Versatile luminescence thermometry via intense green defect emission from an infrared-pumped fluorosilicate optical fiber.

An all-glass optical fiber capable of two distinct methods of optical thermometry is described. Specifically, a silica-clad, barium fluorosilicate glass core fiber, when pumped in the infrared, exhibits visibly intense green defect luminescence whose intensity and upper-state lifetime are strong functions of temperature. Intensity-based optical thermometry over the range from 25°C to 130°C is demonstrated, while a lifetime-based temperature sensitivity is shown from 25°C to 100°C. Time-domain measurements yield a relative sensitivity of 2.85% K -1 at 373 K (100°C). A proof-of-concept distributed sensor system using a commercial digital single-lens reflex camera is presented, resulting in a measured maximum relative sensitivity of 1.13% K -1 at 368 K (95°C). The sensing system described herein stands as a new blueprint for defect-based luminescence thermometry that takes advantage of pre-existing and relatively inexpensive optical components, and allows for the use of standard cameras or simply direct human observation.

Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain.

Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, lrp6 mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor-interacting protein that regulates lateralized neuronal identity in the zebrafish brain.

High-efficiency radiation-balanced Yb-doped silica fiber laser with 200-mW output.

The focus of this study was the development of a second generation of fiber lasers internally cooled by anti-Stokes fluorescence. The laser consisted of a length of a single-mode fiber spliced to fiber Bragg gratings to form the optical resonator. The fiber was single-moded at the pump (1040 nm) and signal (1064 nm) wavelengths. Its core was heavily doped with Yb, in the initial form of CaF2 nanoparticles, and co-doped with Al to reduce quenching and improve the cooling efficiency. After optimizing the fiber length (4.1 m) and output-coupler reflectivity (3.3%), the fiber laser exhibited a threshold of 160 mW, an optical efficiency of 56.8%, and a radiation-balanced output power (no net heat generation) of 192 mW. On all three metrics, this performance is significantly better than the only previously reported radiation-balanced fiber laser, which is even more meaningful given that the small size of the single-mode fiber core (7.8-µm diameter). At the maximum output power (∼2 W), the average fiber temperature was still barely above room temperature (428 mK). This work demonstrates that with anti-Stokes pumping, it is possible to induce significant gain and energy storage in a small-core Yb-doped fiber while keeping the fiber cool.

Raman amplification at 2.2 µm in silicon core fibers with prospects for extended mid-infrared source generation.

Raman scattering provides a convenient mechanism to generate or amplify light at wavelengths where gain is not otherwise available. When combined with recent advancements in high-power fiber lasers that operate at wavelengths ~2 µm, great opportunities exist for Raman systems that extend operation further into the mid-infrared regime for applications such as gas sensing, spectroscopy, and biomedical analyses. Here, a thulium-doped fiber laser is used to demonstrate Raman emission and amplification from a highly nonlinear silicon core fiber (SCF) platform at wavelengths beyond 2 µm. The SCF has been tapered to obtain a micrometer-sized core diameter (~1.6 µm) over a length of 6 cm, with losses as low as 0.2 dB cm-1. A maximum on-off peak gain of 30.4 dB was obtained using 10 W of peak pump power at 1.99 µm, with simulations indicating that the gain could be increased to up to ~50 dB by extending the SCF length. Simulations also show that by exploiting the large Raman gain and extended mid-infrared transparency of the SCF, cascaded Raman processes could yield tunable systems with practical output powers across the 2-5 µm range.

All-fibre heterogeneously-integrated frequency comb generation using silicon core fibre.

Originally developed for metrology, optical frequency combs are becoming increasingly pervasive in a wider range of research topics including optical communications, spectroscopy, and radio or microwave signal processing. However, application demands in these fields can be more challenging as they require compact sources with a high tolerance to temperature variations that are capable of delivering flat comb spectra, high power per tone, narrow linewidth and high optical signal-to-noise ratio. This work reports the generation of a flat, high power frequency comb in the telecom band using a 17 mm fully-integrated silicon core fibre as a parametric mixer. Our all-fibre, cavity-free source combines the material benefits of planar waveguide structures with the advantageous properties of fibre platforms to achieve a 30 nm bandwidth comb source containing 143 tones with <3 kHz linewidth, 12 dB flatness, and >30 dB OSNR over the entire spectral region.

A Structural Atlas of the Developing Zebrafish Telencephalon Based on Spatially-Restricted Transgene Expression.

Zebrafish telencephalon acquires an everted morphology by a two-step process that occurs from 1 to 5 days post-fertilization (dpf). Little is known about how this process affects the positioning of discrete telencephalic cell populations, hindering our understanding of how eversion impacts telencephalic structural organization. In this study, we characterize the neurochemistry, cycle state and morphology of an EGFP positive (+) cell population in the telencephalon of Et(gata2:EGFP)bi105 transgenic fish during eversion and up to 20dpf. We map the transgene insertion to the early-growth-response-gene-3 (egr3) locus and show that EGFP expression recapitulates endogenous egr3 expression throughout much of the pallial telencephalon. Using the gata2:EGFP bi105 transgene, in combination with other well-characterized transgenes and structural markers, we track the development of various cell populations in the zebrafish telencephalon as it undergoes the morphological changes underlying eversion. These datasets were registered to reference brains to form an atlas of telencephalic development at key stages of the eversion process (1dpf, 2dpf, and 5dpf) and compared to expression in adulthood. Finally, we registered gata2:EGFPbi105 expression to the Zebrafish Brain Browser 6dpf reference brain (ZBB, see Marquart et al., 2015, 2017; Tabor et al., 2019), to allow comparison of this expression pattern with anatomical data already in ZBB.

Anti-Stokes fluorescence cooling of nanoparticle-doped silica fibers.

The first observation of cooling by anti-Stokes pumping in nanoparticle-doped silica fibers is reported. Four Yb-doped fibers fabricated using conventional modified chemical vapor deposition (MCVD) techniques were evaluated, namely, an aluminosilicate fiber and three fibers in which the Yb ions were encapsulated in CaF2, SrF2, or BaF2 nanoparticles. The nanoparticles, which oxidize during preform processing, provide a modified chemical environment for the Yb3+ ions that is beneficial to cooling. When pumped at the near-optimum cooling wavelength of 1040 nm at atmospheric pressure, the fibers experienced a maximum measured temperature drop of 20.5 mK (aluminosilicate fiber), 26.2 mK (CaF2 fiber), and 16.7 mK (SrF2 fiber). The BaF2 fiber did not cool but warmed slightly. The three fibers that cooled had a cooling efficiency comparable to that of the best previously reported Yb-doped silica fiber that cooled. Data analysis shows that this efficiency is explained by the fibers' high critical quenching concentration and low residual absorptive loss (linked to sub-ppm OH contamination). This study demonstrates the large untapped potential of nanoparticle doping in the current search for silicate compositions that produce optimum anti-Stokes cooling.

Localised structuring of metal-semiconductor cores in silica clad fibres using laser-driven thermal gradients.

The molten core drawing method allows scalable fabrication of novel core fibres with kilometre lengths. With metal and semiconducting components combined in a glass-clad fibre, CO2 laser irradiation was used to write localised structures in the core materials. Thermal gradients in axial and transverse directions allowed the controlled introduction, segregation and chemical reaction of metal components within an initially pure silicon core, and restructuring of heterogeneous material. Gold and tin longitudinal electrode fabrication, segregation of GaSb and Si into parallel layers, and Al doping of a GaSb core were demonstrated. Gold was introduced into Si fibres to purify the core or weld an exposed fibre core to a Si wafer. Ga and Sb introduced from opposite ends of a silicon fibre reacted to form III-V GaSb within the Group IV Si host, as confirmed by structural and chemical analysis and room temperature photoluminescence.

Raman enhanced four-wave mixing in silicon core fibers.

A strong Raman enhancement to the four-wave mixing (FWM) conversion efficiency is obtained in a silicon core fiber (SCF) when pumped with a continuous-wave (CW) source in the telecom band. By tapering the SCFs to alter the core diameter and length, the role of phase-matching on the conversion enhancement is investigated, with a maximum Raman enhancement of ∼15 dB obtained for an SCF with a zero dispersion wavelength close to the pump. Simulations show that by optimizing the tapered waist diameter to overlap the FWM phase-matching with the peak Raman gain, it is possible to obtain large Raman enhanced FWM conversion efficiencies of up to ∼2 dB using modest CW pump powers over wavelengths covering the extended telecom bands.

High-power single-frequency single-mode all-solid photonic bandgap fiber laser with kHz linewidth.

There have been several demonstrations of single-frequency single-mode ytterbium-doped fiber lasers operating at a few hundred watts of power. A narrow spectral linewidth of these lasers is critical for many applications but has never been properly measured before at high powers. In this work, we report the first spectral linewidth measurement at kHz resolution of high-power single-frequency fiber lasers using a heterodyne technique and can confirm that these lasers can indeed operate at a few kHz spectral linewidth. Furthermore, we have improved the power from single-frequency single-mode all-solid photonic bandgap fiber lasers to 500 W using an improved photonic bandgap fiber.

4.8 mJ pulse energy directly from single-mode Q-switched ytterbium fiber lasers.

Using an ytterbium-doped fiber with a 50 µm core and 0.028 NA, a pulse energy of 4.8 mJ was achieved directly from a single-mode Q-switched fiber laser. The repetition rate was 10 kHz and the average power was 48.4 W. The slope efficiencies with regard to the absorbed and launched pump power were ∼74% and ∼59% respectively. The pulse width decreased with increasing pump power. The 4.8 mJ pulse had a FWHM width of ∼300 ns. A shorter pulse of ∼200 ns FWHM was also achieved at 2.06 mJ in another configuration. The M2 was below 1.3 at all pulse energies. This work demonstrates record pulse energy directly from a single-mode Q-switched fiber laser and the feasibility of operating such a laser with high efficiencies.

kW-level monolithic single-mode narrow-linewidth all-solid photonic bandgap fiber amplifier.

Further power scaling of narrow-linewidth fiber lasers is critical for beam combining. Using all-solid photonic bandgap fibers with large effective mode areas and strong higher-order-mode suppression is an interesting approach. Previously, we demonstrated ∼400W single-frequency single-mode power at 1064 nm from a 50/400 photonic bandgap fiber amplifier, limited only by transverse mode instability (TMI). In this work, we demonstrate a TMI-limited single-mode power of 1.37 kW from a monolithic fiber amplifier with a 25/400 photonic bandgap fiber, the highest output power from a photonic bandgap fiber demonstrated to date, to the best of our knowledge. The spectral linewidth is broadened to ∼8GHz to suppress stimulated Brillouin scattering.

All-optical high-speed modulation of THz transmission through silicon core optical fibers.

High speed optical modulation of THz radiation is of interest for information processing and communications applications. In this paper infrared femtosecond pulses are used to generate free carriers that reduce the THz transmission of silicon based waveguides over a broad spectral range. Up to 96% modulation is observed from 0.5 to 7 THz in an optical fiber with a 210 µm diameter gold-doped silicon core. The observed carrier recombination time of 2.0 ± 0.2 ns makes this material suitable for high speed all-optical signal processing. These results show both enhanced modulation depth and reduced carrier lifetime when compared to the performance of a high resistivity float zone silicon rectangular guide with comparable cross sectional area.

Diverse species-specific phenotypic consequences of loss of function sorting nexin 14 mutations.

Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) in both humans and dogs. Studies implicating the phenotypic consequences of SNX14 mutations to be consequences of subcellular disruption to autophagy and lipid metabolism have been limited to in vitro investigation of patient-derived dermal fibroblasts, laboratory engineered cell lines and developmental analysis of zebrafish morphants. SNX14 homologues Snz (Drosophila) and Mdm1 (yeast) have also been conducted, demonstrated an important biochemical role during lipid biogenesis. In this study we report the effect of loss of SNX14 in mice, which resulted in embryonic lethality around mid-gestation due to placental pathology that involves severe disruption to syncytiotrophoblast cell differentiation. In contrast to other vertebrates, zebrafish carrying a homozygous, maternal zygotic snx14 genetic loss-of-function mutation were both viable and anatomically normal. Whilst no obvious behavioural effects were observed, elevated levels of neutral lipids and phospholipids resemble previously reported effects on lipid homeostasis in other species. The biochemical role of SNX14 therefore appears largely conserved through evolution while the consequences of loss of function varies between species. Mouse and zebrafish models therefore provide valuable insights into the functional importance of SNX14 with distinct opportunities for investigating its cellular and metabolic function in vivo.

Tissue-Specific Requirement for the GINS Complex During Zebrafish Development.

Efficient and accurate DNA replication is particularly critical in stem and progenitor cells for successful proliferation and survival. The replisome, an amalgam of protein complexes, is responsible for binding potential origins of replication, unwinding the double helix, and then synthesizing complimentary strands of DNA. According to current models, the initial steps of DNA unwinding and opening are facilitated by the CMG complex, which is composed of a GINS heterotetramer that connects Cdc45 with the mini-chromosome maintenance (Mcm) helicase. In this work, we provide evidence that in the absence of GINS function DNA replication is cell autonomously impaired, and we also show that gins1 and gins2 mutants exhibit elevated levels of apoptosis restricted to actively proliferating regions of the central nervous system (CNS). Intriguingly, our results also suggest that the rapid cell cycles during early embryonic development in zebrafish may not require the function of the canonical GINS complex as neither zygotic Gins1 nor Gins2 isoforms seem to be present during these stages.

The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages.

Toxoplasma gondii is an obligate intracellular parasite capable of invading any nucleated cell. Three main clonal lineages (type I, II, III) exist and murine models have driven the understanding of general and strain-specific immune mechanisms underlying Toxoplasma infection. However, murine models are limited for studying parasite-leukocyte interactions in vivo, and discrepancies exist between cellular immune responses observed in mouse versus human cells. Here, we developed a zebrafish infection model to study the innate immune response to Toxoplasma in vivo By infecting the zebrafish hindbrain ventricle, and using high-resolution microscopy techniques coupled with computer vision-driven automated image analysis, we reveal that Toxoplasma invades brain cells and replicates inside a parasitophorous vacuole to which type I and III parasites recruit host cell mitochondria. We also show that type II and III strains maintain a higher infectious burden than type I strains. To understand how parasites are cleared in vivo, we further analyzed Toxoplasma-macrophage interactions using time-lapse microscopy and three-dimensional correlative light and electron microscopy (3D CLEM). Time-lapse microscopy revealed that macrophages are recruited to the infection site and play a key role in Toxoplasma control. High-resolution 3D CLEM revealed parasitophorous vacuole breakage in brain cells and macrophages in vivo, suggesting that cell-intrinsic mechanisms may be used to destroy the intracellular niche of tachyzoites. Together, our results demonstrate in vivo control of Toxoplasma by macrophages, and highlight the possibility that zebrafish may be further exploited as a novel model system for discoveries within the field of parasite immunity.This article has an associated First Person interview with the first author of the paper.

Observation of optical nonlinearities in an all-solid transverse Anderson localizing optical fiber.

An all-solid transverse Anderson localizing optical fiber (TALOF) was fabricated using a novel combination of the stack-and-draw and molten core methods. Strong Anderson localization is observed in multiple regions of the fiber cross section associated with the higher index strontium aluminosilicate phases randomly arranged within a pure silica matrix. Further, to the best of our knowledge, nonlinear four-wave mixing is reported for the first time in a TALOF.

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges.

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-ß, the toxic driver of Alzheimer's disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.

Low-loss silicon core fibre platform for mid-infrared nonlinear photonics.

Broadband mid-infrared light sources are highly desired for wide-ranging applications that span free-space communications to spectroscopy. In recent years, silicon has attracted great interest as a platform for nonlinear optical wavelength conversion in this region, owing to its low losses (linear and nonlinear) and high stability. However, most research in this area has made use of small core waveguides fabricated from silicon-on-insulator platforms, which suffer from high absorption losses of the use of silica cladding, limiting their ability to generate light beyond 3 µm. Here, we design and demonstrate a compact silicon core, silica-clad waveguide platform that has low losses across the entire silicon transparency window. The waveguides are fabricated from a silicon core fibre that is tapered to engineer mode properties to ensure efficient nonlinear propagation in the core with minimal interaction of the mid-infrared light with the cladding. These waveguides exhibit many of the benefits of fibre platforms, such as a high coupling efficiency and power handling capability, allowing for the generation of mid-infrared supercontinuum spectra with high brightness and coherence spanning almost two octaves (1.6-5.3 µm).

Insights and Aspects to the Modeling of the Molten Core Method for Optical Fiber Fabrication.

The molten core method (MCM) is a versatile technique to fabricate a wide variety of optical fiber core compositions ranging from novel glasses to crystalline semiconductors. One common feature of the MCM is an interaction between the molten core and softened glass cladding during the draw process, which often leads to compositional modification between the original preform and the drawn fiber. This causes the final fiber core diameter, core composition, and associated refractive index profile to vary over time and longitudinally along the fiber. Though not always detrimental to performance, these variations must, nonetheless, be anticipated and controlled as they directly impact fiber properties (e.g., numerical aperture, effective area). As an exemplar to better understand the underlying mechanisms, a silica-cladding, YAG-derived yttrium aluminosilicate glass optical fiber was fabricated and its properties (core diameter, silica concentration profile) were monitored as a function of draw time/length. It was found that diffusion-controlled dissolution of silica into the molten core agreed well with the observations. Following this, a set of first order kinetics equations and diffusion equation using Fick's second law was employed as an initial effort to model the evolution of fiber core diameter and compositional profile with time. From these trends, further insights into other compositional systems and control schemes are provided.