unknown spectral content, even when the noise shares common cycle frequencies with the non-Gaussian signals of interest. The proposed method completely exploits temporal information (multiple lag ), and also can correctly estimate direction of arrival of desired signals by suppressing undesired signals. Our approach was generalized over direction of arrival estimation of cyclostationary coherent signals. In this paper, we propose a new approach for exploiting cyclostationarity that seems to be more advanced in comparison with the other existing direction finding algorithms.

Fiber-optic liquid level monitoring system using microstructured polymer fiber Bragg grating array sensors:performance analysis

A highly sensitive liquid level monitoring system based on microstructured polymer optical fiber Bragg grating (mPOFBG) array sensors is reported for the first time. The configuration is based on five mPOFBGs inscribed in the same fiber in the 850 nm spectral region, showing the potential to interrogate liquid level by measuring the strain induced in each mPOFBG embedded in a silicone rubber (SR) diaphragm, which deforms due to hydrostatic pressure variations. The sensor exhibits a highly linear response over the sensing range, a good repeatability, and a high resolution. The sensitivity of the sensor is found to be 98 pm/cm of water, enhanced by more than a factor of 9 when compared to an equivalent sensor based on a silica fiber around 1550 nm. The temperature sensitivity is studied and a multi-sensor arrangement proposed, which has the potential to provide level readings independent of temperature and the liquid density.