Guidance of ultraviolet light down to 190 nm in a hollow-core optical fibre.

We report an anti-resonant hollow core fibre with ultraviolet transmission down to 190 nm, covering the entire UV-A, UV-B and much of the UV-C band. Guidance from 190 - 400 nm is achieved apart for a narrow high loss resonance band at 245 - 265 nm. The minimum attenuation is 0.13 dB/m at 235 nm and 0.16 dB/m at 325 nm. With an inscribed core diameter of ∼12 µm, the fibre's bend loss at 325 nm was 0.22 dB per turn for a bend radius of 3 cm at 325 nm.

Developing the OpenFlexure Microscope towards medical use: technical and social challenges of developing globally accessible hardware for healthcare.

The OpenFlexure Microscope is an accessible, three-dimensional-printed robotic microscope, with sufficient image quality to resolve diagnostic features including parasites and cancerous cells. As access to lab-grade microscopes is a major challenge in global healthcare, the OpenFlexure Microscope has been developed to be manufactured, maintained and used in remote environments, supporting point-of-care diagnosis. The steps taken in transforming the hardware and software from an academic prototype towards an accepted medical device include addressing technical and social challenges, and are key for any innovation targeting improved effectiveness in low-resource healthcare. This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'.

Measurement of resonant bend loss in anti-resonant hollow core optical fiber: erratum.

An error on the part of the authors in drafting resulted in Eq. (3) being incorrect in the published paper [Opt. Express25, 20612 (2017)10.1364/OE.25.020612]. We present a corrected version of the equation. It should be noted that this does not affect the presented results or conclusions of the paper.

Fast, high-precision autofocus on a motorised microscope: Automating blood sample imaging on the OpenFlexure Microscope.

The OpenFlexure Microscope is a 3D-printed, low-cost microscope capable of automated image acquisition through the use of a motorised translation stage and a Raspberry Pi imaging system. This automation has applications in research and healthcare, including in supporting the diagnosis of malaria in low-resource settings. The plasmodium parasites that cause malaria require high magnification imaging, which has a shallow depth of field, necessitating the development of an accurate and precise autofocus procedure. We present methods of identifying the focal plane of the microscope, and procedures for reliably acquiring a stack of focused images on a system affected by backlash and drift. We also present and assess a method to verify the success of autofocus during the scan. The speed, reliability and precision of each method are evaluated, and the limitations discussed in terms of the end users' requirements.

Two-group Poisson-Dirichlet mixtures for multiple testing.

The simultaneous testing of multiple hypotheses is common to the analysis of high-dimensional data sets. The two-group model, first proposed by Efron, identifies significant comparisons by allocating observations to a mixture of an empirical null and an alternative distribution. In the Bayesian nonparametrics literature, many approaches have suggested using mixtures of Dirichlet Processes in the two-group model framework. Here, we investigate employing mixtures of two-parameter Poisson-Dirichlet Processes instead, and show how they provide a more flexible and effective tool for large-scale hypothesis testing. Our model further employs nonlocal prior densities to allow separation between the two mixture components. We obtain a closed-form expression for the exchangeable partition probability function of the two-group model, which leads to a straightforward Markov Chain Monte Carlo implementation. We compare the performance of our method for large-scale inference in a simulation study and illustrate its use on both a prostate cancer data set and a case-control microbiome study of the gastrointestinal tracts in children from underdeveloped countries who have been recently diagnosed with moderate-to-severe diarrhea.

A perspective on SOAL, a stochastic model of neuronal outgrowth.

A functional nervous system requires neuronal connections to be made in a highly detailed and stereotypic manner. During development, neurons extend processes that can branch, travel in different directions, and form elaborate patterns. These patterns are essential for forming proper connections. Patterns of outgrowth are produced by complex molecular events that cause a fluid membrane to move. The collective impact of dynamic fluctuating events at the microscale cause the patterns of outgrowth observed at the macroscale. Patterning is genetically controlled, but the effects genes have on membrane movement and patterning are not well understood. To better understand how genes control outgrowth patterns, I propose a statistically-oriented asymmetric localization (SOAL) model. This model is based on the theory that receptor-mediated outgrowth activity is stochastically oriented and when the system is at equilibrium there is an equal probability of outgrowth being oriented in any direction. This concept allows a statistical mechanics approach that can correlate the microscale events of outgrowth to the observed macroscale patterns. Proof-of-concept experiments suggest this approach can be used to study the effect genes have on outgrowth patterns. The SOAL model also provides a new theoretical framework for conceptualizing guidance. According to the model, outgrowth activity becomes asymmetrically localized to the neuron's surface in a statistically dependent manner. Extracellular cues regulate the probability of outgrowth along the surface and the orientation of outgrowth fluctuates across the surface over time. This creates a directional bias that allows the growth cone to navigate in reference to the composition of extracellular cues.

Single-mode solarization-free hollow-core fiber for ultraviolet pulse delivery.

In this paper, we report anti-resonant silica hollow-core fibers (AR-HCFs) for solarization-free ultraviolet (UV) pulse transmission. The new fibers reported have lower attenuation than any previous HCFs for this spectral range. We report a single fiber that guides over a part of the UV-C and the whole of the UV-A spectral regions in adjacent transmission bands. A second AR-HCF is used for delivery of 17 nanosecond laser pulses at 266 nm at 30 kHz repetition rate. The fiber maintained a constant transmission, free of silica fluorescence and solarization-induced fiber degradation while delivering 0.46 µJ pulses for a period of over one hour. By direct comparison, we demonstrate that the single-mode AR-HCF significantly outperforms commercially-available high-OH and solarization-resistant silica multimode fibers for pulsed light delivery in this spectral range.

Measurement of resonant bend loss in anti-resonant hollow core optical fiber.

We present the results of measurements of resonant spectral bend loss using a novel apparatus in a series of hollow core anti-resonant optical fibers, important for their applications in the delivery of industrial power ultra-short laser pulses. The measured bend losses exhibit clear wavelength-bend diameter resonances. We demonstrate, in good agreement with theoretical analysis, that the sensitivity to bend diameter (in terms of minimum bend radii) is dependent on the ratio between cladding and core structure size. By decreasing the cladding capillary diameter: core diameter ratio from 0.70 to 0.43 the minimum bend diameter is decreased from >160 mm to ~15 mm at a wavelength of 800 nm. Furthermore it is demonstrated that the exact position of the loss bands is highly dependent on the orientation of the fiber structure with the bend plane.

Efficient diode-pumped mid-infrared emission from acetylene-filled hollow-core fiber.

We report 3.1-3.2 µm mid-infrared emission from acetylene-filled low loss antiresonant hollow-core fiber pumped with an amplified, modulated, narrowband, tunable 1.5 µm diode laser. The maximum power conversion efficiency of ~30%, with respect to the absorbed pump power, is obtained with a 10.5 m length of fiber at 0.7 mbar. The maximum efficiency with respect to the total incident pump power (~20%) and the minimum pump laser energy required (<50 nJ) are both improved compared to similar work reported previously using an optical parametric oscillator as a pump source. This paper provides an effective route to obtain compact mid-infrared fiber lasers.

Picosecond and nanosecond pulse delivery through a hollow-core Negative Curvature Fiber for micro-machining applications.

We present high average power picosecond and nanosecond pulse delivery at 1030 nm and 1064 nm wavelengths respectively through a novel hollow-core Negative Curvature Fiber (NCF) for high-precision micro-machining applications. Picosecond pulses with an average power above 36 W and energies of 92 µJ, corresponding to a peak power density of 1.5 TWcm⁻² have been transmitted through the fiber without introducing any damage to the input and output fiber end-faces. High-energy nanosecond pulses (>1 mJ), which are ideal for micro-machining have been successfully delivered through the NCF with a coupling efficiency of 92%. Picosecond and nanosecond pulse delivery have been demonstrated in fiber-based laser micro-machining of fused silica, aluminum and titanium.

Fiber optical parametric oscillator for coherent anti-Stokes Raman scattering microscopy.

We present a synchronously pumped fiber optical parametric oscillator for coherent anti-Stokes Raman scattering microscopy. Pulses from a 1 µm Yb-doped fiber laser are amplified and frequency converted to 779-808 nm through normal dispersion four-wave mixing in a photonic crystal fiber. The idler frequency is resonant in the oscillator cavity, and we find that bandpass filtering the feedback is essential for stable, narrow-bandwidth output. Experimental results agree quite well with numerical simulations of the device. Transform-limited 2 ps pulses with energy up to 4 nJ can be generated at the signal wavelength. The average power is 180 mW, and the relative-intensity noise is much lower than that of a similar parametric amplifier. High-quality coherent Raman images of mouse tissues recorded with this source are presented.

Multicolor quantum metrology with entangled photons.

Entangled photons can be used to make measurements with an accuracy beyond that possible with classical light. While most implementations of quantum metrology have used states made up of a single color of photons, we show that entangled states of two colors can show supersensitivity to optical phase and path length by using a photonic crystal fiber source of photon pairs inside an interferometer. This setup is relatively simple and robust to experimental imperfections. We demonstrate sensitivity beyond the standard quantum limit and show superresolved interference fringes using entangled states of two, four, and six photons.

Controlling and scripting laboratory hardware with open-source, intuitive interfaces: OpenFlexure Voice Control and OpenFlexure Blockly.

Making user interaction with laboratory equipment more convenient and intuitive should promote experimental work and help researchers to complete their tasks efficiently. The most common form of interaction in current instrumentation is either direct tactile, with buttons and knobs, or interfaced through a computer, using a mouse and keyboard. Scripting is another function typical of smart and automated laboratory equipment, yet users are currently required to learn bespoke programming languages and libraries for individual pieces of equipment. In this paper, we present two open-source, novel and intuitive ways of interacting with and scripting laboratory equipment. We choose the OpenFlexure family of microscopes as our exemplar, due to their open-source nature and smart control system. Firstly, we demonstrate 'OpenFlexure Voice Control' to enable users to control the microscope hands-free. Secondly, we present 'OpenFlexure Blockly' which uses the Blockly Visual Programming Language to enable users to easily create scripts for the microscope, using a drag and drop Web interface. We explain the design choices when developing these tools, and discuss more typical use cases and more general applications.

Low loss silica hollow core fibers for 3-4 µm spectral region.

We describe a silica hollow-core fiber for mid-infrared transmission with a minimum attenuation of 34 dB/km at 3050 nm wavelength. The design is based on the use of a negative curvature core wall. Similar fiber designed for longer wavelengths has a transmission band extending beyond 4 µm.

Fiber four-wave mixing source for coherent anti-Stokes Raman scattering microscopy.

We present a fiber-format picosecond light source for coherent anti-Stokes Raman scattering microscopy. Pulses from a Yb-doped fiber amplifier are frequency converted by four-wave mixing (FWM) in normal-dispersion photonic crystal fiber to produce a synchronized two-color picosecond pulse train. We show that seeding the FWM process overcomes the deleterious effects of group-velocity mismatch and allows efficient conversion into narrow frequency bands. The source generates more than 160 mW of nearly transform-limited pulses tunable from 775 to 815 nm. High-quality coherent Raman images of animal tissues and cells acquired with this source are presented.

CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin.

Axon migrations are guided by extracellular cues that induce asymmetric outgrowth activity in the growth cone. Several intracellular signaling proteins have been implicated in the guidance response. However, how these proteins interact to generate asymmetric outgrowth activity is unknown. Here, we present evidence that in C. elegans, the CED-10/Rac1 GTPase binds to and causes asymmetric localization of MIG-10/lamellipodin, a protein that regulates actin polymerization and has outgrowth-promoting activity in neurons. Genetic analysis indicates that mig-10 and ced-10 function together to orient axon outgrowth. The RAPH domain of MIG-10 binds to activated CED-10/Rac1, and ced-10 function is required for the asymmetric MIG-10 localization that occurs in response to the UNC-6/netrin guidance cue. We also show that asymmetric localization of MIG-10 in growth cones is associated with asymmetric concentrations of f-actin and microtubules. These results suggest that CED-10/Rac1 is asymmetrically activated in response to the UNC-6/netrin signal and thereby causes asymmetric recruitment of MIG-10/lamellipodin. We propose that the interaction between activated CED-10/Rac1 and MIG-10/lamellipodin triggers local cytoskeletal assembly and polarizes outgrowth activity in response to UNC-6/netrin.

Low-noise, high-brightness, tunable source of picosecond pulsed light in the near-infrared and visible.

We have built a flexible source of picosecond pulsed light in both the near-infrared and visible spectral regions. A photonic crystal fiber (PCF) was pumped with a pulsed 1064 nm fiber laser to generate four-wave mixing (FWM) sidebands at 947 nm and 1213 nm. This process was seeded at the idler wavelength with a tunable diode laser to limit the spectral width of the sidebands to less than 0.5 nm. Subsequently the idler was mixed efficiently with the residual pump in a nonlinear crystal to yield their sum frequency at 567 nm. All three outputs were tunable by adjusting the seed wavelength and all had very low pulse-to-pulse amplitude noise. This technique could be extended to different wavelength ranges by selecting different seed lasers and PCF.

Assembly and tissue functions of early embryonic laminins and netrins.

Vertebrate laminins and netrins share N-terminal domain structure, but appear to be only distantly related. Both families can be divided into different subfamilies on the basis of structural considerations. Recent observations suggest that specific laminin and netrin members have developmental functions that are highly conserved across species. Vertebrate laminin-1 (alpha1beta1gamma1) and laminin-10 (alpha5beta1gamma1), like the two Caenorhabditis elegans laminins, are embryonically expressed and are essential for basement membrane assembly. Basement membrane assembly is a cooperative process in which laminins polymerize through their LN domains and anchor to the cell surface through their G domains; this leads to cell signaling through integrins and dystroglycan (and possibly other receptors) recruited to the adherent laminin. Netrins may associate with this network through heterotypic LN domain interactions. Vertebrate netrin-1, like invertebrate UNC-6/netrins, is well known as an extracellular guidance cue that directs axon migration towards or away from the ventral midline. It also regulates cell adhesions and migrations, probably as a basement membrane component. Although sharing structural features, these two vertebrate protein families are quite distinct, having both retained members that mediate the ancestral developmental functions.

High power red and near-IR generation using four wave mixing in all integrated fibre laser systems.

We demonstrate high power generation of visible red and near IR light by four wave mixing in photonic crystal fibres (PCFs) pumped at 1064 nm with picosecond pulses (30 - 80 ps). 30% conversion efficiency is demonstrated in a single pass using fibre lengths less than 1 m, with signal wavelengths from 650 nm to 820 nm selectable by choice of PCF. An all fibre integrated system delivers 2.16 W at 740 nm with a pulse repetition frequency of 20 MHz. We discuss the overall parameter space for this type of wavelength conversion in PCF with different fibre designs suitable for delivering a particular wavelength at low or high power.