Three stage HCF fabrication technique for high yield, broadband UV-visible fibers.

Hollow-core optical fibers can offer broadband, single mode guidance in the UV-visible-NIR wavelength range, with the potential for low-loss, solarization-free operation, making them desirable and potentially disruptive for a wide range of applications. To achieve this requires the fabrication of fibers with <300nm anti-resonant membranes, which is technically challenging. Here we investigate the underlying fluid dynamics of the fiber fabrication process and demonstrate a new three-stage fabrication approach, capable of delivering long (∼350m) lengths of fiber with the desired thin-membranes.

Transient gas-induced differential refractive index effects in as-drawn hollow core optical fibers.

When a hollow core fiber is drawn, the core and cladding holes within the internal cane geometry are pressurized with an inert gas to enable precise control over the internal microstructure of the fiber and counteract surface tension forces. Primarily by considering the temperature drop as the fiber passes through the furnace and the geometrical transformation of the internal microstructure from preform-to-fiber, we recently established that the gas pressure within the final 'as-drawn' fiber is substantially below atmospheric pressure. We have also established that slight changes in the gas refractive index within the core and surrounding cladding holes induced by changes in gas pressure are sufficient to significantly affect both the modality and loss of the fiber. Here we demonstrate, through both simulations and experimental measurements, that the combination of these effects leads to transient changes in the fiber's attenuation when the fibers are opened to atmosphere post-fabrication. It is important to account for this phenomenon for accurate fiber characterization, particularly when long lengths of fiber are drawn where it could take many weeks for every part of the internal microstructure to reach atmospheric pressure.

Endogenous membrane stress induces T6SS activity in Pseudomonas aeruginosa.

The type 6 secretion system (T6SS) is a dynamic organelle encoded by many gram-negative bacteria that can be used to kill competing bacterial prey species in densely occupied niches. Some predatory species, such as Vibrio cholerae, use their T6SS in an untargeted fashion while in contrast, Pseudomonas aeruginosa assembles and fires its T6SS apparatus only after detecting initial attacks by other bacterial prey cells; this targeted attack strategy has been termed the T6SS tit-for-tat response. Molecules that interact with the P. aeruginosa outer membrane such as polymyxin B can also trigger assembly of T6SS organelles via a signal transduction pathway that involves protein phosphorylation. Recent work suggests that a phospholipase T6SS effector (TseL) of V. cholerae can induce T6SS dynamic activity in P. aeruginosa when delivered to or expressed in the periplasmic space of this organism. Here, we report that inhibiting expression of essential genes involved in outer membrane biogenesis can also trigger T6SS activation in P. aeruginosa Specifically, we developed a CRISPR interference (CRISPRi) system to knock down expression of bamA, tolB, and lptD and found that these knockdowns activated T6SS activity. This increase in T6SS activity was dependent on the same signal transduction pathway that was previously shown to be required for the tit-for-tat response. We conclude that outer membrane perturbation can be sensed by P. aeruginosa to activate the T6SS even when the disruption is generated by aberrant cell envelope biogenesis.

Hyperactivation of the proteasome in Caenorhabditis elegans protects against proteotoxic stress and extends lifespan.

Virtually all age-related neurodegenerative diseases (NDs) can be characterized by the accumulation of proteins inside and outside the cell that are thought to significantly contribute to disease pathogenesis. One of the cell's primary systems for the degradation of misfolded/damaged proteins is the ubiquitin proteasome system (UPS), and its impairment is implicated in essentially all NDs. Thus, upregulating this system to combat NDs has garnered a great deal of interest in recent years. Various animal models have focused on stimulating 26S activity and increasing 20S proteasome levels, but thus far, none have targeted intrinsic activation of the 20S proteasome itself. Therefore, we constructed an animal model that endogenously expresses a hyperactive, open gate proteasome in Caenorhabditis elegans. The gate-destabilizing mutation that we introduced into the nematode germline yielded a viable nematode population with enhanced proteasomal activity, including peptide, unstructured protein, and ubiquitin-dependent degradation activities. We determined these nematodes showed a significantly increased lifespan and substantial resistance to oxidative and proteotoxic stress but a significant decrease in fecundity. Our results show that introducing a constitutively active proteasome into a multicellular organism is feasible and suggests targeting the proteasome gating mechanism as a valid approach for future age-related disease research efforts in mammals.

Near-infrared radiation induced attenuation in nested anti-resonant nodeless fibers.

This Letter reports the first, to the best of our knowledge, spectral radiation induced attenuation (RIA) measurements of nested anti-resonant nodeless hollow-core fibers (NANFs). A 5-tube NANF, alongside a solid-core single-mode radiation resistant fiber (SM-RRF), was irradiated under γ-ray up to 101 kGy (SiO2) and under x-ray up to 241 kGy (SiO2). No RIA was observed in the NANF in the second half of the O-band, the S-band, the C-band, and the L-band. The NANF showed a reduction of absorption bands associated with water and HCl under irradiation. Three new attenuation peaks were radiolytically induced and are attributed to the creation of HNO3. These peaks are centered respectively at 1441 nm, 1532 nm, and 1628 nm, with a full width at half maximum (FWHM) of, respectively, 10 nm, 12 nm, and 12 nm. These results demonstrate that the wide bandwidth range of NANFs is essentially unaffected by radiation, but the internal gas contents of the NANF must be managed to avoid producing undesirable spectral features through radiolytic reactions. Wide spectral regions almost unaffected by the ionizing radiation could open new possibilities for the use of NANF in harsh radiation environments.

Low loss and broadband low back-reflection interconnection between a hollow-core and standard single-mode fiber.

We report simultaneous low coupling loss (below 0.2 dB at 1550 nm) and low back-reflection (below -60 dB in the 1200-1600 nm range) between a hollow core fiber and standard single mode optical fiber obtained through the combination of an angled interface and an anti-reflective coating. We perform experimental optimization of the interface angle to achieve the best combination of performance in terms of the coupling loss and back-reflection suppression. Furthermore, we examine parasitic cross-coupling to the higher-order modes and show that it does not degrade compared to the case of a flat interface, keeping it below -30 dB and below -20 dB for LP11 and LP02 modes, respectively.

Mid-infrared silicon-on-insulator waveguides with single-mode propagation over an octave of frequency.

Increasing the working optical bandwidth of a photonic circuit is important for many applications, in particular chemical sensing at mid-infrared wavelengths. This useful bandwidth is not only limited by the transparency range of waveguide materials, but also the range over which a waveguide is single or multimoded for predictable circuit behaviour. In this work, we show the first experimental demonstration of "endlessly single-mode" waveguiding in silicon photonics. Silicon-on-insulator waveguides were designed, fabricated and characterised at 1.95 µm and 3.80 µm. The waveguides were shown to support low-loss propagation (1.46 ± 0.13 dB/cm loss at 1.95 µm and 1.55 ± 0.35 dB/cm at 3.80 µm) and single-mode propagation was confirmed at 1.95 µm, meaning that only the fundamental mode was present over the wavelength range 1.95 - 3.80 µm. We also present the prospects for the use of these waveguides in sensing applications.

Optical time domain backscattering of antiresonant hollow core fibers.

Today's lowest-loss hollow core fibers are based on antiresonance guidance. They have been shown both theoretically and experimentally to have very low levels of backscattering arising from the fiber structure - 45 dB below that of traditional optical fibers with a solid silica glass core. This makes their longitudinal characterization using conventional reflectometric techniques very challenging. However, it was recently estimated that when filled with air, their backscattering coefficient increases to about 30 dB below that of standard solid core fibers. This level should be measurable with commercially available high performance optical time domain reflectometers (OTDR). Here we demonstrate - for the first time to the best of our knowledge - the measurement of backscattering from the air inside a hollow core fiber. We show that the characterization of multi-km long hollow core fibers with 15 m spatial resolution is possible using a commercial OTDR instrument. To benefit from its full dynamic range, we strongly suppress the 4% back-reflections that ordinarily occur at the OTDR's standard fiber output when directly-connected to a hollow core fiber. Furthermore, low coupling loss into the hollow core fiber (0.3 dB in our experiment) also helps to maximize the achievable OTDR signal-to-noise ratio. This approach enables distributed characterization and fault-finding in low-loss hollow core fibers, a topic of increasing importance as these fibers are now starting to be installed in commercial optical communication networks.

High-energy, mid-IR, picosecond fiber-feedback optical parametric oscillator.

A compact, mid-infrared (MIR), synchronously pumped, fiber-feedback optical parametric oscillator (OPO) based on periodically poled lithium niobate (PPLN) is developed with tunable signal and idler wavelength ranges of 1472.0-1758.2 nm and 2559.1-3562.7 nm, respectively. A solid-core SMF-28 fiber and a hollow-core fiber (HCF) were used as the feedback fibers in order to compare the effect of their substantially different levels of nonlinearity. The OPO generates 1-MHz, 120-ps, MIR pulses with up to 1.50-µJ pulse energy and 11.7-kW peak power.

The shared uncertainty experience of older adults with advanced cancer and their caregivers.

OBJECTIVE: One primary source of psychological distress in patients with cancer and their caregivers is uncertainty. However, the uncertainty trajectory and its relationship between older adults with advanced cancer and their caregivers have rarely been examined. This study describes the uncertainty trajectory in patient-caregiver dyads, explores the effect of geriatric assessment (GA) intervention on trajectory, and examines the interdependent relationship of uncertainty. METHODS: This secondary analysis used longitudinal data from a national cluster-randomized controlled trial examining a GA intervention compared to usual care. Participants completed the modified 9-item Mishel Uncertainty in Illness Scale at enrollment, 4-6 weeks, 3 months, and 6 months. The dyadic growth model and cross-lagged actor-partner interdependence model were used. RESULTS: A total of 397 dyads (patient age M = 76.81 ± SD5.43; caregiver age M = 66.69 ± SD12.52) were included. Both had a trend of decreased uncertainty over time (b = -0.16, p < 0.01). There was a greater decrease in uncertainty among caregivers in the GA group than those in the usual care group (b = -0.46, p = 0.02). For both patients and caregivers, their past uncertainty was a significant predictor of their own current uncertainty (i.e., actor effect, p < 0.01). The individual's past uncertainty was a significant predictor of the other dyad member's current uncertainty (i.e., partner effect, p < 0.05), indicating an interdependent relationship between patient and caregiver uncertainty over time. CONCLUSIONS: Findings suggest patient and caregiver function as a unit with uncertainty levels affecting each other. Future interventions could build on GA to address uncertainty for older patients with advanced cancer and caregivers.

The mitochondrial metal transporters mitoferrin1 and mitoferrin2 are required for liver regeneration and cell proliferation in mice.

Mitochondrial iron import is essential for iron-sulfur cluster formation and heme biosynthesis. Two nuclear-encoded vertebrate mitochondrial high-affinity iron importers, mitoferrin1 (Mfrn1) and Mfrn2, have been identified in mammals. In mice, the gene encoding Mfrn1, solute carrier family 25 member 37 (Slc25a37), is highly expressed in sites of erythropoiesis, and whole-body Slc25a37 deletion leads to lethality. Here, we report that mice with a deletion of Slc25a28 (encoding Mfrn2) are born at expected Mendelian ratios, but show decreased male fertility due to reduced sperm numbers and sperm motility. Mfrn2-/- mice placed on a low-iron diet exhibited reduced mitochondrial manganese, cobalt, and zinc levels, but not reduced iron. Hepatocyte-specific loss of Slc25a37 (encoding Mfrn1) in Mfrn2-/- mice did not affect animal viability, but resulted in a 40% reduction in mitochondrial iron and reduced levels of oxidative phosphorylation proteins. Placing animals on a low-iron diet exaggerated the reduction in mitochondrial iron observed in liver-specific Mfrn1/2-knockout animals. Mfrn1-/-/Mfrn2-/- bone marrow-derived macrophages or skin fibroblasts in vitro were unable to proliferate, and overexpression of Mfrn1-GFP or Mfrn2-GFP prevented this proliferation defect. Loss of both mitoferrins in hepatocytes dramatically reduced regeneration in the adult mouse liver, further supporting the notion that both mitoferrins transport iron and that their absence limits proliferative capacity of mammalian cells. We conclude that Mfrn1 and Mfrn2 contribute to mitochondrial iron homeostasis and are required for high-affinity iron import during active proliferation of mammalian cells.

FilTar: using RNA-Seq data to improve microRNA target prediction accuracy in animals.

MOTIVATION: MicroRNA (miRNA) target prediction algorithms do not generally consider biological context and therefore generic target prediction based on seed binding can lead to a high level of false-positive predictions. Here, we present FilTar, a method that incorporates RNA-Seq data to make miRNA target prediction specific to a given cell type or tissue of interest. RESULTS: We demonstrate that FilTar can be used to: (i) provide sample specific 3'-UTR reannotation; extending or truncating default annotations based on RNA-Seq read evidence and (ii) filter putative miRNA target predictions by transcript expression level, thus removing putative interactions where the target transcript is not expressed in the tissue or cell line of interest. We test the method on a variety of miRNA transfection datasets and demonstrate increased accuracy versus generic miRNA target prediction methods. AVAILABILITY AND IMPLEMENTATION: FilTar is freely available and can be downloaded from https://github.com/TBradley27/FilTar. The tool is implemented using the Python and R programming languages, and is supported on GNU/Linux operating systems. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hollow-core resonator fiber optic gyroscope using nodeless anti-resonant fiber.

Resonator fiber optic gyroscope (RFOG) performance has hitherto been limited by nonlinearity, modal impurity, and backscattering in the sensing fibers. The use of hollow-core fiber (HCF) effectively reduces nonlinearity, but the complex interplay among glass and air-guided modes in conventional HCF technologies can severely exacerbate RFOG instability. By employing high-performance nested anti-resonant nodeless fiber, we demonstrate long-term stability in a hollow-fiber RFOG of 0.05 deg/h, nearing the levels required for civil aircraft navigation. This represents a ${{3}} \times$ improvement over any prior hollow-core RFOG and a factor of ${{500}} \times$ over any prior result at integration times longer than 1 h.

Association of Polypharmacy and Potentially Inappropriate Medications With Physical Functional Impairments in Older Adults With Cancer.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIMs) are prevalent in older adults with cancer, but their associations with physical function are not often studied. This study examined the associations of polypharmacy and PIMs with physical function in older adults with cancer, and determined the optimal cutoff value for the number of medications most strongly associated with physical functional impairment. METHODS: This cross-sectional analysis used baseline data from a randomized study enrolling patients aged ≥70 years with advanced cancer starting a new systemic cancer treatment. We categorized PIM using 2015 American Geriatrics Society Beers Criteria. Three validated physical function measures were used to assess patient-reported impairments: activities of daily living (ADL) scale, instrumental activities of daily living (IADL) scale, and the Older Americans Resources and Services Physical Health (OARS PH) survey. Optimal cutoff value for number of medications was determined by the Youden index. Separate multivariate logistic regressions were then performed to examine associations of polypharmacy and PIMs with physical function measures. RESULTS: Among 439 patients (mean age, 76.9 years), the Youden index identified ≥8 medications as the optimal cutoff value for polypharmacy; 43% were taking ≥8 medications and 62% were taking ≥1 PIMs. On multivariate analysis, taking ≥8 medications was associated with impairment in ADL (adjusted odds ratio [aOR], 1.64; 95% CI, 1.01-2.58) and OARS PH (aOR, 1.73; 95% CI, 1.01-2.98). PIMs were associated with impairments in IADL (aOR, 1.72; 95% CI, 1.09-2.73) and OARS PH (aOR, 1.97; 95% CI, 1.15-3.37). A cutoff of 5 medications was not associated with any of the physical function measures. CONCLUSIONS: Physical function, an important component of outcomes for older adults with cancer, is cross-sectionally associated with polypharmacy (defined as ≥8 medications) and with PIMs. Future studies should evaluate the association of polypharmacy with functional outcomes in this population in a longitudinal fashion.

Compact micro-optic based components for hollow core fibers.

Using micro-optic collimator technology, we present compact, low-loss optical interconnection devices for hollow core fibers (HCFs). This approach is one of the key manufacturing platforms for commercially available fiber optic components and most forms of HCFs can readily be incorporated into this platform without the need for any substantial or complicated adaptation or physical deformation of the fiber structure. Furthermore, this technique can provide for very low Fresnel reflection interconnection between solid-core fiber and HCF and in addition provides a hermetic seal for HCFs, which can be a critical issue for many HCF applications. In this paper, several exemplar HCF components are fabricated with low insertion loss (0.5-2 dB), low Fresnel reflection (-45 dB) and high modal purity (>20 dB) using various state-of-the-art HCFs.

Pilot-scale open-channel raceways and flat-panel photobioreactors maintain well-mixed conditions under a wide range of mixing energy inputs.

Turbulent mixing in pilot-scale cultivation systems influences the productivity of photoautotrophic cultures. We studied turbulent mixing by applying particle image velocimetry and acoustic doppler velocimetry to pilot-scale, flat-panel photobioreactor, and open-channel raceway. Mixing energy inputs were varied from 0.1 to 2.1 W·m-3 . The experimental results were used to quantify turbulence and to validate computational fluid dynamics models, from which Lagrangian representations of the fluid motion in these reactors were derived. The results of this investigation demonstrated that differences in mixing energy input do not significantly impact the structure of turbulence and the light/dark cycling frequencies experienced by photoautotrophic cells within the reactors. The experimental and computational results of our research demonstrated that well-mixed conditions exist in pilot-scale, flat-panel photobioreactors and open-channel raceways, even for relatively low mixing energy inputs.

Fabrication of tubular anti-resonant hollow core fibers: modelling, draw dynamics and process optimization.

The fabrication of hollow core microstructured fibers is significantly more complex than solid fibers due to the necessity to control the hollow microstructure with high precision during the draw. We present the first model that can recreate tubular anti-resonant hollow core fiber draws, and accurately predict the draw parameters and geometry of the fiber. The model was validated against two different experimental fiber draws and very good agreement was found. We identify a dynamic within the draw process that can lead to a premature and irreversible contact between neighboring capillaries inside the hot zone, and describe mitigating strategies. We then use the model to explore the tolerance of the draw process to unavoidable structural variations within the preform, and to study feasibility and limiting phenomena of increasing the produced yield. We discover that the aspect ratio of the capillaries used in the preform has a direct effect on the uniformity of drawn fibers. Starting from high precision preforms the model predicts that it could be possible to draw 100 km of fiber from a single meter of preform.

Local-time averaged maps of H3+ emission, temperature and ion winds.

We present Keck-NIRSPEC observations of Saturn's [Formula: see text] aurora taken over a period of a month, in support of the Cassini mission's 'Grand Finale'. These observations produce two-dimensional maps of Saturn's [Formula: see text] temperature and ion winds for the first time. These maps show surprising complexity, with different morphologies seen in each night. The [Formula: see text] ion winds reveal multiple arcs of 0.5-1 km s-1 ion flows inside the main auroral emission. Although these arcs of flow occur in different locations each night, they show intricate structures, including mirrored flows on the dawn and dusk of the planet. These flows do not match with the predicted flows from models of either axisymmetric currents driven by the Solar Wind or outer magnetosphere, or the planetary periodic currents associated with Saturn's variable rotation rate. The average of the ion wind flows across all the nights reveals a single narrow and focused approximately 0.3 km s-1 flow on the dawn side and broader and more extensive 1-2 km s-1 sub-corotation, spilt into multiple arcs, on the dusk side. The temperature maps reveal sharp gradients in ionospheric temperatures, varying between 300 and 600 K across the auroral region. These temperature changes are localized, resulting in hot and cold spots across the auroral region. These appear to be somewhat stable over several nights, but change significantly over longer periods. The position of these temperature extremes is not well organized by the planetary period and there is no evidence for a thermospheric driver of the planetary period current system. Since no past magnetospheric or thermospheric models explain the rich complexity observed here, these measurements represent a fantastic new resource, revealing the complexity of the interaction between Saturn's thermosphere, ionosphere and magnetosphere. This article is part of a discussion meeting issue 'Advances in hydrogen molecular ions: H3+, H5+ and beyond'.

Reductions in the mitochondrial ABC transporter Abcb10 affect the transcriptional profile of heme biosynthesis genes.

ATP-binding cassette subfamily B member 10 (Abcb10) is a mitochondrial ATP-binding cassette (ABC) transporter that complexes with mitoferrin1 and ferrochelatase to enhance heme biosynthesis in developing red blood cells. Reductions in Abcb10 levels have been shown to reduce mitoferrin1 protein levels and iron import into mitochondria, resulting in reduced heme biosynthesis. As an ABC transporter, Abcb10 binds and hydrolyzes ATP, but its transported substrate is unknown. Here, we determined that decreases in Abcb10 did not result in protoporphyrin IX accumulation in morphant-treated zebrafish embryos or in differentiated Abcb10-specific shRNA murine Friend erythroleukemia (MEL) cells in which Abcb10 was specifically silenced with shRNA. We also found that the ATPase activity of Abcb10 is necessary for hemoglobinization in MEL cells, suggesting that the substrate transported by Abcb10 is important in mediating increased heme biosynthesis during erythroid development. Inhibition of 5-aminolevulinic acid dehydratase (EC 4.2.1.24) with succinylacetone resulted in both 5-aminolevulinic acid (ALA) accumulation in control and Abcb10-specific shRNA MEL cells, demonstrating that reductions in Abcb10 do not affect ALA export from mitochondria and indicating that Abcb10 does not transport ALA. Abcb10 silencing resulted in an alteration in the heme biosynthesis transcriptional profile due to repression by the transcriptional regulator Bach1, which could be partially rescued by overexpression of Alas2 or Gata1, providing a mechanistic explanation for why Abcb10 shRNA MEL cells exhibit reduced hemoglobinization. In conclusion, our findings rule out that Abcb10 transports ALA and indicate that Abcb10's ATP-hydrolysis activity is critical for hemoglobinization and that the substrate transported by Abcb10 provides a signal that optimizes hemoglobinization.

Laser frequency stabilization and spectroscopy at 2051 nm using a compact CO2-filled Kagome hollow core fiber gas-cell system.

We describe a compact, all fiber, frequency stabilized diode laser system at 2051 nm using CO2 gas-filled Kagome Hollow Core Fiber (HCF), capable of tuning continuously over four transitions in 12C16O2: R(24), R(26), R(28), and R(30). This laser system has been designed for use in future space-based atmospheric monitoring using differential absorption lidar (DIAL). The fully spliced Kagome HCF gas cell is filled to 2 kPa CO2 partial pressure and we compare the observed CO2 lineshape features with those calculated using HITRAN, to quantify the properties of the CO2-filled fiber cell. In this first demonstration of Kagome HCF used in a fully sealed gas cell configuration for spectroscopy at 2 µm, we characterize the frequency stability of the locked system by beat frequency comparison against a reference laser. Results are presented for the laser locked to the center of the 12C16O2 R(30) transition, with frequency stability of ∼40 kHz or better at 1 s, and a frequency reproducibility at the 0.4-MHz level over a period of > 1 month. For DIAL applications, we also demonstrate two methods of stabilizing the laser frequency ~3 GHz from this line. Furthermore, no pressure degradation was observed during the ~15-month period in which frequency stability measurements were acquired.