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  • Journal article
    Wang Y, Thipparapu NK, Wang S, Barua P, Richardson DJ, Sahu JKet al., 2019,

    Study on the temperature dependent characteristics of O-band bismuth-doped fiber amplifier.

    , Opt Lett, Vol: 44, Pages: 5650-5653

    We report the temperature dependent performance of an O-band bismuth (Bi)-doped fiber amplifier (BDFA) in the temperature range from -60 to +80°C. At room temperature, maximum gains of 27 and 40 dB with noise figures (NFs) of 4.3 and 4.8 dB are measured for -23  dBm signal power in the single and double pass BDFA, respectively. An increment in gain and reduction in NF is observed as the ambient temperature of the BDFA is reduced. In the double pass BDFA, the temperature dependent gain coefficient from -60 to +80°C is found to be around -0.02 and -0.03  dB/°C across the wavelength band of 1300-1360 nm for -10 and -23  dBm signal powers, respectively. We also study the gain and NF characteristics with pump power and signal power at different temperatures, and a maximum gain of 45 dB is obtained at -60°C for -30  dBm signal power.

  • Journal article
    Davis SPX, Kumar S, Alexandrov Y, Bhargava A, da Silva Xavier G, Rutter GA, Frankel P, Sahai E, Flaxman S, French PMW, McGinty Jet al., 2019,

    Convolutional neural networks for reconstruction of undersampled optical projection tomography data applied to in vivo imaging of zebrafish.

    , Journal of Biophotonics, Vol: 12, ISSN: 1864-063X

    Optical projection tomography (OPT) is a 3D mesoscopic imaging modality that can utilize absorption or fluorescence contrast. 3D images can be rapidly reconstructed from tomographic data sets sampled with sufficient numbers of projection angles using the Radon transform, as is typically implemented with optically cleared samples of the mm-to-cm scale. For in vivo imaging, considerations of phototoxicity and the need to maintain animals under anesthesia typically preclude the acquisition of OPT data at a sufficient number of angles to avoid artifacts in the reconstructed images. For sparse samples, this can be addressed with iterative algorithms to reconstruct 3D images from undersampled OPT data, but the data processing times present a significant challenge for studies imaging multiple animals. We show here that convolutional neural networks (CNN) can be used in place of iterative algorithms to remove artifacts - reducing processing time for an undersampled in vivo zebrafish dataset from 77 to 15 minutes. We also show that using CNN produces reconstructions of equivalent quality to CS with 40% fewer projections. We further show that diverse training data classes, for example ex vivo mouse tissue data, can be used for CNN-based reconstructions of OPT data of other species including live zebrafish.

  • Journal article
    Ramuz M, Hasan A, Gruscheski L, Diakonov I, Pavlaki N, Nikolaev VO, Harding S, Dunsby C, Gorelik Jet al., 2019,

    A software tool for high-throughput real-time measurement of intensity-based ratio-metric FRET

    , Cells, Vol: 8, ISSN: 2073-4409

    Förster resonance energy transfer (FRET) is increasingly used for non-invasive measurement of fluorescently tagged molecules in live cells. In this study, we have developed a freely available software tool MultiFRET, which, together with the use of a motorised microscope stage, allows multiple single cells to be studied in one experiment. MultiFRET is a Java plugin for Micro-Manager software, which provides real-time calculations of ratio-metric signals during acquisition and can simultaneously record from multiple cells in the same experiment. It can also make other custom-determined live calculations that can be easily exported to Excel at the end of the experiment. It is flexible and can work with multiple spectral acquisition channels. We validated this software by comparing the output of MultiFRET to that of a previously established and well-documented method for live ratio-metric FRET experiments and found no significant difference between the data produced with the use of the new MultiFRET and other methods. In this validation, we used several cAMP FRET sensors and cell models: i) isolated adult cardiomyocytes from transgenic mice expressing the cytosolic epac1-camps and targeted pmEpac1 and Epac1-PLN sensors, ii) isolated neonatal mouse cardiomyocytes transfected with the AKAP79-CUTie sensor, and iii) human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) transfected with the Epac-SH74 sensor. The MultiFRET plugin is an open source freely available package that can be used in a wide area of live cell imaging when live ratio-metric calculations are required.

  • Journal article
    Damzen M, Kerridge-Johns W, Geberbauer J, 2019,

    Vortex mode transformation interferometry

    , Journal of Optics, Vol: 22, Pages: 1-9, ISSN: 1464-4258

    Whilst many techniques exist for generation of an optical vortex, there remains a need for new devices and methods that can also provide vortex generation withhigher powers, greater flexibility of wavelength, and generation beyondthe lowest-order Laguerre-Gaussian 𝐿𝐺01modeto address a broader range of practical applications.This work revealshow an all-mirror based interferometricmode transformation system can provide these propertiesincludingrevealing, for the first time,the generation ofa much richer set of vortex mode patterns than might have been thought possible previously.Anew developed theoreticalformulation, confirmed with excellent agreement by experimental demonstrationsin an imbalanced Sagnac interferometer,showsinterferometric transformation is possible for all orders of Laguerre-Gaussian 𝐿𝐺0𝑙modes into a rich set of high quality higher-order vortex and vortex superposition. The interferometric approachis shown to be configurabletoincrease or decrease vorticity. The new mathematical formulation provides the ability to perform a fullmodal power analysis of both the mode-transformed transmitted vortex and the complementary reflected beam at the Sagnac beamsplitter port.A discussion is made on the origin of the orbital angular momentum transferred to the vortex output from the Sagnac beamsplitter.

  • Journal article
    Tawy G, Wang J, Damzen M, 2019,

    Pump-induced lensing effects in diode pumped Alexandrite lasers

    , Optics Express, Vol: 27, Pages: 35865-35883, ISSN: 1094-4087

    It is essential to understand the pump-induced lensing and aberration effects in solid-state lasers, such as Alexandrite, since these set limits on laser power scaling whilst maintaininghigh spatial TEM00beam quality. In this work, we present direct wavefront measurements ofpump-induced lensing and spherical aberration using a Shack-Hartmann wavefront sensor, for thefirst time, in a diode-pumped Alexandrite laser, and under both non-lasing and lasing conditions.The lens dioptric power is found to be weakly sub-linear with respect to the absorbed pumppower, and under lasing, the lensing power is observed to decrease to60 %of its non-lasingvalue. The results are inconsistent with a thermal lens model but a fuller theoretical formulationis made of a combined thermal and population lens model giving good quantitative agreementto the observed pump power dependence of the induced-lensing under non-lasing conditionsand the reduced lensing under lasing conditions. The deduced value for the difference inexcited to ground state polarizability is consistent with prior measurement estimates for otherchromium-doped gain media. The finding of this paper provide new insight into pump-inducedlensing in Alexandrite and also provides a basis for a fast saturable population lens mechanism toaccount for self-Q-switching observed recently in Alexandrite laser systems.

  • Journal article
    Corcoran D, Juskaite V, Xu Y, Gorlitz F, Alexandrov Y, Dunsby C, French P, Leitinger Bet al., 2019,

    DDR1 autophosphorylation is a result of aggregation into dense clusters

    , Scientific Reports, Vol: 9, ISSN: 2045-2322

    The collagen receptor DDR1 is a receptor tyrosine kinase that promotes progression ofa wide range of human disorders. Little is known about how ligand binding triggers DDR1 kinase activity. We previously reported that collagen induces DDR1 activation through lateral dimer association and phosphorylation between dimers, a process that requires specific transmembrane association. Here we demonstrate ligand-induced DDR1 clustering by widefield and super-resolution imaging and provide evidence for a mechanism whereby DDR1 kinase activity is determined by its molecular density. Ligand binding resulted in initial DDR1 reorganisation into morphologically distinct clusters with unphosphorylated DDR1. Further compaction over time led to clusters with highly aggregated and phosphorylated DDR1. Ligand-induced DDR1 clustering was abolished by transmembrane mutations but did not require kinase activity. Our results significantly advance our understanding of the molecular events underpinning ligand-induced DDR1 kinase activity and provide an explanation for the unusually slow DDR1 activation kinetics.

  • Journal article
    Jones DC, Kumar S, Lanigan PMP, McGuinness CD, Dale MW, Twitchen DJ, Fisher D, Martineau PM, Neil M, Dunsby C, French Pet al., 2019,

    Multidimensional luminescence microscope for imaging defect colour centres in diamond

    , Methods and Applications in Fluorescence, Vol: 8, ISSN: 2050-6120

    We report a multidimensional luminescence microscope providing hyperspectral imaging and time-resolved (luminescence lifetime) imaging for the study of luminescent diamond defects. The instrument includes crossed-polariser white light transmission microscopy to reveal any birefringence that would indicate strain in the diamond lattice. We demonstrate the application of this new instrument to defects in natural and synthetic diamonds including N3, nitrogen and silicon vacancies. Hyperspectral imaging provides contrast that is not apparent in conventional intensity images and the luminescence lifetime provides further contrast.

  • Conference paper
    Petropoulos P, Hong Y, Bottrill K, Taengnoi N, Sakr H, Bradley TD, Thipparapu NK, Wang Y, Umnikov AA, Hayes JR, Jasion GT, Sahu JK, Poletti F, Richardson DJet al., 2019,

    Extending the optical bandwidth of optical communication systems

    , ISSN: 2162-108X

    This talk discusses the new avenues facilitated through the adoption of ultra-broadband hollow-core optical transmission fibres, paired with amplifiers covering alternative wavelength bands. Transmission experiments using these technologies over an extended optical bandwidth are presented.

  • Conference paper
    Thipparapu NK, Wang Y, Wang S, Barua P, Sahu JKet al., 2019,

    Bi-doped silica-based fiber amplifier for O-band transmission

    , ISSN: 2162-108X

    Bismuth (Bi)-doped fibers offer a great potential to develop fiber sources in the 1150-1800nm wavelength region. Here, we review our recent work on Bi-doped fiber amplifiers in the O-band covering from 1300-1360nm.

  • Journal article
    Andrew Y, Bähner JP, Battle R, Jirman Tet al., 2019,

    H-Mode Power Threshold Studies on MAST †

    , Plasma, Vol: 2, Pages: 328-338

    Analysis of the L–H and H–L transition power thresholds (Pth) and pedestal parameters are presented for the mega ampere spherical tokamak (MAST). The dependencies of Pth on the average, core plasma electron density, X-point height, and plasma current are described. Increasing X-point distance from the divertor floor over 10–12 cm is found to increase Pth by a factor of three, while X-point heights greater than this have no further influence. The X-point height dependence of Pth is also observed to be sensitive to the plasma current. An Ip decrease from 0.77 MA to 0.65 MA, is observed to lower Pth by a factor of three across the X-point height scan and increases the maximum X-point height at which Pth stops increasing by 3 cm. Finally, a comparison of the experimental results with the predictions by the finite beta drift wave model is made, which provides a reasonable condition for the transition into and out of the H-mode.

  • Journal article
    Christensen-Jeffries K, Brown J, Harput S, Zhang G, Zhu J, Tang M-X, Dunsby C, Eckersley RJet al., 2019,

    Poisson statistical model of ultrasound super-resolution imaging acquisition time

    , IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 66, Pages: 1246-1254, ISSN: 0885-3010

    A number of acoustic super-resolution techniques have recently been developed to visualize microvascular structure and flow beyond the diffraction limit. A crucial aspect of all ultrasound (US) super-resolution (SR) methods using single microbubble localization is time-efficient detection of individual bubble signals. Due to the need for bubbles to circulate through the vasculature during acquisition, slow flows associated with the microcirculation limit the minimum acquisition time needed to obtain adequate spatial information. Here, a model is developed to investigate the combined effects of imaging parameters, bubble signal density, and vascular flow on SR image acquisition time. We find that the estimated minimum time needed for SR increases for slower blood velocities and greater resolution improvement. To improve SR from a resolution of λ/10 to λ/20 while imaging the microvasculature structure modeled here, the estimated minimum acquisition time increases by a factor of 14. The maximum useful imaging frame rate to provide new spatial information in each image is set by the bubble velocity at low blood flows (<;150 mm/s for a depth of 5 cm) and by the acoustic wave velocity at higher bubble velocities. Furthermore, the image acquisition procedure, transmit frequency, localization precision, and desired super-resolved image contrast together determine the optimal acquisition time achievable for fixed flow velocity. Exploring the effects of both system parameters and details of the target vasculature can allow a better choice of acquisition settings and provide improved understanding of the completeness of SR information.

  • Journal article
    Tawy G, Damzen M, 2019,

    Tunable, dual wavelength and self-Q-switched Alexandrite laser using crystal birefringence control

    , Optics Express, Vol: 27, Pages: 17507-17520, ISSN: 1094-4087

    We present a red-diode-pumped Alexandrite laser with continuous wavelength tunability, dual wavelength and self-Q-switching in an ultra-compact resonator containing only the gain medium. Wavelength tuning is obtained by varying the geometrical path length and birefringence by tilting a Brewster-cut Alexandrite crystal. Two crystals from independent suppliers are used to demonstrate and compare the performance. Wavelength tuning between 750 and 764 nm is demonstrated in the first crystal and between 747 and 768 nm in the second crystal. Stable dual wavelength operation is also obtained in both crystals with wavelength separation determined by the crystal free spectral range. Temperature tuning was also demonstrated to provide finer wavelength tuning at a rate of −0.07 nm K −1. Over a narrow tuning range, stable self-Q-switching is observed with a pulse duration of 660 ns at 135 kHz, which we believe is the highest Q-switched pulse rate in Alexandrite to date. Theoretical modelling is performed showing good agreement with the wavelength tuning and dual wavelength results.

  • Journal article
    Lagarto J, Dyer B, Dunsby C, Peters N, French P, Dunsby C, Lyon Aet al., 2019,

    In vivo label-free optical monitoring of structural and metabolic remodeling of myocardium following infarction

    , Biomedical Optics Express, Vol: 10, Pages: 3506-3521, ISSN: 2156-7085

    Cardiac remodeling following myocardial infarction (MI) involves structural and functional alterations in the infarcted and remote viable myocardium that can ultimately lead to heart failure. The underlying mechanisms are not fully understood and, following our previous study of the autofluorescence lifetime and diffuse reflectance signatures of the myocardium in vivo at 16 weeks post MI in rats [Biomed. Opt. Express 6(2), 324 (2015)], we here present data obtained at 1, 2 and 4 weeks post myocardial infarction that help follow the temporal progression of these changes. Our results demonstrate that both structural and metabolic changes in the heart can be monitored from the earliest time points following MI using label-free optical readouts, not only in the region of infarction but also in the remote non-infarcted myocardium. Changes in the autofluorescence intensity and lifetime parameters associated with collagen type I autofluorescence were indicative of progressive collagen deposition in tissue that was most pronounced at earlier time points and in the region of infarction. In addition to significant collagen deposition in infarcted and non-infarcted myocardium, we also report changes in the autofluorescence parameters associated with reduced nicotinamide adenine (phosphate) dinucleotide (NAD(P)H) and flavin adenine dinucleotide (FAD), which we associate with metabolic alterations throughout the heart. Parallel measurements of the diffuse reflectance spectra indicated an increased contribution of reduced cytochrome c. Our findings suggest that combining time-resolved spectrofluorometry and diffuse reflectance spectroscopy could provide a useful means to monitor cardiac function in vivo at the time of surgery.

  • Journal article
    Zhu J, Rowland E, Harput S, Riemer K, Leow CH, Clark B, Cox K, Lim A, Christensen-Jeffries K, Zhang G, Brown J, Dunsby C, Eckersley R, Weinberg P, Tang Met al., 2019,

    3D super-resolution ultrasound imaging of rabbit lymph node vasculature in vivo using microbubbles

    , Radiology, Vol: 291, Pages: 642-650, ISSN: 0033-8419

    Background: Variations in lymph node (LN) microcirculation can be indicative of metastasis. Identifying and quantifying metastatic LNs remains essential for prognosis and treatment planning but a reliable non-invasive imaging technique is lacking. 3D super-resolution (SR) ultrasound has shown potential to noninvasively visualize microvascular networks in vivo.Purpose: To study the feasibility of 3D SR ultrasound imaging of rabbit lymph node (LN) microvascular structure and blood flow using microbubbles.Materials and Methods: In vivo studies were carried out to image popliteal LNs of two healthy male New Zealand White rabbits aged 6-8 weeks. 3D high frame rate contrast enhanced ultrasound was achieved by mechanically scanning a linear imaging probe. Individual microbubbles were identified, localized, and tracked to form 3D SR images and super-resolved velocity maps. Acoustic sub-aperture processing (ASAP)was used to improve image contrast and generateenhanced power Doppler (PD) and color Doppler (CD) images. Vessel size and blood flow velocity distributions were evaluated and assessed by Student’s paired t-test. Results:SR images revealed micro-vessels in the rabbitLN, with branches clearly resolved when separated by 30 μm, which is less than half of the acoustic wavelength and not resolvable by power or color Doppler. The apparent size distribution of most vessels in the SR images was below 80 μm and agrees with micro-CT data whereas most of those detected by Doppler techniques were larger than 80 μm. The blood flow velocity distribution indicated that most of the blood flow in the rabbit popliteal LN was at velocities lower than 5mm/s. Conclusion: 3D super-resolution ultrasound imaging using microbubbles allows non-invasive and non-ionizing visualization and quantification of rabbit lymph node microvascular structures and blood flow dynamics with resolution below the wave diffraction limit.

  • Journal article
    Thipparapu NK, Wang Y, Wang S, Umnikov AA, Barua P, Sahu JKet al., 2019,

    Bi-doped fiber amplifiers and lasers [Invited]

    , Optical Materials Express, Vol: 9, Pages: 2446-2465

    Bismuth (Bi) doped fibers have shown promising potential for lasers and amplifiers in the 1150-1500 nm and 1600-1800nm wavelength region. Bi-doped aluminosilicate, phosphosilicate and germanosilicate fibers provide luminescence around 1150 nm, 1300 nm and 1450 nm, respectively. Recent results have demonstrated the possibility to extend the Bi luminescence window beyond 1600 nm using Bi-doped high (≥ 50 mol %) germanosilicate fibers. These spectral regions can serve a wide range of applications in medicine, astronomy, defense and to extend the optical fiber communication. However, Bi-doped fiber lasers and amplifiers are still far from their optimum performance owing to the unclear nature of the near-infrared emitting Bi active centers. In this paper, we review the current state of the art of Bi-doped silica fiber lasers (CW and pulsed) and amplifiers in different wavelength bands. Also, we present our work on the development of Bi-doped aluminosilicate and phosphosilicate fiber lasers and amplifiers in the 1180 nm and 1330 nm bands. These lasers and amplifiers find applications in generating visible light sources and to access the second telecommunication window. The fibers used here were fabricated by modified chemical vapor deposition-solution doping technique and characterized for their unsaturable loss. Moreover, we present the influence of pump wavelengths on the gain, noise figure and laser efficiency of these Bi-doped fiber amplifiers and lasers. We also discuss Bi-doped fibers for pulsed laser application and demonstrate a mode-locked Bi-doped fiber laser operating at 1340 nm.

  • Journal article
    Guo W, Kumar S, Gorlitz F, garcia EC, Alexandrov Y, Munro I, Kelly D, Warren S, Thorpe P, Dunsby C, French Pet al., 2019,

    Automated fluorescence lifetime imaging high content analysis of Förster resonance energy transfer between endogenously-labeled kinetochore proteins in live budding yeast cells

    , Slas Technology, Vol: 24, Pages: 308-320, ISSN: 2472-6303

    We describe an open-source automated multiwell plate fluorescence lifetime imaging (FLIM) methodology to read out Förster resonance energy transfer (FRET) between fluorescent proteins (FPs) labeling endogenous kinetochore proteins (KPs) in live budding yeast cells. The low copy number of many KPs and their small spatial extent present significant challenges for the quantification of donor fluorescence lifetime in the presence of significant cellular autofluorescence and photobleaching. Automated FLIM data acquisition was controlled by µManager and incorporated wide-field time-gated imaging with optical sectioning to reduce background fluorescence. For data analysis, we used custom MATLAB-based software tools to perform kinetochore foci segmentation and local cellular background subtraction and fitted the fluorescence lifetime data using the open-source FLIMfit software. We validated the methodology using endogenous KPs labeled with mTurquoise2 FP and/or yellow FP and measured the donor fluorescence lifetimes for foci comprising 32 kinetochores with KP copy numbers as low as ~2 per kinetochore under an average labeling efficiency of 50%. We observed changes of median donor lifetime ≥250 ps for KPs known to form dimers. Thus, this FLIM high-content analysis platform enables the screening of relatively low-copy-number endogenous protein–protein interactions at spatially confined macromolecular complexes.

  • Journal article
    Zhang G, Harput S, Hu H, Christensen-Jeffries K, Zhu J, Brown J, Leow CH, Eckersley R, Dunsby C, Tang M-Xet al., 2019,

    Fast acoustic wave sparsely activated localization microscopy (fast-AWSALM): ultrasound super-resolution using plane-wave activation of nanodroplets

    , IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 66, Pages: 1039-1046, ISSN: 0885-3010

    Localization-based ultrasound super-resolution imaging using microbubble contrast agents and phase-change nano-droplets has been developed to visualize microvascular structures beyond the diffraction limit. However, the long data acquisition time makes the clinical translation more challenging. In this study, fast acoustic wave sparsely activated localization microscopy (fast-AWSALM) was developed to achieve super-resolved frames with sub-second temporal resolution, by using low-boiling-point octafluoropropane nanodroplets and high frame rate plane waves for activation, destruction, as well as imaging. Fast-AWSALM was demonstrated on an in vitro microvascular phantom to super-resolve structures that could not be resolved by conventional B-mode imaging. The effects of the temperature and mechanical index on fast-AWSALM was investigated. Experimental results show that sub-wavelength micro-structures as small as 190 lm were resolvable in 200 ms with plane-wave transmission at a center frequency of 3.5 MHz and a pulse repetition frequency of 5000 Hz. This is about a 3.5 fold reduction in point spread function full-width-half-maximum compared to that measured in conventional B-mode, and two orders of magnitude faster than the recently reported AWSALM under a non-flow/very slow flow situations and other localization based methods. Just as in AWSALM, fast-AWSALM does not require flow, as is required by current microbubble based ultrasound super resolution techniques. In conclusion, this study shows the promise of fast-AWSALM, a super-resolution ultrasound technique using nanodroplets, which can generate super-resolution images in milli-seconds and does not require flow.

  • Conference paper
    Chandran AM, Runcorn TH, Murray RT, Taylor JRet al., 2019,

    620 nm source by second harmonic generation of a phosphosilicate raman fiber amplifier

    , Conference on Lasers and Electro-Optics (CLEO), Publisher: IEEE, ISSN: 2160-9020

    We demonstrate a nanosecond-pulsed 620 nm source through frequency doubling a 1240 nm phosphosilicate Raman fiber amplifier. The source emits up to 213 mW of average power, and is repetition rate and pulse duration tunable.

  • Journal article
    Quicke P, Song C, McKimm EJ, Milosevic MM, Howe CL, Neil M, Schultz SR, Antic SD, Foust AJ, Knopfel Tet al., 2019,

    Corrigendum: Single-neuron level one-photon voltage imaging with sparsely targeted genetically encoded voltage indicators

    , Frontiers in Cellular Neuroscience, Vol: 13, ISSN: 1662-5102

    Voltage imaging of many neurons simultaneously at single-cell resolution is hampered bythe difficulty of detecting small voltage signals from overlapping neuronal processes inneural tissue. Recent advances in genetically encoded voltage indicator (GEVI) imaginghave shown single-cell resolution optical voltage recordings in intact tissue throughimaging naturally sparse cell classes, sparse viral expression, soma restricted expression,advanced optical systems, or a combination of these. Widespread sparse and strongtransgenic GEVI expression would enable straightforward optical access to a denselyoccurring cell type, such as cortical pyramidal cells. Here we demonstrate that a recentlydescribed sparse transgenic expression strategy can enable single-cell resolution voltageimaging of cortical pyramidal cells in intact brain tissue without restricting expression tothe soma. We also quantify the functional crosstalk in brain tissue and discuss optimalimaging rates to inform future GEVI experimental design.

  • Journal article
    Thipparapu NK, Wang Y, Umnikov AA, Barua P, Richardson DJ, Sahu JKet al., 2019,

    40  dB gain all fiber bismuth-doped amplifier operating in the O-band.

    , Opt Lett, Vol: 44, Pages: 2248-2251

    In this Letter, we investigate and compare the gain and noise figure characteristics of bismuth (Bi)-doped fiber amplifiers configured in both single and double signal pass implementations. A maximum gain of 25 dB and a noise figure of 4 dB is measured at 1360 nm in the single pass configuration for -23  dBm input signal power, whereas in the double pass configuration the gain of the amplifier is improved significantly by 14 dB allowing us to achieve a gain of 39 dB with a noise figure of 5 dB. To the best of our knowledge, this is the highest gain reported to date using Bi-doped fiber as a gain medium. Furthermore, we also study the gain and noise figure dependency on pump power, signal power, and pump wavelength for the double pass amplifier configuration. We observed similar gain and noise figure performance in the double pass configuration to that of the single pass configuration but with the benefit of less pump power and a shorter length of the Bi-doped fiber.

  • Journal article
    Wu P-J, Masouleh MI, Paterson C, Dini D, Török P, Overby DR, Kabakova IVet al., 2019,

    Detection of proteoglycan loss from articular cartilage using Brillouin microscopy, with applications to osteoarthritis

    , Biomedical Optics Express, Vol: 10, Pages: 2457-2466, ISSN: 2156-7085

    The degeneration of articular cartilage (AC) occurs in osteoarthritis (OA), which is a leading cause of pain and disability in middle-aged and older people. The early disease-related changes in cartilage extra-cellular matrix (ECM) start with depletion of proteoglycan (PG), leading to an increase in tissue hydration and permeability. These early compositional changes are small (<10%) and hence difficult to register with conventional non-invasive imaging technologies (magnetic resonance and ultrasound imaging). Here we apply Brillouin microscopy for detecting changes in the mechanical properties and composition of porcine AC. OA-like degradation is mimicked by enzymatic tissue digestion, and we compare Brillouin microscopy measurements against histological staining of PG depletion over varying digestion times and enzyme concentrations. The non-destructive nature of Brillouin imaging technology opens new avenues for creating minimally invasive arthroscopic devices for OA diagnostics and therapeutic monitoring.

  • Conference paper
    Chandran AM, Runcorn TH, Tmurray R, Taylor JRet al., 2019,

    620nm Source by Second Harmonic Generation of a Phosphosilicate Raman Fiber Amplifier

    We demonstrate a nanosecond-pulsed 620 nm source through frequency doubling a 1240 nm phosphosilicate Raman fiber amplifier. The source emits up to 213 mW of average power, and is repetition rate and pulse duration tunable.

  • Conference paper
    Thipparapu NK, Wang Y, Umnikov AA, Barua P, Richardson DJ, Sahu JKet al., 2019,

    High Gain Bi-Doped All Fiber Amplifier for O-Band DWDM Optical Fiber Communication

    We report a double-pass bismuth-doped fiber amplifier operating in the O-band with a 31dB gain and a 7dB NF for -10dBm input signal. The amplifier power conversion efficiency and gain-coefficient are 11% and 0.06dB/mW, respectively.

  • Journal article
    Kerridge-Johns W, Geberbauer JWT, Damzen M, 2019,

    Vortex laser by transforming Gaussian mode with an interferometric output coupler

    , Optics Express, Vol: 27, Pages: 11642-11650, ISSN: 1094-4087

    Generation of vortex beams directly from the laser source can be limited in power and efficiency, or to specific pump sources and gain media. Here, we propose a new high power and high efficiency vortex laser methodology with interferometric mode transformation as output coupling, which uses high power handling and low loss optics that have wavelength versatility. Experimental demonstration is made in a diode-pumped Nd:YVO4 laser using an imbalanced Sagnac interferometer as output coupler producing high quality vortex output beams (M2 = 2.07) with fully selectable control of handedness whilst the intracavity mode is maintained as a fundamental Gaussian. Vortex output power >3W is produced with only small reduction in efficiency compared to the equivalent TEM00 laser. Continuous variation of vortex output coupling transmission and the quality of the vortex is investigated experimentally showing good agreement with theory. This work reveals a new approach to high power structured laser radiation direct from the source through interferometric spatial mode transformations.

  • Journal article
    Gratus J, Kinsler P, McCall M, 2019,

    Evaporating black-holes, wormholes, and vacuum polarisation: must they always conserve charge?

    , Foundations of Physics, Vol: 49, Pages: 330-350, ISSN: 0015-9018

    A careful examination of the fundamentals of electromagnetic theory showsthat due to the underlying mathematical assumptions required for Stokes’ Theorem,global charge conservation cannot be guaranteed in topologically non-trivial space-times. However, in order to break the charge conservation mechanism we must alsoallow the electromagnetic excitation fieldsD,Hto possess a gauge freedom, just asthe electromagnetic scalar and vector potentialsφandAdo. This has implicationsfor the treatment of electromagnetism in spacetimes where black holes both form andthen evaporate, as well as extending the possibilities for treating vacuum polarisation.Using this gauge freedom ofD,Hwe also propose an alternative to the acceptednotion that a charge passing through a wormhole necessarily leads to an additional(effective) charge on the wormhole’s mouth.

  • Journal article
    Gouveia RM, Lepert G, Gupta S, Mohan RR, Paterson C, Connon CJet al., 2019,

    Assessment of corneal substrate biomechanics and its effect on epithelial stem cell maintenance and differentiation

    , NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723
  • Journal article
    Brown J, Christensen-Jeffries K, Harput S, Zhang G, Zhu J, Dunsby C, Tang M-X, Eckersley RJet al., 2019,

    Investigation of microbubble detection methods for super-resolution imaging of microvasculature

    , IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 66, Pages: 676-691, ISSN: 0885-3010

    Ultrasound super-resolution techniques use the response of microbubble contrast agents (MBs) to visualize the microvasculature. Techniques that localize isolated bubble signals first require detection algorithms to separate the MB and tissue responses. This work explores the three main MB detection techniques for super-resolution of microvasculature. Pulse inversion (PI), differential imaging (DI) and singular value decomposition (SVD) filtering were compared in terms of the localization accuracy, precision and contrast to tissue ratio (CTR). MB responses were simulated based on the properties of Sonovue™ and using the Marmottant model. Non-linear propagation through tissue was modelled using the k-Wave software package. For the parameters studied, the results show that PI is most appropriate for low frequency applications, but also most dependent on transducer bandwidth. SVD is preferable for high frequency acquisition where localization precision on the order of a few microns is possible. PI is largely independent of flow direction and speed compared to SVD and DI, so is appropriate for visualizing the slowest flows and tortuous vasculature. SVD is unsuitable for stationary MBs and can introduce a localization error on the order of hundreds of microns over the speed range 0- 2 mm/s and flow directions from lateral (parallel to probe) to axial (perpendicular to probe). DI is only suitable for flow rates > 0.5 mm/s or as flow becomes more axial. Overall, this study develops a MB and tissue non-linear simulation platform to improve understanding of how different MB detection techniques can impact the super-resolution process and explores some of the factors influencing the suitability of each.

  • Journal article
    Chen L, Li G, Tang L, Zhang M, Liu L, Liu A, McGinty J, Ruan Set al., 2019,

    Hyperspectral scanning laser optical tomography

    , Journal of Biophotonics, Vol: 12, ISSN: 1864-063X

    In order to study physical relationships within tissue volumes or even organism-level systems, the spatial distribution of multiple fluorescent markers needs to be resolved efficiently in three dimensions. Here, rather than acquiring discrete spectral images sequentially using multiple emission filters, a hyperspectral scanning laser optical tomography system is developed to obtain hyperspectral volumetric data sets with 2-nm spectral resolution of optically transparent mesoscopic (millimeter-centimeter) specimens. This is achieved by acquiring a series of point-scanning hyperspectral extended depth of field images at different angles and subsequently tomographically reconstructing the 3D intensity distribution for each wavelength. This technique is demonstrated to provide robust measurements via the comparison of spectral and intensity profiles of fluorescent bead phantoms. Due to its enhanced spectral resolving ability, this technique is also demonstrated to resolve largely overlapping fluorophores, as demonstrated by the 3D fluorescence hyperspectral reconstruction of a dual-labeled mouse thymus gland sample and the ability to distinguish tumorous and normal tissues of an unlabeled mouse intestine sample.

  • Journal article
    Soor N, Quicke P, Howe C, Pang KT, Neil M, Schultz S, Foust Aet al., 2019,

    All-optical crosstalk-free manipulation and readout of Chronos-expressing neurons

    , Journal of Physics D: Applied Physics, Vol: 52, Pages: 1-10, ISSN: 0022-3727

    All optical neurophysiology allows manipulation and readout of neural network activity with single-cell spatial resolution and millisecond temporal resolution. Neurons can be made to express proteins that actuate transmembrane currents upon light absorption, enabling optical control of membrane potential and action potential signalling. In addition, neurons can be genetically or synthetically labelled with fluorescent reporters of changes in intracellular calcium concentration or membrane potential. Thus, to optically manipulate and readout neural activity in parallel, two spectra are involved: the action spectrum of the actuator, and the absorption spectrum of the fluorescent reporter. Due to overlap in these spectra, previous all-optical neurophysiology paradigms have been hindered by spurious activation of neuronal activity caused by the readout light. Here, we pair the blue-green absorbing optogenetic actuator, Chronos, with a deep red-emitting fluorescent calcium reporter CaSiR-1. We show that cultured Chinese hamster ovary cells transfected with Chronos do not exhibit transmembrane currents when illuminated with wavelengths and intensities suitable for exciting one-photon CaSiR-1 fluorescence. We then demonstrate crosstalk-free, high signal-to-noise ratio CaSiR-1 red fluorescence imaging at 100 frames s−1 of Chronos-mediated calcium transients evoked in neurons with blue light pulses at rates up to 20 Hz. These results indicate that the spectral separation between red light excited fluorophores, excited efficiently at or above 640 nm, with blue-green absorbing opsins such as Chronos, is sufficient to avoid spurious opsin actuation by the imaging wavelengths and therefore enable crosstalk-free all-optical neuronal manipulation and readout.

  • Conference paper
    Mathur V, Mathur A, Kumar S, 2019,

    A comparative study of soft computing paradigms for automatic humour detection in Tweets

    , Pages: 975-979

    Humour has been an integral entity of human life with its lingual, social and psychological aspects. Due to its vast applications and increasing popularity on social media platforms, enabling computers to process humour has become very crucial. Therefore, we intent to aid task of computational analysis of humour by employing deep learning and machine learning techniques for humour detection. We use micro-blogging website twitter, being an abundant source of humorous content, as the focus of this study. We created a symmetrically distributed dataset containing 4000 funny and plain tweets and applied seven supervised classification algorithms to perform the task of detecting tweets, which contain humour. Accuracy, recall and precision have been used as the metrics of performance.

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