Femtosecond laser writing of robust waveguides in optical fibers with enhanced photosensitivity.

We report the femtosecond laser writing of meter-long optical waveguides inscribed through the coating of specifically designed optical fibers. In order to improve the material photosensitivity and to ensure non-guiding optical fibers for subsequent laser processing of the waveguiding core, a depressed refractive index core design is implemented by co-doping a large portion of the optical fiber with germanium oxide and fluorine. The enhanced photosensitivity provided by further deuterium loading these fibers allows laser-writing of large refractive index contrast waveguides over wide cross sections. To mitigate the formation of photoinduced color centers causing high propagation losses in the photo-written waveguides, thermal annealing up to 400°C is performed on polyimide-coated laser-written fibers. Although the refractive index contrast decreases, the propagation losses are drastically reduced down to 0.08 dB/cm at 900nm allowing a robust single-mode guiding from visible to near infrared. Our results pave the way towards the development of a new generation of optical fibers and photonic components with arbitrarily complex designs.

Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance.

PURPOSE: Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers. MATERIALS AND METHODS: Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort. RESULTS: PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001). CONCLUSIONS: Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.

Assessment of antioxidative and selenium status by seleno-dependent glutathione peroxidase activity in different blood fractions using a pig model: issues for clinical nutrition and research.

Blood seleno-dependent glutathione peroxidase (SeGPX) activity is widely used as a metabolic indicator of systemic antioxidative status despite inconsistent responses in the literature. This study aimed to compare SeGPX activity profiles in different blood fractions, expressed with different reference units, and assess their impact on interpretation of results. Two studies on selenium (Se) metabolism in gilts, including long-term and peri-oestrus SeGPX activity profiles, were submitted to analysis of variance with double repeated measures, after data set standardization. Differences between studies were experimental period (three post-pubertal oestrus or five post-pubertal oestrus +30 days of gestation) and sample type (whole blood or blood plasma). No difference was observed between whole-blood long-term profiles (three oestrus) for SeGPX activity/mg haemoglobin (SeGPXhb) vs. SeGPX activity/ml whole blood (SeGPXwb; p = 0.29). No long-term difference was observed in whole blood between profiles according to dietary Se provision (basal and dietary Se-supplemented groups; p ≥ 0.12). Blood plasma long-term profiles (five oestrus + 30 days gestation) for SeGPX/mg blood plasma protein (SeGPXpro) were different from SeGPX/ml blood plasma (SeGPXpla) according or not to Se provision (p ≤ 0.007 and p < 0.001 respectively). However, regardless of Se provision (p ≥ 0.80), when excluding gestation from the model, blood plasma profiles were similar. During the peri-oestrus period (day -4 to +3), regardless of Se provision, SeGPX activity profiles differed according to reference units in both studies (p < 0.001). However, considering Se provision, similar profiles were observed in whole blood and blood plasma (p ≥ 0.27) for basal Se groups, whereas in Se-supplemented groups they differed for both sample types (p ≤ 0.02). In conclusion, reference units influence interpretation of SeGPX activity according to physiological state. During oxidative stress periods, this effect depends upon dietary Se provision.

Evidence that oxidative stress is higher in replacement gilts than in multiparous sows.

The recent success obtained in term of increasing the litter size of sows has not correlated with a reduction of replacement rate. There is thus an increased economic demand for gilts with optimal reproductive potential and longevity. Unfortunately, replacement gilts are known to be more susceptible to diseases and less productive than multiparous sows. Interestingly, reproductive performance, resistance to diseases and longevity could all be largely affected by oxidative stress. To investigate whether oxidative stress conditions could account for the poor longevity of gilts, three distinct groups of conventional Yorkshire × Landrace sows were formed based on their similar age and parity (gilts, second parity sows as well as fourth to fifth parity sows). All animals were slaughtered during the post-ovulatory period, and blood as well as tissue samples were collected. Biomarkers of oxidative damage to proteins (carbonyls) and DNA (8-OHdG) were analysed in samples. Specific mRNA expression of major antioxidants such as glutathione peroxidases 1, 3 and 4 (GPx1, GPx3, GPx4) as well as superoxide dismutases 1 and 2 (Sod1, Sod2) were monitored in liver and kidney samples by quantitative RT-PCR. Specific enzymatic activities of both GPx and SOD were measured by spectrophotometric assays. The plasma concentration of protein carbonyls was significantly different between the three groups with the highest concentration being observed in gilts (p ≤ 0.001). The mRNA expression levels of GPx1 and GPx4 were also significantly increased in the liver of gilts when compared to multiparous sows (p ≤ 0.05). SOD2 enzymatic activity was found to be higher in the liver of gilts than multiparous sows (p ≤ 0.05). Taken together, these results indicate that replacement gilts sustain significantly higher oxidative conditions than multiparous sows. Current findings may contribute to the design of nutritional regimens that will increase the productivity of gilts by counteracting oxidative stress.

Mitochondria as promising targets for nutritional interventions aiming to improve performance and longevity of sows.

Genetic selection and management changes during the last decades have significantly increased the average litter size of sows. However, this recent success has not correlated with an extension of longevity and reduction in replacement rate. Longevity or lifetime production of sows is determined by a combination of environmental and genetic factors. Nutrition is an environmental factor of importance, and it has long been appreciated that animals fed with specific diets may perform differently. The advent of modern science revealed that this is partly due to the ability of nutrients to act as signalling molecules that, through appropriate intracellular sensing mechanisms, can control gene expression and modulate cell functions. Based on this concept, nutrigenomics studies now aim to show that not only are certain nutrients essential for general health, but also that specific quantities of precise nutrients are necessary during critical periods of energy deficiency and oxidative stress such as gestation and lactation to ensure long-term productivity. The toxic molecules at the origin of oxidative stress, free radicals, are mainly generated as normal by-products of aerobic energy production by mitochondria. In all cells, mitochondria are dynamic organelles that are mainly known as the primary energy-generating system. Thus, when metabolic demands are elevated as it is for hyperprolific sows, mitochondria are heavily solicited for answering all energetic needs, and substantive amounts of free radicals are generated. As a result, optimal conditions in term of antioxidant protection and metabolic substrates availability are required to support mitochondrial function in these animals. This article discusses how performance and longevity of sows are linked to mitochondrial function and oxidative stress and reviews the major natural nutrients known for their antioxidant and/or energetic properties that are susceptible to impact mitochondria and likely improved sows productivity.

Photonic wire biosensor microarray chip and instrumentation with application to serotyping of Escherichia coli isolates.

A complete photonic wire molecular biosensor microarray chip architecture and supporting instrumentation is described. Chip layouts with 16 and 128 independent sensors have been fabricated and tested, where each sensor can provide an independent molecular binding curve. Each sensor is 50 µm in diameter, and consists of a millimeter long silicon photonic wire waveguide folded into a spiral ring resonator. An array of 128 sensors occupies a 2 × 2 mm2 area on a 6 × 9 mm2 chip. Microfluidic sample delivery channels are fabricated monolithically on the chip. The size and layout of the sensor array is fully compatible with commercial spotting tools designed to independently functionalize fluorescence based biochips. The sensor chips are interrogated using an instrument that delivers sample fluid to the chip and is capable of acquiring up to 128 optical sensor outputs simultaneously and in real time. Coupling light from the sensor chip is accomplished through arrays of sub-wavelength surface grating couplers, and the signals are collected by a fixed two-dimensional detector array. The chip and instrument are designed so that connection of the fluid delivery system and optical alignment are automated, and can be completed in a few seconds with no active user input. This microarray system is used to demonstrate a multiplexed assay for serotyping E. coli bacteria using serospecific polyclonal antibody probe molecules.

Enhanced photonic crystal cavity-waveguide coupling using local slow-light engineering.

This Letter introduces an enhanced cavity-waveguide coupling architecture based upon slow-light engineering in a two-port photonic crystal system. After analyzing the system transmittance using coupled-mode theory, the system is probed experimentally and shown to have increased transmittance due to the enhanced cavity-waveguide coupling. Such a coupling architecture may facilitate next-generation planar lightwave circuitry such as onchip quantum information processing or high precision light-matter sensing applications.

Interplay between crystal phase purity and radial growth in InP nanowires.

The interplay between crystal phase purity and radial growth in InP nanowires is investigated. By modifying the growth rate and V/III ratio, regions of high or low stacking fault density can be controllably introduced into wurtzite nanowires. It is found that regions with high stacking fault density encourage radial growth. Through careful choice of growth conditions pure wurtzite InP nanowires are then grown which exhibit narrow 4.2 K photoluminescence linewidths of 3.7 meV at 1.490 meV, and no evidence of emission related to stacking faults or zincblende insertions.

Intervertebral disk disease with spinal cord penetration in a Yucatan pig.

A 9-month-old female Yucatan pig was euthanized after acute onset of paraplegia. Gross and microscopic examination revealed dorsal dissection of the nucleus of the L2-L3 intervertebral disk through the annulus fibrosus, extrusion of nucleus pulposus material through the overlying dura mater and into the spinal cord, and associated acute spinal hemorrhage and necrosis. This is, to the authors' knowledge, the first reported case of intervertebral disk disease in swine.

Temperature-independent silicon subwavelength grating waveguides.

We demonstrate, by experiment and numerical calculations, temperature-independent subwavelength grating waveguides with a periodic composite core composed of alternating regions of silicon and SU-8 polymer. The polymer has a negative thermo-optic (TO) material coefficient that cancels the large positive TO effect of the silicon. Measurements and Bloch mode calculations were carried out over a range of silicon-polymer duty ratios. The lowest measured TO coefficient at a wavelength of 1550 nm is 1.8×10(-6) K(-1); 2 orders of magnitude smaller than a conventional silicon photonic wire waveguide. Calculations predict the possibility of complete cancellation of the silicon waveguide temperature dependence.

The whey fermentation product malleable protein matrix decreases triglyceride concentrations in subjects with hypercholesterolemia: a randomized placebo-controlled trial.

Malleable protein matrix (MPM) is a unique whey-derived ingredient obtained through a fermentation process using proprietary lactic acid bacteria strains from the Lactobacillus kefiranofaciens species. Because evidence from animal models suggests that MPM decreases serum lipid concentrations, the purpose of the present trial was to assess the hypothesis that MPM exerts lipid-lowering effects in humans. A total of 161 subjects (50% male; age 54.5 ± 9.8 yr, body mass index 26.3 ± 3.6 kg/m(2)) with hypercholesterolemia with baseline low-density lipoprotein cholesterol (LDL-C) levels of 181 ± 30 mg/dL and normal triglyceride (TG) levels (131 ± 55 mg/dL) were randomized to receive MPM (2 × 15 g/d) or matching placebo. A 6-wk run-in phase was followed by a double-blind 12-wk treatment phase after randomization. The data were analyzed on an intention-to-treat basis. The primary outcome measure was the percentage change of LDL-C. The secondary outcome measures were changes in TG and high-density lipoprotein cholesterol concentrations as well as changes in other cardiovascular risk factors. After 12 wk of treatment, the relative TG decrease from baseline reached 9.8%, whereas LDL-C was slightly decreased (by 1.5%) following MPM treatment compared with placebo in the intention-to-treat cohort. The treatment effect on TG reduction was much higher in the subset of subjects having TG levels at baseline of 150 mg/dL or above (n=42), reaching 20.0% compared with placebo. High-density lipoprotein cholesterol concentrations, blood pressure, and fasting blood glucose remained unchanged, whereas a positive treatment effect was seen on hemoglobin A(1c). The MPM product was tolerated well without severe adverse events. In conclusion, MPM has significant TG-lowering properties in subjects with combined hypercholesterolemia and higher TG levels. Its effects on LDL-C concentrations and glucose metabolism deserve further investigation.

Real-time cancellation of temperature induced resonance shifts in SOI wire waveguide ring resonator label-free biosensor arrays.

A comprehensive investigation of real-time temperature-induced resonance shift cancellation for silicon wire based biosensor arrays is reported for the first time. A reference resonator, protected by either a SU8 or SiO(2) cladding layer, is used to track temperature changes. The temperature dependence of resonators in aqueous solutions, pertinent to biosensing applications, is measured under steady-state conditions and the operating parameters influencing these properties are discussed. Real-time measurements show that the reference resonator resonances reflect the temperature changes without noticeable time delay, enabling effective cancellation of temperature-induced shifts. Binding between complementary IgG protein pairs is monitored over 4 orders of magnitude dynamic range down to a concentration of 20 pM, demonstrating a resolvable mass of 40 attograms. Reactions are measured over time periods as long as 3 hours with high stability, showing a scatter corresponding to a fluid refractive index fluctuation of ± 4 × 10(-6) in the baseline data. Sensor arrays with a SU8 protective cladding are easy to fabricate, while oxide cladding is found to provide superior stability for measurements involving long time scales.

Label-free biosensor array based on silicon-on-insulator ring resonators addressed using a WDM approach.

We report a silicon-on-insulator ring resonator biosensor array with one output port, using wavelength division multiplexing as the addressing scheme. With the use of on-chip referencing for environmental drift cancellation, simultaneous monitoring of multiplexed molecular bindings is demonstrated, with a resolution of 0.3 pg/mm(2) (40 ag of total mass) for protein concentrations over 4 orders of magnitude down to 20 pM. Reactions are measured over time periods as long as 3 h with high stability.

Continuously apodized fiber-to-chip surface grating coupler with refractive index engineered subwavelength structure.

We demonstrate a fully etched, continuously apodized fiber-to-chip surface grating coupler for the first time (to our knowledge). The device is fabricated in a single-etch step and operates with TM-polarized light, achieving a coupling efficiency of 3.7 dB and a 3 dB bandwidth of 60 nm. A subwavelength microstructure is employed to generate an effective medium engineered to vary the strength of the grating and thereby maximize coupling efficiency, while mitigating backreflections at the same time. Minimum feature size is 100 nm for compatibility with deep-UV 193 nm lithography.

Tissue-specific profiling reveals modulation of cellular and mitochondrial oxidative stress in normal- and low-birthweight piglets throughout the peri-weaning period.

Weaning is known to induce important nutritional and energetic stress in piglets. Low-birthweight (LBW) piglets, now frequently observed in swine production, are more likely to be affected. The weaning period is also associated with dysfunctional immune responses, uncontrolled inflammation and oxidative stress conditions that are recognized risk factors for infections and diseases. Mounting evidence indicates that mitochondria, the main cellular sources of energy in the form of adenosine 5' triphosphate (ATP) and primary sites of reactive oxygen species production, are related to immunity, inflammation and bacterial pathogenesis. However, no information is currently available regarding the link between mitochondrial energy production and oxidative stress in weaned piglets. The objective of this study was to characterize markers of cellular and mitochondrial energy metabolism and oxidative status in both normal-birthweight (NBW) and LBW piglets throughout the peri-weaning period. To conduct the study, 30 multiparous sows were inseminated and litters were standardized to 12 piglets. All the piglets were weighted at day 1 and 120 piglets were selected and assigned to 1 of 2 experimental groups: NBW (n = 60, mean weight of 1.73 ± 0.01 kg) and LBW piglets weighing less than 1.2 kg (n = 60, 1.01 ± 0.01 kg). Then, 10 piglets from each group were selected at 14, 21 (weaning), 23, 25, 29 and 35 days of age to collect plasma and organ (liver, intestine and kidney) samples. Analysis revealed that ATP concentrations were lower in liver of piglets after weaning than during lactation (P < 0.05) thus suggesting a significant impact of weaning stress on mitochondrial energy production. Oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine, 8-OHdG) and proteins (carbonyls) measured in plasma increased after weaning and this coincides with a rise in enzymatic antioxidant activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) (P < 0.05). Mitochondrial activities of both GPx and SOD are also significantly higher (P < 0.05) in kidney of piglets after weaning. Additionally, oxidative damage to macromolecules is more important in LBW piglets as measured concentrations of 8-OHdG and protein carbonyls are significantly higher (P < 0.05) in plasma and liver samples, respectively, than for NBW piglets. These results provide novel information about the nature, intensity and duration of weaning stress by revealing that weaning induces mitochondrial dysfunction and cellular oxidative stress conditions which last for at least 2 weeks and more severely impact smaller piglets.

Silicon-on-insulator guided mode resonant grating for evanescent field molecular sensing.

We present experimental and theoretical results of label-free molecular sensing using the transverse magnetic mode of a 0.22 mum thick silicon slab waveguide with a surface grating implemented in a guided mode resonance configuration. Due to the strong overlap of the evanescent field of the waveguide mode with a molecular layer attached to the surface, these sensors exhibit high sensitivity, while their fabrication and packaging requirements are modest. Experimentally, we demonstrate a resonance wavelength shift of approximately 1 nm when a monolayer of the protein streptavidin is attached to the surface, in good agreement with calculations based on rigorous coupled wave analysis. In our current optical setup this shift corresponds to an estimated limit of detection of 0.2% of a monolayer of streptavidin.

Silicon photonic wire biosensor array for multiplexed real-time and label-free molecular detection.

We demonstrate a silicon photonic wire waveguide biosensor array chip for the simultaneous monitoring of different molecular binding reactions. The chip is compatible with automated commercial spotting tools and contains a monolithically integrated microfluidic channel for sample delivery. Each array sensor element is a 1.8-mm-long spiral waveguide folded within a 130 microm diameter spot and is incorporated in a balanced Mach-Zehnder interferometer with a near temperature independent response. The sensors are arranged in a 400 microm spacing grid pattern and are addressed through cascaded 1x2 optical power splitters using light from a single input fiber. We demonstrate the real-time monitoring of antibody-antigen reactions using complementary and mismatched immunoglobulin G receptor-analyte pairs and bovine serum albumin. The measured level of detection for each sensor element corresponds to a surface coverage of less than 0.3 pg/mm(2).

High reflectivity gratings on silicon-on-insulator waveguide facets.

We demonstrate by numerical simulations and experiments that highly reflective (HR) facets can be formed on silicon waveguides with high reflectivity diffraction gratings. We use an HR grating with a plane wave reflectivity exceeding 99.99%, as calculated by rigorous coupled wave analysis. Experimentally, we demonstrate the HR effect for silicon-on-insulator waveguide facets patterned lithographically with grating structures. Due to a strong mode size dependence, the maximum facet reflectivity for 1.5 microm thick waveguide is 77%, but finite difference time-domain simulations show that modal reflectivies larger than 90% can be achieved for silicon waveguides with thicknesses of 4 microm or more.

Folded cavity SOI microring sensors for high sensitivity and real time measurement of biomolecular binding.

We demonstrate folded waveguide ring resonators for biomolecular sensing. We show that extending the ring cavity length increases the resonator quality factor, and thereby enhances the sensor resolution and minimum level of detection, while at the same time relaxing the tolerance on the coupling conditions to provide stable and large resonance contrast. The folded spiral path geometry allows a 1.2 mm long ring waveguide to be enclosed in a 150 microm diameter sensor area. The spiral cavity resonator is used to monitor the streptavidin protein binding with a detection limit of approximately 3 pg/mm(2), or a total mass of approximately 5 fg. The real time measurements are used to analyze the kinetics of biotin-streptavidin binding.

A high-resolution silicon-on-insulator arrayed waveguide grating microspectrometer with sub-micrometer aperture waveguides.

We demonstrate a 50-channel high-resolution arrayed waveguide grating microspectrometer with a 0.2 nm channel spacing on a silicon-on-insulator (SOI) platform. The chip size is 8 mm x 8 mm. High channel density and spectral resolution are achieved using high aspect ratio 0.6 mum x 1.5 mum waveguide apertures to inject the light into the input combiner and to intercept different spectral channels at the output combiner focal region. The measured crosstalk is <-10 dB, the 3 dB channel bandwidth is 0.15 nm, and the insertion loss is -17 dB near the central wavelength of lambda = 1.545 mum.