Search

Infant oral mutilation is a practice performed by traditional healers in many Eastern African countries. The sequelae of this practice have been recognised and reported on in many developed countries due to the migration of populations, customs and beliefs. This article describes three cases of infant oral mutilation that have been diagnosed in the Dental Department at Hutt Hospital, Lower Hutt. [ABSTRACT FROM AUTHOR]

In this paper, we quantitatively compare the autofluorescence of stoichiometric low pressure chemical vapor deposition (LPCVD) silicon nitride and sputtered tantalum pentoxide waveguides at a pump wavelength of 532 nm. Through a direct quantitative characterization of comparable waveguides formed from the two films, we find no observable autofluorescence for tantalum pentoxide waveguides. Our experimental sensitivity is limited by Raman scattering of the pump into our detection band and our measurements indicate that the autofluorescence of the tantalum pentoxide waveguides is more than 600 × smaller than that of silicon nitride waveguides. This finding holds promise for visible technologies such as biosensors and quantum devices that require strong optical pumping and minimal background noise.

Objective: To use animal pharmacokinetic data and FluidSIM modeling to estimate human dexamethasone perilymph concentrations from plasma concentration measurements over time following a single intratympanic administration of SPT-2101., Study Design: Perilymph and plasma dexamethasone concentrations were measured in guinea pigs and African green monkeys over 3 to 6 weeks post-intratympanic administration of SPT-2101. Plasma concentrations of dexamethasone were measured in Ménière's disease patients post-intratympanic administration of SPT-2101. FluidSIM was trained on the correlations of animal plasma and animal perilymph levels, allowing the human perilymph drug time course for SPT-2101 to be predicted from measured human plasma dexamethasone concentrations., Setting: Tertiary care neurotology clinic in Perth, Australia., Patients: Nine adults with unilateral definite Ménière's disease per Barany Society criteria., Intervention: Intratympanic SPT-2101, a single injection of a long-acting gel formulation of dexamethasone precisely delivered at the round window., Main Outcome Measure: Estimated dexamethasone levels in human perilymph following a single administration of SPT-2101 at the round window over time., Results: Perilymph dexamethasone concentrations were above estimated therapeutic levels for up to 35 days in guinea pigs and at least 21 days in African green monkeys. In human subjects, plasma dexamethasone concentrations were detected for 2 weeks post-administration. Animal middle ear, plasma and perilymph drug interrelationships were compared to FluidSIM simulations, providing rationale for correlating dexamethasone concentrations in the respective compartments. Comparable simulations of human plasma concentrations predicted perilymph dexamethasone therapeutic levels in humans for 23-55 days., Conclusions: Sustained release dexamethasone from SPT-2101 precisely delivered at the round window provides prolonged and durable estimated perilymph concentrations in clinical subjects., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Public lands worldwide provide diverse resources, uses, and values, ranging from wilderness to extractive uses. Decision-making on public lands is complex as a result and is required by law to be informed by science. However, public land managers may not always have the science they need. We developed a methodology for identifying priority science needs for public land management agencies. We relied on two core data sources: environmental effects analyses conducted for agency decisions and legal challenges to those decisions. We considered needs in four categories: data, science, methods, and mitigation measures. We classified topics as primary science needs when (1) the topic was analyzed frequently in agency environmental analyses, (2) our metric of quality/defensibility was low or mitigation measures were frequently included for the topic, and (3) the agency was challenged on its use of science for the topic. We applied our methodology to the Bureau of Land Management-the largest public land manager in the United States-in Colorado, a state with abundant and diverse public lands. Primary identified needs were data on vegetation; science about effects of oil and gas development and livestock grazing on multiple resources, including terrestrial wildlife; methods for analyzing environmental effects for many topics; and mitigation measures for protecting vegetation, soils, water quality, and archaeological and historic resources. Science needs often reflect needs for facilitating and supporting the use of existing science in agency decision-making. Our method can be applied across agencies, geographies, and timeframes to help strengthen science use in public lands decision-making., Competing Interests: Compliance with Ethical Standards. Conflict of interest: The authors declare no completing interests., (© 2024. Laine E. McCall. Parts of this work were authored by US Federal Government authors and are not under copyright protection in the US; foreign copyright protection may apply.)

The auditory nerve typically degenerates following loss of cochlear hair cells or synapses. In the case of hair cell loss neural degeneration hinders restoration of hearing through a cochlear implant, and in the case of synaptopathy suprathreshold hearing is affected, potentially degrading speech perception in noise. It has been established that neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) can mitigate auditory nerve degeneration. Several potential BDNF mimetics have also been investigated for neurotrophic effects in the cochlea. A recent in vitro study showed favorable effects of M3, a TrkB monoclonal antibody agonist, when compared with BDNF. In the present study we set out to examine the effect of M3 on auditory nerve preservation in vivo. Thirty-one guinea pigs were bilaterally deafened, and unilaterally treated with a single 3-µl dose of 7 mg/ml, 0.7 mg/ml M3 or vehicle-only by means of a small gelatin sponge two weeks later. During the experiment and analyses the experimenters were blinded to the three treatment groups. Four weeks after treatment, we assessed the treatment effect (1) histologically, by quantifying survival of SGCs and their peripheral processes (PPs); and (2) electrophysiologically, with two different paradigms of electrically evoked compound action potential (eCAP) recordings shown to be indicative of neural health: single-pulse stimulation with varying inter-phase gap (IPG), and pulse-train stimulation with varying inter-pulse interval. We observed a consistent and significant preservative effect of M3 on SGC survival in the lower basal turn (approximately 40% more survival than in the untreated contralateral cochlea), but also in the upper middle and lower apical turn of the cochlea. This effect was similar for the two treatment groups. Survival of PPs showed a trend similar to that of the SGCs, but was only significantly higher for the highest dose of M3. The protective effect of M3 on SGCs was not reflected in any of the eCAP measures: no statistically significant differences were observed between groups in IPG effect nor between the M3 treatment groups and the control group using the pulse-train stimulation paradigm. In short, while a clear effect of M3 was observed on SGC survival, this was not clearly translated into functional preservation., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Here we realize the first reported integrated photonic devices fabricated using sputtered niobium-tantalum oxide films. Sputtered niobium-tantalum oxide films are highly promising for integrated photonics as they are scalable to high volume manufacturing, possess high refractive index, and are transparent in the ultraviolet through near infrared wavelength range. At a wavelength near 1550 nm, we observe propagation losses as low as 0.47 dB/cm in waveguides and ring resonators with resonator quality factors as high as 860,000. We also characterize the nonlinear performance of these films and find a Kerr coefficient (n 2 ) of 1.2 ( ± 0.2) × 10 -18 m 2 /W. With this high Kerr coefficient we demonstrate optical parametric oscillation in a ring resonator and supercontinuum generation in a waveguide.

Currently, there are no approved medicines available for the treatment of hearing loss. However, research over the past two decades has contributed to a growing understanding of the pathological mechanisms in the cochlea that result in hearing difficulties. The concept that a loss of the synapses connecting inner hair cells with the auditory nerve (cochlear synaptopathy) contributes to hearing loss has gained considerable attention. Both animal and human post-mortem studies support the idea that these synapses (ribbon synapses) are highly vulnerable to noise, ototoxicity, and the aging process. Their degeneration has been suggested as an important factor in the speech-in-noise difficulties commonly experienced by those suffering with hearing loss. Neurotrophins such as brain derived neurotrophic factor (BDNF) have the potential to restore these synapses and provide improved hearing function. OTO-413 is a sustained exposure formulation of BDNF suitable for intratympanic administration that in preclinical models has shown the ability to restore ribbon synapses and provide functional hearing benefit. A phase 1/2 clinical trial with OTO-413 has provided initial proof-of-concept for improved speech-in-noise hearing performance in subjects with hearing loss. Key considerations for the design of this clinical study, including aspects of the speech-in-noise assessments, are discussed.

Despite a prevalence greater than cancer or diabetes, there are no currently approved drugs for the treatment of hearing loss. Research over the past two decades has led to a vastly improved understanding of the cellular and molecular mechanisms in the cochlea that lead to hearing deficits and the advent of novel strategies to combat them. Combined with innovative methods that enable local drug delivery to the inner ear, these insights have paved the way for promising therapies that are now under clinical investigation. In this review, we will outline this renaissance of cochlear biology and drug development, focusing on noise, age-related, and chemotherapy-induced hearing dysfunction., (© 2022 Otonomy, Inc. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Merging robust statistical methods with complex simulation models is a frontier for improving ecological inference and forecasting. However, bringing these tools together is not always straightforward. Matching data with model output, determining starting conditions, and addressing high dimensionality are some of the complexities that arise when attempting to incorporate ecological field data with mechanistic models directly using sophisticated statistical methods. To illustrate these complexities and pragmatic paths forward, we present an analysis using tree-ring basal area reconstructions in Denali National Park (DNPP) to constrain successional trajectories of two spruce species ( Picea mariana and Picea glauca ) simulated by a forest gap model, University of Virginia Forest Model Enhanced-UVAFME. Through this process, we provide preliminary ecological inference about the long-term competitive dynamics between slow-growing P. mariana and relatively faster-growing P. glauca . Incorporating tree-ring data into UVAFME allowed us to estimate a bias correction for stand age with improved parameter estimates. We found that higher parameter values for P. mariana minimum growth under stress and P. glauca maximum growth rate were key to improving simulations of coexistence, agreeing with recent research that faster-growing P. glauca may outcompete P. mariana under climate change scenarios. The implementation challenges we highlight are a crucial part of the conversation for how to bring models together with data to improve ecological inference and forecasting., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

The neurotrophin growth factors bind and activate two types of cell surface receptors: the tropomyosin receptor kinase (Trk) family and p75. TrkA, TrkB, and TrkC are bound preferentially by nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 (NT3), respectively, to activate neuroprotective signals. The p75 receptors are activated by all neurotrophins, and paradoxically in neurodegenerative disease p75 is upregulated and mediates neurotoxic signals. To test neuroprotection strategies, we engineered NT3 to broadly activate Trk receptors (mutant D) or to reduce p75 binding (mutant RK). We also combined these features in a molecule that activates TrkA, TrkB, and TrkC but has reduced p75 binding (mutant DRK). In neurodegenerative disease mouse models in vivo, the DRK protein is a superior therapeutic agent compared with mutant D, mutant RK, and wild-type neurotrophins and protects a broader range of stressed neurons. This work rationalizes a therapeutic strategy based on the biology of each type of receptor, avoiding activation of p75 toxicity while broadly activating neuroprotection in stressed neuronal populations expressing different Trk receptors. SIGNIFICANCE STATEMENT: The neurotrophins nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 each can activate a tropomyosin receptor kinase (Trk) A, TrkB, or TrkC receptor, respectively, and all can activate a p75 receptor. Trks and p75 mediate opposite signals. We report the engineering of a protein that activates all Trks, combined with low p75 binding, as an effective therapeutic agent in vivo., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Neurotrophins and their mimetics are potential treatments for hearing disorders because of their trophic effects on spiral ganglion neurons (SGNs) whose connections to hair cells may be compromised in many forms of hearing loss. Studies in noise or ototoxin-exposed animals have shown that local delivery of NT-3 or BDNF has beneficial effects on SGNs and hearing. We evaluated several TrkB or TrkC monoclonal antibody agonists and small molecules, along with BDNF and NT-3, in rat cochlea ex vivo models. The TrkB agonists BDNF and a monoclonal antibody, M3, had the greatest effects on SGN survival, neurite outgrowth and branching. In organotypic cochlear explants, BDNF and M3 enhanced synapse formation between SGNs and inner hair cells and restored these connections after excitotoxin-induced synaptopathy. Loss of these synapses has recently been implicated in hidden hearing loss, a condition characterized by difficulty hearing speech in the presence of background noise. The unique profile of M3 revealed here warrants further investigation, and the broad activity profile of BDNF observed underpins its continued development as a hearing loss therapeutic., Competing Interests: S. Szobota, P.D.M., S. Siegel and A.C.F. are employees and shareholders of Otonomy, Inc. H.U.S. is a consultant for Otonomy, Inc. H.S., A.C.F. and K.B. are inventors on patent application US20170029511A1, which is assigned to Otonomy, Inc.

Spruce beetle-induced (Dendroctonus rufipennis (Kirby)) mortality on the Kenai Peninsula has heightened local wildfire risk as canopy loss facilitates the conversion from bare to fire-prone grassland. We collected images from NASA satellite-based Earth observations to visualize land cover succession at roughly five-year intervals following a severe, mid-1990's beetle infestation to the present. We classified these data by vegetation cover type to quantify grassland encroachment patterns over time. Raster band math provided a change detection analysis on the land cover classifications. Results indicate the highest wildfire risk is linked to herbaceous and black spruce land cover types, The resulting land cover change image will give the Kenai National Wildlife Refuge (KENWR) ecologists a better understanding of where forests have converted to grassland since the 1990s. These classifications provided a foundation for us to integrate digital elevation models (DEMs), temperature, and historical fire data into a model using Python for assessing and mapping changes in wildfire risk. Spatial representations of this risk will contribute to a better understanding of ecological trajectories of beetle-affected landscapes, thereby informing management decisions at KENWR., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest.

The N -methyl-d-aspartate receptor coagonist d-serine is a substrate for the neutral amino acid transporters ASCT1 and ASCT2, which may regulate its extracellular levels in the central nervous system (CNS). We tested inhibitors of ASCT1 and ASCT2 for their effects in rodent models of schizophrenia and visual dysfunction, which had previously been shown to be responsive to d-serine. L-4-fluorophenylglycine (L-4FPG), L-4-hydroxyPG (L-4OHPG), and L-4-chloroPG (L-4ClPG) all showed high plasma bioavailability when administered systemically to rats and mice. L-4FPG showed good brain penetration with brain/plasma ratios of 0.7-1.4; however, values for L-4OHPG and L-4ClPG were lower. Systemically administered L-4FPG potently reduced amphetamine-induced hyperlocomotion in mice, whereas L-4OHPG was 100-fold less effective and L-4ClPG inactive at the doses tested. L-4FPG and L-4OHPG did not impair visual acuity in naive rats, and acute systemic administration of L-4FPG significantly improved the deficit in contrast sensitivity in blue light-treated rats caused by retinal degeneration. The ability of L-4FPG to penetrate the brain makes this compound a useful tool to further evaluate the function of ASCT1 and ASCT2 transporters in the CNS., (Copyright © 2018 by The Author(s).)

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.

We present a secure communication system constructed using pairs of nonlinear photonic physical unclonable functions (PUFs) that harness physical chaos in integrated silicon micro-cavities. Compared to a large, electronically stored one-time pad, our method provisions large amounts of information within the intrinsically complex nanostructure of the micro-cavities. By probing a micro-cavity with a rapid sequence of spectrally-encoded ultrafast optical pulses and measuring the lightwave responses, we experimentally demonstrate the ability to extract 2.4 Gb of key material from a single micro-cavity device. Subsequently, in a secure communication experiment with pairs of devices, we achieve bit error rates below 10 -5 at code rates of up to 0.1. The PUFs' responses are never transmitted over the channel or stored in digital memory, thus enhancing the security of the system. Additionally, the micro-cavity PUFs are extremely small, inexpensive, robust, and fully compatible with telecommunications infrastructure, components, and electronic fabrication. This approach can serve one-time pad or public key exchange applications where high security is required.

The N-methyl-d-aspartate receptor (NMDA) co-agonist d-serine is a substrate for the neutral amino acid transporters ASCT1 (SLC1A4) and ASCT2 (SLC1A5). We identified l-phenylglycine (PG) and its analogs as inhibitors of ASCT1 and ASCT2. PG analogs were shown to be non-substrate inhibitors of ASCT1 and ASCT2 with a range of activities relative to other amino acid transport systems, including sodium-dependent glutamate transporters, the sodium-independent d-serine transporter asc-1 and system L. L-4-chloroPG was the most potent and selective ASCT1/2 inhibitor identified. The PG analogs facilitated theta-burst induced long-term potentiation in rat visual cortex slices in a manner that was dependent on extracellular d-serine. For structurally-related PG analogs, there was an excellent correlation between ASCT1/2 transport inhibition and enhancement of LTP which was not the case for inhibition of asc-1 or system L. The ability of PG analogs to enhance LTP is likely due to inhibition of d-serine transport by ASCT1/2, leading to elevated extracellular levels of d-serine and increased NMDA receptor activity. These results suggest that ASCT1/2 may play an important role in regulating extracellular d-serine and NMDA receptor-mediated physiological effects and that ASCT1/2 inhibitors have the potential for therapeutic benefit., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We demonstrate phase-sensitive amplification in hydrogenated amorphous silicon photonic waveguides based on pump-degenerate four-wave mixing at continuous-wave (CW) operation, as well as at repetition rates of both 90 MHz and 10 GHz. At 90 MHz pulsed operation, an 11.7 dB phase-sensitive extinction ratio (ER) is achieved with a peak pump power of 1.6 W. At 10 GHz pulsed operation, a 6.6 dB phase-sensitive ER is achieved with a peak pump power of 0.5 W. At CW operation, a 1.6 dB ER is achieved with a pump power of 38 mW.

Physical unclonable functions (PUFs) serve as a hardware source of private information that cannot be duplicated and have applications in hardware integrity and information security. Here we demonstrate a photonic PUF based on ultrafast nonlinear optical interactions in a chaotic silicon micro-cavity. The device is probed with a spectrally-encoded ultrashort optical pulse, which nonlinearly interacts with the micro-cavity. This interaction produces a highly complex and unpredictable, yet deterministic, ultrafast response that can serve as a unique "fingerprint" of the cavity and as a source of private information for the device's holder. Experimentally, we extract 17.1-kbit binary keys from six different photonic PUF designs and demonstrate the uniqueness and reproducibility of these keys. Furthermore, we experimentally test exact copies of the six photonic PUFs and demonstrate their unclonability due to unavoidable fabrication variations.

Based on four-wave mixing (FWM) with an optical comb source (OCS), we experimentally demonstrate 26-way or 15-way wavelength multicasting of 10-Gb/s differential phase-shift keying (DPSK) data in a highly-nonlinear fiber (HNLF) or a silicon waveguide, respectively. The OCS provides multiple spectrally equidistant pump waves leading to a multitude of FWM products after mixing with the signal. We achieve error-free operation with power penalties less than 5.7 dB for the HNLF and 4.2 dB for the silicon waveguide, respectively.

We demonstrate 15% on-chip conversion efficiency of four-wave mixing Bragg scattering in a hydrogenated amorphous silicon waveguide with only 55 and 194 mW peak pump powers in the waveguide. The lightwaves can be maintained in the telecommunication band, and the operational bandwidth is measured to be larger than 4 nm.

The NMDA subtype of glutamate receptor and its co-agonist d-serine play a key role in synaptic function in the central nervous system (CNS), including visual cortex and retina. In retinal diseases such as glaucoma and macular degeneration, a loss of vision arises from malfunction of retinal cells, resulting in a glutamate hypofunctional state along the visual pathway in the affected parts of the visual field. An effective strategy to remedy this loss of function might be to increase extracellular levels of d-serine and thereby boost synaptic NMDA receptor-mediated visual transmission and/or plasticity to compensate for the impairment. We tested this idea in brain slices of visual cortex exhibiting long-term potentiation, and in rodent models of visual dysfunction caused by retinal insults at a time when the injury had stabilized to look for neuroenhancement effects. An essential aspect of the in vivo studies involved adapting sweep VEP technology to conscious rats and rabbits and combining it with intracortical recording while the animals were actively attending to visual information. Using this technology allowed us to establish complete contrast sensitivity function curves. We found that systemic d-serine dose-dependently rescued the contrast sensitivity impairment in rats with blue light-induced visual dysfunction. In rabbits with inner retinal dysfunction, both systemic and intravitreal routes of d-serine provided a rescue of visual function. In sum, we show that co-agonist stimulation of the NMDA receptor via administration of exogenous d-serine might be an effective therapeutic strategy to enhance visual performance and compensate for the loss of vision resulting from retinal disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A high-speed all-optical NAND logic gate is proposed and experimentally demonstrated using four-wave mixing Bragg scattering in highly nonlinear fiber. NAND/AND logic functions are implemented at two wavelengths by encoding logic inputs on two pumps via on-off keying. A 15.2-dB depletion of the signal is obtained for NAND operation, and time domain measurements show 10-Gb/s NAND/AND logic operations with open eye diagrams. The approach can be readily extended to higher data rates and transferred to on-chip waveguide platforms.

N-methyl-D-aspartate (NMDA) receptors play critical roles in synaptic transmission and plasticity. Activation of NMDA receptors by synaptically released L-glutamate also requires occupancy of co-agonist binding sites in the tetrameric receptor by either glycine or D-serine. Although D-serine appears to be the predominant co-agonist at synaptic NMDA receptors, the transport mechanisms involved in D-serine homeostasis in brain are poorly understood. In this work we show that the SLC1 amino acid transporter family members SLC1A4 (ASCT1) and SLC1A5 (ASCT2) mediate homo- and hetero-exchange of D-serine with physiologically relevant kinetic parameters. In addition, the selectivity profile of D-serine uptake in cultured rat hippocampal astrocytes is consistent with uptake mediated by both ASCT1 and ASCT2. Together these data suggest that SLC1A4 (ASCT1) may represent an important route of Na-dependent D-serine flux in the brain that has the ability to regulate extracellular D-serine and thereby NMDA receptor activity.

The enantiomers of erythro-3-hydroxyaspartate were tested for activity at glutamate transporters and NMDA receptors. Both enantiomers inhibited glutamate transporters in rat hippocampal crude synaptosomes and elicited substrate-like activity at excitatory amino acid transporter 1, 2, and 3 as measured by voltage clamp in the Xenopus oocyte expression system. The enantiomers had similar affinities, but the D-enantiomer showed a lower maximal effect at excitatory amino acid transporter 1, 2, and 3 than the L-enantiomer. Surprisingly, D-erythro-3-hydroxyaspartate was a potent NMDA receptor agonist with an EC 50 value in rat hippocampal neurons of 320 nM, whereas the L-enantiomer was 100-fold less potent. L-erythro-3-hydroxyaspartate showed activity at both glutamate transporters and NMDA receptors at concentrations that are reported to inhibit serine racemase, indicating a lack of selectivity. This enantiomeric pair may assist in shedding further light on the structural requirements for substrate activity at glutamate transporters and for agonist activity at NMDA receptors. The erythro enantiomers of 3-hydroxyaspartate had interesting and surprising effects on glutamate neurotransmitter systems. L-erythro-3-hydroxyaspartate had activity at both glutamate transporters (EAAT1/2/3) and NMDA receptors. D-erythro-3-hydroxyaspartate acted on EAATs, but was also identified as a highly potent NMDA receptor agonist. These enantiomers shed further light on the structural requirements for activity at EAATs and NMDA receptors., (© 2015 International Society for Neurochemistry.)

Understanding the storage and release of the excitatory neurotransmitter, L-glutamate by synaptic vesicles has lagged behind receptor characterizations due to a lack of pharmacological agents. We report that the glutamate analog, 3-aminoglutarate (3-AG) is a "silent" false transmitter for glutamate neurons that may be a useful tool to study storage and release mechanisms. Like L-glutamate itself, 3-AG is a high-affinity substrate for both the plasma membrane (EAATs) and vesicular (vGLUT) glutamate transporters. As such, EAATs facilitate 3-AG entry into neuronal cytoplasm allowing 3-AG to compete with L-glutamate for transport into vesicles thus reducing glutamate content. In a synaptosomal preparation, 3-AG inhibited calcium-dependent endogenous L-glutamate release. Unlike L-glutamate, 3-AG had low affinity for both ionotropic (NMDA and AMPA) and G-protein coupled (mGlu1-8) receptors. Consequently, 3-AG behaves as a "silent" false transmitter that may be used in physiological experiments to probe synaptic vesicle storage and release mechanisms for L-glutamate. The companion paper by Wu et al. (2015) describes initial experiments that explore the effects of 3-AG on glutamate synaptic transmission under physiological and pathophysiological conditions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Pharmacological tools that interact with the mechanisms that regulate vesicular filling and release of the neurotransmitter L-glutamate would be of enormous value. In this study, we provide physiological evidence that the glutamate analog, 3-aminoglutarate (3-AG), acts as a false transmitter to reduce presynaptic glutamate release. 3-AG inhibits glutamate-mediated neurotransmission both in primary neuronal cultures and in brain slices with more intact neural circuits. When assayed with the low affinity glutamate receptor antagonist γ-DGG, we demonstrate that 3-AG significantly reduces the synaptic cleft glutamate concentration, suggesting that 3-AG may act as a false transmitter to compete with glutamate during vesicle filling. Furthermore, using three different epileptic models (Mg(2+)-free, 4-AP, and high K(+)), we demonstrate that 3-AG is capable of suppressing epileptiform activity both before and after its induction. Our studies, along with those of the companion paper by Foster et al. (2015) indicate that 3-AG is a "silent" false transmitter for glutamate neurons that is a useful pharmacological tool to probe the mechanisms governing vesicular storage and release of glutamate under both physiological and pathophysiological conditions. 3-AG may have potential therapeutic value in conditions where the glutamate neurotransmitter system is pathologically overactive., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Using a deposited hydrogenated amorphous silicon (a-Si:H) waveguide, we demonstrate ultra-broad bandwidth (60 THz) parametric amplification via four-wave mixing (FWM), and subsequently achieve the first silicon optical parametric oscillator (OPO) at near-IR wavelengths. Utilization of the time-dispersion-tuned technique provides an optical source with active wavelength tuning over 42 THz with a fixed pump wave.

Background: Muscle dysmorphia (MD) describes a condition characterised by a misconstrued body image in which individuals who interpret their body size as both small or weak even though they may look normal or highly muscular.MD has been conceptualized as a type of body dysmorphic disorder, an eating disorder, and obsessive–compulsive disorder symptomatology. METHOD AND AIM: Through a review of the most salient literature on MD, this paper proposes an alternative classification of MD--the ‘Addiction to Body Image’ (ABI) model--using Griffiths (2005)addiction components model as the framework in which to define MD as an addiction., Results: It is argued the addictive activity in MD is the maintaining of body image via a number of different activities such as bodybuilding, exercise,eating certain foods, taking specific drugs (e.g., anabolic steroids), shopping for certain foods, food supplements,and the use or purchase of physical exercise accessories). In the ABI model, the perception of the positive effects on the self-body image is accounted for as a critical aspect of the MD condition (rather than addiction to exercise or certain types of eating disorder)., Conclusions: Based on empirical evidence to date, it is proposed that MD could be re-classified as an addiction due to the individual continuing to engage in maintenance behaviours that may cause long-term harm.

Background: Following the publication of our paper ‘Muscle Dysmorphia: Could it be classified as an addiction to body image?’ in the Journal of Behavioral Addictions, two commentaries by Jon Grant and Johanna Nieuwoudt were published in response to our paper., Method: Using the ‘addiction components model’, our main contention is that muscle dysmorphia (MD) actually comprises a number of different actions and behaviors and that the actual addictive activity is the maintaining of body image via a number of different activities such as bodybuilding, exercise, eating certain foods, taking specific drugs (e.g., anabolic steroids), shopping for certain foods, food supplements, and purchase or use of physical exercise accessories. This paper briefly responds to these two commentaries., Results: While our hypothesized specifics relating to each addiction component sometimes lack empirical support (as noted explicitly by both Nieuwoudt and Grant), we still believe that our main thesis (that almost all the thoughts and behaviors of those with MD revolve around the maintenance of body image) is something that could be empirically tested in future research by those who already work in the area., Conclusions: We hope that the ‘Addiction to Body Image’ model we proposed provides a new framework for carrying out work in both empirical and clinical settings. The idea that MD could potentially be classed as an addiction cannot be negated on theoretical grounds as many people in the addiction field are turning their attention to research in new areas of behavioral addiction.

We use pump-probe spectroscopy and continuous wave cross-phase and cross-amplitude modulation measurements to study the optical nonlinearity of a hydrogenated amorphous silicon (a-Si:H) nanowire waveguide, and we compare the results to those of a crystalline silicon waveguide of similar dimensions. The a-Si:H nanowire shows essentially zero instantaneous two-photon absorption, but it displays a strong, long-lived non-instantaneous nonlinearity that is both absorptive and refractive. Power scaling measurements show that this non-instantaneous nonlinearity in a-Si:H scales as a third-order nonlinearity, and the refractive component possesses the opposite sign to that expected for free-carrier dispersion.

We demonstrate highly efficient photon-pair generation using an 8 mm long hydrogenated amorphous silicon (a-Si:H) waveguide in far-detuned multiple wavelength channels simultaneously, measuring a coincidence-to-accidental ratio as high as 400. We also characterize the contamination from Raman scattering and show it to be insignificant over a spectrum span of at least 5 THz. Our results highlight a-Si:H as a potential high-performance, CMOS-compatible platform for large-scale quantum applications, particularly those based on the use of multiplexed quantum signals.

We experimentally demonstrate frequency resolved optical gating (FROG) via four-wave mixing (FWM) in ultrahigh nonlinearity hydrogenated amorphous silicon waveguides. We demonstrate FROG characterization using a FWM architecture that mimics second harmonic generation (SHG) FROG for pulsewidths as low as 360 fs. Additionally, we demonstrate for the first time a FWM architecture analogous to third harmonic generation (THG) FROG and validate its ability to overcome the direction of time ambiguity of the SHG-like architecture. Both architectures allow for sensitivities suitable for future telecommunications signals.

Utilizing a 6-mm-long hydrogenated amorphous silicon nanowaveguide, we demonstrate error-free (BER < 10(-9)) 160-to-10 Gb/s OTDM demultiplexing using ultralow switching peak powers of 50 mW. This material is deposited at low temperatures enabling a path toward multilayer integration and therefore massive scaling of the number of devices in a single photonic chip.

We propose a novel optical hybrid plasmonic patch nano-antenna for operation at the standard telecommunication wavelength of 1550 nm. The nano-antenna is designed to be compatible with a hybrid plasmonic waveguide through matching of both the operational mode and the wave impedance. The antenna is designed to receive the optical signal from a planar waveguide and redirect the signal out of plane, and is therefore useful for inter- or intra-chip optical communications and sensing. The transmission line model in conjunction with surface plasmon theory is used to develop analytical formulas for design and analysis, and a 3-dimensional full-wave numerical method is used to validate the design. The proposed device provides a bandwidth of more than 15 THz, a gain of 5.6 dB, and an efficiency of 87%. Furthermore, by designing an 8 × 8 array of the proposed antenna, a directivity of 20 dBi and steering of the beam angle are achieved by controlling the relative phase shift between elements of the array.

We demonstrate wavelength conversion through nonlinear parametric processes in hydrogenated amorphous silicon (a-Si:H) with maximum conversion efficiency of -13 dB at telecommunication data rates (10 GHz) using only 15 mW of pump peak power. Conversion bandwidths as large as 150 nm (20 THz) are measured in continuous-wave regime at telecommunication wavelengths. The nonlinear refractive index of the material is determined by four-wave mixing (FWM) to be n(2)=7.43×10(-13) cm(2)/W, approximately an order of magnitude larger than that of single crystal silicon., (© 2012 Optical Society of America)

We experimentally demonstrate four-wave-mixing (FWM)-based continuous wavelength conversion of optical differential-phase-shift-keyed (DPSK) signals with large wavelength conversion ranges as well as simultaneous wavelength conversion of dual-wavelength channels with mixed modulation formats in 1.1-cm-long dispersion-engineered silicon waveguides. We first validate up to 100-nm wavelength conversion range for 10-Gb/s DPSK signals, showcasing the capability to perform phase-preserving operations at high bit rates in chip-scale devices over wide conversion ranges. We further validate the wavelength conversion of dual-wavelength channels modulated with 10-Gb/s packetized phase-shift-keyed (PSK) and amplitude-shift-keyed (ASK) signals; demonstrate simultaneous operation on multiple channels with mixed formats in chip-scale devices. For both configurations, we measure the spectral and temporal responses and evaluate the performances using bit-error-rate (BER) measurements.

We report the first demonstration of cw wavelength conversion from the telecommunications band to the mid-IR (MIR) region via four-wave mixing in silicon nanowaveguides. We measure a parametric bandwidth of 748 nm by converting a 1636 nm signal to produce a 2384 nm idler and show continuously tunable wavelength conversion from 1792 to 2116 nm. This report indicates that the advantages of silicon photonics may be leveraged to create devices for a large range of MIR applications that require cw operation.

We demonstrate a scalable, energy-efficient, and pragmatic method for high-bandwidth wavelength multicasting using FWM in silicon photonic nanowires. We experimentally validate up to a sixteen-way multicast of 40-Gb/s NRZ data using spectral and temporal responses, and evaluate the resulting data integrity degradation using BER measurements and power penalty performance metrics. We further examine the impact of this wavelength multicasting scalability on conversion efficiency. Finally, we experimentally evaluate up to a three-way multicast of 160-Gb/s pulsed-RZ data using spectral and temporal responses, representing the first on-chip wavelength multicasting of pulsed-RZ data.

We demonstrate a temporal imaging system based on parametric mixing that allows simple triggering from an external clock by using a time-lens-based pump laser. We integrate our temporal imaging system into a time-to-frequency measurement scheme and demonstrate the ability to perform characterization of temporal waveforms with 1.4-ps resolution and a 530-ps record length. We also integrate our system into a temporal-magnification scheme and demonstrate single-shot operation with a 113 x magnification factor, 1.5-ps resolution, and 220-ps record length.

We demonstrate reduction of the free-carrier lifetime in a silicon nanowaveguide from 3 ns to 12.2 ps by applying a reverse bias across an integrated p-i-n diode. This observation represents the shortest free-carrier lifetime demonstrated to date in silicon waveguides. Importantly, the presence of the p-i-n structure does not measurably increase the propagation loss of the waveguide. We derive a figure of merit demonstrating equal dependency of the nonlinear phase shift on free-carrier lifetime and linear propagation loss.

We demonstrate ultrabroad-bandwidth low-power frequency conversion of continuous-wave light in a dispersion engineered silicon nanowaveguide via four-wave mixing. Our process produces continuously tunable four-wave mixing wavelength conversion over two-thirds of an octave from 1241-nm to 2078-nm wavelength light with a pump wavelength in the telecommunications C-band.

We report experimental demonstration of an all-optical continuously tunable delay line based on parametric mixing with a total delay range of 7.34 mus. The bit-error rate performance of the delay line was characterized for a 10-Gb/s NRZ data channel. This result is enabled by cascading a discrete delay line that consists of 16 wavelength-dependent delays and a continuously tunable delay stage. Four wavelength conversion stages based on four-wave mixing in silicon waveguides were performed in order to achieve wavelength-preserving operation. The wavelength-optimized optical phase conjugation scheme employed in the delay line is capable of minimizing the residual dispersion for the entire tuning range.

We experimentally demonstrate wavelength-preserving spectral phase conjugation for compensating chromatic dispersion and self-phase modulation in optical fibers. Our implementation is based on a temporal imaging scheme that uses time lenses realized by broadband four-wave mixing in silicon waveguides. By constructing a temporal analog of a 4-f imaging system, we compensate for pulse distortions arising from second- and third-order dispersion and self-phase modulation in optical fibers.